Search

Domino liver transplantation (DLT) utilizes a phenotypically normal explant from select recipients as a donor graft in another patient. The procedure is not widely employed and remains restricted to a small number of centers. The purpose of this study was to assess the national profile of DLT in the United States (US) and evaluate current survival outcomes.The United Network for Organ Sharing (UNOS) database was queried for all liver transplants (LT) between 1996 and 2020. Outcomes of interest were long-term graft and patient survival.Of 181,976 LTs performed nationally during the study period, 185 (0.1%) were DLTs. Amyloidosis and maple syrup urine disease (MSUD) accounted for 83% of dominoed allografts. Out of 210 explants with amyloidosis, 103 (49%) were dominoed into secondary recipients. Only 50 (22%) of all MSUD explants (n = 227) were dominoed. Graft survival was 79%, 73% and 53% at 3-, 5- and 10-years, respectively, for DLT recipients. Overall patient survival was 83%, 76% and 57% at 3-, 5- and 10-years.Despite excellent long-term survival outcomes, DLT allografts comprise a very small percentage of the liver donor pool. A large proportion of potential DLTs may be unconscionably excluded despite shortages in deceased donor organs.

Background Traditionally, curative resection was considered the cornerstone of treatment for perihilar cholangiocarcinoma. More recently, liver transplantation (LT) offered an alternative for patients with unresectable disease. The purpose of this study was to assess our experience with perihilar cholangiocarcinoma and LT. Methods A perihilar cholangiocarcinoma protocol was commenced in 2006 whereby diagnosed patients were enrolled onto an institutional registry for LT consideration. Data on patient progression and oncologic outcomes were assessed. Results Fifty-eight patients were initially enrolled onto the protocol and 38 proceeded to LT following neoadjuvant chemoradiation (mean age 55.6 ± 11.4 years). Mean time to LT was 3.7 ± 2 months and, among those transplanted, 14 (37%) had underlying primary sclerosing cholangitis (PSC). Thirteen (34%) patients developed malignant recurrence and there were no differences in disease recurrence between PSC (n = 3) and non-PSC (n = 10) patients (p = 0.32). Overall patient survival was 91%, 58% and 52% at 1-, 3- and 5-years corresponding with 81%, 52% and 46% graft survival, respectively. Conclusion Rigorous patient selection and chemoradiation treatment algorithms can be highly effective in treating perihilar cholangiocarcinoma. For appropriately selected candidates, LT can provide a 52% 5-year survival for patients who would otherwise have no surgical treatment option.

Background: Migrants are vulnerable to communicable diseases and face barriers in access to immunization programs. Individual studies suggest that they suffer immunization inequity, but the gap in vaccination compared to non-migrants has not been quantified. This systematic review quantitatively determined the level of vaccination coverage among migrants compared to non-migrants, collating the published literature. Methods: A search without language restrictions was conducted in PubMed, Scopus and Web of Science, from database inception to February 2021. Observational studies that provided the vaccination rates among migrant and non-migrant groups were included. Study quality was assessed using Newcastle-Ottawa scale. Data were synthesized pooling data from individual studies to generate summary odds ratio (OR) with 95% confidence interval (CI) using random effects model, assessing heterogeneity with I2 statistic and publication bias with funnel asymmetry analysis. Findings: There were 44 relevant studies (7,937,996 participants). Overall risk of bias was low in 13 (30%), moderate in 22 (50%) and high in 9 (20%) studies. Point estimates of individual ORs showed lower vaccination coverage among migrants in 36 of 39 meta-analyzable studies. Overall, the odds of vaccination coverage among migrants were lower compared to non-migrants (7,375,184 participants, summary OR 0.50, 95% CI 0.37-0.66, I2 99.9%). There was no funnel asymmetry. Interpretation: Migrants are half as often vaccinated compared to non-migrants. Public health prevention programs need to prioritize vaccination equity, not just to protect migrants but also to protect the host communities. Registration Details: Review protocol was prospectively registered (PROSPERO CRD42021228061). Funding Information: No source of funding. Declaration of Interests: KSK is Distinguished Investigator at University of Granada funded by the Beatriz Galindo (senior modality) program of the Spanish Ministry of Education. All other authors declare no competing interests.

BACKGROUND: Somatic variations in rearranged during transfection (RET) proto-oncogene acts to influence Thyroid cancer (TC) in a low penetrance manner, but their effects tend to vary between different populations. OBJECTIVE: This case-control study was aimed to evaluate effect of RET G691S, S904S and L769L single nucleotide polymorphisms (SNPs) on the risk for differentiated thyroid carcinoma (DTC). METHODS: A total of 180 patients and 220 controls were genotyped by Polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP). Di-Deoxy Sanger sequencing was performed on 100 samples with variations and 20 wild samples for each amplified exon. In addition, In Silico tools were used to evaluate structural and functional impact of individual SNPs in disease progression. RESULTS: In RET G691S/L769L/S904S SNPs, frequency of variant genotypes in DTC cases was 61.1%, 54.4% and 76.6% as compared to 45.9%, 43.6% and 89.09% in controls respectively (P⩽ 0.05). In Silico analysis revealed that different protein formed due to G691S substitution decreases the stability of 3D structure of protein. The RET G691S and L769L SNP followed “Dominant” but RET S904S SNP confirmed an “Additive” mode of inheritance. CONCLUSION: RET G691S/L769L/S904S SNPs are significantly associated with DTC with G691S SNP declining the stability of final protein product.

This cross-sectional study was conducted to determine the occurrence, risk factors, and characteristics of Salmonella isolates recovered from imported fertile broiler hatching eggs, hatcheries, and broiler farms in Trinidad and Tobago. Standard methods were used to isolate and characterize Salmonella isolates from two broiler hatcheries and 27 broiler farms in the country. The frequency of isolation of Salmonella was 0.0% for imported fertile hatching eggs (0 of 45 pools of 10 eggs each, i.e., 450 eggs), 7.6% for hatcheries (12 of 158 samples), and 2.8% for broiler farms (24 of 866 samples) (P = 0.006). Stillborn chicks at hatcheries had the highest prevalence of Salmonella (7 of 28 samples, 28.0%), whereas on broiler farms the cloacal swabs had the highest prevalence of Salmonella (15 of 675 samples, 2.2%). None of the 15 farm management and production practices investigated were significantly associated (P0.05) with the isolation of Salmonella. The predominant Salmonella serotypes were Kentucky (83.3%) and Infantis (62.5%) among hatchery and farm isolates, respectively. The disk diffusion method revealed frequencies of antimicrobial resistance (i.e., resistance to one or more agents) of 44.0% (11 of 25 isolates) and 87.5% (35 of 40 isolates) at hatcheries and broiler farms, respectively (P = 0.0002). Antimicrobial resistance among hatchery isolates was highest (28.0%) to doxycycline and kanamycin and was very high (65%) among farm isolates to sulfamethoxazole-trimethoprim, gentamicin, ceftriaxone, kanamycin, and doxycycline. Multidrug resistance (MDR; i.e., resistance to antimicrobial agents from three or more classes) was exhibited by 4.0 and 85.7% of Salmonella isolates recovered from several environmental and animal sources at the hatcheries and farms, respectively (P0.0001). The high level of antimicrobial resistance and the presence of MDR among Salmonella isolates from broiler farms highlight the therapeutic implications and the potential for MDR strains to enter the food chain.

