Citations

Abstract Background Despite advances in clinical microbiology, the diagnosis of invasive fungal infections remains challenging. Giant magnetoresistance (GMR) is a novel technology that enables the detection of trace amounts of cell-free DNA (cfDNA). We evaluated a high-multiplex molecular diagnostic assay coupled with GMR-enabled lab-on-a-chip technology that can detect 18 different fungal species. Methods Analytical performance was evaluated in spiked plasma samples. After amplification, cfDNA was digested. Residual single-stranded DNA was flowed over a GMR sensor that was surface-coated with probes specific to different fungal species. After hybridization, magnetic beads bound to the probe complexes produced a GMR signal that was detected by the sensors. Clinical performance was determined using residual serum samples collected before the initiation of antifungal treatment from 20 patients with infection. Results The limit of detection of the assay ranged from 5 to 50 copies per polymerase chain reaction (PCR) reaction. Nonspecific signals were not observed in the spiked samples. Fungal cfDNA was detected in 80% of patients with invasive candidiasis (3/4 with candidemia, 5/6 with invasive candidiasis without candidemia), all 3 cases of invasive pulmonary aspergillosis, and all 3 cases of disseminated histoplasmosis. cfDNA was not detected in 2 patients with cryptococcosis (both had negative blood cultures) and 2 patients with Pneumocystis pneumonia. Conclusions We developed a novel GMR-enabled multiplex PCR assay detecting fungal pathogens that have been prioritized for public health action. Clinical sensitivity was highest in cases of presumed angioinvasion and dissemination. This technology has the potential for use in the clinical microbiology laboratory setting.

Importance Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. Objective To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). Design, Setting, and Participants This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. Exposure DBD and DCD livers preserved on NMP or SCS. Main Outcomes and Measures The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. Results A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) ( P < .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P < .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P < .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) ( P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P < .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). Conclusions and Relevance In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Background Short-term outcomes after pancreatoduodenectomy (PD) are well-studied, but long-term reoperation rates and their indications remain poorly characterized. Methods A single-center retrospective chart review was performed on patients who underwent PD for pancreatic adenocarcinoma between 1/2011 and 12/2021. Reoperations occurring >90 days after PD were dichotomized to being related or unrelated to the index PD or pancreatic adenocarcinoma. The Kaplan-Meier analysis estimated the incidence of long-term reoperation at 1 and 5 years postoperatively. Results Six-hundred twenty-eight patients were included. The 5-year incidence of any additional operation >90 days after PD was 30.0% (95% CI 23.2-36.2%), and the 5-year incidence of any long-term related reoperation was 21.2% (95% CI 15.0-26.8%). The most common indications for reoperations by 5-year incidence were cancer recurrence (12.8%, 95% CI 7.6-17.7%), incisional hernia (6.2%, 95% CI 2.6-9.7%), small bowel obstruction (1.3%, 95% CI 0.2-2.4%), and leak, fistula, or infection (1.0%, 95% CI 0.1-2.0%). Of the examined risk factors, only 90-day reoperation was found to be predictive of long-term related reoperations ( P = 0.02). Additionally, the 5-year incidence of endoscopic or interventional radiology procedures was 20.2% (95% CI 14.5-25.4%). However, 40.9% (95% CI 33.6-47.3%) of patients required additional surgery or procedures of any kind between 90 days and 5 years after PD. Discussion Within 5 years of PD, one in three patients required additional surgery, and one in five had operations for related indications. Related reoperative indications included recurrence, hernia, PD-specific complications, and small bowel obstruction. However, the rates of each of these reoperations were relatively low.

ABSTRACT Background Pancreatoduodenectomy (PD) for pancreatic cancer has a profound impact on patients' lives. However, the long‐term financial implications are poorly understood. Objective Assess the financial burden of long‐term survivors who underwent PD. Methods Patients who underwent PD between January 2011 and June 2019 were identified. To evaluate the long‐term financial burden, patients surviving ≥ 3 years post‐resection were prospectively surveyed using the Comprehensive Score for financial Toxicity (COST‐FACIT) and a customized institutionally developed questionnaire. A logistic regression model predicting high financial toxicity was used to identify predictive factors. Results Among 238 eligible patients, 137 (57.6%) responded. Responders had a median age of 66 (59–73) years, with 86.7% identifying as financial prosperous or comfortable. However, 33.3% experienced financial distress due to treatment costs, 27.3% demonstrated high financial toxicity on the COST‐FACIT survey, and 37.2% made sacrifices to afford treatment. Only 8.9% stated that the treatment costs influenced their decisions, and the majority (85.9%) did not discuss financial implications with healthcare providers. Multivariable analysis identified younger age as a risk factor for high financial toxicity. Conclusion One in three long‐term survivors experienced high financial toxicity, with younger age being a predictor. This emphasizes the need for efforts to provide comprehensive support and guidance to patients to navigate their oncological journey.

