Low left ventricular ejection fraction (LEF) can progress undiagnosed. Artificial intelligence-based electrocardiogram (ECG-AI) screening may provide a scalable means to detect LEF. The purpose of this study was to validate a complete ECG-AI software as a medical device for LEF detection. Four geographically diverse sites in the United States identified patients with both ECGs and transthoracic echocardiograms performed within 30 days of each other in clinical practice. Data were electronically extracted to specific guidelines and transmitted to the coordinating center for analysis. Records of 16,000 subjects were extracted, resulting in an evaluable set of 13,960 subjects (mean age 66 years; 52% male). The device demonstrated excellent discrimination (AUROC: 0.92 [95% CI: 0.91-0.93]) and was 84.5% (95% CI: 82.2%-86.6%) sensitive and 83.6% (95% CI: 82.9%-84.2%) specific for LEF. The overall prevalence of LEF in the study data set was 7.9%, with LEF among 1.6% of the ECG-AI negative and 30.5% of ECG-AI positive subjects, contributing to positive and negative predictive values of 30.5% (95% CI: 28.8%-32.1%) and 98.4% (95% CI: 98.2%-98.7%), respectively. External validation studies such as this one provide a rigorous framework to validate an algorithm's performance. This study demonstrated the algorithm's strong diagnostic accuracy over a geographically diverse, independent set of patients. In this generally unselected population, the algorithm produced a test negative result in 78% of the cases, suggesting potential utility as a rule-out strategy to defer echocardiography when other clinical findings are absent.
This guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT) for gastric cancer in a variety of clinical settings, ranging from patients with resectable locoregional disease to metastatic and symptomatic disease. The American Society for Radiation Oncology convened a task force to address 3 key questions: (1) indications for and timing of RT for patients with resectable and nonmetastatic gastric cancer; (2) indications for and timing of RT in patients with unresectable locoregional disease, oligometastases, and/or requiring palliation; and (3) appropriate RT dose-fractionation regimens, target volumes, and techniques in these clinical settings. Recommendations are based on a systematic literature review and were created using a predefined consensus-based methodology with a system for grading evidence quality and recommendation strength. Multidisciplinary evaluation and decision-making are recommended for all patients. For patients with cT2-4 and/or N+ resectable gastric cancer, perioperative chemotherapy is recommended, preferably FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel). Recently, perioperative durvalumab and FLOT has shown a significant improvement in event-free survival versus FLOT only for patients with resectable disease and is now being adopted as a standard of care. Preoperative chemoradiation is recommended for patients who are not candidates for perioperative chemotherapy and conditionally recommended if there is concern for a margin-positive (R1) or incomplete (R2) resection. Postoperative chemoradiation is conditionally recommended for patients who are not candidates for perioperative or postoperative chemotherapy or if a suboptimal resection was done (eg, <D2 or R1-R2) for those who proceeded directly to surgery. Definitive chemoradiation may provide durable control for nonmetastatic patients who are inoperable either at initial diagnosis or at the time of locoregional recurrence. For patients with oligometastatic gastric cancer, metastasis-directed therapy along with systemic therapy is conditionally recommended. Palliative RT is efficacious for patients with bleeding, pain, and obstruction. Target coverage goals and dose guidance for normal tissues are provided. These evidence-based recommendations guide clinical practice on the use of RT for gastric cancer. Future studies will further refine the indications and role of RT in the management of these patients.
