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The vial can help: Standardizing vial design to reduce the risk of medication errors

Bitan, Yuval; O'Connor, Michael F; Nunnally, Mark E
PMID: 38251720
ISSN: 1537-1913
CID: 5624642

A novel SUCNR1 inhibitor alleviates dysbiosis through inhibition of host responses without direct interaction with host microbiota

Thomas, Scott C; Guo, Yuqi; Xu, Fangxi; Saxena, Deepak; Li, Xin
Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein-coupled receptor, SUCNR1. Modulating succinate-induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis-induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host-microbial community structure, with enrichment in succinate producers and consumers and mucin-degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels.
PMID: 37715517
ISSN: 2041-1014
CID: 5593302

Current trends and outcomes for unilateral groin hernia repairs in the United States using the Abdominal Core Health Quality Collaborative database: A multicenter propensity score matching analysis of 30-day and 1-year outcomes

Lima, Diego L; Nogueira, Raquel; Dominguez Profeta, Rebeca; Huang, Li-Ching; Cavazzola, Leandro Totti; Malcher, Flavio; Sreeramoju, Prashanth
BACKGROUND:Different unilateral groin hernia repair approaches have been developed in the last 2 decades. The most commonly done approaches are open inguinal hernia repair by the Lichenstein technique, laparoscopic approach by either total extraperitoneal or transabdominal preperitoneal, and robotic transabdominal preperitoneal approach. Hence, this study aimed to compare early and late postoperative outcomes in patients who underwent unilateral robotic transabdominal preperitoneal, laparoscopic transabdominal preperitoneal, and laparoscopic total extraperitoneal, and open groin hernia repair using a United States national hernia database, the Abdominal Core Health Quality Collaborative Database. METHODS:Prospectively collected data from the Abdominal Core Health Quality Collaborative database was retrospectively reviewed, including all adult patients who underwent elective unilateral groin hernia repair from 2015 to 2022, with a 1:1 propensity score match analysis conducted for balanced groups. The univariate analysis compared the groups across the preoperative, intraoperative, and postoperative timeframes. RESULTS:, the robotic approach had lower rates of surgical site occurrence (n = 12, 4%; P = .002) and seroma (n = 5, 2%; P < .001) compared with the other groups. When evaluating recurrence 1 year after surgery, the robotic transabdominal preperitoneal group had 10% versus 18% open groin hernia repair, 11% laparoscopic transabdominal preperitoneal, and 18% laparoscopic total extraperitoneal, but it was not statistically significant (P = .53). CONCLUSION/CONCLUSIONS:for surgical site occurrence and seroma than in other surgical techniques.
PMID: 38218685
ISSN: 1532-7361
CID: 5628762

Impact of recipient age on mortality among Cytomegalovirus (CMV)-seronegative lung transplant recipients with CMV-seropositive donors

Belga, Sara; Hussain, Sarah; Avery, Robin K; Nauroz, Zeba; Durand, Christine M; King, Elizabeth A; Massie, Allan; Segev, Dorry L; Connor, Avonne E; Bush, Errol L; Levy, Robert D; Shah, Pali; Werbel, William A
BACKGROUND:Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs. METHODS:Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects. RESULTS:We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients. CONCLUSIONS:Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs.
PMID: 38061469
ISSN: 1557-3117
CID: 5591372

ASO Visual Abstract: The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors

Partelli, Stefano; Fermi, Francesca; Fusai, Giuseppe K; Tamburrino, Domenico; Lykoudis, Panagis; Beghdadi, Nassiba; Dokmak, Safi; Wiese, Dominik; Landoni, Luca; Reich, Federico; Busch, O R C; Napoli, Niccolò; Jang, Jin-Young; Kwon, Wooil; Armstrong, Thomas; Allen, Peter J; He, Jin; Javed, Ammar; Sauvanet, Alain; Bartsch, Detlef K; Salvia, Roberto; van Dijkum, E J M Nieveen; Besselink, M G; Boggi, Ugo; Kim, Sun-Whe; Wolfgang, Christofer L; Falconi, Massimo
PMID: 38519785
ISSN: 1534-4681
CID: 5641022

Concomitant midline ventral and inguinal hernia repair: can we create an algorithmic approach?

