A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections.

BACKGROUND: Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. OBJECTIVE: To summarize injection site reaction data in phase 3 trials of all biologic agents. METHODS: MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. RESULTS: There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). CONCLUSIONS: The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.

The appropriateness and quality of patient-reported outcome measures (PROMs) in plastic surgery randomized controlled trials: A systematic review.

BACKGROUND: Patient-reported outcome measures (PROMs) quantify patient perspectives to measure outcomes that matter to patients. The aim of this study was to assess the reporting of appropriateness and quality of PROM selection in plastic surgery randomized controlled trials (RCTs). METHODS: MEDLINE, Embase, and CENTRAL were searched from January 1, 2000, to June 5, 2022, to identify published RCTs within the plastic surgery literature. Included studies were categorized as follows: 1) a clearly defined patient-reported primary outcome; 2) a primary outcome could be inferred; or 3) no clear or implied primary outcome. The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) database was consulted to assess the available literature on the PROMs. RESULTS: There were 130 plastic surgery RCTs identified. Of the 43 studies with a clear or inferred primary outcome, the percentage of studies that commented with supporting references on the PROM's appropriateness for the population, disease/condition, and outcome were 20.9% (n = 9/43), 18.6% (n = 8/43), and 27.9% (n = 12/43), respectively. The percentage of studies that commented on the PROM's validity, reliability, and responsiveness with supporting references were 34.9% (n = 15/43), 14.0% (n = 6/43), and 11.7% (n = 5/43), respectively. There were 21 unique PROMs identified; 28.6% (n = 6/21) were available in the COSMIN database. CONCLUSION: The majority of plastic surgery RCTs assessing patient-reported primary outcomes lack transparency surrounding PROM selection and quality. We recommend investigators conducting plastic surgery clinical research report explicitly why they used a particular PROM and support its appropriateness and psychometric properties with supporting references. Finally, they should familiarize themselves with the COSMIN initiative.

"Spin" in Observational Studies in Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Systematic Review.

The deep inferior epigastric artery perforator (DIEP) flap is widely used in autologous breast reconstruction. However, the technique relies heavily on nonrandomized observational research, which has been found to have high risk of bias. "Spin" can be used to inappropriately present study findings to exaggerate benefits or minimize harms. The primary objective was to assess the prevalence of spin in nonrandomized observational studies on DIEP reconstruction. The secondary objectives were to determine the prevalence of each spin category and strategy. Methods: MEDLINE and Embase databases were searched from January 1, 2015, to November 15, 2022. Spin was assessed in abstracts and full-texts of included studies according to criteria proposed by Lazarus et al. Results: There were 77 studies included for review. The overall prevalence of spin was 87.0%. Studies used a median of two spin strategies (interquartile range: 1-3). The most common strategies identified were causal language or claims (n = 41/77, 53.2%), inadequate extrapolation to larger population, intervention, or outcome (n = 27/77, 35.1%), inadequate implication for clinical practice (n = 25/77, 32.5%), use of linguistic spin (n = 22/77, 28.6%), and no consideration of the limitations (n = 21/77, 27.3%). There were no significant associations between selected study characteristics and the presence of spin. Conclusions: The prevalence of spin is high in nonrandomized observational studies on DIEP reconstruction. Causal language or claims are the most common strategy. Investigators, reviewers, and readers should familiarize themselves with spin strategies to avoid misinterpretation of research in DIEP reconstruction.

A comparison of skin grafts versus local flaps for facial skin cancer from the patient perspective: protocol for a feasibility study.

