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Importance Adjuvant chemotherapy regimens may be administered after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMNs), although the evidence supporting their use is limited. Objective To evaluate the survival benefit associated with contemporary adjuvant chemotherapy regimens after resection in A-IPMNs between 2017 and 2023. Design, Setting, and Participants This retrospective cohort study was an international, multicenter study with 69 participating centers across Europe, North America, South America, and the Asia-Pacific region. Patients undergoing resection for A-IPMNs were included. Data were analyzed from May to August 2025. Intervention Contemporary adjuvant chemotherapy regimens, such as gemcitabine-capecitabine (GemCap); 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX), modified FOLFIRINOX (mFOLFIRINOX), and S-1. Main Outcome and Measure Overall survival (months). Results Among 1321 patients (median [IQR] age 70 [63 to 76] years; 713 males [54.0%] and 608 females [46.0%]), 781 patients (59.1%) received adjuvant chemotherapy, while in 181 patients (13.7%) it was omitted due to poor patient fitness. Of patients who received adjuvant chemotherapy, 568 patients (72.6%) received contemporary regimens, including GemCap (232 patients [29.7%]), FOLFIRINOX (176 patients [22.5%]), mFOLFIRINOX (71 patients [9.1%]), and S-1 (70 patients [9.0%]). The median (IQR) follow-up for the cohort was 64.2 (40.4 to 85.0) months, and the median overall survival was 73.8 months (95% CI, 66.4 to 81.9 months). After 90-day landmark analysis and exclusion of patients ineligible for chemotherapy, adjuvant chemotherapy vs no adjuvant chemotherapy (propensity score–matched populations, 243:243 patients) was not associated with improved overall survival (median, 82.3 months; 95% CI, 78.2 months to not applicable [NA] vs not reached; 95% CI, 75.3 months to NA; P = .58). Contemporary regimens vs no adjuvant chemotherapy (propensity score–matched populations, 309:309 patients) was not associated with longer survival, and a mean survival benefit greater than 4.2 months over 5 years was excluded (difference in restricted mean survival, 1.26 months; 95%, −1.72 to 4.24 months). Treatment outcomes did not vary by chemotherapy regimen or disease characteristic (eg, N stage or carbohydrate antigen 19-9 level). Conclusions and Relevance In this study, contemporary adjuvant chemotherapy was not associated with improved overall survival in A-IPMNs, and a randomized clinical trial is indicated.

There have been no large comparisons of the clinical and laboratory features of familial neonatal hemophagocytosis (f-nHLH) and infectious neonatal hemophagocytosis (i-nHLH). The objectives of this study were the following: (1) Describe the demographic, diagnostic, and clinical features of patients with familial nHLH (F-nHLH) and infectious HLH (i-nHLH). (2) Compare key variables between f-nHLH and i-nHLH. (3) Compare the clinical outcomes of f-nHLH and i-nHLH. (4) Summarize literature on cytokine levels in patients with nHLH. Data from a previously published nHLH meta-analysis report were used to describe and compare features of infants with f-nHLH versus i-nHLH. Variables were tested with the χ 2 test or Fisher exact test, Cochran-Armitage test, independent 2-sample t test, or Wilcoxon rank-sum test as appropriate. Odds ratios were calculated for any comparison with a P -value of <0.05. Data extracted from 99 cases of f-nHLH and 54 cases of i-nHLH were included in this analysis. Infants with f-HLH met HLH criteria at the following rates: fever (84%); organomegaly (100%); pancytopenia (75%); hypofibrinogenemia (84%); hypertriglyceridemia (48%); hypofibrinogenemia or hypertriglyceridemia (82%); hemophagocytosis (81%); hyperferritinemia (99%); low or absent NK cell activity (91%); and elevated soluble CCD25 (91%). Infants with i-nHLH had higher median ferritin levels (22,537 ng/mL) than infants with f-nHLH (7587 ng/mL) ( P =0.072). Infants with f-nHLH had higher rates of symptoms in utero, preterm birth, family history of HLH, and family history of infant death. The overall survival among infants with familial nHLH was lower than infectious nHLH ( P =0.037). Management of nHLH requires rapid diagnosis and prompt treatment, as current literature suggests nHLH has high mortality rates. Distinguishing between familial and infectious causes of nHLH can aid in determining the correct treatment of choice.