Toward the goal of using more livers for transplantation, transplant centers are looking to increase the use of organs from "marginal" donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury.Using a porcine model of donation after circulatory death, we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 min of warm ischemia time followed by the administration of CD47 monoclonal antibody (CD47mAb) treatment or immunoglobulin G control antibodies and 6 h of normothermic extracorporeal liver perfusion.After 6 h of normothermic extracorporeal liver perfusion, CD47mAb-treated livers with 30 or 60 min warm ischemia time had significantly lower alanine transaminase levels and higher bile production compared with their respective control groups. Blockade of the CD47 signaling pathway resulted in significantly lower thrombospondin-1 protein levels, lower expression of caspase-3, and higher expression of phosphorylated extracellular signal-regulated kinase.These findings suggested that CD47mAb treatment decreases ischemia/reperfusion injury through CD47/thrombospondin-1 signaling downregulation and the presence of necrosis/apoptosis after reperfusion and could increase liver regeneration during normothermic perfusion of the liver.

Excess deaths during the coronavirus disease 2019 (COVID-19) pandemic have been largely attributed to cardiovascular disease (CVD); however, patterns in CVD hospitalizations after the first surge of the pandemic have not well-documented. Our brief report, examining trends in health care avoidance documents that CVD hospitalizations decreased in Chicago before significant burden of COVID-19 cases or deaths and normalized during the first COVID-19 surge. These data may help to inform health care systems responses in the coming months while mobilizing vaccinations to the population at large.

Establishing and arriving at a diagnosis is the key to treatment planning and often practitioners tend to create a treatment plan overlooking the fundamental principles that must be taken into consideration prior to performing implant surgeries. The sequential process of clinical examination, laboratory tests, radiographic analysis, diagnostic protocols, casts wax ups, along with the treatment needs and desires of the patient have to be factored in for the overall diagnosis and prognosis of implant therapy. A step-by-step methodology has been created to help the implant practitioner with a checklist that aims to create the optimal treatment plan for each case.

BACKGROUND South Asian Americans experience disproportionately high burden of cardiovascular diseases. Estimating predicted heart failure (HF) risk distribution may facilitate targeted prevention. We estimated the distribution of 10-year predicted risk of incident HF in South Asian Americans and evaluated the associations with social determinants of health and clinical risk factors. METHODS AND RESULTS In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, we calculated 10-year predicted HF risk using the Pooled Cohort Equations to Prevent Heart Failure multivariable model. Distributions of low (

Head-to-head comparisons of the efficacy of treatments for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have not yet been reported. This study used a series of matching-adjusted indirect comparisons to indirectly compare the effectiveness of [177Lu]Lu-DOTA-TATE to everolimus, sunitinib and best supportive care (BSC) for extending progression-free survival and overall survival in patients with advanced, unresectable gastrointestinal (GI)-NETs and P-NETs. The results of the main analysis suggest that after accounting for differences in key prognostic variables, the hazard of progression was 62% (hazard ratio [HR], 0.38; confidence interval [CI]95 0.25–0.58) and 65% (HR 0.35 CI95 0.21–0.59) lower in patients with GI-NETs treated with [177Lu]Lu-DOTA-TATE than in those treated with everolimus and BSC, respectively. Similarly, the hazard of progression was 64% (HR 0.36 CI95 0.18–0.70), 54% (HR 0.46 CI95 0.30–0.71) and 79–87% (HR 0.21 CI95 0.13–0.32; HR 0.13 CI95 0.08–0.22) lower in patients with P-NET treated with [177Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. The hazard of death was 58% (HR 0.42 CI95 0.25–0.72), 47% (HR 0.53 CI95 0.33–0.87) and 44–64% (HR 0.56 CI95 0.36–0.90; HR 0.34 CI95 0.20–0.57) lower in P-patients with NET treated with [177Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. While our results must be interpreted with caution given the non-randomised nature of the comparisons and the potential for residual confounding, the magnitude of the effect sizes we observe and their consistency across comparators suggest that [177Lu]Lu-DOTA-TATE may be a more effective treatment option than everolimus, sunitinib and BSC in advanced, unresectable GEP-NETs.

Liver transplantation (LT) is a complex operation that most transplant surgeons learn in fellowship. Training varies as there is lack of objective data that can be used to standardize teaching. We performed a retrospective review of our adult LT database with aim of looking at fellow's experience. Using American Society of Transplant Surgery cutoff of, at least 45 LT during fellowship, data for first 45 LT were compared to LT 45-90. Fellow's cases were also clustered in sequential groups of 15 LT and analyzed to estimate the learning curve (LC). Comparison of LT 1-45 with LT 46-90 showed significantly lower total operative times (TOT) (324 vs. 344 min) and warm ischemia times (WIT) (28 vs. 31 min) in the 45-90 group. Rates of biliary complications (23.8% vs. 16.4%) and bile leaks alone (10.3% vs. 5.5%) were significantly higher for first 45 LT. Analysis of fellows experience in sequential clusters of 15 LT showed decreasing TOT, WIT, biliary complications and rates of unplanned return to the OR with progression of fellowship. This study validates the current ASTS requirement of at least 45 LT. LC generated using these data can help individualize training and optimize outcomes through identification of areas in need of improvement.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF., In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking.

The trial was prospectively registered on ISRCTN (12146519). The trial was approved by the NHS LondonBrighton and Sussex Research Ethics Committee and the NHS Confidentiality Advisory Group. The study was funded by Barts Charity. We would like to acknowledge the support of the Joint Research Management Office, Queen Mary University of London as sponsor for the study; the contributions of members of Katie's Team, the East London women's health research patient and public advisory group; and the clinical, laboratory and maternity research teams at Barts Health NHS Trust hospitals and Homerton University Hospital. We are also grateful for all the support and advice provided by the project steering committee chaired by an independent consultant anaesthetist (M. Wilson, University of Sheffield), with four other independent members: A. Khalil, St George's University Hospital; B. Leurent, London School of Hygiene and Tropical Medicine; N. Moss, lay representative; and S. Robinson, Guy's and St Thomas' NHS Trust. No other external funding or competing interests declared., There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23–41%) in the intervention group vs. 81% (95%CI 70–90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference 0.6 units, 95%CI 1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3–1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1–1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation., Barts Charity, Joint Research Management Office, Queen Mary University of London

