UPMC

Background Natriuretic peptides (NP) are widely used to diagnose heart failure (HF), but their role in guiding treatment remains uncertain. We performed a randomized trial meta‐analysis comparing NP‐guided therapy to usual care in acute decompensated HF. Methods We searched PubMed, Embase, and Cochrane for RCTs comparing NP‐guided therapy to usual care in acute decompensated HF. Outcomes included all‐cause mortality, cardiovascular death, and a composite of mortality and HF hospitalizations (reported as RR and 95% CI). Heterogeneity was assessed using I², and a random‐effects model was applied when appropriate. Analyses were performed in R Studio 4.3.2. Results We included 9 RCTs with 3992 patients, of whom 2007 (50.3%) underwent NP‐guided treatment. The median follow‐up was 12 months. All‐cause mortality (RR: 0.84; 95% CI: 0.69–1.01; p = 0.069; I² = 41%), cardiovascular death (RR: 0.91; 95% CI: 0.78–1.08; p = 0.287; I² = 0%), and the composite outcome of HF hospitalization or cardiovascular death (RR: 0.91; 95% CI: 0.77–1.09; p = 0.308; I² = 56%) were not significantly different between groups. The time to event analysis of all‐cause mortality had a slightly significant advantage in favor of NP‐guided therapy (HR: 0.81; 95% CI: 0.69–0.95; p = 0.01; I² = 0%). Conclusion Although NP‐guided therapy showed a statistically significant benefit in time to all‐cause mortality, this was not consistently reflected across other endpoints, and its overall clinical impact remains uncertain.

Hypertension is a leading cause of morbidity and mortality, with pathologic consequences on multiple end-organ systems. Smooth muscle plasticity and its epigenetic regulation promote disease pathogenesis, but the genetic levers that control such activity are incompletely defined. In this issue of the JCI, Mangum et al. utilized high-density genomic data to define the causal and pathogenic role of a variant at the JMJD3 locus - one that is associated with systolic blood pressure and governs an allele-specific molecular mechanism controlling smooth muscle behavior in hypertension. These findings have clinical implications relevant to patient risk stratification and personalized therapeutics.

Background Chordomas are rare, aggressive tumors of notochordal origin, commonly affecting the spine and skull base. Skull Base Chordomas (SBCs) comprise approximately 39% of cases, with an incidence of less than 1 per million annually in the U.S. Prognosis remains poor due to resistance to chemotherapy, often requiring extensive surgical resection and adjuvant radiotherapy. Current classification methods based on chromosomal deletions are invasive and costly, presenting a need for alternative diagnostic tools. Radiomics allows for non-invasive SBC diagnosis and treatment planning. Methods We developed and validated radiomic-based models using MRI data to predict Overall Survival (OS) and Progression-Free Survival following Surgery (PFSS) in SBC patients. Machine learning classifiers, including eXtreme Gradient Boosting (XGBoost), were employed along with feature selection techniques. Unsupervised clustering identified radiomic-based subgroups, which were correlated with chromosomal deletions and clinical outcomes. Results Our XGBoost model demonstrated superior predictive performance, achieving an area under the curve (AUC) of 83.33% for OS and 80.36% for PFSS, outperforming other classifiers. Radiomic clustering revealed two SBC groups with differing survival and molecular characteristics, strongly correlating with chromosomal deletion profiles. These findings indicate that radiomics can non-invasively characterize SBC phenotypes and stratify patients by prognosis. Conclusions Radiomics shows promise as a reliable, non-invasive tool for the prognostication and classification of SBCs, minimizing the need for invasive genetic testing and supporting personalized treatment strategies.