BRIEF ABSTRACT: This is a protocol to assess feasibility of conducting a prospective cohort study comparing local flaps versus skin grafts for surgical excision of skin cancer from the face. INTRODUCTION: Skin cancer is the most common malignancy worldwide and the face is one of the most common locations of occurrence. Surgical excision is the most popular treatment for small lesions of the face. Defects can be reconstructed using local flaps or skin grafts. There is a paucity of literature evaluating outcomes after skin cancer surgery from the patient's perspective using valid measurement tools. The purpose of this study is to assess the feasibility of conducting a prospective observational cohort study. The primary outcomes include recruitment rates, eligibility rate, compliance of intervention and rate of completion of the primary outcome (FACE-Q scales) at 3 months. Secondary outcomes include examining patient characteristic and FACE-Q score differences between local flaps to skin grafts and adverse events. METHODS AND ANALYSIS: This study is a prospective cohort study consisting of an anticipated 30 patients aged ≥18 years. The study population will consist of a consecutive sample of non-melanoma facial skin cancer patients undergoing a skin graft or local flap. Patients will be followed and evaluated with the FACE-Q questionnaire at 2 weeks, 3 months, 6 months and 1 year post-operation. The following criteria will determine success: patients who meet eligibility criteria >70%; recruitment rate >70%; compliance with intervention >90%; rate of completion of full-scale prospective study primary outcome (FACE-Q at 3 months) >80%; retention rate at 6-month follow-up visit >70%. DISCUSSION: The findings of this study will be used to guide the sample size calculation for a future, large-scale prospective study.Trial registration: ClinicalTrials.gov (NCT04842279).

Incidence of melanoma and non-melanoma skin cancer in patients with celiac disease: a systematic review and meta-analysis.

There is conflicting observational evidence regarding the association between skin cancer and celiac disease (CD). The purpose of this review was to investigate the incidence rate ratio (IRR) of skin cancer incidence between patients with and without CD. MEDLINE and EMBASE databases were searched on October 27th, 2021 and eight articles were identified for review. Quality assessment was conducted using the Newcastle Ottawa Scale. Seven articles were included in meta-analysis for a pooled estimate of IRR across all skin cancers, malignant melanoma (MM), and non-melanoma skin cancers (NMSC). In total, 74,860 CD patients were followed for 710,214 person-years in the meta-analysis. Overall combined incidence was 99.8 cases per 100,000 person-years. Meta-analysis of all skin cancer incidence showed no significant difference in CD patients compared to controls (IRR: 1.06; 95% CI: 0.95, 1.17; p=0.29; I2: 0%). Five studies reported on MM incidence; there was no significant difference in incidence compared to controls (IRR: 0.87, 95% CI: 0.72, 1.06; p=0.22; I2: 9%). Five studies reported on NMSC incidence, revealing a significantly increased risk of NMSC in CD patients (IRR: 1.14; 95% CI: 1.01, 1.28; p=0.04; I2: 0%). Our findings suggest a significantly increased incidence of NMSC in CD patients compared to control data and no significant association between CD and MM incidence. The findings are limited by the quantity and quality of the evidence. Nonetheless, clinicians should emphasize the importance of sun protection, such as sunscreen usage and self-examination for patients with CD.

Post mortem computed tomography is highly sensitive for pyelonephritis. A radiologic-pathologic correlation series.

Pyelonephritis is a potentially lethal disease occasionally encountered in the forensic setting. Post mortem computed tomography (PMCT) is an important investigative tool for the forensic pathologist. In particular, it may be used to document and screen disease prior to traditional autopsy methods. While the sensitivity and specificity of computed tomography for pyelonephritis is well studied in the antemortem clinical setting, the test characteristics of PMCT are not yet described in the forensic pathology literature. A series of all cases of fatal pyelonephritis identified at the Ontario Forensic Pathology Service, over the course of 1 year was studied. Radiologic, clinical and pathologic findings were reviewed. A fulsome autopsy, including histopathologic examination, was considered the gold standard for sensitivity and specificity calculations. A control group consisting of 16 cases without pyelonephritis (ex: opiate toxicity) in which both PMCT and histologic data were available by way of comparison. Sixteen cases of pyelonephritis were identified. Post mortem computed tomographical signs of pyelonephritis included asymmetric renal enlargement, perinephric fat stranding, and ectopic renal air. The most (57%) individually sensitive of these findings was perinephric fat stranding but sensitivity increased to 100% if any of the three signs were present. The control group analysis revealed the specificity of air asymmetry (81%), asymmetric renal enlargement (81%), and fat stranding (69%). PMCT findings may rule in a diagnosis of pyelonephritis, and should prompt the pathologist to grossly and microscopically examine the kidneys.

Stewart-Treves syndrome and other cutaneous malignancies in the context of chronic lymphedema: a systematic review.

