No abstract available
https://ift.tt/2N756YO
Δευτέρα 20 Αυγούστου 2018
Grover Disease With Epidermal Dysmaturation Pattern: A Common Histopathologic Finding
Background: Grover disease is an entity whose diagnosis is based on clinicopathologic correlation. Histopathologically, focal acantholysis is the most common finding. In some cases, there is prominent squamous atypia which can prove to be very challenging and the lesion may be confused with an epidermal neoplasm. Objective: To report on atypical histopathological changes in Grover disease and to provide helpful clues to differentiate between the epidermal atypia seen in some cases of Grover disease and epithelial neoplasms. Material and Methods: We analyzed 33 cases of Grover disease histologically diagnosed at Wake Forest Baptist Medical Center, NC, between 2011 and 2017. Atypical changes in keratinocytes were defined as epithelial buds, nuclear pleomorphism, and dyskeratosis in all layers of epidermis or altered granular layer. Results: Twenty cases (64%) showed foci with alteration of the normal keratinocytic maturation, whereas 18 cases demonstrated nuclear pleomorphism. Buds of epithelial cells emanating from the basal layer of the epidermis and granular cell alteration was present in 19 cases. Conclusions: The findings especially the presence of an altered granular layer may represent a diagnostic clue in cases of Grover disease with atypical changes.https://ift.tt/2PqWnSv
PD-L1 Expression is Increased in Metastasizing Squamous Cell Carcinomas and Their Metastases
Abstract: Programmed cell death ligand 1 (PD-L1) expression by tumor cells plays an important role in the inhibition of T cell–mediated immune response in cancer. PD-L1 expression by tumor cells has been linked to poor prognosis in a wide variety of cancers. However, PD-L1 expression in cutaneous squamous cell carcinoma (cSCC) has been scarcely studied, and its role as a prognosis biomarker remains controversial. The association of PD-L1 expression and the metastatic risk in a series of cSCC was assessed. PD-L1 and CD8 immunostainings of full excision sections of 99 primary tumors and 24 lymphatic metastases were semiquantitatively evaluated. Primary cSCCs were grouped according to the development of lymphatic metastatic spread [metastasizing squamous cell carcinoma (MSCC)] (n = 48) or the absence of progression [nonmetastasizing squamous cell carcinoma (NMSCC)] (n = 51). PD-L1–positive expression (cut off ≥1%) was found in 26% NMSCCs and in 50% MSCCs (P = 0.02). PD-L1 association with an increased metastatic risk was confirmed in the multivariate analysis (Phttps://ift.tt/2PqVYPZ
Cytotoxic CD8+ Granulomatous Cutaneous T-Cell Lymphoma Associated With Human Immunodeficiency Virus Infection: A Diagnostic Challenge
No abstract availablehttps://ift.tt/2N7XULJ
Using Stratum Corneum Thickness and Configuration to Distinguish Lichenoid Dermatoses
Background: Clues in the stratum corneum (SC) can aide in histopathologic diagnosis of many conditions. Objective: To determine if SC configuration and thickness could help differentiate the lichenoid dermatoses. Methods: A retrospective study was performed. A total of 305 cases (55 lichenoid keratosis, 51 lichen planus, 7 hypertrophic lichen planus, 40 lichenoid drug eruption, 19 lichenoid graft-vs.-host disease, 14 hypertrophic lupus, 46 lichenoid actinic keratosis, 73 lentigo maligna) fulfilled the selection criteria. Cases were digitally scanned using the 40× (0.23 μm/pixel) mode of a Hamamatsu NanoZoomer 2.0-HT Slide Scanner (Hamamatsu Photonics, Hamamatsu City, Japan), allowing for the creation of virtual (digital) slides. SC thicknesses and configuration were assessed for each case. Results: Mixed SC patterns were common in cases of lichenoid keratoses. Compact parakeratosis was the most common pattern in lichenoid drug eruption. Tiered parakeratosis was the most predominant pattern in cases of lichenoid graft versus host disease and lichenoid actinic keratosis. Hypertrophic lupus had the highest average SC thickness. Limitations: The sample size for cases of hypertrophic lupus and hypertrophic lichen planus was low. Conclusions: SC thickness and configuration can be utilized to help differentiate the lichenoid dermatoses.https://ift.tt/2PqVSYD
Role of Direct Immunofluorescence in Cutaneous Small-Vessel Vasculitis: Experience From a Tertiary Center
Abstract: Skin is commonly affected by vasculitic process and often subjected to biopsy. Cutaneous vasculitis can be either primary or part of a systemic vasculitic process. This study was conducted to evaluate the diagnostic utility of direct immunofluorescence (DIF) in determination of etiology of cutaneous vasculitis. All histologically proven cases of cutaneous vasculitis over the past two and half years were retrospectively analyzed along with their clinical and DIF findings (IgG, IgA, IgM, and C3). Within this study period, a total of 198 cases of small-vessel vasculitis were diagnosed based on skin biopsy and DIF findings. The mean age of patients was 31.2 years (range 1–84 years) with slight male dominance (M:F ratio 1.06:1). Henoch–Schonlein purpura/IgA vasculitis was the commonest clinical diagnosis (31%), followed by urticarial vasculitis (11%) and others. Idiopathic vasculitis was suspected in 33% cases. Overall, DIF was positive in 60% (119/198) cases, with vascular deposition of IgA being commonest, followed by C3. The clinical diagnosis of Henoch–Schonlein purpura could be confirmed in 61.5% (40/65) cases by DIF, whereas another 20 unsuspected cases were picked up as IgA vasculitis based on DIF findings. DIF findings confirmed lupus vasculitis in 50% cases. Other cases showed variable nonspecific deposition of C3 and IgM in 42% cases. DIF can be highly useful to classify cutaneous vasculitis, with maximum efficacy for diagnosis of IgA vasculitis and lupus vasculitis. It can aid in the accurate diagnosis even when the histological changes are minimal. All cases of suspected cutaneous vasculitis should be subjected to DIF.https://ift.tt/2PqVlWD
Practice of Teledermatopathology: A Systematic Review
Introduction: Teledermatopathology has the potential to revolutionize the practice of diagnosing skin diseases. This review provides an overview of the advantages, limitations, and future directions of teledermatopathology. Methods: MEDLINE was searched via PubMed and Google Scholar databases for relevant articles published from 2012 to the present. Additional articles were also identified by hand-searching. Results: A total of 2675 citations were identified in the initial search. Two thousand five hundred seventy-three were excluded based on duplicates and review of titles and abstracts. Eighty studies failed to meet the inclusion criteria, resulting in a total of 22 articles for analysis. Nine additional articles were hand-searched. Conclusions: Recent studies report that telepathology increases access to specialists, reduces interpretive errors and health care expenditures, improves the efficiency of workflow, and optimizes patient outcomes. It also facilitates international collaboration by widening global access to dermatopathology services and providing educational resources in underserved areas. However, the quality and regulations of digital slide imaging in teledermatopathology need to be improved.
