Citations

BACKGROUND: Rising health care costs necessitate a reassessment of routine preoperative practices. Despite low transfusion rates in elective colorectal operations, many hospitals continue to perform routine preoperative type and screen testing. OBJECTIVE: To assess perioperative blood transfusion rates and determine preoperative and surgical factors associated with transfusions to determine whether the routine preoperative type and screen testing are necessary for elective abdominal colorectal surgeries, particularly in the setting of minimally invasive surgery. DESIGN: Retrospective cohort study. SETTINGS: Mayo Clinic, 2019–2023. PATIENTS: Adult patients undergoing elective abdominal colorectal operations. Exclusion criteria included emergent operations and nonabdominal procedures. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was the incidence of intraoperative and immediate postoperative (≤72 hours) blood product transfusion. Secondary outcomes assessed associations between transfusion rates, surgical approach, and preoperative variables. RESULTS: Among 4652 patients, 2770 underwent minimally invasive surgery and 1882 underwent open procedures. Perioperative red blood cell transfusion rates were lower in minimally invasive procedures (3.0% colectomy, 4.5% proctectomy) compared to open procedures (8.7% colectomy, 21.5% proctectomy). Open proctectomy was the strongest predictor of transfusion (OR 12.05; 95% CI, 8.94–16.26; p < 0.0001) followed by open colectomy (OR 2.59; 95% CI, 2.04–3.30; p < 0.0001). Preoperative factors including ASA class IV (OR 5.21; 95% CI, 1.09–24.82; p < 0.0382) and anemia (OR 4.14; 95% CI, 3.09–5.55; p < 0.0001) were also significantly associated with red blood cell transfusion. LIMITATIONS: The retrospective nature of the study may introduce selection bias. In addition, institutional practice patterns may limit the generalizability of findings. CONCLUSIONS: Patients undergoing elective minimally invasive colorectal surgery have very low rates of perioperative blood transfusions; thus, routine preoperative type and screen testing is likely unnecessary for this patient cohort. However, patients undergoing planned open operations, likely due to procedural complexity, and those who are ASA class IV, have preoperative anemia, or have anal cancer have higher transfusion risks and may benefit from selective testing. Implementing a risk-stratified approach based on surgical technique and patient comorbidities could potentially reduce unnecessary testing and associated health care costs. See Video Abstract. RE-TIPIFICACIÓN Y EVALUACIÓN PREOPERATORIAS: CÓMO IDENTIFICAR CUÁNDO ES NECESARIA UNA CIRUGÍA COLORRECTAL ELECTIVA ANTECEDENTES: El aumento en los costos de la atención médica exigen la reevaluación de las practicas preoperatorias de rutina. A pesar de las bajas tasas de transfusión en la cirugía colorrectal electiva, muchos hospitales continúan realizando pruebas de tipo y de cribado preoperatorios de forma rutinaria. El poresente estudio evalúa las tasas de transfusiones sanguíneas perioperatorias e identifica los factores asociados con éstas transfusiones para determinar la necesidad de pruebas de tipo y de cribado preoperatorios de forma rutinaria en cirugías colorrectales abdominales electivas. OBJETIVO: Evaluar las tasas de transfusión sanguínea perioperatoria y determinar los factores preoperatorios y quirúrgicos asociados con las transfusiones, con el fin de determinar si las pruebas de tipo y de cribado preoperatorias de forma rutinaria son necesarias en cirugías colorrectales abdominales electivas, en particular en el contexto de la cirugía mínimamente invasiva. DISEÑO: Estudio de cohortes retrospectivo. ESCENARIO: Clínica Mayo, 2019-2023. PACIENTES: Pacientes adultos sometidos a cirugías colorrectales abdominales electivas. Los criterios de exclusión incluyeron operaciones de emergencia y procedimientos no abdominales. INTERVENCIONES: Ninguna. PRINCIPALES MEDIDAS DE RESULTADOS: El resultado primario fue la incidencia de transfusión de hemoderivados intraoperatoriamente y postoperatoria inmediata (≤72 horas). Los resultados secundarios evaluaron la asociación entre las tasas de transfusión, el abordaje quirúrgico y las variables preoperatorias. RESULTADOS: De 4652 pacientes, 2770 se sometieron a cirugía mínimamente invasiva y 1882 a laparotomía. Las tasas de transfusión eritrocitaria perioperatoria fueron menores en los procedimientos mínimamente invasivos (3,0 % colectomía, 4,5 % proctectomía) que en los procedimientos abiertos (8,7 % colectomía, 21,5 % proctectomía). La proctectomía abierta fue el predictor más sólido de transfusión (OR: 12,05; IC del 95 %: 8,94-16,26; p < 0,0001), seguida de la colectomía abierta (OR: 2,59; IC del 95 %: 2,04-3,30; p < 0,0001). Los factores preoperatorios, incluyendo la clase ASA IV (OR 5,21; IC del 95 %: 1,09-24,82; p < 0,0382) y la anemia (OR 4,14; IC del 95 %: 3,09-5,55; p < 0,0001), también se asociaron significativamente con la transfusión de glóbulos rojos. LIMITACIONES: La naturaleza retrospectiva del estudio puede introducir sesgo de selección. Además, los patrones de práctica institucional pueden limitar la generalización de los hallazgos. CONCLUSIONES: Los pacientes sometidos a cirugía colorrectal mínimamente invasiva electiva tienen tasas muy bajas de transfusiones sanguíneas perioperatorias, por lo que las pruebas de detección y tipo de sangre preoperatorias de rutina probablemente sean innecesarias para esta cohorte de pacientes. Sin embargo, los pacientes sometidos a cirugías abiertas planificadas, probablemente debido a la complejidad del procedimiento, y aquellos con clase ASA IV, anemia preoperatoria o cáncer anal, tienen mayor riesgo de transfusión y podrían beneficiarse de pruebas selectivas. La implementación de un enfoque estratificado por riesgo basado en la técnica quirúrgica y las comorbilidades del paciente puede reducir las pruebas innecesarias y los costos de atención médica asociados. (Traducción—Dr. Xavier Delgadillo)

