A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels

xlomafota13 shared this article with you from Inoreader A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels Via American Journal of Blood Research Am J Blood Res. 2021 Aug 15;11(4):399-404. eCollection 2021. ABSTRACT INTRODUCTION: PCSK9 inhibitors (PCSK9i) are often used in statin-intolerant patients, aiming to reduce low-density lipoprotein cholesterol (LDL-C). Along with the growing experience with their use, there is a lack of evidence regarding the safety, tolerability, and clinical utility of PCSK9i in patients with markedly elevated creatine phosphokinase (CPK) levels. METHODS: We screened a comprehensive HMO database for patients treated with PCSK9i (Jan 2016-Dec 2019), in whom elevated CPK levels (>1,000 U/L) were documented prior to the initiation of therapy. Treatment plans, adherence, and the levels of CPK and LDL-C were analyzed. RESULTS: Of the 1,600 patients initiating treatment with PCSK9i, 26 had prior CPK values >1,000 U/L [median (IQR): 3,687 (1,876-8,344) U/L]. All 26 patients were previously treated with statins, which presumably resulted in adverse effects (myalgia in 24, and rhabdomyolysis in 5 patients) therefore mandating their discontinuation. Concomitant secondary factors for CPK elevation were present in 11 patients, and included renal failure, rheumatoid disorders, hypothyroidism, intensive exercise, proteinuria and genetic muscular disease. Of the 26 patients treated with PCSK9i, alirocumab was administered to 12 patients, and evolocumab to 14. Following the initiation of treatment with either drug, 24 patients (92%) demonstrated a reduction in CPK of >50%, and in 12 (46%) CPK levels have returned to normal values. With regard to treatment goals, 17 patients (65%) have achieved an LDL-C level of <70 mg/dL, and 12 (46%) have reached a level of <55 mg/dL. No serious adverse reactions were documented, and only 2 patients discontinued the treatment (not due to muscle symptoms or CPK elevation). CONCLUSIONS: PCSK9i constitute a safe, tolerable, and effective treatment for hyperlipidemia in patients wi th markedly elevated CPK. While statin intolerance is a major cause for CPK elevation, concomitant etiologies for increased CPK values were rather common. PMID:34540348 | PMC:PMC8446829 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analysing 'tear-drop' prints of acute promyelocytic leukemia (APML): immunophenotypic prognostication of APML by FCM

xlomafota13 shared this article with you from Inoreader Analysing "tear-drop" prints of acute promyelocytic leukemia (APML): immunophenotypic prognostication of APML by FCM Via American Journal of Blood Research Am J Blood Res. 2021 Aug 15;11(4):446-457. eCollection 2021. ABSTRACT INTRODUCTION: Acute promyelocytic leukemia (APML), although genetically and morphologically distinct from other AML (acute myeloid leukemia) subtypes, is one of the most best responsive acute myeloid leukemia. -Conventional diagnostic methods and morphological hints often fail in the majority of the cases in the peripheral laboratories owing to resource constraints, unavailability of cytogenetic work-up, hypogranular variants, morphological mimicry by AML-monocytic and myelo-monocytic, etc. Flowcytometry (FCM), however, can be utilized as a feasible and reliable immunophenotypic diagnostic and prognostic tool for prompt identification of APML. In order to rapidly and sensitively diagnose APML we intended to suggest a cost effective, sensitive FCM panel and also to prognositicate patients. MATERIAL AND METHODS: In this retrospective study, flowcytometry characte ristics of 123 cases of acute promyelocytic leukemia were studied including 40 hypogranular variants. The expression of markers was compared with the Mean flurescent Intensity (MFI) and percent expression of markers. A non-statistical comparison was made with cases of acute monocytic leukemia. The cases were grouped according to their immunophenotype characteristics and expression with comparison of MFI by multivariate logistic regression. The aberrant markers positive at diagnostic and remission flow test were compared with the survival outcomes, and their positive predictive values were calculated. RESULTS: The most common feature of side scatter property was the absence of blasts in the window and high side scatter, except hypogranular variants which had low side scatter. Immunophenotypically characterised by positivity for CD117, cMPO, and bright CD33 and CD13 positivity and lack of CD34 and HLA-DR was seen in the majority of APML including hypo-granular variant. We sugges t a rapid diagnostic four-tube panel for fast and rapid diagnosis of APML, including hypogranular variants with 100% sensitivity. The study also identified six groups of immunophenotypes with significant prediction values of APML, including hypogranular variants. The study also highlights CD2, CD56, and CD9 as prognostic markers for acute promyelocytic leukemia. PMID:34540354 | PMC:PMC8446832 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prognostic factors for descending necrotizing mediastinitis development in deep space neck infections-a retrospective study