A majority of the 8.9 million Americans with opioid misuse have mild or no symptoms of opioid use disorder (OUD), but they may be at elevated risk of developing more severe OUD, overdose, or other health consequences of opioid use. The “Subthreshold Opioid Use Disorder Prevention”(STOP) Trial is evaluating a collaborative care intervention for risky opioid use in primary care. Here, we describe baseline characteristics of participants to understand their needs and assess the generalizability of the sample. Recruitment at five primary care sites spanned March 2021-May 2023. Adult patients who screened positive for subthreshold OUD (current illicit or non-medical opioid use without meeting DSM-5 criteria for moderate-severe OUD) were eligible. Baseline assessments measured self-reported demographic characteristics, other substance use, pain, and physical and mental health symptoms. Descriptive statistics summarize characteristics of the enrolled sample across sites. Among the 202 participants, the majority identified as female (63.4%), white (70.8%), and non-Hispanic (96.5%), with mean age 55.7 (SD: 12.7) years. Nearly half (49.0%) had problem or high-risk use of prescription opioids, and most received a prescription for opioid medication in the past six months (74.8%). Many participants reported current problem use or high-risk use of alcohol (47.0%) or cannabis (31.2%). Approximately one-third endorsed mental health symptoms, including moderate-severe anxiety (35.6%), depression (31.2%), or sleep disturbance (29.7%), and 20.3% reported a past suicide attempt. In the prior six months, 14.7% had experienced a nonfatal overdose. Moderate-severe pain was reported by 63.4%, and 60.4% rated their general health as fair or poor. Patients with subthreshold OUD had high rates of polysubstance use and comorbidities that may present challenges to reducing risky opioid use. The STOP trial presents an opportunity to detect and address subthreshold OUD in a cohort with considerable medical and social needs, within primary care settings. ClinicalTrials.gov NCT04218201

The MYC oncoprotein regulates numerous genes involved in processes such as cell cycle control and mitochondrial and ribosomal structure and function. This requires heterodimerization with its partner, MAX, and binding to specific promoter and enhancer elements. Here, it is shown that MYC and MAX also bind near transcriptional end sites (TESs) of over one‐sixth of all annotated genes. These interactions are dose‐dependent, evolutionarily conserved, stabilize the normally short‐lived MYC protein and regulate expression both in concert with and independent of MYC's binding elsewhere. MYC's TES‐associated binding, occurring in coordination with other transcription factors, alters the chromatin landscape, increases nuclease susceptibility and alters transcriptional read‐through, particularly in response to certain stresses. MYC‐bound TESs can directly contact promoters and appear to fine‐tune gene expression in response to both physiologic and pathologic stimuli. Collectively, these findings support a previously unrecognized role for MYC in regulating transcription and its read‐through via direct intragenic contacts between TESs and promoters.

Background: The clinical significance of serum potassium levels at admission in patients with blunt hepatic trauma remains insufficiently defined. This study aimed to evaluate the prevalence and prognostic value of admission hypokalemia in this patient population. Methods: We conducted a retrospective analysis of 164 patients with radiologically confirmed blunt liver trauma admitted between 2016 and 2023. Preoperative, intraoperative, and postoperative data were collected to assess the association between serum potassium levels and trauma severity (AAST grade—American Association for the Surgery of Trauma, ISS—Injury Severity Score), in-hospital morbidity, mortality, and length of stay. Univariate and multivariate analyses were performed, including checks for normality and multicollinearity. Results: Serum potassium levels showed a significant positive correlation with age (p = 0.0064), and an inverse correlation with liver injury severity (AAST grade; p = 0.01). Lower potassium levels were associated with longer hospital stays (p = 0.0459) and higher morbidity (p = 0.022). In multivariate analysis, only age (p = 0.036) and AAST grade (p = 0.014) were independent predictors of serum potassium concentration. Potassium levels were not independently associated with mortality. Conclusions: Admission hypokalemia is a common finding in blunt liver trauma and correlates with injury severity and adverse clinical outcomes. Potassium concentration may serve as a readily available, low-cost biomarker for early risk stratification in these patients. Further prospective studies are warranted to confirm its prognostic utility.