https://ift.tt/2PqVKID
https://ift.tt/2PqVKID
Unusual Case of Dactylitis With Nail Unit Involvement: Challenge
No abstract availablehttps://ift.tt/2N7DkLw
Unusual Neuroendocrine Differentiation in a Small Round Cell Angiosarcoma: A Potential Histologic Mimicker of Superficial Ewing Sarcoma
Abstract: Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon in angiosarcomas (AS) and creates a challenging differential diagnosis with other superficial or soft tissue tumors. Herein, we report a new case of superficial AS presenting as a tumor lesion on the little finger of the right hand of a 52-year-old man. The tumor displayed CD56, chromogranin-A, and synaptophysin immunoreactivity. Tumor cells were positive for vascular markers (CD31, FLI1, ERG, D2-40, VE-cadherin, VEGR1,2, and 3), CD99, and EMA, but were negative for S100, CK (AE1/AE3), CK20, polyomavirus, and myogenic (desmin and myogenin) and melanocyte markers (melan-A and HMB45). Ki67 immunostains indicated high proliferative activity (>50%). The whole-body computed tomography did not reveal distant disease. The initial assessment considered several tumor subtypes as possible histological diagnoses, including Ewing sarcoma, Ewing-like sarcoma, Merkel cell carcinoma, and undifferentiated "small round cell sarcoma". Fluorescence in situ hybridization analysis was negative for EWSR1 translocation and molecular analysis failed to detect any EWSR1, CIC, SYT or BCOR rearrangement. As a follow-up investigation, we tested 17 cutaneous/superficial AS for neuroendocrine markers; however, only one of these showed focal CD56 and synaptophysin expression. In conclusion, the present findings indicate that neuroendocrine differentiation is a very infrequent feature in AS. We report an AS of the finger with an uncommon histological appearance and immunohistochemical profile: predominant round cell tumor proliferation and neuroendocrine differentiation. Pathologists should be aware of these potential histological and immunohistochemical pitfalls in AS.https://ift.tt/2PqVglN
Pilomatrixoma: A Comprehensive Review of the Literature
Introduction: Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a superficial benign skin tumor that arises from hair follicle matrix cells. Although pilomatrixomas are well-recognized lesions, clinically they are frequently misdiagnosed as other skin conditions. By reviewing all the literature over the past 10 years, the aims of this article are to analyze the cause, clinical presentation, management, and outcome of pilomatrixoma among children and adults to gain a more complete understanding of this lesion in today's clinical context. Methods: A MEDLINE and EMBASE search was conducted from January 2005 to February 2015 using a combination of the terms: "child," "childhood," "adult," and keywords: "pilomatrixoma," "pilomatricoma," and "calcifying epithelioma of Malherbe." A total of 150 articles were reviewed. Results: The lesions occurred most commonly in the first and second decades (mean age 16 years and 7 months). The commonest presentation was of an asymptomatic, firm, slowly growing, mobile nodule. Only 16% were accurately diagnosed on clinical examination. Imaging in the form of ultrasound, computed tomography, and magnetic resonance imaging has been reported. Pathological diagnosis was achieved through incision, punch, and shave biopsies. Pathological findings are discussed and summarized in this review. Conclusion: Pilomatrixomas are thought to arise from mutation in the Wnt pathway and has been linked to several genetic conditions. It is commonly misdiagnosed preoperatively; however, with better awareness of the lesion, it can be appropriately treated while avoiding unnecessary diagnostic tests. Complete surgical excision with clear margins is almost always curative.https://ift.tt/2N4LmVo
T-Lymphoblastic Leukemia/Lymphoma With Annular Skin Rash and Epidermotropism
Abstract: Leukemia cutis is uncommon in patients with acute lymphoblastic leukemia. It typically presents with dermal papules or subcutaneous nodules, with no epidermal or upper papillary dermal involvement on histopathology. We present an unusual clinical presentation of leukemia cutis, with annular plaques and epidermotropism.https://ift.tt/2PqVCZF
A Case of a Malignant Cutaneous Mixed Tumor (Chondroid Syringoma) of the Scapula Treated With Staged Margin-Controlled Excision
Abstract: Cutaneous mixed tumor (chondroid syringoma) is the cutaneous counterpart of pleomorphic adenoma of salivary glands, comprised of both epithelial and mesenchymal components. Malignant transformation is exceptionally rare, with only a few cases reported. We report a case of a malignant cutaneous mixed tumor in an 86-year-old white man who presented with a pink indurated plaque on his left scapula. He had a history of nonmelanoma skin cancers, a stage IB malignant melanoma of a lower extremity and Gleason 4 + 3 prostate cancer treated with brachytherapy, external beam irradiation, and bicalutamide. A shave biopsy was performed and histologic examination revealed infiltrative single-unit atypical cells and small ducts in a superficially transected sclerotic dermis suggestive of a poorly differentiated adenocarcinoma. No epidermal connection was identified. Immunohistochemical studies revealed that the tumor was positive for CK7, CAM5.2, and mCEA and negative for CK20, epithelial membrane antigen, P63, prostate-specific antigen, prostatic specific acid phosphatase, and alpha-methylacyl-coenzyme A racemase. A metastasis of the breast or upper digestive tract was favored, although a primary eccrine carcinoma was also considered. Imaging was performed and no other masses were identified. A slow Mohs excision was performed with negative margins. Microscopic examination revealed a biphasic neoplasm comprised of infiltrative epithelial strands and tubules consistent with an eccrine carcinoma in a hyalinized and chondromyxoid stroma within the dermis, arising from a well-circumscribed chondroid syringoma located in the deep dermis and subcutis. Areas of clear cell change, intracytoplasmic vacuolization, and mucin pools were noted. Multiple foci of perineural invasion were identified. Additional immunohistochemical studies revealed that the tumor was positive for S100 and negative for CK5/6, calponin, glial fibrillary acidic protein, GATA3, GCDFP-15, and mammoglobin. Based on the morphologic features and immunoprofile, this was diagnosed as a malignant cutaneous mixed tumor. This case highlights the importance of obtaining adequate tissue for histologic evaluation, as they can be confused with other skin neoplasms because of their clinically ambiguous presentations. Although rare, an accurate diagnosis is important given that long-term follow-up is recommended because of the risk of local recurrence and both lymph node and distant metastases.https://ift.tt/2PqV4TB
Livedoid Vasculopathy Presenting in a Patient With Sickle Cell Disease
Abstract: We report a case in which a 43-year-old African American male with medical history of sickle cell disease (SCD) presented with a nonhealing ulcer. Biopsy revealed features of livedoid vasculopathy. Previously, livedoid vasculopathy had only been described in a patient with sickle cell trait, but never in a patient with SCD. Livedoid vasculopathy most commonly affects the distal lower extremities and is characterized by irregular, punched-out, painful ulcers that heal with stellate white scars of atrophie blanche. Histologically, it reveals segmental hyalinizing vessels, focal thrombosis, and endothelial proliferation. The etiology is currently unclear, but it has been shown to be related to procoagulant states and a diagnosis of livedoid vasculopathy should prompt a thorough hypercoagulable workup, including testing for SCD in high-risk patients.https://ift.tt/2PqUTHV
Cutaneous Metastases of Melanoma Mimicking Interstitial Granulomatous Processes
No abstract availablehttps://ift.tt/2N0CwIm
Rare Variant of Agminated Spitz Nevi on a Hypopigmented Background and Segmental Distribution: Case Report and Review of Literature
Abstract: Spitz nevus is a type of melanocytic nevus that can arise as a solitary lesion or as multiple lesions either disseminated or agminated (grouped) in different skin backgrounds (eg, grossly normal, hyperpigmented, or hypopigmented). Agminated Spitz nevi have been rarely reported and are even rarer in a background of hypopigmented skin. We present the case of a 2-month-old girl with multiple, grouped, dome-shaped, red papules arising on a hypopigmented patch with a segmental distribution. Biopsy of 2 lesions showed findings characteristic of Spitz nevus, confirming the diagnosis. We also review 4 other cases of agminated Spitz nevi arising on hypopigmented skin reported in the literature.https://ift.tt/2Po2VBw
Serum antibodies against the insulin-like growth factor-1 receptor (IGF-1R) in Graves’ disease and Graves’ orbitopathy
Abstract
Background
A role of the insulin-like growth factor-1 receptor (IGF-1R) in the pathogenesis of Graves' orbitopathy (GO) has been proposed, but the existence and function of anti-IGF-1R-antibodies (IGF-1R-Abs) are debated.
Methods
We designed a cross-sectional investigation to measure serum IGF-1R-Abs by a commercial assay in consecutive patients with Graves' disease (GD) compared with healthy subjects and patients with autoimmune thyroiditis (AT). A total of 134 subjects were screened including 27 healthy subjects, 80 GD patients (54 of whom with GO), and 27 AT patients. The main outcome measure was the prevalence of positive serum IGF-1R-Abs in GO, compared with GD without GO and with the other study groups.
Results
Having established a cut-off value at 55.2 ng/ml for positive tests, positive IGF-1R-Abs were more frequent in GD (25%), than in AT (3.7%, P = 0.003) and healthy subjects (0%, P = 0.006). Within GD, there was no difference between patients with or without GO. Serum levels of IGF-1R-Abs differed across the study population (P < 0.0001), reflecting their higher concentrations in GD (P < 0.0001 vs both AT and healthy subjects), but with no difference between patients with or without GO. In patients with GO, there was an inverse correlation between serum IGF-1R-Abs and CAS (R = − 0.376, 95% CI: from − 0.373 to − 0.631; P = 0.005), the significance of which remains to be investigated.
Conclusions
Serum autoantibodies against the IFG-1R are present in one-fourth of GD patients, regardless of the presence of GO. Further functional studies are needed to investigate the significance of their inverse correlation with GO activity.
https://ift.tt/2nUEHT5
Effects of compost containing oxytetracycline on enzyme activities and microbial communities in maize rhizosphere soil
Abstract
Veterinary antibiotics can enter agricultural fields via the application of livestock manure containing antibiotics. However, the response of soil microorganisms to compost containing antibiotics is not well understood. A 120-day pot experiment was conducted to investigate the impact of compost containing oxytetracycline (OTC) on the enzyme activities and microbial communities in maize rhizosphere soil. Swine manure was artificially spiked with OTC at four concentrations, 35, 70, 105, and 140 mg kg−1, and combined with straw to produce compost. The compost products were applied to soil planted with maize. Rhizosphere soil samples were collected on days 1, 15, 30, 60, and 120. The results indicated that the urease activities first increased and then declined, while in contrast, the alkaline phosphatase activities first decreased and then increased slightly. Catalase exhibited dose-related activation during the maize growth period. At the end of the experiment, the soil enzyme activities were similar to their initial values, indicating that the soil enzymes showed a level of recovery. The carbon metabolic activity levels were higher in the soils with high OTC concentrations than in the control, whereas the Shannon diversity index was higher in the control soil. The results of principal component analysis (PCA) indicated that the application of compost containing OTC shifted the structure of the soil microbial community and negatively affected its stability. These results suggest that the compost containing OTC exerted selective pressure on enzyme activities and microbial communities in maize rhizosphere soil and decreased their resilience to antibiotic pollution.
https://ift.tt/2vX1OAu
Bullous erythroderma: novel association of pityriasis rubra pilaris with bullous pemphigoid
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2MsYAPK
The potential for constructed wetland mechanisms to treat alkaline bauxite residue leachate: carbonation and precipitate characterisation
Abstract
Leachates emanating from bauxite residue disposal areas are alkaline and require neutralisation prior to discharge. The use of passive technologies such as constructed wetlands has received increasing interest as possible treatments for alkaline leachates, including bauxite residues. Mechanisms proposed for wetland effectiveness have included calcite precipitation but it is not clear if such a pathway is feasible in the relatively low Ca residue leachates. Carbonation of Ca-spiked residue leachate treatments was conducted to observe rates of pH decrease and precipitate formation. For all treatments, carbonation effectively decreased pH to ca. 10.5 which remained stable following aeration. Decreases in Al content of 83–93% were also observed. Precipitates retrieved from carbonation experiments and from a constructed wetland trial were characterised using XRD, SEM, XPS and EDX. Calcium carbonates formed in Ca-spiked treatments and dawsonite precipitation occur in the absence of Ca. Rinsing of precipitates removes surface calcium indicating soluble forms adsorbed on precipitates. The results demonstrate that carbonation of bauxite residue leachate is an important component of passive treatments and neutralisation.