INTRODUCTION: Angiosarcoma developing in chronically lymphedematous tissue, or Stewart-Treves syndrome (STS), is a rare and lethal complication of lymphedema. This systematic review summarizes characteristics and outcomes of STS and other cutaneous malignancies arising in chronic lymphedema. METHODS: MEDLINE and EMBASE databases were searched on February 19th, 2021, to identify 200 articles included in the analysis. RESULTS: Of 369 included patients, 89.7% (n = 331/369) had STS and 10.3% (n = 38/369) had other associated malignancies. Mean age of onset was 61.2 years, and 85.9% (n = 317/369) of cases were female. Common risk factors were previous cancer history (69.8%, n = 258/369) and radiation history (53.7%, n = 198/369). Lymphedema was most commonly attributed to surgical causes (68.3%, n = 252/369). STS begins on average 14.9 years after lymphedema with mortality of 53.9% (n = 178/331) and remission rate of 16.1% (n = 53/331). Other malignancies begin on average 23.7 years after lymphedema, with mortality of 10.5% (n = 4/38) and remission rate of 31.6% (n = 12/38). STS and other malignancies had 5-year survivals of 22.4% and 65.2%, respectively (P = 0.00145). For all patients, patients initially treated with excision had the best survival (median: 48 months, 5-year survival: 43.3%) and radiotherapy had the worst survival (median: 10 months, 5-year survival: 6.5%) (P = 0.0141). CONCLUSION: Malignancy can appear in lymphedematous tissue many years after lymphedema onset. STS has poorer prognosis compared to other malignancies. Further research should be conducted to better understand the causes, risk factors, and management of this phenomenon.

Valve-in-valve prosthesis-late morphological findings.

Since its implantation in 2002, transcatheter aortic valve implantation (TAVI) has become the preferred intervention for patients with severe aortic stenosis and significant co-morbidities. In 2007, it was adopted as a rescue procedure for failed bioprosthetic valves, now known as the valve-in-valve (VIV) procedure. Unlike other modes of treatment with a multitude of phase 4 post-marketing surveillance (PMS) data, use of these valves have increased rapidly even without long term durability data on this procedure and the near lack of information on the pathology of failed transcatheter aortic valve replacement (TAVR) bioprosthesis and especially after the VIV procedure. We present a case of a late explanted VIV bioprosthesis (ten (10) years post-initial aortic valve replacement and five (5) years post-VIV procedure) in a 65-year-old male with multiple morphologic findings. Further availability of standardized morphologic data from explanted bioprosthetic valves is essential to aid in understanding the pathophysiology of tissue degeneration of the TAVI valve, and ultimately to improve patient outcomes by identifying possible early interventional strategies.

Rapid disappearance of influenza following the implementation of COVID-19 mitigation measures in Hamilton, Ontario.

BACKGROUND: Public health measures, such as physical distancing and closure of schools and non-essential services, were rapidly implemented in Canada to interrupt the spread of the coronavirus disease 2019 (COVID-19). We sought to investigate the impact of mitigation measures during the spring wave of COVID-19 on the incidence of other laboratory-confirmed respiratory viruses in Hamilton, Ontario. METHODS: All nasopharyngeal swab specimens (n=57,503) submitted for routine respiratory virus testing at a regional laboratory serving all acute-care hospitals in Hamilton between January 2010 and June 2020 were reviewed. Testing for influenza A and B, respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus, and rhinovirus/enterovirus was done routinely using a laboratory-developed polymerase chain reaction multiplex respiratory viral panel. A Bayesian linear regression model was used to determine the trend of positivity rates of all influenza samples for the first 26 weeks of each year from 2010 to 2019. The mean positivity rate of Bayesian inference was compared with the weekly reported positivity rate of influenza samples in 2020. RESULTS: The positivity rate of influenza in 2020 diminished sharply following the population-wide implementation of COVID-19 interventions. Weeks 12-26 reported 0% positivity for influenza, with the exception of 0.1% reported in week 13. CONCLUSION: Public health measures implemented during the COVID-19 pandemic were associated with a reduced incidence of other respiratory viruses and should be considered to mitigate severe seasonal influenza and other respiratory virus pandemics.