Introduction Prompt recognition and treatment of patients with sepsis improve survival. Patients transported to hospital with sepsis often do not receive treatment until they are assessed in emergency departments. Initiation of treatments by paramedics at the point of first contact may improve outcomes for these patients. Methods and analysis The study design involves two randomised controlled trials (RCTs) conducted using a 2×2 factorial design comparing use of (1) early intramuscular ceftriaxone versus placebo and (2) an early liberal intravenous fluid strategy (up to 2 L normal saline) versus usual care resuscitation guided by paramedic medical directives. Patients who are ≥18 years of age will be eligible for inclusion if they have sepsis, defined as (1) paramedic suspicion of infection, (2) fever (temperature ≥38.0°C measured by paramedic or history of fever during the previous 24 hours), and (3) hypotension: SBP <100 mm Hg. The primary outcome is mortality prior to hospital discharge or within 90 days of admission. Secondary outcomes are all-cause mortality at 90 days after enrolment; organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy, dialysis) and hospitalisation (mechanical ventilation; dialysis); rates and duration of hospital admission; rates of ICU admission during index hospitalisation; discharge destination; proportion of patients with positive blood cultures obtained in hospital (first 24 hours); microbiological profile including distribution of microorganism species and resistant organisms; proportion of patients receiving additional antibiotics within 6 hours and within 24 hours of hospital admission; frequency distribution of first antibiotics (if any) delivered within 24 hours of hospital arrival; mean time to antibiotics delivered within 24 hours of hospital arrival (if any); proportion of patients receiving fluid bolus (>250 mL) within 24 hours of hospital arrival; total amount of crystalloid infused during transport and first 24 hours of hospitalisation; and proportion of enrolled patients not suspected to have sepsis or infection by emergency department physicians. Safety outcomes include the proportion of patients with pulmonary oedema during transport to hospital and on initial chest X-ray and the proportion of patients with anaphylaxis or suspected allergic reactions to study medication. Ethics and dissemination This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre). It will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. The final results will be disseminated to participating paramedic services through educational materials, presentations and interactive training. We anticipate our trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of prehospital and emergency medicine, resuscitation and critical care. Trial registration number NCT03068741 .

Purpose This study aims to assess anterior cruciate ligament reconstruction (ACLR) outcomes and return to pre‐injury sports (RTPS) characteristics in athletes participating in martial arts. Methods Martial arts athletes over the age of 14 years who underwent primary ACLR with a minimum 1‐year follow‐up were eligible for this study. This study defined RTPS as reaching pre‐injury levels of martial arts participation. Patients completed a questionnaire assessing sports participation, reinjury, and patient reported outcomes (PROs) including International Knee Documentation Committee Subjective Knee Form (IKDC SKF), Marx activity score, Tegner activity scale, and visual analogue scale (VAS). Demographics, surgical data, and preoperative PROs were collected retrospectively. Patients were grouped into those who achieved RTPS and those who did not. Statistical analyses included chi‐square, Fisher's exact, Mann–Whitney U, and t‐tests. Statistical significance was set at p < 0.05. Results Fifty‐two individuals who participated in martial arts (mean age 30.6 ± 11.0 years, 21% female) completed the questionnaire at a mean follow‐up of 12.1 ± 7.8 years. Of the cohort, 35 patients (67%) participated in competitive, varsity, or elite martial arts prior to injury. Of those who did not return to martial arts at all, fear of reinjury was the most common reason. The rate of RTPS was 58%. Age, pre‐injury martial arts participation (frequency and competitiveness), and surgical characteristics did not differ between groups. Those who did not achieve RTPS had a higher rate of minor and major postoperative complication (41% vs. 13%, p = 0.02), which included stiffness, infection, effusion, and reinjury. The RTPS group reported statistically higher IKDC SKF scores (71.4 ± 11.7 vs. 68.4 ± 7.2, p < 0.01) and Tegner activity scores (6.9 vs. 5.6, p = 0.04) at final follow‐up. Graft failure rate for all study participants was 12% and did not differ between groups (p = 0.69). Reinjury rate of the RTPS group was 17%. Conclusion Martial arts athletes demonstrated a rate of 58% return to pre‐injury participation levels after ACLR. Level of evidence Case series; level IV.