https://ift.tt/2OUyySh
A Phase III Study to Compare the Efficacy and Safety of Paclitaxel Versus Irinotecan in Patients with Metastatic or Recurrent Gastric Cancer Who Failed in First‐line Therapy (KCSG ST10‐01)
AbstractLessons Learned. Irinotecan could not be proven noninferior to paclitaxel as a second‐line treatment for patients with metastatic or recurrent gastric cancer.The failure to demonstrate noninferiority may have been a result of insufficient patient enrollment.Both agents were tolerable but showed different toxicity profiles.Background.This phase III study compared the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer (MRGC) who had experienced disease progression following first‐line chemotherapy.Methods.Patients were randomized to receive either paclitaxel (70 mg/m2; days 1, 8, 15, every 4 weeks) or irinotecan (150 mg/m2 every other week). The primary endpoint was progression‐free survival (PFS).Results.This study was stopped early due to low accrual rate. A total of 112 patients were enrolled; 54 were allocated to paclitaxel and 58 to irinotecan. Median PFS for the paclitaxel and irinotecan groups was 3.5 and 2.1 months, respectively (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.86–1.88; p = .234). Noninferiority of irinotecan to paclitaxel was not proved because the upper boundary of the 95% CI (1.88) exceeded the predefined upper margin of noninferiority (1.32). Median overall survival (OS) was 8.6 months in the paclitaxel group and 7.0 months in the irinotecan group (HR, 1.39; 95% CI, 0.91–2.11; p = .126). Among toxicities greater than or equal to grade 3, neutropenia (11.5%) was the most common, followed by peripheral neuropathy (7.7%) in the paclitaxel group, and neutropenia (34.5%) followed by nausea, vomiting, and anemia (8.6%, respectively) in the irinotecan group.Conclusion.Although paclitaxel showed numerically longer PFS and OS compared with irinotecan, this was statistically insignificant. Both irinotecan and paclitaxel are valid second‐line treatment options in MRGC.
https://ift.tt/2PmxR5j
Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib
AbstractBackground.Oncogenic KIT/PDGFRA signaling inhibition with imatinib achieves disease control in most patients with advanced/metastatic gastrointestinal stromal tumor (GIST), but resistance eventually develops after 20–24 months. Notably, a small subset of these patients obtain durable benefit from imatinib therapy.Methods.We analyzed clinical, pathological, and molecular characteristics and long‐term outcomes in patients with metastatic GIST treated with continuous daily dosing of frontline imatinib in a cohort of patients benefiting for ≥5 years. A control group was obtained from the national Spanish Group for Sarcoma Research database and used as comparator.Results.Sixty‐four imatinib long‐term responders (LTRs) and 70 control cases were identified. Compared with controls, LTRs at baseline had better performance status (PS) 0–1 (100% vs. 81%), lower mitotic count (median, 8 vs. 15), and tumor burden (number of metastases, 3 vs. 7). KIT exon 11 was the only region found mutated in LTRs. LTRs achieved 34% complete responses and a median progression‐free survival of 11 years, compared with 4% and 2 years, respectively, in the control cohort. Prognostic factors that independently predicted long‐term benefit with imatinib were PS, number of metastases prior to imatinib, and response to imatinib. Fifteen LTR patients developed new side effects attributable to imatinib after ≥5 years of continuous treatment. No resistance mutations were found in metastatic samples from three patients progressing on imatinib.Conclusion.GISTs in LTRs are a distinctive entity with less aggressive behavior and marked sensitivity to KIT inhibition. Patients reaching 5 or more years on imatinib have a higher chance of remaining progression free over time.Implications for Practice.This work demonstrates that clinical and inherent tumor characteristics define a subset of patients with gastrointestinal stromal tumor (GIST) with increased likelihood to achieve durable response to first‐line imatinib therapy. Patients reaching ≥5 years on imatinib have a greater chance of remaining progression free over time, although the disease is unlikely to be cured. Imatinib is well tolerated for >5 years, and emergent toxicities are overall manageable. Resistance to imatinib emerging in patients with GISTs after long‐term imatinib treatment does not involve polyclonal expansion of KIT secondary mutations.
https://ift.tt/2N4bDDz
Alerta Rosa: Novel Alert and Navigation Breast Cancer Program in Nuevo Leon, Mexico, for Reducing Health System Interval Delays
AbstractBackground.In Mexico, the median time between breast cancer (BC) symptom detection and treatment initiation is approximately 7 months. Alerta Rosa is a program that was developed with the intent of breaking down medical care barriers and reduce delays.Patients and Methods.Through several media campaigns, we reached out to patients with breast symptoms or abnormal imaging studies. Patients contacted our call center or Facebook page. A navigator recorded their main complaint and scheduled a medical consultation with a specialist. We prioritized patients according to clinical risk. Those diagnosed with BC were referred to their health affiliation unit for care.Results.To date, 656 patients have contacted our program. Median age was 44 years (range, 7–82). Patients reported becoming aware of Alerta Rosa mainly by word of mouth and TV. A total of 446 medical consultations were scheduled, and 309 patients attended their appointments. A biopsy procedure was solicited for 39 patients, and 22 were diagnosed with BC. Most patients had stage II (45%) or stage III (32%) disease. The median time from alert activation to treatment initiation was 33 days (range, 19–56) and from first medical evaluation to treatment initiation was 28 days (range, 16–48).Conclusion.In low‐ or middle‐income countries, where BC screening programs do not effectively reach the target population, it is crucial to focus efforts in identifying and prioritizing symptomatic patients or those with abnormal imaging studies to ultimately downstage BC. Alerta Rosa proved to be successful in reducing health system intervals and could be replicated and adapted for other limited resource settings.Implications for Practice.In countries such as Mexico, infrastructure and financial drawbacks limit the implementation of effective screening mammography programs. This article presents a novel and effective alternative to optimize resources and reduce health system intervals, so that patients in limited‐resource settings can have access to prompt quality care. This strategy for early breast cancer detection focused efforts in prioritizing symptomatic women and those with abnormal breast imaging studies. This article presents novel information that will be useful for the development of effective early breast cancer detection with a focus on opportunistic rather than population‐screening mammography in low‐resource settings.
https://ift.tt/2PqnJIz
Monitoring Serum VEGF in Neoadjuvant Chemotherapy for Patients with Triple‐Negative Breast Cancer: A New Strategy for Early Prediction of Treatment Response and Patient Survival
AbstractBackground.This study aimed to investigate the clinical utility of serum biomarker changes during neoadjuvant chemotherapy (NAC) for triple‐negative breast cancer (TNBC).Methods.A total of 303 patients with TNBC were included in this study. Serum samples were taken at three time points during NAC: baseline, prior to the third cycle, and prior to surgery. Luminex multibiomarker panel for 29 serum biomarkers was used to detect their correlation with NAC response. The predictive and prognostic value of each selected biomarker was then studied.Results.Vascular endothelial growth factor (VEGF) was the only biomarker that correlated with treatment response, with a decreasing trend in pCR patients relative to non‐pCR patients (p < .001). Univariable and multivariable analyses revealed that the relative change in VEGF prior to the third cycle of NAC had a remarkable predictive value for both pCR and pathological nonresponse with high sensitivity and specificity. VEGF was also independently correlated with disease‐free survival.Conclusion.Our findings indicate that monitoring serum VEGF could help identify patients with different responses at an early time point of NAC and at varying risk of disease relapse. Serum VEGF may also serve as an alternative to traditional response‐evaluating methodologies in tailoring and modifying the NAC strategy for both operable and advanced TNBCs.Implications for Practice.Neoadjuvant chemotherapy (NAC) followed by definitive surgery is a standard of care for locally advanced breast cancer. The identification of sensitive responders to neoadjuvant therapy is highly significant for breast cancer, especially triple‐negative breast cancer (TNBC). Results of this study indicate that the monitoring of serum vascular endothelial growth factor (VEGF) could identify patients with favorable or poor responses at an early time point of NAC. Furthermore, the prediction power of VEGF was better than traditional response‐evaluating methods. VEGF might serve as a complement or alternative to traditional imaging‐based response‐evaluating methodologies in tailoring systemic treatment strategies for both operable and advanced TNBCs.
https://ift.tt/2N4zJhj
A Phase II Trial of Sorafenib and Dacarbazine for Leiomyosarcoma, Synovial Sarcoma, and Malignant Peripheral Nerve Sheath Tumors
AbstractBackground.Sorafenib and dacarbazine have low single‐agent response rates in metastatic sarcomas. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of sorafenib and dacarbazine in select sarcoma subtypes.Materials and Methods.Patients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function received 3‐week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m2 intravenously (later reduced to 850 mg/m2). Patients were evaluated for response every 6 weeks. The primary objective was to determine the disease control rate (DCR) of sorafenib plus dacarbazine in the selected sarcoma subtypes.Results.The study included 37 patients (19 female); median age was 55 years (range 26–87); and histologies included LMS (22), SS (11), and MPNST (4). The DCR was 46% (17/37). Median progression‐free survival was 13.4 weeks. The RECIST response rate was 14% (5/37). The Choi response rate was 51% (19/37). Median overall survival was 13.2 months. Of the first 25 patients, 15 (60%) required dacarbazine dose reductions for hematologic toxicity, with one episode of grade 5 neutropenic fever. After reducing the starting dose of dacarbazine to 850 mg/m2, only 3 of the final 12 (25%) patients required dose reduction.Conclusion.This phase II study met its primary endpoint with an 18‐week DCR of 46%. The clinical activity of dacarbazine plus sorafenib in patients with these diagnoses is modest.Implications for Practice.Metastatic soft tissue sarcomas are a heterogeneous group of relatively rare malignancies. Most patients are treated with cytotoxic chemotherapy or targeted therapy in the form of tyrosine kinase inhibitors. Response rates are relatively low, and there is a need for better therapies. This clinical trial demonstrates that combining a cytotoxic therapy (dacarbazine) with an antiangiogenic small molecule (sorafenib) is feasible and associated with favorable disease‐control rates; however, it also increases the potential for significant toxicity.
