Rejuvenation Research, Ahead of Print.
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Δευτέρα 15 Οκτωβρίου 2018
Diagnostic and Prognostic Relevance of Red Blood Cell Distribution Width for Vascular Aging and Cardiovascular Diseases
18F-fluorodeoxyglucose positron emission tomography-based evaluation of systemic and vascular inflammation and assessment of the effect of systemic treatment on inflammation in patients with moderate-to-severe psoriasis: A randomized placebo-controlled pilot study
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):660-666
Background: Psoriasis is a systemic inflammatory disorder associated with an increased risk of cardiovascular disease. Objective: To evaluate the utility of [[18]F]-fluorodeoxyglucose positron emission tomography/computed tomography in identifying vascular and systemic inflammation in psoriasis patients with moderate-to-severe disease and to analyze its usefulness in assessing the effect of systemic treatment. Methods: This was a randomized, double-blind pilot study conducted in a tertiary care center. Baseline standardized uptake value score was estimated by18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with moderate-to-severe psoriasis and compared with historical controls. Patients were then randomized using computer-generated randomization list into methotrexate or placebo (with or without pioglitazone) groups.18F-fluorodeoxyglucose positron emission tomography/computed tomography was repeated at 12 weeks and composite standardized uptake value score determined. The correlation between Psoriasis Activity and Severity Index and SUVmax was assessed. Results: A total of 16 patients were randomized to different treatment groups. Significant increase in mean SUVmax was observed in the ascending aorta in psoriasis patients as compared to historical controls (2.03 ± 0.53 vs 1.51 ± 0.36, P < 0.03). There was no difference in composite standardized uptake value score after 12 weeks of treatment in any of the treatment groups (P = 0.82), although an improvement in Psoriasis Activity and Severity Index score in the methotrexate arm was observed. No correlation was found between mean SUVmax and Psoriasis Activity and Severity Index scores in various aortic segments (r = 0.3–0.7). Limitations: Small sample size, short follow-up, historical controls, exclusion of patients with comorbid conditions and lack of surrogate markers of systemic inflammation. Conclusion: 18F-fluorodeoxyglucose positron emission tomography imaging showed higher vascular inflammation in ascending aorta of psoriasis patients as compared to historical controls. Systemic treatment with methotrexate and pioglitazone did not influence the vascular inflammation in the short term.
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A treatise on topical corticosteroids in dermatology. Use, misuse and abuse
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):761-762
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Histoid leprosy presenting with figurate lesions: A unique and rare presentation
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):736-739
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N-acetylcysteine in dermatology
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):652-659
N-acetylcysteine is a mucolytic drug which is commonly used as an antidote for acetaminophen toxicity. It is a thiol compound, which acts as a donor of cysteine, leading to replenishment of glutathione and thus acts as an antioxidant. It also has anti-inflammatory effects, alters the levels of neurotransmitters, inhibits proliferation of fibroblasts and keratinocytes and causes vasodilatation. Due to these actions, n-acetylcysteine has found use in several dermatologic conditions in systemic and topical form. The drug has been used as an adjuvant in the management of conditions such as toxic epidermal necrolysis, drug hypersensitivity syndrome, trichotillomania, skin picking disorders and onychotillomania, ichthyoses, contact dermatitis, atopic dermatitis, melasma, pseudoporphyria, connective tissue diseases, wound healing and alopecia. It also has a role in protection from radiation-induced skin damage including photo-ageing, photocarcinogenesis and radiation dermatitis. Most indications in dermatology are supported by case reports, small case series and small trials. Higher quality of evidence is needed for its wider use. The drug is cheap and is generally safe with few adverse effects. Thus a greater role is possible for use of n-acetylcysteine in various skin conditions. This review explores the various uses of n-acetylcysteine in the field of dermatology, the evidence supporting the same, the possible mechanisms of action and the adverse effects of the drug.
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Differential expression of capecitabine-induced hand foot syndrome on paretic limb
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):720-722
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Four views of trichomycosis axillaris: Clinical, Wood's lamp, dermoscopy and microscopy
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):748-749
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A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):667-671
Background: Lichen planus is a common chronically relapsing autoimmune skin condition with poorly understood etiology. Apart from cellular immunity, presence of various antibodies has been hypothesized. Various studies have found the presence of serum anti-nuclear antibody, anti-mitochondrial antibody, anti-desmoglein 1 and 3 antibodies, anti-keratinocyte antibody and anti-thyroglobulin antibody in patients of cutaneous and oral lichen planus. Aim: To study the prevalence of autoantibodies and the clinical spectrum of disease in an Indian patient subpopulation with lichen planus. Methods: A cross-sectional epidemiological study comprising 100 lichen planus patients was conducted in the dermatology outpatient department of Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India. Serum concentrations of circulating anti-nuclear antibodies, anti-desmoglein 1 antibody, anti-desmoglein 3 antibody, anti-keratinocyte antibodies, anti-mitochondrial antibodies and anti-thyroglobulin antibodies were determined by indirect immunofluorescence. Pairs of groups were compared using "Student's t-test" for normally distributed continuous data. The "χ2-test" was used for the categorical variables as needed. Statistical significance was set at P < 0.05. Results: It was found that 65 (65%) patients showed the presence of at least one of the six autoantibodies that we studied, while 35 (35%) tested negative for all six of them. Positivity of anti-keratinocyte antibody in 26 (26%), anti-nuclear antibody in 22 (22%), anti-desmoglein 1 antibody in 19 (19%), anti-desmoglein 3 antibody in 16 (16%), anti-mitochondrial antibody in 9 (9%) and anti-thyroglobulin antibody in 6 (6%) patients was detected. It was observed that 55 (71.4%) patients of cutaneous lichen planus, 6 (46.1%) patients of mucosal lichen planus and 4 (40%) patients of cutaneous and mucosal lichen planus overlap showed presence of at least one autoantibody. Conclusion: This study provides the serological parameters of a population of lichen planus from western India. Presence of autoantibodies in lichen planus suggests the possible role of humoral immunity in lichen planus. Identifying antibodies linked to lichen planus may help in identifying suitable diagnostic tests and therapeutic targets. Well-controlled studies with larger sample size are the need of the hour to confirm the role of humoral immunity in lichen planus. Limitations: Studies with a larger number of patients as well as controls should be undertaken to further evaluate the role of autoantibodies in lichen planus.
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Medical journalism and social media: A boon and a bane?
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):647-651
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Proposed global drooping and wrinkles classification and scoring system for aging face with validation and experience on 54 Indian subjects
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):672-677
Background: Aging is an inevitable biological change, but understanding the process of aging of face is important to customize the treatment options for facial rejuvenation. Evidence-based estimation of global facial aging is necessary for the validation of various treatment modalities. Aims: Classification and implementation of a scoring system for aging face based upon volume loss and surface changes as evident by drooping of different areas of the face and appearance of fine and deep wrinkles, respectively, and to apply this drooping–wrinkles classification on 54 participants to evaluate and understand the validity of scoring. Methods: An observational study was conducted, and scores were calculated based on 13 parameters (7 areas of drooping and 6 areas of wrinkles on the face) at Aura Skin Institute, Chandigarh, India. Accordingly, age was divided in different age groups followed by clinical estimation of facial age and calculation of scores. Results: According to our classification and scoring system, 61% (33 out of 54) of the participants were correlated with their chronological age group. Out of the remaining 21 (39%) participants who were aging faster, 13 (24%) were in the age group of 25–35 years. Approximately one-fourth of the patients in the age groups 36–45 and 46–55 years were aging faster. Only 1 patient had scores showing younger age in comparison to chronological age. Overall, there was a good correlation between the calculated score and the chronological age of patients. Moreover, a gradual increase in scores was noticed with increasing age groups. Conclusions: This is a new clinical classification and scoring system for facial age which is much easier to apply in daily clinical practice for easy calculation of baseline scores and customizing their antiaging treatment options. Moreover, it will also make it easier to compare the efficacy of treatment in their future follow-ups. The limitation of this study is that it has been proposed for all skin types but validation has been done only for Indian participants.
