Citations

Introduction Video visits in primary care have decreased significantly since their surge early in the COVID-19 pandemic. Methods Clinicians including physicians, nurse practitioners, and physician assistants in the Mayo Clinic Department of Family Medicine were invited to dedicate one to two half-days per month exclusively to video visits. Schedules for these half-day sessions remained restricted to video appointments until the day prior. If at least 80% of slots were not filled by then, remaining openings were converted to in-person visits. If the half-day sessions were at least 80% full with video visits, clinicians had the option of performing these sessions remotely. Results Of 155 eligible clinicians, 34 (22%) participated voluntarily in this scheduling intervention. For the participating clinicians, the average video visit rate increased from 6.3% per month preintervention to 11.5% postintervention ( p < 0.001). On a departmental level, the trend line for the percent of outpatient visits via video visit was decreasing by −0.1% per month preintervention. The postintervention slope of the trend line was 0.3% per month ( p < 0.001). The majority (65%) of the time the half-day video visit schedules filled at least 80% and did not require conversion to allow in-person visits allowing clinicians to work remotely if they chose. Conclusion Allowing family medicine clinicians to perform 1–2 half-day schedules dedicated to only video visits increases the percentage of video visit performed per month both for individual clinicians and on a departmental level.

Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) exhibit great therapeutic potential in ischemia-associated conditions and diseases such as myocardial infarction, ischemic stroke, and wound healing. Enhancing the therapeutic efficacy of MSC-EVs could advance their clinical application. Diverse cargos (proteins, mRNA, microRNA, etc.) in MSC-EVs contribute to the therapeutic effects in various diseases. Vascular endothelial growth factor (VEGF) is one of the primary driving molecules in promoting angiogenesis and protecting endothelial cells lining blood vessels from apoptosis. In this study, we explored the feasibility of engineering parent MSCs with VEGF mRNA to potentiate therapeutic effects of their derived EVs. We first detected elevated levels of VEGF mRNA and protein in transfected MSCs and demonstrated the bioactivity of secreted VEGF by an angiogenesis assay. Furthermore, EVs derived from VEGF mRNA-engineered MSCs (VEGF-MSC-EVs) contained high levels of VEGF mRNA and protein and showed superior ability to protect human umbilical vein endothelial cells (HUVECs) from apoptosis compared to EVs derived from control MSCs (control MSC-EVs). To our knowledge, this is the first report demonstrating that VEGF-MSC-EVs boost therapeutic efficacy by promoting endothelial cell survival. Our findings offer a novel approach for cell-free therapy in ischemia-associated conditions and diseases.

Abstract Coccidioidomycosis is an invasive fungal infection that can disseminate and cause severe disease. Fosmanogepix (“gepix”), a first-in-class antifungal available via expanded access (NCT06433128), was successful in 8/11 patients (meningitis, 6/8 [75%]; nonmeningeal dissemination, 2/3 [66%]) and was well tolerated for a median treatment duration of 208 days.

Abstract Background Substituting group A whole blood (GAWB) might relieve some of the burden on the low titer group O whole blood (LTOWB) inventory. This simulation examined the effect of implementing GAWB at a large trauma hospital. Study Design and Methods A civilian trauma center with LTOWB and GAWB par levels set to 22 and 10 units, respectively, was modeled as the baseline. The average daily number of WB recipients was 0.5 who received an average of four WB units per patient. LTOWB was issued in packages of five and all had to be consumed before a group A patient could be switched to GAWB. Several variations on the baseline simulation were also modeled. Results In the baseline simulation, there was a median (interquartile range, IQR) of 1 (0–2) GAWB and 16 (13–19) LTOWB recipients per month. The median (IQR) GAWB and LTOWB units transfused per month was 2 (0–9) and 56 (42–72), respectively. Fourteen percent of group A patients received any quantity of GAWB. The variations that had the most impact on GAWB usage included increasing the number of WB recipients to 2.5 per day where the median (IQR) monthly number of GAWB recipients and units transfused increased to 4 (3–5) recipients and 21 (12–29) units, respectively, and when the average WB requirements increased to eight units per patient resulting in transfusing a median (IQR) of 10 (5–15) GAWB units per month to 3 (1–4) recipients. Discussion Under routine civilian hospital circumstances, implementing GAWB will have a modest impact on LTOWB inventory.

