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Background. Epstein-Barr virus (EBV) chronic high viral load (CHVL) may be defined by >16 000 copies/mL whole blood or >200 copies/105 peripheral blood mononuclear cells in >50% samples exceeding 6 mo. EBV CHVL has only been characterized in a few small pediatric studies, with heterogeneous results and unclear clinical significance. Methods. This single-center observational study evaluated adult and pediatric kidney transplant recipients transplanted between 2010 and 2021 on tacrolimus/mycophenolate-based/prednisone immunosuppression. The primary outcome was EBV CHVL prevalence. Secondary outcomes included recipient characteristics, DNAemia kinetics, and posttransplant lymphoproliferative disorder (PTLD) in recipients with EBV CHVL versus low-grade DNAemia or no DNAemia. Results. Five hundred forty-one recipients had a mean follow-up of 4.6 y. Fourteen recipients (2.6%) developed EBV CHVL, 70 (12.9%) had low-grade EBV DNAemia, and 457 (84.5%) had no EBV DNAemia. EBV CHVL was more common in recipients who were Caucasian (P = 0.04), younger (P = 0.04), received induction immunosuppression (P = 0.02), and had high-risk donor–recipient EBV serologic mismatch (P

Summary: Despite their key role in the distribution of essential goods, seafarers were often overlooked in international COVID-19 responses. Border closures isolated them at sea, often for months beyond contract. Distributing vaccines to seafarers was inconsistent and often depended on the creativity of charities and industry and labour stakeholders. Even seafarers who received vaccinations often had them unrecognised in the ports they visited. These oversights should not be repeated in preparation for future pandemics. As a vulnerable population and as key international workers, seafarers’ health should be prioritised by national and international health policy.

Summary:. Adult-acquired buried penis (AABP) is an acquired clinical entity where a normal sized phallus is concealed by prepubic skin, fat, or subcutaneous tissue, often caused by obesity, lymphedema, or trauma. Surgical repair is the standard of care in management of AABP; however, up to 60% of patients have developed bothersome genital lymphedema postoperatively. Despite the rates of postoperative scrotal lymphedema, and lymphedema itself representing a risk for AABP, very little data exist on the role of lymphatic evaluation in this patient population. We present the previously unreported use of indocyanine green (ICG) for lymphatic mapping as an adjunct to buried penis repair. Using 0.1 mL 25 mg per mL of indocyanine green and SPY Portable Handled Imaging, lymph mapping is performed, identifying lymph channels that seem obstructed as possible targets for lymphovenous bypass. In addition, lymph mapping can be used as an adjunct to surgical resection so as to not disrupt the intact channels, reducing the risk of postoperative lymphedema. Through this article, we offer emerging clinical insight into the possible use of lymphovenous bypass, particularly in patients with AABP due to lymphedema or those who experience lymphedema as a complication of AABP repair.

Objective: Surgery for heart defects in children with trisomy 13 or 18 is controversial. We analyzed our 20-year experience. Methods: Since 2002, we performed 21 operations in 19 children with trisomy 13 (n = 8) or trisomy 18 (n = 11). Age at operation was 4 days to 12 years (median, 154 days). Principal diagnosis was ventricular septal defect in 10 patients, tetralogy of Fallot in 7 patients, arch hypoplasia in 1 patient, and patent ductus arteriosus in 1 patient. Results: The initial operation was ventricular septal defect closure in 9 patients, tetralogy of Fallot repair in 7 patients, pulmonary artery banding in 1 patient, patent ductus arteriosus ligation in 1 patient, and aortic arch/coarctation repair in 1 patient. There were no operative or hospital deaths. Median postoperative intensive care and hospital stays were 189 hours (interquartile range, 70-548) and 14 days (interquartile range, 8.0-37.0), respectively, compared with median hospital stays in our center for ventricular septal defect repair of 4.0 days and tetralogy of Fallot repair of 5.0 days. On median follow-up of 17.4 months (interquartile range, 6.0-68), 1 patient was lost to follow-up after 5 months. Two patients had reoperation without mortality. There have been 5 late deaths (4 with trisomy 18, 1 with trisomy 13) predominately due to respiratory failure from 4 months to 9.4 years postoperatively. Five-year survival was 66.6% compared with 24% in a group of unoperated patients with trisomy 13 or 18. Conclusions: Cardiac operation with an emphasis on complete repair can be performed safely in carefully selected children with trisomy 13 or trisomy 18. Hospital resource use measured by postoperative intensive care and hospital stays is considerably greater compared with nontrisomy 13 and 18.

Abstract. Objectives:. (1) The purpose of this study was to investigate immediate postoperative weight-bearing status and other potential risk factors for nonunion after locked plating of distal femur fractures and (2) to compare clinical and radiographic union using the previously validated Radiographic Union Scale for Tibia (RUST) and modified RUST scores. Design:. This is a retrospective cohort analysis. Setting:. Academic Level-1 trauma center. Patients/Participants:. Ninety patients with distal femur fractures (OTA/AO 33-A, including periprosthetic) treated with lateral locked plating over a 10-year period. Intervention:. Distal femur fracture fixation with lateral locked plating; surgical intervention to facilitate bone healing in cases of nonunion. Main Outcome Measurements:. Nonunion rate, construct rigidity scores, RUST, and modified RUST scores. Results:. Seventy-eight of 90 patients (87%) achieved clinical union (13% nonunion rate). Rigidity score was significantly associated with risk of nonunion (P = 0.003). No significant association was detected between nonunion and postoperative weight-bearing status (P = 0.77) or other previously identified risk factors. Patients who achieved fracture union had significantly higher mean (SD) RUST (10.67 [1.37] vs. 6.53 [1.48], P < 0.001) and modified RUST (13.47 [2.20] vs. 6.94 [1.79], P < 0.001) scores than patients who developed nonunion. Sensitivity (Sn) analyses identified a RUST score threshold of 9 for diagnosing clinical union (Sn 93.6% and specificity [Sp] 91.7%) and a modified RUST score threshold of 8 (Sn 93.6%, Sp 91.7%). Conclusions:. Immediate postoperative weight-bearing status does not seem to affect nonunion rates. We observed a statistically significant association between rigidity score and nonunion. This study supports the utility of the RUST and modified RUST scores in distal femur metaphyseal fractures. Level of Evidence:. Therapeutic Level IV.