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Dermatoscopy of multiple piloleiomyomas with disseminated and segmental distribution
Mirjana Popadić, Dimitrije Brasanac, Mirjana Milinković, Danijela Milčić
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):726-729
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Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):726-729
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A prospective study of the epidemiological and clinical patterns of recurrent dermatophytosis at a tertiary care hospital in India
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):678-684
Background: Recurrent and clinically unresponsive dermatophytosis is being increasingly encountered in our country. It runs a protracted course with exacerbations and remissions. However, there is little information regarding the extent of the problem and the characteristics of recurrent dermatophytosis in published literature. Aims: We sought to determine the prevalence, risk factors and clinical patterns of recurrent dermatophytosis in our institution. We also investigated the causative dermatophyte species and antifungal susceptibility patterns in these species. Methods: One hundred and fifty patients with recurrent dermatophytosis attending the outpatient department of the Postgraduate Institute of Medical Education and Research, Chandigarh, India were enrolled in the study conducted from January 2015 to December 2015. A detailed history was obtained in all patients, who were then subjected to a clinical examination and investigations including a wet preparation for direct microscopic examination, fungal culture and antifungal susceptibility tests. Results: Recurrent dermatophytosis was seen in 9.3% of all patients with dermatophytosis in our study. Trichophyton mentagrophytes was the most common species identified (36 patients, 40%) samples followed by T. rubrum (29 patients, 32.2%). In-vitro antifungal susceptibility testing showed that the range of minimum inhibitory concentrations (MIC) on was lowest for itraconazole (0.015–1), followed by terbinafine (0.015–16), fluconazole (0.03–32) and griseofulvin (0.5–128) in increasing order. Limitation: A limitation of this study was the absence of a suitable control group (eg. patients with first episode of typical tinea). Conclusion: Recurrence of dermatophytosis was not explainable on the basis of a high (MIC) alone. Misuse of topical corticosteroids, a high number of familial contacts, poor compliance to treatment over periods of years, and various host factors, seem to have all contributed to this outbreak of dermatophytosis in India.
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Congenital alopecia of eyebrow
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):743-744
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Acral angioosteoma cutis: A rare case
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):685-686
Acral angioosteoma cutis is a rare and benign cutaneous lesion clinically characterized by an exophytic growth resembling pyogenic granuloma on the acral skin; first described in 2006. Its pathogenesis is still unclear while well-formed capillaries, pale stroma, bland fibroblast-like cells, and multiple tiny spicules of woven bone constitute the histological hallmarks. Here, we present a case of acral angioosteoma cutis in a 34-year-old man to increase awareness regarding this rare condition.
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Transepidermal elimination: Historical evolution, pathogenesis and nosology
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):753-757
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Bilateral “turkey ear” as a cutaneous manifestation of lupus vulgaris
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):687-689
Lupus vulgaris is a common form of cutaneous tuberculosis in China, mostly involving the head and neck region. Turkey ear is a clinically descriptive term, used for a massively enlarged earlobe with bluish-red or violaceous indurated plaques and nodules, which can be a sign of lupus vulgaris. A 47-year-old female presented with edema and reddish ulcerated lesions on both ears which was diagnosed as lupus vulgaris by conventional laboratory investigations and the patient showed good response to antituberculous therapy. Occurrence of turkey ears in lupus pernio (sarcoidosis) should also be mentioned here as this presentation was originally described in this condition. Two case reports of turkey ear have been reported with cutaneous tuberculosis (not bilateral). However, occurrence of bilateral turkey ears in cutaneous tuberculosis has not been described so far in the literature.
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Reversible twisted and rolled hairs due to manual twisting: Two case reports
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):763-763
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Revisiting the role of the slit-skin smear in the diagnosis of Indian post-kala-azar dermal leishmaniasis
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):690-695
Background: Post kala azar dermal leishmaniasis (PKDL) is a neglected dermatosis that develops as a sequel to kala azar after apparent complete treatment. Being a non life threatening condition, patients often delay treatment thereby maintaining a reservoir of infection. The diagnosis of PKDL rests on the demonstration of the parasite in tissue smears, immune diagnosis by detection of parasite antigen or antibody in blood, or detection and quantitation of parasite DNA in tissue specimens. Sophisticated molecular tests are not only expensive but also need skilled hands and expensive equipment. To be useful, diagnostic methods must be accurate, simple and affordable for the population for which they are intended. Aims: This study was designed to assess functionality and operational feasibility of slit-skin smear examination. Methods: Sensitivity and specificity was evaluated by performing slit-skin smear and histo-pathological examination in 46 PKDL patients and the results were compared with the parasite load in both the slit aspirate and tissue biopsy specimens by performing quantitative Real-time PCR (Q-PCR). Results: The slit-skin smear examination was more sensitive than tissue biopsy microscopy. The parasite loads significantly differed among various types of clinical lesions (P < 0.05). The threshold of parasite load for detection by SSS microscopy was 4 parasites/μl in slit aspirate and 60 parasites/μg tissue DNA in tissue biopsy while that for tissue microscopy was 63 parasites/μl and 502 parasites/μg tissue DNA respectively. As detection of Leishmania donovani bodies may be challenging in inexperienced hands, the microscopic structure of these has been detailed along with a comprehensive discussion of pre analytical, analytical and post analytical variables affecting its identification. To facilitate the diagnosis of PKDL, some scenarios have been suggested taking into consideration the clinical, epidemiological, immunological and microscopic aspects. Conclusion: Such evidence based medicine helps minimize intuition, systematize clinical experience and provides a diagnostic rationale as sufficient grounds for a clinical decision.
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Adverse cutaneous events after laser epilation in patients with photodermatosis
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):718-720
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Study of the relation between two common cyclooxygenase 2 gene polymorphisms with risk of developing and subtypes of vitiligo in Egyptian patients
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):696-700
Background/Purpose: Genetic factors play an important role in the pathogenesis of vitiligo. Cyclooxygenase 2 (COX2) gene induced by ultraviolet radiation controls the synthesis of prostaglandins, which are are found to be beneficial in treating vitiligo. COX2 gene polymorphism has been previously evaluated in Chinese population. We aimed to study the relation between two common COX2 gene polymorphisms with vitiligo and its subtypes amongEgyptian patients. Patients and Methods: This study included 200 participants (100 vitiligo patients and 100 healthy controls). COX2-765G/C and -1195A/G gene polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction analysis and the results were compared between the two groups and among different subtypes of vitiligo. Results: Frequency of COX2-1195 AA, AG, GG genotypes showed no significant association among patients with vitiligo (P = 0.626, 0.321, 0.08, respectively); those with generalized vitiligo (P = 0.739, 0.291, 0.101, respectively) and those with segmental vitiligo (P = 0.410, 1.00, 0.676, respectively) compared to the control group. Regarding COX2-765G/C genotypes, GG genotype was more frequent among patients with vitiligo [84 (84%)] compared to controls [63 (63%)] (P = 0.001). GC genotype was significantly less frequent [15 (15%)] among patients compared to controls [32 (32%)] (P = 0.005). Generalized and segmental types of vitiligo also showed no significant difference in the frequency of COX2-765G/C genotypes compared with controls. Limitations: Being a pilot study, a relatively small number of participants were included. Conclusion: COX2-1195A/G gene polymorphism is not associated with the risk of developing vitiligo or with vitiligo subtypes. COX2-765 GG genotype is associated with vitiligo, especially of the generalized type.
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Docetaxel induced pellagroid dematitis
Indian Journal of Dermatology, Venereology, and Leprology 2018 84(6):723-725
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Methotrexate polyglutamate levels and co-distributions in childhood acute lymphoblastic leukemia maintenance therapy
Abstract
Purpose
Methotrexate polyglutamates (MTXpg) facilitate incorporation of thioguanine nucleotides into DNA (DNA-TG, the primary cytotoxic thiopurine metabolite and outcome determinant in MTX/6-mercaptopurine treatment of childhood ALL). We hypothesized that mapping erythrocyte levels of MTXpg with 1–6 glutamates and their associations with DNA-TG formation would facilitate future guidelines for maintenance therapy dosing.
