Search

Background. Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners’ clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants’ attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author’s Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations.

Background: Acute kidney injury (AKI) is a frequent complication of transcatheter aortic valve implantation (TAVI) and has been linked to preexisting comorbidities, peri-procedural hypotension, and systemic inflammation. The extent of systemic inflammation after TAVI is not fully understood. Our aim was to characterize the inflammatory response after TAVI and evaluate its contribution to the mechanism of post-procedural AKI. Methods: One hundred and five consecutive patients undergoing TAVI at our institution were included. We analyzed the peri-procedural inflammatory and oxidative stress responses by measuring a range of biomarkers (including C-reactive protein [hsCRP], cytokine levels, and myeloperoxidase [MPO]), before TAVI and 6, 24, and 48 hours post-procedure. We correlated this with changes in renal function and patient and procedural characteristics. Results: We observed a significant increase in plasma levels of pro-inflammatory cytokines (hsCRP, interleukin 6, tumor necrosis factor alpha receptors) and markers of oxidative stress (MPO) after TAVI. The inflammatory response was significantly greater after trans-apical (TA) TAVI compared to trans-femoral (TF). This was associated with a higher incidence of AKI in the TA cohort compared to TF (44% vs. 8%, respectively, p < 0.0001). The incidence of AKI was significantly lower when N-acetylcysteine (NAC) was given peri-procedurally (12% vs. 38%, p < 0.005). In multivariate analysis, only the TA approach and no use of NAC before the procedure were independent predictors of AKI. Conclusions: TAVI creates a significant post-procedural inflammatory response, more so with the TA approach. Mechanisms of AKI after TAVI are complex. Inflammatory response, hypoperfusion, and oxidative stress may all play a part and are potential therapeutic targets to reduce/prevent AKI.

SummaryAfrican populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multigenerational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within the African continent, as well as how within-Africa variation can be informative for broader variant interpretation; many variants appearing rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity within Africa.

We investigated patient outcomes in relation to their postoperative length of stay after minimally invasive valve surgery.All adults who survived elective, uncomplicated minimally invasive aortic or mitral valve surgery at a single center between 2012 and 2019 were classified by postoperative length of stay: early discharge (≤3 days) or late discharge (3 days). The trend in early discharge was investigated over the study period, predictors of early discharge were identified using multivariate logistic regression modeling, and 1:1 propensity score matching was used to determine which patients in the late-discharge cohort had similar health to patients discharged early. Adjusted outcomes of 30-day mortality, readmission, and direct costs were analyzed.Among 1262 consecutive patients undergoing minimally invasive valve surgery, 618 were elective and uncomplicated, 25% (n = 162) of whom were discharged early. The proportion of early-discharge patients increased over time (P for trend.05). A history of congestive heart failure, stroke, or smoking and higher Society of Thoracic Surgeons predictive risk of mortality score negatively predicted early discharge (P.05). Propensity score matching identified 101 (22%) late-discharge patients comparable with early-discharge patients. Adjusted 30-day mortality and readmission rates were comparable between cohorts. The median direct costs per patient ($20,046 vs $22,124, P.05) were significantly lower in the early-discharge cohort.In well-selected patients early discharge after minimally invasive valve surgery was associated with lower costs but comparable postoperative outcomes. About one-fifth of patients who remain in the hospital beyond postoperative day 3 may be candidates for earlier discharge.

Clinical Practice Points • New metastatic sites in non-small cell lung cancer (NSCLC) patients have been shown to have the potential to transform into another histologic subtype that is different from the original histology of the patient while on treatment. • These histological transformations can indicate potential resistance mechanisms to current or prior treatments and can prompt a change in management in patients. • However, little is known about histologic transformations in NSCLC patients and what are the next steps in management. • New reports have shown that epidermal growth factor receptor tyrosine kinase inhibitors such as osimertinib can also lead to these histologic transformations in NSCLC cases and rarely to either large cell neuroendocrine carcinomas or small cell carcinoma. • This case highlights the important implications for these patients since the treatment plans are different and changes in prognosis and for clinicians to be aware of these possibilities and consider repeat biopsies and genomic testing to optimize treatment.

BACKGROUND There is concern that the polyunsaturated fatty acid (PUFA) composition of ready-to-use therapeutic food (RUTF) for treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. OBJECTIVE We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high oleic (HO) peanuts without added DHA (HO-RUTF) or with added DHA (DHA-HO-RUTF), improves cognition when compared to standard RUTF (S-RUTF). METHODS A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF: DHA-HO-RUTF, HO-RUTF and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global z-score and a modified Willatts problem solving assessment (PSA) intention score for 3 standardized problems, measured 6 months and immediately after completing RUTF therapy, respectively. MDAT domain z-scores, plasma fatty acid content, anthropometry and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. RESULTS Among the 2565 SAM children enrolled, mean global MDAT z-scores were -0.69 ± 1.19 and -0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI 0.01, 0.38). Children receiving DHA-HO-RUTF had higher gross motor and social domain z-scores than those receiving S-RUTF. The PSA problem 3 scores did not differ by dietary group (Odds Ratios 0.92, 95% CI 0.67, 1.26 for DHA-HO-RUTF). After 4 weeks of treatment, plasma phospholipid EPA and α-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared to S-RUTF (for all 4 comparisons P values

