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Complications of ovarian metastases from well-differentiated small bowel neuroendocrine neoplasms: a focus on bowel and ureteral obstruction
No full textOvarian metastasis from small bowel neuroendocrine neoplasms (SBNENs) was traditionally considered rare, but more recent series have suggested a higher prevalence. This case series seeks to examine the features and outcomes of patients with neuroendocrine ovarian metastases (NOM). Female patients with histologically confirmed well-differentiated SBNENs were identified using a prospectively maintained database (2014–2024). The electronic medical record was reviewed for details of diagnosis, histopathology, biomarkers, and outcomes among patients with and without NOM. 175 patients met inclusion criteria. 35 patients (20 %) had ovarian metastasis; for this group, 31.4 % had small bowel obstruction only, 5.7 % had ureteral obstruction only, and 14.3 % had both SBO and ureteral obstruction. 22 (62.9 %) also had peritoneal metastasis. 13 patients had ovarian metastasis but no peritoneal metastasis; within this group, 38.5 % had SBO, 15.4 % had ureteral obstruction, 76.9 % developed carcinoid syndrome, and 7.69 % died. There were no significant differences in rate of SBO (p = 0.280), ureteral obstruction (p = 0.716), or death (p = 0.091) between those with ovarian metastasis only and those with peritoneal metastasis only. Median overall survival was not reached. This case series of female patients with SBNENs represents one of the largest available in the literature and demonstrates high rates of complications for those with ovarian metastasis, even in the absence of peritoneal metastasis. Prophylactic oophorectomy may be considered for SBNEN patients given the known development of severe complications throughout the progression of this disease where expectation for survival is lengthy
Dual membrane receptor degradation via folate receptor targeting chimera
No full textCancer drug resistance poses a significant challenge in oncology, often driven by intricate cross-talk among membrane-bound receptors that compromise mono-targeted therapies. We develop a dual membrane receptor degradation strategy leveraging Folate Receptor α (FRα) to address this issue. Folate Receptor α Targeting Chimeras-dual (FolTAC-dual) are engineered degraders designed to selectively and simultaneously degrade distinct receptor pairs: (1) EGFR/HER2 and (2) PD-L1/VISTA. Through modular optimization of modality configurations and geometries, we identify the “string” format as the most effective construct. Mechanistic studies demonstrate an ~85% increase in EGFR-binding affinity compared to the conventional knob-into-hole design, likely contributing to the improved efficiency of dual-target degradation. Proof-of-concept studies reveal that EGFR and HER2 FolTAC-dual effectively counteracts resistance in Trastuzumab/Lapatinib-resistant HER2-positive breast cancer models, while PD-L1 and VISTA FolTAC-dual rejuvenates immune responses in PD-L1 antibody-resistant syngeneic mouse models. These findings establish FolTAC-dual as a promising dual-degradation platform for clinical translation
Low Unintended Dural Puncture Rate Using a Flush-Measure-Check-Advance Technique to Perform Combined Spinal-Epidural Anesthesia in Parturients: A Quality Improvement Clinical Series
No full textBackground: Reported rates of unintended dural puncture during performance of continuous epidural anesthesia (CEA) or combined spinal-epidural anesthesia (CSEA) have remained steady at approximately 0.5% to 1% since the 1970s. Methods: A modified method of inserting the Tuohy epidural catheterization needle was used during performance of CSEA in 393 parturients. A single staff/faculty anesthesiologist performed or supervised resident use of a flush-measure-check-advance Tuohy needle insertion algorithm. Results: The rate of evident Tuohy needle dural puncture during the series was 0%. One parturient experienced a post-dural puncture headache possibly because of intentional subarachnoid puncture with a very small diameter (25 gauge) needle during 2 CSEAs. In 19 parturients, the initial spinal anesthesia portion of CSEA failed, prompting conversion to CEA in 18 parturients and to spinal anesthesia in 1 parturient. Conclusion: The use of a flush-measure-check-advance Tuohy needle insertion algorithm to reduce the likelihood of unintended dural puncture during performance of CSEA in parturients deserves further study
Synthetic Electrospun Fiber Matrix in the Management of Acute Wounds Following Excision of Hidradenitis Suppurativa Lesions: A Prospective Pilot Study
No full textHurley Stage II or III hidradenitis suppurativa (HS) may necessitate surgical excision of diseased skin and subcutaneous fat for symptom control and disease management. These excisions result in open wounds in topographically challenging regions and typically cannot be primarily closed. This study evaluates the use of a synthetic electrospun fiber matrix (SEFM) as a post-resection regeneration template to accelerate re-granulation and improve subsequent skin graft incorporation. This prospective pilot study enrolled Hurley Stage II or III patients undergoing surgical resection of HS lesions. SEFM was applied to the resulting wounds in conjunction with negative pressure wound therapy (NPWT). Patients were monitored post-operatively for granulation tissue formation and underwent skin grafting once granulation was sufficient. Skin graft incorporation was assessed at follow-up visits. Complications, including graft loss (partial or complete) and infection, were assessed at each encounter. A total of 21 wounds in eight patients met the inclusion criteria and were enrolled. The average time to skin grafting was 14 ± 3.2 days. After grafting, the average graft incorporation was 71 ± 28%. No complications occurred during the study. These initial results indicate that by supporting granulation tissue formation, combined use of SEFM and NPWT may aid in successful engraftment of topographically challenging areas post-HS excision
Temperature-Dependent Regulation and Mitochondrial Targeting of the Cytochrome c Oxidase Subunit LmCOX4 in Leishmania
No full textThe Loss of Serotonin 2A Receptor (5-HT2AR) Activity Contributes to Aging Phenotypes and Ferroptotic Pressures in the Retinal Pigmented Epithelium (RPE)
No full textPP2A B\u27 subunit regulates synaptic development and cognition – A fly model to study intellectual disability (ID).
No full textBromelain-Based Enzymatic Debridement of a Third-Degree Burn to Skin-Grafted Bowel
No full textBurn injuries over previously grafted tissue present a formidable challenge for excision and debridement, particularly when there are critical underlying structures such as bowel. Enzymatic debridement with the recently approved anacaulase-bcdb, a bromelain-based enzymatic debridement gel (Nexobrid), presents an additional method of burn excision that may be useful in such a situation. This brief report presents the management of a complex third-degree burn over a remotely skin-grafted bowel mass using anacaulase-bcdb gel. This report is written with documented patient consent and approval by the Human Research Protection Program office in compliance with institutional policy. A 52-year-old man presented to our level I burn center with a third-degree 3% total body surface area contact burn to a remotely skin-grafted bowel mass. The patient was admitted with the decision to proceed with anacaulase-bcdb debridement of his wound to minimize the risk of compromising his underlying bowel. The patient underwent the debridement without any sign of succus emanating from the wound. Post-debridement, he was transitioned to a negative pressure wound dressing and discharged home. He continued receiving wound care at clinic follow-ups and eventually underwent complex open ventral hernia repair. This brief report provides a safe alternative to operative excision of wounds with underlying critical structures