https://ift.tt/2Pqo3af
Osimertinib for EGFR‐Mutant Lung Cancer with Brain Metastases: Results from a Single‐Center Retrospective Study
AbstractIntroduction.Osimertinib is a third‐generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non‐small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first‐line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone.Methods.Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups.Results.The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression‐free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5–11.8), 8.8 months (95% CI, 6.2–12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7–28.5), 7.7 months for group B (95% CI, 0–15.5), and 10.7 months for group C (95% CI, 9.0–12.5). The median PFS was 8.8 months for group A (95% CI, 4.3–13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6–11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups.Conclusion.Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation‐related toxicity, delaying radiation could be considered for some patients with EGFR‐mutant NSCLC with brain metastases who initially respond to osimertinib in the second‐line setting.Implications for Practice.Osimertinib is a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first‐line treatment of EGFR‐mutant non‐small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.
https://ift.tt/2N559nV
An integrated modelling framework and a modified method for evaluating non-carcinogenic health risks from nonylphenol-contaminated food consumption in Long An, Vietnam
Abstract
This study proposed an integrated modelling framework and a modified method for evaluating non-carcinogenic health risks from nonylphenol (NP)-contaminated food consumption. First, a fugacity-based multimedia model and a food web bioaccumulation model were adopted to predict the distribution of NP in the Can Giuoc river and the bioaccumulative concentrations in biota. Next, local people's exposure to NP was quantified using the accumulative concentrations and the data of fishery products intake from a questionnaire survey distributed among 203 local people. Then, human health risk was evaluated in terms of fishery products intake and intake frequency which were each derived from the same survey. The study revealed that human health risk would exist, although the obtained bioaccumulation factors for the consumed organisms were lower than the bioaccumulation criteria. Consuming 141 g or more per serving of riverine food products resulted in an average NP intake exceeding 0.005 mg/kg of body weight per day among 45–73% of the local adults, of whom pregnant women or young and potential mothers accounted for 10–21%. Seventy-nine percent was the highest rate of the population to be at risk under medium river flow rate when food-intake amount and intake frequency were taken into account. Ingesting 70 g per serving of more contaminated species, such as whiteleg shrimp and small fish, less frequently could lead to less risk exposure than ingesting 267 g per serving of less contaminated species, such as sand goby and climbing pearch, more frequently. By coupling food intake with intake frequency, the modified method enables the studying of human health risk from NP-contaminated food consumption to be conducted with more care, and so benefits risk communication at local level.
https://ift.tt/2vZFTZA
A cost compensation model for construction and demolition waste disposal in South China
Abstract
Construction and demolition waste (C&D waste) is a worldwide issue that concerns the sustainable development of the construction industry. In this paper, detailed formulas are listed for calculating the costs of four typical kinds of disposal routes of C&D waste. They are illegal dumping, controlled dumping (landfill), centralized recycling, and on-site recycling. Through the specific formulas, the costs of the new construction project in Guangzhou are also estimated. Then, a cost compensation model of construction waste disposal is constructed, which serves to calculate the amount of compensation that the government shall make to the contractor's disposal cost. The results of this study include the following: (1) steps taken to ensure the appropriate measures for C&D waste disposal sites and recycling centers; (2) the on-site recycling will become the future trend of C&D waste disposal due to its lowest cost; (3) the brick cement mortar and scattered concrete take a relatively larger proportion in the total C&D waste generated during the new construction project, and their disposal costs are higher; (4) we find that the cost of illegal dumping is the lowest among four varieties of waste treatment options if only the direct cost of waste treatment is taken account. However, the cost of on-site recycling becomes the lowest if the total cost is considered; (5) according to the case study, the full estimated cost of construction waste disposal is 9074.56 CNY and the total cost compensation is 15,084.21 CNY. The amount of compensation is greater than the disposal cost and contractors make a profit, thus stimulating them to recycle and reuse construction waste. Based on the empirical findings, we make several policy proposals. The research puts forward some operational advice as a reference for decision-makers of C&D waste management.
https://ift.tt/2OQYDBv
Assessing the utility of preoperative serum thyroglobulin in differentiated thyroid cancer: a retrospective cohort study
Abstract
Purpose
Serum thyroglobulin (TG) is used to monitor for recurrence or progression of differentiated thyroid cancer (DTC). The role of preoperative TG measurement is more ambiguous, yet still being used in some centers. We aimed to determine whether preoperative TG correlates with disease stage or metastatic burden.
Methods
A retrospective review of patients with TG measured before thyroidectomy was conducted. Data collected included demographics, preoperative TG, pathology, and cancer stage. Associations between preoperative TG levels and size of largest malignant nodule, thyroid gland size, stage of cancer, and presence of metastasis using Wilcoxon rank sum tests and Spearman correlations were performed. Receiver operator curve (ROC) was generated for metastasis status.
Results
Of 598 patients, we excluded those with positive TG antibodies (n = 176); 422 patients were included in the final analysis. Median age was 55 years and 76% were female. Of 78% with malignancy, papillary thyroid cancer was the most frequent (92%). 18% had TG levels >500 ng/mL and 29% <45 ng/mL. 4% had distant metastasis and 18% had lymph node metastasis. Median follow-up was 52 months. Significant positive correlations between preoperative TG and thyroid size (rho 0.49, p < 0.001), and malignant nodule size (rho 0.27, p < 0.001). Using a cut-off of 500 ng/mL, sensitivity to detect metastasis was 10.3% (95% CI 2.5–18.2), specificity 90.0% (95% CI 86.0–93.9). The area under curve for ROC (0.46, 95% CI 0.38–0.54) indicated poor diagnostic ability for metastasis.
Conclusion
Although preoperative TG correlated significantly with the size of the gland and T stage, there was no correlation with metastasis. Preoperative TG is of limited utility in today's value-based healthcare environment.
https://ift.tt/2N4ksgD
More sugar? No, thank you! The elusive nature of low carbohydrate diets
Abstract
In the past decades, dietary guidelines focused on reducing saturated fat as the primary strategy for cardiovascular disease prevention, neglecting the many other potential effects of diet on health, in particular the harmful effects of sugar. A greater intake of soft drinks (sugar-sweetened beverages), for example, is associated with a 44% increased prevalence of metabolic syndrome, a higher risk of obesity, and a 26% increased risk of developing diabetes mellitus. Carbohydrates comprise around 55% of the typical western diet, ranging from 200 to 350 g/day in relation to a person's overall caloric intake. For long-term weight gain, food rich in refined grains, starches, and sugar appear to be major culprits. Low-carbohydrate diets restrict daily carbohydrates between 20 and 50 g, as in clinical ketogenic diets. The results of controlled trials show that people on ketogenic diets (a diet with no more than 50 g carbohydrates/day) tend to lose more weight than people on low-fat diets. Moreover, there is no good evidence for recommending low-fat diets, as low-carbohydrate diets lead to significantly greater weight loss (1.15 kg) than did low-fat interventions. However, the magnitude of such a benefit is small. As the quality of ingested carbohydrates seems more important than the quantity for health outcomes, people with metabolic disorders should avoid or substantially reduce low-fiber, rapidly digested, refined grains, starches, and added sugars. So, the consumption of the right carbohydrates (high-fiber, slowly digested, and whole grains), in a moderately lower amount (between 40 and 50% of daily energy content), is compatible with a state of good health and may represent a scientifically-based and palatable choice for people with metabolic disorders.
https://ift.tt/2N418jz
Serum calcitonin gene-related peptide facilitates adipose tissue lipolysis during exercise via PIPLC/IP3 pathways
Abstract
Purpose
Calcitonin gene-related peptide (CGRP) is formed by alternative transcription of the calcitonin/α-CGRP gene, which also gives rise to calcitonin (CT). Recently, CGRP has been the focus of research for its metabolic effects in vitro. In the present study, the in vivo effects of CGRP on epididymal fat pads lipolysis at rest and during exercise were investigated in trained male Wistar rats.
Methods
Male Wistar rats were assigned to control and trained groups, which underwent endurance training for 12 weeks. The control (at rest) and trained (during acute exercise) animals were subjected to an intravenous injection of rat recombinant CGRP (2 µg kg−1) and CGRP-(8–37), a competitive CGRP receptors antagonist, to evaluate if and how CGRP can affect adipose tissue lipolysis at rest and during exercise.
Results
Intravenous injection of rat CGRP recombinant at rest upregulated major lipolysis pathways (cyclic AMP (cAMP), AMP-activated protein kinase (AMPK), and phospholipase C (PIPLC/IP3)) in fat pads, causing an elevation in plasma-free fatty acid (FFA) and a decrease in plasma triglyceride (TG). All the effects were eliminated by pretreating the animals with CGRP-(8–37), suggesting that CGRP receptors were necessary for lipolytic effects of CGRP in fat pads. In trained animals, acute exercise augmented CGRP in serum, cerebrospinal fluid (CSF), and the cortex. Pretreating the animals with CGRP-(8–37) attenuated PIPLC/IP3 pathway in fat pads and had no effect on cAMP and AMPK pathways.
