Citations

Abstract Given the heterogeneous clinical behavior of pancreatic neuroendocrine tumors (pNETs), improved prognostic markers are needed to guide management and post‐resection surveillance. Patients who underwent resection of large (≥3 cm) sporadic well‐differentiated pNETs from 2000 to 2019 were identified. The Ki‐67 proliferation index was determined using immunohistochemistry, and alternative lengthening of telomeres (ALT) status was assessed using fluorescence in situ hybridization. Recurrence‐free and overall survival were estimated using Kaplan–Meier analysis. Multivariable Cox regression analysis evaluated factors associated with recurrence‐free survival. A total of 106 patients were identified. ALT was positive in 57 (54%) and negative in 49 (46%). Ki‐67 was ≥3% in 74 (70%) and <3% in 32 (30%). Tumors with Ki‐67 ≥3% were more likely to be ALT positive (61% vs. 38%, p = .046). Stratifying by ALT status and Ki‐67 proliferation index, median recurrence‐free survival was 4.6 years for patients with ALT‐positive/Ki‐67 ≥3% tumors, 3.1 years for patients with ALT‐positive/Ki‐67 <3% tumors, 12.4 years for patients with ALT‐negative/Ki‐67 ≥3% tumors, and 20.2 years for patients with ALT‐negative/Ki‐67 <3% tumors ( p < .001). Initial recurrence was distant in 82% and locoregional in 18%. Across all groups, overall survival was similar ( p = .19). In multivariable analysis, advanced age, ALT positivity, perineural invasion, and lymph node metastases were associated with increased recurrence risk (all p < .05). ALT and Ki‐67 provide complementary information on post‐resection recurrence risk, which can guide subsequent surveillance and management strategies. These data support the incorporation of ALT testing into routine clinical practice.

ABSTRACT We report a case of a primary cutaneous spindle cell sarcoma (SCS) with FN1 :: FGFR1 fusion. The tumor lacked the typical histologic and immunohistochemical features associated with other FN1 ‐rearranged neoplasms, such as phosphaturic mesenchymal tumors (PMT) and calcified chondroid mesenchymal neoplasms (CCMN). Unlike PMTs, which often feature a cartilaginous matrix and are associated with tumor‐induced osteomalacia (TIO), the present case lacked these characteristics and did not show FGF23 mRNA expression. Immunohistochemically, the tumor cells showed patchy staining for CD34 but were negative for markers such as ERG, desmin, S100, and pan‐TRK. The fusion event in this case involves the loss of the FGFR1 Ig1 (D1) domain, a mechanism proposed to drive oncogenesis by releasing FGFR1 from autoinhibition. Despite the preservation of other FGFR1 domains, no evidence of FGF23 signaling was detected, and the patient had no clinical history of TIO. This case underscores the complexity of oncogenesis in FN1 :: FGFR1 ‐rearranged neoplasms, a form of “promiscuous” gene fusion, where similar fusions lead to diverse tumor phenotypes. It emphasizes the importance of incorporating molecular testing in diagnosing spindle cell sarcomas, particularly those occurring in acral sites, to identify this underrecognized entity.