ABSTRACT Purpose Malignant rhabdoid tumor of the kidney (MRTK) is a rare, aggressive tumor seen in young children. The optimal timing of resection for locally advanced tumors is not well‐defined. The purpose of this study is to evaluate modern oncologic outcomes and the impact of surgical timing. Methods A multicenter retrospective review was performed by institutions participating in the Pediatric Surgical Oncology Research Collaborative. Children younger than 21 years old with MRTK diagnosed between 2000 and 2022 were included. Results Sixty‐nine patients were identified with MRTK and met the inclusion criteria. Median age of diagnosis was 10.1 months. Overall survival (OS) at 1, 5, and 10 years was 49%, 32%, and 19%, respectively. Patients with local Stage III disease who underwent upfront resection ( n = 18) compared to those who had delayed resection after NAT ( n = 15) had a similar OS, median OS greater than 60 months versus 14.6 months, respectively; p = 0.396. The surgical timing groups were balanced in terms of the presence of metastasis, length of follow‐up, and tumor characteristics. There was one occurrence of primary intraoperative tumor spill and two occurrences of organ injury in the upfront resection group compared to none in the delayed resection group. Conclusion MRTK carries a poor prognosis despite multimodal treatment. Histologic diagnosis may not be confirmed at presentation, and MRTK cannot be reliably distinguished from Wilms tumor on imaging alone. As overall survival is similar, the decision regarding surgical timing in locally advanced tumors should be individualized based on perceived resectability, balancing the risk of intraoperative complications against the possibility of tumor progression during neoadjuvant therapy.

Summary Evidence for an association between insulin‐like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF‐I concentrations and risk of MM by combining baseline serological data among UK Biobank participants ( n = 444 187; 732 incident MM) with a two‐sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF‐I and IGF‐binding protein 3 (IGFBP‐3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF‐I level was positively associated with MM risk Hazard ratio‐HR‐per one standard deviation‐SD‐increase (HR 1‐SD = 1.11, 95% confidence interval [CI]: 1.01–1.22; p ‐value = 0.03), especially closer to diagnosis. Genetically inferred IGF‐I levels were associated with increased MM risk (odds ratio [OR] = 1.27, 95% CI: 1.05–1.54) but not with any other LNs. Genetically inferred IGFBP‐3 levels showed no associations with any LN evaluated. Corroborating previous findings, in a secondary analysis, IGF‐I levels were associated with the risk of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in males with higher body mass index (HR 1‐SD in obese male = 1.36, 95% CI: 1.14–1.61). Our serological and MR analyses suggest a contributing role of IGF‐I in the susceptibility of MM; the CLL/SLL findings warrant further investigation considering sex‐specific adiposity.

Most palliative care (PC) physicians will change jobs over the course of their career, yet few supports exist to guide them through this often unfamiliar process. Job transitions frequently elicit stress and uncertainty, as individuals balance personal and professional priorities, navigate complex negotiations, and assume the inherent risks of pursuing new opportunities. Yet, when approached intentionally, a job transition can also be a transformative process that allows for self-discovery, cultivation of new skills and connections, and reshaping of one’s professional identity. This article, written by a team of PC physicians who have made job transitions themselves, offers 10 tips for navigating this professional step successfully. With emphases on authentic communication, skilled mentorship, relationship building, and exploration of local culture—the article offers practical advice to help PC physicians navigate a job transition confidently, while staying grounded in their personal values and the work they find most meaningful.

BACKGROUND AND OBJECTIVES: Contemporary skull base surgeons must understand transcranial and endoscopic endonasal approaches to the petrous apex (PA). We provide an anatomic overview and comparison of main approaches to the PA through illustrative anatomic dissections. METHODS: On 10 sides of 5 specimens, transcranial approaches to the PA including the anterior petrosal, transcochlear, and retrosigmoid with suprameatal extension were performed. For endoscopic endonasal approaches, the transclival approach was performed in the midline of 5 specimens and its contralateral transmaxillary extension was performed on 10 sides. RESULTS: The anterior petrosal approach offers an anterolateral view of the PA bounded by petrous ridge posteromedially, internal auditory canal posterolaterally, greater superficial petrosal nerve anterolaterally, and lateral boundary of cranial nerve V, the Gasserian ganglion, and V3 anteromedially; it exposes the middle fossa and, once the PA is removed, the superomedial cerebellopontine angle. The transcochlear approach affords a lateral view of the PA defined medially and inferiorly by inferior petrosal sinus, posteriorly by posterior fossa dura, anteriorly by the petrous internal carotid artery, and superiorly by the superior petrosal sinus and middle fossa dura. Through a retrosigmoid approach, the PA is bounded by the superior petrosal sinus superiorly, the sagittal plane of cranial nerve VI medially, and the axial and sagittal plane of the internal auditory canal porus inferiorly and laterally, respectively. It affords a panoramic view of the posterior fossa and access to Meckel's cave after PA drilling. Endoscopic endonasal approaches target the anteromedial PA, and it is demarcated by a triangle consisting of cranial nerve VI posterolaterally, the paraclival segment of the internal carotid artery anteriorly, and the petroclival synchondrosis inferiorly and medially. The addition of the contralateral transmaxillary approach enhances lateral access up to the internal auditory canal. CONCLUSION: We provide a comprehensive overview of the main approaches to the PA through illustrative anatomic dissections and representative cases.