Purpose: Radiation-associated angiosarcoma (RAAS) is a rare complication among patients treated with radiation therapy for breast cancer. Hyperfractionated-accelerated reirradiation (HART) improves local control after surgery. Proton therapy may further improve the therapeutic ratio by mitigating potential toxicity. Materials and Methods: Six patients enrolled in a prospective registry with localized RAAS received HART with proton therapy between 2015 and 2021. HART was delivered twice or thrice daily in fraction sizes of 1.5 or 1.0 Gy, respectively. All patients received 45 Gy to a large elective volume followed by boosts to a median dose of 65 (range, 60–75) Gy. Toxicity was recorded prospectively by using the Common Terminology Criteria for Adverse Events, version 4.0. Results: The median follow-up duration was 1.5 (range, 0.25-2.9) years. The median age at RAAS diagnosis was 73 (range, 60-83) years with a median latency of 8.9 (range, 5-14) years between radiation therapy completion and RAAS diagnosis. The median mean heart dose was 2.2 (range, 0.1–4.96) Gy. HART was delivered postoperatively (n = 1), preoperatively (n = 3), preoperatively for local recurrence after initial management with mastectomy (n = 1), and as definitive treatment (n = 1). All patients had local control of disease throughout follow-up. Three of 4 patients treated preoperatively had a pathologic complete response. The patient treated definitively had a complete metabolic response on her post-treatment PET/CT (positron emission tomography–computed tomography) scan. Two patients developed distant metastatic disease despite local control and died of their disease. Acute grade 3 toxicity occurred in 3 patients: 2 patients undergoing preoperative HART experienced wound dehiscence and 1 postoperatively developed grade 3 wound infection, which resolved. Conclusion: HART with proton therapy appears effective for local control of RAAS with a high rate of pathologic complete response and no local recurrences to date. However, vigilant surveillance for distant metastasis should occur. Toxicity is comparable to that in photon/electron series. Proton therapy for RAAS may maximize normal tissue sparing in this large-volume reirradiation setting.

BACKGROUND: Cardiovascular disease has emerged as the leading cause of maternal morbidity and mortality, making planned pregnancy, and thereby reliable contraception among people with cardiovascular disease, vital. OBJECTIVE: This study aimed to compare postpartum contraceptive practices among people with cardiovascular disease (cardiac cohort) cared for by a Pregnancy Heart Team to people with other chronic comorbidities (high-risk cohort), and people without comorbidities (low-risk cohort). We hypothesized that the Pregnancy Heart Team influenced baseline contraception counseling and practices among those with cardiovascular disease. STUDY DESIGN: This was a retrospective cohort study comparing postpartum contraceptive practices between a cardiac cohort who received care by a multidisciplinary team between 2012 and 2020 and high-risk and low-risk cohorts delivering at a single academic center between 2016 and 2019. We investigated presence of a contraceptive plan (at birthing admission, discharge, and postpartum visit) and uptake of reliable contraception by 8 weeks postpartum. RESULTS: We included 1464 people: 189 with cardiovascular disease, 197 with other chronic comorbidities, and 1078 low-risk people. At birth hospitalization admission, reliable contraception was planned among 42% of the cardiac cohort, 40% of the high-risk cohort, and 31% of the low-risk cohort, with similar distributions at the time of discharge and at 8 weeks postpartum. Compared with the cardiac cohort, by 8 weeks postpartum, the high-risk cohort had similar odds of using highly reliable forms of contraception (39% vs 36%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50–1.21) and similar odds of having a plan to use the most reliable forms of contraception (intrauterine device, implant, bilateral tubal ligation) at the time of birthing admission (42% vs 40%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50–1.22), discharge (47% vs 45%; adjusted odds ratio, 0.95; 95% confidence interval, 0.61–1.48), and postpartum visit (35% vs 29%; adjusted odds ratio, 0.76; 95% confidence interval, 0.49–1.17). The low-risk cohort had lower odds of using a reliable form of contraception (39% vs 27%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37–0.75) and was less likely to have a plan for reliable contraception at the time of birthing admission (42% vs 31%; adjusted odds ratio, 0.54; 95% confidence interval, 0.38–0.76), discharge (47% vs 33%; adjusted odds ratio, 0.58; 95% confidence interval, 0.4–0.82), and postpartum visit (35% vs 21%; adjusted odds ratio, 0.50; 95% confidence interval, 0.35–0.71). CONCLUSION: People with cardiovascular disease cared for by a Pregnancy Heart Team had higher odds of reliable postpartum contraception planning and uptake compared with a low-risk cohort and similar odds compared with a high-risk cohort. Pregnancy could serve as a critical period for contraception counseling and family planning among people with cardiovascular disease. A multidisciplinary team should be used to address postpartum contraception as a modifiable risk factor to reduce maternal morbidity and mortality among those with cardiovascular disease.

