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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.

ABSTRACT Background Intrathecal opioids are widely used for postoperative analgesia in pediatric spine surgery, but optimal dosing remains undefined. We evaluated the relationship between intrathecal hydromorphone (ITH) dose, analgesia, and adverse effects in adolescents undergoing posterior spinal fusion (PSF). Methods In this single‐center, prospective, blinded dose‐escalation study using a biased‐coin up‐down sequential allocation design, patients aged 10–17 years undergoing PSF received ITH starting at 3.5 mcg kg −1 , with dose adjustments based on analgesic response (range 2.0 to 7 mcg kg −1 with a maximum of 400 mcg). The primary outcome was maximum postoperative pain within 18 h. Secondary outcomes included pain burden (area under the curve), 24‐h systemic opioid consumption (oral morphine equivalents [OME], excluding ITH), adverse effects, supplemental diazepam use, and rescue opioid use. Associations between dose and outcomes were assessed using Spearman correlation and logistic regression. Results Twenty‐seven patients completed the study. The median ITH dose received was 5.5 mcg kg −1 (IQR, 3.5–7.0), with a median absolute dose of 370 mcg (IQR, 180–400). No significant association was observed between ITH dose and maximum pain ( r = 0.16, p = 0.41), pain burden ( r = 0.32, p = 0.10), or 24‐h OME ( r = 0.13, p = 0.52). ITH dose was not significantly associated with the time to rescue opioid (HR = 1.24; 95% CI 0.68–2.25; p = 0.485) or diazepam (HR = 1.10; 95% CI 0.72–1.71; p = 0.655). Adverse respiratory events occurred at doses > 5 mcg kg −1 without improved analgesia. Conclusions Increasing ITH dose was not associated with improved analgesia or change in supplemental opioid or diazepam use. Doses > 5 mcg kg −1 were associated with adverse respiratory effects. These findings support conservative dosing strategies and underscore the need to define the minimum effective dose in pediatric populations.

Hepatic resection (HR) and liver transplantation (LT) are curative-intent treatments for hepatocellular carcinoma (HCC). Patients without cirrhosis are typically analyzed as a single group, obscuring potentially important differences between those with histologically normal liver and those with non-cirrhotic parenchymal disease. We aimed to characterize long-term outcomes following HR stratified by underlying parenchymal quality, with a contemporary LT cohort as an external benchmark. Retrospective cohort study of 662 adults undergoing curative-intent surgery for HCC at 2 tertiary centers (2010–2024). Resection patients (n=380) were stratified by non-tumor parenchymal histology into HR-Normal (n=84), HR-Diseased non-cirrhotic (n=159), and HR-Cirrhotic (n=137). A total of 282 LT recipients served as an external reference but were not entered into comparative models. Overall survival (OS) was analyzed by Kaplan–Meier and multivariable Cox regression, and recurrence by Fine–Gray competing-risks regression. Ninety-day mortality was low across resection strata (1.2%–3.2%). OS differed significantly across parenchymal groups (log-rank p =0.01), driven by superior outcomes in HR-Normal patients compared with both HR-Cirrhotic ( p =0.008) and HR-Diseased ( p =0.005). HR-Cirrhotic and HR-Diseased did not differ ( p =0.97). Five-year OS was 74.4%, 59.8% and 57.2%, respectively. On multivariable Cox regression, both cirrhosis (HR 2.03, 95% CI 1.16–3.54, p =0.01) and diseased non-cirrhotic parenchyma (HR 2.04, 95% CI 1.21–3.43, p =0.008) independently predicted death versus normal liver. Fine–Gray analysis confirmed higher recurrence risk in cirrhotic (sHR 2.09, p =0.01) and diseased non-cirrhotic (sHR 1.80, p =0.04) groups. The LT benchmark cohort achieved a 5-year OS of 82.4%. Histologically normal liver identifies a distinct HR subgroup with favorable oncologic outcomes. The conventional cirrhotic/non-cirrhotic dichotomy underestimates the prognostic impact of underlying parenchymal disease.