Purpose of review In this review, we will discuss the current status and recent developments in precision medicine in chronic obstructive pulmonary disease (COPD) through the lens of treatable traits. Recent findings Although the term 'treatable traits' in the treatment of COPD is relatively recent, this concept has been used for many years if one considers interventions such as long-term oxygen therapy or alpha-1 antitrypsin replacement therapy. Recent advances have included expanding the definition of COPD to include a broader population of people with lower respiratory disease but not meeting the strict criteria for obstruction, advances in imaging to aid in the diagnosis and treatment of COPD, advances in understanding symptoms and exacerbations to define severity, using biomarkers to guide therapy and better understanding and addressing polymorbidity and frailty. In addition, there is a concerted effort to use these concepts to identify COPD patients earlier in the disease process wherein disease modification may be possible. Summary Focusing on subsets of patients with COPD with certain characteristics should lead to better outcomes and fewer adverse effects from treatment. Video abstract http://links.lww.com/COPM/A30.

Sexual minority youth have a higher risk of suicidal behaviors than their straight peers. Despite this alarming trend, there is limited information on how health-risk factors are systematically associated with suicidal outcomes in relation to the intersection of sex and sexual orientation identity. Data from the 2017 Youth Risk Behavior Survey (Grades 9–12, N = 14,108) were analyzed to examine three distinct suicidal outcomes (i.e., suicidal ideation, suicide planning, and suicide attempt). Separate hierarchical logistic regression models were performed to gradually adjust for influencing factors in examining the association between suicidal outcomes and sexual orientation identity (i.e., heterosexual, gay/lesbian, bisexual, and unsure), stratified by self-reported sex. There exist significant differences in youth suicidal behaviors based on sexual orientation identity and sex: lesbians (adjusted odds ratio [AOR] = 2.7, 95% CI [1.5, 5.0]), bisexual girls (AOR = 1.9, 95% CI [1.3, 2.6]) and bisexual boys (AOR = 2.6, 95% CI [1.3, 5.2]) had higher odds of suicide attempts than their straight peers. Unsure boys and girls also reported higher risks of suicidal ideation and suicide plan as compared with their straight peers. Having a very short sleep duration, reporting ever use of illicit drugs, being bullied, and feeling sad/hopeless were associated with elevated risks of suicidality across males and females. This study identified potential disparities in suicidal outcomes by sexual orientation identity as well as factors that attenuate or strengthen this relationship in a representative sample of adolescents across the United States. An improved understanding of the differences in suicidal outcomes will serve as an opportunity to ameliorate any potential inequalities and improve sexual minority youth’ health outcomes.

Leptin—a protein hormone that plays vital role in the regulation of glucose homeostasis and insulin sensitivity, involved in regulating the circadian rhythms of gonadotropic, thyrotropic and adrenal axes in the endocrine system. This cross-sectional study was undertaken to correlate serum leptin levels and other demographic and biochemical parameters between prediabetic cases and control subjects of Kashmiri population. Furthermore, association of serum leptin levels with various demographic and biochemical parameters along with insulin resistance in pre-diabetic subjects was elucidated. In our study, pre-diabetic cases (n = 212) and healthy controls (n = 196) were enrolled. All study subjects underwent anthropometric assessment. Serum samples of all study subjects were analysed for biochemical parameters employing the principle of spectrophotometry and leptin levels using sandwich enzyme-linked immunosorbent assay (ELISA). Insulin levels of prediabetic cases were deduced by chemiluminescent micro particle immunoassay (CMIA) technology and thereby calculating their insulin resistance. The cases had statistically increased leptin levels, lipid profile and obesity as compared to controls (p ≤ 0.05). Our study, showed a positive correlation between elevated leptin levels and increased lipid levels (total cholesterol, triglycerides; TG and very low density lipoproteins-cholesterol; VLDL-C) in prediabetics (p

Purpose This study investigated the relationships between eating habits and sleep quality among university students. Methods In a cross-sectional study, university students completed a self-report questionnaire to assess eating habits and meal timing. We assessed subjective sleep quality using the Pittsburgh Sleep Quality Index (PSQI) questionnaire and examined the associations between eating habits and overall sleep quality and its components. Results Four hundred ninety-eight students participated in the study. Students who used to skip breakfast, ate late-night snacks, and replaced meals with snacks were at 1.20 times, 1.24 times, and 1.25 times higher likelihood of having poor overall sleep quality, respectively. Multiple logistic regression analysis showed that skipping breakfast (r = - 0.111, P = 0.007), late-night snacks (r = - 0.109, P = 0.007), replacing meals with snacks (r = - 0.126, P = 0.002), and irregular mealtimes (r = - 0.094, P = 0.018) were the best correlates with poor sleep quality. After adjustment to demographic variables, replacing meals with snacks followed by skipping breakfast were the best independent associations with poor sleep quality by the PSQI. Conclusions Eating habits and meal timing were significantly associated with sleep quality. We speculate that healthy eating habits may lead to improved sleep quality and sleep components among university students.

Tetrahydrolipstatin (THL, 1a) has been shown to inhibit both mammalian and bacterial α/β hydrolases. In the case of bacterial systems, THL is a known inhibitor of several Mycobacterium tuberculosis hydrolases involved in mycomembrane biosynthesis. Herein we report a highly efficient eight-step asymmetric synthesis of THL using a route that allowed modification of the THL α-chain substituent to afford compounds 1a through 1e. The key transformation in the synthesis was use of a (TPP)CrCl/Co(2)(CO)(8) -catalyzed regioselective and stereospecific carbonylation on an advanced epoxide intermediate to yield a trans-β-lactone. These compounds are modest inhibitors of Ag85A and Ag85C, two α/β hydrolases of M. tuberculosis involved in the biosynthesis of the mycomembrane. Among these compounds, 10d showed the highest inhibitory effect on Ag85A (34 ± 22 μM) and Ag85C (66 ± 8 μM) and its X-ray structure was solved in complex with Ag85C to 2.5 Å resolution. In contrast, compound 1e exhibited the best-in-class MICs of 50 μM (25 μg/mL) and 16 μM (8.4 μg/mL) against M. smegmatis and M. tuberculosis H37Ra, respectively, using a microtiter assay plate. Combining 1e with 13 well-established antibiotics synergistically enhanced the potency of few of these antibiotics in M. smegmatis and M. tuberculosis H37Ra. Compound 1e applied at concentrations 4-fold lower than its MIC enhanced the MIC of the synergistic antibiotic by 2 to 256-fold. In addition to observing synergy with first-line drugs, rifamycin and Isoniazid, the MIC of vancomycin against M. tuberculosis H37Ra is 65 μg/mL; however, the MIC was lowered to 0.25 μg/mL in the presence of 2.1 μg/mL 1e demonstrating the potential of targeting mycobacterial hydrolases involved in mycomembrane and peptidoglycan biosynthesis.

