Background Postbariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective. Methods Patients with PBH were enrolled in a double-blind, placebo-controlled, crossover trial to evaluate a closed-loop glucose-responsive automated glucagon delivery system designed to reduce severe hypoglycemia. A hypoglycemia detection and mitigation algorithm was embedded in the artificial pancreas system connected to a continuous glucose monitor (CGM, Dexcom) driving a patch infusion pump (Insulet) filled with liquid investigational glucagon (Xeris) or placebo (vehicle). Sensor/plasma glucose responses to mixed meal were assessed during 2 study visits. The system delivered up to 2 doses of study drug (300/150 μg glucagon or equal-volume vehicle) if triggered by the algorithm. Rescue dextrose was given for plasma glucose <55 mg/dL or neuroglycopenia. Results Twelve participants (11 females/1 male, age 52 ± 2, 8 ± 1 years postsurgery, mean ± SEM) completed all visits. Predictive hypoglycemia alerts prompted automated drug delivery postmeal, when sensor glucose was 114 ± 7 vs 121 ± 5 mg/dL (P = .39). Seven participants required rescue glucose after vehicle but not glucagon (P = .008). Five participants had severe hypoglycemia (<55 mg/dL) after vehicle but not glucagon (P = .03). Nadir plasma glucose was higher with glucagon vs vehicle (67 ± 3 vs 59 ± 2 mg/dL, P = .004). Plasma glucagon rose after glucagon delivery (1231 ± 187 vs 16 ± 1 pg/mL at 30 minutes, P = .001). No rebound hyperglycemia occurred. Transient infusion site discomfort was reported with both glucagon (n = 11/12) and vehicle (n = 10/12). No other adverse events were observed. Conclusion A CGM-guided closed-loop rescue system can detect imminent hypoglycemia and deliver glucagon, reducing severe hypoglycemia in PBH. Clinical Trials Registration NCT03255629
Cryptococcal pulmonary nodule in an immunocompetent individual is rare. Here, we perform a literature review on management of asymptomatic pulmonary cryptococcus detected incidentally on radiological imaging. CASE PRESENTATION: An 80-year-old African American male with past medical history of stage II prostate cancer and hypertension presented to our hospital with subacute onset of bilateral lower limb weakness. Extensive workup was inconclusive for etiological diagnosis but showed an incidental 1.2 x 0.9 cm spiculated left upper lobe nodular density on CT chest. Biopsy of the lesion was performed to determine cause and to rule out paraneoplastic syndrome. Cytology was negative for malignant cells but, in fact showed localized granulomatous reaction with fungal forms consistent with Cryptococcus. Serum and CSF were negative for Cryptococcal antigen. He was HIV negative and had no respiratory symptoms. Treatment with fluconazole 400 mg once a day was initiated.
Current therapies for post-bariatric hypoglycemia (PBH) are incompletely effective. We previously reported feasibility of an open-loop glucagon system for this challenging syndrome. In this study, patients with PBH were enrolled in a double-masked, placebo-controlled, crossover trial to determine the efficacy of a closed-loop mini-dose glucagon delivery system to reduce severe hypoglycemia after a mixed meal. A novel hypoglycemia detection & mitigation algorithm was embedded in the Artificial Pancreas System connected to a continuous glucose monitor (CGM, Dexcom) driving a patch infusion pump (Insulet) filled with study drug (Xeris liquid glucagon or vehicle). After screening and enrollment, CGM were placed; participants returned after an overnight fast for the 1 st of 2 study visits. A liquid mixed meal (Ensure Compact: 64 g CHO, 18 g protein, 236 mL) was consumed, and sensor/plasma glucose were measured serially. The system autonomously delivered up to 2 doses of study drug (300/150 mcg of glucagon or equal volume vehicle) if triggered by the hypoglycemia mitigation algorithm. If plasma glucose fell to <55 mg/dL or neuroglycopenia occurred, rescue IV dextrose was given per protocol. During a 2 nd study visit, the protocol was repeated, with pump filled with the other study drug. Twelve participants (11F/1M, age 52+2, postoperative duration 8+1 years, mean+SEM) completed all study visits. In an additional 3 participants, the mixed meal did not trigger either alarm or hypoglycemia, so study drug was not administered, and a second visit was not conducted. For the 12 participants receiving glucagon vs. vehicle during 2 study visits, predictive hypoglycemia alerts prompted automated drug delivery at mean 94+6 vs. 89+5 (p=0.41) minutes post meal, when sensor glucose was 114+7 vs. 121+5 mg/dL (p=0.39). Four participants did not require rescue during either visit; 1 participant required rescue during both visits. Seven participants required rescue glucose after vehicle but not after glucagon (p=0.0082). Similarly, 5 participants had severe hypoglycemia (plasma glucose <55 mg/dL) after vehicle but not after glucagon (p=0.03). Nadir plasma glucose was higher in study visits with glucagon vs. vehicle delivery (67.4±2.7 vs. 58.5±1.9 mg/dL, p=0.004). Glucagon levels were not elevated at time of alert (14.6±1.4 pg/mL) but rose after glucagon delivery (1231±187 vs. vehicle 16 ±1.4 pg/mL at 30 minutes, p = 0.001). No rebound hyperglycemia occurred. Emesis occurred before study drug delivery in 2 visits. Transient pain at infusion site was reported during both glucagon (n=11 of 12) and vehicle (n=10 of 12) study visits. No other adverse advents were observed. Our data demonstrate that a CGM-guided glucagon closed-loop system can detect imminent hypoglycemia and deliver mini-dose glucagon, yielding improvements in post-meal glucose and reducing severe hypoglycemia in patients with PBH.
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