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1.
Hernia ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888837

RESUMEN

PURPOSE: The Ventral Hernia Working Group (VHWG) proposed a ventral hernia grading guideline, primarily supported by expert opinion, recommending biologic mesh placement in high-risk patients. We investigated the relationship between this industry-sponsored guideline and discourse around ventral hernia repair (VHR). METHODS: Medline platform from Web of Science's database identified publications "pre-VHWG"(1999-01-01 to 2009-12-31), and "post-VHWG"(2010-01-01 to 2020-12-31) describing VHR and complications or recurrence of VHR with the following comorbidities: COPD, smoking, diabetes, immunosuppression, or obesity. Poisson regression analyzed keyword frequency over time using logarithmically transformed data. RESULTS: Of 1291 VHR publications identified pre-VHWG and 3041 publications identified post-VHWG, 172 (13.3%) and 642 (21.1%) publications respectively included prespecified keywords. The keyword groups "biologic"(IRR 3.39,95%CI1.34-11.4,p = 0.022) and "comorbid"(IRR 1.95, 95%CI1.09-3.74,p = 0.033) significantly increased with frequency after publication of the VHWG. CONCLUSION: The VHWG publication likely contributed to a focus on comorbidities and biologic mesh in the ensuing literature within the field of VHR.

2.
Hernia ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890182

RESUMEN

PURPOSE: Although intraoperative music is purported to mitigate postoperative pain after some procedures, its application has never been explored in abdominal wall reconstruction (AWR). We sought to determine whether intraoperative music would decrease early postoperative pain following AWR. METHODS: We conducted a placebo-controlled, patient-, surgeon-, and assessor-blinded, randomized controlled trial at a single center between June 2022 and July 2023 including 321 adult patients undergoing open AWR with retromuscular mesh. Patients received noise-canceling headphones and were randomized 1:1 to patient-selected music or silence after induction, stratified by preoperative chronic opioid use. All patients received multimodal pain control. The primary outcome was pain (NRS-11) at 24 ± 3 h. The primary outcome was analyzed by linear regression with pre-specified covariates (chronic opioid use, hernia width, operative time, myofascial release, anxiety disorder diagnosis, and preoperative STAI-6 score). RESULTS: 178 patients were randomized to music, 164 of which were analyzed. 177 were randomized to silence, 157 of which were analyzed. At 24 ± 3 h postoperatively, there was no difference in the primary outcome of NRS-11 scores (5.18 ± 2.62 vs 5.27 ± 2.46, p = 0.75). After adjusting for prespecified covariates, the difference of NRS-11 scores at 24 ± 3 h between the music and silence groups remained insignificant (p = 0.83). There was no difference in NRS-11 or STAI-6 scores at 48 ± 3 and 72 ± 3 h, intraoperative sedation, or postoperative narcotic usage. CONCLUSION: For patients undergoing AWR, there was no benefit of intraoperative music over routine multimodal pain control for early postoperative pain reduction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05374096.

3.
Surg Endosc ; 38(7): 4006-4013, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38862822

RESUMEN

BACKGROUND: Mediumweight (40-60 g/m2) polypropylene (MWPP) mesh has been shown to be safe and effective in CDC class II-III retromuscular ventral hernia repairs (RMVHR). However, MWPP has the potential to fracture, and it is possible that heavyweight (> 75 g/m2) polypropylene mesh has similar outcomes in this context. However, there is limited data on HWPP mesh performance in clean-contaminated and contaminated scenarios. We aimed to compare HWPP to MWPP mesh in CDC class II-III wounds during open RMVHR. METHODS: The Abdominal Core Health Quality Collaborative database was retrospectively queried for a cohort of patients who underwent open RMVHR with MWPP or HWPP mesh placed in CDC class II/III wounds from 2012 to 2023. Mesh types were compared using a 3:1 propensity score-matched analysis. Covariates for matching included CDC classification, BMI, diabetes, smoking within 1 year, hernia, and mesh width. Primary outcome of interest included wound complications. Secondary outcomes included reoperations and readmissions at 30 days. RESULTS: A total of 1496 patients received MWPP or HWPP (1378 vs. 118, respectively) in contaminated RMVHR. After propensity score matching, 351 patients remained in the mediumweight and 117 in the heavyweight mesh group. There were no significant differences in surgical site infection (SSI) rates (13.4% vs. 14.5%, p = 0.877), including deep SSIs (0.3% vs. 0%, p = 1), surgical site occurrence rates (17.9% vs. 22.2%, p = 0.377), surgical site occurrence requiring procedural intervention (16% vs. 17.9%, p = 0.719), mesh removal (0.3% vs. 0%, p = 1), reoperations (4.6% vs. 2.6%, p = 0.428), or readmissions (12.3% vs. 9.4%, p = 0.504) at 30 days. CONCLUSION: HWPP mesh was not associated with increased wound morbidity, mesh excisions, reoperations, or readmissions in the early postoperative period compared with MWPP mesh in open RMVHR for CDC II/III cases. Longer follow-up will be necessary to determine if HWPP mesh may be a suitable alternative to MWPP mesh in contaminated scenarios.