Methods and results
Summed MTX with 1–6 glutamates resolved by LCMS [median (interquartile): 5.47 (3.58–7.69) nmol/mmol hemoglobin] was in agreement with total MTX by radio ligand assay. In 16,389 blood samples from 1426 ALL maintenance therapy patients, MTXpg3 21.0 (15.2–27.4)% was the predominant metabolite, and MTXpg1 (the maternal drug) constituted 38.6 (27.2–50.2)% of MTXpg1–6. All subsets correlated; the strongest associations were between metabolites with similar polyglutamate lengths. Correlations of MTXpg1 with MTXpg2 and MTXpg3,4,5,6 were rs = 0.68 and rs = 0.25–0.42, respectively. Intercorrelations of MTXpg3,4,5,6 were all rs ≥ 0.51. MTXpg4 accounted for 29.8 (24.7–33.3)% of MTXpg3–6, yet explained 96% of the summed MTXpg3–6 variation. MTXpg1–4, MTXpg1–6, MTXpg2–6 and MTXpg3 were all associated with DNA-TG levels (p < 0.00001), but collinearity precluded identification of the most informative subset.
Conclusions
Measuring erythrocyte MTXpg4 simplifies and can replace longer chain MTXpg monitoring. Resolving individual MTXpg identifies samples that are unsuitable for dose guidance due to high levels of MTXpg1 remaining in the plasma fraction because of recent MTX intake. All tested MTXpg subsets correlated with DNA-TG and may be used for ALL maintenance therapy dose adjustments, but the most informative subset remains to be identified.
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Awakening the “guardian of genome”: reactivation of mutant p53
Abstract
The role of tumor suppressor protein p53 is undeniable in the suppression of cancer upon oncogenic stress. It induces diverse conditions such as cell-cycle arrest, cell death, and senescence to protect the cell from carcinogenesis. The rate of mutations in p53 gene nearly accounts for 50% of the human cancers. Upon mutations, the conformation gets altered and becomes non-native. Mutant p53 displays long half-life and accumulates in the nucleus and interacts with oncoproteins to promote carcinogenesis and these interactions present a formidable challenge for clinicians in therapy of the disease. Variety of approaches have been developed, through which native-like function of p53 can be restored, such as restoration of the native-like structure of p53, activating the p53 family members, etc. Modern scientific techniques have led to the discovery of a variety of molecules to reactivate mutant p53 and restore its transcriptional activity. These compounds include small molecules, various peptides, and phytochemicals. In this review article, we comprehensively discuss these molecules to reactivate mutant p53 to restore the normal function with a particular focus on molecular mechanisms.
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Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis
Abstract
Background
Microvascular free flap reconstruction has become a standard technique in head and neck reconstructive surgery. Pre-operative radiotherapy is associated with a higher incidence of free flap malperfusion and the need for operative revision. Irradiated vessels present characteristic histomorphological and structural changes. Alterations in endothelial cells of irradiated arteries remain incompletely investigated especially with regard to long-term changes in endothelial dysfunction supporting an intraluminal pro-thrombotic and pro-inflammatory milieu.
Methods
Endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E‑ and P‑selectin, endothelial NO-synthase (eNOS), thrombomodulin and plasminogen activator inhibitor-1 (PAI-1) in irradiated and non-irradiated arteries was analysed using immunohistochemistry and Remmele scale grading. The average radiation dose was 58.7 ± 7.0 Gy; the time interval between end of radiation and tissue sampling was 106.0 ± 86.8 months.
Results
Endothelial expression of ICAM-1, VCAM-1, E‑ and P‑selectin as well as PAI-1 was significantly increased in previously irradiated arteries compared with non-irradiated controls, whereas thrombomodulin and eNOS expression did not show any differences. However, when comparing non-irradiated free flap arteries with irradiated arteries from the head and neck area in respective individuals, eNOS expression was significantly lower in irradiated vessels whereas ICAM-1, VCAM-1, E‑/p-Selectin and PAI-1 showed significantly higher expression levels.
Conclusion
There is ongoing endothelial dysfunction in terms of increased expression of pro-thrombotic and pro-inflammatory markers in irradiated arteries even years after radiotherapy. Treating this endothelial dysfunction might reduce the complication rates associated with microvascular free flap reconstructions in irradiated patients.
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Influence of static forces on the expression of selected parameters of inflammation in periodontal ligament cells and alveolar bone cells in a co-culture in vitro model
Abstract
Objective
Aim of this study was to investigate the impact of human PDL-derived fibroblasts (HPDF) and human alveolar bone-derived osteoblasts (HABO) co-culture on the expression of cytokines involved in tissue remodeling using an in vitro compressive force (CF) model.
Materials and methods
Static compressive force (CF) of 47.4 g/cm2 was applied on mono- and co-cultured HPDFs and HABOs for 1, 2, or 4 h at 30 °C. TNFA, PTGS2, and IL6 gene expressions were determined by quantitative real-time polymerase chain reaction. TNF, PGE2, and IL6 concentrations were measured using enzyme-linked immunosorbent assay.
Results
In mono-culture, TNFA, PTGS2, and IL6 gene expressions were upregulated under CF as compared to controls for each time period in both cell types. PGE2 increased at 1 and 2 h in both cell types, and IL6 increased only at 2 and 4 h in HPDFs. Co-culture alleviated the force-induced increase of the expression of TNFA, PTGS2, IL6, PGE2, and IL6 in HPDFs at any time point. In HABOs, co-cultivation decreased the expression of PGE2 after 1 h and 4 h, and that of IL6 after 1 h compared to mono-culture.
Conclusions
CF application on co-cultures of HPDFs and HABOs causes significant changes of TNFA, PTGS2, and IL6 gene expressions and PGE2 and IL6 production in comparison to mono-culture indicating intercellular communication.
Clinical relevance
Mechanical stimulation of HPDFs and HABOs in co-culture induces a different gene expression pattern than stimulation of individual cell types alone. Co-culture might therefore be a relevant method to elucidate periodontal regeneration during orthodontic therapy.
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Strategies to reduce readmissions for hyponatremia after transsphenoidal surgery for pituitary adenomas
Abstract
Purpose
Disorders of water balance, particularly hyponatremia from altered antidiuretic hormone (ADH) secretion, are a common post-operative complication of transsphenoidal surgery (TSS). We present our results from implementation of a 2-week 1.5 liter/daily fluid restriction on readmission rates for hyponatremia.
Methods
A retrospective chart review was performed on 295 patients that underwent TSS for pituitary adenomas at the University of Colorado, between March 2014 and March 2017. Groups were divided into those before and after the implementation of a two-week, 1.5 liter daily fluid restriction and measurement of a serum sodium level 7 days (+/− 2 days) after discharge. A standard-of-care approach for variable degrees of hyponatremia was also utilized to guide hyponatremia management. Patient demographics, hospital course, post-operative complication rates, and rates of hospital admissions for hyponatremia were then evaluated.
Results
Readmissions for symptomatic hyponatremia within 30 days of TSS occurred in 9 of 118 (7.6%) of patients prior to fluid restriction implementation and in four of 169 (2.4%) of patients in the post-implementation, fluid-restricted group (p-value = 0.04): a 70% reduction in hospitalizations. The two groups were similarly matched for pituitary tumor sub-type, age and gender. None of these factors were predictive for hyponatremia. Importantly, the mild fluid restriction did not result in any hospital readmissions for hypernatremia.
Conclusions
Mild fluid restriction (to 1.5 liters daily), in addition to a single post-operative serum sodium level, is an effective approach to preventing readmission for hyponatremia after TSS for pituitary adenomas.
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Psychiatric disorders in women with polycystic ovary syndrome: a systematic review and meta-analysis
Abstract
Purpose
Polycystic ovary syndrome (PCOS) is a common disorder affecting up to 15% of women in the reproductive age. Prior studies suggest that PCOS can be associated with mood and psychiatric disorders. The purpose of this study is to examine the prevalence of any psychiatric disorder in women with PCOS.
