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Background/Objectives: Family history is a known risk factor for multiple myeloma (MM) and its precursor condition, monoclonal gammopathy of undetermined significance (MGUS). Previous genome-wide association studies (GWASs) have identified 35 common loci associated with MM risk and 21 associated with MGUS. The objective of this study was to identify less common and rare genetic loci predisposing to MM/MGUS through whole-exome sequencing (WES)-based linkage analysis. Methods:Multipoint linkage analysis was conducted using the Multipoint Engine for Rapid Likelihood Inference (MERLIN) with the Lander–Green algorithm on germline WES data from 79 pedigrees with 2 or more affected relatives (120 MM, 86 MGUS, and 21 unaffected). Genome-wide linkage was evaluated using 12,946 independent single-nucleotide variants (linkage disequilibrium r2 < 0.05). Results: Significant linkage was observed at chromosome 6q22.33–q24.2 by the non-parametric model (logarithm-of-odds (LOD) = 3.3) and suggestive linkage by the dominant parametric model (heterogeneity LOD (HLOD) = 2.5). Fourteen rare variants within this region were prioritized using family-specific partial LOD scores and in silico functional prediction tools. Nine of these variants, REPS1, THEMIS, TAAR6, AHI1, VNN1, VNN3, MTFR2/FAM54A, LAMA2, and PHACTR2, overlapped immune-regulatory regions in blood cell lines and were not previously identified in GWASs. Conclusions: This study demonstrates the utility of applying a linkage analysis framework to familial WES data for identifying genomic regions and candidate genes that may contribute to MM/MGUS predisposition. These findings provide new insight into the inherited risk and etiology of familial MM and MGUS.

