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To assess outcomes and complications of conservatively managed humeral diaphyseal fractures in elderly patients, with an emphasis on the subgroup diagnosed with dementia.Retrospective.Upper extremity surgery unit at an academic Level I trauma center.Consecutive patients 65 years of age and older who were managed conservatively for humeral diaphyseal fractures between 2007 and 2015.Conservatively managed humeral diaphyseal fractures.Complications and radiographic outcomes.One-hundred twenty-four patients who were conservatively managed for humeral diaphyseal fractures were identified. Their mean age was 77 (65-92) years, 36 (30%) of them were male and 88 (70%) were female. Fifty-seven (46%) patients experienced complications associated with their treatment, and 33 (27%) patients were eventually treated surgically. Seventeen (14%) patients were diagnosed with dementia. This subgroup had 64% fracture-related complications, and all of them were operated (P-value0.01 compared with age-matched patients among the other 107 participants in the study).Conservative management of humeral diaphyseal fractures seems to be associated with greater morbidity in elderly patients, especially in those diagnosed with dementia. Therefore, early surgical treatment should be considered.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

In 2014, the number of coordinated specialty care (CSC) programs in the United States greatly expanded. The proliferation of CSC programs was likely due in part to the availability of Mental Health Block Grant (MHBG) set-aside funds for treatment of first-episode psychosis. This study aimed to explore the characteristics of CSC programs across 44 states, the District of Columbia, and three U.S. territories that received funding through the MHBG set-aside program in 2018.Leadership at 88% (N=215) of the 244 MHBG-funded CSC programs identified through state mental health authorities participated in an online survey.Overall, 69% of the CSC programs were initiated after 2014. More than 90% of programs included services that were consistent with federal guidance. CSC programs showed variability in training received, program size, and enrollment criteria.The results of this study emphasize that clear federal guidance can help shape national CSC implementation efforts, although decisions at the state and local levels can influence how implementation occurs. The strategy of states administering federal funds for CSC may be adapted for the rollout of other behavioral health interventions. Future studies could investigate factors that may shape national dissemination efforts, such as leadership within the state, funding, availability of programs established before the influx of funding, and considerations about sustainability after the funding is no longer available.

Long-acting injectable antiretroviral therapy (LAI-ART) for the treatment and prevention of human immunodeficiency virus (HIV) holds great potential to shift treatment paradigms by offering an alternative to daily oral medication. However, significant challenges at the drug, patient, and system levels risk impeding the uptake and implementation of LAI-ART. This review aims to describe the known and anticipated barriers to uptake of LAI-ART in high-income countries, as well as the ongoing research addressing some of these barriers to improve the delivery and uptake of LAI-ART products.

As the composition and work of surgical teams evolve, the role of advanced practice providers (APPs) has expanded. We explored how APPs influence the training experience of surgeons from the perspectives of faculty, residents, and APPs.Qualitative data were obtained from semi-structured open-ended interviews. A codebook was developed blending deductive and inductive logics. Dyads independently coded the transcripts using a constant comparative approach; differences were reconciled by consensus.During 2-day site visits to 15 general surgery programs, 393 individual and small focus group interviews were conducted with residents, faculty, staff, and program leadership. Forty transcripts representing 51 interviewees (15 APPs, 23 residents, 13 faculty) were collected. We identified 4 major themes:APPs have an active and essential role in the well-being and education of surgeons during training. Surgical residency programs and hospitals have an opportunity to decrease the "invisibility" of the work of APPs through increased recognition of these roles and elevation of APP expertise through formal career development pathways.

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Recent recommendations describe a set of core anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia (UGRA). This project aimed to generate consensus recommendations for core structures to identify during the performance of intermediate and advanced blocks. An initial longlist of structures was refined by an international panel of key opinion leaders in UGRA over a three-round Delphi process. All rounds were conducted virtually and anonymously. Blocks were considered twice in each round: for “orientation scanning” (the dynamic process of acquiring the final view) and for “block view” (which visualizes the block site and is maintained for needle insertion/injection). A “strong recommendation” was made if ≥75% of participants rated any structure as “definitely include” in any round. A “weak recommendation” was made if >50% of participants rated it as “definitely include” or “probably include” for all rounds, but the criterion for strong recommendation was never met. Structures which did not meet either criterion were excluded. Forty-one participants were invited and 40 accepted; 38 completed all three rounds. Participants considered the ultrasound scanning for 19 peripheral nerve blocks across all three rounds. Two hundred and seventy-four structures were reviewed for both orientation scanning and block view; a “strong recommendation” was made for 60 structures on orientation scanning and 44 on the block view. A “weak recommendation” was made for 107 and 62 structures, respectively. These recommendations are intended to help standardize teaching and research in UGRA and support widespread and consistent practice.

Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced practitioners. Current evidence shows that unrecognised oesophageal intubation occurs sufficiently frequently to be a major concern and to merit a co-ordinated approach to address it. Harm from unrecognised oesophageal intubation is avoidable through reducing the rate of oesophageal intubation, combined with prompt detection and immediate action when it occurs. The detection of 'sustained exhaled carbon dioxide' using waveform capnography is the mainstay for excluding oesophageal placement of an intended tracheal tube. Tube removal should be the default response when sustained exhaled carbon dioxide cannot be detected. If default tube removal is considered dangerous, urgent exclusion of oesophageal intubation using valid alternative techniques is indicated, in parallel with evaluation of other causes of inability to detect carbon dioxide. The tube should be removed if timely restoration of sustained exhaled carbon dioxide cannot be achieved. In addition to technical interventions, strategies are required to address cognitive biases and the deterioration of individual and team performance in stressful situations, to which all practitioners are vulnerable. These guidelines provide recommendations for preventing unrecognised oesophageal intubation that are relevant to all airway practitioners independent of geography, clinical location, discipline or patient type.

The past 4 years have been consequential in the world of surgery to correct pelvic organ prolapse. In 2018, results of a large, multicenter randomized trial demonstrated very disappointing cure rates of traditional native tissue repairs at 5 years or more. In 2019, a vaginal mesh hysteropexy kit was removed from the market by the U.S. Food and Drug Administration only to subsequently demonstrate it provided better cure rates and similar risk profile to vaginal hysterectomy plus native tissue repair in its own 5-year study published in 2021. Meanwhile, the use and techniques of laparoscopic sacrocolpopexy with or without robotic assistance have evolved such that it is commonly adapted to treat all support defects for patients with uterovaginal or posthysterectomy prolapse. This article is intended to provide an overview of the contemporary use and techniques of laparoscopic sacrocolpopexy based on the evidence and our clinical experience.

Vascular malformations of the head and neck represent a spectrum of complex vascular anomalies, requiring a multidisciplinary approach toward diagnosis and treatment. Several intralesional therapeutic agents have been devised and pioneered over the years, some of which are now primary and standard of care for the management of these lesions. In this article, the authors discuss the currently available intralesional therapeutic agents for the management of vascular malformations in the head and neck region.

Congenital ventricular diverticulum (VD) and aneurysm are rare cardiac developmental anomalies and their pathophysiology is still unclear. They present as an anomaly of the four chambers view, cardiomegaly, arrhythmia, pericardial effusion, or hydrops. They are usually isolated anomalies. Differential diagnosis between diverticulum and aneurysm is challenging during the prenatal period. Management policy is not uniform either conservative or repeated pericardial puncture.We wanted to describe prenatal features and post-natal outcomes of fetal cardiac out pouching.We retrospectively report 6 cases of VD and aneurysm prenatally managed in our fetal medicine unit between 2010 and 2020. All cases were evaluated from the first or second trimester of pregnancy until postnatal follow-up (3 months to 3 years).All six cases underwent a monthly ultrasound follow-up with spontaneous regression of pericardial effusion, and normal hemodynamics at birth No pericardial puncture was done and postnatal outcome was favorable in all cases.Based on our experience and on cases previously published, prenatal counseling should be prudent regarding the final diagnosis. Referral and monthly prenatal ultrasound follow-up, birth in a tertiary center after multidisciplinary evaluation and cardiological evaluation at birth still seem mandatory.

The corneal epithelium serves to protect the underlying cornea from the external environment and is essential for corneal transparency and optimal visual function. Regeneration of this epithelium is dependent on a population of stem cells residing in the basal layer of the limbus, the junction between the cornea and the sclera. The limbus provides the limbal epithelial stem cells (LESCs) with an optimal microenvironment, the limbal niche, which strictly regulates their proliferation and differentiation. Disturbances to the LESCs and/or their niche can lead to the pathologic condition known as limbal stem cell deficiency (LSCD) whereby the corneal epithelium is not generated effectively. This has deleterious effects on the corneal and visual function, due to impaired healing and secondary corneal opacification. In this concise review, we summarize the characteristics of LESCs and their niche, and present the current and future perspectives in the management of LSCD with an emphasis on restoring the function of the limbal niche.

