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BACKGROUND: Anemia affects more than two billion people worldwide and is common among surgical patients. Despite growing recognition of the risks associated with preoperative anemia, we have limited understanding of the epidemiology of anemia development and recovery. METHODS: This is an observational cohort study of adults undergoing surgery at a large tertiary care medical center from August 2012 to July 2023. Hemoglobin concentrations were obtained preoperatively, during postoperative hospitalization, and through 12 months after surgery. Anemia was defined primarily using World Health Organization criteria (hemoglobin <12 g/dL in women, <13 g/dL in men) and secondarily with a gender-neutral threshold of <13 g/dL. Descriptive analyses summarize preoperative anemia prevalence, postoperative anemia prevalence and incidence, and post-hospitalization anemia recovery across demographic, clinical, and surgical features. RESULTS: 281,217 patients undergoing 423,066 procedures (51.9% among women) were included. Among those with available preoperative hemoglobin assessments (n = 308,959), 28.9% had anemia, with similar prevalence in men (29.5%) and women (28.4%) using World Health Organization (WHO) definitions, but with prevalence increasing to 51.0% in women when using the gender-neutral anemia definition. Preoperative anemia was most common in Black patients (44.0%) and in those ≥75 years (39.6%). Surgical subspecialties showed wide variation in preoperative anemia prevalence, ranging from 18.6% in spine surgery to 45.8% in vascular surgery. Among previously nonanemic patients admitted to the hospital postoperatively, 76.9% developed new postoperative anemia, with the highest incidence in cardiac surgery (97.5%). Women experienced more severe postoperative anemia than men. Overall, 81.1% of patients were anemic at hospital discharge. Recovery was gradual and incomplete: among those discharged with mild, moderate, or severe anemia, 28.5%, 51.9%, and 66.3%, respectively, remained anemic at 12 months. Among patients who were nonanemic preoperatively but developed new postoperative anemia, 29.3% remained anemic at 12 months. CONCLUSIONS: Preoperative and postoperative anemia are highly prevalent, and anemia frequently persists for months after hospitalization. Older adults, women, and Black patients bear a disproportionate burden. Despite this, anemia evaluations and treatments remain underutilized. These findings highlight substantial opportunities for patient blood management (PBM) programs to improve perioperative anemia detection, optimization, and post-discharge management.

Background: The limb symmetry index (LSI) is a measure comparing strength and functional movement between the surgical and nonsurgical limbs, used after anterior cruciate ligament reconstruction (ACLR) to guide rehabilitation and assess return-to-sport readiness. With increasing use of the quadriceps tendon autograft (QT-ACLR), limited data exist on whether the LSI score correlates with patient-reported outcome measures (PROMs). Hypothesis/Purpose: To evaluate the predictive value of postoperative strength and functional LSI tests at 3, 6, and 9 months for short-term PROMs, determine Patient Acceptable Symptom State (PASS) thresholds, and assess differences based on PASS achievement. It was hypothesized that quadriceps strength LSI score would more strongly predict 2-year PROMs than hamstring strength LSI score, and that higher 9-month isokinetic quadriceps LSI scores would be associated with higher International Knee Documentation Committee (IKDC) and Lysholm scores. Study Design: Case series; Level of evidence, 4. Methods: Patients undergoing primary QT-ACLR from 2021 to 2024 with LSI testing during rehabilitation (isometric and isokinetic lower extremity strength, Y-Balance, hop testing) and no revision or additional knee surgery were included. The LSI score was assessed at 3, 6, and 9 months, and PROMs, including Lysholm and IKDC scores, were collected at a mean follow-up of 2.0 ± 0.7 years. Multivariable linear regression was used to evaluate associations between LSI measures and PROMs after adjusting for age, sex, and body mass index (BMI). Receiver operating characteristic analysis was used to determine PASS thresholds. Results: A total of 100 knees in 100 patients (mean age, 25.3 ± 11.2 years; BMI, 25.9 ± 6.5 kg/m 2 ; 52% male) were included. Quadriceps and hamstring strength and functional performance progressively improved from 3 to 9 months, with the LSI score reaching 77% to 81% for quadriceps strength and 98% to 100% for hamstring strength by 9 months postoperatively. At a mean follow-up of 2.0 ± 0.7 years, the mean satisfaction score was 8.4 of 10, the Lysholm score was 90.7, and the IKDC score was 77.8. Linear regression, adjusted for age, sex, and BMI, demonstrated that 3-month isometric quadriceps LSI score had a strong effect on IKDC score, explaining substantial variance (β = 3.9; adjusted R 2 [Adj R 2 ] = 0.36; P < .03); 6-month isokinetic quadriceps and hamstrings showed moderate but significant effects (β = 2.9-3.7; Adj R 2 = 0.13-0.17; P < .05) on IKDC score; and 9-month fast quadriceps had a strong effect explaining substantial variance in Lysholm and IKDC scores (β = 3.9-4.7; Adj R 2 = 0.34-0.35; P ≤ .003). Lysholm and IKDC scores correlated with satisfaction and accurately discriminated PASS thresholds (area under the curve, 0.927-0.937; P < .001). Patients achieving the IKDC PASS demonstrated higher LSI scores across time points and all PROMs. Conclusion: After QT-ACLR, strength-associated LSIs were independently associated with PROMs at a mean 2-year follow-up, after adjusting for age, sex, and BMI. Early isometric quadriceps strength at 3 months predicted higher 2-year IKDC scores, with PASS achievers generally attaining a 60% to 70% LSI score by 3 months. Isokinetic quadriceps strength at 9 months predicted both IKDC and Lysholm scores. These findings highlight the importance of early quadriceps strength recovery and the value of LSI measures in predicting PROMs and informing early rehabilitation.