Conclusions
Epididymal fat pads is a metabolic target for CGRP during exercise and CGRP effects on adipose tissue metabolism during exercise could be related to PIPLC/IP3 pathway.
https://ift.tt/2PnJ71d
Does the ACR TI-RADS scoring allow us to safely avoid unnecessary thyroid biopsy? single center analysis in a large cohort
Abstract
Introduction
The American College of Radiology (ACR) has recently proposed a guideline that recommends clinicians to perform thyroid fine-needle aspiration biopsy (FNAB) on the basis of ultrasound features. In this study, we focused on nodules for which no biopsy is recommended by the ACR Thyroid Imaging, Reporting and Data System (TI-RADS) guideline.
Subjects and methods
Two-thousand eight-hundred and forty-seven consecutive patients with thyroid nodules who underwent FNAB according to the 2009 American Thyroid Association (ATA) guideline were included. The nodules were re-classified according to the ACR TI-RADS guideline as benign (TR1), not suspicious (TR2), mildly suspicious (TR3), moderately suspicious (TR4) and highly suspicious (TR5). The TR3 category was stratified into two subcategories as regard to the nodule size (TR3; <25 mm and TR3; ≥25 mm).
Results
Two-hundred and thirty-three (8.2%) patients with non-diagnostic FNABs were excluded. When the TR2 and TR3; <25 mm categories were merged, FNAB was suggestive of thyroid cancer in 17 of 1382 patients (1.2%). FNAB revealed Bethesda IV–VI in 5 of 273 patients with the TR3; ≥25 mm category (1.8%), in 61 of 896 patients with the TR4 category (6.8%), and in 18 of 63 of patients with the TR5 category (28.6%). The ACR TI-RADS scoring was 98.8% (95% CI: 98 to 99.3) specific for identification of a benign nodule.
Conclusion
Our data suggest that ACR TI-RADS scoring is an applicable and potentially cost-effective approach to determine thyroid nodules to be biopsied, although a small proportion of thyroid cancers would be missed.
https://ift.tt/2BA2gtI
Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis
Abstract
Background
Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years.
Methods
All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988–2013). Kaplan–Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression.
Results
There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01).
Conclusion
In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.
https://ift.tt/2N83jTm
TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma
Abstract
Purpose
Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined.
Methods
Analysis of the presence of TERTp (−124C > T and −146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes.
Results
Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5–360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression.
Conclusions
TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.
https://ift.tt/2MFXgYQ
Lack of functional remission in Cushing’s syndrome
Abstract
Introduction
Hypercortisolism leads to severe clinical consequences persisting after the onset of remission. These physical sequelae of cortisol exposure are known to profoundly impact the patient's quality of life. As psychological factors may be correlated with this quality of life, our objective was to determine the specific weight of psychological determinants of quality of life in patients in remission from hypercortisolism.
Patients and methods
In an observational study, 63 patients with hypercortisolism in remission were asked to complete exhaustive self-administered questionnaires including quality of life (WHOQoL-BREF and Cushing QoL), depression, anxiety, self-esteem, body image, and coping scales. Multivariate analyses were performed. Psychological variables relevant to the model were: anxiety, depression, self-esteem, body image, and positive thinking dimension of the Brief-COPE. Cortisol deficiency was defined as a potential confounder.
Results
The median time since remission was 3 years. Patients had significantly lower quality of life and body satisfaction score than the French population and patients with chronic diseases. Depression significantly impaired all WHOQoL and Cushing QoL domains. A low body satisfaction score significantly impaired social relationships quality of life score. In total, 42.9% of patients still needed working arrangements, 19% had disability or cessation of work.
Conclusion
Patients in biological remission of hypercortisolism can rarely be considered as functionally cured: this is evidenced by altered quality of life, working arrangements, and chronic depression. A multidisciplinary management of these patients is thus mandatory on a long-term basis.
https://ift.tt/2BFhpdF
The posterior pharyngeal wall thickness is associated with OSAHS in patients with acromegaly and correlates with IGF-1 levels
Abstract
Purpose
To evaluate the incidence of obstructive sleep apnea-hypopnea syndrome (OSAHS), explore the structural changes in pharyngeal soft tissue underlying OSAHS development and analyze the correlation between hormone levels and pharyngeal soft tissue changes in patients with untreated acromegaly.
Methods
Twenty-five patients with untreated acromegaly were prospectively enrolled. Pituitary hormones were tested, sellar magnetic resonance imaging was confirmed, overnight polysomnography was conducted, and upper airway computed tomography was performed on these patients.
Results
Patients with untreated acromegaly had a high incidence of OSAHS (52.0%, 13/25). The average age of the patients with OSAHS was 12 years older than that of patients without OSAHS (47.0 ± 8.5 years vs. 35.1 ± 9.5 years, p = 0.003). The posterior pharyngeal soft tissues were thicker in four different planes, including the planes of the soft palate, uvula, tongue and epiglottis (p = 0.003, 0.008, 0.027, and 0.003, respectively), and the soft palate (p = 0.024) was more hypertrophic in patients with acromegaly presenting with OSAHS than patients without OSAHS. The posterior pharyngeal wall thickness (cm) positively correlated with the serum insulin-like growth factor 1 (IGF-1) level (ng/ml) in the planes of the soft palate (slope = 0.001, p = 0.006) and epiglottis (slope = 0.002, p = 0.039).
Conclusions
OSAHS is a common complication in patients with untreated acromegaly, and advanced age is a risk factor. Posterior pharyngeal soft tissue thickening and soft palate hypertrophy are structural changes underlying OSAHS development in patients with acromegaly. Higher IGF-1 levels predict an increase in the posterior pharyngeal soft tissue thickness in patients with acromegaly.
https://ift.tt/2N1v9QN
Incidence and management of postoperative hyperglycemia in patients undergoing insulinoma resection
Abstract
Purpose
It has been proposed that rebound hyperglycemia after resection of insulinoma indicates a biochemical cure. However, there is scant objective data in the literature on the rate and need for intervention in hyperglycemia in patients undergoing resection of insulinoma. The goal of our study was to evaluate the rate of postoperative hyperglycemia, any predisposing factors, and the need for intervention in a prospective cohort study of all patients undergoing routine glucose monitoring.
Methods
A retrospective analysis of 33 patients who had an insulinoma resected and who underwent routine postoperative monitoring of blood glucose (every hour for the first six hours then every four hours for the first 24 h) was performed. Hyperglycemia was defined as glucose greater than 180 mg/dL (10 mmol/l).
Results
Twelve patients (36%) developed hyperglycemia within 24 h (range 1–16 h). In patients with hyperglycemia, the mean maximum plasma glucose level was 221.5 mg/dL (range 97–325 mg/dL) (12.3 mmol/l), and four (33%) patients were treated with insulin. There was no significant difference in age, gender, body mass index (BMI), tumor size, biochemical profile, or surgical approach and extent of pancreatectomy between patients who developed hyperglycemia and those who did not. Pre-excision and post-excision intraoperative insulin levels were evaluated in 14 of 33 patients. The percentage decrease of the intraoperative insulin levels was not significantly different between patients who developed hyperglycemia and those who did not. All patients with postoperative hyperglycemia had normalization of their glucose levels, and none were discharged on anti-hyperglycemic agents.
Conclusions
Hyperglycemia is common after insulinoma resection, and a subset of patients require transient treatment with insulin.
https://ift.tt/2N1WJgU
Patients’ knowledge about the outcomes of thyroid biopsy: a patient survey
Abstract
Purpose
Fine-needle aspiration biopsy of the thyroid is an increasingly common outpatient procedure. Patients are counseled about the indications and risks of this procedure and informed consent is obtained. We aimed to assess the extent to which patients acquired necessary knowledge during this process.
Methods
Survey study conducted in a thyroid nodule clinic at a referral center. Adult patients who had just undergone a thyroid biopsy were asked to complete a survey, including eight questions regarding the indications and potential outcomes of thyroid biopsy. The main outcome of the study was to assess the patients' knowledge based on the response to each individual survey question.
Results
Two-hundred and ninety-seven patients were eligible, of which 196 (66%) completed the survey: most were women (76%), had adequate reading health literacy (95%) and a mean age of 58 years. Although 86% of patients correctly identified evaluation for thyroid cancer as the main indication for their biopsy, 56% were not aware of the likelihood of this diagnosis. Almost all (>90%) of respondents knew that results could be benign or malignant; fewer were aware of non-diagnostic (71%) or indeterminate (68%) outcomes, or of the need for additional diagnostic testing after the biopsy (33%).
Conclusions
After undergoing thyroid biopsy, a high proportion of well-educated patients remained unaware of their risk for thyroid cancer, potential outcomes, and downstream consequences of their biopsy. This quality gap raises the possibility that informed consent procedures that meet legal standards may leave patients undergoing thyroid biopsy paradoxically uninformed.
https://ift.tt/2MqQKWU
Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database
Abstract
Purpose
Epidemiological data are pivotal for the estimation of disease burden in populations.
Aim
Of the study was to estimate the incidence and prevalence of acromegaly in Italy along with the impact of comorbidities and hospitalization rates as compared to the general population.
Methods
Retrospective epidemiological study (from 2000 to 2014) and case control-study. Data were extracted from the Health Search Database (HSD). HSD contains patient records from about 1000 general practitioners (GPs) throughout Italy, covering a population of more than 1 million patients. It includes information about patient demographics and medical data including clinical diagnoses and diagnostic tests.