Pacheco, T B S; Cordero, K; Arias-Espinosa, L; Hurwitz, J C; Malcher, F; Halpern, D
PURPOSE/OBJECTIVE:International guidelines exist for surgical treatment of either ventral or inguinal hernias repair (VHR; IHR). However, approach for managing both of them remains unestablished and is further complicated by newly developed surgical techniques and modalities (namely, robotic). This highlights the need for a tailored, algorithmic strategy to streamline surgical management. METHODS:An algorithm was developed by the directors of the NYU Langone Abdominal Core Health program of which four treatment groups were described: Group 1: open VHR and either laparoscopic or robotic IHR; Group 2: robotic transabdominal pre-peritoneal (TAPP) approach for both VHR and IHR; Group 3: robotic retro-muscular VHR and IHR; and Group 4: open repair for both. Demographics, comorbidities, operative characteristics, and surgical outcomes from November 2021 to July 2023 were retrospectively compared. RESULTS:, and 73% (n = 67) were ASA class II. Distribution of groups was: 48% (n = 44) in 1A, 8% (n = 7) in 1B, 8% (n = 7) in 2A, 3% (n = 3) in 2B, 23% (n = 21) in 3A, 8% (n = 7) in 3B, and 3% (n = 3) in 4. Ventral hernia size, OR time, and postoperative length of stay varied across groups. Postoperative outcomes at 30 days including emergency consults, readmissions, and complications, showed no differences across groups. CONCLUSION/CONCLUSIONS:Access without guidance to new minimally invasive surgical approaches can be a challenge for the general surgeon. We propose an algorithm for decision-making based on our experience of incorporating robotic surgery, when available, for repair of concomitant VHR and IHR with consistent favorable outcomes within a small sample of patients.
PMID: 38512506
ISSN: 1248-9204
CID: 5640732

The IASLC Mesothelioma Staging Project: Proposals for Revisions of the 'T' Descriptors in the Forthcoming 9th Edition of the TNM Classification for Pleural Mesothelioma

Gill, Ritu R; Nowak, Anna K; Giroux, Dorothy J; Eisele, Megan; Rosenthal, Adam; Kindler, Hedy; Wolf, Andrea; Ripley, Robert T; Billé, Andre; Rice, David; Opitz, Isabelle; Rimner, Andreas; dePerrot, Marc; Pass, Harvey I; Rusch, Valerie W; ,; ,
BACKGROUND:edition of the PM staging system. METHODS:edition data. Overall survival (OS) was calculated by the Kaplan-Meier method and differences in OS assessed by the log-rank test. RESULTS:edition analyses. CONCLUSION/CONCLUSIONS:Given reproducible prognostication by Psum, size criteria will be incorporated into cT1-T3 categories in the 9th edition. Current cT4 category and all pT descriptors will be maintained, with reclassification of fissural invasion as pT2.
PMID: 38521202
ISSN: 1556-1380
CID: 5641112

Pancreatic cyst prevalence and detection with photon counting CT compared with conventional energy integrating detector CT