Background ADVISE (ADaptiVe biomarker trial that InformS Evolution of therapy) ( NCT03335540 ) was a biomarker-adapted feasibility clinical trial of immunohistochemistry (IHC) to inform combination immuno-oncology (I-O) treatment. Methods To inform I-O combination selection, messenger RNA expression analyses from The Cancer Genome Atlas evaluated associations between programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and other I-O-associated genes. Tumor tissue blocks of melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, and gastroesophageal junction/gastric cancer were stained by IHC to assess expression of CD8, colony-stimulating factor 1 receptor, glucocorticoid-induced tumor necrosis factor receptor (GITR), indoleamine 2,3-dioxygenase 1, lymphocyte-activation gene 3, NKp46, forkhead box P3, and PD-L1. These results facilitated an I-O treatment selection algorithm where patient biopsy results dictated allocation into combinations of nivolumab with cabiralizumab, urelumab, linrodostat mesylate, relatlimab, BMS-986156 (anti-GITR), lirilumab, ipilimumab, or irradiation. The primary endpoint was the proportion of patients with qualified baseline tumor biopsy specimens where decision-enabling biomarker analysis was completed within 12 business days to select an I-O combination therapy. Results Correlation of PD-1/L1 and I-O-associated genes varied across the spectrum of T-cell-inflamed versus non-inflamed tumors; however, tumors with low/intermediate PD-L1 expression demonstrated distinct upregulation of immune markers grouped by cell type (T cell, macrophage, etc). IHC analyses of I-O naïve tumors corroborated these findings with distinct immune target upregulation in low-to-intermediate inflamed tumors and significant associations between IHC-detected markers and T-cell inflammation score across most markers. In the clinical trial, 20/23 (87%) of eligible patients were successfully allocated and started on treatment within the 12-day window, meeting the primary endpoint. The safety profile appeared to generally align with those reported for the individual combinations from other trials. No treatment responses occurred. Most patients were allocated to the cabiralizumab treatment arm. Conclusions Actualization of a patient-specific I-O combination treatment selection strategy is feasible, however, determination of de novo integral biomarker thresholds of novel I-O targets to facilitate effective treatment of PD-1-refractory cancer remains fraught. These data emphasize the difficulty of integral biomarker development for I-O in translating from immunotherapy treatment-naïve biospecimens to the selection of patients in the PD-1-refractory state. Trial registration number NCT03335540 .

Background Fixation of the first tarsometatarsal joint has been known to improve the rigidity of the construct and reduce angular deformity in surgical correction of hallux valgus. Although some authors employ an intercuneiform screw between the medial and intermediate cuneiform, others provide fixation using a suspensory fixation device between the metatarsals. We aimed to investigate whether there was a difference in clinical outcomes between the suspensory fixation device and the intermediate cuneiform screw. Methods This was a retrospective comparative study between patients who underwent the modified Lapidus procedure (or 1TMT arthrodesis) using the suture button fixation (MT1-2 SB) and the first metatarsal intermediate cuneiform screw fixation (MT1C2 screw) between January 2015 and January 2023. Demographic variables (age, sex, and body mass index) and outcome variables including union rate, hardware removal, recurrence rate, and revision rate were collected. Patients were matched in a 1:1 fashion for age and body mass index. The radiographic variables are first metatarsal declination angle, intermetatarsal angle (IMA), hallux valgus angle (HVA), and sesamoid station. Results We had a total of 40 feet in the MT1-2 SB cohort and 40 in the MT1C2 screw cohort. Although there were no differences found in the preoperative measures of angular deformity, we discovered that suture button fixation was associated with a better average postoperative IMA when compared to intermediate cuneiform screw fixation. However, both techniques offered a similar magnitude of initial correction for IMA and HVA. Furthermore, there were no differences in loss of angular correction at an average follow-up period of 2.36 ± 1.91 years in the MT1-2 SB cohort and 2.35 ± 1.62 years in the MT1C2. Conclusion Suture button fixation and first metatarsal intermediate cuneiform screw fixation demonstrate similar union rates, deformity correction, and maintenance of correction at early follow-up.