Results
At the end of the study period, 74 acromegaly patients (out of 1,066,871 people) were identified, resulting in a prevalence of 6.9 per 100,000 inhabitants [95% CI 5.4–8.5]. Prevalence was higher in females than men (p = 0.004), and showed a statistically significant trend of increase over time (p < 0.0001). Overall, incidence during the study period was 0.31 per 100,000 person-years. Hypertension and type II diabetes mellitus were the comorbidities more frequently associated with acromegaly (31.3 and 14.6%, respectively) and patients were more likely to undergo a high frequency of yearly hospitalization (≥3 accesses/year, p < 0.001) compared to sex-age matched controls.
Conclusions
This epidemiological study on acromegaly carried out using a large GP-based database, documented a disease prevalence of about 7 cases per 100,000 inhabitants. As expected, acromegaly was associated with a number of comorbidities (mainly hypertension and type II diabetes mellitus) and a high rate of patients' hospitalization.
https://ift.tt/2whcgCn
Role of the ubiquitin/proteasome system on ACTH turnover in rat corticotropes
Abstract
Purpose
A large number of studies has investigated proopiomelanocortin processing in anterior pituitary corticotropes but little is known on proopiomelanocortin/ACTH degradation within these cells. The ubiquitin-proteasome system is an intracellular protein degradation pathway which has garnered considerable interest in recent times, given its role in maintenance of protein homeostasis. Aim of the present study was to evaluate the role of the ubiquitin-proteasome system in proopiomelanocortin/ACTH turnover in pituitary corticotropes.
Methods
Rat anterior pituitary primary cultures were treated with 0.01–100 nM MG132, a proteasome inhibitor, or 0.1–100 nM K48R, an inhibitor of polyubiquitylation, for 4 and 24 h and ACTH concentrations in medium and cell lysates estimated by immunometric assay. Co-immunoprecipitation for ubiquitin and ACTH was carried out to establish ubiquitin-tagged protein products.
Results
Inhibition of proteasome-mediated degradation with MG132 lead to an increase in ACTH concentrations, both as regards secretion and cell content. Likewise, inhibition of polyubiquitylation was associated with increased ACTH secretion and cell content. Ubiquitin/ACTH co-immunoprecipitation revealed that proopiomelanocortin was a target of ubiquitylation.
Conclusions
We provide the first evidence that the ubiquitin-proteasome system is involved in proopiomelanocortin/ACTH degradation in corticotropes. Indeed, proopiomelanocortin is a target of ubiquitylation and modulation of ubiquitin-proteasome system affects ACTH turnover. This study shows that regulation of ACTH proteolytic degradation may represent a means to control ACTH secretion.
https://ift.tt/2PqkiS2
Giant pituitary adenoma: histological types, clinical features and therapeutic approaches
Abstract
Giant pituitary adenomas comprise about 6–10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.
https://ift.tt/2wb1PjM
A phase I trial of topotecan plus tivantinib in patients with advanced solid tumors
Abstract
Purpose
Tyrosine kinase inhibitors (TKI) that target MET signaling have shown promise in various types of cancer, including lung cancer. Combination strategies have been proposed and developed to increase their therapeutic index. Based on preclinical synergy between inhibition of MET and topoisomerase I, a phase I study was designed to explore the combination of topotecan with the MET TKI tivantinib.
Methods
Eligible patients with advanced solid malignancies for which there was no known effective treatment received topotecan at doses of 1.0–1.5 mg/m2/day for five consecutive days in 21-day cycles with continuous, oral tivantinib given at escalating doses of 120–360 mg orally twice daily. Pharmacokinetic analyses of tivantinib were included. Circulating tumor cells (CTC) were collected serially to identify peripheral changes in MET phosphorylation.
Results
The trial included 18 patients, 17 of whom received treatment. At the planned doses, the combination of topotecan and tivantinib was not tolerable due to thrombocytopenia and neutropenia. The addition of G-CSF to attenuate neutropenia did not improve tolerability. Greater tivantinib exposure, assessed through pharmacokinetic analysis, was associated with greater toxicity. No responses were seen. MET phosphorylation was feasible in CTC, but no changes were seen with therapy.
Conclusions
The combination of topotecan and oral tivantinib was not tolerable in this patient population.
https://ift.tt/2L9xaJf
Analyzing the significant environmental factors on the spatial and temporal distribution of water quality utilizing multivariate statistical techniques: a case study in the Balihe Lake, China
Abstract
The assessment of surface water quality is significant to the management of aquatic ecosystem. In this research, in Balihe Lake which is an agricultural watershed lake, 11 environmental parameters (pH, water temperature, water depth, turbidity, DO, COD, TN, NH4+-N, NO3−-N, TP, Chl-a) are monitored at 45 sampling sites in four seasons (winter of 2016, spring, summer, and autumn of 2017). With these monitoring data, two kinds of multivariate statistical methods including cluster analysis (CA) and principal component analysis (PCA) are applied to evaluate the spatial and temporal characteristics of the surface water quality. The results reveal that the spatial clusters (less, moderately, and highly polluted sections) of 45 sampling sites classified by the CA method are exactly consistent with the geographical distribution of these sampling sites, which rely on water quality meliorating downstream. From the perspective of time scale, the correlations between environmental parameters generated by the PCA method reveal that the main factors affecting the surface water quality are different in the four seasons. For the whole study period, which is a longer time scale rather than season, the main factors are also different to that of any season. Large time scale may weaken the effect and potential risk of nutrients on water quality, and it is therefore reasonable to select seasonal scale for the study of water quality in an agricultural watershed by using PCA. The results of this research may demonstrate significance to the identification of the main pollution factors and water quality assessment in freshwater lake with multivariate statistical methods.
https://ift.tt/2PqRlFQ
Effect of vitamin A and vitamin C on attenuation of ivermectin-induced toxicity in male Wistar rats
Abstract
An in vivo study was performed to assay the effects of ivermectin on adult male Wistar rats. Twenty-five male Wistar rats aged 6 to 8 weeks and weighing 150–250 g were divided into five groups of five animals each for the purpose of this study. The groups received ivermectin; a mixture of ivermectin and vitamin A; a mixture of ivermectin and vitamin C; and a mixture of ivermectin, vitamin A, and vitamin C, respectively. One group served as the control group and was treated with double-distilled water. The treatment was carried out once a week for 3 weeks. The results of the study revealed that the animals were less affected as detected by slight changes in the body weight, stress oxidative parameters, serum levels of liver enzymes, kidney function indexes, cell blood counts, and sperm analysis upon exposure to ivermectin. Nevertheless, the use of vitamins A and C might have a promising effect against oxidant-antioxidant imbalance. Although, the administration of free ivermectin has fewer reactions on mammals, use of the drug supplemented with antioxidants such as vitamins A and C moderates its effects.
https://ift.tt/2N0zC6n
Assessing the utility of preoperative serum thyroglobulin in differentiated thyroid cancer: a retrospective cohort study
Abstract
Purpose
Serum thyroglobulin (TG) is used to monitor for recurrence or progression of differentiated thyroid cancer (DTC). The role of preoperative TG measurement is more ambiguous, yet still being used in some centers. We aimed to determine whether preoperative TG correlates with disease stage or metastatic burden.
Methods
A retrospective review of patients with TG measured before thyroidectomy was conducted. Data collected included demographics, preoperative TG, pathology, and cancer stage. Associations between preoperative TG levels and size of largest malignant nodule, thyroid gland size, stage of cancer, and presence of metastasis using Wilcoxon rank sum tests and Spearman correlations were performed. Receiver operator curve (ROC) was generated for metastasis status.
Results
Of 598 patients, we excluded those with positive TG antibodies (n = 176); 422 patients were included in the final analysis. Median age was 55 years and 76% were female. Of 78% with malignancy, papillary thyroid cancer was the most frequent (92%). 18% had TG levels >500 ng/mL and 29% <45 ng/mL. 4% had distant metastasis and 18% had lymph node metastasis. Median follow-up was 52 months. Significant positive correlations between preoperative TG and thyroid size (rho 0.49, p < 0.001), and malignant nodule size (rho 0.27, p < 0.001). Using a cut-off of 500 ng/mL, sensitivity to detect metastasis was 10.3% (95% CI 2.5–18.2), specificity 90.0% (95% CI 86.0–93.9). The area under curve for ROC (0.46, 95% CI 0.38–0.54) indicated poor diagnostic ability for metastasis.