Abstract Background Some centres advocate preoperative radiotherapy in patients with pancreatic cancer and arterial involvement despite a lack of Level 1 evidence on survival benefit. Although it has been suggested that preoperative radiotherapy may increase the risk of postpancreatectomy haemorrhage (PPH) and morbidity, evidence is again lacking. This study investigated the association between preoperative radiotherapy and both PPH and major morbidity following arterial divestment/resection during pancreatic adenocarcinoma resection after chemotherapy. Methods Consecutive patients diagnosed with pancreatic adenocarcinoma and &gt; 180° arterial involvement who were treated with preoperative chemotherapy with or without radiotherapy followed by pancreatic resection with arterial divestment/resection were included in the study. Logistic regression analyses including propensity score-based overlap weighting were performed to investigate associations between radiotherapy and in-hospital PPH grade B/C and major morbidity, expressed as adjusted risk differences (aRDs). Results Overall, 246 patients undergoing pancreatic resection with arterial resection (169, 69%) or divestment (77, 31%) were included. Radiotherapy was not associated with PPH (aRD 6%; 95% confidence interval (c.i.) −3 to 14), regardless of arterial divestment (aRD 3%; 95% c.i. −5 to 11) or arterial resection (aRD 12%; 95% c.i. 1 to 23; Pinteraction = 0.189). Radiotherapy was associated with a 14% (95% c.i. 2 to 25) higher risk of major morbidity, especially after arterial resection (aRD 27%; 95% c.i. 11 to 43) compared with arterial divestment (aRD −12%; 95% c.i. −35 to 11; Pinteraction = 0.006) and after external beam radiotherapy (aRD 21%; 95% c.i. 8 to 32) compared with stereotactic body radiotherapy (aRD −12%; 95% c.i. −27 to 6; Pinteraction = 0.0001). Ninety-day mortality was increased, albeit not significantly, after preoperative radiotherapy (10 (8%) versus 3 (3%) deaths with versus without preoperative radiotherapy, respectively; P = 0.067). Conclusions Radiotherapy before resection of pancreatic cancer with &gt; 180° arterial involvement was associated with an increased risk of postoperative major morbidity when arterial resection, but not arterial divestment, was performed. This risk should be taken into account when considering preoperative radiotherapy in patients who may require arterial resection.

Abstract Background The increased use of superior mesenteric artery (SMA) divestment has been a driver behind the increased resection rate for locally advanced pancreatic cancer following preoperative therapy. This has also resulted in an increase in the rate of postoperative neurogenic diarrhoea, but knowledge about postoperative neurogenic diarrhoea is lacking. The aims of this study were to determine the incidence, risk factors, management, and outcomes of neurogenic diarrhoea after SMA divestment/resection for pancreatic adenocarcinoma. Methods This multicentre retrospective study included consecutive patients undergoing pancreatic adenocarcinoma resection, including SMA divestment/resection, after preoperative chemotherapy with or without radiotherapy between 2016 and 2022. Primary endpoints were the incidence of postoperative neurogenic diarrhoea, associated factors, treatment strategies, and outcomes. Secondary endpoints were the rate of adjuvant chemotherapy and the impact of neurogenic diarrhoea on overall survival (OS). Results Overall, 291 patients who underwent pancreatic resection with concomitant SMA divestment (240, 82%) or resection (51, 18%) were included in the study. Postoperative neurogenic diarrhoea was diagnosed in 193 patients. The adjusted risk of developing neurogenic diarrhoea was 59% (95% confidence interval (c.i.) 46 to 73) after ≤ 180° SMA divestment, 80% (95% c.i. 67 to 93) after &gt; 180° SMA divestment, and 77% (95% c.i. 66 to 88) after SMA resection. Postoperative neurogenic diarrhoea was treated with non-opioid drugs (29, 15%), non-opium opioids (140, 73%), opium tincture (69, 36%), and/or octreotide (49, 25%), and normalized in 51% of patients. After adjusting for confounders, neurogenic diarrhoea was not significantly associated with OS (hazard ratio 0.83; 95% c.i. 0.55 to 1.25). Conclusion Neurogenic diarrhoea occurred in two-thirds of patients following resection of pancreatic adenocarcinoma with concomitant SMA divestment/resection, particularly after &gt; 180° SMA divestment or SMA resection. Although challenging to manage, neurogenic diarrhoea is not associated with impaired OS. Evidence-based treatment strategies are needed for adequate management.