Minimally invasive locoregional therapies have become important treatment options for patients with intermediate or late-stage hepatocellular carcinoma (HCC) who are ineligible for surgical resection or liver transplantation. Imaging modalities are essential for procedural guidance and for assessing treatment response thereafter. We report a unique finding of a patient with multifocal HCC treated with transarterial radioembolization (TARE) with yttrium-90 (Y90) and transarterial chemoembolization (TACE). We compared contrast-enhanced ultrasound (CEUS) with contrast-enhanced magnetic resonance imaging (CE-MRI) in the evaluation of treatment response to demonstrate advantages of CEUS imaging technique and its early detection of viable tumor.

Vulvar dermatology represents a challenge for many providers. Given that the vulva is both a gynecologic and dermatologic organ, patients with cutaneous lesions involving the vulva may present to primary care, gynecology, or dermatology. Particularly within dermatology, the vulva remains understudied, which can lead to anxiety among providers regarding appropriate next steps in the diagnosis and management of vulvar lesions. Thus, the purpose of this review is to highlight commonly encountered anatomic variants and benign neoplasms of the vulva, distinguish them from key pathologic mimickers, and provide guidance to practicing dermatologists on what may constitute normal vulvar variations.

Mobile thrombus of the nonaneurysmal, nonatherosclerotic aorta is a rare condition but presents with catastrophic embolic events. We describe two cases that demonstrate differences in presentation and treatment strategies. We review the literature to discuss initial management as well as surgical options. However, due to the limited number of cases, no definitive guidelines for management exist.

Introduction: The central nervous system (CNS) is a common site of progression among patients with ROS1-rearranged lung cancer receiving crizotinib. We conducted a phase 2 study to evaluate the intracranial efficacy of lorlatinib in patients with ROS1-rearranged lung cancer who developed CNS-only progression on crizotinib. Methods: Patients with metastatic ROS1-rearranged lung cancer with CNS-only progression on crizotinib received lorlatinib 100 mg daily. The primary end point was intracranial disease control rate at 12 weeks per modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included intracranial and extracranial progression-free survival, intracranial objective response rate, and safety/tolerability. Results: A total of 16 patients were enrolled between November 2016 and January 2019. Nine patients (56%) had received prior CNS radiation, with a median of 10.9 months between radiation and lorlatinib. At 12 weeks, the intracranial disease control rate was 100% and intracranial objective response rate was 87%. While on study, the complee intracranial response rate was 60%. With median follow-up of 22 months, seven patients experienced disease progression, including five patients with CNS relapse. The median intracranial and extracranial progression-free survivals were 38.8 months (95% confidence interval: 16.9–not reported) and 41.1 months (95% confidence interval: 17.6–not reported), respectively. Molecular analysis of plasma or tissue from patients with extracranial progression on lorlatinib revealed ROS1 G2032R (n = 1), ROS1 L2086F (n = 1), and CCDC6-RET fusion plus ROS1 G2032R (n = 1). The safety profile of lorlatinib was consistent with prior studies. There were 11 patients (69%) who required dose reduction, including one patient who discontinued treatment for grade 3 edema. No grade greater than or equal to 4 adverse events were observed. Conclusions: Lorlatinib induced durable intracranial responses in patients with ROS1-rearranged NSCLC and prior isolated CNS progression on crizotinib.

Background: High-power short-duration (HPSD) ablation has been explored for pulmonary vein isolation. Early data suggest similar efficacy with shorter procedure times and perhaps greater safety. Data are lacking on the use of this ablation strategy for other arrhythmias. Objective: The purpose of this study was to evaluate the safety, efficacy, and clinical outcomes of HPSD ablation in patients with typical atrial flutter compared to those undergoing ablation with conventional settings. Methods: Consecutive patients undergoing cavotricuspid isthmus (CTI) ablation using standard power settings were compared to those performed after transitioning to HPSD ablation. Demographics, procedural details, and ablation outcomes were prospectively collected. The primary endpoint was duration of radiofrequency energy delivery. Secondary endpoints were radiation duration and analgesia requirements. Results: A total of 114 consecutive subjects undergoing CTI ablation (57 standard power, 57 HPSD) were included. HPSD ablation and electroanatomic mapping/contact force (EAM/CF) use were associated with 66% (95% confidence interval [CI] 58%–73%) and 50% (95% CI 37%–60%) shorter ablation times compared to standard power and not using EAM/CF, respectively. Patients in the HPSD group required 50 mcg less fentanyl relative to the standard ablation arm after adjusting for sex, age, and comorbidities (P = .048). At a median follow-up of 6 months, 4 patients (7%) in the standard arm had recurrence of atrial flutter, compared to none in HPSD group (P = .057). Conclusion: HPSD is a safe and effective approach to CTI ablation. This strategy may reduce ablation time and analgesia requirements. Larger studies and longer follow-up are needed to further evaluate this strategy.

Objectives: Breast reconstruction helps patients enhance their body image after mastectomy. Metallic ports in tissue expanders lead to dose attenuation during radiotherapy. Tissue expander volume shifts the metallic port position, possibly causing various dose alterations. This study aimed to evaluate the impact of the MAGNA-SITE TM tissue expander volume on tomotherapy. Methods: Boluses and MAGNA-SITE TM were placed on a Rando phantom to simulate the tissue expander under the pectoralis major. Computed tomography simulation images were transformed through replacing the electron density of (a) metallic artifact region only (Image metallic port) and (b) metallic port and artifact regions (Image Homo). Planning was calculated using fixed-beam and helical-mode techniques. Radiation was delivered with different volumes of the tissue expander. Results: Integrated 997 dose points were calculated. Planning with Image metallic port provided a calculated dose significantly closer to a realistic dose. The percentage of doses achieving the prescribed dose was significantly higher in the helical mode. In layer 2, the 100-mL tissue expander had a significantly lower measurement dose than all other volumes. Volume 150 mL had the highest increase in the measured dose difference from the plan dose at layer 2. Volume 250 mL had the highest percentage of measurement doses passing the 5% dose difference from plan dose. The coldest dose areas were noted in layers 1 and 2, especially in the metallic port–direct image mode. The average dose reduction of the measured cold areas was 6.03 ± 1.94%. Conclusion: Dose distribution was affected by the volume of the metallic port tissue expander. Tomotherapy with proper image heterogeneity correction and helical mode can reduce the attenuation from the metallic port. A tissue expander volume of 150 to 250 mL is suitable. Patients with high risk at the chest wall should be evaluated carefully to avoid underdosing. Radiation oncologists should closely cooperate with plastic surgeons to optimize treatment for each patient.