Objective To characterize regional brain atrophy patterns, evaluate their association with regional leucine‐rich glioma‐inactivated‐1 ( LGI1 ) gene expression, and identify clinical predictors of hippocampal atrophy in LGI1 autoimmune encephalitis (AE). Methods This study compared regional brain volumes in LGI1‐AE patients versus age‐ and sex‐matched healthy controls (HC) and Alzheimer's disease (AD) patients. LGI1 gene expression was derived from the Allen Human Brain Atlas. Multivariable linear regression and generalized linear models were utilized. Results A total of 55 LGI1‐AE patients were included. Median age was 68 years (IQR 62.5–74.2 years) at volumetric analysis, after 19 months (IQR 11–45 months) from symptom onset. Compared with HC ( n = 55) and AD patients ( n = 55), LGI1‐AE patients had greater regional atrophy of the hippocampus, insula, caudate, and putamen ( p < 0.002). Longitudinal analyses demonstrated hippocampal and pallidal atrophy after covariate adjustment. Among those who did not fulfill limbic encephalitis criteria and/or had non‐lesional magnetic resonance imaging, limbic and striatal atrophy were identified compared with HC ( p < 0.01). Regions with the greatest differential atrophy corresponded to higher LGI1 gene expression (Spearman ρ = 0.7, p = 0.005). Severe cognitive deficits at diagnosis ( β = −0.56; p = 0.002) and longer disease duration ( β = −0.01; p = 0.001) independently predicted total hippocampal volume ( R 2 = 0.31). Interpretation LGI1‐AE demonstrates a distinct pattern of limbic and striatal atrophy that differs from AD and aligns with regional LGI1 expression, supporting a model of selective network vulnerability. Greater baseline cognitive impairment and longer disease duration independently associated with hippocampal atrophy, underscoring the potential importance of early diagnosis and treatment to limit structural brain injury. ANN NEUROL 2026

ABSTRACT We characterize copine‐4 (CPNE4)‐IgG and report clinical associations. Among 844 samples with unclassified neural IgGs identified by mouse‐brain indirect immunofluorescence assay over 2 years, 5 samples (serum, 3; CSF, 2) from 3 patients produced a distinctive cerebrum‐restricted synaptic pattern. Protein microarray disclosed CPNE4 “top hit” in those 3 patients; specificity was confirmed by 3 CPNE4‐specific assays (confocal IFA, cell‐based, and western blot). Median onset age was 67 years (range 60–68); all had encephalitis: a brainstem syndrome during immune checkpoint inhibitor therapy for lung cancer (2) and anti‐NMDA‐receptor encephalitis accompanied by neuroectoderm‐lineage cancer (1). To date, CPNE4‐IgG has paraneoplastic encephalitis significance.

ABSTRACT Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is a serious complication which may necessitate temporary mechanical support in refractory cases. Here we describe a 63‐year‐old man with end‐stage ischemic cardiomyopathy and severe combined pre‐ and post‐capillary pulmonary hypertension who developed persistent RV failure post‐LVAD. He was intolerant to speed optimization secondary to preload mismatch, and invasive hemodynamics confirmed LV underfilling. An Impella RP Flex was placed for RV support, and biventricular (BiV) pressure‐volume (PV) loops were utilized to ascertain hemodynamic response. With increasing Impella RP Flex support, left ventricular end‐diastolic volume increased with subsequent improvement in left ventricular performance. This case represents the first reported use of BiV PV loop analysis to characterize the physiological effects of Impella RP Flex in a patient with LVAD support, underscoring its utility in understanding device‐ventricular interactions.