OBJECTIVES To evaluate the prevalence of PTSD symptoms in individuals who are further removed from injury (up to three years) and to identify injury specific characteristics that are associated with an increased risk for persistent PTSD symptoms. DESIGN Cross-sectional, retrospective cohort. SETTING Level I Trauma CenterPATIENTS/PARTICIPANTS: 243 patients operatively treated for orthopaedic trauma between March 2017 through June 2018. INTERVENTION Orthopaedic trauma requiring operative intervention. MAIN OUTCOME MEASUREMENTS The primary outcome was score on the PTSD Checklist for the DSM-5 (PCL-5) survey. A score of 31 or higher was considered concerning for PTSD. RESULTS 49 respondents scored positive for PTSD out of 239 (20.5%). Multivariate analysis demonstrated an increased risk of PTSD for patients with a history of smoking and those that required delayed re-operation (greater than 90 days post-operative). Caucasian race and low energy mechanisms of injury were associated with decreased risk of PTSD. Fracture locations were not associated with a higher likelihood of PTSD. CONCLUSIONS The prevalence of PTSD symptoms in patients up to three years after surgery remains higher than the estimated prevalence of PTSD in the general United States population. It is similar to previously documented rates of PTSD for patients less than one year after injury. Long-term complication requiring re-operation was associated with an increased risk of persistent PTSD symptoms. Orthopaedic providers should be mindful of PTSD symptoms not only in the immediate post-operative period but throughout the treatment course particularly for those with identified PTSD risk factors. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background: Although the assessment of right ventricular (RV) diastolic function is feasible, it has garnered far less momentum for use compared with its left ventricular counterpart. The scarcity of data defining normative RV diastolic function and the fact that implications of RV diastolic dysfunction in different disease states on outcomes are less well known both hinder integration into routine clinical assessment. The aim of this study was to establish normal values of RV diastolic parameters stratified by sex, age, and race using data from the World Alliance Societies of Echocardiography study. Methods: A subset of 888 normal subjects from the World Alliance Societies of Echocardiography database were analyzed, including measurements of tricuspid valve (TV) inflow E- and A-wave velocities, E-wave deceleration time, and TV annular tissue Doppler e′ and a′ velocities. Additionally, right atrial (RA) maximal volume and RA peak reservoir strain were measured. Patients were grouped by age ([removed]65 years) and stratified by sex and race. Differences were analyzed using unpaired t tests. Results: Compared with men, women had significantly higher TV e′ and E-wave and A-wave velocities, though differences were modest. Increasing age was associated with stepwise lower TV E wave, e′ velocity, and TV E/A ratio and higher a′ velocity and E/e′ ratio. RA peak reservoir strain was also lower, and RA end-systolic volume trended toward being smaller for older age groups. Asian subjects demonstrated significantly higher a′ velocities, lower E wave, the smallest RA end-systolic volumes, and the lowest RA peak strain values compared with white subjects of both sexes. Conclusions: This study provides normal values for parameters used in the assessment of RV diastolic function stratified by race, sex, and age. The results demonstrate significant differences in RV diastolic parameters between age groups, which manifest in both individual parameters and composite ratios of TV inflow and annular velocities. Although limited sex- and race-related differences were also noted, age appears to have the most significant impact on RV diastolic parameters. These findings may aid in refining current normative values.

Background : Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life (QoL). Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO2), physical function (distance walked in six minutes, 6MWD) and QoL (Kansas City Cardiomyopathy Questionnaire, KCCQ). Methods : We compared 75 older, obese, HFpEF patients to 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its three distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’, by Doppler ultrasound) and LA reservoir strain. Results : HFpEF had decreased reservoir strain (16.4±4.4% vs. 18.2±3.5%, p=0.018), lower conduit strain (7.7±3.3% vs. 9.1±3.4%, p=0.028), and increased stiffness index (0.86±0.39 vs. 0.53±0.18, p Conclusion : LA stiffness is independently associated with impaired exercise tolerance and QoL and may be an important therapeutic target in obese HFpEF. Registration : NCT00959660

Introduction Mutations in the IDH1 or IDH2 genes are detected in approximately 20% of cases of acute myeloid leukemia (AML). Few studies have examined the impact of IDH mutations in AML on allogeneic bone marrow transplant (alloBMT) outcomes. Patients and methods In this single center study, alloBMT outcomes for 61 patients with IDH-mutated (mIDH) AML were compared to those for 146 patients with IDH-wildtype (wtIDH) AML. Results Patients with mIDH AML had a 2-year overall survival (OS) of 85% (95% CI 76%-95%), 2-year relapse free survival (RFS) of 71% (95% CI 59%-85%), 1-year cumulative incidence of relapse (CIR) of 14% (95% CI 5%-23%) and a 1-year cumulative incidence of transplant related mortality (CITRM) of 3% (95% CI 0%-8%). Patients with wtIDH had a 2-year OS of 61% (95% CI 53%-70%), 2-year RFS of 58% (95% CI 50%-67%), 1-year CIR of 27% (95% CI 20%-35%), and a 1-year CITRM of 9% (95% CI 5%-14%). In a univariate analysis cox-proportional hazard model, mIDH was associated with significantly better OS (HR 0.52, 95% CI 0.29-0.96) and a trend toward better RFS (HR 0.60, 95% CI 0.35-1.01). After controlling for donor age, diagnosis, and ELN risk category, mIDH was associated with a nonsignificantly improved OS (HR 0.54, 95% CI 0.29-1.01) and RFS (HR 0.67, 95% CI 0.39-1.15). Conclusion Among patients with mIDH AML, patients who received a peritransplant IDH inhibitor had improved OS (P = .03) compared to those who did not, but there was no detectable difference for RFS (P = .29).

OBJECTIVE Evaluate injury patterns from wheeled recreational devices (WRD) in the public space and explore risk factors for hospital admission. METHOD A cross-sectional analysis of WRD injury prevalence and risk factors for hospital admissions was conducted using data from the Queensland Injury Surveillance Unit (QISU) database for 2007 to 2017. Descriptive statistics and a log-binomial regression model were used to calculate adjusted relative risk for hospital admission. RESULTS Most WRD injury in the public space was related to stand-alone WRD injury events such as falls, with few reported WRD users being hit by vehicles from 2007 to 2017. Stand-alone WRD injury events had a higher independent risk of hospital admissions when injured in the head/neck/face (RR 2.08, 95%CI 1.6 to 2.8, p

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated megakaryocytes (62% vs. 20%; P = 0.06), and a higher frequency of SETBP1 (69% vs. 5%; P = 0.002) and SRSF2 (63% vs. 5%; P = 0.006) mutations that were frequently co-existent (44% vs. 0%; P = 0.01). TP53 mutations were rare. The mutation profile of MDS/MPN-U-i(17q) was similar to other myeloid neoplasms with i(17q) including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, myelodysplastic syndrome and acute myeloid leukemia, with frequent concomitant SETBP1/SRSF2 mutations observed across all the diagnostic entities. Over a median follow-up of 52 months, patients with MDS/MPN-i(17q) showed a shorter median overall survival (11 vs. 28 months; P < 0.001). The presence of i(17q) retained independent poor prognostic value in multivariable Cox-regression analysis [HR 3.686 (1.17-11.6); P = 0.026] along with splenomegaly. We suggest that MDS/MPN-i(17q) warrants recognition as a distinct subtype within the MDS/MPN-U category based on its unique clinico-biologic features and uniformly poor prognosis.