Conclusion
Although preoperative TG correlated significantly with the size of the gland and T stage, there was no correlation with metastasis. Preoperative TG is of limited utility in today's value-based healthcare environment.
https://ift.tt/2N4ksgD
More sugar? No, thank you! The elusive nature of low carbohydrate diets
Abstract
In the past decades, dietary guidelines focused on reducing saturated fat as the primary strategy for cardiovascular disease prevention, neglecting the many other potential effects of diet on health, in particular the harmful effects of sugar. A greater intake of soft drinks (sugar-sweetened beverages), for example, is associated with a 44% increased prevalence of metabolic syndrome, a higher risk of obesity, and a 26% increased risk of developing diabetes mellitus. Carbohydrates comprise around 55% of the typical western diet, ranging from 200 to 350 g/day in relation to a person's overall caloric intake. For long-term weight gain, food rich in refined grains, starches, and sugar appear to be major culprits. Low-carbohydrate diets restrict daily carbohydrates between 20 and 50 g, as in clinical ketogenic diets. The results of controlled trials show that people on ketogenic diets (a diet with no more than 50 g carbohydrates/day) tend to lose more weight than people on low-fat diets. Moreover, there is no good evidence for recommending low-fat diets, as low-carbohydrate diets lead to significantly greater weight loss (1.15 kg) than did low-fat interventions. However, the magnitude of such a benefit is small. As the quality of ingested carbohydrates seems more important than the quantity for health outcomes, people with metabolic disorders should avoid or substantially reduce low-fiber, rapidly digested, refined grains, starches, and added sugars. So, the consumption of the right carbohydrates (high-fiber, slowly digested, and whole grains), in a moderately lower amount (between 40 and 50% of daily energy content), is compatible with a state of good health and may represent a scientifically-based and palatable choice for people with metabolic disorders.
https://ift.tt/2N418jz
Serum calcitonin gene-related peptide facilitates adipose tissue lipolysis during exercise via PIPLC/IP3 pathways
Abstract
Purpose
Calcitonin gene-related peptide (CGRP) is formed by alternative transcription of the calcitonin/α-CGRP gene, which also gives rise to calcitonin (CT). Recently, CGRP has been the focus of research for its metabolic effects in vitro. In the present study, the in vivo effects of CGRP on epididymal fat pads lipolysis at rest and during exercise were investigated in trained male Wistar rats.
Methods
Male Wistar rats were assigned to control and trained groups, which underwent endurance training for 12 weeks. The control (at rest) and trained (during acute exercise) animals were subjected to an intravenous injection of rat recombinant CGRP (2 µg kg−1) and CGRP-(8–37), a competitive CGRP receptors antagonist, to evaluate if and how CGRP can affect adipose tissue lipolysis at rest and during exercise.
Results
Intravenous injection of rat CGRP recombinant at rest upregulated major lipolysis pathways (cyclic AMP (cAMP), AMP-activated protein kinase (AMPK), and phospholipase C (PIPLC/IP3)) in fat pads, causing an elevation in plasma-free fatty acid (FFA) and a decrease in plasma triglyceride (TG). All the effects were eliminated by pretreating the animals with CGRP-(8–37), suggesting that CGRP receptors were necessary for lipolytic effects of CGRP in fat pads. In trained animals, acute exercise augmented CGRP in serum, cerebrospinal fluid (CSF), and the cortex. Pretreating the animals with CGRP-(8–37) attenuated PIPLC/IP3 pathway in fat pads and had no effect on cAMP and AMPK pathways.
Conclusions
Epididymal fat pads is a metabolic target for CGRP during exercise and CGRP effects on adipose tissue metabolism during exercise could be related to PIPLC/IP3 pathway.
https://ift.tt/2PnJ71d
Does the ACR TI-RADS scoring allow us to safely avoid unnecessary thyroid biopsy? single center analysis in a large cohort
Abstract
Introduction
The American College of Radiology (ACR) has recently proposed a guideline that recommends clinicians to perform thyroid fine-needle aspiration biopsy (FNAB) on the basis of ultrasound features. In this study, we focused on nodules for which no biopsy is recommended by the ACR Thyroid Imaging, Reporting and Data System (TI-RADS) guideline.
Subjects and methods
Two-thousand eight-hundred and forty-seven consecutive patients with thyroid nodules who underwent FNAB according to the 2009 American Thyroid Association (ATA) guideline were included. The nodules were re-classified according to the ACR TI-RADS guideline as benign (TR1), not suspicious (TR2), mildly suspicious (TR3), moderately suspicious (TR4) and highly suspicious (TR5). The TR3 category was stratified into two subcategories as regard to the nodule size (TR3; <25 mm and TR3; ≥25 mm).
Results
Two-hundred and thirty-three (8.2%) patients with non-diagnostic FNABs were excluded. When the TR2 and TR3; <25 mm categories were merged, FNAB was suggestive of thyroid cancer in 17 of 1382 patients (1.2%). FNAB revealed Bethesda IV–VI in 5 of 273 patients with the TR3; ≥25 mm category (1.8%), in 61 of 896 patients with the TR4 category (6.8%), and in 18 of 63 of patients with the TR5 category (28.6%). The ACR TI-RADS scoring was 98.8% (95% CI: 98 to 99.3) specific for identification of a benign nodule.
Conclusion
Our data suggest that ACR TI-RADS scoring is an applicable and potentially cost-effective approach to determine thyroid nodules to be biopsied, although a small proportion of thyroid cancers would be missed.
https://ift.tt/2BA2gtI
Novel mutation of PPOX gene in a patient with abdominal pain and syndrome of inappropriate antidiuresis
Abstract
Purpose
Acute porphyrias are metabolic disorders of heme biosynthesis characterized by acute life-threatening attacks. The diagnosis is often missed since clinical presentation is aspecific mimicking other medical and surgical conditions. Variegate porphyria (VP) is an autosomal dominant inherited disease with incomplete penetrance due to decreased activity of the Protoporphyrinogen Oxydase (PPOX) gene; most VP mutations are family specific. We report the case of a 40 year-old woman who presented many times to the emergency department complaining of unexplained abdominal pain and laboratory investigations showed repeatedly hyponatremia. Syndrome of inappropriate antidiuresis (SIAD) was confirmed and measurement of urine porphobilinogen and delta-aminolevulinic acid disclosed the diagnosis of acute porphyria. The genetic analysis of PPOX gene was performed.
Methods
The entire coding sequence and exon/intron boundaries of PPOX gene were amplified in 5 different Polymerase Chain Reaction (PCR) fragments. In silico prediction of the pathogenicity of the mutation was determined by using different tools, Polyphen2, SNPs&GO, SNPs3D.
Results
The genetic analysis of PPOX gene revealed a novel missense variant c.1376 G > A (p.Cys459Tyr) in heterozygous state. The same variant was later found in one of her cousins with skin lesions and other three younger asymptomatic relatives. We provided evidence that this novel mutation is likely to be pathogenetic.
Conclusions
Our case highlights the importance of considering VP in the differential diagnosis of SIAD and underlines the role of genetic screening in the management of such patients. The finding of a novel mutation of PPOX gene in our index case has allowed to recognize an affected family.
https://ift.tt/2FxjtVr
Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis
Abstract
Background
Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years.
Methods
All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988–2013). Kaplan–Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression.
Results
There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01).
Conclusion
In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.
https://ift.tt/2N83jTm
TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma
Abstract
Purpose
Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined.
Methods
Analysis of the presence of TERTp (−124C > T and −146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes.
Results
Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5–360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression.
Conclusions
TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.
https://ift.tt/2MFXgYQ
Lack of functional remission in Cushing’s syndrome
Abstract
Introduction
Hypercortisolism leads to severe clinical consequences persisting after the onset of remission. These physical sequelae of cortisol exposure are known to profoundly impact the patient's quality of life. As psychological factors may be correlated with this quality of life, our objective was to determine the specific weight of psychological determinants of quality of life in patients in remission from hypercortisolism.
Patients and methods
In an observational study, 63 patients with hypercortisolism in remission were asked to complete exhaustive self-administered questionnaires including quality of life (WHOQoL-BREF and Cushing QoL), depression, anxiety, self-esteem, body image, and coping scales. Multivariate analyses were performed. Psychological variables relevant to the model were: anxiety, depression, self-esteem, body image, and positive thinking dimension of the Brief-COPE. Cortisol deficiency was defined as a potential confounder.
Results
The median time since remission was 3 years. Patients had significantly lower quality of life and body satisfaction score than the French population and patients with chronic diseases. Depression significantly impaired all WHOQoL and Cushing QoL domains. A low body satisfaction score significantly impaired social relationships quality of life score. In total, 42.9% of patients still needed working arrangements, 19% had disability or cessation of work.
Conclusion
Patients in biological remission of hypercortisolism can rarely be considered as functionally cured: this is evidenced by altered quality of life, working arrangements, and chronic depression. A multidisciplinary management of these patients is thus mandatory on a long-term basis.
https://ift.tt/2BFhpdF
The posterior pharyngeal wall thickness is associated with OSAHS in patients with acromegaly and correlates with IGF-1 levels
Abstract
Purpose
To evaluate the incidence of obstructive sleep apnea-hypopnea syndrome (OSAHS), explore the structural changes in pharyngeal soft tissue underlying OSAHS development and analyze the correlation between hormone levels and pharyngeal soft tissue changes in patients with untreated acromegaly.
Methods
Twenty-five patients with untreated acromegaly were prospectively enrolled. Pituitary hormones were tested, sellar magnetic resonance imaging was confirmed, overnight polysomnography was conducted, and upper airway computed tomography was performed on these patients.
Results
Patients with untreated acromegaly had a high incidence of OSAHS (52.0%, 13/25). The average age of the patients with OSAHS was 12 years older than that of patients without OSAHS (47.0 ± 8.5 years vs. 35.1 ± 9.5 years, p = 0.003). The posterior pharyngeal soft tissues were thicker in four different planes, including the planes of the soft palate, uvula, tongue and epiglottis (p = 0.003, 0.008, 0.027, and 0.003, respectively), and the soft palate (p = 0.024) was more hypertrophic in patients with acromegaly presenting with OSAHS than patients without OSAHS. The posterior pharyngeal wall thickness (cm) positively correlated with the serum insulin-like growth factor 1 (IGF-1) level (ng/ml) in the planes of the soft palate (slope = 0.001, p = 0.006) and epiglottis (slope = 0.002, p = 0.039).