PURPOSE Deficient mismatch repair/microsatellite instability (dMMR, MSI-H) in biliary tract cancers (BTCs) is observed in 1%-5% of tumors. MSI-H across solid tumors has demonstrated durable response to immune checkpoint inhibitors (ICIs) regardless of the anatomic location. Here, we describe clinical outcomes and surgical conversion of MSI-H BTC treated with ICIs. Patients and Methods We conducted a multicenter, retrospective analysis of BTC patients with dMMR/MSI-H between 2017 and 2024 at Mayo Clinic, University of Michigan, and University Hospitals Seidman Cancer Center. Outcomes of interest were surgical resection rate, rate of pathologic response, 2-year overall survival (OS; time from initiation of treatment to death/last follow-up), and time to treatment discontinuation (TTD; time from initiation of treatment to cessation because of any cause). Analyses were descriptive. RESULTS Thirty patients with MSI-H BTC were identified: 19 with cholangiocarcinoma, three with gallbladder cancer, and 8 with BTC undefined. The median age at diagnosis was 61.5 years (range, 26-86). Twenty-six (86.7%) patients had advanced stage at diagnosis. Twenty-seven patients (90%) received first-line systemic therapy, and 13 (48.1%) continued onto second line. Six patients (23.1%) were restaged to resectable from advanced disease after ICI therapy and underwent resection; all remained recurrence-free at last follow-up. Of these six patients, 3 (50%) achieved a pathologic complete response. Among those receiving first-line therapy, the median TTD was 9.9 months (95% CI, 5.7 to 14.5 months) and the 2-year OS was 73% (95% CI, 56% to 94%). CONCLUSION ICI therapy in patients with MSI-H BTC demonstrated durable response and downstaged some BTC to a resectable stage. dMMR/MSI-H should be performed up-front to guide treatment decisions.

Abstract Genetic studies have significantly advanced our understanding of tauopathies, yet the genetic aetiology of Pick’s disease, a rare 3-Repeat tauopathy, remains unclear. The MAPT p.A152T variant has been identified as a risk factor for Alzheimer’s disease and progressive supranuclear palsy, but its role in Pick’s disease is unknown. In this study, we examined the prevalence of MAPT p.A152T in the largest series of neuropathologically confirmed Pick’s disease cases to date (n = 401). Through genotyping, we identified a single mutation carrier in the Pick’s disease cohort (minor allele frequency = 0.12%). We previously reported MAPT p.A152T at a 0.20% frequency in healthy controls (n = 2456), suggesting that it does not associate with 3-Repeat tauopathy risk. To further investigate the effect of the variant on MAPT transcript expression, we used bulk RNA sequencing in Alzheimer’s disease and progressive supranuclear palsy A152T mutation carriers. We did not detect significant differences in 4-Repeat tau levels, though preliminary trends may indicate more nuanced effects that need to be examined with long-read sequencing in a larger series. Overall, our study suggests that MAPT p.A152T does not increase Pick’s disease risk and may instead be linked to 4-Repeat or mixed tau pathologies, warranting further functional investigation.

Abstract Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

Abstract Carcinoid heart disease (CHD) is associated with advanced neuroendocrine tumor liver metastases (NETLM) and may preclude surgical cytoreduction. We assessed perioperative and long‐term outcomes of hepatectomy in patients with CHD. We retrospectively analyzed 311 patients undergoing cytoreductive hepatectomy for intestinal NETLM: non‐functional ( n = 163), carcinoid syndrome (CS) without CHD ( n = 110), and CHD ( n = 38), including patients undergoing pre‐hepatectomy valve replacement. CHD patients more frequently had >10 liver metastases (78%) and larger lesions (median 9.5 cm) and required major hepatectomy more often (58%). Major morbidity was higher in CHD (up to 47%), yet 90‐day mortality remained low (≤4%). Median overall survival after hepatectomy was comparable across groups (12.5 vs. 9.1 vs. 11.4 years; p = .19), including matched analyses. With optimal cardiac management, cytoreductive hepatectomy in CHD is feasible and provides long‐term survival comparable to patients without CHD.

Pharmacological plasminogen reduction enhanced liver regeneration experimentally and clinically. siRNA-induced plasminogen deficiency promoted hepatocyte proliferation after partial hepatectomy in mice, contrasting genetic deficiency models. In the HeLiX trial, tranexamic acid reduced post-hepatectomy liver failure odds, suggesting a novel therapeutic strategy.