The field of cardio-oncology aims to optimize the cardiac health of cancer patients. The goals of this study are to (1) describe the demographics of a cardio-oncology clinic and (2) apply the American Society of Clinical Oncology (ASCO) cardiac risk stratification guidelines among breast cancer patients to assess the development of cardiovascular events, primarily heart failure (HF). We performed a retrospective chart review on 203 consecutive cardio-oncology patients who were seen between January 2019 and March 2020. Mean follow-up for the cohort was 29.2 ± 3.1 months (range 0–113). We applied the ASCO guidelines to the breast cancer subgroup. The plurality of patients 82/203 (40%) referred to clinic had breast cancer. The most common reason for referral was asymptomatic left ventricular (LV) dysfunction or HF (40%). Only 36/203 (18%) of patients were referred for a pre-chemotherapy evaluation. In breast cancer patients, there was a trend toward significance in up-titrating or initiating beta-blockers in the high vs. low risk ASCO groups [46/69 (67%) vs. 5/13 (38%), p = 0.054]. Approximately 13/82 (16%) of breast cancer patients required alterations to their anti-cancer therapy. HF events occurred in 1/36 (3%) of cancer treatment naive patients and 14/167 (8%) of those with prior therapy, specifically 9% of the breast cancer subset. Our study provides insight into referral practices, interventions, and outcomes at a cardio-oncology clinic. Furthermore, breast cancer patients continue to have high rates of HF. These findings suggest a need to shift referral practices upstream for a pre-chemotherapy evaluation to optimize cardiovascular health.

ObjectiveDiuretics reduce congestion in patients with heart failure with preserved ejection fraction (HFpEF). However, comparison of clinical effects across diuretic classes or combinations of diuretics in patients with HFpEF are not well described. Therefore, we sought to conduct a scoping review to map trial data of diuretic efficacy and safety in patients with HFpEF.Review methods and resultsWe searched multiple bibliometric databases for published literature and ClinicalTrials.gov, and hand searched unpublished studies comparing different classes of diuretics to usual care or placebo in patients with HFpEF. We included randomised controlled trials or quasi-experimental studies. Two authors independently screened and extracted key data using a structured form. We identified 13 published studies on diuretics in HFpEF, with 1 evaluating thiazide use, 7 on mineralocorticoid receptor antagonists (MRAs) and 5 on sodium-glucose co-transporter 2 inhibitors (SGLT2i). There remain 17 ongoing trials evaluating loop diuretics (n=1), MRAs (n=5), SGLT2i (n=10) and a polydiuretic (n=1), including 2 well-powered trials of SGLT2i that will be completed in 2021.ConclusionsThe limited number of published trials evaluating different classes of diuretics in patients with HFpEF have been generally small and short term. Ongoing and emerging trials of single or combination diuretics with greater power will be useful to better define their safety and efficacy.Scoping review registrationdoi:10.18131/g3-dejv-tm77.

BACKGROUND: Atrial fibrillation (AF) is a leading cause of cardiovascular morbidity and mortality. While neighborhood-level factors, such as poverty, have been related to prevalence of AF risk factors, the association between neighborhood poverty and incident AF has been limited. OBJECTIVE: Using a large cohort from a health system serving the greater Chicago area, we sought to determine the association between neighborhood-level poverty and incident AF. DESIGN: Retrospective cohort study. PARTICIPANTS: Adults, aged 30 to 80 years, without baseline cardiovascular disease from January 1, 2005, to December 31, 2018. MAIN MEASURES: We geocoded and matched residential addresses of all eligible patients to census-level poverty estimates from the American Community Survey. Neighborhood-level poverty (low, intermediate, and high) was defined as the proportion of residents in the census tract living below the federal poverty threshold. We used generalized linear mixed effects models with a logit link function to examine the association between neighborhood poverty and incident AF, adjusting for patient demographic and clinical AF risk factors. KEY RESULTS: Among 28,858 in the cohort, patients in the high poverty group were more often non-Hispanic Black or Hispanic and had higher rates of AF risk factors. Over 5 years of follow-up, 971 (3.4%) patients developed incident AF. Of these, 502 (51.7%) were in the low poverty, 327 (33.7%) in the intermediate poverty, and 142 (14.6%) in the high poverty group. The adjusted odds ratio (aOR) of AF was higher for the intermediate poverty compared with that for the low poverty group (aOR 1.23 [95% CI 1.01–1.48]). The point estimate for the aOR of AF incidence was similar, but not statistically significant, for the high poverty compared with the low poverty group (aOR 1.25 [95% CI 0.98–1.59]). CONCLUSION: In adults without baseline cardiovascular disease managed in a large, integrated health system, intermediate neighborhood poverty was significantly associated with incident AF. Understanding neighborhood-level drivers of AF disparities will help achieve equitable care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06976-2.

Background Little is known about what factors predict better outcomes for patients who undergo minimally invasive pancreaticoduodenectomy (MIPD) versus open pancreaticoduodenectomy (OPD). We hypothesized that patients with dilated pancreatic ducts have improved postoperative outcomes with MIPD compared to OPD. Methods All patients undergoing pancreaticoduodenectomy were prospectively followed over a time period of 47 months, and perioperative and pathologic covariates and outcomes were compared. Ideal outcome after PD was defined as follows: (1) no complications, (2) postoperative length of stay

INTRODUCTION: The American Heart Association (AHA) introduced the construct of “cardiovascular health (CVH)”, to focus on primordial prevention to reduce the burden of cardiovascular disease (CVD). The CVH score includes 7 health and behavioral metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, blood glucose), which are characterized as being ideal, intermediate, or poor. AREAS COVERED: In this review, we describe the utility of the CVH score for monitoring and promoting wellness, overall and by key sociodemographic groups, and for tracking of temporal trends. EXPERT COMMENTARY: Notably, the 7 factors are all modifiable, which differs from 10-year CVD risk scores that include non-modifiable components such as age, sex, and race. Numerous epidemiological studies have shown that achievement of a greater number of ideal CVH metrics is associated with lower incidences of CVD, cardiovascular mortality, and all-cause mortality. Longer duration of favorable CVH is associated with greater longevity and compressed morbidity. Nevertheless, the prevalence of favorable CVH is low, with

Type III gastric neuroendocrine neoplasms (g-NENs) have historically been regarded as aggressive tumours, hence current guidelines advocate radical surgery with lymph node dissection. Data on the roles of endoscopic or less extensive surgical resections are more limited. The aim of our study is to evaluate the clinicopathological features and long-term outcomes of patients undergoing endoscopic or limited surgical resection for localised grade 1 or 2 type III g-NENs when compared to radical surgery. Retrospective analysis of all patients diagnosed with a localised grade 1 or 2 type III g-NENs across six tertiary NEN centers between 2006 and 2019. Forty-five patients were diagnosed with a potentially resectable grade 1 or 2 type III g-NEN of whom 36 underwent either endoscopic or surgical resection. No statistically significant differences were found between the three resection groups in terms of patient age, tumour location, grade or size. Only tumour size was found to be significantly associated with poor clinical outcome (p = 0.012) and ROC curve analysis identified tumour size >10 mm as a negative predictor (AUC:0.8030, p = 0.0021). Tumours >10 mm were also more likely to be associated with lymph node metastases on imaging and histology (p = 0.039 and p = 0.026 respectively). Localised grade 1 or 2 type III g-NENs had a good prognosis in this series. Tumour size >10 mm was the most significant prognostic factor affecting patient outcome. Endoscopic resection or limited surgical resection is feasible and safe in small type III g-NENs which demonstrate favourable grade 1/2, well differentiated histology.