We investigated short and long-term remission rates after splenectomy in patients with primary and secondary autoimmune hemolytic anemia (AIHA).All adults who underwent splenectomy for primary or secondary AIHA at a single center (2004-2018) were retrospectively reviewed. Short-term response was determined at 30-day postoperatively and long-term at one year. Complete response was defined as hemoglobin 10 g/dL without hemolysis, transfusions, or need for additional medical therapy for 6 months.Short-term complete response was attained in 22 of 36 patients (61%), partial response in 3 (8%), no response in 11 (31%). The response rate at 1 year was complete in 14/36 (39%), partial in 14 (39%), and 8 non-response (22%). At last available follow-up (median 33.1 months (IQR 19-59), 16/37 patients had experienced a complete response (43%), 14 partial response (38%), 7 non-response (19%). 80% of partial responders with primary AIHA required maintenance therapy compared to 100% with secondary AIHA.Splenectomy is associated with short- and long-term improvement in anemia and hemolysis in the majority of patients with AIHA. Immunosuppressants remain important supplemental therapy.

Epigenetic diseases can be produced by a stable alteration, called an epimutation, in DNA methylation, in which epigenome alterations are directly involved in the underlying molecular mechanisms of the disease. This review focuses on the epigenetics of two inherited metabolic diseases, epi-cblC, an inherited metabolic disorder of cobalamin (vitamin B

Follicular keratosis (FK) is a poorly understood disorder presenting with multiple, grouped hyperkeratotic follicular papules typically affecting the chin or jawline. This study describes the clinical presentation, histopathology, management, and outcomes of a series of pediatric patients of color with FK of the face, thought to be related to rubbing or friction on the skin.Retrospective review of 20 pediatric patients with FK of the face who presented to our pediatric dermatology practice between April 2019 and October 2021.Twenty patients (mean age 12.1 years, 13 females), all self-identified as Black/African American, were included. All presented with an initially asymptomatic, hyperpigmented patch containing multiple hyperkeratotic follicular papules, located on the cheek, chin, upper lip, and/or jawline. Five patients endorsed a history of rubbing the site. Nine patients had onset of the lesions during the COVID-19 pandemic. Treatments included topical vitamin D analogs, corticosteroids, and/or retinoids. Topical vitamin D analogs and retinoids improved the texture and hyperpigmentation of the follicular lesions in only four patients, while topical corticosteroids had no effect. Histopathological examination of two patients revealed multiple dilated follicles containing keratinized material and associated with a sparse dermal inflammatory infiltrate in one patient and granulomatous inflammation within the dermis in the other.In our cohort of pediatric patients with FK, patients of color were preferentially affected, and all cases were associated with hyperpigmentation. Some patients presented during the COVID-19 pandemic suggesting that friction from facial mask wearing may have induced or exacerbated this uncommon condition.

The biological and clinical significance of the p.E88del variant in the transcobalamin receptor, CD320, is unknown. This allele is annotated in ClinVar as likely benign, pathogenic, and of uncertain significance. To determine functional consequence and clinical relevance of this allele, we employed cell culture and genetic association studies. Fibroblasts from sixteen CD320 p.E88del homozygotes exhibited reduced binding and uptake of cobalamin. Complete ascertainment of newborns with transiently elevated C3 (propionylcarnitine) in New York State demonstrated that homozygosity for CD320 p.E88del was over-represented (7/348, p

Immunotherapy is a treatment modality that has a broad and rapidly growing range of applications to treat both chronic and acute diseases, including rheumatoid arthritis, Crohn disease, cancer, and COVID-19. Emergency physicians must be aware of the breadth of applications and be able to consider the effects of immunotherapies when patients on these treatments present to the hospital. This article provides a review of the mechanisms of action, indications for use, and potential complications of immunotherapy treatments that are relevant in the emergency care setting.