BACKGROUND: Early recognition of postoperative ileus remains difficult. OBJECTIVE: To determine whether myoelectric activity recorded by a noninvasive, wireless patch system correlated with the onset of postoperative ileus/bowel dysfunction. DESIGN: Single-arm, prospective study. The surgeon was blinded to myoelectric bowel activity until study completion. SETTINGS: Single surgeon, tertiary referral center. PATIENTS: Consecutive adult patients undergoing abdominal colorectal surgery. INTERVENTIONS: Three wireless patches acquiring myoelectrical GI activity were placed on the abdomen after surgery and removed before hospital discharge/reoperation. All patients followed an enterprise-specific enhanced recovery protocol. MAIN OUTCOME MEASURES: Ileus (nausea, vomiting, abdominal distention requiring nasogastric tube placement) or bowel dysfunction (similar symptoms without nasogastric tube needed) detected clinically within 30 postoperative days. Daily gut activity prints (histograms of the frequencies of all peaks detected in 10-minute time windows) were created for each patient for every 4-hour period after surgery, and activity was averaged and plotted for each group. Peaks in the 8 to 12 cycles per minute range were assigned to intestinal activity, and the energy under the peaks was summed through day 1, day 2, and day 3 and compared among patients. RESULTS: Patch application on 46 enrolled cases undergoing abdominal colorectal surgery (open in 17, robotic in 11, laparoscopic in 18) was not associated with any adverse events. Hyperactive intestinal activity was significantly higher in 12 patients who developed postoperative ileus/bowel dysfunction within 16 hours postoperatively ( p = 0.041), with a more pronounced difference at 20 and 24 hours ( p = 0.016 and p = 0.013, respectively). LIMITATIONS: Data were collected blindly during standard postoperative care; therefore, the integration of technology into clinical practice remains to be tested. CONCLUSIONS: Noninvasive measurement of intestinal myoelectrical activity allowed early identification of postoperative ileus/bowel dysfunction. Future studies will assess the possible advantages deriving from the integration of this system into clinical practice. See Video Abstract . LOS PICOS INTESTINALES HIPERACTIVOS OBSERVADOS POCAS HORAS DESPUÉS DE LA CIRUGÍA COLORRECTAL IDENTIFICAN A LOS PACIENTES QUE DESARROLLAN ÍLEO POSOPERATORIO ANTECEDENTES: El reconocimiento precoz del íleo posoperatorio sigue siendo difícil. OBJETIVO: Determinar si la actividad mioeléctrica registrada por un sistema de parches inalámbricos no invasivos se correlacionaba con la aparición de íleo posoperatorio/disfunción intestinal. DISEÑO: Estudio prospectivo de un solo grupo. El cirujano desconocía la actividad mioeléctrica intestinal hasta la finalización del estudio. ENTORNO: Un solo cirujano, centro de referencia terciario. PACIENTES: Pacientes adultos consecutivos sometidos a cirugía colorrectal abdominal. INTERVENCIONES: Se colocaron tres parches inalámbricos que registraban la actividad mioeléctrica gastrointestinal en el abdomen después de la cirugía y se retiraron antes del alta hospitalaria o la reintervención. Todos los pacientes siguieron un protocolo de recuperación mejorada específico de la empresa. PRINCIPALES MEDIDAS DE RESULTADO: Íleo (náuseas, vómitos, distensión abdominal que requiere la colocación de una sonda nasogástrica) o disfunción intestinal (síntomas similares sin necesidad de sonda nasogástrica) detectados clínicamente en los 30 días posteriores a la operación. Se crearon GutPrints (histogramas de frecuencias de todos los picos detectados en intervalos de 10 minutos) de la actividad intestinal diaria para cada periodo de 4 horas tras la cirugía, se promediaron y se representaron gráficamente para cada uno de los grupos. Los picos en el rango de 8 a 12 cpm (ciclos por minuto) se asignaron a la actividad intestinal y la energía bajo los picos se sumó a lo largo del día 1, el día 2 y el día 3 y se comparó entre los pacientes. RESULTADOS: La aplicación del parche en 46 casos inscritos sometidos a cirugía colorrectal abdominal (abierta en 17, robótica en 11 y laparoscópica en 18) no se asoció con ningún evento adverso. La actividad intestinal hiperactiva fue significativamente mayor en 12 pacientes que desarrollaron íleo postoperatorio/disfunción intestinal en las 16 horas posteriores a la operación ( p = 0,041), con una diferencia más pronunciada a las 20 y 24 horas ( p = 0,016 y p = 0,013, respectivamente). LIMITACIONES: Los datos se recopilaron de forma ciega durante la atención posoperatoria estándar, por lo que aún queda por comprobar la integración de la tecnología en la práctica clínica. CONCLUSIONES: La medición no invasiva de la actividad mioeléctrica intestinal permitió la identificación temprana del íleo/disfunción intestinal posoperatoria. En futuros estudios se evaluarán las posibles ventajas derivadas de la integración de este sistema en la práctica clínica. ( AI-generated translation )

Background Outcome selection in regional anesthesia and acute pain research is inconsistent, often lacking patient-centered priorities and validated instruments. We aimed to prioritize key outcomes and propose suitable measurement tools to improve the quality, consistency, and relevance of regional anesthesia research. Methods We conducted a multiround Delphi process, including two electronic voting rounds, a multiday in-person meeting, and a patient panel. Experts and patients evaluated existing and proposed outcomes for importance, validity, and relevance. Outcomes reaching ≥70% agreement were prioritized, and appropriate measurement instruments were identified. Results Thirty-two experts and three patients participated. Across three Delphi rounds, 10 outcomes were prioritized for future regional anesthesia research: seven efficacy outcomes (pain scores; opioid consumption; Brief Pain Inventory; functional outcomes; cognitive function; length of stay; block duration); two multidimensional outcomes (quality of recovery and development of a regional anesthesia-specific quality-of-recovery instrument); one safety outcome (chronic postsurgical pain). Patients prioritized cognitive recovery, function, chronic pain, and pain scores. Conclusions This consensus-based, patient-centered framework defines the core priorities for future regional anesthesia and acute pain research. Future work should focus on developing and validating a regional anesthesia-specific quality-of-recovery instrument, refining multidimensional measures such as functional recovery, cognitive outcomes, and the Brief Pain Inventory, and standardizing the reporting of chronic pain and opioid-related outcomes. Adoption of these priorities will enhance methodological consistency, comparability, and patient relevance in future clinical trials.