BACKGROUND In hypertrophic cardiomyopathy (HCM), the mechanisms through which pathogenic sarcomere variants (G+) lead to left ventricular hypertrophy (LVH) are not understood. METHODS VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) was a multicenter, double-blind, placebo-controlled randomized trial testing valsartan’s ability to attenuate phenotypic progression in early sarcomeric (G+LVH+) and subclinical HCM (G+LVH-). The outcome was a composite Z score reflecting cardiac remodeling from baseline to year 2 (end of study). Baseline and year 2 blood samples were used to quantify 276 proteins using a proximity extension assay (Olink, Sweden). We explored relative differences in protein abundance between early and subclinical HCM at baseline. In addition, we compared proteomic changes between baseline and year 2 in subclinical HCM participants who experienced phenotypic conversion to early HCM (converters) versus nonconverters; early HCM participants receiving valsartan versus placebo; and in association with changes in Z score. Comparisons were made using t test/Mann-Whitney U test, linear mixed models, and generalized linear models, correcting for multiple testing. RESULTS Circulating proteins were analyzed in 192 participants (32 subclinical and 160 early HCM [81 allocated to valsartan]). NT-proBNP (N-terminal pro-B-type natriuretic peptide) differentiated early from subclinical HCM and tracked with phenotypic progression in early HCM (1-unit worsening in Z score associated with a 27% increase in NT-proBNP [95% CI, 17–37%]). Some extracellular matrix remodeling proteins showed higher abundance (tissue-type plasminogen activator) in early compared with subclinical HCM or tracked with disease progression (decorin) in early HCM. Growth factors had higher relative abundance in early HCM (fibroblast growth factor-21). While no individual protein was able to distinguish converters from nonconverters, multiprotein the panels lipocalin 2, lectin-like oxidized low-density lipoprotein receptor 1, and either NT-proBNP or interleukin-17 receptor A, could distinguish these groups. CONCLUSIONS NT-proBNP was the most robust protein to track progression. Studying pathways involving growth factors and extracellular matrix remodeling may yield additional insights into mechanisms behind disease progression. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01912534.

Background: The COVID-19 (coronavirus disease 2019) pandemic has presented a serious challenge to nephrologists, since it can lead to severe kidney injury in the form of acute tubular necrosis, with many patients requiring renal replacement therapy. This is predominantly seen in people who develop severe respiratory manifestations like ARDS (acute respiratory distress syndrome) from the viral infection, a cytokine storm or septic shock with unstable hemodynamics. It also presents with various glomerular injuries, mainly collapsing glomerulopathy in high-risk APOL1 (Apolipoprotein L1) genotype patients, thrombotic microangiopathy-related renal failure due to hyper coagulopathy and occasionally pauci-immune glomerulonephritis due to immune dysregulation. All the glomerular disorders that are caused by COVID-19 infection have been described under the designation COVAN (COVID-19-associated nephropathy). Proteinuria is a predominant presentation in glomerular disorders. Gross hematuria and AKI without any respiratory symptoms from COVID-19 infection have not been described so far in the literature. We are presenting one such rare case here. Methods: We have encountered a rare case of gross hematuria and severe acute renal failure. His serological work up was negative for all autoimmune etiologies that can cause Glomerulonephritis. He was found to have infection-related crescentic glomerulonephritis due to active COVID-19 infections discovered via kidney biopsy. He tested positive for SARS-CoV-2 but didn’t have any clinical respiratory symptoms. He has responded well to treatment with a steroid taper and antiviral medication (Remdesivir). This is a very rare renal manifestation of COVID-19 infection. Results: COVID-19 infection can result in crescentic glomerulonephritis. This can be diagnosed by kidney biopsy which shows extensive c3 deposits, tubuloreticular inclusion bodies along with crescentic lesions. This responds to treatment with steroids and Antiviral agents. Conclusions: Crescentic Glomerulonephritis should be considered as a possible etiology for severe acute kidney injury with hematuria in patients with active covid-19 infection without any respiratory symptoms. Kidney biopsy helps in diagnosing it and responds to treatment with steroids and antivirals.