Objective To determine if impairment in motor imagery processes is present in Achilles tendinopathy (AT), as demonstrated by a reduced ability to quickly and accurately identify the laterality (left-right judgement) of a pictured limb. Additionally, this study aimed to use a novel data pooling approach to combine data collected at 3 different sites via meta-analytical techniques that allow exploration of heterogeneity. Design Multi-site case-control study. Methods Three independent studies with similar protocols were conducted by separate research groups. Each study-site evaluated left/right judgement performance for images of feet and hands using Recognise© software and compared performance between people with AT and healthy controls. Results from each study-site were independently collated, then combined in a meta-analysis. Results In total, 126 participants (40 unilateral, 22 bilateral AT cases, 61 controls) were included. There were no differences between AT cases and controls for hand image accuracy and reaction time. Contrary to the hypothesis, there were no differences in performance between those with AT and controls for foot image reaction time, however there were conflicting findings for foot accuracy, based on four separate analyses. There were no differences between the affected and unaffected sides in people with unilateral AT. Conclusions Impairments in motor imagery performance for hands were not found in this study, and we found inconsistent results for foot accuracy. This contrasts to studies in persistent pain of limbs, face and knee osteoarthritis, and suggests that differences in pathoetiology or patient demographics may uniquely influence proprioceptive representation.

© 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Shoulder arthrodesis is generally considered a last resort procedure for patients with refractory shoulder pain or instability due to brachial plexus injuries, arthritis, trauma, or following resection of a neoplasm. Failure of a shoulder arthrodesis is thus a devastating and highly challenging complication with limited salvage options. Various factors may inhibit bone healing including inadequate fixation, poor bone stock, and poor bone surface preparation[ 1 ]. For effective bony fusion, vascularized bone stock is preferential to promote osseous regeneration[ 2 , 3 , 4 ]. Patients requiring shoulder arthrodesis have often undergone multiple procedures to the glenohumeral region rendering the area relatively devoid of normally perfused tissue. There are multiple adjuncts to encourage bone regeneration. Among the more effective options is transfer of vascularized tissue to the site. Here we present a patient with chronic pseudoarthrosis following shoulder arthrodesis and multiple attempts at revision. Given a lack of vascular recipient options, a pedicled osteofascial flap from the scapula was performed to introduce vascularized bone to the joint.

Background COVID-19 infection is known to cause a wide array of clinical chronic sequelae, but little is known regarding the long-term cardiac complications. We aim to report echocardiographic follow-up findings and describe the changes in left (LV) and right ventricular (RV) function that occur following acute infection. Methods Patients enrolled in the World Alliance Societies of Echocardiography-COVID study with acute COVID-19 infection were asked to return for a follow-up transthoracic echocardiogram. Overall, 198 returned at a mean of 129 days of follow-up, of which 153 had paired baseline and follow-up images that were analyzable, including LV volumes, ejection fraction (LVEF), and longitudinal strain (LVLS). Right-sided echocardiographic parameters included RV global longitudinal strain, RV free wall strain, and RV basal diameter. Paired echocardiographic parameters at baseline and follow-up were compared for the entire cohort and for subgroups based on the baseline LV and RV function. Results For the entire cohort, echocardiographic markers of LV and RV function at follow-up were not significantly different from baseline (all P > .05). Patients with hyperdynamic LVEF at baseline (>70%), had a significant reduction of LVEF at follow-up (74.3% ± 3.1% vs 64.4% ± 8.1%, P < .001), while patients with reduced LVEF at baseline (−20%) at baseline had significant improvement at follow-up (−15.2% ± 3.4% vs −17.4% ± 4.9%, P = .004). Patients with abnormal RV basal diameter (>4.5 cm) at baseline had significant improvement at follow-up (4.9 ± 0.7 cm vs 4.6 ± 0.6 cm, P = .019). Conclusions Overall, there were no significant changes over time in the LV and RV function of patients recovering from COVID-19 infection. However, differences were observed according to baseline LV and RV function, which may reflect recovery from the acute myocardial injury occurring in the acutely ill. Left ventricular and RV function tends to improve in those with impaired baseline function, while it tends to decrease in those with hyperdynamic LV or normal RV function.

Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.

The management of neck nodes in head and neck cancer is critical, given a markedly increased poor prognosis in patients with nodal metastasis. The surgical management of neck nodes has undergone radical changes secondary to a paradigm shift from curative surgery to nonsurgical organ and function-preserving options, such as radiation therapy. In the neck after treatment, radiologists should be familiar with imaging findings in various types of neck dissections and post-chemoradiation changes, along with signs of residual or recurrent disease. A multidisciplinary approach is essential with well-designed evidence-based surveillance imaging protocols and standardized reporting.