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

Most patients with advanced-stage indolent non-Hodgkin lymphoma have multiple relapses. We assessed axicabtagene ciloleucel autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory indolent non-Hodgkin lymphoma.ZUMA-5 is a single-arm, multicentre, phase 2 trial being conducted at 15 medical cancer centres in the USA and two medical cancer centres in France. Patients were eligible if they were aged 18 years or older, with histologically confirmed indolent non-Hodgkin lymphoma (follicular lymphoma or marginal zone lymphoma), had relapsed or refractory disease, previously had two or more lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients underwent leukapheresis and received conditioning chemotherapy (cyclophosphamide at 500 mg/mBetween June 20, 2017, and July 16, 2020, 153 patients were enrolled and underwent leukapheresis, and axicabtagene ciloleucel was successfully manufactured for all enrolled patients. As of data cutoff (Sept 14, 2020), 148 patients had received an infusion of axicabtagene ciloleucel (124 [84%] who had follicular lymphoma and 24 [16%] who had marginal zone lymphoma). The median follow-up for the primary analysis was 17·5 months (IQR 14·1-22·6). Among patients who were eligible for the primary analysis (n=104, of whom 84 had follicular lymphoma and 20 had marginal zone lymphoma), 96 (92%; 95% CI 85-97) had an overall response and 77 (74%) had a complete response. The most common grade 3 or worse adverse events were cytopenias (104 [70%] of 148 patients) and infections (26 [18%]). Grade 3 or worse cytokine release syndrome occurred in ten (7%) patients and grade 3 or 4 neurological events occurred in 28 (19%) patients. Serious adverse events (any grade) occurred in 74 (50%) patients. Deaths due to adverse events occurred in four (3%) patients, one of which was deemed to be treatment-related (multisystem organ failure).Axicabtagene ciloleucel showed high rates of durable responses and had a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma.Kite, a Gilead Company.

BACKGROUND AND OBJECTIVE: To examine whether new cases of retinal artery occlusion (RAO) or retinal vein occlusion (RVO) increased during the coronavirus 209 (COVID-19) pandemic. PATIENTS AND METHODS: This was a retrospective cohort study of patients visiting retina clinics with a new diagnosis in two time periods: between January 1, 2019, and February 29, 2020 (the pre–COVID-19 period), and between March 1, 2020, and December 31, 2020 (the COVID-19 period). The key outcome was the percentage of newly diagnosed central RAO (CRAO), branch RAO (BRAO), central RVO (CRVO), and branch RVO (BRVO) seen in each period. RESULTS: The study population included 285,759 new patients in the pre–COVID-19 period and 156,427 new patients in the COVID-19 period. The overall number of new patients dropped dramatically during the first few months of the COVID-19 pandemic (24%, 66%, and 51% less new patients in March, April, and May 2020 than in the same months in 2019; P < .0001 for all 3 months). However, the decrease in the number of newly diagnosed patients with CRAO, CRVO, and BRAO during these months was less dramatic. As most states reopened in June and the number of patients in retina clinics started to increase, the newly diagnosed patients with these conditions as a percentage of all new diagnoses returned to similar trends as seen in the pre–COVID-19 period. CONCLUSIONS: The percentage of new cases of RAO and RVO with respect to all new diagnoses in retina clinics remained stable for the majority of the COVID-19 period. There was an increase in these percentages during the first few months of the COVID-19 pandemic, particularly for CRAO, CRVO, and BRAO, which may have led to the presumption that more patients presented with these conditions during the COVID-19 period evaluated in this study. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:22–30.

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease. However, additional de-regulated genes and the resulting pathophysiology is unknown. Therefore, we have generated mouse models of this disease. In addition to exhibiting loss of Mmachc, metabolic perturbations, and developmental defects previously observed in cblC, we uncovered reduced expression of target genes that encode ribosome protein subunits. We also identified specific phenotypes that we ascribe to deregulation of ribosome biogenesis impacting normal translation during development. These findings identify HCFC1/RONIN as transcriptional regulators of ribosome biogenesis during development and their mutation results in complex syndromes exhibiting aspects of both cblC and ribosomopathies., Combined methylmalonic acidemia (MMA) and hyperhomocysteinemias are inborn errors of vitamin B12 metabolism, and mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) underlie some forms of these disorders. Here the authors generated mouse models of a human syndrome due to mutations in RONIN (THAP11) and HCFC1, and show that this syndrome is both an inborn error of vitamin B12 metabolism and displays some features of ribosomopathy.