Background: The purpose of this project is to identify prognostic features in resectable pancreatic head adenocarcinoma and use these features to develop a machine learning algorithm that prognosticates survival for patients pursuing pancreaticoduodenectomy. Methods: A retrospective cohort study of 93 patients who underwent a pancreaticoduodenectomy was performed. The patients were analyzed in 2 groups: Group 1 (n = 38) comprised of patients who survived 2 years. After comparing the two groups, 9 categorical features and 2 continuous features (11 total) were selected to be statistically significant (p

Background. Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation accounts for the majority of allograft failures in children with primary FSGS. Although current research focuses on FSGS pathophysiology, a common etiology and mechanisms of disease recurrence remain elusive. Methods. We performed a retrospective review of the Scientific Registry of Transplant Recipients to determine the association of specific HLA recurrence of FSGS. Kidney transplants recipients under the age of 19 who were diagnosed with FSGS, who were transplanted after January 1, 2000, and who had complete HLA data were included in the study. We performed simple logistic regression on all HLA A, B, C, DR, and DQ represented in the dataset and FSGS recurrence and then determined those associated with recurrence using the Benjamini–Hochberg method for multiple comparisons. For those HLAs that were associated with recurrence, we further determined the effect of matching recipient and donor HLA with recurrence. Results. HLA DR7, DR53, DQ2, DR52, and DQ7 were associated with increased or decreased risk of recurrent disease after transplantation. We identified a risk haplotype consisting of HLA-DR7, DR53, and DQ2 that was consistently associated with an increased risk of recurrence (odds ratio 1.91; 95% confidence interval, 1.44-2.54, P < 0.001). We also found that donor/recipient concordance for HLA-DQ7 was associated with a decreased risk of recurrence (odds ratio 0.42; 95% confidence interval, 0.37-0.53, P = 0.009). Conclusions. HLA profiles may be used for risk stratification of recurrence of FSGS in pediatric kidney transplant recipients and deserves further study.

Background. Livers from “nonideal” but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not assess how OPO-specific practices contribute to these trends. In this analysis, we evaluated nonideal liver donor avoidance or risk aversion among OPOs and within US donation service areas (DSAs). Methods. Adult donors in the United Network for Organ Sharing registry who donated ≥1 organ for transplantation between 2007 and 2019 were included. Nonideal donors were defined by any of the following: age > 70, hepatitis C seropositive, body mass index > 40, donation after circulatory death, or history of malignancy. OPO-specific performance was evaluated based on rates of nonideal donor pursuit and consent attainment. DSA performance (OPO + transplant centers) was evaluated based on rates of nonideal donor pursuit, consent attainment, liver recovery, and transplantation. Lower rates were considered to represent increased donor avoidance or increased risk aversion. Results. Of 97 911 donors, 31 799 (32.5%) were nonideal. Unadjusted OPO-level rates of nonideal donor pursuit ranged from 88% to 100%. In a 5-tier system of overall risk aversion, tier 5 DSAs (least risk-averse) and tier 1 DSAs (most risk-averse) had the highest and lowest respective rates of non-ideal donor pursuit, consent attainment, liver recovery, and transplantation. On average, recovery rates were over 25% higher among tier 5 versus tier 1 DSAs. If tier 1 DSAs had achieved the same average liver recovery rate as tier 5 DSAs, approximately 2100 additional livers could have been recovered during the study period. Conclusion. Most OPOs aggressively pursue nonideal liver donors; however, recovery practices vary widely among DSAs. Fair OPO evaluations should consider early donation process stages to best disentangle OPO and center-level practices.

Objectives:. Mediation analysis to assess the protective impact of sentinel lymph node (SLN) mapping on prognosis and survival of patients with colon cancer through a more precise evaluation of the lymph node (LN) status. Background:. Up to 20% of patients with node-negative colon cancer develop disease recurrence. Conventional histopathological LN examination may be limited in describing the real metastatic burden of LN. Methods:. Data of 312 patients with stage I & II colon cancer was collected prospectively. Patients were either staged using intraoperative SLN mapping with multilevel sectioning and immunohistochemical staining of the SLN or conventional techniques. The value of the SLN mapping for the detection of truly node-negative patients was assessed using Cox regression and mediation analysis. Results:. SLN mapping was performed in 143 patients. Disease recurrence was observed in 13 (9.1%) patients staged with SLN mapping and in 27 (16%) staged conventionally. Five-year overall survival (OS) rate was 82.7% (95% confidence interval [CI], 76.5–89.4%) with SLN mapping compared with 65.8% (95% CI, 58.8–73.7%). Five-year cancer-specific survival (CSS) was 95.1% (95% CI, 91.3–99.0%) with SLN mapping compared with 92.5% (95% CI, 88.0–97.2%). Node-negative staging with SLN mapping was associated with significantly better OS (hazard ratio [HR], 0.64; 95% CI, 0.56–0.72; P < 0.001) and CSS (HR, 0.49; 95% CI, 0.39–0.61; P < 0.001) in multivariate analysis. Mediation analysis confirmed a direct protective effect of SLN mapping on OS (HR, 0.78; 95% CI, 0.52–0.96; P < 0.01) and disease-free survival (DFS) (HR, 0.75; 95% CI, 0.48–0.89; P < 0.01). Conclusions:. Staging performed by SLN mapping with multilevel sectioning provides more accurate results than conventional staging. The observed clinically relevant and statistically significant benefit in OS and DFS is explained by a more accurate detection of positive LN by SLN mapping.