Introduction Breast conservation surgery (BCS) is the treatment of choice for unifocal, early-stage breast cancer. The ability to offer BCS to a wider subset of patients, including those with multifocal/multicentric cancer as well as extensive ductal carcinoma in situ, has emerged over time, especially in those undergoing joint oncoplastic reconstruction and those treated with neoadjuvant therapy. However, localization techniques using multiple radioactive seeds for bracketing in this patient subset have not been validated. Materials and Methods A single-institution retrospective review was conducted of all patients with breast cancer who underwent BCS, guided by multiple bracketed iodine I 125 radioactive seeds between January 2014 and April 2017. Results Bracketing of breast cancer using 2 or more radioactive seeds was performed in 157 breasts in 156 patients. Negative margins were achieved in 124 of 157 (79%) breasts, including 33 cases (21%) that underwent targeted margin reexcision at the time of surgery after intraoperative, multidisciplinary margin assessment. Thirty-three cases (21%) resulted in close or positive margins, of which 11 (7%) and 10 (6.4%) underwent completion mastectomy or repeat lumpectomy, respectively. Twelve patients (7.6%) did not undergo reexcision. En bloc resection was successful in 134 of 157 (85.4%) lumpectomies. Eighty-nine percent of the procedures were coupled with oncoplastic reconstruction. Conclusion Bracketing techniques using multiple radioactive seeds expands the indications for breast conservation therapy in patients who would have traditionally required mastectomy. Intraoperative margin assessment improves surgical and pathologic success. Larger defects created by multifocal resection are optimally managed in concert with oncoplastic reconstruction to minimize asymmetries and aesthetic defects.

Nivolumab and pembrolizumab, anti–programmed cell death protein 1 monoclonal antibodies, have revolutionized oncology but are expensive. Using an interventional pharmacoeconomic approach, these drugs can be administered less often to reduce costs and increase patient convenience while maintaining efficacy. Both drugs are good candidates for less frequent dosing because of long half-lives and no evidence of a relationship of dose to efficacy. Established population pharmacokinetic models for both nivolumab and pembrolizumab were used to simulate profiles for multiple dosing regimens on 1000 randomly generated virtual patients. Simulations were initially performed on standard dose regimens to validate these in silico predictions. Next, simulations of nivolumab 0.3 mg/kg every 3 weeks revealed that >95% of patients maintained ≥1.5 μg/mL at steady state, which was inferred as the minimum effective concentration (MEC) for both drugs. Various alternative dosing regimens were simulated for both drugs to determine which regimen(s) can maintain this MEC in >95% of patients. Extended dosing regimens of nivolumab 240 mg every 4 weeks and 480 mg every 8 weeks along with pembrolizumab 200 mg every 6 weeks were simulated, showing that >95% of patients maintained MEC or greater. These simulations demonstrate the potential to reduce drug exposure by at least 50%, thus substantially reducing patient visits (as well as costs), while maintaining equivalent efficacy. These models provide the scientific justification for an ongoing prospective randomized clinical trial comparing standard interval fixed dosing with extended interval fixed dosing, and ultimately an efficacy-driven comparative trial.

OCDs of the ankle are the third most common lesion in the body and a physician should include this in the differential while evaluating the pediatric population with the history of injury and/or pain in the ankle. Pain, stiffness, and swelling are the most common presenting complaints about the pediatric and adolescent patients with an OCD. Conservative treatment options should be attempted before attempting surgical intervention. Multiple surgical procedures exist to manage the lesion based on location, size, and other factors.

OBJECTIVE We examined relationships between plasma biomarkers and neurodevelopment in children from sub-Saharan Africa with perinatal HIV (PHIV) with controlled viremia on antiretroviral therapy (ART). DESIGN Longitudinal retrospective cohort study of children with controlled blood HIV replication. METHODS Children (N = 213; 57% girls) started ART at less than 3 years of age, had neurodevelopmental assessments (cognition, attention/impulsivity, motor proficiency, global executive functions) at 5-11 years, and achieved controlled viremia (HIV-1 RNA

Refereed/Peer-reviewed

Background There is evidence that people with persistent shoulder pain exhibit findings consistent with the presence of sensorimotor dysfunction. Sensorimotor impairments can manifest in a variety of ways, and further developing our understanding of sensorimotor dysfunction in shoulder pain may improve current models of care. The Fremantle Back Awareness Questionnaire (FreBAQ) has been developed to assess disturbed body perception specific to the back. The purpose of the present study was to develop a shoulder-specific self-perception questionnaire and evaluate the questionnaire in people with persistent shoulder pain. Methods The Fremantle Shoulder Awareness Questionnaire (FreSHAQ-J) was developed by modifying the FreBAQ. One hundred and twelve consecutive people with persistent shoulder pain completed the FreSHAQ-J. Thirty participants completed the FreSHAQ-J again two-weeks later to assess test-retest reliability. Rasch analysis was used to assess the psychometric properties of the FreSHAQ-J. Associations between FreSHAQ-J total score and clinical status was explored using correlational analysis. Results The FreSHAQ-J has acceptable category order, unidimensionality, no misfitting items, and excellent test-retest reliability. The FreSHAQ-J was moderately correlated with disability and pain catastrophization. Conclusions The FreSHAQ-J fits the Rasch measurement model well and is suitable for use with people with shoulder pain. Given the relationship between the FreSHAQ-J score and clinical status, change in body perception may be worth assessing when managing patients with shoulder pain.

Summary Background Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. Methods In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. Findings Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI −0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI −3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. Interpretation The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. Funding Abbott.

The current study aims to investigate the impact of left ventricular assist device (LVAD) implantation on weight loss and functional status in obese patients bridged to transplantation (BTT). The United Network for Organ Sharing (UNOS) database was queried to identify patients with body mass index (BMI) ≥ 30 who underwent LVAD implantation as BTT from 2008 to 2018. Patients were divided into three groups based the World Health Organization classification of obesity: obesity class I (BMI, 30.0-34.9 kg/m2), obesity class II (BMI, 35-39.9 kg/m2), and obesity class III (BMI, >40 kg/m2). Patients with incomplete data on BMI were excluded. The primary outcome was a change in BMI while listed. Secondary outcomes included a change in functional status after LVAD implantation and posttransplant morbidity and survival. Out of 14,191 patients who had an LVAD while listed within the study period, 5,354 (37.7%) had a BMI ≥30 kg/m2. Obesity was classified as class I in 3,909 (73%), class II in 1,275 (23.8%), and class III in 170 (3.2%) patients. Among patients with complete data on BMI, 18.9% (n = 394) reported a change in BMI, leading to an improvement in their obesity class, and this was similar for all obesity classes (22% [n = 331], 50% [n = 111], and 60% [n = 43] for classes I, II, and III, respectively). All groups reported an improvement in functional status (65% vs. 62% and 61% for classes I, II, and III, respectively). Posttransplant survival was not significantly different between obese groups (p = 0.787). Compared with classes I and II, the incidence of thrombosis (p = 0.0006) and device malfunction (p = 0.036) was significantly higher in the class III group. About one out of every five obese patients listed for heart transplantation with an LVAD loses weight, leading to a change in their BMI class. Most patients reported a significant improvement in their functional status. Among those successfully BTT, posttransplant survival was similar.