Alcohol use disorder is linked to a multitude of diseases and disorders, many of which can be diagnosed with imaging techniques such as US, CT, and MRI, enabling early detection and potentially preventing further damage and improving outcomes.

Abstract Background: mTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation can cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS. Methods: We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6 mg/week) was administered, and core ME/CFS symptoms were assessed on days 30 (T1), 60 (T2), and 90 (T3). Plasma levels of autophagy metabolites, such as pSer258-ATG13 and BECLIN-1, were measured and correlated with clinical outcomes, specifically MFI. Results: Rapamycin (6 mg/week) was tolerated without any SAEs. Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, and OI, along with improvements in MFI fatigue domains and SF-36 aspects. High levels of BECLIN-1 were detected in T3. Plasma pSer258-ATG13 levels were strongly downregulated at T1. Spearman’s correlation analysis indicated an association between autophagy impairment and reduced activity. Conclusions: Low-dose rapamycin effectively reduced PEM and other key symptoms in patients with ME/CFS, as measured by BAS, SSS, MFI, and SF-36. Future studies should encompass dose optimization and develop a diagnostic tool to identify responders with mTOR-mediated autophagy disruption.

Abstract Objective To examine the effectiveness of treatment strategies for medication‐overuse headache (MOH) in children and adolescents. Background There are no guidelines for the treatment of adult or pediatric patients with MOH. However, research pertaining to MOH in adults is far outpacing research in children and adolescents. Methods A systematic review of evidence on treatment for MOH in children and adolescents was performed via PubMed, Embase, Web of Science, PsycINFO, and Cochrane from database inception to October 2024 for articles with the subject headings and keywords for MOH and pediatric, children, and/or adolescent. Inclusion criteria were: (i) randomized controlled trials and retrospective and prospective observational studies, (ii) children and adolescents aged <18 years with chronic headaches and with medication overuse (MO) or MOH, and (iii) interventions addressing MO or MOH, including pharmacologic and behavioral interventions. At least two independent reviewers screened citations and full‐text articles independently. Results A total of 16 studies (one randomized control trial, six prospective observational studies and nine retrospective observational studies) were identified as meeting final inclusion criteria, resulting in 7978 total participants with a subset of those having MO, MOH or probable MOH. Participants ranged in mean age from 10 to 14.7 years, with 7.1%–46.2% male participants. All the studies recruited patients from an outpatient setting. Interventions used in the studies included withdrawal of the overused acute medication, initiation of preventive medication, patient education, physiotherapy and psychological treatment, and motivational interviewing. Multimodal therapy was studied more than single therapeutic intervention. There was vast heterogeneity across the studies, including study design, diagnostic criteria, intervention type, and outcomes. Conclusion From the data available, there does not seem to be a singular superior treatment approach. Accordingly, the most appropriate treatment modality will need to be tailored to the patient and their caregivers. Further research is required regarding management of MOH in children and adolescents.

