Gregory J. Beilman

Background: Total pancreatectomy with islet auto‐transplantation (TPIAT) alleviates pain and preserves islet function in patients with severe pancreatitis. Although approximately one third of recipients achieve insulin independence, spontaneous hypoglycemia has been observed in this population. Its frequency, risk factors, and management remain poorly characterized. Methods: Using prospectively collected data on insulin‐independent (TPIAT) recipients at the University of Minnesota (2010–2023), we compared patients who developed hypoglycemia (defined as documented blood glucose < 70 mg/dL) to those with no reported hypoglycemia. Demographic, clinical, surgical, and metabolic variables were evaluated, and treatment strategies were reviewed. Results: Among 503 TPIAT recipients, 156 (31%) achieved insulin independence; of these, 45 (28.8%) experienced hypoglycemia, including 32 (20.5%) with level 2 hypoglycemia (< 54 mg/dL). Severe hypoglycemia events requiring external assistance occurred in 25% of affected individuals. Hypoglycemia developed a mean of 2.4 ± 2.2 years posttransplant, most commonly postprandial or exercise‐related. Patients who developed hypoglycemia were older at the time of TPIAT ( p = 0.036) and had higher preoperative BMI ( p = 0.016) and a greater prevalence of malabsorptive disorders ( p < 0.001), whereas islet yield and metabolic testing results were similar between patients with and without hypoglycemia. Most patients with hypoglycemia (78%) were managed with non‐pharmacological interventions (dietary, continuous glucose monitoring); pharmacologic therapies included acarbose (22%), diazoxide (13%), and minidose glucagon (7%). Conclusions: Spontaneous hypoglycemia is a frequent, clinically relevant complication among insulin‐independent TPIAT recipients. Older age, higher BMI, and malabsorptive disorders were associated with increased susceptibility. Routine surveillance, dietary counseling, and continuous glucose monitoring (CGM) are common components of management.

Introduction: Targets for continuous glucose monitoring (CGM) are well established for type 1 and type 2 diabetes. In total pancreatectomy with islet autotransplantation (TPIAT), stricter glycemic targets are needed to avoid metabolic stress on transplanted islets, but no guidelines exist for CGM targets. Methods: We aimed to determine CGM targets for TPIAT clinical management by associating CGM metrics with goal hemoglobin A1c (HbA1c) ≤ 6.5%. Targets for time in range (TIR) 70–140, TIR 70–180, mean CGM glucose, and time in hyperglycemia (>140, >180, >250 mg/dL) were chosen to give good sensitivity and specificity for identifying HbA1c ≤6.5%. Results: We included 256 pairs of 14‐day CGM metrics with a concurrent HbA1c value ( n = 82 patients, age 35 [IQR 19–46] years at surgery, 70% female) who were ≥0.5 years post TPIAT (median 4.1 years) and wearing Dexcom G6. Most patients had more than one HbA1c and corresponding CGM available (median 2 [IQR 1–4] per patient). Conclusion: We found that TIR 70–140 ≥ 50% and TIR 70–180 mg/dL ≥ 75% may be reasonable minimum targets for patients and providers using CGM data to manage diabetes long‐term after TPIAT. Failure to meet these targets should prompt starting or adjusting insulin therapy, especially if hypoglycemia is not a concern.

BACKGROUND: NK cell function is impaired in people with HIV (PWH), hindering their potential to reduce the lymphoid tissue (LT) reservoir. The IL-15 superagonist N-803 has been shown to enhance NK and T cell function and thus may reduce viral reservoirs. METHODS: To determine the impact of N-803 on LTs, we conducted a clinical trial where 10 PWH on effective antiretroviral therapy (ART) were given 3 subcutaneous 6 mcg/kg doses of N-803. We obtained PBMCs and lymph node (LN) and gut biopsies at baseline and after the last N-803 dose. RESULTS: We found a nonstatistically significant approximately 0.50 median log reduction in the frequency of viral RNA ⁺ (vRNA ⁺ ) and vDNA ⁺ cells/g in the 6 participants with baseline and posttreatment LN biopsies. In the ileum, we observed reductions of vRNA ⁺ cells in 8/10 participants and vDNA ⁺ cells in all participants. We also found significant inverse correlations between NK cell proliferation and the frequency of vRNA ⁺ cells and between NKG2A expression on NK cells and the frequency of vRNA ⁺ cells. CONCLUSION: Our findings suggest N-803 may reduce the HIV reservoir in LTs of PWH on ART, an effect likely mediated by enhanced NK cell function. Controlled studies assessing the impact of NK cell therapy on HIV LTs are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT04808908. FUNDING: NIH grants 5UM1AI126611, UL1TR002494, R01 AI147912, R35 CA283892, and UM1AI164561.