Dolutegravir (DTG) is now a component of preferred first-line antiretroviral therapy (ART) worldwide. ADVANCE and NAMSAL were two landmark clinical trials conducted exclusively in sub-Saharan Africa, which studied the effectiveness of DTG-based first-line regimens for ART-naive individuals. In this review, we examine the data from these studies to consider the contributions of adherence and HIV drug resistance to treatment failure on DTG-based ART, as compared with efavirenz (EFV)-based ART, which has a lower genetic barrier to resistance. We also discuss the implications of virologic failure on DTG and consolidate currently available data to conclude with recommendations for virologic monitoring on DTG-based ART.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background: In patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), selecting an antithrombotic regimen requires balancing risks of ischemic cardiac events, stroke, and bleeding. Methods: We studied 467 patients with AF undergoing PCI in the time period from December 2015 to July 2018 identified via a chart audit by 47 Canadian cardiologists in the CONNECT AF+PCI (the Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) study, to determine patterns of initial antithrombotic therapy selection. Results: The median (25th, 75th percentile) CHADS2 score was 2 (1, 3), and PCI was performed in the setting of acute coronary syndrome in 62.1%. Triple antithrombotic therapy (TAT) was the initial treatment in 62.7%, dual-pathway therapy in 25.7%, and dual antiplatelet therapy in 11.6%, with a temporal increase in use of dual-pathway therapy during the course of the study; median intended TAT duration was 1 (1, 3) month. Compared with patients selected for TAT, patients selected for dual-pathway therapy were less likely to have prior myocardial infarction (35.8% vs 25.8%, P = 0.045) and prior PCI (33.8% vs 23.3%, P = 0.03), and they received shorter total length of stents (38 [23, 56] vs 30 [20, 46] mm, P = 0.03). Patients selected for dual-pathway therapy had a higher prevalence of prior stroke/transient ischemic attack (13.0% vs 23.3%, P = 0.01). There was no difference in prevalence of anemia (21.5% vs 25.8%, P = 0.30). Use of dual-pathway therapy was similar among patients with acute coronary syndrome and those with stable disease (24.1% vs 28.2%, P = 0.32). Conclusions: Approximately one-quarter of AF patients undergoing PCI are treated with dual-pathway therapy in Canadian practice, with its use increasing during the studied period. Patients selected for dual-pathway therapy have less-complex coronary disease history and intervention. Résumé: Introduction: Les patients atteints de fibrillation auriculaire (FA) qui subissent une intervention coronarienne percutanée (ICP) et choisissent un schéma posologique antithrombotique ont besoin de peser les risques d’événements cardiaques d’origine ischémique, d’accidents vasculaires cérébraux et d’hémorragies. Méthodes: Les 467 patients atteints de FA ayant subi une ICP de décembre 2015 à juillet 2018 qui ont fait l’objet de notre étude ont été trouvés lors de la vérification des dossiers par 47 cardiologues canadiens de l’étude CONNECT AF+PCI (Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) pour déterminer les schémas de sélection du traitement antithrombotique initial. Résultats: Le score CHADS2 médian (25e, 75e percentile) était de 2 (1, 3), et l’ICP avait été réalisée dans le cadre du syndrome coronarien aigu chez 62,1 % des patients. La trithérapie antithrombotique (TTA) était le traitement initial chez 62,7 % des patients, la bithérapie, chez 25,7 % des patients, et la bithérapie antiplaquettaire, chez 11,6 % des patients, mais il y avait une augmentation temporelle dans l’utilisation de la bithérapie durant l’étude; la durée médiane prévue de la TTA était de 1 (1, 3) mois. Comparativement aux patients sélectionnés pour la TTA, les patients sélectionnés pour la bithérapie étaient moins susceptibles d’avoir eu un infarctus du myocarde précédent (35,8 % vs 25,8 %, P = 0,045) et une ICP précédente (33,8 % vs 23,3 %, P = 0,03), et recevaient des endoprothèses de longueur totale plus courte (38 [23, 56] vs 30 [20, 46] mm, P = 0,03). Les patients sélectionnés pour la bithérapie montraient une prévalence plus élevée d’accidents vasculaires cérébraux/accidents ischémiques transitoires (13,0 % vs 23,3 %, P = 0,01). Il n’existait aucune différence dans la prévalence de l’anémie (21,5 % vs 25,8 %, P = 0,30). L’utilisation de la bithérapie était similaire chez les patients atteints d’un syndrome coronarien aigu et chez les patients dont la maladie était stable (24,1 % vs 28,2 %, P = 0,32). Conclusions: Dans la pratique canadienne, environ le quart des patients atteints de FA qui subissent une ICP sont traités par bithérapie, mais durant la période étudiée, son utilisation avait augmenté. Les patients sélectionnés pour la bithérapie ont des antécédents et des interventions liées aux maladies coronariennes moins complexes.

ContextNonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate.ObjectiveThe aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients.MethodsPancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease.ResultsFive of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET–free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively.ConclusionAnalyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.

