Tamoxifen Alters TGF‐β1/Smad Signaling in Vocal Fold Injury

alexandrossfakianakis shared this article with you from Inoreader Tamoxifen Alters TGF‐β1/Smad Signaling in Vocal Fold Injury via The Laryngoscope This study investigated the effects of tamoxifen on acute vocal fold injury in a preclinical model. The antifibrotic actions of tamoxifen appear to be mediated by transforming growth factor beta 1/Smad signaling providing a novel target for intervention. Objectives Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF-β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis. Methods In vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF-β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real-time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre-injury day 5 to post-injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture. Results TAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF-β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF-β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment. Conclusions TAM has antifibrotic potential via the regulation of TGF-β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis. Level of Evidence NA Laryngoscope, 2022 View on Web

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Monkeypox treatment: current evidence and future perspectives

alexandrossfakianakis shared this article with you from Inoreader Monkeypox treatment: current evidence and future perspectives via Journal of Medical Virology Abstract As of 11 September 2022, 57,669 reports of monkeypox infection raised global concern. Previous vaccinia virus vaccination can protect from monkeypox. However, after smallpox eradication, immunization against that was stopped. Indeed, therapeutic options following the disease onset are of great value. This study aimed to review the available evidence on virology and treatment approaches for monkeypox and provide guidance for patient care and future studies. Since no randomized clinical trials were ever performed, we reviewed monkeypox animal model studies and clinical trials on the safety and pharmacokinetics of available medications. Brincidofovir and tecovirimat were the most studied medications that got approval for smallpox treatment according to the Animal Rule. Due to the conserved virology among orthopoxviruses, available medications might also be effective against monkeypox. However, tecovirimat has the strongest evidence to be effective and saf e for monkeypox treatment, and if there is a choice between the two drugs, tecovirimat has shown more promise so far. The risk of resistance should be considered in patients who failed to respond to tecovirimat. Hence, the target-based design of novel antivirals will enhance the availability and spectrum of effective anti-orthopoxvirus agents. This article is protected by copyright. All rights reserved. View on Web

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Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham)

alexandrossfakianakis shared this article with you from Inoreader Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham) via Pediatric Blood & Cancer Abstract Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin. View on Web

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Posterior nasal neurectomy for intractable rhinitis: a systematic review of the literature

alexandrossfakianakis shared this article with you from Inoreader Posterior nasal neurectomy for intractable rhinitis: a systematic review of the literature via Clinical Otolaryngology Abstract Background Rhinitis affects up to 40% of the population worldwide and can significantly reduce quality of life. Some patients remain symptomatic despite maximal medical therapy. In refractory cases, posterior nasal neurectomy (PNN - the endoscopic division of the intranasal nerve branches containing postganglionic parasympathetic fibres) is postulated to reduce symptom burden. Objectives of review To establish whether PNN is effective and safe in the management of allergic and non-allergic rhinitis. Type of review Systematic review Methods A comprehensive literature search was undertaken using PubMed, EMBASE, MEDLINE, and Cochrane. The inclusion criteria were: studies published in English, studies where PNN was performed either with or without additional procedures, and where measures of objective/subjective outcomes and/or complications were reported. Extracted data included study type, sample size, surgical technique, study population characteristics, follow-up period, outcome measures, complications of surgery, and symptom outcomes. Results Twenty-three articles satisfied the inclusion criteria studying in total 2282 patients. Sample size ranged from 8-1056. There were three randomised controlled trials, three case control studies, and the remaining seventeen were case series using both objective and subjective outcome measures. All but one study found improved patient reported outcomes following PNN. Complications were reported in 14 studies - epistaxis was the most common complication and was observed in 30 patients (1.5% of subjects). Conclusions Posterior nasal neurectomy had a low rate of complications. Although most studies reported significant symptomatic improvement, their heterogeneity, level of evidence, study design, and/or quality was not sufficient to draw any firm conclusions on the effectiveness of the procedure. Larger, well designed studies are needed to clarify its role in the management of difficult-to-treat rhinitis. This article is protected by copyright. All rights reserved. View on Web

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Exposure, Susceptibility, and Recovery: A Framework for Examining the Intersection of the Social and Physical Environment and Infectious Disease Risk

alexandrossfakianakis shared this article with you from Inoreader Exposure, Susceptibility, and Recovery: A Framework for Examining the Intersection of the Social and Physical Environment and Infectious Disease Risk via American Journal of Epidemiology - Advance Access Abstract Despite well-documented evidence that structurally disadvantaged populations are disproportionately affected by infectious diseases, our understanding of the pathways that connect structural disadvantage to the burden of infectious diseases is limited. We propose a conceptual framework to facilitate more rigorous examination and testing of hypothesized mechanisms through which social and environmental factors shape the burden of infectious diseases and lead to persistent inequities. Drawing upon the principles laid out by Link and Phelan in their landmark paper on social conditions, we offer an explication of potential pathways through which structural disadvantage (e.g., racism, sexism, and economic deprivation) operates to produce infectious disease inequities. Specifically, we describe how the social environment impacts an individual's risk of infectious disease through 1) increasing exposure to infectious pathogens; and 2) increasing suscep tibility to infection. This framework will facilitate both the systematic examination of the ways in which structural disadvantage shapes the burden of infectious disease and the design of interventions that can disrupt these pathways. View on Web

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Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial

alexandrossfakianakis shared this article with you from Inoreader Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial via Annals of Surgery - Most Popular Articles Objective: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. Background: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. Methods: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. Results: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P=0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P=0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. Conclusion: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF. View on Web