Asunto(s)
Hernia Ventral , Herniorrafia , Polipropilenos , Mallas Quirúrgicas , Infección de la Herida Quirúrgica , Humanos , Hernia Ventral/cirugía , Estudios Retrospectivos , Mallas Quirúrgicas/efectos adversos , Masculino , Femenino , Herniorrafia/métodos , Herniorrafia/efectos adversos , Persona de Mediana Edad , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Anciano , Resultado del Tratamiento , Readmisión del Paciente/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
4.
JAMA Surg ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38865142

RESUMEN

Importance: Durable parastomal hernia repair remains elusive. There is limited evidence comparing the durability of the open retromuscular Sugarbaker and keyhole mesh configurations. Objective: To determine if the open retromuscular Sugarbaker mesh placement technique would lower parastomal hernia recurrence rates. Design, Setting, and Participants: In this single-center, randomized clinical trial, 150 patients with a permanent stoma and associated parastomal hernia who were candidates for open retromuscular parastomal hernia repair were enrolled and randomized from April 2019 to April 2022 and followed up for 2 years. Interventions: Following intraoperative assessment to determine the feasibility of either technique, enrolled patients were randomized to receive either retromuscular Sugarbaker or keyhole synthetic mesh placement. Main Outcomes and Measures: The primary outcome was parastomal hernia recurrence at 2 years. Secondary outcomes included mesh-related complications, wound complications, reoperations, as well as patient-reported pain, abdominal wall-specific quality of life, stoma-specific quality of life, and decision regret at 1 year and 2 years. Results: A total of 150 patients were randomized, and with 91% follow-up at 2 years, there were 13 (17%) parastomal hernia recurrences in the retromuscular Sugarbaker arm and 18 (24%) in the keyhole arm (adjusted risk difference, -0.029; 95% CI, -0.17 to 0.153, and adjusted risk ratio, 0.87; 95% CI, 0.42 to 1.69). There were no statistically significant differences between the Sugarbaker and keyhole groups regarding reoperations for recurrence (2 vs 7, respectively), nonhernia intra-abdominal pathology (4 vs 10, respectively), stoma necrosis (1 vs 0, respectively), mesh-related complications (4 vs 1, respectively), patient-reported pain, abdominal wall-specific quality of life, stoma-specific quality of life, and decision regret at any time point. Conclusions and Relevance: In the setting of open parastomal hernia repair, a retromuscular Sugarbaker mesh placement technique was not superior to a keyhole configuration 2 years after repair. Further innovation is necessary to improve parastomal hernia repair outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03972553.