To determine the accuracy of radioisotope, blue dye and implanted fiducial marker for identification of the histopathologically positive percutaneous/previously biopsied lymph node (PBLN) following neoadjuvant chemotherapy (NAC). Detection of the PBLN is critical for monitoring disease response and guiding subsequent treatment decisions. However, conventional sentinel lymph node biopsy (SLNB) techniques have shown unacceptable false negative rates. Recommendations for improvement suggest using dual tracers, removing more lymph nodes and implantable markers in the PBLN. This study evaluated the accuracy of PBLN identification using each of the 3 most common localization techniques: blue dye (lymphazurin), radioisotope (Technetium-99m sulfur colloid), and implanted fiducial marker (SAVI SCOUT). Patients with PBLN marked with a SAVI SCOUT, with or without a metallic clip, and who received NAC were identified from our breast cancer surgery database. The accuracy of the 3 localizing techniques was evaluated. Secondary outcomes included total number of lymph nodes retrieved and number of sampling events per patient for each technique. We identified 65 patients who underwent percutaneous lymph node biopsy prior to NAC. The clip marking the PBLN was identified in 64 patients (98%). The PBLN was identified by the SAVI SCOUT in 61 (95%) of 64 patients, radioisotope in 44 (71%) of 62 patients and blue dye in 28 (64%) of 44 patients. A SAVI SCOUT was placed at the time of biopsy instead of a clip in 13 patients and identification of the PBLN was 100% for those patients. The mean number of lymph nodes removed with the SAVI SCOUT was 2.7, with radioisotope was 4.3 and with blue dye was 3.6 (P = .004). The mean number of SLN sampling events with the SAVI SCOUT was 1, with radioisotope was 2.0 (range: 0-6) and with blue dye was 1.8 (range: 0-5) (P < .005). When radioisotope was used, the clip was found in the hottest lymph node 40% of the time, in the second and third hottest lymph node 5% and 11% of the time, respectively. The clipped node was not hot in 29% of cases. This study demonstrates that the most accurate method for identifying the PBLN is with placement of a fiducial marker. Furthermore, the addition of radioisotope and blue dye may result in an excessive number of lymph nodes removed and more retrieval events during SLNB following NAC. Placement of the SAVI SCOUT marker at the time of percutaneous lymph node biopsy may subsequently obviate the need for additional mapping techniques of blue dye and radioisotope during sentinel lymph node surgery.
Nipah virus (NiV) remains a persistent public-health threat in Bangladesh. The national sentinel surveillance system has operated since 2006, yet fatal infections that occur before assessment often go untested. We piloted a post-mortem surveillance component at three sentinel hospitals (December 2023-April 2024). Trained anthropologists obtained written informed consent from the next of kin. Oral swabs were collected non-invasively shortly after death and tested for NiV RNA by qRT-PCR at the national reference laboratory, using standard controls and established protocols. Specimens were handled in BSL-2 plus conditions on site and transported in liquid-nitrogen dry shippers per national SOPs. Where indicated by epidemiologic risk, shipments were prioritized for rapid testing. Of 246 deceased individuals screened, 10 met the suspected NiV case definition and were enrolled; all died after admission. One decedent tested NiV-positive (Ct value of 27.3), which activated same-day outbreak investigation by IEDCR's National Rapid Response Team. Contacts (close contacts and one same-source exposed individual) were traced and tested (RT-qPCR/IgM acutely; IgG at 6 weeks); no secondary cases were detected. Operational timelines (death → enrolment → collection → testing) demonstrated that post-mortem sampling and confirmation can be completed rapidly within routine hospital workflows. Post-mortem oral-swab testing is feasible, acceptable, and operationally compatible with Bangladesh's national surveillance system. While not intended to improve detection among living patients, this non-invasive approach closes a critical gap by identifying previously untested fatal infections and providing a trigger for timely public-health response. Scaling this approach across sentinel sites could strengthen early detection and outbreak control in NiV-affected regions.
Antimicrobial resistant (AMR) bacteria are frequently detected in wildlife and are often considered an indicator of anthropogenic pathogen exposure to wildlife. However, the role of bats in AMR dissemination remains poorly understood. We conducted a cross-sectional study to investigate the prevalence and risk factors associated with AMR patterns in Staphylococcus spp. and Escherichia coli isolated from frugivorous bats in Bangladesh. We collected 369 noninvasive fecal samples from Pteropus medius and Rousettus leschenaultii individual bats. Bacterial isolation was performed using selective media, biochemical tests and performed polymerase chain reaction (PCR) for confirmation of Staphylococcus spp. and E. coli. Antimicrobial susceptibility testing for antimicrobials was conducted using the Kirby-Bauer disc diffusion technique. The prevalence of E. coli and Staphylococcus spp. was 29.8 % and 28.5 % respectively. Overall, 28.2 % of E. coli and 26.3 % of Staphylococcus spp. exhibited resistance to at least one antimicrobial. Logistic regression analysis revealed that resistant Staphylococcus spp. colonisation was significantly higher in rural areas (OR = 2.6) and in R. leschenaulti i species (OR = 2.6), while resistant E. coli was higher in urban areas (OR = 2.0) and in P. medius bat (OR = 1.7). Staphylococcus spp. showed the highest resistance to ampicillin (56 %), followed by clindamycin (23 %). On the other hand, E. coli showed the highest resistance against cefepime (16 %) followed by ampicillin (13 %). While the source of AMR bacteria in bats remains unclear, bat drinking habits on the contaminated water bodies with people and domestic animals might be source of resistant bacteria to bats. Future One Health research is recommended to understand the ecology of AMR and role of bats in the transmission of resistant bacteria across ecosystems.