Summary: Background: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27–0·37]) and 82% at 8 weeks (0·18 [0·14–0·23]) following the week in which significant changes in population movements were recorded. Interpretation: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. Funding: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

Mycotic pseudoaneurysms (MPs) rarely affect the aortic arch vessels and usually require surgical resection for definitive treatment. In this case, a 58-year-old woman developed a bleeding innominate artery MP after primary lung cancer resection complicated by an infected chest wound. Because of her previous surgery, irradiation, and chest wall reconstruction, she was not a candidate for open resection. A hybrid endovascular approach successfully excluded her innominate artery MP through placement of an aortic arch stent graft. Cerebral circulation was maintained through a periscoped left common carotid artery stent graft to the descending thoracic aorta graft, which supplied a left-to-right carotid-carotid bypass.

Introduction: Taletrectinib (AB-106/DS-6051b) is an oral, potent selective ROS1 and pan-NTRK tyrosine kinase inhibitor (TKI). Preclinically, taletrectinib has activity against ROS1 G2032R solvent-front mutation. Methods: Patients with ROS1+ NSCLC enrolled into two phase 1 studies conducted in United States (U101, NCT02279433) and Japan (J102, NCT02675491) were analyzed for objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors version 1.1, progression-free survival, and safety. Results: A total of 22 patients with ROS1+ NSCLC out of the total 61 patients enrolled were analyzed. Taletrectinib was given at the oral dose of 400 mg, 600 mg, 800 mg, and 1200 mg once daily and 400 mg twice daily as part of the dose-escalation schema. Data cutoff was August 19, 2020. Median follow-up time for all 22 patients was 14.9 months (95% confidence interval [CI]: 4.1–33.8). A total of 18 patients with ROS1+ were assessable for response. The confirmed ORR for ROS1 TKI-naive patients (N = 9) was 66.7% (95% CI: 35.4–87.9) with a disease control rate of 100% (70.1–100). The confirmed ORR for crizotinib pretreated patients (N = 6) was 33.3% (95% CI: 9.7–70.0) with a disease control rate of 88.3% (95% CI: 443.6–97.0). The median progression-free survival for ROS1 TKI-naive patients (N = 11) was 29.1 months (95% CI: 2.6–not reached) and 14.2 months (95% CI: 1.5–not reached) for crizotinib-refractory only patients (N = 8). The most common treatment-related adverse events were alanine transaminase elevations (72.7%), aspartate transaminase elevations (72.7%), nausea (50.0%), and diarrhea (50.0%). Grade 3 or higher adverse events were alanine transaminase elevations (18.2%), aspartate transaminase (9.1%), and diarrhea (4.5%). Conclusions: Taletrectinib (AB106/DS6051b) has a meaningful clinical activity in patients with advanced ROS1+ NSCLC who are ROS1 TKI-naive or crizotinib-refractory and a manageable safety profile.

Introduction: RET rearrangements define a distinct molecular subset of NSCLC. The multikinase inhibitor ponatinib reveals potent activity in preclinical models of RET-rearranged NSCLC. Methods: In this single-arm, multicenter, phase II trial, we evaluated the clinical activity of ponatinib in patients with advanced, previously treated, RET-rearranged NSCLC (NCT01813734). RET rearrangements were identified through fluorescence in situ hybridization or next-generation sequencing. Ponatinib was administered at a dose of 30 mg once daily. Patients without a documented objective response were eligible to dose-escalate ponatinib to 45 mg daily. The primary end point was objective response rate. Results: Between August 2014 and December 2017, nine patients were enrolled. The median age was 58 years (range 49–73 y). Eight patients (89%) had a history of brain metastases. The median number of previous lines of therapy was three (range 1–5). Of the nine evaluated patients, five (55%) experienced tumor shrinkage from baseline, but no confirmed responses were observed (objective response rate 0%). The disease control rate was 55%. With a median follow-up of 9.33 months, the median progression-free survival and overall survival were 3.80 months (95% CI: 1.83–5.30) and 17.47 months (95% CI: 6.57–19.20), respectively. The most common treatment-related adverse events were rash (n = 5; 56%), constipation (n = 4; 44%), and diarrhea (n = 4; 44%). No treatment-related thromboembolic or cardiac events were observed. The study was stopped prematurely owing to slow accrual and lack of clinical activity. Conclusions: Ponatinib has limited clinical activity in patients with RET-rearranged NSCLC. Continued development of more potent and selective RET inhibitors is needed.

