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The spleen contains a reservoir of red blood cells that are mobilized into circulation when under physiological stress. Despite the spleen having an established role in compensation to acute hypoxia, no previous work has assessed the role of the spleen during ascent to high altitude. Twelve participants completed 2 min of handgrip exercise at 30% of maximal voluntary contraction at 1,045, 3,440, and 4,240 m. In a subset of eight participants, an infusion of phenylephrine hydrochloride was administered at a dosage of 30 µg/l of predicted blood volume at each altitude. The spleen was imaged by ultrasound via a 2- to 5.5-MHz curvilinear probe. Spleen volume was calculated by the prolate ellipsoid formula. Finger capillary blood samples were taken to measure hematocrit. Spleen images and hematocrit were taken both before and at the end of both handgrip and phenylephrine infusion. No changes in resting spleen volume were observed between altitudes. At low altitude, the spleen contracted in response to handgrip [272.8 ml (SD 102.3) vs. 249.6 ml (SD 105.7), P = 0.009], leading to an increase in hematocrit (42.6% (SD 3.3) vs. 44.3% (SD 3.3), P = 0.023] but did not contract or increase hematocrit at the high-altitude locations. Infusion of phenylephrine led to spleen contraction at all altitudes, but only lead to an increase in hematocrit at low altitude. These data reveal that the human spleen may not contribute to acclimatization to chronic hypoxia, contrary to its response to acute sympathoexcitation. These results are explained by alterations in spleen reactivity to increased sympathetic activation at altitude. NEW & NOTEWORTHY The present study demonstrated that, despite the known role of the human spleen in increasing oxygen delivery to tissues during acute hypoxia scenarios, the spleen does not mobilize red blood cells during ascent to high altitude. Furthermore, the spleen’s response to acute stressors at altitude depends on the nature of the stressor; the spleen’s sensitivity to neurotransmitter is maintained, while its reflex response to stress is dampened.

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Objective: To examine the acute and chronic effects of structured exercise on glucose outcomes assessed by continuous glucose monitors in adults with type 2 diabetes. Methods: PubMed, Medline, EMBASE were searched up to January 2020 to identify studies prescribing structured exercise interventions with continuous glucose monitoring outcomes in adults with type 2 diabetes. Randomized controlled trials, crossover trials, and studies with pre-and post-designs were eligible. Short-term studies were defined as having exercise interventions lasting ≤2 weeks. Longer-term studies were defined as >2 weeks. Results: A total of 28 studies were included. Of these, 23 studies were short-term exercise interventions. For all short-term studies, the same participants completed a control condition as well as at least one exercise condition. Compared to the control condition, exercise decreased the primary outcome of mean 24-h glucose concentrations in short-term studies (−0.5 mmol/L, [−0.7, −0.3]; p < 0.001). In longer-term studies, mean 24-h glucose was not significantly reduced compared to control (−0.9 mmol/L [−2.2, 0.3], p = 0.14) but was reduced compared to pre-exercise values (−0.5 mmol/L, [−0.7 to −0.2] p < 0.001). The amount of time spent in hyperglycemia and indices of glycemic variability, but not fasting glucose, also improved following short-term exercise. Among the shorter-term studies, subgroup, and regression analyses suggested that the timing of exercise and sex of participants explained some of the heterogeneity among trials. Conclusion: Both acute and chronic exercise can improve 24-h glucose profiles in adults with type 2 diabetes. The timing of exercise and sex of participants are among the factors that may explain part of the heterogeneity in acute glycemic improvements following exercise.

A1c can be reduced after eight-twelve weeks of AquaEx. However, at this time few studies have examined whether changes in A1c are different from LandEx or Crtl.

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Sepsis is a clinical syndrome with physiologic and biochemical derangements caused by dysregulated inflammatory response to an infection. A recent retrospective study showed that vitamin C, hydrocortisone and thiamine in intensive care unit (ICU) patients with septic shock when added to standard care improved mortality and outcomes. We undertook a prospective single-blinded study to evaluate effects of addition of this triple therapy to standard ICU care on 28-day mortality in patients with septic shock. METHODS: Patients at LAC+USC Medical Center with septic shock defined as sepsis-induced hypotension requiring vasopressors with serum lactate level >2 mmol/L were enrolled within 24 hours of identification. Exclusion criteria included inability to obtain consent, incarceration, active malignancy, dementia, pregnancy or lactation, active ischemic or hemorrhagic stroke, active cardiogenic or other causes of shock, history of renal stones and current use of steroids. Patients were blinded as to treatment group and randomized by a blinded operator in block randomization in a 1:1 fashion in groups of 8. Patients received either standard ICU care (control) or standard care plus intravenous (IV) Vitamin C 1.5 gram every 6 hours for 4 days or until ICU discharge, IV hydrocortisone 50 mg every 6 hours for 7 days or until ICU discharge, and IV thiamine 200 mg every 12 hours for 4 days or until ICU discharge. Data were analyzed using SPSS with a chi squared test. P-value <0.05 was considered statistically significant.

IntroductionType 2 diabetes mellitus (T2DM) onset before 40 years of age has a magnified lifetime risk of cardiovascular disease. Diastolic dysfunction is its earliest cardiac manifestation. Low energy diets incorporating meal replacement products can induce diabetes remission, but do not lead to improved diastolic function, unlike supervised exercise interventions. We are examining the impact of a combined low energy diet and supervised exercise intervention on T2DM remission, with peak early diastolic strain rate, a sensitive MRI-based measure, as a key secondary outcome.Methods and analysisThis prospective, randomised, two-arm, open-label, blinded-endpoint efficacy trial is being conducted in Montreal, Edmonton and Leicester. We are enrolling 100 persons 18–45 years of age within 6 years’ T2DM diagnosis, not on insulin therapy, and with obesity. During the intensive phase (12 weeks), active intervention participants adopt an 800–900 kcal/day low energy diet combining meal replacement products with some food, and receive supervised exercise training (aerobic and resistance), three times weekly. The maintenance phase (12 weeks) focuses on sustaining any weight loss and exercise practices achieved during the intensive phase; products and exercise supervision are tapered but reinstituted, as applicable, with weight regain and/or exercise reduction. The control arm receives standard care. The primary outcome is T2DM remission, (haemoglobin A1c of less than 6.5% at 24 weeks, without use of glucose-lowering medications during maintenance). Analysis of remission will be by intention to treat with stratified Fisher’s exact test statistics.Ethics and disseminationThe trial is approved in Leicester (East Midlands – Nottingham Research Ethics Committee (21/EM/0026)), Montreal (McGill University Health Centre Research Ethics Board (RESET for remission/2021-7148)) and Edmonton (University of Alberta Health Research Ethics Board (Pro00101088). Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial.Trial registration numberISRCTN15487120.