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Repetitive contractions of the platysma muscle may result in vertical neck bands that blunt the jawline (i.e., platysma prominence [PP]). We report patient-reported outcomes (PROs) from a phase 2 study evaluating onabotulinumtoxinA (onabotA) for moderate or severe PP. Subjects were randomized 1:1:1 to onabotA dose 1 (26 U, 31 U, or 36 U), onabotA dose 2 (52 U, 62 U, or 72 U), or placebo. De novo, validated, fit-for-purpose PROs were used to assess treatment satisfaction, bother with vertical neck bands and jawline, jawline definition, and psychosocial impact. Subjects with PRO data (N = 164; mean age, 50.0 years) were predominantly female (95.1%) and White (93.9%). Response rates for improvement in both onabotA dose groups were higher than placebo for treatment satisfaction, bother with vertical neck bands and jawline, as well as jawline definition (unadjusted p < 0.05 for all). Greater improvements in treatment satisfaction and psychosocial impact were observed in both dose groups versus placebo based on the mean total scores on the Appearance of Neck and Lower Face Questionnaire (ANLFQ): Satisfaction and the mean change from baseline in ANLFQ: Impacts total score, respectively (unadjusted p < 0.0001 for all). Response rates generally peaked across all measures at day 14 or 30 for both dose groups, with a trend in improvement continuing through day 120. Compared with placebo, both onabotA dose groups reported greater satisfaction with the effect of treatment, improvements in jawline definition and psychological impact, as well as reductions in bother due to vertical neck bands and jawline. ClinicalTrials.gov: NCT03915067.
Metastases to the thyroid gland are uncommon, with renal cell carcinoma (RCC) representing a rare but clinically significant occurrence. RCC may metastasize after a prolonged dormancy and remain clinically silent for years before detection. We present a case of a 61-year-old man who initially presented with hematuria. Imaging at the time revealed RCC confined to the kidney. Several years later, during surveillance imaging for newly diagnosed prostate cancer via prostate-specific membrane antigen (PSMA) positron emission tomography (PET), bilateral thyroid nodules were incidentally detected. Histopathological examination of the resected multinodular thyroid revealed an unexpected finding of metastatic RCC, initially masquerading as a primary thyroid neoplasm. Awareness of RCC's propensity to masquerade as a primary thyroid tumor is paramount for the surveillance and management of patients with a history of RCC.
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To demonstrate the detection of circulating human papillomavirus (HPV) DNA fragments can serve as a biomarker for presence of tumor and provide a universal, non-invasive tool for monitoring treatment response in HPV-related cervical cancers (CC). A multi-site prospective study of HPV-positive high-grade cervical dysplasia (CIN2/3) and CC was conducted. Serum samples were collected pre-, during, and post-treatment. NavDx® (Naveris,Inc) digital droplet polymerase chain reaction testing was used to detect tumor tissue modified viral (TTMV)-HPV DNA. The expanded panel included 14 HPV subtypes. Sensitivity and specificity were calculated for the pre-treatment Score only. Scores were quantified for on-treatment timepoints and trends were compared against treatment response. 80 patients were included in the analysis: 46 (57.5%) CC, 26 (32.5%) CIN2/3, 8 (10.0%) benign. TTMV-HPV DNA was undetectable in all CIN 2/3 and benign cases. For CC, 38 (82.6%) had primary disease and 8 (17.4%) recurrent. For primary CC, 28 (73.7%) had stage I/II and 10 (26.3%) stage III/IV. Specificity for TTMV-HPV DNA for CC detection was 100% (95% CI: 89.7%-100.0%) for all stages. Sensitivity was 39.2% (95% CI: 21.5-59.4%) for stage I/II, 90% (95% CI: 55.5-99.7%) for stage III/IV, and 62.5% (95% CI: 24.4-91.48%) at recurrence. Disease progression/persistence occurred in 7 patients with corresponding increased Scores. TTMV-HPV DNA is a sensitive and specific biomarker for advanced CC, with Scores dynamically corresponding to treatment response, and has the potential to serve an unmet need as a universal biomarker for patients with HPV-related CC.