5.
Ann Surg ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38860367

RESUMEN

OBJECTIVE: To determine the epidemiology of post-operative complications among general surgery patients, inform their relationships with 30-day mortality, and determine the attributable fraction of death of each postoperative complication. BACKGROUND: The contemporary causes of post-operative mortality among general surgery patients are not well characterized. METHODS: VISION is a prospective cohort study of adult non-cardiac surgery patients across 28 centres in 14 countries, who were followed for 30 days after surgery. For the subset of general surgery patients, a cox proportional hazards model was used to determine associations between various surgical complications and post-operative mortality. The analyses were adjusted for preoperative and surgical variables. Results were reported in adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 7950 patients included in the study, 240 (3.0%) patients died within 30 days of surgery. Five post-operative complications (myocardial injury after non-cardiac surgery [MINS], major bleeding, sepsis, stroke, and acute kidney injury resulting in dialysis) were independently associated with death. Complications associated with the largest attributable fraction (AF) of post-operative mortality (i.e., percentage of deaths in the cohort that can be attributed to each complication, if causality were established) were major bleeding (n=1454, 18.3%, HR 2.49 95%CI 1.87-3.33, P<0.001, AF 21.2%), sepsis (n=783, 9.9%, HR 6.52, 95%CI 4.72-9.01, P<0.001, AF 15.6%), and MINS (n=980, 12.3%, HR 2.00, 95%CI 1.50-2.67, P<0.001, AF 14.4%). CONCLUSION: The complications most associated with 30-day mortality following general surgery are major bleeding, sepsis, and MINS. These findings may guide the development of mitigating strategies, including prophylaxis for perioperative bleeding.

6.
BJU Int ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38881297

RESUMEN

OBJECTIVE: To investigate whether preoperative body morphometry analysis can identify patients at risk of parastomal hernia (PH), which is a common complication after radical cystectomy (RC). PATIENTS AND METHODS: All patients who underwent RC between 2010 and 2020 with available cross-sectional imaging preoperatively and at 1 and 2 years postoperatively were included. Skeletal muscle mass and total fat mass (FM) were determined from preoperative axial computed tomography images obtained at the level of the L3 vertebral body using Aquarius Intuition software. Sarcopenia and obesity were assigned based on consensus definitions of skeletal muscle index (SMI) and FM index (FMI). PH were graded using both the Moreno-Matias and European Hernia Society criteria. Binary logistic regression and recursive partitioning were used to identify patients at risk of PH. The Kaplan-Meier method with log-rank and Cox proportional hazards models included clinical and image-based parameters to identify predictors of PH-free survival. RESULTS: A total of 367 patients were included in the final analysis, with 159 (43%) developing a PH. When utilising binary logistic regression, high FMI (odds ratio [OR] 1.63, P < 0.001) and low SMI (OR 0.96, P = 0.039) were primary drivers of risk of PH. A simplified model that only relied upon FMI, SMI, and preoperative albumin improved the classification of patients at risk of PH. On Kaplan-Meier analysis, patients who were obese or obese and sarcopenic had significantly worse PH-free survival (P < 0.001). CONCLUSION: Body morphometry analysis identified FMI and SMI to be the most consistent predictors of PH after RC.

7.
Am Surg ; : 31348241256064, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776896

RESUMEN

At Cleveland clinic, an incorrect surgical count triggers Code Rust; a protocol that mandates an intraoperative patient X-ray, staff radiology read, and discussion with the surgeon before the incision is closed. Code Rust calls from November 2014 to December 2022 were retrospectively reviewed. Realtime workflow and operative details of Code Rust cases were analyzed.1277 Code Rusts were identified. Average time from ordering the X-ray to final radiology report was 50 minutes, totalling $2,362,450.00 spent on operating room time. Code Rust was called twice as frequently during urgent or emergent cases, compared to elective. There were more staff in Code Rust rooms compared to non-Code Rust rooms. A foreign body on X-ray was identified in 42/1277 (3.3%) cases. Code Rust is a resource intensive process that is more common in emergent cases that involve multiple staff. While retained foreign bodies are identified in a small percentage of cases, the current system should be revisited to reduce operating time and expense.

8.
Inflamm Bowel Dis ; 30(Supplement_2): S39-S54, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38778628

RESUMEN

Precision medicine is part of 5 focus areas of the Challenges in IBD Research 2024 research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and pragmatic clinical research. Building on Challenges in IBD Research 2019, the current Challenges aims to provide a comprehensive overview of current gaps in inflammatory bowel diseases (IBDs) research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient-centric research prioritization. In particular, the precision medicine section is focused on the main research gaps in elucidating how to bring the best care to the individual patient in IBD. Research gaps were identified in biomarker discovery and validation for predicting disease progression and choosing the most appropriate treatment for each patient. Other gaps were identified in making the best use of existing patient biosamples and clinical data, developing new technologies to analyze large datasets, and overcoming regulatory and payer hurdles to enable clinical use of biomarkers. To address these gaps, the Workgroup suggests focusing on thoroughly validating existing candidate biomarkers, using best-in-class data generation and analysis tools, and establishing cross-disciplinary teams to tackle regulatory hurdles as early as possible. Altogether, the precision medicine group recognizes the importance of bringing basic scientific biomarker discovery and translating it into the clinic to help improve the lives of IBD patients.