Methods
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through February 08, 2017 for studies that examined the prevalence of any psychiatric disorder in adolescents or adults with a clinical or biochemical diagnosis of PCOS. We used a random-effects model to generate pooled estimates and 95% confidence intervals (CI).
Results
We included 57 studies reporting on 172,040 patients. The majority of studies addressed depression and anxiety. Studies had fair methodological quality although most estimates were unadjusted. Women with PCOS were more likely to have a clinical diagnosis of depression (odds ratio (OR), 2.79; 95% CI, 2.23–3.50), anxiety (OR, 2.75; 95% CI, 2.10–3.60), bipolar disorder (OR, 1.78; 95% CI, 1.43–2.23) and obsessive compulsive disorder (OCD) (OR, 1.37; 95% CI 1.22–1.55), but not social phobia or panic disorder. Using various scales, the severity of symptoms of depression, anxiety, obsessive compulsive disorder, and somatization disorders were higher compared to women without PCOS.
Conclusions
PCOS is associated with an increased risk of diagnosis of depression, anxiety, bipolar disorder, and obsessive compulsive disorder. It is associated with worse symptoms of depression, anxiety, OCD, and somatization. Screening for these disorders to allow early intervention may be warranted.
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New modified Friedewald formulae for estimating low-density lipoprotein cholesterol according to triglyceride levels: extraction and validation
Abstract
Purpose
The most commonly used method for estimating low-density lipoprotein cholesterol (LDLC) is Friedewald formula (FF). This study aims to extract and validate new modified Friedewald formulae for estimating LDLC according to triglyceride (TG) levels in Iranians.
Methods
Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), LDLC, and TG were measured in 5030 fasted subjects. The original FF was used for estimating LDLC. Data were divided into training and validation data sets. For extracting modified Friedewald formulae, linear regression was used with TG as independent and TC, HDLC, and directly measured LDLC (D-LDLC) as dependent variables, respectively. An overall modified formula was extracted for TG concentrations <400 mg/dL. The specific modified formulae were extracted for different TG categories. The performance of the modified formulae was assessed in the validation data set.
Results
The overall derived formula for calculating LDLC was M-LDLC = TC–HDLC–TG/4. The coefficients of TG (specific TG terms) in modified formulae were 2.7, 3.7, 4.6, and 5 for TG <100, 100–200, 200–300, and 300–400 mg/dL, respectively. Compared to the original FF, applying a new modified formula with TG/4 to a validation data set provided a less mean difference (4.03 vs. 10.86 mg/dL), greater kappa coefficient (0.691 vs. 0.505), and better subject classification (80.8 vs. 67.1%). After applying modified formulae with specific TG terms, the difference between M-LDLC and D-LDLC decreased to 1.41 mg/dL.
Conclusions
Modified formulae were developed and validated for LDLC estimation that compared to the original FF, provided more accurate estimation of LDLC and better classification of subjects. These findings shall be useful for preventive, diagnostic, and therapeutic purposes.
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The association of smoking and risk of diabetic retinopathy in patients with type 1 and type 2 diabetes: a meta-analysis
Abstract
Purpose
To clarify the relevance between smoking and diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus.
Methods
Published evidence were searched in MEDLINE and EMBASE from the databases began until Feb. 2017. Studies evaluating the association between smoking and diabetic retinopathy or evaluating the risk factors of diabetic retinopathy including smoking were included.
Results
Totally 73 studies were identified, among which 19 studies included type 1 diabetes patients and 56 studies included type 2 diabetes patients. In type 1 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers (risk ratio (RR) = 1.23, 95% CI 1.14, 1.33, P < 0.001), and the risk of proliferative diabetic retinopathy also significantly increased in smokers (RR = 1.48, 95% CI 1.20, 1.81, P < 0.001). In type 2 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly decreased in smokers (RR = 0.92, 95% CI 0.86, 0.98, P = 0.02) and the risk of proliferative diabetic retinopathy also significantly decreased in smokers (RR = 0.68, 95% CI 0.61, 0.74, P < 0.001).
Conclusions
Compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers with type 1 diabetes while significantly decreased in smokers with type 2 diabetes. However, this result did not change the importance of smoking cessation for public health.
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Cabergoline for the treatment of bromocriptine-resistant invasive giant prolactinomas
Abstract
Purpose
Few studies have specifically focused on the effect of cabergoline on invasive giant prolactinomas (IGPs) resistant to bromocriptine. This study aims to evaluate whether cabergoline could be used as an effective therapy for patients with bromocriptine-resistant IGPs.
Methods
This retrospective study included 15 patients with bromocriptine-resistant IGPs who received treatment at our department during 2007–2015. Cabergoline was administered in all 15 patients, with the dose adjusted depending on the prolactin response of each patient. Parameters for outcome assessment included prolactin level, pituitary function, tumor size, improvement of the clinical symptoms, visual field defects, drug tolerance, and disease recurrence.
Results
Cabergoline was effective for the treatment of the patients with bromocriptine -resistant IGPs as represented by normalization of the prolactin level in 12/15 patients; improvement or normalization of the pituitary function in 4/5 patients with hypopituitarism; significant reduction in tumor size in 14/15 patients; and relief of the clinical symptoms in 11/15 patients. All 15 patients showed good tolerance to cabergoline. In addition, no recurrence was observed during the mean follow-up period of 63.47 (range 30–145) months.
Conclusions
Data of this retrospective study demonstrate that cabergoline is an excellent option for the treatment of patients with bromocriptine-resistant IGPs.
https://ift.tt/2QRhTjg
Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study
Abstract
Introduction
Pasireotide, a multi-somatostatin receptor (SSTR)-ligand with high affinity for SSTR5 was recently approved for acromegaly treatment.
Patients and methods
A retrospective multicenter study investigating the efficacy and safety of long-acting (LAR) pasireotide treatment in 35 patients (20 males) with active acromegaly (28 macroadenomas).
Results
Mean baseline insulin-like growth factor-1 (IGF-1) at diagnosis was 3.1 ± 1.3 × ULN. All but five patients have undergone pituitary surgery and six received sellar radiotherapy. All remained with active acromegaly despite first-generation somatostatin analogue (SSA) treatment. Immediately before pasireotide-LAR initiation, eighteen patients were under SSA monotherapy and one with pegvisomant. The remaining patients received combination therapy with SSA and pegvisomant, n = 9 (two received cabergoline also); SSA and cabergoline, n = 4; pegvisomant and cabergoline, n = 1. Two were untreated. Mean IGF-1 was 1.76 ± 0.9 ULN before pasireotide. Pasireotide-LAR starting dose was 40 mg/4 weeks in most patients. IGF-1 normalized in 19 patients, IGF-1 between 1-1.2 × ULN was reached in five, and in additional two patients IGF-1 was significantly suppressed. No effect was seen in nine patients. Pasireotide dose was reduced by 20 mg in six patients with excellent response, with preserved IGF-1 control in five. Severe headaches in six patients disappeared or improved with pasireotide. Side effects consisted of symptomatic cholelithiasis in one patient and deterioration of glucose control in 22 patients, requiring initiation or intensification of antidiabetic treatment in seventeen. One patient developed diabetic ketoacidosis.
Conclusions
In the real-life scenario ~54% of patients with acromegaly resistant to first-generation SSA, may normalize IGF-1 with pasireotide; however, 63% experienced glucose control deterioration.
https://ift.tt/2QRhPQy
Insights on the phenotypic heterogenity of 11β-hydroxylase deficiency: clinical and genetic studies in two novel families
Abstract
Purpose
11β-hydroxylase deficiency accounts for 5% of congenital adrenal hyperplasia cases. Diagnosis suspiction is classically based on the association between abnormal virilization, precocious puberty, and hypertension in 46XX or 46XY subjects. We investigated two families with siblings presenting with opposed clinical features, and provided a review of the mechanisms involved in mineralocorticoid-dependent phenotypic heterogeneity.