xlomafota13 shared this article with you from Inoreader Prognostic factors for descending necrotizing mediastinitis development in deep space neck infections-a retrospective study Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 Sep 20. doi: 10.1007/s00405-021-07081-0. Online ahead of print. ABSTRACT OBJECTIVES: Descending necrotizing mediastinitis (DNM) is the most serious complication of deep neck infections (DNI). The objective of this retrospective study was to evaluate prognostic factors for DNM development in deep space neck infections. METHODS: The study enrolled patients admitted to the Emergency Center of Vojvodina with the diagnosis of multispace DNI with or without DNM either as the primary diagnosis or with discharged diagnosis after surgical treatment during 7-year period. The data were obtained from patient medical records. RESULTS: After final analysis total of 141 charts were randomized for statystical analysis, 124 charts in DNI and 17 in DNI + DNM groups. The most common cause of infection in both groups was odontogenic. On multivariate regression analysis of collected data infection of retropharyng eal, pretracheal and carotid space, C-reactive protein and procalcitonine values were statistically significant predictors for DNM development. CONCLUSIONS: Treatment and diagnosis of DNM requires multidisciplinary approach, with prompt clinical and radiological examinations, empirical broad spectrum antibiotic therapy and radical surgical debridement. Multispace neck infection and especially infection of retropharyngeal, carotid and pretracheal spaces are the most sensitive predictors for DNM development in deep space neck infections. CLINICAL RELEVANCE: If the infection from deep neck spaces reach retropharyngeal, carotid or pretracheal space, the DNM is probable to occur. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT04865003. Date of registration 27.4.2021. PMID:34542654 | DOI:10.1007/s00405-021-07081-0 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mental health indicators in the later phase of lockdown due to COVID-19 pandemic in healthy youth combined elderly people: a web-based cross-sectional survey

xlomafota13 shared this article with you from Inoreader Mental health indicators in the later phase of lockdown due to COVID-19 pandemic in healthy youth combined elderly people: a web-based cross-sectional survey Via International Journal of Physiology, Pathophysiology and Pharmacology Int J Physiol Pathophysiol Pharmacol. 2021 Aug 15;13(4):117-125. eCollection 2021. ABSTRACT Lockdown was implemented throughout the world in March 2020 to control the spread of covid-19 infection. It affected the mental health of people in various ways. This web-based cross-sectional survey was conducted in the general population of India with an aim to evaluate the mental health of the healthy individuals in the later stage of the lockdown period. Data on socio-demographic factors, anxiety, depression (HADS scale), perceived stress (PSS scale), insomnia (insomnia severity index), subjective psychological feeling of well-being (WHO-5 well-being Index), and attitude towards covid-19 (7-point Likert scale) was collected. Univariate regression analysis and Karl Pearson's correlation were used to analyze the correlation of mental health abnormalities with socio-demographic factors. 119 subjects of mean age of 36.03 ± 18.04 years took part in the study. Their average number of days of stay at home during the lockdown and the average number of days of the lifestyle changes was 49.07 ± 31.92 and 61.39 ± 20.03 days, respectively. Depression, anxiety, stress, and clinical insomnia due to covid-19 were reported in 13.45%, 10.92%, 14.29%, and 11.76% subjects, respectively. There was a significant correlation of depression, anxiety, stress, and WHO-5 well-being score with age, socio-economic status, and the average number of days of the change in lifestyle due to the COVID-19 pandemic (P < 0.05). Therefore, the study concluded that the abnormalities of mental health were less prevalent in the older age group and lower socioeconomic status in the later phase of lockdown. PMID:34540132 | PMC:PMC8446773 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Complications of Robot‐assisted Thymectomy: A Single‐arm Meta‐analysis and Systematic Review