PURPOSE Despite varying treatment responses and vastly different clinicopathologic characteristics, invasive lobular carcinoma (ILC) is treated similar to other subtypes of breast cancer. Serial personalized and tumor-informed, circulating tumor DNA (ctDNA) analysis may enable real-time treatment monitoring in metastatic ILC (mILC). METHODS In this retrospective analysis of real-world data, we analyzed ctDNA longitudinally in 66 patients with mILC using a clinically validated, personalized, tumor-informed 16-plex polymerase chain reaction-next generation sequencing assay (Signatera). We evaluated the predictive value on survival of a single ctDNA test result and correlated ctDNA detection rates and on-treatment ctDNA dynamics with disease status. RESULTS A total of 355 plasma samples were analyzed from 66 patients with mILC (median age at diagnosis, 62.6 years [range, 32.2-79.7 years]). On treatment, ctDNA dynamics correlated well with clinical response to treatment as assessed by imaging. Ninety-two percent (11 of 12) of patients with either ctDNA decrease (6 of 6) or no change in ctDNA levels (5 of 6) while on treatment showed clinical benefit from their prescribed regimen, whereas only 31% (4 of 13) of patients who showed an increase in their ctDNA had a clinical benefit on imaging. Finally, patients with a positive ctDNA test showed a greater probability of death compared with those with negative results, and the positive predictive value of ctDNA testing continued to increase exponentially with each positive result. Similarly, a negative ctDNA result was associated with 97% overall survival at 6 months and remained high (approximately 90%) at the 12-month follow-up. CONCLUSION Serial ctDNA testing in patients with mILC is feasible and may enable personalized surveillance and real-time therapeutic monitoring.

Non-Langerhans cell histiocytoses are a diverse group of histiocytic diseases. Different entities are defined based on clinical, histopathologic, and/or molecular characteristics. This study aimed to define NTRK-rearranged histiocytosis. Through international collaboration, we investigated 50 cases of histiocytosis with pan-tropomyosin receptor kinase (pan-TRK) expression and/or in-frame NTRK rearrangement. We also analyzed 45 control xanthogranulomas by pan-TRK immunohistochemistry and targeted RNA sequencing. Slides were centrally reviewed; clinical and molecular data were collected. The 50 cases comprised 30 children and 20 adults, with a median age of 11.5 years (range 0-73 years) and a male predominance (64%). Most patients (88%) had disease limited to the skin, including a single skin nodule in 41 patients and multiple skin lesions in 3 others. Four newborns presented with skin lesions, hepatomegaly, and thrombocytopenia requiring transfusions. The 2 remaining patients had life-threatening lesions of the brain or bronchus. All cases displayed xanthogranuloma histology, often including foamy histiocytes and Touton giant cells. Histiocytes stained positive for pan-TRK in 50/50 cases, whereas all 45 control xanthogranulomas without in-frame NTRK fusions stained negative. NTRK1 fusion partners included IRF2BP2 (23/46), TPM3 (12/46), SQSTM1 (3/46), PRDX1 (3/46), NPM1 (2/46), LMNA (2/46) and ARHGEF2 (1/46). Clinical outcomes were favorable, including spontaneous disease regression in 3/4 newborns with systemic disease, and rapid clinical response in both patients with a brain or bronchial tumor treated with the TRK inhibitor larotrectinib. This study advances the molecular characterization of histiocytoses and may guide the diagnosis and personalized treatment of patients.

Background Current methods are insufficient alone for outbreak detection in hospitals. Real-time genomic surveillance offers the potential to detect otherwise unidentified outbreaks. We initiated and evaluated the Enhanced Detection System for Healthcare-associated Transmission (EDS-HAT), a real-time genomic surveillance program for outbreak detection and mitigation. Methods This study was conducted at UPMC Presbyterian Hospital from November 2021 to October 2023. Whole genome sequencing (WGS) was performed weekly on healthcare-associated clinical bacterial isolates to identify otherwise undetected outbreaks. IP&C interventions were implemented in real-time based on identified transmission. A clinical and economic impact analysis was conducted to estimate infections avoided and net cost savings. Results There were 3921 bacterial isolates from patient healthcare-associated infections that underwent WGS, of which 476 (12.1%) clustered into 172 outbreaks (size 2–16 patients). Of the outbreak isolates, 292 (61.3%) had an identified epidemiological link. Among the outbreaks with interventions, 95.6% showed no further transmission on the intervened transmission route. The impact analysis estimated that, over the 2-year period, 62 infections and 4.8 deaths were avoided, with gross cost savings of $1,011,146, and net savings of$695,706, which translates to a 3.2-fold return on investment. Probabilistic sensitivity analysis showed EDS-HAT was cost saving and more effective in 98% of simulations. Conclusions Real-time genomic surveillance enabled the rapid detection and control of outbreaks in our hospital and resulted in patient and economic benefits. This study demonstrates the feasibility and effectiveness of integrating genomic surveillance into routine infection prevention practice, offering a paradigm shift in healthcare outbreak detection and control.