Place of death is a key indicator of quality of end-of-life care, and most people with a terminal diagnosis prefer to die at home. Home has surpassed the hospital as the most common location of all-cause and total cancer-related deaths in the United States. However, trends in place of death due to hepatocellular carcinoma (HCC), which is uniquely comanaged by hepatologists and oncologists, have not been described. We analysed US death certificate data from 2003 to 2018 for the proportion of deaths over time at medical facilities, nursing facilities, hospice facilities and home, for HCC and non-HCC cancer. The proportion of deaths increased from 0.6% to 15.2% in hospice facilities (P trend < 0.0001) but did not change at home. In multivariable analysis, persons with HCC were more likely than persons with non-HCC cancer to die in medical facilities, while persons with HCC were less likely to die at home.

BACKGROUND: Neighborhood-level characteristics, such as poverty, have been associated with risk factors for heart failure (HF), including hypertension and diabetes mellitus. However, the independent association between neighborhood poverty and incident HF remains understudied. OBJECTIVE: To evaluate the association between neighborhood poverty and incident HF using a “real-world” clinical cohort. DESIGN: Retrospective cohort study of electronic health records from a large healthcare network. Individuals’ residential addresses were geocoded at the census-tract level and categorized by poverty tertiles based on American Community Survey data (2007–2011). PARTICIPANTS: Patients from Northwestern Medicine who were 30–80 years, free of cardiovascular disease at index visit (January 1, 2005–December 1, 2013), and followed for at least 5 years. MAIN MEASURES: The association of neighborhood-level poverty tertile (low, intermediate, and high) and incident HF was analyzed using generalized linear mixed effect models adjusting for demographics (age, sex, race/ethnicity) and HF risk factors (body mass index, diabetes mellitus, hypertension, smoking status). KEY RESULTS: Of 28,858 patients included, 75% were non-Hispanic (NH) White, 43% were men, 15% lived in a high-poverty neighborhood, and 522 (1.8%) were diagnosed with incident HF. High-poverty neighborhoods were associated with a 1.80 (1.35, 2.39) times higher risk of incident HF compared with low-poverty neighborhoods after adjustment for demographics and HF risk factors. CONCLUSIONS: In a large healthcare network, incident HF was associated with neighborhood poverty independent of demographic and clinical risk factors. Neighborhood-level interventions may be needed to complement individual-level strategies to prevent and curb the growing burden of HF. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06785-7.

People living with dementia (PLwD) often exhibit behavioral and psychological symptoms, such as episodes of agitation and aggression. Agitated behavior in PLwD causes distress and increases the risk of injury to both patients and caregivers. In this paper, we present the use of a multi-modal wearable device that captures motion and physiological indicators to detect agitation in PLwD. We identify features extracted from sensor signals that are the most relevant for agitation detection. We hypothesize that combining multi-modal sensor data will be more effective to identify agitation in PLwD in comparison to a single sensor. The results of this unique pilot study are based on 17 participants’ data collected during 600 days from PLwD admitted to a Specialized Dementia Unit. Our findings show the importance of using multi-modal sensor data and highlight the most significant features for agitation detection.

Purpose: The temporary cessation and profound changes in ophthalmic care delivery that occurred as a result of the coronavirus disease 2019 (COVID-19) pandemic have yet to be fully understood. Our objective is to assess patients’ self-reported impact of health care lockdown measures on their fears and anxieties during the crisis period of the COVID-19 pandemic in New York City. Methods: We conducted a digital, self-reported, patient care survey distributed by an e-mail at Columbia University’s Department of Ophthalmology outpatient faculty practice. Inclusion criteria were age greater than or equal to 18 years, a diagnosis of either retinal disease or glaucoma, and a canceled or rescheduled ophthalmology established patient appointment during the acute phase of the COVID-19 pandemic in New York City. Patients without an e-mail address listed in their electronic medical records were excluded. The survey occurred between March 2, 2020, to May 30, 2020. Primary measures were survey responses to assess key areas of patient anxiety or concern during the pandemic including the safety of care delivery in a COVID pandemic, difficulties contacting or being seen by their ophthalmologist, concern of vision loss or disease progression, and concern over missed or access to treatments. Secondary measures were correlating survey response to factors such as visual acuity, intraocular pressure, diagnosis, disease severity, follow-up urgency, recent treatments, and diagnostic testing data. Results: Of the 2594 surveys sent out, 510 (19.66%) were completed. Over 95% of patients were at least as concerned as in normal circumstances about their ocular health during the peak of the pandemic. Overall, 76% of respondents were more concerned than normal that they could not be seen by their ophthalmologist soon enough. Increased concern over ocular health, disease progression, and access to care all showed positive correlations (P

Antibiotic resistance (ABR) has been identified as a critical threat to global health at the highest policy fora. A leading cause of ABR is the inappropriate use of antibiotics by both patients and healthcare providers. Although countries around the world have committed to developing and implementing national action plans to tackle ABR, there is a considerable gap in evidence about effective behaviour change interventions addressing inappropriate use of antibiotics in low- and middle-income countries (LMICs), where ABR is growing at an alarming rate. We conducted a systematic review to synthesize evidence about the effectiveness and cost-effectiveness of behaviour change interventions to reduce inappropriate use of antibiotics in LMICs. Three databases were searched using a set of predefined search terms and exclusion criteria. The search identified 43 relevant articles. A narrative synthesis of results was conducted using the Behaviour Change Wheel framework to categorize intervention components. The majority of the reviewed studies were set in lower-middle-income or low-income countries located in Sub-Saharan Africa or East Asia and the Pacific. Twenty-four articles evaluated multi-faceted interventions over a period of 12 months or less. Despite the widespread use of antibiotics in the community, interventions were primarily implemented in public health facilities, targeting health professionals such as doctors, nurses, and other allied medical staff. Although education for providers was the most widely used strategy for influencing antibiotic use, it was shown to be most effective when used in conjunction with training or other enabling and supportive measures to nudge behaviour. Six articles included an evaluation of costs of interventions and found a reduction in costs in inpatient and outpatient settings, and one article found a training and guidelines implementation-based intervention to be highly cost-effective. However, the small number of articles conducting an economic evaluation highlights the need for such analyses to be conducted more frequently to support priority setting in resource-constrained environments.