Conclusions
OSAHS is a common complication in patients with untreated acromegaly, and advanced age is a risk factor. Posterior pharyngeal soft tissue thickening and soft palate hypertrophy are structural changes underlying OSAHS development in patients with acromegaly. Higher IGF-1 levels predict an increase in the posterior pharyngeal soft tissue thickness in patients with acromegaly.
https://ift.tt/2N1v9QN
Incidence and management of postoperative hyperglycemia in patients undergoing insulinoma resection
Abstract
Purpose
It has been proposed that rebound hyperglycemia after resection of insulinoma indicates a biochemical cure. However, there is scant objective data in the literature on the rate and need for intervention in hyperglycemia in patients undergoing resection of insulinoma. The goal of our study was to evaluate the rate of postoperative hyperglycemia, any predisposing factors, and the need for intervention in a prospective cohort study of all patients undergoing routine glucose monitoring.
Methods
A retrospective analysis of 33 patients who had an insulinoma resected and who underwent routine postoperative monitoring of blood glucose (every hour for the first six hours then every four hours for the first 24 h) was performed. Hyperglycemia was defined as glucose greater than 180 mg/dL (10 mmol/l).
Results
Twelve patients (36%) developed hyperglycemia within 24 h (range 1–16 h). In patients with hyperglycemia, the mean maximum plasma glucose level was 221.5 mg/dL (range 97–325 mg/dL) (12.3 mmol/l), and four (33%) patients were treated with insulin. There was no significant difference in age, gender, body mass index (BMI), tumor size, biochemical profile, or surgical approach and extent of pancreatectomy between patients who developed hyperglycemia and those who did not. Pre-excision and post-excision intraoperative insulin levels were evaluated in 14 of 33 patients. The percentage decrease of the intraoperative insulin levels was not significantly different between patients who developed hyperglycemia and those who did not. All patients with postoperative hyperglycemia had normalization of their glucose levels, and none were discharged on anti-hyperglycemic agents.
Conclusions
Hyperglycemia is common after insulinoma resection, and a subset of patients require transient treatment with insulin.
https://ift.tt/2N1WJgU
Histology-proven recurrence in the lateral or central neck after systematic neck dissection for medullary thyroid cancer
Abstract
Purpose
To delineate risk factors for, and examine temporal patterns of, histology-proven recurrent medullary thyroid cancer (MTC) after compartment-oriented surgery.
Methods
Multivariate Cox regression on overall, node, and soft tissue infiltrate recurrence per previously dissected neck compartment.
Results
Mean follow-up for the 203 (and 158) patients with central (and ipsilateral lateral) neck dissection was 56.1 months. On multivariate Cox regression, tumor size > 20 mm predicted overall and node recurrence in the central neck, whereas extranodal growth predicted overall and node recurrence in the ipsilateral lateral neck. Extrathyroidal extension alone predicted soft tissue infiltrate recurrence in the central neck, and extranodal growth alone soft tissue infiltrate recurrence in the ipsilateral lateral neck. When analyses were restricted to patients not biochemically cured after initial surgery, only extranodal growth predicted overall and node recurrence in the dissected neck compartments.
Conclusions
Patients not biochemically cured, specifically those with extranodal growth at the initial operation, carry greater risks of node recurrence.
https://ift.tt/2JplWmW
Patients’ knowledge about the outcomes of thyroid biopsy: a patient survey
Abstract
Purpose
Fine-needle aspiration biopsy of the thyroid is an increasingly common outpatient procedure. Patients are counseled about the indications and risks of this procedure and informed consent is obtained. We aimed to assess the extent to which patients acquired necessary knowledge during this process.
Methods
Survey study conducted in a thyroid nodule clinic at a referral center. Adult patients who had just undergone a thyroid biopsy were asked to complete a survey, including eight questions regarding the indications and potential outcomes of thyroid biopsy. The main outcome of the study was to assess the patients' knowledge based on the response to each individual survey question.
Results
Two-hundred and ninety-seven patients were eligible, of which 196 (66%) completed the survey: most were women (76%), had adequate reading health literacy (95%) and a mean age of 58 years. Although 86% of patients correctly identified evaluation for thyroid cancer as the main indication for their biopsy, 56% were not aware of the likelihood of this diagnosis. Almost all (>90%) of respondents knew that results could be benign or malignant; fewer were aware of non-diagnostic (71%) or indeterminate (68%) outcomes, or of the need for additional diagnostic testing after the biopsy (33%).
Conclusions
After undergoing thyroid biopsy, a high proportion of well-educated patients remained unaware of their risk for thyroid cancer, potential outcomes, and downstream consequences of their biopsy. This quality gap raises the possibility that informed consent procedures that meet legal standards may leave patients undergoing thyroid biopsy paradoxically uninformed.
https://ift.tt/2MqQKWU
Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database
Abstract
Purpose
Epidemiological data are pivotal for the estimation of disease burden in populations.
Aim
Of the study was to estimate the incidence and prevalence of acromegaly in Italy along with the impact of comorbidities and hospitalization rates as compared to the general population.
Methods
Retrospective epidemiological study (from 2000 to 2014) and case control-study. Data were extracted from the Health Search Database (HSD). HSD contains patient records from about 1000 general practitioners (GPs) throughout Italy, covering a population of more than 1 million patients. It includes information about patient demographics and medical data including clinical diagnoses and diagnostic tests.
Results
At the end of the study period, 74 acromegaly patients (out of 1,066,871 people) were identified, resulting in a prevalence of 6.9 per 100,000 inhabitants [95% CI 5.4–8.5]. Prevalence was higher in females than men (p = 0.004), and showed a statistically significant trend of increase over time (p < 0.0001). Overall, incidence during the study period was 0.31 per 100,000 person-years. Hypertension and type II diabetes mellitus were the comorbidities more frequently associated with acromegaly (31.3 and 14.6%, respectively) and patients were more likely to undergo a high frequency of yearly hospitalization (≥3 accesses/year, p < 0.001) compared to sex-age matched controls.
Conclusions
This epidemiological study on acromegaly carried out using a large GP-based database, documented a disease prevalence of about 7 cases per 100,000 inhabitants. As expected, acromegaly was associated with a number of comorbidities (mainly hypertension and type II diabetes mellitus) and a high rate of patients' hospitalization.
https://ift.tt/2whcgCn
Role of the ubiquitin/proteasome system on ACTH turnover in rat corticotropes
Abstract
Purpose
A large number of studies has investigated proopiomelanocortin processing in anterior pituitary corticotropes but little is known on proopiomelanocortin/ACTH degradation within these cells. The ubiquitin-proteasome system is an intracellular protein degradation pathway which has garnered considerable interest in recent times, given its role in maintenance of protein homeostasis. Aim of the present study was to evaluate the role of the ubiquitin-proteasome system in proopiomelanocortin/ACTH turnover in pituitary corticotropes.
Methods
Rat anterior pituitary primary cultures were treated with 0.01–100 nM MG132, a proteasome inhibitor, or 0.1–100 nM K48R, an inhibitor of polyubiquitylation, for 4 and 24 h and ACTH concentrations in medium and cell lysates estimated by immunometric assay. Co-immunoprecipitation for ubiquitin and ACTH was carried out to establish ubiquitin-tagged protein products.
Results
Inhibition of proteasome-mediated degradation with MG132 lead to an increase in ACTH concentrations, both as regards secretion and cell content. Likewise, inhibition of polyubiquitylation was associated with increased ACTH secretion and cell content. Ubiquitin/ACTH co-immunoprecipitation revealed that proopiomelanocortin was a target of ubiquitylation.
Conclusions
We provide the first evidence that the ubiquitin-proteasome system is involved in proopiomelanocortin/ACTH degradation in corticotropes. Indeed, proopiomelanocortin is a target of ubiquitylation and modulation of ubiquitin-proteasome system affects ACTH turnover. This study shows that regulation of ACTH proteolytic degradation may represent a means to control ACTH secretion.
https://ift.tt/2PqkiS2
Giant pituitary adenoma: histological types, clinical features and therapeutic approaches
Abstract
Giant pituitary adenomas comprise about 6–10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.
https://ift.tt/2wb1PjM
A review on the direct effect of particulate atmospheric pollution on materials and its mitigation for sustainable cities and societies
Abstract
Particulate matter (PM) has gained significant attention due to the increasing concerns related to their effects on human health. Although several reviews have shed light on the effect of PM on human health, their critical adverse effect on material's structure and sustainability was almost neglected. The current study is an attempt to fill this gap related to PM impact on structural materials under the overall consideration of sustainability. More specifically, this review highlights the existing knowledge by providing an overview on PM classification, composition, and sources in different locations around the world. Then, it focuses on PM soiling of surfaces such as solar panels due to an increasing need to mitigate the impact of soiling on reducing photovoltaic (PV) power output and financial competitiveness in dusty regions. This topic is of critical importance for sustainable deployment of solar energy in arid and desert areas around the world to help in reducing their impact on overall climate change and life quality. In addition, this review summarizes climate change phenomena driven by the increase of PM concentration in air such as radiative forcing and acid rain deposition due to their impact on human health, visibility and biodiversity. To this end, this work highlights the role of process management, choice of fuel, the implementation of clean technologies and urban vegetation as some possible sustainable mitigation policies to control PM pollution in cities and urban regions. This research is designed to conduct a comprehensive narrative literature review which targets broad spectrum of readers and new researchers in the field. Moreover, it provides a critical analysis highlighting the need to fill main research gaps in this domain. The findings of this review paper show that PM pollution imposes severe adverse impacts on materials, structures and climate which directly affect the sustainability of urban cities. The advantages of this review include the value of the extensive works that elaborate on the negative impacts of PM atmospheric pollution towards high level of public awareness, management flexibility, stakeholder's involvements, and collaboration between academy, research, and industry to mitigate PM impact on materials and human welfare.
https://ift.tt/2LcKE77
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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