Objective Compare outcomes, stratified by frailty, of patients with eight common conditions with plausible operative and nonoperative management strategies. Summary Background Data A surgical pause, evaluating potential adverse outcomes among frail patients, improves postoperative outcomes; however, the outcomes among patients opting for nonoperative management are unknown. Methods In an observational cohort study across a multi-hospital healthcare system including adults presenting to outpatient surgical clinics (2016-2023) for evaluation of eight conditions feasibly managed operatively or nonoperatively as defined by modified Delphi consensus. In a landmarked analysis, we compared 2-year survival by management strategies across frailty categories (robust, normal, frail, very frail) as defined by the Risk Analysis Index (RAI). Secondarily we compared 365-day hospital free days (HFD-365), postoperative length of stay, and discharge disposition. Results Among 49,169 patients (mean±SD age, 60.4±14.6 y; 54.6% female), operative management was associated with lower observed and adjusted mortality (1.3% vs 2.5%; aHR=0.55 [95% CI, 0.47-0.66], P <0.0001) overall and among all frailty categories expect the very frail (8.1% vs 12.1%, P =0.1). Additionally, operative management was associated with fewer HFD-365 again overall which was specifically prominent among the very frail (median 365 [IQR, 358-365] vs 361 days [IQR, 357-363], P <0.0001). Postoperatively, frailty portended more protracted recoveries with greater postoperative lengths of stay (1.7±2.6 vs 1.2±2.1) days, P< 0.0001) and fewer discharges home (370 [85.1%] vs 5,087 [91.8%], P< 0.0001; odds ratio=2.0 [95%CI 1.5-2.6]). Conclusions Considering the protracted postoperative recovery of very frail patients, nonoperative management might be the preferred treatment option for those presenting with these eight clinical conditions.

Group medical visits (GMVs) are effective in addressing care gaps for chronic diseases and patient education on healthy lifestyle interventions. This quality improvement project modified a previously piloted sleep and stress management GMV program, implemented the enhanced program, then evaluated its efficacy through pre- and post-surveys. Patients self-identified or were identified by a provider as having poor stress management skills, generalized anxiety disorders, insomnia, and/or poor sleep habits. The virtual GMV series compromised four 90-minute, biweekly visits from April to May 2024. Sleep was measured via the Pittsburgh Sleep Quality Index (PSQI) and stress with the Perceived Stress Scale (PSS). Twenty-two patients were initially enrolled, eight dropped out, four did not attend any visits, and one attended only one visit without completing surveys. Surveys included demographic questions, the PSQI, the PSS, and were completed before the first visit and after the last visit. The final sample included ten participants, and the majority (90%) attended 3 or 4 GMVs. The mean age (SD) was 53.10 (17.36) years, the majority were female (90%), and worked full-time (60%). Participants who attended 2-4 GMVs experienced a statistically significant increase in sleep quality; however, there was no significant improvement in perceived stress.