There has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66–0.92), MB (HR: 0.76; 95% CI: 0.65–0.88), and CRNMB (HR: 0.86; 95% CI: 0.80–0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

Background and Purpose: Older adults with lower balance confidence demonstrate a reduced willingness to experience instability as the task of walking becomes more challenging (i.e., walking with a faster speed). However, the specific reason why is not known. The purpose of this study was to investigate the extent to which capacity of increasing walking speeds relates to the attentional requirements (i.e., automaticity) of walking. Methods: Sixteen young (31 ± 5.85 years) and 15 older participants (69 ± 3.04 years) began walking on a treadmill at 0.4 m/s, and speed was increased by 0.2 m/s until the participant either chose to stop or reached a speed of 2.0 m/s. Sixty steps were collected at steady-state speed for each walking trial. Kinematic data were collected, and the margin of stability in the anterior direction (MOSAP) at heelstrike was quantified for each step. The timed up and go (TUG) and TUG dual (TUGdual) task were performed, from which an automaticity index (TUG/TUGdual × 100) was calculated. Older individuals were grouped based on whether they did or did not complete all walking speeds (i.e., completers [n = 9] or noncompleters [n = 6]). The fastest walking speed attempted (FSA), automaticity index, and MOSAP were compared, and correlations were assessed between the FSA/MOSAP and the automaticity index. Results: A significant difference was identified in an average MOSAP at heelstrike between older completer and noncompleter groups (p < 0.001). Further, older adults with lower automaticity index choose to stop walking at lower speeds (p = 0.001). The FSA was positively correlated with the automaticity index (ρ = 0.81, p < 0.001). Finally, the average MOSAP at FSA and the automaticity index were also negatively correlated (r = −0.85, p < 0.001). Conclusion: Older adults with lower automaticity of walking choose to stop walking at speeds before they completed all walking speeds, which may relate with increased attentional demands required to maintain dynamic stability at higher walking speeds. Given that these were otherwise healthy adults, the combination of FSA and an automaticity of walking may help to identify individuals who should be considered for an assessment to identify walking problems.

Objective To explore the association between measures of obesity and measures of trip-induced fall risk among community-dwelling older adults. Design Case-control. Setting Gait laboratory. Participants Voluntary sample of 55 community-dwelling older adults (aged ≥65y; N=55) with body mass index (BMI) of 18.84-44.68 kg/m2. Interventions Not applicable. Main Outcome Measures Measures of obesity included 6 anthropometry-based measures (BMI; thigh, hip and waist circumferences; ratio of waist-to-hip circumference; index of central obesity) and 4 dual-energy x-ray absorptiometry–based measures (percentage trunk, leg, and total fat; fat mass index). Measures of risk of tripping during overground walking included median and interquartile range of toe clearance and area under the swing phase toe trajectory. Measures of trip recovery after a laboratory-induced trip included trunk angle and angular velocity at ground contact of the first recovery step, anteroposterior distance from stepping foot to center of mass at the same instant, and step time of the first recovery step. Results Risk of tripping was associated with waist-to-hip ratio and thigh circumference. After grouping participants by waist-to-hip ratio, those with high ratios (≥0.9 cm for men and ≥0.85 cm for women) exhibited significantly greater variability in toe clearance. Trip recovery was associated with hip circumference, thigh circumference, fat mass index, and total fat. After grouping participants by fat mass index, those with high indices (>9 kg/m2 for men and >13 kg/m2 for women) exhibited less favorable trunk kinematics after a laboratory-induced trip (Cohen d=0.84). Conclusions Waist-to-hip ratio and fat mass index may more closely relate to trip-induced fall risk than BMI among community-dwelling older adults.

