F18-Choline PET/CT or MIBI SPECT/CT in the Surgical Management of Primary Hyperparathyroidism: A Diagnostic Randomized Clinical Trial.

Importance: Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a first-line imaging technique for preoperative localization of parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (PHPT) is unclear. Objective: To compare first-line FCH PET/CT vs MIBI SPECT/CT for optimal care in patients with PHPT needing parathyroidectomy and to compare the proportions of patients in whom the first-line imaging method resulted in successful minimally invasive parathyroidectomy (MIP) and normalization of calcemia 1 month after surgery. Design, Setting, and Participants: A French multicenter randomized open diagnostic intervention phase 3 trial was conducted. Patients were enrolled from November 2019 to May 2022 and participated up to 6 months after surgery. The study included adults with PHPT and an indication for surgical treatment. Patients with previous parathyroid surgery or multiple endocrine neoplasia type 1 (MEN1) were ineligible. Interventions: Patients were assigned in a 1:1 ratio to receive first-line FCH PET/CT (FCH1) or MIBI SPECT/CT (MIBI1). In the event of negative or inconclusive first-line imaging, they received second-line FCH PET/CT (FCH2) after MIBI1 or MIBI SPECT/CT (MIBI2) after FCH1. All patients underwent surgery under general anesthesia within 12 weeks following the last imaging. Clinical and biologic (serum calcemia and parathyroid hormone levels) assessments were performed 1 and 6 months after surgery. Main Outcomes and Measures: The primary outcome was a true-positive first-line imaging-guided MIP combined with uncorrected serum calcium levels of 2.55 mmol/l or less 1 month after surgery, corresponding to the local upper limit of normality. Results: Overall, 57 patients received FCH1 (n = 29) or MIBI1 (n = 28). The mean (SD) age of patients was 62.8 (12.5) years with 15 male (26%) and 42 female (74%) patients. Baseline patient characteristics were similar between groups. Normocalcemia at 1 month after positive first-line imaging-guided MIP was observed in 23 of 27 patients (85%) in the FCH1 group and 14 of 25 patients (56%) in the MIBI1 group. Sensitivity was 82% (95% CI, 62%-93%) and 63% (95% CI, 42%-80%) for FCH1 and MIBI1, respectively. Follow-up at 6 months with biochemical measures was available in 43 patients, confirming that all patients with normocalcemia at 1 month after surgery still had it at 6 months. No adverse events related to imaging and 4 adverse events related to surgery were reported. Conclusions: This randomized clinical trial found that first-line FCH PET/CT is a suitable and safe replacement for MIBI SPECT/CT. FCH PET/CT leads more patients with PHPT to correct imaging-guided MIP and normocalcemia than MIBI SPECT/CT thanks to its superior sensitivity. Trial Registration: ClinicalTrials.gov Identifier: NCT04040946.

Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma.

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL. OBJECTIVE: Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL. DESIGN: We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. Patients were divided into two groups: genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and historic patients, who only benefited from the genetic test several years after initial PPGL diagnosis. RESULTS: Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127). CONCLUSION: Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.

Manual Closed-Loop Insulin Delivery Using a Saddle Point Model Predictive Control Algorithm: Results of a Crossover Randomized Overnight Study.

BACKGROUND: The purpose was to assess the efficacy of a new closed-loop algorithm (Saddle Point Model Predictive Control, SP-MPC) in achieving nocturnal normoglycemia while reducing the risk of hypoglycemia in patients with type 1 diabetes. METHOD: In this randomized crossover study, 10 adult patients (mean hemoglobin A1c 7.35 ± 1.04%) were assigned to be treated overnight by open loop using sensor-augmented pump therapy (open-loop SAP) or manual closed-loop delivery. During closed loop, insulin doses were calculated using the SP-MPC algorithm and administered as manual boluses every 15 minutes from 9:00 pm to 8:00 am. Patients consumed a self-selected meal (65-125 g of carbohydrates) at 7:00 pm accompanied by their usual prandial bolus. Blood glucose was measured every 30 minutes. The primary endpoints were the time spent in target (70-145 mg/dl) and time spent below 70 mg/dl from 11:00 pm to 8:00 am. RESULTS: Time spent in target did not differ between closed-loop and open-loop SAP. The number of hypoglycemic events (<70 mg/dl) was reduced 2.8-fold in closed loop (n = 5, median = 0/patient/hour; interquartile range: 0-0.11) as compared to open-loop SAP (n = 14, median = 0.22/patient/hour, 0.02-0.22) ( P = .02). The area under the curve for sensor glucose values >145 mg/dl was significantly lower during closed-loop than during open-loop SAP ( P = .03) as well as HBGI ( P = .02). CONCLUSIONS: This pilot study suggests that the use of the SP-MPC algorithm may improve mean overnight glucose control and reduce the number of hypoglycemic events as compared to SAP therapy.

Insulin Pump Failures: Has There Been an Improvement? Update of a Prospective Observational Study.

BACKGROUND: Insulin pump failures had been assessed in our center by a prospective observational study from 2001 to 2007. The aim of this study was to update our data since 2008 and to determine whether there exist specific risk factors for insulin pump failures. METHODS: All insulin pump defects were prospectively collected between 2008 and 2013 in a monocentric cohort of 350 new pumps. Clinical consequences were recorded. Brand and model of pumps and type of defects and patients' characteristics (gender, type of diabetes, age at diabetes diagnosis, age at first pump, pump treatment duration, number of previous pumps, and number of previous pump failures) were tested for possible association with insulin pump failure. RESULTS: Malfunctions occurred in 239 (68%) pumps. The incidence rate was 33/100 pump-years. There were 28 (12%) complete failures, 17 (7%) alarms, 83 (35%) mechanical defects, and 105 (44%) minor defects. Survival curves did not differ according to pump brand and model. Hyperglycemia occurred in 2.9% of cases. In multivariate analysis, only patient age less than 40 years at the initiation of pump therapy was associated with higher risk of malfunction (hazard ratio 1.64; 95% confidence interval 1.19-2.24; P = 0.002). CONCLUSIONS: Pump malfunctions remain common with modern pumps. We report less complete failures than in our previous study. This could be because of improvement in quality of pumps or to our strategy of systematic screening and replacement in case of mechanical defects.