Precision medicine is the practice of getting the most suitable drug or treatment option to each individual patient at the right time. In Crohn's disease and ulcerative colitis, we need to learn more about the diversity of patients to deliver precision medicine.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Enfermedades Inflamatorias del Intestino/terapia , Biomarcadores/análisis , Investigación Biomédica
9.
Surg Endosc ; 38(6): 3433-3440, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38710888

RESUMEN

INTRODUCTION: Fixation of mesh during minimally invasive inguinal hernia repair is thought to contribute to chronic post-herniorrhaphy groin pain (CGP). In contrast to permanent tacks, absorbable tacks are hypothesized to minimize the likelihood of CGP. This study aimed to compare the rates of CGP after laparoscopic inguinal hernia repair between absorbable versus permanent fixation at maximum follow-up. METHODS: This is a post hoc analysis of a randomized controlled trial in patients undergoing laparoscopic inguinal hernia repair (NCT03835351). All patients were contacted at maximum follow-up after surgery to administer EuraHS quality of life (QoL) surveys. The pain and restriction of activity subdomains of the survey were utilized. The primary outcome was rate of CGP, as defined by a EuraHS QoL pain domain score ≥ 4 measured at ≥ 1 year postoperatively. The secondary outcomes were pain and restriction of activity domain scores and hernia recurrence at maximum follow-up. RESULTS: A total of 338 patients were contacted at a mean follow-up of 28 ± 11 months. 181 patients received permanent tacks and 157 patients received absorbable tacks during their repair. At maximum follow-up, the rates of CGP (27 [15%] vs 28 [18%], P = 0.47), average pain scores (1.78 ± 4.38 vs 2.32 ± 5.40, P = 0.22), restriction of activity scores (1.39 ± 4.32 vs 2.48 ± 7.45, P = 0.18), and the number of patients who reported an inguinal bulge (18 [9.9%] vs 15 [9.5%], P = 0.9) were similar between patients with permanent versus absorbable tacks. On multivariable analysis, there was no significant difference in the odds of CGP between the two groups (OR 1.23, 95% CI [0.60, 2.50]). CONCLUSION: Mesh fixation with permanent tacks does not appear to increase the risk of CGP after laparoscopic inguinal hernia repair when compared to fixation with absorbable tacks. Prospective trials are needed to further evaluate this relationship.


Asunto(s)
Implantes Absorbibles , Dolor Crónico , Ingle , Hernia Inguinal , Herniorrafia , Laparoscopía , Dolor Postoperatorio , Mallas Quirúrgicas , Humanos , Hernia Inguinal/cirugía , Laparoscopía/métodos , Laparoscopía/efectos adversos , Herniorrafia/métodos , Herniorrafia/efectos adversos , Masculino , Dolor Postoperatorio/etiología , Persona de Mediana Edad , Femenino , Ingle/cirugía , Dolor Crónico/etiología , Anciano , Calidad de Vida , Estudios de Seguimiento , Adulto
10.
Front Med (Lausanne) ; 11: 1373593, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756942

RESUMEN

Objective: The objective of this study was to examine the impact of the introduction of the Universal Anaesthesia Machine (UAM), a device designed for use in clinical environments with limited clinical perioperative resources, on the choice of general anesthesia technique and safe anesthesia practice in a tertiary-care hospital in Sierra Leone. Methods: We introduced an anesthesia machine (UAM) into Connaught Hospital, Freetown, Sierra Leone. We conducted a prospective observational study of anesthesia practice and an examination of perioperative clinical parameters among surgical patients at the hospital to determine the usability of the device, its impact on anesthesia capacity, and changes in general anesthesia technique. Findings: We observed a shift from the use of ketamine total intravenous anesthesia to inhalational anesthesia. This shift was most demonstrable in anesthesia care for appendectomies and surgical wound management. In 10 of 17 power outages that occurred during inhalational general anesthesia, anesthesia delivery was uninterrupted because inhalational anesthesia was being delivered with the UAM. Conclusion: Anesthesia technologies tailored to overcome austere environmental conditions can support the delivery of safe anesthesia care while maintaining fidelity to recommended international anesthesia practice standards.