To determine the preferences and attitudes of members of regional anesthesia societies during the COVID-19 pandemic.We distributed an electronic survey to members of the American Society of Regional Anesthesia and Pain Medicine, Regional Anaesthesia-UK, and the European Society of Regional AnaesthesiaPain Therapy. A questionnaire consisting of 19 questions was developed by a panel of experienced regional anesthesiologists and distributed by email to the participants. The survey covered the following domains: participant information, practice settings, preference for the type of anesthetic technique, the use of personal protective equipment, and oxygen therapy.The survey was completed by 729 participants from 73 different countries, with a response rate of 20.1% (729/3,630) for the number of emails opened and 8.5% (729/8,572) for the number of emails sent. Most respondents (87.7%) identified as anesthesia staff (faculty or consultant) and practiced obstetric and non-obstetric anesthesia (55.3%). The practice of regional anesthesia either expanded or remained the same, with only 2% of respondents decreasing their use compared with the pre-pandemic period. The top reasons for an increase in the use of regional anesthesia was to reduce the need for an aerosol-generating medical procedure and to reduce the risk of possible complications to patients. The most common reason for decreased use of regional anesthesia was the risk of urgent conversion to general anesthesia. Approximately 70% of the responders used airborne precautions when providing care to a patient under regional anesthesia. The most common oxygen delivery method was nasal prongs (cannula) with a surgical mask layered over it (61%).Given the perceived benefits of regional over general anesthesia, approximately half of the members of three regional anesthesia societies seem to have expanded their use of regional anesthesia techniques during the initial surge of the COVID-19 pandemic.RéSUMé: OBJECTIF: Déterminer les préférences et les attitudes des membres des sociétés d’anesthésie régionale pendant la pandémie de COVID-19. MéTHODE: Nous avons distribué un sondage électronique aux membres de l’American Society of Regional Anesthesia and Pain Medicine, de Regional Anesthesia-UK et de l’European Society of Regional AnaesthesiaPain Therapy. Un questionnaire composé de 19 questions a été élaboré par un panel d’anesthésiologistes régionaux d’expérience et distribué par courriel aux participants. Le sondage couvrait les domaines suivants : les renseignements sur les participants, les contextes de pratique, leur préférence quant au type de technique d’anesthésie, l’utilisation d’équipement de protection individuelle et l’oxygénothérapie RéSULTATS: Le sondage a été complété par 729 participants provenant de 73 pays différents, avec un taux de réponse de 20,1 % (729/3630) pour le nombre de courriels ouverts et de 8,5 % (729/8572) pour le nombre de courriels envoyés. La plupart des répondants (87,7 %) se sont identifiés comme anesthésiologistes (académique ou consultant) et pratiquaient l’anesthésie obstétricale et non obstétricale (55,3 %). Leur pratique de l’anesthésie régionale s’est étendue ou est demeurée inchangée, et seulement 2 % des répondants ont indiqué avoir diminué leur utilisation de cette pratique par rapport à la période pré-pandémique. Les principales raisons d’une augmentation de l’utilisation de l’anesthésie régionale étaient de réduire la nécessité d’une intervention médicale générant des aérosols et de réduire le risque de complications potentielles pour les patients. La raison la plus courante de diminution du recours à l’anesthésie régionale était le risque de conversion urgente à une anesthésie générale. Environ 70 % des intervenants ont utilisé des précautions en matière de propagation des aérosols lorsqu’ils procuraient des soins à un patient sous anesthésie régionale. La méthode d’administration d’oxygène la plus fréquemment utilisée était les canules nasales avec un masque chirurgical superposé (61 %). CONCLUSION: Compte tenu des avantages perçus de l’anesthésie régionale par rapport à l’anesthésie générale, environ la moitié des membres de trois sociétés d’anesthésie régionale semblent avoir élargi leur utilisation des techniques d’anesthésie régionale pendant la vague initiale de la pandémie de COVID-19.

The American Society of Anesthesiologists; All India Difficult Airway Association; European Airway Management Society; European Society of Anaesthesiology and Intensive Care; Italian Society of Anesthesiology, Analgesia, Resuscitation and Intensive Care; Learning, Teaching and Investigation Difficult Airway Group; Society for Airway Management; Society for Ambulatory Anesthesia; Society for Head and Neck Anesthesia; Society for Pediatric Anesthesia; Society of Critical Care Anesthesiologists; and the Trauma Anesthesiology Society present an updated report of the Practice Guidelines for Management of the Difficult Airway.