TPS9607 Background: The majority of 100,000 annual new U.S. cases of mel consist of localized early-stage disease that undergo wide local excision (WLE) +/- SLN biopsy (SLNB). The tumor draining lymph node is the initial site of immune response including formation of tumor mediated immune suppression and pre-metastatic niches. SLN positivity is a key prognostic factor in early stage mel. Thus, the SLN is a target for local immune intervention to boost the antitumor response. Vusolimogene oderparepvec (RP1) is an intratumorally administered oncolytic immunotherapy with unique potential for neo-adjuvant therapeutic application. RP1 is constructed from a high potency HSV1 strain (RH018A) modified to replicate selectively in tumors (deletion of neurovirulence factors ICP34.5 and ICP47). RP1 encodes GM-CSF and a fusogenic GALV-GP R- protein to maximize oncolytic potency and induce immunogenic cell death. Preclinical and clinical data demonstrate robust antitumor efficacy (including non-injected lesions) of RP1 alone and in combination with checkpoint inhibitors in advanced mel. This trial addresses a crucial gap in understanding the impact of RP1 on SLN dynamics and preventing disease recurrence in high-risk patients (pts). We hypothesize that in pts with high risk, clinically node negative mel (pT3b-T4b), RP1 will reduce rates of SLN positivity as compared to a historic control by favorably reshaping the immune landscape of the primary tumor, SLN, and the peripheral blood. Methods: This is an investigator-initiated, single arm phase 1/2 trial (NCT06216938) designed to assess efficacy and safety of neo-adjuvant RP1 in high-risk, clinically node-negative, non-uveal mel. Eligibility criteria: pT3b, T4a, or T4b non-uveal mel with visible residual tumor or positive biopsy margins, ECOG ≤1, and no prior oncolytic virus therapy. Pts receive 3 doses of neo-adjuvant RP1 (10e6 PFU day 1, 10e7 PFU on days 15 and 21), injected at the primary tumor site followed by standard WLE and SLNB within 35 days of dose 1. Biopsy of residual tumor or archival tumor tissue is obtained pre-RP1 and archival tissue from WLE and SLNB is obtained post-RP1. Blood samples are obtained with each RP1 dose and 3 months post-therapy. Pts are followed for 3 years. Primary endpoint: rate of SLN positivity in the overall cohort. Secondary endpoints: treatment related adverse events (per CTCAE), recurrence free survival, and overall survival. Exploratory endpoints: immunophenotype and microenvironment of the primary tumor, SLN and peripheral blood pre- and post- RP1 (via IHC, IF, and flow cytometry). The observed rate of SLN positivity will be compared to the predicted rate (Melanoma Institute of Australia Prediction Tool for SLN metastatic risk) with a one-sided, one-sample proportion test. Kaplan-Meier estimates will be provided for survival endpoints. The trial is active with 13 of 25 pts enrolled in January 2025. Clinical trial information: NCT06216938 .

TPS615 Background: The TAILORx and RxPONDER trials demonstrated that RS identifies many postmenopausal pts with node-neg and node-pos BC and RS ≤25, who do not benefit from addition of ACT to endocrine therapy (ET). Both trials also showed that certain subsets of premenopausal pts (node-neg/high clinical risk/RS 16-20, node-neg/RS 21-25, and node-pos/RS ≤25) benefited from adding ACT to ET. Most premenopausal pts in these trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR+/HER2- BC in the SOFT/TEXT trials, many questioned whether all or part of the observed ACT benefit in the TAILORx/RxPONDER trials may have been the result of chemotherapy-induced OFS. To address this question, we developed OFSET, a phase III, multicenter clinical trial comparing OFS+ET v ACT+OFS+ET. Methods: We hypothesize that addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage BC pts with HR+/HER2- tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival, overall survival, distant recurrence-free interval, breast cancer-free interval, and health-related quality of life (HRQOL). Pts must be node-neg with RS 16-20 (plus high clinical risk), or RS 21-25, or have 1-3 positive nodes with RS ≤25. Stratification is by nodal status/RS status (pN0 RS 16-25 v pN1 RS 0-15 and pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39 v ≥40). Pts are randomized after surgery to either OFS+ET or ACT+OFS+ET v ET is an aromatase inhibitor (AI). Choice is per investigator discretion; tamoxifen is allowed if AI is not tolerated or if OFS is incomplete. Radiotherapy will be administered per investigator discretion per protocol guidelines. The HRQOL sub-study will assess differences in severe menopausal symptoms, measured by the FACT ESS-19 score between arms, as well as increased pain severity (PROMIS). Blood and tumor specimens will be collected for future research. Accrual of 3,960 pts is anticipated to be completed in 7 yrs, 7 mos. Per NSABP B-28 and RxPONDER data, 5yr IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Based on TAILORx data, 5yr IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of pts to be pN0 and 44% pN1, and a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET v OFS+ET, with one-sided α of 0.025 and 80% power, will require 380 IBCFS events, expected to occur~11 yrs after study initiation. OFSETwas activated Aug 2023. As of 1-6-25, accrual is: 188/3,960. NCT #: NCT05879926. Support: U10CA180868, -80822, UG1CA189867, U24CA196067. Clinical trial information: NCT05879926 .