Introduction: Coronavirus has caused more than a million deaths as of October 2020. Hospitals consider tracheostomy after the patient is virus negative, usually after 3 weeks. Prevalence and timing of tracheostomy and its impact on survival among COVID patients are unknown. Methods: A retrospective, single-center study of all patients with COVID-19 ARDS who underwent tracheostomy was conducted. Patients with age Results: We found that tracheostomies were performed only in 21 out of 196 patients (10.8%). Tracheostomies were performed after 3 weeks on average (22.1 ± 7.5 days). Survival was significantly higher in patients who underwent tracheostomy (85.7 vs. 42.5%, p = 0.001). LOSICU was longer for tracheostomy patients than patients without tracheostomy (median [IQR]: 35 [23–47] vs. 15 [9–21], p = 0.001). Patients who underwent tracheostomy had a higher proportion of treatment with continuous renal replacement therapy (CRRT) (52 vs. 30%, p = 0.04), more COVID-19 swab testing (6.5 [4.5–8.5] vs. 5 [3–7], p = 0.002), more days on mechanical ventilation (34.5 [24–45] vs. 11 [5.5–16.5], p = 0.001), and more length of stay in the hospital (54 [38–70] vs. 20 [10.5–29.5], p = 0.001). All other factors were not statistically different between the 2 groups. Approximately 29% of patients had possible false-negative testing as their swab became positive after being negative. Conclusion: Tracheostomy was performed only in 10% of our patients with COVID-19 ARDS. Time to tracheostomy was after 3 weeks on average. Survival was better in patients with tracheostomy, but tracheostomized patients stayed longer in the ICU and hospital and utilized more days of mechanical ventilation and CRRT.

Aims The CANVAS Program identified the effect of canagliflozin on major adverse cardiovascular events (MACE) differed according to whether participants were using diuretics at study commencement. We sought to further evaluate this finding related to baseline differences, treatment effects, safety, and risk factor changes.Methods and results The CANVAS Program enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomized to canagliflozin or placebo and followed for a mean of 188 weeks. The primary outcome was major cardiovascular events, a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included multiple cardiovascular, renal, and safety events. In this post hoc subgroup analysis, participants were categorized according to baseline use of any diuretic. The effect on outcomes was compared using Cox proportional hazards models, while risk factor changes were compared using mixed-effect models. At baseline, 4490 (44.3%) participants were using a diuretic. Compared with those not using a diuretic, participants using a diuretic were more likely to be older (mean age +/- standard deviation, 64.3 +/- 8.0 vs. 62.5 +/- 8.3), be female (38.9% vs. 33.4%), and have heart failure (19.6% vs. 10.3%) (all P-difference < 0.0001). The effect of canagliflozin on major cardiovascular events was greater for those using diuretic at baseline than for those who were not [adjusted hazard ratio 0.65 (95% confidence interval 0.54-0.78) vs. adjusted hazard ratio 1.13 (95% confidence interval 0.93-1.36), P-heterogeneity < 0.0001]. Changes in most risk factors, including blood pressure, body weight, and urine albumin-to-creatinine ratio, were similar between groups (all P-difference > 0.11), although the effect of canagliflozin on haemoglobin A1c reduction was slightly weaker in participants using compared with not using diuretics at baseline (-0.52% vs. -0.64%, P-heterogeneity = 0.0007). Overall serious adverse events and key safety outcomes, including adverse renal events, were also similar (all P-heterogeneity > 0.07).Conclusions Participants on baseline diuretics derived a greater benefit for major cardiovascular events from canagliflozin, which was not fully explained by differences in participant characteristics nor risk factor changes.

Introduction: Maternal near miss is a major global health issue; approximately 7 million women worldwide experience it each year. Maternal near miss can have several different health consequences and can affect the women’s quality of life, yet little is known about the size and magnitude of this association. The aim of this study was to assess the evidence of the association between women who have experienced maternal near miss and quality of life and women who had an uncomplicated pregnancy and delivery. Material and methods: Cochrane library, Embase, CINAHL, Web of Science, MEDLINE, Scopus and PubMed were searched for published studies. Studies were selected according to the PECO model (population, exposure, control and outcome) and were included if they investigated quality of life as an outcome after maternal near miss among women of all ages with no limitation on country or time (up to June 2020). Maternal near miss was defined as a life-threatening condition arising from complications related to pregnancy and/or childbirth. The quality of the studies was assessed according to the Newcastle-Ottawa scale and a Forest plot was constructed based on quality of life outcomes and study quality. PROSPERO registration number: CRD42020169232. Results: Fifteen studies were included in the review with a total of 31 558 women. Quality of life was reported in various ways, and 25 different confounders were controlled for. Compared with women who did not experience maternal near miss, women exposed to maternal near miss had an overall lower quality of life (n = 2/2), had poorer mental (n = 6/10) and social health (n = 2/3), and maternal near miss had negative economic consequences (n = 4/4). Maternal near miss was not associated with sexual dysfunction (n = 1/5). Ten of 15 studies were assessed as being of poor quality. Conclusions: Evidence shows that maternal near miss is negatively associated with various aspects of quality of life. This highlights the importance of addressing the adverse effects associated with maternal near miss and follow up maternal near miss after discharge. Quality of life is a multidimensional concept that is assessed in various ways, and the literature on the field is heterogeneous. More high-quality studies are needed.

Background The emergence of multi-drug-resistant (MDR) micro-organisms prompted new interest in older antibiotics, such as colistin, that had been abandoned previously due to limited efficacy or high toxicity. Over the years, several chromosomal-encoded colistin resistance mechanisms have been described; more recently, 10 plasmid-mediated mobile colistin resistance (mcr) genes have been identified. Spread of these genes among MDR Gram-negative bacteria is a matter of serious concern; therefore, reliable and timely mcr detection is paramount. Aim To design and validate a multiplex real-time polymerase chain reaction (PCR) assay for detection and differentiation of mcr genes. Methods All available mcr alleles were downloaded from the National Center for Biotechnology Information Reference Gene Catalogue, aligned with Clustal Omega and primers designed using Primer-BLAST. Real-time PCR monoplexes were optimized and validated using a panel of 120 characterized Gram-negative strains carrying a wide range of resistance genes, often in combination. Melt-curve analysis was used to confirm positive results. Findings In-silico analysis enabled the design of a ‘screening’ assay for detection of mcr-1/2/6, mcr-3, mcr-4, mcr-5, mcr-7, mcr-8 and mcr-9/10, paired with an internal control assay to discount inhibition. A ‘supplementary’ assay was subsequently designed to differentiate mcr-1, mcr-2, mcr-6, mcr-9 and mcr-10. Expected results were obtained for all strains (100% sensitivity and specificity). Melt-curve analysis showed consistent melting temperature results. Inhibition was not observed. Conclusions The assay is rapid and easy to perform, enabling unequivocal mcr detection and differentiation even when more than one variant is present. Adoption by clinical and veterinary microbiology laboratories would aid the surveillance of mcr genes amongst Gram-negative bacteria.