11.
Proc Natl Acad Sci U S A ; 121(22): e2403013121, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38781207

RESUMEN

Biomolecular condensates are cellular compartments that concentrate biomolecules without an encapsulating membrane. In recent years, significant advances have been made in the understanding of condensates through biochemical reconstitution and microscopic detection of these structures. Quantitative visualization and biochemical assays of biomolecular condensates rely on surface passivation to minimize background and artifacts due to condensate adhesion. However, the challenge of undesired interactions between condensates and glass surfaces, which can alter material properties and impair observational accuracy, remains a critical hurdle. Here, we introduce an efficient, broadly applicable, and simple passivation method employing self-assembly of the surfactant Pluronic F127 (PF127). The method greatly reduces nonspecific binding across a range of condensates systems for both phase-separated droplets and biomolecules in dilute phase. Additionally, by integrating PF127 passivation with the Biotin-NeutrAvidin system, we achieve controlled multipoint attachment of condensates to surfaces. This not only preserves condensate properties but also facilitates long-time fluorescence recovery after photobleaching imaging and high-precision single-molecule analyses. Using this method, we have explored the dynamics of polySIM molecules within polySUMO/polySIM condensates at the single-molecule level. Our observations suggest a potential heterogeneity in the distribution of available polySIM-binding sites within the condensates.


Asunto(s)
Avidina , Condensados Biomoleculares , Biotina , Poloxámero , Condensados Biomoleculares/química , Condensados Biomoleculares/metabolismo , Poloxámero/química , Biotina/química , Biotina/metabolismo , Avidina/química , Avidina/metabolismo , Recuperación de Fluorescencia tras Fotoblanqueo/métodos , Propiedades de Superficie , Tensoactivos/química , Tensoactivos/metabolismo , Imagen Individual de Molécula/métodos
12.
Am J Surg ; 234: 99-104, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38580567

RESUMEN

INTRODUCTION: Abdominal surgery following transversus abdominis release (TAR) procedure commonly involves incisions through the previously implanted mesh, potentially creating vulnerabilities for hernia recurrence. Despite the popularity of the TAR procedure, current literature regarding post-AWR surgeries is limited. This study aims to reveal the incidence and outcomes of post-TAR non-hernia-related abdominal surgeries of any kind. METHODS: Adult patients who underwent non-hernia-related abdominal surgery following ventral hernia repair with concurrent TAR procedure and permanent synthetic mesh in the Cleveland Clinic Center for Abdominal Core Health between January 2014 and January 2022 were queried from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, and long-term hernia recurrence. RESULTS: A total of 1137 patients who underwent TAR procedure were identified, with 53 patients (4.7%) undergoing subsequent non-hernia-related abdominal surgery post-TAR. Small bowel obstruction was the primary indication for reoperation (22.6%), and bowel resection was the most frequent procedure (24.5%). 49.1% of the patients required urgent or emergent surgery, with the majority (70%) having open procedures. Fascia closure was achieved by absorbable sutures in 50.9%, and of the open cases, fascia closure was achieved by running sutures technique in 35.8%. 20.8% experienced SSO, the SSOPI rate was 11.3%, and 26.4% required more than a single reoperation. A total of 88.7% were available for extended follow-up, spanning 17-30 months, resulting in a 36.1% recurrent hernia diagnosis rate. CONCLUSIONS: Abdominal surgery following TAR surgery is associated with significant comorbidities and significantly impacts hernia recurrence rates. Our study findings underscore the significance of making all efforts to minimize reoperations after TAR procedure and offers suggestions on managing the abdominal wall of these complex cases.