Background The prognostic significance of an adverse acid–base milieu despite venoarterial extracorporeal membrane oxygenation support in patients with cardiogenic shock remains poorly defined. We examined metabolic and respiratory disturbances in the ELSO (Extracorporeal Life Support Organization) Registry among patients who received venoarterial extracorporeal membrane oxygenation support for refractory cardiogenic shock. Methods Arterial blood gas acid–base values at 24 hours following venoarterial extracorporeal membrane oxygenation initiation were analyzed, with patients classified by pH, arterial partial pressure of carbon dioxide, and bicarbonate. Multivariable logistic regression and exploratory machine learning analyses were used to assess predictors of in‐hospital mortality. Results Among 15 144 adult patients, 74.6% (10 860) had neither respiratory nor metabolic acidosis, 13.1% (1909) had isolated respiratory acidosis, 11.6% (1684) had isolated metabolic acidosis, and 0.7% (100) had combined acidosis. In‐hospital mortality occurred in 7719 (51.0%) patients and increased incrementally across patients with lower pH (adjusted odds ratio [OR], 2.03 with each 0.1‐unit decrease in pH, using 7.4 as a reference point [95% CI, 1.82–2.26]), bicarbonate (adjusted OR, 1.93 per each 5‐mEq/L <24 mEq/L [95% CI, 1.76–2.12]) or base excess (adjusted OR, 1.90 per each 5‐mEq/L <0 mEq/L [95% CI, 1.75–2.07]) (all P <0.01). Mortality varied significantly, being highest for the low‐pH metabolic acidosis cluster (adjusted OR, 1.90 [95% CI, 1.70–2.12], P <0.01). Conclusions Survival decreased progressively with worse acidemia or metabolic acidosis despite 24 hours of hemodynamic support with venoarterial extracorporeal membrane oxygenation among patients with cardiogenic shock. Our findings emphasize the prognostic significance of metabolic parameters as potentially modifiable risk factors and underscore the need for early recognition and interventions to mitigate severe metabolic derangements.

In this study, we propose two new mathematical models able to quantify glucagon secretion during a graded glucose infusion, in the presence and absence of amino acids. The models provide an index of α-cell responsivity, G 50 , i.e., the glucose increase required to suppress glucose secretion rate (GSR) by 50%. Results show that the presence of amino acids reduced α-cell responsivity to glucose.

Background: Frequent pivoting, rotation, and deep hip flexion place football players at high risk for femoroacetabular impingement (FAI), a leading cause of hip pain in this population. Previous studies have primarily focused on professional National Football League athletes undergoing mixed surgical techniques, including labral debridement. Limited data exist on outcomes in younger, amateur players treated with labral repair. Purpose: To report return to sport (RTS) rates and functional outcomes at a minimum 5-year follow-up in primarily active high school and college football players undergoing primary hip arthroscopy with labral repair for FAI. Study Design: Case series, Level of evidence, 4. Methods: All football players who underwent primary hip arthroscopy with labral repair for FAI between 2010 and 2019 were identified from an institutional database. Collected data included descriptive data, radiographic parameters, surgical details, and reoperations. At a minimum 5-year follow-up, RTS outcomes and patient-reported outcome measures (PROMs), such as the Modified Harris Hip Score (mHHS) and Hip Outcome Score (HOS), were evaluated. Results: A total of 36 hips in 27 male athletes (mean age, 18 years; body mass index, 28.1 kg/m 2 ) were included. The majority of athletes competed at the high school (70%) or collegiate level (26%). Mean preoperative radiographic measurements were as follows: lateral center-edge angle, 31.6°; Tönnis angle, 4.1°; and alpha angle, 61.4°. Femoroplasty and acetabuloplasty were performed in 100% and 86% of cases, respectively. Also, 84% of players returned to football, all at the same or higher level than before surgery. At a mean follow-up of 9.8 years, all PROMs improved significantly from baseline ( P < .002). Outcome scores at follow-up were as follows: mHHS 90.5; HOS-Activities of Daily Living, 94.5; HOS-Sports-Specific Subscale, 91.1; and visual analog scale (VAS) pain with use, 2.3/10; VAS pain at rest, 1.3/10; and surgical satisfaction, 8.5/10. No patients required revision surgery. However, 2 patients (7%) underwent reoperations—including 1 for heterotopic ossification excision and 1 for periacetabular osteotomy. Conclusion: American football players who underwent primary hip arthroscopy with labral repair for FAI achieved excellent long-term outcomes, with high RTS rates at the same or higher levels, and improvements in PROMs and patient satisfaction. Despite favorable outcomes, nonmedical factors, such as graduation, may influence RTS in competitive athletes, particularly at the high school and collegiate levels.