Objectives: Chronic pancreatitis is a debilitating and progressive inflammatory disease with an altered quality of life due to severe abdominal pain. Pancreaticoduodenectomy is a surgical option for patients with bulky disease involving the head of the pancreas, especially when this disease has progressed to stricture of the bile duct, duodenum, or both. A long-term issue associated with this procedure is the stricture of the pancreatic anastomosis. Reoperative and endoscopic interventions are difficult related to difficulty in reaching the anastomosis endoscopically. We describe a variation of this procedure with the potential to lead to longer-term improvement in the drainage of the residual pancreas. Methods: We reviewed electronic medical records of patients undergoing pancreaticoduodenectomy for chronic pancreatitis performed by 1 surgeon at the University of Minnesota Medical Center, Minneapolis, MN, between 2014 and 2023. Information gathered from the patient’s records included preoperative demographics, perioperative outcomes, and postoperative follow-up information. Results: The described procedure was performed on 8 patients between 2014 and 2023. Three patients have died since surgery at 1.5, 5.5, and 8 years postop, with no deaths related to pancreatitis or surgical complications. Of the remaining 5 patients, the median time from surgery is 7.5 years. Conclusions: We describe a surgical technique that may reduce the risk of pancreaticojejunal stricture in patients undergoing pancreaticoduodenectomy for chronic pancreatitis. In a small series of patients, this procedure can be performed safely with acceptable results.

INTRODUCTIONTraumatic brain injury (TBI) represents a major health issue in the United States (U.S.) with over 1.7 million injuries annually(1). Approximately 15% are categorized as moderate to sev...

BACKGROUND: There is conflicting evidence regarding emergency medical service (EMS) provider level of training and outcomes in trauma. We hypothesized that advanced life support (ALS) provider transport is associated with lower mortality compared with basic life support transport. METHODS: We performed secondary analysis of a combined prehospital and in-hospital database of trauma patients utilizing ESO electronic medical records from 2018 to 2022. We included encounters with patients aged 15 years to 100 years transported by ground to a Level I or II trauma center with trauma-specific ICD-10-CM codes. Patients dead upon EMS arrival and transfers were excluded. We matched patients using 1:1 nearest neighbor propensity scores based on demographic, injury, and EMS characteristics, prehospital vitals, and trauma center designation. The exposure variable was EMS level of training and outcome was mortality. We conducted subgroup analyses on predefined cohorts (age > 50 years, mechanism of injury, prehospital EMS time > 30 minutes). RESULTS: We identified 30,735 ALS and 1,758 basic life support encounters, representing 1,154 pairs following propensity matching. Mortality was lower among patients transported by ALS providers (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.18–0.88; p = 0.023). Mortality was also lower in the subgroups of patients aged > 50 years (OR, 0.35; 95% CI, 0.13–0.98; p = 0.046), and in patients with mechanisms of injury excluding falls (OR, 0.35; 95% CI, 0.13–0.98; p = 0.047). In those with prolonged prehospital time, the association approached significance (OR, 0.30; 95% CI, 0.08–1.08; p = 0.067). In those with mechanisms of injury of fall, the association was not significant. CONCLUSION: In this retrospective, propensity matched cohort study using a national sample of trauma patients, attendance by ALS providers was associated with reduced mortality. This was observed in the entire cohort, in those aged > 50 years, and those with a higher-risk mechanism of injury. It approached significance in those with prolonged prehospital time. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Venous waveform analysis is an emerging technique to estimate intravascular fluid status by fast Fourier transform deconvolution. Fluid status has been shown proportional to f₀, the amplitude of the fundamental frequency of the waveform's cardiac wave upon deconvolution. Using a porcine model of distributive shock and fluid resuscitation, we sought to determine the influence of norepinephrine on f₀ of the central venous waveform. Eight pigs were anesthetized, catheterized and treated with norepinephrine after precipitation of endotoxemic hypotension, and subsequent fluid resuscitation to mimic sepsis physiology. Hemodynamic parameters and central venous waveforms were continually transduced throughout the protocol for post-hoc analysis. Central venous waveform f₀ before, during and after norepinephrine administration were determined using Fourier analysis. Heart rate increased, while central venous pressure, pulmonary capillary wedge pressure and stroke volume decreased throughout norepinephrine administration (p < 0.05). Mean f₀ at pre-norepinephrine, and doses 0.05, 0.10, 0.15, 0.20 and 0.25 mcg/kg/min, were 2.5, 1.4, 1.7, 1.7, 1.6 and 1.4 mmHg², respectively (repeated measures ANOVA; p < 0.001). On post-hoc comparison to pre-norepinephrine, f₀ at 0.05 mcg/kg/min was decreased (p = 0.04). As the performance of f₀ was previously characterized during fluid administration, these data offer novel insight into the performance of f₀ during vasopressor delivery. Central venous waveform f₀ is a decreased with norepinephrine, in concordance with pulmonary capillary wedge pressure. This allows contextualization of the novel, venous-derived signal f₀ during vasopressor administration, a finding that must be understood prior to clinical translation.

Alterations in the gut microbiome have been implicated in various pathologies. Fecal microbiota transplantation (FMT) has been offered as a novel treatment for conditions implicated in the disruption of the gut-microbiota axis. This case report details the successful treatment of recurrent nonobstructive cholangitis following a single FMT application in a patient who had previously undergone a hepatobiliary tract surgical diversion. Cholangitis was suspected secondary to reflux of an altered microbiome into the surgically reanastomosed biliary tract, and FMT was justified based on the history of recurrent Clostridioides difficile infections. This case supports the further evaluation of the utility of FMT as one potential treatment of post hepatobiliary surgical diversion cholangitis.