Asunto(s)
Músculos Abdominales , Pared Abdominal , Hernia Ventral , Herniorrafia , Complicaciones Posoperatorias , Reoperación , Mallas Quirúrgicas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hernia Ventral/cirugía , Herniorrafia/métodos , Reoperación/estadística & datos numéricos , Pared Abdominal/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano , Recurrencia , Estudios Retrospectivos , Adulto
13.
Int J Comput Assist Radiol Surg ; 19(6): 1213-1222, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38642297

RESUMEN

PURPOSE: Teamwork in surgery depends on a shared mental model of success, i.e., a common understanding of objectives in the operating room. A shared model leads to increased engagement among team members and is associated with fewer complications and overall better outcomes for patients. However, clinical training typically focuses on role-specific skills, leaving individuals to acquire a shared model indirectly through on-the-job experience. METHODS: We investigate whether virtual reality (VR) cross-training, i.elet@tokeneonedotexposure to other roles, can enhance a shared mental model for non-surgeons more directly. Our study focuses on X-ray guided pelvic trauma surgery, a procedure where successful communication depends on the shared model between the surgeon and a C-arm technologist. We present a VR environment supporting both roles and evaluate a cross-training curriculum in which non-surgeons swap roles with the surgeon. RESULTS: Exposure to the surgical task resulted in higher engagement with the C-arm technologist role in VR, as measured by the mental demand and effort expended by participants ( p < 0.001 ). It also has a significant effect on non-surgeon's mental model of the overall task; novice participants' estimation of the mental demand and effort required for the surgeon's task increases after training, while their perception of overall performance decreases ( p < 0.05 ), indicating a gap in understanding based solely on observation. This phenomenon was also present for a professional C-arm technologist. CONCLUSION: Until now, VR applications for clinical training have focused on virtualizing existing curricula. We demonstrate how novel approaches which are not possible outside of a virtual environment, such as role swapping, may enhance the shared mental model of surgical teams by contextualizing each individual's role within the overall task in a time- and cost-efficient manner. As workflows grow increasingly sophisticated, we see VR curricula as being able to directly foster a shared model for success, ultimately benefiting patient outcomes through more effective teamwork in surgery.


Asunto(s)
Grupo de Atención al Paciente , Realidad Virtual , Humanos , Femenino , Masculino , Curriculum , Competencia Clínica , Adulto , Cirugía Asistida por Computador/métodos , Cirugía Asistida por Computador/educación , Cirujanos/educación , Cirujanos/psicología
14.
Surgery ; 176(1): 148-153, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38641542

RESUMEN

BACKGROUND: Abdominal wall reconstruction requires extensive dissection of the abdominal wall, exposure of the retroperitoneum, and aggressive chemoprophylaxis to reduce the risk of thromboembolic complications. The need for early anticoagulation puts patients at risk for bleeding. We aimed to quantify postoperative blood loss, incidence of transfusion and reoperation, and associated risk factors in patients undergoing complex abdominal wall reconstruction. METHODS: All patients underwent a posterior component separation with transversus abdominis release and placement of retromuscular mesh for ventral hernias <20 cm wide and were enrolled in a clinical trial assessing the utility of trans-fascial mesh fixation. A post hoc analysis was performed to quantify postoperative hemoglobin drop, blood transfusions, and procedural interventions for ongoing bleeding during the first 30 postoperative days. Multivariate logistic regression was used to identify predictors of transfusion. RESULTS: In 325 patients, hemoglobin decreased by 3.61 (±1.58) g/dL postoperatively. Transfusion incidence was 9.5% (n = 31), and 3.1% (n = 10) required a surgical intervention for bleeding. Initiation of therapeutic anticoagulation postoperatively resulted in a higher likelihood of requiring surgical intervention for bleeding (odds ratio 10.4 [95% confidence interval 2.75-43.8], P < .01). Use of perioperative therapeutic anticoagulation was associated with higher rates of transfusion (odds ratio 3.51 [95% confidence interval 1.34-8.53], P < .01). Neither intraoperative blood loss nor operative times were associated with an increased transfusion requirement or need for operative intervention. CONCLUSION: Patients undergoing transversus abdominis release are at a high risk of postoperative bleeding that can require transfusion and reoperation. Patients requiring postoperative therapeutic anticoagulation are at particularly high risk.