Engineered heat dissipation and current distribution boron nitride-graphene layer coated on polypropylene separator for high performance lithium metal battery.

Li metal as a battery anode has been intensively studied because of its high gravimetric capacity (3860 mAh g-1), a low standard electrode potential (-3.04 vs. SHE), a reasonable electronic conductivity and low density. However, lithium metal suffers from a continuous Li dendrite growth upon charge-discharge cycling, delivering a poor coulombic efficiency and consequently its early failure. Here, engineered bilayer separators demonstrate that a boron nitride-graphene (BNxGry) layer coated on one side of polypropylene (PP) membrane remarkably reduces the polarization and impedance, and significantly improve the performance and stability of Li/Cu half-cells. Moreover, Li/LiFePO4 full cell with the modified BN50Gr50/PP separator presents a remarkably stable 1000 charge-discharge cycles with a specific capacity of 114 mAh g-1 at 1C-rate. The superiority of the modified separator is orginated from an effective synergistic effect between physico-chemical properties of Gr (reducing local current density) and BN (dissipating local heat) and its enhanced structural and mechanical stability.

Rapid disappearance of influenza following the implementation of COVID-19 mitigation measures in Hamilton, Ontario.

Background: Public health measures, such as social distancing and closure of schools and non-essential services, were rapidly implemented in Canada to interrupt the spread of the novel coronavirus disease 2019 (COVID-19). Objective: We sought to investigate the impact of mitigation measures during the spring wave of COVID-19 on the incidence of other laboratory-confirmed respiratory viruses in Hamilton, Ontario. Methods: All nasopharyngeal swab specimens (n = 57,503) submitted for routine respiratory virus testing at a regional laboratory serving all acute-care hospitals in Hamilton, Ontario between January 2010 and June 2020 were reviewed. Testing for influenza A/B, respiratory syncytial virus, human metapneumovirus, parainfluenza Iâ€"III, adenovirus and rhinovirus/enterovirus was done routinely using a laboratory-developed polymerase chain reaction multiplex respiratory viral panel. A Bayesian linear regression model was used to determine the trend of positivity rates of all influenza samples for the first 26 weeks of each year from 2010 to 2019. The mean positivity rate of Bayesian inference was compared with the weekly reported positivity rate of influenza samples in 2020. Results: The positivity rate of influenza in 2020 diminished sharply following the population-wide implementation of COVID-19 interventions. Weeks 12-26 reported 0% positivity for influenza, with the exception of 0.1% reported in week 13. Conclusions: Public health measures implemented during the COVID-19 pandemic were associated with a reduced incidence of other respiratory viruses and should be considered to mitigate severe seasonal influenza and other respiratory virus pandemics.

Surface Functionalization of Carbon Architecture with Nano-MnO2 for Effective Polysulfide Confinement in Lithium-Sulfur Batteries.

Li-S batteries have received tremendous attention owing to their high theoretical capacity (1672 mA h g-1 ), sulfur abundance, and low cost. However, main systemic issues, associated with polysulfide shuttling and low Coulombic efficiency, hinder the practical use of the sulfur electrode in commercial batteries. Herein, we demonstrate an effective strategy of decorating nano-MnO2 (less than 10 wt %) onto the sulfur reservoir to capture the out-diffused polysulfides through chemical interaction and thereby improve the electrochemical performance of the sulfur electrode without increasing the mass burden of total battery configuration. Pistachio shell-derived sustainable carbon (PC) was employed as effective sulfur containers owing to its structural characteristics (interconnected macro channels and micropores). With the aids of the structural benefits of the PC scaffold and the uniform decoration of nano-MnO2 , polysulfide shuttling was significantly suppressed and the cycling performance of the sulfur cathode was dramatically improved over 250 cycles.

Toward High-Performance Lithium-Sulfur Batteries: Upcycling of LDPE Plastic into Sulfonated Carbon Scaffold via Microwave-Promoted Sulfonation.