Abstract. Purpose:. The Surgical Implant Generation Network (SIGN) intramedullary nail was designed for use in resource limited settings which often lack fluoroscopy, specialized fracture tables, and power reaming. A newer design iteration, the SIGN Fin nail, was developed to further simplify retrograde femoral nailing by making proximal interlocking screw placement unnecessary. Instead, the leading end of the Fin nail achieves stability through an interference fit within the proximal femoral canal. While the performance of the traditional SIGN nail has been reported previously, no large series has examined long-term clinical and radiographic outcomes of femoral shaft fractures treated with the SIGN Fin nail. Methods:. The SIGN online surgical database was used to identify all adult femoral shaft fractures treated with the SIGN Fin nail since its introduction. All patients with minimum 6 month clinical and radiographic follow-up were included in the analysis. Available demographic, injury, and surgical characteristics were recorded. Fracture alignment was evaluated on final follow-up radiographs using a previously validated on-screen protractor tool. Coronal and sagittal plane alignment measurements were recorded as deviation from anatomic alignment (DFAA), with units in degrees. Fracture healing was assessed on final follow-up radiographs, with union defined as any bridging callus and/or cortical remodeling across one cortex on orthogonal views. Clinical outcomes available in the database included knee range of motion (ROM) greater than 90° and weight-bearing status at final follow-up. Clinical and radiographic outcomes were then compared between patients with united and nonunited fractures. Results:. The database query identified 249 femoral shaft fractures stabilized with the Fin nail in 242 patients who had minimum 6 month clinical and radiographic follow-up. Final follow-up radiographs were performed at an average of 48 weeks postoperatively. Average coronal and sagittal plane alignment measured on final follow-up radiographs were 2.18° and 2.58°, respectively. The rate of malalignment (DFAA > 10° in either plane) at final follow-up was 6%. Two hundred twenty-nine fractures (92%) were united at final follow-up. Overall, 209 (84%) of patients achieved full weight bearing and 214 (86%) achieved knee ROM >90° at final follow-up. Compared to patients with united fractures, those with nonunion were less likely to achieve full weight bearing (20% vs 90%, P 90° (30% vs 91%, P

Abstract. Purpose:. Orthopaedic residents are increasingly seeking international health electives (IHEs) during training, and many such experiences involve providing orthopaedic trauma care. However, little is known about the availability of IHEs during orthopaedic trauma fellowship training. The purpose of our study is to assess the global health opportunities available to US orthopaedic trauma fellows. Method:. We conducted an online, Research Electronic Data Capture (REDCap)-based survey of orthopaedic trauma fellowship program directors (PDs) in the United States. The survey link was sent by the Orthopaedic Trauma Association (OTA) Fellowship Committee to all US OTA-approved orthopaedic trauma fellowship PDs. Follow-up reminder e-mails were delivered at set time intervals from baseline over a period of 4 weeks. Results:. The overall response rate was 80% (43/54). Only 3 of 43 responding programs (7%) offer a structured global health program, but over the last 10 years, 12.5% of the remaining programs (5/40) have had a fellow participate in an IHE during fellowship training. Around 100% of PDs reported fellow satisfaction with their IHEs, and all PDs agreed that the educational experience provided by their fellows’ IHE participation was valuable. Among programs with no recent fellow IHE participation and without a structured global health program, 9% of PDs (3/35) expect to institute such a program. Lack of funding, lack of established international partner sites, and fellow time away were the most common perceived barriers to IHE participation. A total of 54% of PDs agree that participation in an IHE during training plays a major role in shaping fellows’ future professional and volunteer activities. Conclusion:. There are limited global health opportunities among US orthopaedic trauma fellowship programs, with only 7% (3/43) offering a structured global health program. Perceived barriers include lack of funding, lack of established partner sites, and concerns related to clinical/call coverage. Greater efforts to establish sustainable funding and international partnerships may increase opportunities for IHEs during orthopaedic trauma fellowship training.

The mainstay of treatment for unresectable hepatocellular carcinoma is locoregional therapy including percutaneous ablation and transarterial chemo- and radioembolization. While monitoring for tumor response after transarterial chemoembolization is crucial, current imaging strategies are suboptimal. The standard of care is contrast-enhanced magnetic resonance imaging or computed tomography imaging performed at least 4 to 6 weeks after therapy. We present a case in which contrast-enhanced ultrasound identified a specific extra-hepatic collateral from the gastroduodenal artery supplying residual viable tumor and assisting with directed transarterial management. Keywords: Transarterial chemoembolization, Contrast-enhanced ultrasound, Hepatocellular carcinoma

Purpose: Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post–radiation therapy (RT) memory impairment. Methods and materials: Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. Results: Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P

A 7-year-old boy with a history of spasticity, global developmental delay, and seizures was given the general diagnosis of cerebral palsy at an early age. Chromosomal array analysis performed at an outside center was normal. The patient's family sought neurodevelopmental pediatric care at a new institution following a move out of state. Electroencephalography confirmed abnormal epileptogenic activity. Brain magnetic resonance imaging showed findings consistent with a tubulin gene defect (tubulinopathy) and of focal cortical dysplasia, as well as evidence of a remote occipital lobe injury. This case report describes the various brain magnetic resonance findings suggestive of a tubulin gene defect and raises the possibility of focal cortical dysplasia manifesting as a result of tubulin dysfunction.

Management of limb ischemia caused by radiation injury can be challenging. Atypical conduits or tunnels have been used for bypass through or around the injured area. Application of endovascular therapy for revascularization has not been widely published. Standard and alternative access sites with or without hybrid arterial adjuncts can be used successfully in cases in which surgical bypass is prohibitive. We describe a case of limb salvage in a patient treated with high-dose radiation for recurrent endocervical adenocarcinoma using a hybrid open surgical and endovascular approach.