Aims Surveillance imaging is often used to detect remodelling, a change in cardiac geometry, and/or function; however, there are limited data in patients with chronic heart failure (HF). We sought to characterize cardiac remodelling in patients with chronic HF and evaluate its association with outcome. Methods and results A prospective cohort of patients at risk for HF or with chronic HF underwent cardiac magnetic resonance (CMR) at baseline and 1 year. Ventricular function, volumes, mass, left atrial volume, global longitudinal strain, and myocardial scar were measured. The primary outcome was a composite of death or cardiovascular hospitalization up to 5 years from the 1 year scan. Cox regression was used to identify 1 year CMR predictors of outcome after adjusting for baseline risk. A total of 262 patients (median age 68 years, 57% males) including 96 at risk for HF, 97 with HF and preserved ejection fraction, and 69 with HF and reduced ejection fraction were included. In the patients with HF, 55 events were identified during follow‐up. After adjustment for baseline clinical risk, Cox proportion hazard regressions only identified 1 year change in left ventricular (LV) mass index as a CMR predictor of outcome, adjusted hazard ratio 1.21 (1.02, 1.44) per 10% increase, P = 0.031. Cardiac remodelling defined as a 1 year change in LV mass index ≥15% was observed in 35% of patients with HF. Patients with adverse remodelling of LV mass index had more events on Kaplan–Meier analyses compared to those with no remodelling, log‐rank P = 0.004 for overall cohort, P = 0.035 for heart failure with preserved ejection fraction and P = 0.035 for heart failure and reduced ejection fraction. Conclusions Cardiac remodelling is common during serial CMR assessment of patients with chronic HF. Change in LV mass predicted long‐term outcomes whereas change in left ventricular ejection fraction did not.

Background and Purpose: Reversible cerebral vasoconstriction syndrome (RCVS) is a well-established cause of stroke, but its demographics and outcomes have not been well delineated. Methods: Analysis of the United States Nationwide Inpatient Sample database (2016–2017) to characterize the frequency of hospitalizations for RCVS, demographic features, inpatient mortality, and discharge outcomes. Results: During the 2-year study period, 2020 patients with RCVS were admitted to Nationwide Inpatient Sample hospitals, representing 0.02 cases per 100 000 national hospitalizations. The mean age at admission was 47.6 years, with 85% under 65 years of age, and 75.5% women. Concomitant neurological diagnoses during hospitalization included ischemic stroke (17.1%), intracerebral hemorrhage (11.0%), subarachnoid hemorrhage (32.7%), seizure disorders (6.7%), and reversible brain edema (13.6%). Overall, 70% of patients were discharged home, 29.7% discharged to a rehabilitation facility or nursing home and 0.3% died before discharge. Patient features independently associated with the poor outcome of discharge to another facility or death were advanced age (odds ratio [OR], 1.04 [95% CI, 1.03–1.04]), being a woman (OR, 2.45 [1.82–3.34]), intracerebral hemorrhage (OR, 2.91 [1.96–4.31]), ischemic stroke (OR, 5.72 [4.32–7.58]), seizure disorders (OR, 2.61 [1.70–4.00]), reversible brain edema (OR, 6.26 [4.41–8.89]), atrial fibrillation (OR, 2.97 [1.83–4.81]), and chronic kidney disease (OR, 3.43 [2.19–5.36]). Conclusions: Projected to the entire US population, >1000 patients with RCVS are hospitalized each year, with the majority being middle-aged women, and about 300 required at least some rehabilitation or nursing home care after discharge. RCVS-related inpatient mortality is rare.

Background: Joint denervation of the wrist, basal joint of the thumb, and the finger is an option for patients with chronic pain. Compared with other surgical treatment options, function is preserved and the rehabilitation time is limited. A systematic review and meta-analysis were performed for each joint to determine whether the choice of technique and choice of denervation of specific articular sensory branches lead to a different outcome. Methods: Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed publisher, Cochrane, and Google Scholar database searches yielded 17 studies with reported outcome on denervation of the wrist, eight on the basal joint of the thumb, and five on finger joints. Results: Overall, the level of evidence was low; only two studies included a control group, and none was randomized. Meta-analysis for pain showed a 3.3 decrease in visual analogue scale score for wrist pain. No difference was found between techniques (total versus partial denervation), nor did different approaches influence outcome. The first carpometacarpal joint showed a decrease for visual analogue scale score for pain of 5.4. Patient satisfaction with the treatment result was 83 percent and 82 percent, respectively. Reported pain in finger joints decreased 96 percent in the metacarpophalangeal joints, 81 percent in the proximal interphalangeal joint, and 100 percent in the distal interphalangeal joint. The only reported case in the metacarpophalangeal joint of the thumb reported an increase of 37 percent. Conclusions: Only denervation of the metacarpophalangeal joint of the thumb reported an increase in pain; however, this was a single patient. Wrist and first carpometacarpal joint and finger joint denervation have a high satisfaction rate and decrease the pain. There was no difference between techniques.

Background: A significant number of patients experience recurrent atrial fibrillation (AF) after ablation. Various risk scores have been described that may predict outcomes after AF ablation. In this study, we aimed to compare ten previously described risk scores with regard to their predictive value for post-ablation AF recurrence and procedural complications. Methods: A total of 482 AF patients (63% paroxysmal AF, 66% male, mean age 62 ± 9 years) undergoing initial radiofrequency pulmonary vein isolation (PVI) were included in the present analysis. Prior to ablation, all patients underwent both transthoracic echocardiography (TTE) and either cardiac CT imaging or CMR imaging. The following risk scores were calculated for each patient: APPLE, ATLAS, BASE-AF 2, CAAP-AF, CHADS 2, CHA 2DS 2-VASc, DR-FLASH, HATCH, LAGO and MB-LATER. Results: Median follow-up was 16 (12–31) months. AF recurrence after a 90-day blanking period was observed in 199 patients (41%), occurring after a median of 183 (124–360) days. AF recurrence was less frequent in paroxysmal AF patients compared to non-paroxysmal AF patients (34% vs. 54%, p < 0.001). Overall periprocedural complication rate was 6%. All scores, except the HATCH score, demonstrated statistically significant but poor predictive value for recurrent AF after ablation (area under curve [AUC] 0.553–0.669). CHA 2DS 2-VASc and CAAP-AF were the only risk scores with predictive value for procedural complications (AUC 0.616, p = 0.043; AUC 0.615, p = 0.044; respectively). Conclusions: Currently available risk scores perform poorly in predicting outcomes after AF ablation. These data suggest that the utility of these scores for clinical decision-making is limited.