Methods
The coding region of the CYP11B1 gene of 4 patients was sequenced and familial segregation was confirmed. Clinical characterization and blood steroid profile were performed.
Results
Family 1 comprised a female and a male siblings who presented in middle childhood with genital ambiguity (Prader II) and precocious puberty, respectively, associated with hypertension. In the second decade of life, the woman had three full-term pregnancies, and then evolved normotensive with no treatment over a 5-year follow up. On the other hand, her brother had hypertensive end-organ damage at age 24. In family 2, a 2.9 year-old boy presented with precocious puberty and hypertension, whereas his 21 days-old sister had genital ambiguity (Prader III) and salt wasting. A homozygous exon 4 splice site mutation was identified (IVS4ds-1G > A; c.799 G > A) in family 1, while a nonsense mutation in exon 6 (p. Q356X; c.1066 C > T) was found in family 2.
Conclusion
CYP11B1 mutations were associated with highly variable phenotypes, from mild to severe virilization, and early-onset hypertension or salt wasting. Further analysis of variants in other hypertension-related genes, steroid synthesis and metabolism compensatory pathways, and/or the investigation of chimeric CYP11B genes are needed to clarify the phenotypic heterogeneity in 11β-hydroxylase deficiency.
https://ift.tt/2AaaMNl
Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study
Abstract
Aim
Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile.
Methods
The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A—half an hour before breakfast; timing regimen B—an hour before the main meal of the day; timing regimen C—at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study.
Results
Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = −0.017 95% C.I. (−0.400–0.192); baseline vs. B = −0.325 95% C.I. (−0.562–0.023); baseline vs. C = −0.260 95% C.I. (−0.475–0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline.
Conclusion
The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.
https://ift.tt/2QRhsp8
Temporal relationship of sleep apnea and acromegaly: a nationwide study
Abstract
Purpose
Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.
Methods
Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.
Results
Of the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.
Conclusion
Sleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.
https://ift.tt/2Ab1IYB
Melatonin treatment suppresses appetite genes and improves adipose tissue plasticity in diet-induced obese zebrafish
Abstract
Purpose
Overweight and obesity are important risk factors for diabetes, cardiovascular diseases, and premature death in modern society. Recently, numerous natural and synthetic compounds have been tested in diet-induced obese animal models, to counteract obesity. Melatonin is a circadian hormone, produced by pineal gland and extra-pineal sources, involved in processes which have in common a rhythmic expression. In teleost, it can control energy balance by activating or inhibiting appetite-related peptides. The study aims at testing effects of melatonin administration to control-fed and overfed zebrafish, in terms of expression levels of orexigenic (Ghrelin, orexin, NPY) and anorexigenic (leptin, POMC) genes expression and morphometry of visceral and subcutaneous fat depots.
Methods
Adult male zebrafish (n = 56) were divided into four dietary groups: control, overfed, control + melatonin, overfed + melatonin. The treatment lasted 5 weeks and BMI levels of every fish were measured each week. After this period fishes were sacrificed; morphological and morphometric studies have been carried out on histological sections of adipose tissue and adipocytes. Moreover, whole zebrafish brain and intestine were used for qRT-PCR.
Results
Our results demonstrate that melatonin supplementation may have an effect in mobilizing fat stores, in increasing basal metabolism and thus in preventing further excess fat accumulation. Melatonin stimulates the anorexigenic and inhibit the orexigenic signals.
Conclusions
It seems that adequate melatonin treatment exerts anti-obesity protective effects, also in a diet-induced obesity zebrafish model, that might be the result of the restoration of many factors: the final endpoint reached is weight loss and stabilization of weight gain.
https://ift.tt/2QRhrl4
Strategies to reduce readmissions for hyponatremia after transsphenoidal surgery for pituitary adenomas
Abstract
Purpose
Disorders of water balance, particularly hyponatremia from altered antidiuretic hormone (ADH) secretion, are a common post-operative complication of transsphenoidal surgery (TSS). We present our results from implementation of a 2-week 1.5 liter/daily fluid restriction on readmission rates for hyponatremia.
Methods
A retrospective chart review was performed on 295 patients that underwent TSS for pituitary adenomas at the University of Colorado, between March 2014 and March 2017. Groups were divided into those before and after the implementation of a two-week, 1.5 liter daily fluid restriction and measurement of a serum sodium level 7 days (+/− 2 days) after discharge. A standard-of-care approach for variable degrees of hyponatremia was also utilized to guide hyponatremia management. Patient demographics, hospital course, post-operative complication rates, and rates of hospital admissions for hyponatremia were then evaluated.
Results
Readmissions for symptomatic hyponatremia within 30 days of TSS occurred in 9 of 118 (7.6%) of patients prior to fluid restriction implementation and in four of 169 (2.4%) of patients in the post-implementation, fluid-restricted group (p-value = 0.04): a 70% reduction in hospitalizations. The two groups were similarly matched for pituitary tumor sub-type, age and gender. None of these factors were predictive for hyponatremia. Importantly, the mild fluid restriction did not result in any hospital readmissions for hypernatremia.
Conclusions
Mild fluid restriction (to 1.5 liters daily), in addition to a single post-operative serum sodium level, is an effective approach to preventing readmission for hyponatremia after TSS for pituitary adenomas.
https://ift.tt/2AbM6Eg
Psychiatric disorders in women with polycystic ovary syndrome: a systematic review and meta-analysis
Abstract
Purpose
Polycystic ovary syndrome (PCOS) is a common disorder affecting up to 15% of women in the reproductive age. Prior studies suggest that PCOS can be associated with mood and psychiatric disorders. The purpose of this study is to examine the prevalence of any psychiatric disorder in women with PCOS.
Methods
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through February 08, 2017 for studies that examined the prevalence of any psychiatric disorder in adolescents or adults with a clinical or biochemical diagnosis of PCOS. We used a random-effects model to generate pooled estimates and 95% confidence intervals (CI).
Results
We included 57 studies reporting on 172,040 patients. The majority of studies addressed depression and anxiety. Studies had fair methodological quality although most estimates were unadjusted. Women with PCOS were more likely to have a clinical diagnosis of depression (odds ratio (OR), 2.79; 95% CI, 2.23–3.50), anxiety (OR, 2.75; 95% CI, 2.10–3.60), bipolar disorder (OR, 1.78; 95% CI, 1.43–2.23) and obsessive compulsive disorder (OCD) (OR, 1.37; 95% CI 1.22–1.55), but not social phobia or panic disorder. Using various scales, the severity of symptoms of depression, anxiety, obsessive compulsive disorder, and somatization disorders were higher compared to women without PCOS.
Conclusions
PCOS is associated with an increased risk of diagnosis of depression, anxiety, bipolar disorder, and obsessive compulsive disorder. It is associated with worse symptoms of depression, anxiety, OCD, and somatization. Screening for these disorders to allow early intervention may be warranted.
https://ift.tt/2QRhXzw
New modified Friedewald formulae for estimating low-density lipoprotein cholesterol according to triglyceride levels: extraction and validation
Abstract
Purpose
The most commonly used method for estimating low-density lipoprotein cholesterol (LDLC) is Friedewald formula (FF). This study aims to extract and validate new modified Friedewald formulae for estimating LDLC according to triglyceride (TG) levels in Iranians.
Methods
Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), LDLC, and TG were measured in 5030 fasted subjects. The original FF was used for estimating LDLC. Data were divided into training and validation data sets. For extracting modified Friedewald formulae, linear regression was used with TG as independent and TC, HDLC, and directly measured LDLC (D-LDLC) as dependent variables, respectively. An overall modified formula was extracted for TG concentrations <400 mg/dL. The specific modified formulae were extracted for different TG categories. The performance of the modified formulae was assessed in the validation data set.