Background The use of balloon guide catheter (BGC) has been associated with better reperfusion and clinical outcomes in mechanical thrombectomy (MT) for large vessel occlusion stroke. However, the impact of BGC on angiographic and clinical outcomes in patients with distal medium vessel occlusion (DMVO) strokes undergoing MT has not been extensively investigated. Methods This is a retrospective analysis of a prospectively collected database from 14 comprehensive stroke centers in the United States and Europe. Patients with anterior circulation DMVO due to middle cerebral artery (MCA) M3/M4 or anterior cerebral artery (ACA) A1/A2-3 were included. The cohort was divided into BGC and non-BGC groups. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) were used for comparison. The primary outcome was first pass effect (FPE) defined as modified treatment in cerebral infarction (mTICI) grade 2C/3 after single device pass. Results Among 199 patients who were eligible for analysis, 81 (40.7%) were female. The median age was 69 (60-81) years, and National Institutes of Health Stroke Scale score was 13 (7–18). The BGC group (n=73) had higher rates of FPE (53.4% vs 13.7%; IPTW aOR 5.63, 95%CI (2.43 to 13.10), P<0.001) compared with the non-BGC group (n=126). The BGC group had higher rates of modified Rankin Scale (mRS) 0-1 (42.9% vs 27.1%; IPTW aOR 2.78, 95% CI (1.10 to 7.07), P=0.031), mRS 0-2 (60.3% vs 41.5%; IPTW aOR 4.31, 95% CI (1.66 to 11.19), P=0.003), and lower rates of mortality at 90-days (12.7% vs 25.4%; IPTW aOR 0.32, 95% CI (0.11 to 0.98), P=0.047) compared with the non-BGC group. The rates of successful reperfusion at the end of the procedure and symptomatic intracerebral hemorrhage were comparable between both groups. Conclusion The present study suggests that the use of BGC in DMVO undergoing MT may be associated with improved angiographic and clinical outcomes with no safety concerns. Prospective studies are warranted.

Myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) classification requires integration of mutational and cytogenetic data. MDS with biallelic TP53 inactivation (biTP53) is an established category, and MDS and MDS/MPN with biallelic TET2 (biTET2) inactivation is an emerging one. Biallelic genetic inactivation is established by both a mutation and copy loss or copy-neutral loss of heterozygosity (CNLOH) of the other allele, or it can be inferred by identifying multiple or single mutations at a sufficiently high variant allele fraction (VAF). The purpose of this study was to determine whether CNLOH genotyping data is needed to assign patients to biTP53 or biTET2 categories. We studied 157 patients with MDS or MDS/MPN who had sequencing, karyotype, and microarray performed at our institution and assigned patients to biTP53 and biTET2 categories using thresholds established in prior studies. We identified 24 biTP53 and 27 biTET2 patients. In the biTP53 group, 8 patients had > 1 mutation, 9 had a single mutation with 17p loss identified by karyotype and microarray, 2 had a single mutation with 17p loss identified only by microarray, and 3 had a single mutation and 17p CNLOH. All patients with 17p CNLOH had TP53 mutant VAF > 55%. In the biTET2 group, 24 patients had > 1 TET2 mutation with VAFs summing to > 50% and 3 had 4q CNLOH. All patients with 4q CNLOH had TET2 mutant VAF > 50%. In this cohort, CNLOH in 17p and 4q by microarray did not provide information in addition to that provided by inferring the allelic status of TP53 and TET2 using the VAF. This supports that platforms such as optical genome mapping that do not readily detect CNLOH would, in conjunction with sequencing, be adequate to identify MDS and MDS/MPN patients in the biTP53 and biTET2 categories in the great majority of cases.

There are significant gaps in care for patients with atrial fibrillation (AF) and is a need to focus on improving guideline-concordant care. Recognizing challenges encountered in pursuing sustainable quality improvement (QI) in AF care, the Heart Rhythm Society spearheaded a multifaceted collaboration grounded in the principles of Improvement Science to develop a robust platform aimed specifically at demystifying QI for clinicians and health care systems interested in closing care gaps for patients with AF. Solution development included an innovative discovery process, a design phase, piloting, and refinement, and finished with transformation into a comprehensive digital platform. End-users were engaged throughout the 4-phase process to help ensure the final platform would meet the needs of clinicians and health care systems. The result was the launch of www.CardiQ.org featuring the Atrial Fibrillation QI Framework and an extensive, curated Resource Library that has been accessed by more than 10 000 users spanning over 100 countries.