Background Acute therapies targeting calcitonin gene-related peptide (CGRP) for episodic migraine (EM) demonstrate efficacy in women, but evidence of efficacy in men remains to be established. By contrast, CGRP targeting therapies for migraine prevention are effective in both men and women with frequent EM or chronic migraine (CM). Preclinical studies have shown that supradural application of CGRP preferentially produces migraine-like pain behaviors in female rodents. We hypothesized that, in male mice, increased frequency of migraine-like pain may sensitize to nociceptive effects of CGRP and this might be associated with altered expression of CGRP in trigeminal ganglion (TG) neurons and/or in their dural projections. Methods CM was modeled in male and female mice by repeated administration of nitroglycerin (NTG). Medication overuse headache (MOH), a form of CM, was modeled by repeated daily administration of sumatriptan. Following resolution of transient cutaneous allodynia (CA) elicited by NTG or sumatriptan, mice received a sex specific subthreshold dose of supradural CGRP that does not elicit CA in naïve male or female mice, and CA was evaluated. CGRP-positive cell bodies in the ophthalmic V1 region of the trigeminal ganglion (TGV1) and CGRP-positive nerve fibers innervating the dura mater were assessed. Results Supradural administration of 1 pg of CGRP produced migraine-like pain behaviors in female, but not male, mice; a ten-fold lower dose was established as subthreshold in naïve female mice. Repeated NTG or sumatriptan produced transient CA in both female and male mice that resolved within 8–11 days after treatment cessation. Following resolution of CA, previously subthreshold doses of CGRP elicited CA in CM and MOH models in mice of both sexes, with no effects observed in vehicle treated controls. A higher number of CGRP-positive neurons in the TGV1 was found in naïve female compared to male mice. The number of CGRP-positive TGV1 neurons was increased in both sexes following repeated NTG. Similar nerve fiber density was observed in the dura mater of male and female mice and no differences were detected following repeated NTG. Conclusions As previously reported, CGRP produced female-selective migraine-like pain behaviors in naïve mice. Consistent with behavioral effects, female mice demonstrated a higher number of CGRP-positive cells in the TGV1. These findings appear relevant to clinical observations of female efficacy of CGRP-receptor antagonists for acute treatment in EM patients. In models of CM or MOH that are characterized by increased frequency of migraine-like pain, previously subthreshold doses of supradural CGRP now elicited migraine-like nociceptive behaviors in mice of both sexes. The increased pain responses were accompanied by increased number CGRP positive TGV1 cells in the NTG model in both female and male mice. These data suggest that increased frequency of migraine promotes physiological changes including increased expression of TGV1 CGRP along with sensitization to CGRP-induced nociception in both males and females. Thus, as EM transforms to CM, CGRP-dependent mechanisms may become increasingly important, consistent with observations of efficacy of CGRP targeting therapies for migraine prevention in both men and women. Our results also suggest the possibility of enhanced efficacy of CGRP-receptor antagonists for the acute treatment of migraine in men as migraine frequency increases.

Background We undertook this study to evaluate the efficacy of an on-table extubation protocol and to assess the magnitude of benefits when implemented as a routine practice in a developing country. Methods This prospective observational study at a single tertiary care referral hospital was designed to determine the efficacy of an on-table extubation protocol when applied to children undergoing cardiac surgery in the developing world. The study included 226 patients who were 1 month to 18 years of age undergoing cardiac surgery (including grown-up congenital heart disease [GUCHD] patients). Patients with RACHS score ≥ 4, neonates, preoperatively ventilated children, and emergency surgeries were excluded from the study. All pediatric elective cardiac surgical patients belonging to RACHS 1, 2, and 3 categories were considered as potential candidates for on-table extubation. Trial registration: Clinical Trials Registry of India (CTRI/2020/07/026567). Results Among the 226 children who underwent elective cardiac surgeries, we were able to extubate 142 patients (62.83%) in the operating room. This included 46.6% (54/116) infants, 80.8% (38/47) children less than 5 years of age, 79.3% (46/58) children between 5 years to 18 years age, and 80% (4/5) GUCHD. The duration of intensive care unit (ICU) stay, hospital stay, and hospital cost were significantly less in the on-table extubation group (23 [20, 26] hours; 102 [97, 125] hours; INR 2,09,011 [181032, 244298]) as compared with those patients extubated in the ICU within 6 hours (28 [22, 46] hours; 122 [100, 168] hours; INR 2,25,430 [162203, 273831]) and beyond 6 hours (71 [45, 121] hours; 184 [127, 243] hours; INR 2,53,541 [226838, 306871]). Conclusions This protocol shows a significant reduction in ICU stay, hospital stay, and total hospital cost when compared with either extubation within 6 h in the ICU or delayed extubation (beyond 6 h) in patients undergoing pediatric cardiac surgery.

Artificial intelligence (AI) is not merely a tool for the future of clinical medicine; it is already reshaping the landscape, challenging traditional paradigms, and expanding the horizons of what is achievable in healthcare [...]