Asunto(s)
Pared Abdominal , Transfusión Sanguínea , Hernia Ventral , Hemorragia Posoperatoria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/prevención & control , Hemorragia Posoperatoria/terapia , Transfusión Sanguínea/estadística & datos numéricos , Pared Abdominal/cirugía , Anciano , Hernia Ventral/cirugía , Mallas Quirúrgicas/efectos adversos , Anticoagulantes/uso terapéutico , Herniorrafia/efectos adversos , Herniorrafia/métodos , Reoperación/estadística & datos numéricos , Factores de Riesgo , Adulto , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Incidencia , Modelos Logísticos
15.
Cancer Discov ; 14(6): 994-1017, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38593348

RESUMEN

RAS-driven cancers comprise up to 30% of human cancers. RMC-6236 is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential for the aforementioned unmet medical need. RMC-6236 exhibited potent anticancer activity across RAS-addicted cell lines, particularly those harboring mutations at codon 12 of KRAS. Notably, oral administration of RMC-6236 was tolerated in vivo and drove profound tumor regressions across multiple tumor types in a mouse clinical trial with KRASG12X xenograft models. Translational PK/efficacy and PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses, respectively, in patients with RAS-driven tumors. Consistent with this, we describe here objective responses in two patients (at 300 mg daily) with advanced KRASG12X lung and pancreatic adenocarcinoma, respectively, demonstrating the initial activity of RMC-6236 in an ongoing phase I/Ib clinical trial (NCT05379985). SIGNIFICANCE: The discovery of RMC-6236 enables the first-ever therapeutic evaluation of targeted and concurrent inhibition of canonical mutant and wild-type RAS-GTP in RAS-driven cancers. We demonstrate that broad-spectrum RAS-GTP inhibition is tolerable at exposures that induce profound tumor regressions in preclinical models of, and in patients with, such tumors. This article is featured in Selected Articles from This Issue, p. 897.


Asunto(s)
Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Ratones , Línea Celular Tumoral , Proteínas Proto-Oncogénicas p21(ras)/genética , Femenino , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Guanosina Trifosfato/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Masculino
17.
J Pediatr Gastroenterol Nutr ; 78(5): 1126-1134, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38482890

RESUMEN

OBJECTIVES: Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. METHODS: We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. RESULTS: Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. CONCLUSIONS: UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Fármacos Gastrointestinales , Ustekinumab , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Ustekinumab/uso terapéutico , Femenino , Masculino , Niño , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adolescente , Fármacos Gastrointestinales/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Inducción de Remisión/métodos , Puntaje de Propensión , Sistema de Registros
18.
J Am Coll Surg ; 238(6): 1115-1120, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38372372

RESUMEN

BACKGROUND: Ventral hernias result in fibrosis of the lateral abdominal wall muscles, increasing tension on fascial closure. Little is known about the effect of abdominal wall tension on outcomes after abdominal wall reconstruction. We aimed to identify an association between abdominal wall tension and early postoperative outcomes in patients who underwent posterior component separation (PCS) with transversus abdominis release (TAR). STUDY DESIGN: Using a proprietary, sterilizable tensiometer, the tension needed to bring the anterior fascial elements to the midline of the abdominal wall during PCS with TAR was recorded. Tensiometer measurements, in pounds (lb), were calibrated by accounting for the acceleration of Earth's gravity. Baseline fascial tension, change in fascial tension, and fascial tension at closure were evaluated with respect to 30-day outcomes, including wound morbidity, hospital readmission, reoperation, ileus, bleeding, and pulmonary complications. RESULTS: A total of 100 patients underwent bilateral abdominal wall tensiometry, for a total of 200 measurements (left and right side for each patient). Mean baseline anterior fascial tension was 6.78 lb (SD 4.55) on each side. At abdominal closure, the mean anterior fascial tension was 3.12 (SD 3.21) lb on each side. Baseline fascial tension and fascial tension after PCS with TAR at abdominal closure were not associated with surgical site infection, surgical site occurrence, readmission, ileus, and bleeding requiring transfusion. The event rates for all other complications were too infrequent for statistical analysis. CONCLUSIONS: Baseline and residual fascial tension of the anterior abdominal wall do not correlate with early postoperative morbidity in patients undergoing PCS with TAR. Further work is needed to determine if abdominal wall tension in this context is associated with long-term outcomes, such as hernia recurrence.