xlomafota13 shared this article with you from Inoreader Complications of Robot‐assisted Thymectomy: A Single‐arm Meta‐analysis and Systematic Review Via The International Journal of Medical Robotics and Computer Assisted Surgery Abstract Background Recently, thymectomy using minimally invasive approaches has been increasing with the development of robotic video-assisted thoracoscopic surgery (R-VATS). Although multimodal approach is effective for robot assisted thymectomy, it is necessary to determine the approach (left, right or sub xiphoid) associated with the least complications. Methods An electronic retrieval from PubMed, Embase, Web of Science, GreyNet International, and The Cochrane Library. The single-arm meta-analysis was performed to compare the rate of complications of right and left-side approaches by R-VATS. Results A total of 21 studies including 930 patients were identified. The pooled incidence of total complications was 12.2% (CI: 10.0%−14.8%) for all studies. The overall complication rate was 17.3% for the right side compared with 7.4% for the left side (P<0.001, OR=2.484, 1.601−3.852). The pooled incidence of air leak was significantly higher for the right vs. left side (5.1% vs. 1.2%, respectively; P=0.004). The incidence of atrial fibrillation was higher for the right- compared with the left-side approach (4% vs. 1.2%, respectively; P=0.004). The open conversion rate was significantly higher for the right vs. the left side (6.5% vs. 2.9%, respectively; P=0.004). However, there was no significant difference in the pooled incidence of pleural effusion and thoracic duct fistula when comparing the right- and left-side approaches. In subgroup analysis, In the left approach, The incidence of overall complications (28.6% vs 5.5%, respectively;p=0.002) and pleural effusion(14.3% vs 1%, respectively;p=0.002) was higher for the "Old Age" group compared with the "Youth" group; there was no significant difference in the incidence of complications after thymectomy. Conclusion R-VATS can be performed on the left- and right-sides; However, complications are minimal with the left-side approach. These data demonstrate that the incidence of overall complications, atrial fibrillation, open conversion ratios, and air leak rate of left-side R-VATS thymectomy are lower than those of right-side. Further subgroup analysis showed that the incidence of postoperative complications was higher in the older group. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

External Auditory Canal Pleomorphic Adenoma: A Rare Case Presentation

xlomafota13 shared this article with you from Inoreader External Auditory Canal Pleomorphic Adenoma: A Rare Case Presentation Via Otolaryngology Indian Abstract Pleomorphic adenoma originating from the external auditory canal is extremely rare, benign tumor. Ceruminal glands are modified sweat glands of the skin, present in the external auditory canal that may give rise to (a) benign tumors such as ceruminous adenoma, pleomorphic adenoma, and syringocystadenoma papilliferum, or (b) malignant tumors such as ceruminous adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma. We report a case where a 25-year-old woman presented with right aural swelling and otalgia since 1 year. A canal-filling aural mass was noted on clinical examination. Computed tomography imaging showed no intracranial extension or any association with the adjacent parotid gland. Subsequent excision biopsy and histologic examination revealed features suggestive of pleomorphic adenoma. Similar to the pleomorphic adenoma of salivary glands, recurrence or malignant degeneration with cellular atypia and metastasis can occur on rare occasions. Care must be taken to distinguish this from adenoid cystic carcinomas, ceruminous adenocarcinomas, and mucoepidermoid carcinomas. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Stratum corneum lipidomics analysis reveals altered ceramide profile in atopic dermatitis patients across body sites with correlated changes in skin microbiome