Results
The overall derived formula for calculating LDLC was M-LDLC = TC–HDLC–TG/4. The coefficients of TG (specific TG terms) in modified formulae were 2.7, 3.7, 4.6, and 5 for TG <100, 100–200, 200–300, and 300–400 mg/dL, respectively. Compared to the original FF, applying a new modified formula with TG/4 to a validation data set provided a less mean difference (4.03 vs. 10.86 mg/dL), greater kappa coefficient (0.691 vs. 0.505), and better subject classification (80.8 vs. 67.1%). After applying modified formulae with specific TG terms, the difference between M-LDLC and D-LDLC decreased to 1.41 mg/dL.
Conclusions
Modified formulae were developed and validated for LDLC estimation that compared to the original FF, provided more accurate estimation of LDLC and better classification of subjects. These findings shall be useful for preventive, diagnostic, and therapeutic purposes.
https://ift.tt/2AblzqU
The association of smoking and risk of diabetic retinopathy in patients with type 1 and type 2 diabetes: a meta-analysis
Abstract
Purpose
To clarify the relevance between smoking and diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus.
Methods
Published evidence were searched in MEDLINE and EMBASE from the databases began until Feb. 2017. Studies evaluating the association between smoking and diabetic retinopathy or evaluating the risk factors of diabetic retinopathy including smoking were included.
Results
Totally 73 studies were identified, among which 19 studies included type 1 diabetes patients and 56 studies included type 2 diabetes patients. In type 1 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers (risk ratio (RR) = 1.23, 95% CI 1.14, 1.33, P < 0.001), and the risk of proliferative diabetic retinopathy also significantly increased in smokers (RR = 1.48, 95% CI 1.20, 1.81, P < 0.001). In type 2 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly decreased in smokers (RR = 0.92, 95% CI 0.86, 0.98, P = 0.02) and the risk of proliferative diabetic retinopathy also significantly decreased in smokers (RR = 0.68, 95% CI 0.61, 0.74, P < 0.001).
Conclusions
Compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers with type 1 diabetes while significantly decreased in smokers with type 2 diabetes. However, this result did not change the importance of smoking cessation for public health.
https://ift.tt/2Ab9ge2
Cabergoline for the treatment of bromocriptine-resistant invasive giant prolactinomas
Abstract
Purpose
Few studies have specifically focused on the effect of cabergoline on invasive giant prolactinomas (IGPs) resistant to bromocriptine. This study aims to evaluate whether cabergoline could be used as an effective therapy for patients with bromocriptine-resistant IGPs.
Methods
This retrospective study included 15 patients with bromocriptine-resistant IGPs who received treatment at our department during 2007–2015. Cabergoline was administered in all 15 patients, with the dose adjusted depending on the prolactin response of each patient. Parameters for outcome assessment included prolactin level, pituitary function, tumor size, improvement of the clinical symptoms, visual field defects, drug tolerance, and disease recurrence.
Results
Cabergoline was effective for the treatment of the patients with bromocriptine -resistant IGPs as represented by normalization of the prolactin level in 12/15 patients; improvement or normalization of the pituitary function in 4/5 patients with hypopituitarism; significant reduction in tumor size in 14/15 patients; and relief of the clinical symptoms in 11/15 patients. All 15 patients showed good tolerance to cabergoline. In addition, no recurrence was observed during the mean follow-up period of 63.47 (range 30–145) months.
Conclusions
Data of this retrospective study demonstrate that cabergoline is an excellent option for the treatment of patients with bromocriptine-resistant IGPs.
https://ift.tt/2QRhTjg
Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study
Abstract
Introduction
Pasireotide, a multi-somatostatin receptor (SSTR)-ligand with high affinity for SSTR5 was recently approved for acromegaly treatment.
Patients and methods
A retrospective multicenter study investigating the efficacy and safety of long-acting (LAR) pasireotide treatment in 35 patients (20 males) with active acromegaly (28 macroadenomas).
Results
Mean baseline insulin-like growth factor-1 (IGF-1) at diagnosis was 3.1 ± 1.3 × ULN. All but five patients have undergone pituitary surgery and six received sellar radiotherapy. All remained with active acromegaly despite first-generation somatostatin analogue (SSA) treatment. Immediately before pasireotide-LAR initiation, eighteen patients were under SSA monotherapy and one with pegvisomant. The remaining patients received combination therapy with SSA and pegvisomant, n = 9 (two received cabergoline also); SSA and cabergoline, n = 4; pegvisomant and cabergoline, n = 1. Two were untreated. Mean IGF-1 was 1.76 ± 0.9 ULN before pasireotide. Pasireotide-LAR starting dose was 40 mg/4 weeks in most patients. IGF-1 normalized in 19 patients, IGF-1 between 1-1.2 × ULN was reached in five, and in additional two patients IGF-1 was significantly suppressed. No effect was seen in nine patients. Pasireotide dose was reduced by 20 mg in six patients with excellent response, with preserved IGF-1 control in five. Severe headaches in six patients disappeared or improved with pasireotide. Side effects consisted of symptomatic cholelithiasis in one patient and deterioration of glucose control in 22 patients, requiring initiation or intensification of antidiabetic treatment in seventeen. One patient developed diabetic ketoacidosis.
Conclusions
In the real-life scenario ~54% of patients with acromegaly resistant to first-generation SSA, may normalize IGF-1 with pasireotide; however, 63% experienced glucose control deterioration.
https://ift.tt/2QRhPQy
Insights on the phenotypic heterogenity of 11β-hydroxylase deficiency: clinical and genetic studies in two novel families
Abstract
Purpose
11β-hydroxylase deficiency accounts for 5% of congenital adrenal hyperplasia cases. Diagnosis suspiction is classically based on the association between abnormal virilization, precocious puberty, and hypertension in 46XX or 46XY subjects. We investigated two families with siblings presenting with opposed clinical features, and provided a review of the mechanisms involved in mineralocorticoid-dependent phenotypic heterogeneity.
Methods
The coding region of the CYP11B1 gene of 4 patients was sequenced and familial segregation was confirmed. Clinical characterization and blood steroid profile were performed.
Results
Family 1 comprised a female and a male siblings who presented in middle childhood with genital ambiguity (Prader II) and precocious puberty, respectively, associated with hypertension. In the second decade of life, the woman had three full-term pregnancies, and then evolved normotensive with no treatment over a 5-year follow up. On the other hand, her brother had hypertensive end-organ damage at age 24. In family 2, a 2.9 year-old boy presented with precocious puberty and hypertension, whereas his 21 days-old sister had genital ambiguity (Prader III) and salt wasting. A homozygous exon 4 splice site mutation was identified (IVS4ds-1G > A; c.799 G > A) in family 1, while a nonsense mutation in exon 6 (p. Q356X; c.1066 C > T) was found in family 2.
Conclusion
CYP11B1 mutations were associated with highly variable phenotypes, from mild to severe virilization, and early-onset hypertension or salt wasting. Further analysis of variants in other hypertension-related genes, steroid synthesis and metabolism compensatory pathways, and/or the investigation of chimeric CYP11B genes are needed to clarify the phenotypic heterogeneity in 11β-hydroxylase deficiency.
https://ift.tt/2AaaMNl
Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study
Abstract
Aim
Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile.
Methods
The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A—half an hour before breakfast; timing regimen B—an hour before the main meal of the day; timing regimen C—at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study.
Results
Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = −0.017 95% C.I. (−0.400–0.192); baseline vs. B = −0.325 95% C.I. (−0.562–0.023); baseline vs. C = −0.260 95% C.I. (−0.475–0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline.
Conclusion
The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.
https://ift.tt/2QRhsp8
Temporal relationship of sleep apnea and acromegaly: a nationwide study
Abstract
Purpose
Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.
Methods
Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.
Results
Of the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.
Conclusion
Sleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.
https://ift.tt/2Ab1IYB
Melatonin treatment suppresses appetite genes and improves adipose tissue plasticity in diet-induced obese zebrafish
Abstract
Purpose
Overweight and obesity are important risk factors for diabetes, cardiovascular diseases, and premature death in modern society. Recently, numerous natural and synthetic compounds have been tested in diet-induced obese animal models, to counteract obesity. Melatonin is a circadian hormone, produced by pineal gland and extra-pineal sources, involved in processes which have in common a rhythmic expression. In teleost, it can control energy balance by activating or inhibiting appetite-related peptides. The study aims at testing effects of melatonin administration to control-fed and overfed zebrafish, in terms of expression levels of orexigenic (Ghrelin, orexin, NPY) and anorexigenic (leptin, POMC) genes expression and morphometry of visceral and subcutaneous fat depots.