BACKGROUND Minimally invasive heart valve surgery has previously been shown to be safe and feasible in obese patients. Within this population, we investigated the effect of obesity class on the patient outcomes of minimally invasive aortic valve replacement (mini-AVR). METHODS A single-center retrospective cohort study of consecutive patients with obese body mass indices (BMIs) who underwent mini-AVR between 2012 and 2020. Patients were stratified into three groups according to Centers for Disease Control and Prevention adult obesity classifications: Class I (BMI: 30.0

BACKGROUND Intra-aortic balloon pumps (IABP) are used to bridge select end-stage heart disease patients to heart transplant (HT). IABP use and exception requests both increased dramatically after the UNOS policy change (PC). The purpose of this study was to evaluate the effect of PC and exception status requests on waitlist and post-transplant outcomes in patients bridged to HT with IABP support. METHODS We analyzed adult, first-time, single-organ HT recipients from the UNOS Registry either on IABP at the time of registration for HT or at the time of HT. We compared waitlist and post-HT outcomes between patients from the PRE (October 18, 2016 to May 30, 2018) and POST (October 18, 2018 to May 30, 2020) eras using Kaplan-Meier curves and time-to-event analyses. RESULTS A total of 1267 patients underwent HT from IABP (261 pre-policy/1006 post-policy). On multivariate analysis, PC was associated with an increase in HT (sub-distribution hazard ratio (sdHR): 2.15, p

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection.METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis.RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives.CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.).

Thousands of babies are given toys for their zeroth birthday … But what happens if that baby is admitted to neonatal intensive care? In a global first, we describe the population of toys found in incubators on neonatal intensive care unit.

OBJECTIVE To validate the diagnoses and to investigate epidemiological data from an international, non-clinic-based, and large (n = 1604) survey of participants with cluster headache. BACKGROUND There are several limitations in current epidemiological data in cluster headache including a lack of large non-clinic-based studies. There is also limited information on several aspects of cluster headache, such as pediatric incidence. METHODS The International Cluster Headache Questionnaire was an internet-based survey that included questions on cluster headache demographics, criteria from the International Classification of Headache Disorders (ICHD), and medications. RESULTS A total of 3251 subjects participated in the survey, and 1604 respondents met ICHD criteria for cluster headache. For validation, we interviewed a random sample of 5% (81/1604) of participants and confirmed the diagnosis of cluster headache in 97.5% (79/81). Pediatric onset was found in 27.5% (341/1583) of participants, and only 15.2% (52/341) of participants with pediatric onset were diagnosed before the age of 18. Men were more likely to have episodic cluster headache between ages 10 and 50, but the sex ratio was approximately equal for other ages. An overwhelming majority of respondents had at least one autonomic feature (99.0%, 1588/1604) and had restlessness (96.6%, 1550/1604), but many also had prototypical migrainous features including photophobia or phonophobia (50.1%, 804/1604), pain aggravated by physical activity (31.4%, 503/1604), or nausea and vomiting (27.5%, 441/1604). Interestingly, the first-line medications for acute treatment (oxygen) and preventive treatment (calcium channel blockers) were perceived as significantly less effective in chronic cluster headache (3.2 ± 1.1 and 2.1 ± 1.0 respectively on a 5-point ordinal scale) compared with episodic cluster headache (3.5 ± 1.0 and 2.4 ± 1.1, respectively, p

Background Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)–related and all-cause mortality. However, routine measurement of CRF is not always feasible. Objectives The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO2peak) (measure of CRF) early post–breast cancer therapy to help inform CVD risk. Methods Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 ± 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO2peak using a cycle ergometer. Regression models were used to examine the association between VO2peak and clinical, imaging, and cardiac biomarkers individually and in combination. Results Among 147 patients (age 52.2 ± 9.3 years), the mean VO2peak was 19.1 ± 5.0 mL O2·kg−1·min−1 (84.2% ± 18.7% of predicted); 44% had a VO2peak below threshold for functional independence (, Central Illustration

Staging of primary musculoskeletal bone and soft-tissue tumors is most commonly performed using the AJCC and the Enneking or Musculoskeletal Tumor Society (MSTS) staging systems. Radiologic imaging...

The sinuses of Valsalva are outpouchings in the aortic root just distal to the aortic valve that serve several physiologic functions. Aneurysm of this segment of the aorta is quite rare and infrequently encountered in clinical practice. Due to the rarity of sinus of Valsalva aneurysms, there is a lack of controlled trials and most of the literature consists of case reports and series. Here, the authors review the currently available literature to discuss the anatomy and normal function of the aortic root, as well as disease pathology and diagnostic imaging considerations. Using reported cases, the authors also will discuss considerations for cardiac anesthesiologists in the perioperative period.

Summary Background & aims Feeding intolerance (FI) is a common phenomenon experienced in preterm infants in neonatal intensive care units, as well as being a focus of many research studies into feeding methods, particularly in relation to comorbidities. There is no widely accepted definition of FI. This systematic review aimed to explore the range of definitions used for FI and provide an estimate of the prevalence amongst preterm infants. Methods Searches were completed on MEDLINE (includes the Cochrane library), Embase, PsycInfo, CINAHL, NHS Evidence and Web of Science. Inclusion criteria; preterm infants in neonatal units, a clear definition of FI, >10 patients and be available in English language. Case reports were excluded. Results One hundred studies were included. Definitions of FI were inconsistent. Studies were grouped according to definition used into: Group A − measuring gastric residual volume (GRV) only; group B − GRV and abdominal distension (AD); group C − GRV, AD and gastrointestinal symptoms (GI) which included any of vomiting, bilious vomiting and blood in stool; group D- GRV and GI; group E − AD and GI; group F − GI only and group G − any other elements used. Meta-analysis demonstrated that prevalence of FI between groups varied from 15 to 30% with an overall prevalence of 27% (95% confidence interval 23–31%). Group A had the highest prevalence. Review of time to full enteral feed was performed (37 studies) which demonstrated a range of 11.3–18.3 days depending on which FI definition used. Discussion Definitions of FI in research are inconsistent, a similar finding to that seen in studies in both paediatric and adult critical care populations. The difficulty of defining FI in the preterm population is the concern regarding necrotising enterocolitis, with some studies using an overlap in their definitions, despite differing pathophysiology and management. Due to the heterogeneity of data obtained in this review regarding definitions used, further robust research is required in order to conclude which elements which should be used to define FI in this population. PROSPERO number CRD42019155596. Registered November 2019.