xlomafota13 shared this article with you from Inoreader Stratum corneum lipidomics analysis reveals altered ceramide profile in atopic dermatitis patients across body sites with correlated changes in skin microbiome Via Experimental Dermatology Abstract Background Atopic dermatitis (AD) is driven by the interplay between a dysfunctional epidermal barrier and a skewed cutaneous immune dysregulation. As part of the complex skin barrier dysfunction, abnormalities in lipid organization and microbiome composition have been described. We set out to systematically investigate the composition of the stratum corneum lipidome, skin microbiome and skin physiology parameters at three different body sites in patients with AD and healthy volunteers. Methods We analysed tape strips from different body areas obtained from 10 adults with AD and 10 healthy volunteers matched for FLG mutation status for 361 skin lipid species using the Metabolon mass spectrometry platform. 16S rRNA data were available from all probands. Results Our study showed that the lipid composition differs significantly between body sites and between AD patients and healthy individuals. Ceramide species NS was significantly higher in AD patients compared to healthy volunteers and was also higher in AD patients with a FLG mutation compared to AD patients without a FLG mutation. The correlation analysis of skin lipid alterations with the microbiome showed that Staphylococcus colonization in AD is positively correlated with ceramide subspecies AS, ADS, NS and NDS. Conclusion This is the first study to reveal site-specific lipid alterations and correlations with the skin microbiome in AD. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparison of the skin microbiota in acne and rosacea

xlomafota13 shared this article with you from Inoreader Comparison of the skin microbiota in acne and rosacea Via Experimental Dermatology Abstract Acne and rosacea, despite their similar clinical presentations, follow distinct clinical courses, suggesting that fundamental differences exist in their pathophysiology. We performed a case-control study profiling the skin microbiota in rosacea and acne patients compared to matched controls. Nineteen rosacea and eight acne patients were matched to controls by age ± 5 years, sex and race. DNA was extracted from facial skin swabs. The V3V4 region of the bacterial 16S rRNA gene was sequenced using Illumina MiSeq and analysed using QIIME/Metastats 2.0 software. The mean relative abundance of Cutibacterium acnes in rosacea with inflammatory papules and pustules (20.454% ±16.943%) was more similar to that of acne (19.055% ±15.469%) than that of rosacea without inflammatory papules and pustules (30.419% ±21.862%). C acnes (P = .048) and Serratia marcescens (P = .038) were significantly enriched in individuals with rosacea compared to acne. Investigating the differences between the skin microbiota in acne and rosacea can provide important clues towards understanding the disease progression in each condition. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lower melanoma pulmonary metastatic burden in obese mice: role of FGF-21

xlomafota13 shared this article with you from Inoreader Lower melanoma pulmonary metastatic burden in obese mice: role of FGF-21 Via Melanoma Research - Published Ahead-of-Print Obesity is a risk factor for malignant melanoma. The lungs are main target organs for metastization and their immune response is a key modulator of this mechanism. The concept that the metastatic potential of some types of cancer is reduced or inhibited by obesity, known as the obesity paradox, drives major concerns on the prognosis of metastasized patients. The aim of this study was to investigate how high-fat diet (HFD)-induced obesity affects melanoma metastization. C57Bl6/J mice were fed with HFD or standard diet for 180 days and inoculated intravenously with B16F10 melanoma cells. Upon 21 days of inoculation, lung tissue of overweight and lean mice was assessed for histology and immunohistochemistry assays. Adipokine antibody arrays were performed in mice serum. In vitro RAW 264.7 macrophage cultures were established and incubated with FGF-21 and/or lipopolysaccharide (LPS). Conditioned media was added to B16F10 cells for viability quantification. HFD-fed mice presented a reduced number of metastases with lower proliferative rates. The high content of inflammatory foci observed in noninoculated obese mice was significantly decreased upon B16F10 inoculation, concurrent with a slight fibrosis reduction. Plasma levels of fibroblast growth factor-21 (FGF-21), an endocrine regulator, were elevated in noninoculated HFD mice and the expression of FGF receptor 1 (FGFR-1) was significantly upregulated after inoculation. FGF-21 reduced melanoma viability in LPS-stimulated macrophages. Altogether, these findings suggest that higher amounts of FGF-21 are able to counterbalance the proinflammatory effects associated with obesity, protecting the lungs from melanoma metastization. Received 17 December 2020 Accepted 17 August 2021 Correspondence to Pedro Coelho, PhD, Chemical Sciences and Biomolecules, School of Health, Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida, 400 4200 - 072 Porto, Portugal, Tel: +351 222 061 000; e-mail: pvc@ess.ipp.pt Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Efficacy of Septal Quilting Sutures Versus Nasal Packing in Septoplasty