ABSTRACT Background The impact of psychosocial health and socioeconomic status (SES) on long‐term lung transplant survival remains unclear. Methods We conducted a single‐center, retrospective 2:1 matched case‐control study of adult lung transplant recipients (1999–2019). Cases survived ≥6 years post‐transplant; controls survived <6 years. Matching was based on transplant year (±5 years) and indication. Psychosocial health and SES were assessed using the Psychosocial Assessment of Candidates for Transplant (PACT) score, Mayo Clinic Housing‐Based Socioeconomic Status (HOUSES) index, and Area Deprivation Index (ADI). Secondary covariates included insurance, marital status, employment, caregiver relationship, and proximity to the transplant center. Conditional logistic regression adjusted for age and gender was used. Results Among 189 patients (63 cases, 126 controls), PACT score, HOUSES index, and ADI were not significantly associated with long‐term survival. Patients with non‐family caregivers had lower odds of survival compared to those with a spouse or partner (OR = 0.16, p = 0.022). Regional residents had lower odds of long‐term survival compared to local recipients (OR = 0.55, p = 0.001). Conclusions Pre‐transplant psychosocial and SES measures were not significantly associated with long‐term survival. Caregiver relationships and geographic proximity may have a greater impact on outcomes, highlighting the importance of support systems and access to care.

Abstract BACKGROUND Ovarian cancer rarely metastasises to the brain, thus studies reporting the outcomes of affected patients are lacking. Stereotactic radiosurgery (SRS) is now the mainstay of management for patients with brain metastases (BM) from most primary sites, but little evidence of its efficacy in ovarian cancer is available. The current study was undertaken to provide guidance for SRS management using pooled data from multiple institutions. MATERIAL AND METHODS Centers participating in the IRRF (International Radiosurgery Research Foundation) were asked to provide outcome data for patients who had SRS for ovarian cancer brain metastases between 2020 and 2024 and at least one clinical and imaging follow-up after the procedure. Primary endpoints included survival from SRS, local tumor response according to RANO-BM criteria and occurrence of adverse radiation effects (ARE). Cox regression analyses were performed to identify variables impact each endpoint. RESULTS 128 patients had SRS for a total of 532 BM treated. Epithelial histology was the most common (91%). Median age at SRS was 62 years (IQR 56-70). Median KPS was 80% (IQR 80-90%) and 71.9% of patients had neurological symptoms at presentation. Other active systemic metastases were present in 41.4%. The median number of treated BM was 2 (IQR1-3) and the median cumulative treatment volume was 6 cc (IQR 2-12.9). The median margin dose was 18 Gy (IQR 16-20). At last follow-up, 19.5% of patients were still alive. The median overall survival (OS) after SRS was 27 months, and 6-, 12- and 24-month OS was 83.8%, 74.2% and 52.2%, respectively. Multivariate analyses revealed that increasing age at SRS (HR 1.02, p=0.05), active systemic metastases (HR 2, p=0.005) and increasing number of brain metastases (HR 1.05, p=0.04) were associated with worse survival, while repeating SRS (HR 0.4, p=0.002) led to improved survival. Local failure occurred in 12.8% of treated BM. Actuarial progression-free survival (PFS) at 6, 12 and 24 months was 92.3%, 86.6% and 70.3%, respectively. Only prior WBRT (HR 4.36, p=0.03) led to worse local control on multivariate analyses. New remote BM appeared in 49.5% of patients and 14.5% suffered from leptomeningeal dissemination. ARE were seen in 12.1% of BM but were symptomatic in only 3.2%. On multivariate analyses, prior SRS (HR 3.13, p=0.002) was associated with increased risk of ARE. CONCLUSION Ovarian cancer brain metastases can be safely and effectively managed with SRS as the primary treatment modality in most patients.