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Long-Term Oncological Outcomes After Colorectal Anastomotic Leakage: A Retrospective Dutch Population-based Study

alexandrossfakianakis shared this article with you from Inoreader Long-Term Oncological Outcomes After Colorectal Anastomotic Leakage: A Retrospective Dutch Population-based Study via Annals of Surgery - Most Popular Articles Objective: The aim was to evaluate the impact of anastomotic leak (AL) after colon cancer (CC) and rectal cancer (RC) surgery on 5-year relative survival, disease-free survival (DFS), and disease recurrence. Background: AL after CC and RC resection is a severe postoperative complication with conflicting evidence whether it deteriorates long-term outcomes. Methods: Patients with stage I to IV CC and RC who underwent resection with primary anastomosis were included from the Netherlands Cancer Registry (2008–2018). Relative survival, measured from day of resection, and multivariable relative excess risks (RERs) were analyzed. DFS and recurrence were evaluated in a subset with stage I to III patients operated in 2015. All analyses were performed with patients who survived 90 days postoperatively. Results: A total of 65,299 CC and 22,855 RC patients were included. Five-year relative survival after CC resection with and without AL was 95% versus 100%, 89% versus 94%, 66% versus 76%, and 28% versus 25% for stage I to IV disease. AL was associated with a significantly higher RER for death in stage II and III CC patients. Stage-specific 5-year relative survival in RC patients with and without AL was 97% versus 101%, 90% versus 95%, 74% versus 83%, and 32% versus 41%. AL was associated with a significantly higher RER for death in stage III and IV RC patients. DFS was significantly lower in CC patients with AL, but disease recurrence was not associated with AL after colorectal cancer resection. Conclusion: AL has a stage-dependent negative impact on survival in both CC and RC, but no independent association with disease recurrence. View on Web

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Factors Considered Important by Healthcare Professionals for the Management of Using Complementary Therapy in Diabetes: A Text-Mining Analysis

alexandrossfakianakis shared this article with you from Inoreader Factors Considered Important by Healthcare Professionals for the Management of Using Complementary Therapy in Diabetes: A Text-Mining Analysis via Computers Informatics Nursing - Published Ahead-of-Print Text-mining algorithms can identify the most prevalent factors of risk-benefit assessment on the use of complementary and integrative health approaches that are found in healthcare professionals' written notes. The aims of this study were to discover the key factors of decision-making on patients' complementary and integrative health use by healthcare professionals and to build a consensus-derived decision algorithm on the benefit-risk assessment of complementary and integrative health use in diabetes. The retrospective study of an archival dataset used a text-mining method designed to extract and analyze unstructured textual data from healthcare professionals' responses. The techniques of classification, clustering, and extraction were performed with 1398 unstructured clinical notes made by healthcare professionals between 2019 and 2020. The most important factor for decision-making by healthcare professionals about complementary and integrative health use in patients with diabetes was the ingredients of the product. Other important factors were the patient's diabetes control, the undesirable effects from complementary and integrative health, evidence-based complementary and integrative health, medical laboratory data, and the product's affordability. This exploratory text-mining study provides insight into how healthcare professionals decide complementary and integrative health use for patients with diabetes after a risk-benefit assessment from clinical narrative notes. View on Web

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The Contribution of Health Behaviors to Depression Risk Across Birth Cohorts

alexandrossfakianakis shared this article with you from Inoreader The Contribution of Health Behaviors to Depression Risk Across Birth Cohorts via Epidemiology - Current Issue Background: More recent birth cohorts are at a higher depression risk than cohorts born in the early 20th century. We aimed to investigate to what extent changes in alcohol consumption, smoking, physical activity, and obesity contribute to these birth cohort variations. Methods: We analyzed panel data from US adults born 1916–1966 enrolled in the Health and Retirement Study (N = 163,760 person-years). We performed a counterfactual decomposition analysis by combining age-period-cohort models with g-computation. We thereby compared the predicted probability of elevated depressive symptoms (CES-D 8 score ≥3) in the natural course to a counterfactual scenario where all birth cohorts had the health behaviors of the 1945 birth cohort. We stratified analyses by sex and race-ethnicity. Results: We estimated that depression risk of the 1916–1949 and 1950–1966 birth cohort would be on average 2.0% (–2.3 to –1.7) and 0.5% (–0.9 to –0.1) higher with the alcohol consumption levels of the 1945 cohort. In the counterfactual with the 1945 BMI distribution, depression risk is on average 2.1% (1.8 to 2.4) higher for the 1916–1940 cohorts and 1.8% (–2.2 to –1.5) lower for the 1950–1966 cohorts. We find no cohort variations in depression risk for smoking and physical activity. The contribution of alcohol is more pronounced for Whites than for other race-ethnicity groups, and the contribution of BMI more pronounced for women than for men. Conclusion: Increased obesity levels were associated with exacerbated depression risk in recent birth cohorts in the United States, while drinking patterns only played a minor role. View on Web

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Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis in Denmark: A Bayesian Hierarchical Analysis

alexandrossfakianakis shared this article with you from Inoreader Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis in Denmark: A Bayesian Hierarchical Analysis via Epidemiology - Current Issue Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. Methods: In this population-based case–control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989–2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NOx), carbon monoxide (CO), and fine particles (PM2.5) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NOx, CO). Results: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m3) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = –1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NOx (SD = 20 µg/m3) (–4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m3) (–3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM2.5) (SD = 2.37 µg/m3) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. Conclusions: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis. View on Web

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