Dane, Bari; Kim, Jesi; Qian, Kun; Megibow, Alec
PURPOSE/OBJECTIVE:To calculate the prevalence of pancreatic cysts on photon counting CT (PCCT) and compare with that of 128-slice conventional energy-integrating detector CT (EIDCT). METHOD/METHODS:A retrospective single institution database search identified all contrast-enhanced abdominal CT examinations performed at an outpatient facility that has both a PCCT and EIDCT between 4/11/2022 and 7/26/2022. The presence and size of pancreatic cysts were recorded. In patients with PCCT reported pancreatic cysts, prior CT imaging (EIDCT) was reviewed for reported pancreatic cysts. Fisher's exact test was used to compare the pancreatic cyst detection rate for PCCT and EIDCT. Wilcoxon rank sum test was used to compare cyst size and patient age. A p <.05 indicated statistical significance. RESULTS:2494 patients were included. Our pancreatic cyst detection rate was 4.9 % (49/1009) with PCCT and 3.0 % (44/1485) for EIDCT (p =.017). For CT angiograms, pancreatic cysts were detected in 6.6 % (21/319) with PCCT and 0.0 % (0/141) with EIDCT (p <.001). Pancreatic cyst detection rate was not statistically different for portal venous, enterography, renal mass, pancreas, 3-phase liver, or venogram protocols (all p >.05). Mean[SD] pancreatic cyst size was 13.7[9.7]mm for PCCT and 15.3[14.7] for EIDCT (p =.95). 55.1 % (27/49) of PCCT and 61.4 % (27/44) of EIDCT that described pancreatic cysts had prior contrast-enhanced EIDCTs. Of these, 40.7 % (11/27) of PCCT and 14.8 % (4/27) of EIDCT described pancreatic cysts were not previously reported (p =.027). CONCLUSIONS:Photon-counting CT afforded greater pancreatic cyst detection than conventional energy-integrating detector CT, particularly with CT angiograms.
PMID: 38520805
ISSN: 1872-7727
CID: 5641102

Primary abandonment of the sac in the management of scrotal hernias: a dual-institution experience of short-term outcomes

Nikolian, V C; Pereira, X; Arias-Espinosa, L; Bazarian, A N; Porter, C G; Henning, J R; Malcher, F
PURPOSE/OBJECTIVE:Management of scrotal hernias presents as a common challenge, with operative interventions to address these hernias associated with higher rates of morbidity compared to those of less-complex pathology. Surgeons have advocated for the use of techniques such as primary abandonment of the distal sac as a potential means to reduce complications for operative intervention, with preliminary findings demonstrating feasibility. We sought to assess outcomes related to primary sac abandonment among patients undergoing minimally invasive (MIS) repair of scrotal hernias. METHODS:A review of prospectively maintained databases among two academic hernia centers was conducted to identify patients who underwent MIS inguinal hernia repairs with primary sac abandonment. Patient demographics, hernia risk factors, intraoperative factors, and postoperative outcomes were evaluated. Short-term outcomes related to patient-reported experiences and surgical-site occurrences requiring procedural intervention were queried. RESULTS:Sixty-seven male patients [median age: 51.6 years; interquartile range (IQR): 45-65 years] underwent inguinal hernia repair with primary sac abandonment. Anatomic polypropylene mesh was used in 98.5% cases. Rates of postoperative complications were low and included postoperative urinary retention (6%), clinically identified or patient-reported seromas/hematomas within a 30-day follow-up period (23.9%), deep venous thrombosis (1.5%), and pelvic hematoma (1.5%). No seromas or hematomas necessitated procedural interventions, with resolution of symptoms within three months of their operation date. CONCLUSION/CONCLUSIONS:We report a multi-center experience of patients managed with primary abandonment of the sac technique during repair of inguinoscrotal hernias. Utilization of this technique appears to be safe and reproducible with a low burden of short-term complications.
PMID: 38502368
ISSN: 1248-9204
CID: 5640402

Research Opportunities and Ethical Considerations for Heart and Lung Xenotransplantation Research: A report from a National Heart, Lung, and Blood Institute workshop

Khush, Kiran K; Bernat, James L; Pierson, Richard N; Silverman, Henry J; Parent, Brendan; Glazier, Alexandra K; Adams, Andrew B; Fishman, Jay A; Gusmano, Michael; Hawthorne, Wayne J; Homan, Mary E; Hurst, Daniel J; Latham, Stephen; Park, Chung-Gyu; Maschke, Karen J; Mohiuddin, Muhammad M; Montgomery, Robert A; Odim, Jonah; Pentz, Rebecca D; Reichart, Bruno; Savulescu, Julian; Wolpe, Paul Root; Wong, Renee P; Fenton, Kathleen N
Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including non-human primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potential novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions, and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.
PMID: 38514013
ISSN: 1600-6143
CID: 5640772