Abstract. Purpose:. In developing countries, long bone fractures following trauma are a significant contributor to morbidity, and operating room resources are often limited in these settings. The Surgical Implant Generation Network (SIGN) Fin nail may reduce the challenges of retrograde intramedullary nailing of femoral fractures without fluoroscopy. In contrast to the traditional SIGN nail placed in a retrograde fashion, the Fin nail does not require proximal interlocking screws. Instead, the nail achieves stability through an interference fit within the proximal femoral canal. The purpose of this study is to compare postoperative alignment in femoral shaft fractures treated with either a retrograde SIGN Fin nail or a standard retrograde SIGN nail. Method:. Using the SIGN online surgical database, we identified all femoral shaft fractures treated with a retrograde SIGN Fin nail at 2 African hospitals. Two examiners independently classified fracture patterns using the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) classification system. Using an on-screen protractor tool, postoperative coronal and sagittal plane alignment were measured and recorded as deviation from anatomic alignment (DFAA), with units in degrees. Available patient demographics and surgical details were also recorded. Fin nail cases were matched in a 1:1 ratio to retrograde standard SIGN nail cases based on AO/OTA fracture type. Results:. Twenty-eight retrograde Fin nail cases were identified, and 28 matched retrograde SIGN nail cases were selected. The Fin nail and retrograde SIGN nail groups were well matched in terms of demographics, AO/OTA fracture type, and surgical characteristics. There was no significant difference in postoperative coronal or sagittal plane alignment between the groups. There were no cases in either group of average postoperative malalignment >5° in any plane. Conclusion:. The SIGN Fin nail appears to achieve satisfactory radiographic alignment without the need for proximal interlocking screws, making it an attractive implant for retrograde femoral shaft fracture fixation in resource-limited settings. Further research is required to validate these findings and determine long-term Fin nail clinical outcomes.

Posterior fossa syndrome is a severe transient loss of language that frequently complicates resection of tumors of the cerebellum. The associated pathophysiology and relevant anatomy to this language deficit remains controversial. We performed a retrospective analysis of all cerebellar tumor resections at Seattle Children's Hospital from 2010 to 2015. Diffusion tensor imaging was performed on each of the patients as part of their clinical scan. Patients included in the study were divided into groups based on language functioning following resection: intact (N = 19), mild deficit (N = 19), and posterior fossa syndrome (N = 9). Patients with posterior fossa syndrome showed white matter changes evidenced by reductions in fractional anisotropy in the left and right superior cerebellar peduncle following resection, and these changes were still evident 1-year after surgery. These changes were greater in the superior cerebellar peduncle than elsewhere in the cerebellum. Prior to surgery, posterior fossa patients did not show changes in fractional anisotropy however differences were observed in mean and radial diffusivity measures in comparison to other groups which may provide a radiographic marker of those at greatest risk of developing post-operative language loss.

Background. Head and neck cancer (HNC) patients are at an increased risk for developing second primary tumors (SPTs). Diets rich in fruits and vegetables (FVs) may lower HNC risk. FV concentrates may offer a potential alternative to increasing FV intake. Methods. We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether Juice PLUS+ (JP; a commercial product with multiple FV concentrates) has an effect on p27 and Ki-67, biomarkers associated with the risk of SPTs. During 2004-2008, we randomized 134 HNC patients to 12 weeks of JP (n = 72) or placebo (n = 62). Oral cavity mucosal biopsies and whole blood were obtained at baseline and after 12 weeks. All participants were given the opportunity to receive JP for 5 years following the end of the intervention period, and they were followed yearly for the development of SPTs. Results. After 12 weeks, patients on JP had significantly higher serum α-carotene ( P = .009), β-carotene ( P < .0001), and lutein ( P = .003) but did not differ significantly in p27 ( P = .23) or Ki-67 ( P = .95). JP use following the initial 12-week trial was not significantly associated with SPT prevention. Conclusions. Despite increased serum micronutrient levels, our results do not suggest a clinical benefit of JP in HNC patients. Future studies should focus on longer intervention periods and/or modified supplement formulations with demonstrated chemopreventive properties.

Refractory otalgia or deep ear pain is a complex clinical problem that poses significant challenges to the physicians. Here we report a case of a 39 year old female who presented to us with deep right ear pain which started following cholesteatoma excision 11 years ago. Since onset of right ear pain, she had multiple ear surgeries including microvascular decompression and excision of right temporal bone before presentation. Following neuropsychological assessment and excluding underlying depression/anxiety, she underwent peripheral nerve field stimulation (PFNS) trial. She had a successful PFNS trial and underwent permanent implantation of PFNS and pulse generator. She had >50% reduction in her pain intensity on VAS and pain medications. She required explantation due to superficial infection; however she was satisfied with her therapy and looking forward for reimplantation. We report the first case of successful management of refractory deep ear pain using PFNS with a review of pertinent literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disease caused by excessive immune activation. Acquired HLH is seen in adults and is often caused by infection or malignancy. Diagnosis is difficult and usually missed as clinical and laboratory findings are nonspecific. Moreover, the pathophysiology of the systemic inflammatory response syndrome and/or sepsis is remarkably similar to HLH. Thus, in patients presenting with presumed severe sepsis or septic shock complicated by multiorgan failure without a clear infectious source, HLH should be considered. A disproportionately high ferritin may be one of the earlier laboratory findings to suggest HLH. We discuss a case of a young male who presented with presumed septic shock with multiorgan failure who was eventually found to have Epstein-Barr virus–induced HLH.