The mainstay of treatment for obstructive sleep apnea is positive airway pressure therapy, which may be difficult for some patients to tolerate leading to compromised adherence and requiring alternative therapies. Hypoglossal nerve stimulation has become an option for those who meet implantation criteria. Implantation of the device is an ambulatory surgical procedure and is generally well-tolerated, though rare adverse events have been reported. We report an unusual complication of hypoglossal nerve stimulation in a patient who had initial success with this therapy. After 3 years of treatment, the sensor lead penetrated into the pleural space. Components of the hypoglossal nerve stimulation were explanted, and a new sensor lead and generator were reimplanted. The new device was activated, and therapy was successfully resumed. This case demonstrates that there is a potential for a delayed complication of sensor lead penetration into the pleural space, which has only rarely been reported. CITATION: Lou B, Hahn S, Korotun M, Quintero L, Shikowitz M, Greenberg H. Space invader: pleural penetration of a hypoglossal nerve stimulator sensor lead. J Clin Sleep Med. 2021;17(11):2329–2332.

Background Neoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC. Methods We reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded. Results Overall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p Conclusion CS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.

INTRODUCTION AND OBJECTIVES Data are scarce on outcomes of transvenous lead removal (TLR) in adult congenital heart disease (CHD). We evaluated the safety of the TLR procedure in adult CHD patients from a 10-year national database. METHODS We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample to identify TLR procedures in adult patients with and without CHD from 2005 to 2014. Outcomes included in-hospital mortality and complications. RESULTS Of 132 068 adult patients undergoing TLR, 1939 had simple CHD, 657 had complex CHD, and 626 had unclassified CHD. The number of TLR procedures in adult CHD slightly increased from 236 in 2005 to 445 in 2014, with fluctuations over the study period. The overall rate of any complications in the TLR procedure was 16.6% in patients with CHD vs 10.1% in patients without CHD (P

Aims Studies on long-term patient-reported outcomes after open surgery for triangular fibrocartilage complex (TFCC) are scarce. Surgeons and patients would benefit from self-reported outcome data on pain, function, complications, and satisfaction after this surgery to enhance shared decision-making. The aim of this study is to determine the long-term outcome of adults who had open surgery for the TFCC. Methods A prospective cohort study that included patients with open surgery for the TFCC between December 2011 and September 2015. In September 2020, we sent these patients an additional follow-up questionnaire, including the Patient-Rated Wrist Evaluation (PRWE), to score satisfaction, complications, pain, and function. Results A total of 113 patients were included in the analysis. At ≥ 60 months after an open TFCC reinsertion, we found a mean PRWE total score of 19 (SD 21), a mean PRWE pain score of 11 (SD 11), and a PRWE function score of 9 (SD 10). The percentage of patients obtaining minimum clinically important difference rose from 77% at 12 months to 83% at more than 60 months (p < 0.001). Patients reported fewer complications than surgeons, and overall complication rate was low. Conclusion Outcomes of patient-reported pain, function scores, and satisfaction are improved five years after open surgery for the TFCC. Cite this article: Bone Jt Open 2021;2(11):981–987.

Purpose We investigated clinical risk factors that predict poor 30-day headache outcomes among patients evaluated in the emergency department (ED) for post-traumatic headache (PTH). Methods This was an analysis of data from a randomized, placebo-controlled study of IV metoclopramide + diphenhydramine for acute PTH. Patients were enrolled during an ED visit and received telephone follow-up with a structured questionnaire 30 days later. The primary outcome was frequency of headaches 30 days after ED discharge. We used multivariable logistic regression models to determine which clinical variables were associated with frequent headaches at 30 days. Results In total, 160 patients were enrolled in the study. 134 (84%) patients completed the 30-day questionnaire and were included in the analysis, including 90 females and 44 males. 30 patients (22%, 95% CI = 0.16 to 0.30) reported frequent headaches at 30-day follow-up. In the multivariable analysis, female sex (OR = 4.03, 95% CI = 1.23±13.13), patients who blamed themselves for their injury (OR = 0.13, 95% CI = 0.04±0.45), and patients who were unsure if they sustained loss of consciousness during the traumatic incident (OR = 5.63, 95% CI = 1.89±16.78) were found to be associated with poor 30-day outcomes. Medication received in the ED and age were not associated. Conclusions More than 1 out of five patients treated in the ED for acute PTH experienced frequent headaches 30 days later. Women and patients who were uncertain as to whether they had experienced loss of consciousness were at increased risk of frequent PTH. Blaming oneself for the head trauma was associated with less frequent PTH.

PURPOSE OF REVIEW With an aging cardiac surgery population, prefrail and frail patients are becoming more common. Anesthesiologists will be faced with the decision of how best to provide care to frail patients. Identification, management, and outcomes in frail patients will be discussed in this review. RECENT FINDINGS Frailty is associated with a variety of poor outcomes, such as increased hospital length of stay, medical resource utilization, readmission rates, and mortality. Prehabilitation may play a greater role in the management of frail cardiac surgery patients. SUMMARY As frailty will likely only increase amongst cardiac surgery patients, it is important to develop multicenter trials to study management and treatment options. Until those studies are performed, the care of frail cardiac surgery patients may be best provided by high-volume surgical centers with expertise in the management of frail patients.