Background and Objectives The genetic basis of adult-onset multiple sclerosis (MS) is well-studied, but less is known about pediatric-onset MS (pedMS), comprising approximately 5% of all MS onsets. Mendelian randomization (MR) studies have demonstrated evidence for a causal association between MS and both 25-hydroxyvitamin D [25(OH)D] serum levels and genetic variation related to vitamin D receptor (VDR) binding. The objective was to identify whether VDR binding variants (VDR-BVs) previously implicated in adult-onset MS were associated with pedMS using genetic instrumental variables (GIVs). Methods Using previously identified VDR-BVs to construct individual GIVs with two-sample MR, we investigated associations with pedMS in 725 cases and 592 controls of European ancestry from the US Network of Pediatric MS Centers. Associations between each VDR-BV and pedMS were estimated using logistic regression adjusting for the first three genome-wide principal components. A significant interaction between a VDR-BV and 25(OH)D GIV provided evidence for a causal association unbiased by pleiotropy. Results One VDR-BV, rs2531804, previously associated with adult-onset MS, was also significantly associated with pedMS after multiple testing correction. Discussion This study is the first to use VDR-BVs from previous MR studies to demonstrate causal differences in VDR binding at a locus contributing to pedMS susceptibility.

Increased intracranial pressure (ICP) is increasingly recognized in myelin oligodendrocyte glycoprotein antibody-associated disease but has not been systematically explored in other demyelinating conditions. This cross-sectional study examines the features of raised ICP in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Lumbar puncture opening pressure (OP) done within 30 days of an attack was identified in 41 NMOSD patients and 37 MS patients. Raised OP was present in 7 (17.1%) NMOSD patients and 4 (10.8%) MS patients who were largely asymptomatic, partially explained by obesity, and did not require ICP lowering medications beyond acute treatment with corticosteroids.

BACKGROUND AND OBJECTIVES: Despite many publications about cavernous malformations (CMs), controversy remains regarding diagnostic and management strategies. To update evidence-based guidelines for the clinical management of brain and spinal cord CMs. METHODS: The Alliance to Cure CMs, the patient support group in the United States advocating on behalf of patients and research in CM, convened a multidisciplinary writing group comprising expert CM clinicians to help summarize the existing literature related to the clinical care of CM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and imaging standards, (4) neurosurgical considerations, and (5) neurological considerations. Building on prior evidence-based recommendations reflecting literature review through October 2014, the group conducted a systematic review of the more recent literature, identified references for mandatory citation, rated evidence, developed recommendations, and established consensus according to a prespecified protocol. Finally, the writing group outlined remaining knowledge gaps and controversies to guide future research. RESULTS: From 2672 publications published between October 1, 2014, and March 15, 2023, and meeting key word criteria, 234 were selected based on prearticulated criteria for mandatory consideration in evidence-based recommendations. Topic authors used these and other supporting references to summarize current knowledge and arrive at 53 management recommendations, with unanimous consensus based on a Delphi process. These were rated by class (strength of recommendation) and level (quality of evidence) per the American Heart Association/American Stroke Association criteria. Eighteen recommendations were class 1 (34%), class 2 in 31 (58%), and class 3 in 4 (8%). Three were level A (6%), 19 (36%) were level B, and 31 (58%) were level C. CONCLUSION: Current evidence supports prior and new recommendations for the management of CMs, but many reflect moderate classes and low levels, mandating further research to better inform clinical practice.