Abstract Medical imaging is undergoing a transformation driven by the advent of new, highly effective, machine learning techniques paired with increases in computational capabilities (Cheng et al. 2021; Gilson et al. 2023; Almeida et al. 2024; Krishna et al. 2024). These advanced algorithms have the potential to improve disease detection, diagnosis, prognosis, and treatment outcomes. However, the complexity of machine learning models, the large amounts of curated and annotated data required by some methods, and the potential for bias and error make it challenging for individuals to safely and effectively leverage these methods (Lin et al. 2024; Guo et al. 2024; Xu et al. 2024; Linguraru et al. 2024; Wood et al. 2019). To address these challenges, the American Association of Physicists in Medicine (AAPM), American College of Radiology (ACR), Radiological Society of North America (RSNA), and Society for Imaging Informatics in Medicine (SIIM) have worked together to develop a syllabus detailing a recommended set of competencies for medical imaging professionals interacting with these systems. This guide is aimed at four different personas: users of AI systems, purchasers of AI systems, individuals who provide clinical expertise during the development of AI systems (“clinical collaborators”), and developers of AI systems.1 This is a syllabus, not a curriculum, and is intentional in this scope. Recognizing that individuals may benefit from different presentations of the same material, this work enumerates a series of relevant competencies but does not prescribe, nor offer, a method of instruction (Schuur, Rezazade Mehrizi, and Ranschaert 2021; Garin et al. 2023). By addressing the task‐specific demands of each role, this guide will enable medical imaging professionals to utilize machine learning systems more safely and effectively, ultimately improving patient care and outcomes.

A three year old male neutered mixed breed dog presented with a mass on the right carpus and accompanying lameness. A Jamshidi bone biopsy was performed, and histopathology results were consistent with a sarcoma. The dog received oncolytic virotherapy (OV) with vesicular stomatitis virus (VSV) as part of a clinical trial in dogs with osteosarcoma (OSA). Ten days after VSV treatment, the affected limb was amputated, and histopathology was consistent with intramedullary HSA. Considering the new diagnosis, standard doxorubicin chemotherapy was prescribed. With this combination of therapies, the dog had an extended survival of more than seven years and remains alive at the time of writing. This is the first case report documenting OV given in conjunction with the standard of care for canine appendicular HSA.

Abstract Extracellular matrix (ECM) stiffening correlates with tumor invasion in various cancer types, including glioblastoma (GBM). Increased matrix stiffness promotes a migratory phenotype through dysregulation of cell-ECM bidirectional communication. Exposure to stiffer environments is sensed by cells, which then adapt in ways that promote invasive behavior. These adaptive changes are imprinted onto the cells and persist even after they are placed in new, softer microenvironments via a process known as “mechanical memory.” Mechanical memory is believed to be driven by mechanosensitive transcription factor activity and epigenetic remodeling. Glioblastoma recurrence is linked to the ability of cells to disperse and infiltrate the surrounding healthy tissue. Extracellular matrix stiffness in GBM is heterogeneous; it starts with a softer tumor core and becomes progressively stiffer toward the tumor’s edges, potentially promoting sustained tumor invasion through mechanical memory. This review discusses the role of ECM stiffness in cancer cell behavior and the implications of ECM stiffening in GBM. We then describe the findings associated with mechanical memory and relay underlying mechanisms currently understood to drive the preservation of mechanically primed phenotypes. Finally, we discuss how matrix stiffness can drive migratory phenotypes in GBM cells and the potential role that progressive ECM dysregulation at the tumor periphery can link the formation of invasive tumor niches to the aggressive, resistant, and mesenchymal-like phenotypes present in GBM recurrent tumors.