xlomafota13 shared this article with you from Inoreader The Efficacy of Septal Quilting Sutures Versus Nasal Packing in Septoplasty Via Otolaryngology Indian Abstract Nasal packing is the classic method adopted by many otolaryngologists to stabilize the nasal septum and decrease the occurrence of postoperative bleeding and septal hematoma after septoplasty. However, because of its associated postoperative morbidity, many surgeons started to adopt alternative methods. This study aimed to assess the outcome and benefits of septal quilting sutures in comparison to nasal packing after septoplasty. A prospective non-randomized comparative interventional study was carried out at two teaching hospitals in Mosul city from January 2020 to January 2021. A total of 60 patients who were candidates for septoplasty, were included in the study. According to the surgeon's preference; 30 patients had placement of septal quilting sutures (group A), and in the other 30 patients nasal packing was performed (group B). Patients were assessed for postoperative morbidity and early outcome in the first 24 h, 1 week and 1 month postopera tively. In the first 24 h after septoplasty, patients in group B had significantly higher levels of nasal/facial pain, headache, sleep disturbance, breathing difficulties and swallowing difficulties compared to group A (p < 0.001). Over the follow up period of 1 month, no significant differences were recorded regarding postoperative bleeding, hematoma, infection, adhesions formation and septal perforation between the two groups (p > 0.05). Septal quilting sutures technique is more favorable in the early period in terms of patient discomfort after septoplasty, better nasal block and nasal/facial pain, the absence of misery on pack removal, with minimal bleeding after surgery. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lesser Known Uses of γ‐Aminobutyric Acid Analogue Medications in Otolaryngology

xlomafota13 shared this article with you from Inoreader Lesser Known Uses of γ‐Aminobutyric Acid Analogue Medications in Otolaryngology Via The Laryngoscope Objectives/Hypothesis In otolaryngology, γ-aminobutyric acid (GABA) analogues have been previously analyzed for their roles in neuropathic pain, chronic cough, tinnitus, and perioperative analgesia. The primary aim of this study is to comprehensively summarize and synthesize the existing evidence for lesser known uses of gabapentin and pregabalin in otolaryngology. Study Design A scoping review conducted of the available English-language literature was performed by two authors through April 1, 2021. Methods The Preferred Reporting Items for Systematic Review and Meta-Analysis criteria were followed, and a quality assessment of included studies was performed using the Methodological Index for Non-Randomized Studies. Results Ten studies met inclusion criteria. Three studies found that gabapentin may reduce gastrostomy tube usage and improve swallowing function in head and neck cancer patients undergoing radiation therapy (RT). Three studies suggested that gabapentin may help reduce opiate use when used as a primary analgesic in patients with radiation-induced mucositis. One study demonstrated that pregabalin-reduced trismus severity in patients with radiotherapy-induced trismus. One study demonstrated gabapentin may be useful in patients with phonasthenia. Two studies demonstrated that GABA analogues may be a useful adjunct in patients with globus pharyngeus in the context of likely laryngeal sensory neuropathy. Conclusions The most promising potential uses for GABA analogues identified in this review are for improving swallowing, trismus, and narcotic overuse after RT. The benefit of GABA analogues for improving nonorganic voice disorders is also promising while the benefit for globus pharyngeus when possibly related to laryngeal sensory neuropathy is inconclusive. Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.