Lithium-sulfur batteries were intensively explored during the last few decades as next-generation batteries owing to their high energy density (2600 Wh kg-1) and effective cost benefit. However, systemic challenges, mainly associated with polysulfide shuttling effect and low Coulombic efficiency, plague the practical utilization of sulfur cathode electrodes in the battery market. To address the aforementioned issues, many approaches have been investigated by tailoring the surface characteristics and porosities of carbon scaffold. In this study, we first present an effective strategy of preparing porous sulfonated carbon (PSC) from low-density polyethylene (LDPE) plastic via microwave-promoted sulfonation. Microwave process not only boosts the sulfonation reaction of LDPE but also induces huge amounts of pores within the sulfonated LDPE plastic. When a PSC layer was utilized as an interlayer in lithium-sulfur batteries, the sulfur cathode delivered an improved capacity of 776 mAh g-1 at 0.5C and an excellent cycle retention of 79% over 200 cycles. These are mainly attributed to two materialistic benefits of PSC: (a) porous structure with high surface area and (b) negatively charged conductive scaffold. These two characteristics not only facilitate the improved electrochemical kinetics but also effectively block the diffusion of polysulfides via Coulomb interaction.

Acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis.

We report a case of acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis. A 48-year-old previously healthy male was found dead in his locked apartment. At autopsy he was found to be malnourished, and his lungs showed gross evidence of bilateral pneumonia with abscess formation and bullous emphysema. Multiple petechial hemorrhages were observed in the brain and mainly involved white matter in the cerebral hemispheres including the corpus callosum and internal capsule, as well as the cerebellum, brainstem, and spinal cord. Microscopy of the brain and spinal cord revealed perivenular hemorrhages, central microthrombi in venules with fibrin exudation into the subcortical white matter, and early perivenular demyelination associated with scanty mixed cellular infiltrates. Other microscopic features included widespread diffuse viral myocarditis, extensive suppurative bronchopneumonia, and chronic bronchitis. This case illustrates the death of a man with a rare fatal disease associated with two other potentially lethal diseases. The case also illustrates the importance of a holistic approach when determining the cause of death, especially when there are competing causes of death.

Osmium impregnation detection of pulmonary intravascular fat in sudden death: A study of 65 cases.

Pulmonary fat embolism is widely recognised in forensic pathology. Pulmonary fat embolism requires mobilisation of free fat, entry of free fat into the circulation and lodging of fat globules in fine venous capillaries. This paradigm of fat embolisation has been used to support the evidence of antemortem fat depot disruption when the presence of intravascular fat is confirmed at autopsy. However, sporadic reports of intravascular fat in various medical conditions, which contradict the above mechanism, have opened questions about the alternative pathogenesis. In this study, 65 cases of sudden deaths were examined for the presence of pulmonary intravascular fat (PIF) by osmium impregnation. Cases were selected based on the criteria that were designed to eliminate the possible confounding effect from medical intervention or postmortem changes. Slides were graded based on their ease of search and only the fat droplets confined by the blood vessel or capillary wall were considered as a positive finding. The results show surprisingly high PIF incidences of varying degrees in all the categories of sudden deaths. Further study is needed to devise criteria for diagnosis of fatal fat embolism since the histological appearance of the high-grade PIF in natural sudden death may not be easily distinguishable from the traumatic fat embolism.

Sudden death related myocarditis: a study of 56 cases.

Fifty-six cases of sudden death from myocarditis were reviewed to characterize the range of histologic appearances of myocarditis. All autopsy cases of myocarditis over 13 years (1996-2008) in the Toronto Forensic Pathology Unit, Ontario Forensic Pathology Service, were studied. In each case, historical documentation and histological slides were reviewed. The severity of myocarditis was graded qualitatively and quantitatively (the inflammatory index). We established the inflammatory index in order to classify the severity of myocarditis, by counting the mean number of inflammatory foci per section of myocardium. Based on the inflammatory index, myocardial inflammation was classified into four grades. Based on this classification, 47% of the cases were classified as marked myocarditis having an inflammatory index over 5, with the number of foci per slide varying from 3 to more than 10, while 20% were classified as mild myocarditis with an inflammatory index between 1.1 and 1.9 with the number of foci per slide varying from 0 to 6. The diagnosis of mild myocarditis is dependent on adequate sampling. We believe that the use of this inflammatory index enhances the post-mortem diagnostic sensitivity of myocarditis, especially in its mild form and correlates with qualitative assessment of the histologic severity of myocarditis.