Background The Impella 5.5 is employed to provide left ventricular support in cardiogenic shock. Mechanistic understanding of biventricular relationships is essential in device optimization. Using a porcine model of acute myocardial infarction in tandem with pressure–volume loops, this study aimed to understand the impact of Impella 5.5 on biventricular hemodynamics. Methods Using Domestic Yorkshire pigs, an Impella 5.5 was inserted percutaneously under fluoroscopic guidance via carotid/aortic access and an acute myocardial infarction was created. Biventricular pressure–volume loops and derived parameters were generated for each level of support before (n=6) and after myocardial infarction (n=6). Results With increasing Impella 5.5 support, left ventricular pressure–volume loops shifted left, and right ventricular (RV) loops shifted right. In a healthy porcine heart, the RV adequately compensated for increased preload from the device, demonstrated by increased RV performance at higher P levels. After myocardial infarction, pigs were unable to tolerate speeds beyond P7 from diminished RV stroke volume reserve compared to healthy hearts. Median RV stroke volume percentage change from P1 to P9 before myocardial infarction was from 5.7% (interquartile range, −15.1% to 9.7%) to 50.6% (interquartile range, −11.6% to 60.2; P <0.05), and following acute myocardial infarction from P1 to P7 was from 3.9% (interquartile range, −2.7 to 78.4) to 13.4% (interquartile range, −8.9% to 147.2; P =0.94). Conclusions Impella 5.5 speed modulation highlights significant interventricular interactions with opposing biventricular trends. While the heart can mount an improvement in RV stroke volume with increasing Impella 5.5 support, these data suggest an attenuated response following acute myocardial infarction, which may relate to inadequate response to increased preload needed by the device after infarction affecting the interventricular septum.

Abstract Objective To evaluate whether systemic hormone replacement therapy (HRT) influences recurrence outcomes in postmenopausal patients with idiopathic subglottic stenosis (iSGS). Study Design Retrospective cohort study. Setting Tertiary academic medical center. Methods Postmenopausal women (≥50 years) with iSGS who underwent laser‐wedge excision between 2002 and 2024 were included. Patients were categorized by systemic HRT exposure (oral estrogen, progesterone, combined estrogen‐progesterone, or transdermal estrogen) at or before their first surgery. Overdispersion was assessed for all Poisson models; given significant overdispersion, negative binomial regression with a log‐offset for follow‐up time was used as the primary model. Surgery‐free intervals were analyzed using linear mixed models, and time to first recurrence using Cox regression. Models were adjusted for age, body mass index (BMI), parity, oophorectomy, follow‐up length, surgery type, and serial intralesional steroid injections (SILSI) use. Results Among 125 patients, 96 had never used HRT (Never HRT) and 29 used HRT, including 19 actively using HRT at presentation (Current HRT), 5 past users, and 5 subsequent users. The HRT versus Never‐HRT recurrence rate comparison was not significant (adjusted incidence rate ratio [IRR] = 0.81, 95% CI: 0.48‐1.37, P = .422). However, Current HRT use was associated with a 53% lower adjusted recurrence rate versus Never‐HRT use (adjusted IRR = 0.47, 95% CI: 0.25, 0.89, P = .0203). Surgery‐free intervals and time to first recurrence trended longer in Current HRT users but were not statistically significant. Conclusion Current HRT use at presentation was associated with significantly fewer recurrences in postmenopausal iSGS patients. These findings may inform individualized, shared decision‐making regarding HRT use in this population. Level of Evidence 3.

Objective To evaluate the efficacy of cytokine‐directed therapies in VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory somatic) syndrome using previously proposed treatment response criteria. Methods All patients with genetically confirmed VEXAS syndrome who received targeted therapies with JAK inhibitors (JAKi), tumor necrosis factor α inhibitors (TNFαi), or interleukin‐1 (IL‐1) or IL‐6 inhibitors were identified. Clinical and biochemical data were recorded for patients at time of targeted therapy initiation, and at 3‐, 6‐, and 12‐month follow‐up time points. Treatment response was labeled as complete response (CR; normalization of C‐reactive protein [CRP], prednisone <10 mg/day, and resolution of disease activity), partial response (PR; >50% improvement in CRP, >50% prednisone dose reduction, improvement or resolution of disease features), treatment failure (TF; worsening CRP, increasing prednisone, worsening of disease features), or no response (not meeting criteria for CR, PR, or TF). Results Overall, 52 patients received an IL‐1i, IL‐6i, or JAKi therapy. At six‐month follow‐up, 3 of 19 IL‐6i patients experienced CR, 4 of 19 experienced PR, and 7 of 19 experienced TF. 2 of 17 patients receiving JAKi experienced CR, 3 of 17 experienced PR, and 6 of 17 experienced TF. No patients receiving IL‐1i or TNFαi experienced CR, and only 1 of 5 IL‐1i patients experienced PR. Among those still receiving biologic therapy at 12 months, only 1 of 11 receiving IL‐6i and 0 of 7 receiving JAKi experienced CR. Conclusion IL‐6i and JAKi therapies demonstrated limited, unsustained efficacy for management of VEXAS syndrome. IL‐1i and TNFαi therapies were not efficacious. Useful application of previously reported treatment response criteria was demonstrated, but future incorporation of hematologic parameters may be beneficial.