Methods
Adult male zebrafish (n = 56) were divided into four dietary groups: control, overfed, control + melatonin, overfed + melatonin. The treatment lasted 5 weeks and BMI levels of every fish were measured each week. After this period fishes were sacrificed; morphological and morphometric studies have been carried out on histological sections of adipose tissue and adipocytes. Moreover, whole zebrafish brain and intestine were used for qRT-PCR.
Results
Our results demonstrate that melatonin supplementation may have an effect in mobilizing fat stores, in increasing basal metabolism and thus in preventing further excess fat accumulation. Melatonin stimulates the anorexigenic and inhibit the orexigenic signals.
Conclusions
It seems that adequate melatonin treatment exerts anti-obesity protective effects, also in a diet-induced obesity zebrafish model, that might be the result of the restoration of many factors: the final endpoint reached is weight loss and stabilization of weight gain.
https://ift.tt/2QRhrl4
Cortical Balance Between ON and OFF Visual Responses Is Modulated by the Spatial Properties of the Visual Stimulus
Abstract
The primary visual cortex of carnivores and primates is dominated by the OFF visual pathway and responds more strongly to dark than light stimuli. Here, we demonstrate that this cortical OFF dominance is modulated by the size and spatial frequency of the stimulus in awake primates and we uncover a main neuronal mechanism underlying this modulation. We show that large grating patterns with low spatial frequencies drive five times more OFF-dominated than ON-dominated neurons, but this pronounced cortical OFF dominance is strongly reduced when the grating size decreases and the spatial frequency increases, as when the stimulus moves away from the observer. We demonstrate that the reduction in cortical OFF dominance is not caused by a selective reduction of visual responses in OFF-dominated neurons but by a change in the ON/OFF response balance of neurons with diverse receptive field properties that can be ON or OFF dominated, simple, or complex. We conclude that cortical OFF dominance is continuously adjusted by a neuronal mechanism that modulates ON/OFF response balance in multiple cortical neurons when the spatial properties of the visual stimulus change with viewing distance and/or optical blur.https://ift.tt/2yia1AC
Prevention of Dermatitis in Epoxy Exposed Workers
Conditions: Contact Dermatitis; Sensitization Dermatitis
Intervention: Device: Fluorescence visualization (feedback)
Sponsors: Aarhus University Hospital; Arbejdsmiljøforskningsfonden; Vestas Wind Power; Siemens Gamesa Renewable Energy; Skane University Hospital; Herning Hospital; National Research Centre for the Working Environment, Denmark; Aalborg Universitetshospital
Not yet recruiting
https://ift.tt/2yeM8Kc
Intervention: Device: Fluorescence visualization (feedback)
Sponsors: Aarhus University Hospital; Arbejdsmiljøforskningsfonden; Vestas Wind Power; Siemens Gamesa Renewable Energy; Skane University Hospital; Herning Hospital; National Research Centre for the Working Environment, Denmark; Aalborg Universitetshospital
Not yet recruiting
https://ift.tt/2yeM8Kc
Effects of Mobilization and Perceptive Rehabilitation on Patients With Fibromyalgia Syndrome
Condition: Fibromyalgia
Interventions: Other: Perceptive Rehabilitation; Other: Mobilisation Techniques
Sponsor: European University of Lefke
Not yet recruiting
https://ift.tt/2yHtLNg
Interventions: Other: Perceptive Rehabilitation; Other: Mobilisation Techniques
Sponsor: European University of Lefke
Not yet recruiting
https://ift.tt/2yHtLNg
Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: Influence of the disease severity and therapy on the ovarian reserve
Abstract
Purpose
Systemic lupus erythematosus (SLE) mainly affects childbearing age women and pharmacological treatments may negatively influence the ovarian reserve. Anti-Müllerian hormone (AMH) could be a good biomarker for ovarian reserve.
Methods
AMH serum levels were assessed in 86 consecutive SLE female patients with regular menstrual cycle compared with 44 aged matched healthy controls. Clinical and demographic characteristics, disease duration, pattern of organ involvement, and previous and current therapies were recorded.
Results
AMH levels were comparable between patients and controls (4.2 ± 3.1 ng/ml vs. 5.0 ± 3.1 ng/ml, p = 0.21). According to disease severity, AMH levels were lower in SLE patients with major organ involvement than in controls (3.8 ± 2.7 ng/ml vs. 5.0 ± 3.1 ng/ml, p = 0.08); no difference was found between SLE patients with mild organ involvement (4.5 ± 3.4 ng/ml) and controls (p = 0.43). Grouping patients based on the pharmacological treatments, AMH serum levels did not differ among SLE patients treated with antimalarials only (4.7 ± 3.3 ng/ml), conventional disease-modifying antirheumatic drugs (cDMARDs) only (4.8 ± 3.2 ng/ml), cDMARDs and antimalarials (3.9 ± 2.9 ng/ml) or cyclophosphamide (CYC) only (4.9 ± 3.9 ng/ml), compared to controls, but patients sequentially treated with cDMARDs and CYC, had significantly lower AMH serum levels than controls (p = 0.01).
Conclusions
SLE patients showed comparable AMH levels than controls, however, a reduction of the ovarian reserve was associated with sequentially therapy with CYC and cDMARDs and with the disease severity. AMH could be a sensitive and specific biomarker of ovarian reserve in SLE and it could be useful for therapeutic strategy and family planning.
https://ift.tt/2AbfTwV
Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: Influence of the disease severity and therapy on the ovarian reserve
Abstract
Purpose
Systemic lupus erythematosus (SLE) mainly affects childbearing age women and pharmacological treatments may negatively influence the ovarian reserve. Anti-Müllerian hormone (AMH) could be a good biomarker for ovarian reserve.
Methods
AMH serum levels were assessed in 86 consecutive SLE female patients with regular menstrual cycle compared with 44 aged matched healthy controls. Clinical and demographic characteristics, disease duration, pattern of organ involvement, and previous and current therapies were recorded.
Results
AMH levels were comparable between patients and controls (4.2 ± 3.1 ng/ml vs. 5.0 ± 3.1 ng/ml, p = 0.21). According to disease severity, AMH levels were lower in SLE patients with major organ involvement than in controls (3.8 ± 2.7 ng/ml vs. 5.0 ± 3.1 ng/ml, p = 0.08); no difference was found between SLE patients with mild organ involvement (4.5 ± 3.4 ng/ml) and controls (p = 0.43). Grouping patients based on the pharmacological treatments, AMH serum levels did not differ among SLE patients treated with antimalarials only (4.7 ± 3.3 ng/ml), conventional disease-modifying antirheumatic drugs (cDMARDs) only (4.8 ± 3.2 ng/ml), cDMARDs and antimalarials (3.9 ± 2.9 ng/ml) or cyclophosphamide (CYC) only (4.9 ± 3.9 ng/ml), compared to controls, but patients sequentially treated with cDMARDs and CYC, had significantly lower AMH serum levels than controls (p = 0.01).
Conclusions
SLE patients showed comparable AMH levels than controls, however, a reduction of the ovarian reserve was associated with sequentially therapy with CYC and cDMARDs and with the disease severity. AMH could be a sensitive and specific biomarker of ovarian reserve in SLE and it could be useful for therapeutic strategy and family planning.
https://ift.tt/2AbfTwV
Maternal estradiol and progesterone concentrations among singleton spontaneous pregnancies during the first trimester
Abstract
Background
Pregnancy hormonal milieu represents a crucial determinant of fetal outcome. We aim to determine 17β-estradiol (E2) and progesterone (PGT) concentrations in spontaneous pregnancies during the first trimester. In addition, we aim to determine E2 concentrations as a function of gestational age (GA) and PGT.