In recent years, increasing attention has been paid to the role of neutrophils in cardiovascular (CV) disease (CVD) with evidence supporting their role in the initiation, progression, and rupture of atherosclerotic plaque. Although these cells have long been considered as terminally differentiated cells with a relatively limited spectrum of action, recent research has revealed intriguing novel cellular functions, including neutrophil extracellular trap (NET) generation and inflammasome activation, which have been linked to several human diseases, including CVD. While most research to date has focused on the role of neutrophils in coronary artery and cerebrovascular diseases, much less information is available on lower limb peripheral artery disease (PAD). PAD is a widespread condition associated with great morbidity and mortality, though physician and patient awareness of the disease remains low. To date, several studies have produced some evidence on the role of certain biomarkers of neutrophil activation in this clinical setting. However, the etiopathogenetic role of neutrophils, and in particular of some of the newly discovered mechanisms, has yet to be fully elucidated. In the future, complementary assessment of neutrophil activity should improve CV risk stratification and provide personalized treatments to patients with PAD. This review aims to summarize the basic principles and recent advances in the understanding of neutrophil biology, current knowledge about the role of neutrophils in atherosclerosis, as well as available evidence on their role of PAD.

Understanding the utility of virtual visits in pediatric dermatology practice has become increasingly important in the telehealth era. We compared the conditions diagnosed in pediatric dermatology between traditional in-person visits and virtual telehealth visits during the initial 8-month phase of the COVID-19 pandemic at an urban medical institution. When given the option, pediatric dermatology patients and their families were more likely to choose telehealth visits for the diagnosis and/or management of acne, hemangiomas, and contact dermatitis; however, they were more likely to choose in-person visits for atopic dermatitis, viral warts, and alopecia areata. These differences may be attributed to clinical features of pediatric skin conditions, treatment options, and other factors which may influence patient preference for telehealth or in-person care for their condition. J Drugs Dermatol. 2022;21(11):1260-1263. doi:10.36849/JDD.6843.

Lanosterol synthase is required for cholesterol synthesis, and deficiencies have been associated with hypotrichosis as well as neuroectodermal syndromes including intellectual delay and epilepsy. Here, we report a case of lanosterol synthase deficiency in a 4-day-old patient who presented with alopecia and a previously unreported dermatologic manifestation of congenital localized hyperpigmentation.

Epithelial cells use the process of extrusion to promote cell death while preserving a tight barrier. To extrude, a cell and its neighbors contract actin and myosin circumferentially and basolaterally to seamlessly squeeze it out of the epithelium. Recent research highlights how early apical pulsatile contractions within the extruding cell might orchestrate contraction in three dimensions so that a cell extrudes out apically. Along with apical constrictions, studies of ion channels and mathematical modeling reveal how differential contraction between cells helps select specific cells to extrude. In addition, several studies have offered new insights into pathways that use extrusion to eliminate transformed cells or cause an aberrant form of extrusion that promotes cell invasion.

Introduction Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. Methods Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p

Background and aim Infection is associated with substantial morbidity and mortality in cirrhosis, but presumably, not all infections carry the same risk of mortality. We compared outcomes of different sites of infection in a nationally representative sample of inpatients with cirrhosis. Methods We queried the Nationwide Readmissions Database for patients with cirrhosis from 2011 to 2014. Cirrhosis and infection diagnoses were identified by previously used algorithms of ICD-9 codes. The following infections were compared: urinary tract infection (UTI), pneumonia, cellulitis, spontaneous bacterial peritonitis (SBP), and Clostridium difficile infection (CDI). The primary outcome was inpatient mortality. Secondary outcomes included sepsis, any organ failure, multiple organ failures, and 30-day readmission. Outcomes were analyzed using logistic regression and included a priori covariates. Results A total of 1 798 830 weighted index admissions were identified. Infection was present in 29.2% overall-including UTI (13.7%), pneumonia (8.9%), cellulitis (5.2%), CDI (2.8%), and SBP (2.0%). Mortality was significantly higher in pneumonia (19.6%), SBP (18.6%), and CDI (17.4%) compared with cellulitis (7.6%) and UTI (11.8%). Sepsis, any, and multiple organ failures were most commonly seen in pneumonia, SBP, and CDI. Multivariable analysis demonstrated that pneumonia had the highest associated mortality (odds ratio [OR] 2.73, confidence interval [CI] 2.68-2.80) and multiple organ failures (OR 3.59, CI 3.50-3.68). Significantly increased 30-day readmission was seen only with SBP (24.9%). Conclusions Outcomes of inpatients with cirrhosis vary significantly depending on the type of infection. The severity and epidemiology of infection in cirrhosis appears to be shifting with pneumonia, not SBP, having the highest prevalence of multiple organ failures and inpatient mortality.