The assessment of iron deficiency anemia in infants is a clinical challenge because of the high requirements for iron to support expansion of the blood volume during rapid growth and development. Infants are endowed with only adequate storage iron to support this iron requirement for the first 4 to 6 months of life and premature infants even less than that. Hemoglobin is a measure of anemia but is not specific to iron deficiency, which requires the additional measurement of ferritin, soluble transferrin receptor, and protoporphyrin levels to assess iron nutrition. Premature infants that receive transfusion or erythropoietin therapy are special diagnostic challenge. An accurate classification of iron status requires multiple biomarkers of iron storage and transport adequacy and in the absence of standardized assay material for several tests, becomes quite problematic. [ABSTRACT FROM AUTHOR]

Parasitengona (velvet mites, chiggers and water mites) is a highly diverse and globally distributed mite lineage encompassing over 11,000 described species, inhabiting terrestrial, freshwater and marine habitats. Certain species, such as chiggers (Trombiculidae), have a great medical and veterinary importance as they feed on their vertebrate hosts and vector pathogens. Despite extensive previous research, the classification of Parasitengona is still contentious, particularly regarding the boundaries between superfamilies and families, exacerbated by the absence of a comprehensive phylogeny. The ontogeny of most Parasitengona is distinct by the presence of striking metamorphosis, with parasitic larvae being heteromorphic compared to the predatory free-living deutonymphs and adults. The enigmatic superfamily Allotanaupodoidea is an exception, with larvae and active post-larval stages being morphologically similar, suggesting that the absence of metamorphosis may be either an ancestral state or a secondary reversal. Furthermore, there is disagreement in the literature on whether Parasitengona had freshwater or terrestrial origin. Here, we inferred phylogenetic relationships of Parasitengona (89 species, 36 families) and 307 outgroups using five genes (7,838 nt aligned). This phylogeny suggests a terrestrial origin of Parasitengona and a secondary loss of metamorphosis in Allotanaoupodoidea. We recovered the superfamily Trombidioidea (Trombidioidea sensu lato) as a large, well-supported, higher-level clade including 10 sampled families. We propose a new classification for the terrestrial Parasitengona with three new major divisions (epifamilies) of the superfamily Trombidioidea: Trombelloidae (families Audyanidae, Trombellidae, Neotrombidiidae, Johnstonianidae, Chyzeriidae); Trombidioidae (Microtrombidiidae, Neothrombiidae, Achaemenothrombiidae, Trombidiidae, Podothrombiidae); and Trombiculoidae (=Trombiculidae sensu lato). Adding them to previously recognized superfamilies Allotanaupodoidea, Amphotrombioidea, Calyptostomatoidea, Erythraeoidea, Tanaupodoidae and Yurebilloidae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

For the past 50 years, superconducting detectors have offered exceptional sensitivity and speed for detecting faint electromagnetic signals in a wide range of applications. These detectors operate at very low temperatures and generate a minimum of excess noise, making them ideal for testing the non-local nature of reality 1,2 , investigating dark matter 3,4 , mapping the early universe 5-7 and performing quantum computation 8-10 and communication 11-14 . Despite their appealing properties, however, there are at present no large-scale superconducting cameras-even the largest demonstrations have never exceeded 20,000 pixels 15 . This is especially true for superconducting nanowire single-photon detectors (SNSPDs) 16-18 . These detectors have been demonstrated with system detection efficiencies of 98.0% (ref.  19 ), sub-3-ps timing jitter 20 , sensitivity from the ultraviolet 21 to the mid-infrared 22 and microhertz dark-count rates 3 , but have never achieved an array size larger than a kilopixel 23,24 . Here we report on the development of a 400,000-pixel SNSPD camera, a factor of 400 improvement over the state of the art. The array spanned an area of 4 × 2.5 mm with 5 × 5-μm resolution, reached unity quantum efficiency at wavelengths of 370 nm and 635 nm, counted at a rate of 1.1 × 10 5  counts per second (cps) and had a dark-count rate of 1.0 × 10 -4  cps per detector (corresponding to 0.13 cps over the whole array). The imaging area contains no ancillary circuitry and the architecture is scalable well beyond the present demonstration, paving the way for large-format superconducting cameras with near-unity detection efficiencies across a wide range of the electromagnetic spectrum., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: In Canada, endoscopy is primarily performed by gastroenterologists and surgeons, and some studies report that colonoscopies performed by nongastroenterologists have more complications and higher rates of future colorectal cancer. Our objective was to determine whether rural-based nongastroenterologist endoscopists are achieving quality benchmarks in colonoscopy., Methods: This quality improvement initiative prospectively evaluated 6 key performance indicators (KPIs) (cecal intubations, polyp detection [males and females; for first-time colonoscopies on patients aged ≥ 50 yr], bowel preparations, patient comfort and withdrawal times) on consecutive colonoscopies performed by participating Alberta North Zone endoscopists. The study period was June 2018 to March 2020. Overall and individual endoscopist's KPIs were compared with standard benchmarks. Additional performance indicators included mean number of polyps per colonoscopy and an exploration of study-defined sedation-related level of consciousness., Results: Data were collected on 6212 colonoscopies performed by 16 endoscopists (9 surgeons, 5 family physicians and 2 internists) in 6 hospitals. All 6 KPI benchmarks were achieved when results were pooled over all endoscopists in the study. Overall, cecal intubation occurred in 6006 of 6209 (96.7%, 95% confidence interval 94.5%-99.0%) cases. Polyp detection was 65.9% (592/898) and 49.8% (348/699) for male and female patients, respectively, aged 50 years or older. Variability in individual endoscopist results existed, especially for the mean number of polyps per 100 colonoscopies and sedation-related level of consciousness., Interpretation: Overall, Alberta North Zone endoscopists are performing high-quality colonoscopies, collectively achieving all 6 KPIs. To understand endoscopic performance and encourage individual and group reflection on endoscopic practices, Canadian endoscopists are encouraged to participate in similar colonoscopy quality initiative studies., Competing Interests: Competing interests: Michael Kolber founded EMPRSS, a University of Alberta spin-off company that supported the data collection, synthesis and reporting of results to the participants and their teams. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)