Background Little is known about the timing of preclinical heart failure (HF) development, particularly among blacks. The primary aims of this study were to delineate age-related left ventricular (LV) structure and function evolution in a biracial cohort and to test the hypothesis that young-adult LV parameters within normative ranges would be associated with incident stage B–defining LV abnormalities over 25 years, independent of cumulative risk factor burden. Methods Data from the Coronary Artery Risk Development in Young Adults study were analyzed. Participants (n = 2,833) had a mean baseline age of 30.1 years; 45% were black, and 56% were women. Generalized estimating equation logistic regression was used to estimate age-related probabilities of stage B LV abnormalities (remodeling, hypertrophy, or dysfunction) and logistic regression to examine risk factor–adjusted associations between baseline LV parameters and incident abnormalities. Cox regression was used to assess whether baseline LV parameters associated with incident stage B LV abnormalities were also associated with incident clinical (stage C/D) HF events over >25 years’ follow-up. Results Probabilities of stage B LV abnormalities at ages 25 and 60 years were 10.5% (95% CI, 9.4%–11.8%) and 45.0% (95% CI, 42.0%–48.1%), with significant race-sex disparities (e.g., at age 60, black men 52.7% [95% CI, 44.9%–60.3%], black women 59.4% [95% CI, 53.6%–65.0%], white men 39.1% [95% CI, 33.4%–45.0%], and white women 39.1% [95% CI, 33.9%–44.6%]). Over 25 years, baseline LV end-systolic dimension indexed to height was associated with incident systolic dysfunction (adjusted odds ratio per 1 SD higher, 2.56; 95% CI, 1.87–3.52), eccentric hypertrophy (1.34; 95% CI, 1.02–1.75), concentric hypertrophy (0.69; 95% CI, 0.51–0.91), and concentric remodeling (0.68; 95% CI, 0.58–0.79); baseline LV mass indexed to height2.7 was associated with incident eccentric hypertrophy (1.70; 95% CI, 1.25–2.32]), concentric hypertrophy (1.63; 95% CI, 1.19–2.24), and diastolic dysfunction (1.24; 95% CI, 1.01–1.52). Among the entire cohort with baseline echocardiographic data available (n = 4,097; 72 HF events), LV end-systolic dimension indexed to height and LV mass indexed to height2.7 were significantly associated with incident clinical HF (adjusted hazard ratios per 1 SD higher, 1.56 [95% CI, 1.26–1.93] and 1.42 [95% CI, 1.14–1.75], respectively). Conclusions Stage B LV abnormalities and related racial disparities were present in young adulthood, increased with age, and were associated with baseline variation in indexed LV end-systolic dimension and mass. Baseline indexed LV end-systolic dimension and mass were also associated with incident clinical HF. Efforts to prevent the LV abnormalities underlying clinical HF should start from a young age.

Aims To investigate factors that contribute to patient decisions regarding attendance for arthroplasty during the COVID-19 pandemic. Methods A postal questionnaire was distributed to patients on the waiting list for hip or knee arthroplasty in a single tertiary centre within the UK. Patient factors that may have influenced the decision to attend for arthroplasty, global quality of life (QoL) (EuroQol five-dimension three-level (EQ-5D-3L)), and joint-specific QoL (Oxford Hip or Knee Score) were assessed. Patients were asked at which ‘COVID-alert’ level they would be willing to attend an NHS and a “COVID-light” hospital for arthroplasty. Independent predictors were assessed using multivariate logistic regression. Results Of 540 distributed questionnaires, 400 (74.1%; 236 awaiting hip arthroplasty, 164 awaiting knee arthroplasty) complete responses were received and included. Less than half (48.2%) were willing to attend for hip or knee arthroplasty while a UK COVID-19 epidemic was in circulation (COVID-alert levels 3 to 5). Patients with worse joint-specific QoL had a preference to proceed with surgery at COVID-alert levels 3 to 5 compared to levels 1 and 2 (hip arthroplasty odds ratio (OR) 1.54 (95% confidence interval (CI) 1.45 to 1.63); knee arthroplasty OR 1.16 (1.07 to 1.26)). The odds of patients with worse joint-specific QoL being willing to attend for surgery at COVID-alert levels 3 to 5 increased further if surgery in a private, “COVID-light” hospital was available (hip arthroplasty OR 3.50 (95% CI 3.26 to 3.71); knee arthroplasty OR 1.41 (95% CI 1.29 to 1.53). Conclusion Patient decisions surrounding elective surgery have been influenced by the global COVID-19 pandemic, highlighting the importance of patient involvement in ensuring optimized provision of elective surgery during these challenging times. Cite this article: Bone Jt Open 2021;2(4):261–270.

Background Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF. Methods and Results Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th–75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1–379.5 RU/mL) and 90.3 pg/mL (68.6–128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes. Conclusions In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline.

Rapidly growing, symptomatic, non-hematological, malignant neck masses are unusual in young adults. We report a case of a 34-year-old African American male with sickle cell trait who presented with a large left supraclavicular/cervical mass comprising of poorly differentiated malignant epithelial cells consistent with metastatic carcinoma of unknown origin. Upon immunohistochemistry, the tumor showed loss of INI1 (BAF47) and retained PAX-8 expression. After extensive clinical and radiological work-up the primary tumor was found to be a 2.6 cm renal medullary carcinoma. This case highlights the role of multidisciplinary approach to the diagnosis of a neck mass and to understanding that certain genetically-defined tumors can occur at and metastasize to any site.

Highlights • Intensification of chemoradiation with hyperthermia was feasible in nine patients with LAPC. • Only one grade three toxicity was reported and two tumours became resectable. • The 24 months median OS and 100% 1 year OS are superior to historical series., Introduction Driven by the current unsatisfactory outcomes for patients with locally advanced pancreatic cancer (LAPC), a biologically intensified clinical protocol was developed to explore the feasibility and efficacy of FOLFORINOX chemotherapy followed by deep hyperthermia concomitant with chemoradiation and subsequent FOLFORINOX chemotherapy in patients with LAPC. Methods Nine patients with LAPC were treated according to the HEATPAC Phase II trial protocol which consists of 4 cycles of FOLFORINOX chemotherapy followed by gemcitabine-based chemoradiation to 56 Gy combined with weekly deep hyperthermia and then a further 8 cycles of FOLFORINOX chemotherapy. Results One grade three related toxicity was reported and two tumours became resectable. The median overall survival was 24 months and 1 year overall survival was 100%. Conclusions Intensification of chemoradiation with deep hyperthermia was feasible in nine consecutive patients with LAPC.