Neck lacerations sustained while playing ice hockey are rare but potentially fatal. Neck laceration protectors (NLPs) have been around for decades but only lately are becoming required by leagues given recent fatalities. To outline the relevant neck anatomy at risk, describe rink-side evaluation and management techniques, review historical and contemporary NLP mandates, and conclude with evidence-based recommendations. Narrative review; Level of evidence, 5. A review of the literature regarding neck lacerations in ice hockey was utilized for content collection. Google Scholar and PubMed were queried for peer-reviewed articles relevant to the topic. Keywords including "ice hockey," "neck lacerations," "neck laceration protector," and combinations thereof were used to identify relevant literature. Neck lacerations are rare but can be fatal given that they often damage zone II neurovascular structures. While numerous international leagues require mandates for NLPs, notable holdouts include the National Hockey League and the National Collegiate Athletic Association. Numerous materials and builds for NLPs are capable of withstanding penetration from a skate slash, although they possess differences in comfort and neck range of motion. NLPs have the capacity to prevent significant and potentially fatal laceration injuries in ice hockey. Based on the available data, implementing NLP mandates appears to be in the interest of player safety.
Accurate assessment of skin and skin changes across diverse populations is critical for patient health. To promote the knowledge and skills nurses need in practice to identify skin changes, nurse educators must include content on assessment of diverse skin tones in nursing education programs. This study's objective was to develop and pilot education modules about the assessment of diverse skin tones to be part of an undergraduate nursing course. In this quality improvement project, modules highlighted the importance of skin assessment and appropriate techniques for assessing erythema, pallor, cyanosis, and jaundice on diverse skin tones. Undergraduate nursing students completed a questionnaire evaluating the modules and their learning experience. The majority of students (≥70%) agreed or highly agreed that the modules were interesting, informative, engaging, and increased their knowledge. Comments to open-ended questions supported their evaluation ratings. Undergraduate nursing students positively received education modules on assessing patients with diverse skin tones. Students perceived the modules as having the potential to enhance their learning and assessment skills to prevent and detect skin changes associated with pressure injury. The modules serve as an example of a strategy to integrate education content about diverse skin tones into nursing curricula.
Urinothorax is a somewhat vaguely defined entity in the pulmonary literature. It is believed to be due to obstructive renal failure resulting in translocation of urine into the pleural space, presenting as transudative pleural effusions. The literature is sparse, and much of the reported data revolves around case reports and series, with less than 100 cases reported to date. The hallmark finding defining urinothorax is a pleural fluid to serum creatinine ratio greater than 1, although this ratio has not been verified in the literature. Further, the utility of this ratio beyond identification of urinothorax is unknown. Pleural fluid creatinine values may be useful beyond identification of urinothorax, and may have diagnostic value in identifying pleural effusions from persistent volume overload, although further studies are needed to verify this. More likely however, there is a paucity of data in the current literature to support the use of pleural fluid creatinine routinely in the identification of urinothorax, as we have identified in this study. This study aims to elucidate the normal values of pleural fluid creatinine and its utility in pleural disease. Here we report a large retrospective study on pleural fluid analyses at a tertiary care center, correlating pleural fluid to serum creatinine ratios with the etiology of pleural effusion. We present a retrospective study on the analysis of over 300 pleural fluid studies, with a focus on pleural fluid to serum creatinine ratio and its relation to pleural disease. A pleural fluid to serum creatinien ratio of 1:1 is not specific for the diagnosis of urinothorax given its nearly universal distribution amongst pleural effusions of all etiologies. Further studies are needed to establish normal values of pleural fluid creatinine and specifically its utility in true urinothorax and challenging cases such as pseudoexudates.
Fluorescent protein-based Genetically Encoded Voltage Indicators (GEVI) offer a remarkable system for high-throughput screening of membrane potential phenotypes. The GEVI MARINA is a derivative from ArcLight, which conversely to ArcLight increases its fluorescence intensity alongside depolarization. Here we created knock-in reporter human iPS cell lines carrying the MARINA reporter using SpCas9 programmable nuclease and characterize a heterozygous clone.