Background: Stable osteochondritis dissecans (OCD) lesions are primarily treated nonoperatively. Nonoperative treatment includes several recommendations, including the use of an unloader brace. However, little is known about the clinical effectiveness of unloader bracing and its influence on OCD healing, return to sports, and patient-reported outcomes (PROs). The purpose of this investigation was to evaluate the impact of unloader bracing on patients with stable medial femoral condyle (MFC) OCD lesions treated nonoperatively. Purpose: To investigate the influence of valgus unloader bracing on the success of treating stable MFC OCD with nonoperative treatment strategies. Study Design: Cohort study; Level of evidence, 2. Methods: The authors used a prospective cohort of patients receiving nonoperative care for stable MFC knee OCD lesions. The primary variable of interest was the efficacy of bracing. The primary outcomes were transition from nonoperative care to surgical intervention, return-to-play (RTP) clearance, and PROs. Bivariate testing was used to determine if there were differences between groups. Chi-square testing was used to determine if there were differences in rates of transition to surgery by group. The timing of the transition by each group was assessed using a Wilcoxon rank-sum test, given the nonparametric nature of the data. Kaplan-Meier survival analysis was used to calculate time at risk, incidence rate, and survival times for each group. Results: A total of 185 knees (bracing group: 123 [66.5%] knees; no-bracing group: 62 [33.5%] knees) were analyzed. Overall, 142 (76.8%) knees were successfully treated nonoperatively. Transition to surgery occurred in 43 (23.2%) knees. There were no differences in transition to surgery by groups, with no differences seen by group. Of the knees that did not transition to surgical care, 65 (71.4%) in the bracing group and 38 (74.5%) in the no-bracing group received RTP clearance ( P = .693). PRO scores were similar between the 2 groups at the time of RTP clearance. Conclusion: The inclusion of an unloader brace in the nonoperative treatment for stable MFC OCD lesions did not decrease the likelihood of patients undergoing surgical intervention or improve their PRO scores at the time of RTP clearance. Registration: NCT02771496 (ClinicalTrials.gov identifier).

PURPOSE GBM AGILE (ClinicalTrials.gov identifier: NCT03970447 ) is a phase II/III Bayesian adaptive platform registration trial testing multiple arms against a common control; the primary end point is overall survival (OS). Regorafenib, a multikinase inhibitor, showed OS benefit in recurrent (RD) glioblastoma in the phase II REGOMA trial and entered GBM AGILE as the first investigational arm. METHODS Patient subtypes included in the regorafenib arm of GBM AGILE were newly diagnosed unmethylated (NDU) and RD glioblastoma. Prospective defined sets of subtypes, or arm signatures, were NDU, RD, and all (NDU + RD). As the first investigational arm in GBM AGILE, regorafenib was equally randomized to the control arm. Treatment in the control arm is temozolomide + radiotherapy (in newly diagnosed) or lomustine (in RD). Efficacy was assessed by OS hazard ratio (HR), arm/control, and demonstrated when the Bayesian probability of benefit (HR <1.00) was ≥98%. Analysis was performed monthly for limited efficacy, which occurs when the Bayesian predictive power is <25% for all signatures, and determines stopping enrollment. Follow-up continued for 12 months after accrual stopped. RESULTS When the predictive power was <25% in all predefined signatures for regorafenib, accrual stopped for limited efficacy. The final analysis did not demonstrate OS improvement in the regorafenib arm in RD nor NDU glioblastoma. Median HRs were 1.05 (NDU), 1.07 (RD), and 1.07 (all) with final probabilities of benefit (HR <1.00) of 0.421 (NDU), 0.312 (RD), and 0.296 (all). Regorafenib was associated with increased toxicity relative to control. CONCLUSION GBM AGILE did not show superiority of regorafenib over control in RD (lomustine) or NDU (temozolomide + radiotherapy) glioblastoma, yet caused increased toxicities. Regorafenib has been removed from National Comprehensive Cancer Network guidelines as a treatment option for RD.

Epidural and dorsal root stimulation have emerged as promising therapies to restore function after spinal cord injury. However, how each modality uniquely or jointly engages spinal circuits remains unclear. To address this, we analyzed leg electromyography (EMG) responses to epidural stimulation (ES) and dorsal root ganglia stimulation (DRGS) delivered to the lumbosacral cord in the same individuals.