Asunto(s)
Músculos Abdominales , Pared Abdominal , Hernia Ventral , Herniorrafia , Humanos , Femenino , Masculino , Hernia Ventral/cirugía , Persona de Mediana Edad , Pared Abdominal/cirugía , Músculos Abdominales/cirugía , Herniorrafia/métodos , Resultado del Tratamiento , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Adulto , Técnicas de Cierre de Herida Abdominal , Estudios Retrospectivos
19.
Surg Endosc ; 38(4): 2019-2026, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38424284

RESUMEN

INTRODUCTION: Intraperitoneal onlay mesh (IPOM) placement for small to medium-sized hernias has garnered negative attention due to perceived long-term risk of mesh-related complications. However, sparse data exists supporting such claims after minimally invasive (MIS) IPOM repairs and most is hindered by the lack of long-term follow-up. We sought to report long-term outcomes and mesh-related complications of MIS IPOM ventral hernia repairs. METHODS AND PROCEDURES: Adult patients who underwent MIS IPOM ventral hernia repair at our institution were identified in the Abdominal Core Health Quality Collaborative database from October 2013 to October 2020. Outcomes included hernia recurrence and mesh-related complications or reoperations up to 6 years postoperatively. RESULTS: A total of 325 patients were identified. The majority (97.2%) of cases were elective, non-recurrent (74.5%), and CDC class I (99.4%). Mean hernia width was 4.16 ± 3.86 cm. Median follow-up was 3.6 (IQR 2.8-5) years. Surgeon-entered or patient-reported follow-up was available for 253 (77.8%) patients at 3 years or greater postoperatively. One patient experienced an early small bowel obstruction and was reoperated on within 30 days. Two-hundred forty-five radiographic examinations were available up to 6 years postoperatively. Twenty-seven patients had hernia recurrence on radiographic examination up to 6 years postoperatively. During long-term follow-up, two mesh-related complications required reoperations: mesh removed for chronic pain and mesh removal at the time of colon surgery for perforated cancer. Sixteen additional patients required reoperation within 6 years for the following reasons: hernia recurrence (n = 5), unrelated intraabdominal pathology (n = 9), obstructed port site hernia (n = 1), and adhesive bowel obstruction unrelated to the prosthesis (n = 1). The rate of reoperation due to intraperitoneal mesh complications was 0.62% (2/325) with up to 6 year follow-up. CONCLUSION: Intraperitoneal mesh for repair of small to medium-sized hernias has an extremely low rate of long-term mesh-related complications. It remains a safe and durable option for hernia surgeons.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Hernia Ventral , Hernia Incisional , Obstrucción Intestinal , Laparoscopía , Adulto , Humanos , Mallas Quirúrgicas/efectos adversos , Hernia Ventral/cirugía , Herniorrafia/efectos adversos , Prótesis e Implantes , Obstrucción Intestinal/cirugía , Hernia Incisional/cirugía , Recurrencia
20.
bioRxiv ; 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38405951

RESUMEN

Biomolecular condensates are cellular compartments that concentrate biomolecules without an encapsulating membrane. In recent years, significant advances have been made in the understanding of condensates through biochemical reconstitution and microscopic detection of these structures. Quantitative visualization and biochemical assays of biomolecular condensates rely on surface passivation to minimize background and artifacts due to condensate adhesion. However, the challenge of undesired interactions between condensates and glass surfaces, which can alter material properties and impair observational accuracy, remains a critical hurdle. Here, we introduce an efficient, generically applicable, and simple passivation method employing self-assembly of the surfactant Pluronic F127 (PF127). The method greatly reduces nonspecific binding across a range of condensates systems for both phase-separated droplets and biomolecules in dilute phase. Additionally, by integrating PF127 passivation with the Biotin-NeutrAvidin system, we achieve controlled multi-point attachment of condensates to surfaces. This not only preserves condensate properties but also facilitates long-time FRAP imaging and high-precision single-molecule analyses. Using this method, we have explored the dynamics of polySIM molecules within polySUMO/polySIM condensates at the single-molecule level. Our observations suggest a potential heterogeneity in the distribution of available polySIM-binding sites within the condensates.

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