A case of a 36-year-old male with no known comorbidities presented because of chest discomfort after using ecstasy and was noted to have an evolving anteroseptal myocardial infarction (MI). Left heart catheterization showed mild obstructive coronary disease with red thrombus in the proximal left anterior descending (LAD) artery seen on optical coherence tomography (OCT) and with note of improvement and decrease in thrombus burden on repeat coronary angiogram the next day after starting the patient on eptifibatide. Echocardiogram revealed mildly reduced systolic function with an apical akinesis. Cardiac magnetic resonance imaging (CMR) showed a small-sized infarct involving the apical inferior, apical lateral, and basal septum, with myocardial edema at the apex and septum, and a note of a small apical clot. He improved significantly during his course and was maintained on ticagrelor, apixaban, and atorvastatin.
Nipah virus (NiV) causes severe diseases in humans with a high case fatality rate. The primary risk factors for NiV infection in Bangladesh are drinking raw date palm sap (DPS) contaminated with Pteropus fruit bat secretions/excretions or close contact with or exposure to the body fluid of an individual with NiV infection. During the 2023 NiV outbreak investigation in Bangladesh, the breast milk of a NiV-infected nursing mother was tested by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for detection of NiV-RNA. The newborn was also tested as a suspected NiV-infected subject. NiV, specifically NiV RNA, was detected in the breast milk sample. Through the investigation, it was determined that the mother consumed raw DPS 9 days before the delivery. The newborn was also confirmed as NiV positive and had exposure to maternal bodily fluid while breastfeeding, and was in prolonged maternal contact during caregiving. Although the detection of NiV RNA in breast milk does not equate to viability and transmissibility of the virus, this finding provides preliminary evidence that warrants further investigation into the potential role of breast milk in postnatal transmission of NiV. Our findings advocate incorporating breast milk testing into NiV diagnostic protocols for symptomatic mothers. This advancement will broaden our understanding of postnatal transmission of NiV and pave the way for more effective containment strategies.
Dias-Logan syndrome (DLS) is a rare condition caused by heterozygous germline BCL11A pathogenic variants associated with global developmental delay, distinctive facial features, and asymptomatic persistence of fetal hemoglobin. There has been no evidence of an association between DLS and increased risk of cancer. We report the first instance of a child with DLS diagnosed with cancer, a Wilms tumor (WT), who is notably much older than the typical onset. Although this case alone is insufficient to warrant routine WT screening in DLS, given the extreme rarity, we cannot rule out an association with DLS and WT predisposition.
This is the second part of a 2-part article that proposes improving the United States (US) clozapine package insert. Part II focuses on fatal outcomes and the 5 boxed warnings, 4 specifically for clozapine: severe neutropenia, seizure, orthostatic hypotension and myocarditis, and 1 for all antipsychotics (elderly with dementia). US reports to the World Health Organization's global pharmacovigilance database were analyzed from clozapine's introduction to January 15, 2023. The US was the top reporter worldwide for clozapine with 56,003 reports and 9587 associated fatal outcomes. The 4 clozapine boxed warnings were associated with 534 fatal outcomes (218 with severe neutropenia, 131 with seizures, 125 with orthostasis, 36 with myocarditis, 24 with cardiomyopathy, and 0 with mitral valve prolapse). With no boxed warnings, pneumonia was associated with 674 fatal outcomes and increased white blood cell count (a sign of infection) with 596 fatal outcomes. After considering overlaps, pneumonia and increases in white blood cell count explained 900 fatalities, or 9.4% of 9587 fatal outcomes. The Food and Drug Administration continues to focus on severe neutropenia which was associated with only 218 or 2.3% of fatal outcomes, whereas 97.7% of fatal outcomes reported in US clozapine-treated patients had another cause. To help prevent future deaths in clozapine-treated patients, the clozapine package insert should focus on fatal outcomes during infections. Part II offers detailed solutions regarding current boxed warnings and lack of a warning for pneumonia and other infections. The Supplementary Material includes letters of support from 124 non-US clozapine experts from 44 countries/regions who support Parts I and II.
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