Artificial Intelligence (AI) has the potential to revolutionize cytopathology by enhancing diagnostic accuracy, efficiency, and accessibility. However, the implementation of AI in this field presents significant challenges and opportunities. This review paper explores the current landscape of AI applications in cytopathology, highlighting the critical challenges, including data quality and availability, algorithm development, integration and standardization, and clinical validation. We discuss challenges such as the limitation of only one optical section and z-stack scanning, the complexities associated with acquiring high-quality labeled data, the intricacies of developing robust and generalizable AI models, and the difficulties in integrating AI tools into existing laboratory workflows. The review also identifies substantial opportunities that AI brings to cytopathology. These include the potential for improved diagnostic accuracy through enhanced detection capabilities and consistent, reproducible results, which can reduce observer variability. AI-driven automation of routine tasks can significantly increase efficiency, allowing cytopathologists to focus on more complex analyses. Furthermore, AI can serve as a valuable educational tool, augmenting the training of cytopathologists and facilitating global health initiatives by making high-quality diagnostics accessible in resource-limited settings. The review underscores the importance of addressing these challenges to harness the full potential of AI in cytopathology, ultimately improving patient care and outcomes.

Context.— A monthly pathology journal club has met for 24 years. It was established to help members stay apprised of the literature relevant to diagnostic pulmonary pathology. Objective.— To assess whether the journal club met its goal and to report on opportunities identified for improvement. Design.— To determine whether articles chosen for discussion as opposed to notation were more significant, Scopus citation indices for article types reviewed from January 2007 to November 2023 were compared. A survey of current faculty was undertaken to determine if the club was meeting expectations and to identify improvement opportunities. Results.— Articles from January 2007 to November 2023 included 858 discussed and 3385 noted. Mean (SD) citation count was 103.0 (409.80) for discussion and 64.9 (259.77) for notation articles ( P < .001). The citation count was noticeably right skewed, as articles with high citation counts inflated the mean. Members were mostly satisfied with the way the journal club was structured and managed. Members most valued the summary of the articles, followed by the live discussion. Opportunities for improvement included decreasing the number of journals scanned, decreasing detail in summaries, and using generative artificial intelligence (AI) to facilitate summary generation. A pilot using AI anecdotally reduced preparatory time, but the human-edited summary included more specific context, critical commentary, and enhanced take-home messages, providing a more nuanced analysis. Conclusions.— The journal club met its initial goal. Opportunities for improvement have been identified including the use of generative AI to facilitate article summarization.

Significant progress has been made in treating Coronavirus disease (COVID) – an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post–COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.

Abstract Introduction Despite the widespread use of telemedicine to assess patients with intestinal failure (IF) receiving home parenteral nutrition (HPN), satisfaction with remote consultation methods has not been comprehensively assessed. Here, we assessed patient and clinician attitudes to telephone and video IF consultations. Methods Telemedicine questionnaires were designed and distributed in paper form to patients with IF receiving HPN under the care of a UK national IF reference center and electronically to IF clinicians in Europe, North America, Australia, and New Zealand. Results Seventy‐eight patients (53 women and 25 men) and 110 clinicians agreed to complete the questionnaires. Sixty seven percent of patients who had telephone consultations and 50% of patients who had video consultations were satisfied with their consultations. Forty nine percent and 83% of patients who had telephone and video consultations, respectively, felt they were of the same standard as their face‐to‐face consultations. Despite 60% of clinicians feeling telemedicine training would be useful, 55% of clinicians stated they mostly or always met all of the needs of their patients via telephone consultations, whereas 96% of clinicians felt similarly for video consultations ( P = 0.002). A total of 33% and 57% of clinicians felt telephone and video consultations, respectively, were of the same standard as face‐to‐face consultations ( P = 0.004). Conclusion This study comprehensively assesses attitudes to IF telemedicine consultations. Our data show that a large proportion of patients and clinicians are satisfied with IF telephone and video consultations. However, there is an unmet need amongst clinicians for telemedicine training.