In this work, an attempt is made to improve the electrochemical corrosion resistance of Zircaloy-4 by helium ions implantation. For this purpose, the Zircaloy-4 was implanted with 300 keV helium ions of fluences 1 × 1013, 1 × 1015, and 1 × 1016 ions-cm−2 by using Pelletron Accelerator. Electrochemical tests of pristine and ion-implanted samples were performed in NaCl solution and their potentiodynamic polarization curves were obtained. The results showed enhancement of the corrosion resistance of Zircaloy-4 after helium ions implantation. The corrosion rate and current density of the material were significantly reduced by the helium implantation. The decrease in corrosion parameters was attributed to helium ions diffusion inside Zircaloy-4 that reduced the electrons flow from the samples.

Objective To conduct a systematic review and meta-analysis of the efficacy of anti-nerve growth factor (NGF) monoclonal antibodies in osteoarthritis pain (hip and knee). Design Grade the evidence for anti-NGF use. Methods An interdisciplinary work group conducted a literature search for anti-NGF use in osteoarthritis. The systematic review was performed in accordance with methods described by the Cochrane collaboration. General inclusion criteria included all osteoarthritis trials studying any monoclonal anti-NGF antibody at any dose/phase. Excluded studies were those where participants received NSAIDs or analgesics other than anti-NGF antibodies. The Jadad Scale score was used to assess the quality of the included studies. Results Thirteen studies were included in the analysis, involving 8145 participants with a diagnosis of hip and/or knee osteoarthritis. Anti-NGF antibody treatment was associated with a significant improvement in all Western Ontario and McMaster Universities Arthritis Index (WOMAC) indices when compared to placebo. These agents were not associated with a significantly increased incidence of serious adverse events but were associated with significant increases in therapy discontinuation due to adverse events or side effects (e.g., peripheral neuropathy). Conclusions Future randomized clinical trials are needed to characterize the overall risk-to-benefit ratio of anti-NGF antibodies in managing pain associated with OA, particularly with long-term use, in order to verify their efficacy and safety in clinical practice.

SIRT1 prevents retinal ganglion cell (RGC) loss in models of optic neuropathy following pharmacologic activation or genetic overexpression. The exact mechanism of loss is not known, prior evidence suggests this is through oxidative stress to either neighboring cells or RGC specifically. We investigated the neuroprotective potential of RGC-selective SIRT1 gene therapy in the optic nerve crush (ONC) model. We hypothesized that AAV-mediated overexpression of SIRT1 in RGCs reduces RGC loss, thereby preserving visual function. Cohorts of C57Bl/6J mice received intravitreal injection of experimental or control AAVs using either a ganglion cell promoter or a constitutive promoter and ONC was performed. Visual function was examined by optokinetic response (OKR) for 7 days following ONC. Retina and optic nerves were harvested to investigate RGC survival by immunolabeling. The AAV7m8-SNCG.SIRT1 vector showed 44% transduction efficiency for RGCs compared with 25% (P > 0.05) by AAV2-CAG.SIRT1, and AAV7m8-SNCG.SIRT1 drives expression selectively in RGCs in vivo. Animals modeling ONC demonstrated reduced visual acuity compared to controls. Intravitreal delivery of AAV7m8-SNCG.SIRT1 mediated significant preservation of the OKR and RGC survival compared to AAV7m8-SNCG.eGFP controls, an effect not seen with the AAV2 vector. RGC-selective expression of SIRT1 offers a targeted therapy for an animal model with significant ganglion cell loss. Over-expression of SIRT1 through AAV-mediated gene transduction suggests a RGC selective component of neuro-protection using the ONC model. This study expands our understanding of SIRT1 mediated neuroprotection in the context of compressive or traumatic optic neuropathy, making it a strong therapeutic candidate for testing in all optic neuropathies.

Introduction Somatostatin analogs (SSAs) are used to treat neuroendocrine tumors (NETs) and acromegaly. Two first-generation SSAs, octreotide long-acting release (OCT LAR) and lanreotide autogel/depot (LAN), are available. A systematic literature review (SLR) was conducted to investigate which characteristics beyond efficacy are most important in patient and healthcare practitioner (HCP) experience of LAN and OCT when used to treat acromegaly and NETs. Methods MEDLINE, Embase, the Cochrane Library, and Database of Abstracts of Reviews of Effect were searched from database inception to January 2019 with terms for first-generation SSAs, NETs, acromegaly, preferences, decision-making, and human factors. Key congresses in 2016–2018 and SLR bibliographies were hand-searched. Two independent reviewers screened articles at title/abstract and full-text stage. Publications fulfilling pre-specified inclusion criteria reported patient or HCP perspectives of LAN or OCT, or any factors affecting treatment perspectives for NETs or acromegaly. Results A total of 1110 unique records were screened, of which 21 studies were included, reporting from the perspectives of patients (n = 18) and/or HCPs (n = 9). Perspectives were collected using shared decision-making frameworks, questionnaires, informal patient opinion, and a Delphi panel. Where patient preference was specifically reported, LAN was preferred in 4/5 studies and OCT LAR in 1/5. Common factors underlying treatment experience included technical problems with injections and associated pain, emotional quality/anxiety of injections, time and convenience of treatment administration, and independence. Immediate aspects of injections appeared most important to patients, though the possibilities of extended dosing intervals and self-/partner-injection with LAN were also notable factors. Conclusions Study outcomes favored LAN in this SLR, with factors surrounding injection administration most influential in treatment experience. The findings of this SLR provide a basis that could inform development of decision-making criteria, with patient and HCP treatment perspectives considered. Future studies should utilize a common method to report preference and associated drivers. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-020-01600-x.

Background The prevalence of burnout and depressive symptoms is high among physician trainees. Research Question What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics? Study Design and Methods We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms. Results Five hundred two of the 976 fellows who received the survey completed it—including both outcome measures—giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms. Interpretation Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.

Hip-fracture patients are vulnerable to the outcomes of COVID-19. We performed a cross-sectional survey to determine measures employed to limit nosocomial spread of COVID-19 in 23 orthopaedic trauma departments in the North-West of England. Nineteen (87%) hospitals admitted patients to a ward prior to a negative swab, and only 9 (39%) patients were barrier nursed. Hip-fracture patients were operated in non-COVID-19-free theatres in 21 (91%) hospitals. Regular screening of doctors working in trauma and elective areas for COVID-19 was undertaken in three (13%) and five (22%) hospitals, respectively. Doctors moved freely between trauma and elective areas in 22 (96%) hospitals.