Methods
Between November 2015 and March 2017, 104 healthy women of at least 18 years undergoing medical consultation for voluntary interruption of pregnancy were enrolled in an observational study at University Hospital ASST Fatebenefratelli Sacco, Milan, Italy. Only singleton pregnancies between 5+0 and 13+6 weeks of gestation were eligible. First trimester ultrasound scans were performed for dating and one fasting venous blood sample was collected for E2 and PGT determinations.
Results
E2 and PGT concentrations steadily increased according to GA. The correlation between E2 on a logarithmic scale and PGT concentrations was expressed by the following equation, explaining 12.6% of E2 variance: logE2 = 2.57 + 0.1 × PGT, (r = 0.34, p < 0.001). By performing a multivariable linear regression analysis adjusted for variables significantly correlated with E2 concentrations, we obtained a model explaining the 53.5% of E2 variance. The final equation to determine E2 concentrations among Caucasian women was: logE2 = 1.96 + 0.01 × GA + 0.004 × PGT.
Conclusions
Gestational week-specific reference intervals are reported for maternal E2 and PGT concentrations during early pregnancy, further providing a model for E2 assessment in this period. This will represent a starting point for further evaluations between twin and ART pregnancies, as well as to potentially improve pregnancy outcome and future health of the offspring.
https://ift.tt/2yityAK
Comparison of diagnostic effects of infrared imaging and bitewing radiography in proximal caries of permanent teeth
Abstract
This study aimed to compare the diagnostic efficacy of VistaCam iX intraoral camera system using infrared light and bitewing radiography for detection of proximal caries in permanent teeth. This in vitro study was performed on 108 teeth. The proximal surfaces of the teeth were examined for caries using ICDAS II criteria, bitewing radiography, and the Proxi head of VistaCam iX. The teeth were then sectioned and histologically analyzed (gold standard). Data were analyzed using SPSS version 25 via the correlation test at P < 0.05 level of significance. The overall and segmental sensitivity and specificity values were calculated for (1) the contact area and higher regions, (2) below the contact area to the cementoenamel junction (CEJ), and (3) below the CEJ. Radiography had the highest specificity. VistaCam had the highest overall and segmental sensitivity for enamel caries. Radiography had the highest segmental sensitivity for dentin. In region 1, VistaCam had the highest sensitivity and lowest specificity, and radiography and ICDAS II had the highest specificity and lowest sensitivity. In region 2, radiography showed the highest sensitivity and specificity. VistaCam had the lowest sensitivity and ICDAS II had the lowest specificity in this region. In region 3, VistaCam did not detect any caries and radiography had a better performance than ICDAS II. The specificity value was equal for both methods. VistaCam had the highest diagnostic efficacy among the three methods for caries in region 1; however, bitewing radiography had a superior efficacy in regions 2 and 3.
https://ift.tt/2AatPXT
Systematic analysis of parameters predicting pathological axillary status (ypN0 vs. ypN+) in patients with breast cancer converting from cN+ to ycN0 through primary systemic therapy (PST)
Abstract
Optimization of axillary staging among patients converting from clinically node-positive disease to clinically node-negative disease through primary systemic therapy is needed. We aimed at developing a nomogram predicting the probability of positive axillary status after chemotherapy based on clinical/pathological parameters. Patients from study arm C of the SENTINA trial were included. Univariable/multivariable analyses were performed for 13 clinical/pathological parameters to predict a positive pathological axillary status after chemotherapy using logistic regression models. Odds ratios and 95%-confidence-intervals were reported. Model performance was assessed by leave-one-out cross-validation. Calculations were performed using the SAS Software (Version 9.4, SAS Institute Inc., Cary, NC, USA). 369 of 553 patients in Arm C were included in multivariable analysis. Stepwise backward variable selection based on a multivariable analysis resulted in a model including estrogen receptor (ER) status (odds ratio (OR) 3.916, 95% confidence interval (CI) 2.318–6.615, p < 0.001), multifocality (OR 2.106, 95% CI 1.203–3.689, p = 0.0092), lymphovascular invasion (OR 9.196, 95% CI 4.734–17.864, p < 0.001), and sonographic tumor diameter after PST (OR 1.034, 95% CI 1.010–1.059, p = 0.0051). When validated, our model demonstrated an accuracy of 70.2% using 0.5 as cut-point. An area under the curve of 0.81 was calculated. The use of individual parameters as predictors of lymph node status after chemotherapy resulted in an inferior accuracy. Our model was able to predict the probability of a positive axillary nodal status with a high accuracy. The use of individual parameters showed reduced predictive performance. Overall, tumor biology was the strongest parameter in our models.
https://ift.tt/2pRggGO
Monitoring treatment response in patients affected by actinic keratosis: dermoscopic assessment and metalloproteinases evaluation after piroxicam 0.8% and sunfilter cream
Dermatologic Therapy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2OqCVJ2
Pretarsal roll augmentation with dermal hyaluronic acid filler injection
Abstract
Pretarsal roll augmentation with dermal hyaluronic acid filler injection focuses on restoring pretarsal fullness. This study aimed to introduce a method of pretarsal roll augmentation with dermal hyaluronic acid filler injection and establish the level of difficulty, safety, and effectiveness of this method. Eighty female patients were enrolled in this study. Hyaluronic acid filler was used to perform pretarsal roll augmentation. Physician and patient satisfaction at 1 month and 4 months after surgery was investigated. The level of satisfaction was graded from points 1 to 5. The patient satisfaction and physician scores were 4.7 ± 1.1 (mean ± standard deviation) points at 1 month and 4.8 ± 0.9 points at 4 months and 4.6 ± 0.9 points at 1 month and 4.8 ± 1.0 points at 4 months, respectively. No major complications were observed. Our technique provided a natural and younger appearance with pretarsal fullness. This technique was easy to perform for the restoration of pretarsal fullness, and it improved periorbital contouring, rejuvenated the pretarsal roll, and provided excellent esthetic results.
Level of Evidence: Level V, therapeutic study.
https://ift.tt/2RVeUIa
Response to Critical appraisal of LIBERTY AD CHRONOS: reply from authors
British Journal of Dermatology, EarlyView.
https://ift.tt/2IXQCcn
Response to critical appraisal of LIBERTY AD CHRONOS
British Journal of Dermatology, EarlyView.
https://ift.tt/2OnCzCS
Shared Decision Making in Psoriasis: A Systematic Review of Quantitative and Qualitative Studies
Abstract
Background
Patients with psoriasis face numerous treatment and self-management decisions. Shared decision making is a novel approach where patients' preferences and values are considered in cooperation with healthcare professionals before making treatment decisions.
Objective
The objective of this systematic review was to explore what is illuminated in psoriasis research regarding shared decision making, and to estimate the effects of shared decision-making interventions in this context.
Methods
Qualitative, quantitative, and mixed-methods studies were eligible for inclusion. We searched six electronic databases up to January 2018. Two reviewers independently applied inclusion and quality criteria. The SPIDER framework was used to identify eligibility criteria for study inclusion. Narrative and thematic syntheses were utilized to identify prominent themes emerging from the data.
Results
A total of 23 studies were included in the review. Of these, we included 18 studies (19 papers) to describe what was illuminated with regard to shared decision making in psoriasis research. Four major themes emerged: interpersonal communication; exchange of competence and knowledge; different world view; and involvement and preference, organized under two analytical themes; "Co-creation of decisions" and "Organization of treatment and treatment needs". For shared decision-making effects, we included four controlled studies. These varied in scope and interventional length and showed limited use of shared decision making-specific outcome measures, reflecting the early stage of the literature. Because of study heterogeneity, a meta-synthesis was not justified.
Conclusions
There appears to be a need to strengthen the relationship between medical doctors and patients with psoriasis. The evident lack of knowledge about each other's competence and the lack of self-efficacy for both patients and providers challenges the basic principles of shared decision making. The effects of shared decision making in psoriasis are inconclusive, and more research appears necessary to determine the possible benefits of shared decision-making interventions.
https://ift.tt/2IWfP74
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