Background: Despite numerous potential benefits of outpatient surgery, there is currently a lack of national benchmarking data available for hospitals and surgeons to compare their own outcomes as they transition toward outpatient surgery. Materials and methods: Patients who underwent 14 common general surgery operations from 2016 to 2020 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Operations were selected based on frequency and the ability to be performed both inpatient and outpatient. Postoperative complications and readmissions were compared between patients who underwent inpatient vs outpatient surgery. After adjusting for patient comorbidities, multivariable models assessed the effect of patient characteristics on the odds of experiencing postoperative complications. A separate multi-institutional study of 21 affiliated hospitals assessed practice variation. Results: In 13 of the 14 studied procedures, complications were lower for patients who were selected for outpatient surgery (all P<0.01); minimally invasive (MIS) adrenalectomy showed no difference (P=0.61). Multivariable analysis confirmed these findings; the odds of experiencing any adverse events were lower following outpatient surgery in all operations but MIS adrenalectomy (OR 0.97; 95% CI: 0.47–2.02). Analysis of institutional practices demonstrated variation in the rate of outpatient surgery in certain breast, endocrine, and hernia repair operations. Conclusions: Institutional practice patterns may explain the national variation in the rate of outpatient surgery. While the present data does not support the adoption of outpatient surgery to less optimal candidates, addressing unexplained practice variations could result in improved utilization of outpatient surgery.

AbstractBackground and ObjectivesWe assessed the accuracy of preoperative gallium‐68 DOTA‐Tyr3‐octreotate (DOTATATE) positron emission tomography (PET) imaging in estimating multifocality and nodal metastases of small bowel neuroendocrine tumors (sbNETs).MethodsA multicenter analysis was performed on patients with sbNETs who underwent preoperative DOTATATE PET imaging and surgical resection, with manual palpation of the entire length of the small bowel, between January 2016 and August 2022. Preoperative imaging reports and blinded secondary imaging reviews were compared to the final postoperative pathology reports. Descriptive statistics were applied.ResultsOne‐hundred and four patients met inclusion criteria. Pathology showed 53 (51%) patients had multifocal sbNETs and 96 (92%) had nodal metastases. The original preoperative DOTATATE PET imaging identified multifocal sbNET in 28 (27%) patients and lymph node (LN) metastases in 80 (77%) patients. Based on original radiology reports, sensitivity for multifocal sbNET identification was 45%, specificity was 92%, positive predictive value (PPV) was 86%, and negative predictive value (NPV) was 62%. For the identification of LN metastases, sensitivity was 82%, specificity was 88%, PPV was 99%, and NPV was 29%.ConclusionsAlthough DOTATATE PET imaging is specific and relatively accurate, sensitivity and NPV are insufficient to guide surgical planning. Preoperative use should not replace open palpation to identify additional synchronous lesions or to omit regional lymphadenectomy.

Objective: To describe long-term quality of life (QOL) and gastrointestinal (GI) symptoms in patients who underwent pancreatoduodenectomy for pancreatic cancer in the modern era. Background: As advances in pancreatic cancer management improve outcomes, it is essential to assess long-term patient-reported outcomes after surgery. Methods: Patients who underwent curative intent pancreatoduodenectomy for pancreatic cancer between January 2011 and June 2019 from a single center were identified. Patients alive ≥3 years after surgery were considered long-term survivors (LTS). LTS who were alive in June 2022 received a 55-question survey to assess their QOL (EORTC-QLQ-C30) and GI symptoms (EORTC-PAN26 and Problem Areas in Diabetes Questionnaire). Responses were compared against population norms. Clinicodemographic characteristics in LTS versus non-LTS and survey completion were compared. Results: Six hundred seventy-two patients underwent pancreatoduodenectomy for pancreatic cancer; 340 were LTS. One hundred thirty-seven patients of the 238 eligible to complete the survey responded (response rate: 58%). Compared to the US general population, LTS reported significantly higher QOL (75 vs 64; P<0.001), less nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and constipation, but more diarrhea (all P<0.001). Most patients (n=136/137, 99%) reported experiencing postoperative GI symptoms related to pancreatic insufficiency (n=71/135, 53%), reflux (n=61/135, 45%), and delayed gastric emptying (n=31/136, 23%). Most patients (n=113/136, 83%) reported that digestive symptoms overall had little to no impact on QOL, and 91% (n=124/136) would undergo surgery again. Conclusions: Despite known long-term complications following pancreatoduodenectomy, cancer survivors appear to have excellent QOL. Specific long-term gastrointestinal symptoms data should be utilized for preoperative education and follow-up planning.

BACKGROUND: Although the overall psychosocial benefits and body image gains of postmastectomy breast reconstruction are well-established, there is limited information on how postoperative complications affect patient quality of life (QOL). STUDY DESIGN: A single-institution cross-sectional survey analysis was performed on patients who underwent postmastectomy breast reconstruction between 2008 and 2020. QOL was assessed using the BREAST-Q and the Was It Worth It questionnaires. The results were compared among patients who had major complications, minor complications, and no complications. Responses were compared using 1-way ANOVA and chi-square tests as appropriate. RESULTS: A total of 568 patients met inclusion criteria, and 244 patients responded (43% response rate). Most patients did not have any complications (n = 128; 52%), 41 had minor complications (17%), and 75 had major complications (31%). There were no differences in any of the BREAST-Q well-being metrics based on degree of complication. Across all 3 groups, patients reported that surgery was worthwhile (n = 212; 88%), they would choose reconstruction again (n = 203; 85%), and they would recommend it to a friend (n = 196; 82%). Overall, 77% reported that their overall experience either met or exceeded expectations, and 88% of patients had unchanged or improved overall QOL. CONCLUSIONS: Our study demonstrates that QOL and well-being are not negatively impacted by postoperative complications. Although patients who had no complications had an overall more positive experience, nearly two-thirds of all patients, no matter the degree of complication, stated that their overall experience either met or exceeded their expectations.