The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience.

Introduction: Recently published case reports suggest the benefit of empagliflozin use in subjects with glycogen storage disease Ib (GSD Ib). Methods: We present the clinical and laboratory data of 2 adult brothers with GSD Ib treated with empagliflozin for 12 months. Results: There was no severe infection during administration of empagliflozin. The improvement of clinical symptoms of inflammatory bowel disease and arthritis along with reduction in serum CRP levels and urinary albumin excretion was noted. Neutrophil count increased, allowing for reduction or temporary withdrawal of G-CSF treatment. Conclusions: Empagliflozin may be a new safe treatment in GSD Ib patients with an advanced stage of the disease.

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

PURPOSE: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib.

Peripheral arterial embolism and pyrexia in a young patient without comorbidities.

Peripheral arteries embolism can be located in various organs. It can be caused by many medical conditions, diagnosis and treatment of which allows to prevent further complications. A CASE REPORT: 26-year-old male patient was admitted to the Department of Internal Medicine, Hypertension and Vascular Diseases due to lasting over two months fatigue, recurrent pyrexia, weight loss and abdominal pain. Prior to that, he presented to physician several times. First time because of left foot pain with oedema and fever. USG revealed embolus in anterior tibial artery. Outpatient antibiotic, antithrombotic and anti-inflammatory treatment was given. The symptoms subsided, but appeared in other limb. After a while patient presented with pyrexia, fatigue, abdominal and lumbar region pain and melaena. CT showed infarction of spleen and left kidney. Once again outpatient treatment with amoxicillin with clavulanate was administered. Eventually, at admission to the clinic, infective endocarditis (IE) with dental origin was suspected. Echocardiography showed vegetation on bicuspid aortic valve, causing regurgitation. Blood culture was taken and empiric antimicrobial therapy with ampicillin, gentamicin and cloxacillin was administered. Blood culture was positive for Streptococcus sanguinis. Carious teeth were extracted, then the aortic valve replacement surgery was performed. Ampicillin was replaced with vancomycin, and gentamicin was continued. After the surgery, patient's condition improved. He was discharged on demand without completing antibiotic treatment, so he had follow-up appointment and IE prophylaxis recommended. CONCLUSIONS: Despite peripheral embolism is common manifestation of IE, this disease is relatively rare and not suspected in young people. The symptoms can be non-specific, what makes diagnosis challenging, as described in this case.

Tonic activity of carotid body chemoreceptors contributes to the increased sympathetic drive in essential hypertension.

Carotid chemoreceptors provoke an increase in muscle sympathetic nerve activation (MSNA) in response to hypoxia; they are also tonically active during normoxic breathing. The contribution of peripheral chemoreceptors to sympathetic activation in hypertension is incompletely understood. The aim of our study was to investigate the effect of chemoreceptor deactivation on sympathetic activity in untreated patients with hypertension. A total of 12 untreated hypertensive males and 11 male controls participated in this randomized, crossover, placebo-controlled study. MSNA, systolic blood pressure(BP), diastolic BP, heart rate (HR), electrocardiogram, hemoglobin oxygen saturation (Sat%) and respiratory movements were measured during repeated 10-min periods of respiration with 100% oxygen or 21% oxygen in a blinded fashion. Compared with controls, hypertensives had higher resting MSNA (38 ± 10 vs. 29 ± 0.9 burst per min, P<0.05), systolic BP (150 ± 12 vs. 124 ± 10 mm Hg, P< 0.001) and diastolic BP (92 ± 10 vs. 77 ± 9 mm Hg, P<0.005). Breathing 100% oxygen caused significant decrease in MSNA in hypertensive patients (38 ± 10 vs. 26 ± 8 burst per min and 100 ± 0 vs. 90 ± 10 arbitrary units, P<0.05) and no change in controls (29 ± 9 vs. 27 ± 7 burst per min and 100 ± 0 vs. 96 ± 11 arbitrary units). BP, respiratory frequency and end tidal CO(2) did not change during chemoreceptor deactivation with hyperoxia. HR decreased and Sat% increased in both the study groups. These results confirm the role of tonic chemoreceptor drive in the development of sympathetic overactivity in hypertension.

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia.

Beyond their hypolipidemic effect, statins reduce cardiovascular risk in hypertensive subjects via various mechanisms; one suggested mechanism is that they reduce sympathetic activity. We investigated the hypothesis that simvastatin decreased muscle sympathetic nerve activity (MSNA) in 31 hypertensive subjects with hypercholesterolemia (aged 38.7 ± 10 years). In this randomized, placebo-controlled, double-blinded study, patients were treated with simvastatin (40 mg day(-1); n=15) or placebo (n=16) for 8 weeks. Before and after treatment, we measured MSNA, blood pressure and heart rate. Baroreceptor control of the heart rate, or baroreceptor sensitivity (BRS), was computed by the sequence method, a cross-analysis of systolic blood pressure and the electrocardiogram R-R interval. Blood samples were tested for plasma levels of catecholamines, neuropeptide Y, aldosterone, endothelin and renin activity. Simvastatin significantly reduced MSNA (from 36.5 ± 5 to 27.8 ± 6 bursts per min, P=0.001), heart rate (from 77 ± 6.7 to 71 ± 6.1 beats per min, P=0.01) and both total and low-density lipoprotein cholesterol (from 249 ± 30.6 to 184 ± 28.3 mg dl(-1), P=0.001 and from 169 ± 30.6 to 117 ± 31.2 mg dl(-1), P=0.01, respectively). Simvastatin also improved BRS (from 10.3 ± 4.1 to 17.1 ± 4.3 ms per mm Hg, P=0.04). No changes were observed in systolic or diastolic blood pressures, or in plasma levels of catecholamines, neuropeptide Y, endothelin, aldosterone and renin activity. After simvastatin therapy, MSNA and BRS were inversely related (r=-0.94, P<0.05). In conclusion, we found that, in patients with hypertension and hypercholesterolemia, simvastatin reduced MSNA, and this was related to increased baroreceptor sensitivity.

Atorvastatin reduces sympathetic activity and increases baroreceptor reflex sensitivity in patients with hypercholesterolaemia and systemic arterial hypertension.

BACKGROUND: Increased sympathetic activity might be related to pathogenesis of hypertension as well as to end organ damage. Animal studies suggest that statins decrease sympathetic activity and increase baroreceptor reflex sensitivity (BRS). AIM: To examine whether atorvastatin decreases muscle sympathetic nerve activity (MSNA) and BRS in hypercholesterolaemic and hypertensive patients. METHODS: Ten patients with essential hypertension and untreated hypercholesterolaemia (aged 43 +/- 12 years) and eight healthy subjects (aged 37 +/- 7 years) were enrolled in the study. In both groups the recordings of microneurography, ECG, blood pressure and BRS were performed twice, before and after 8 weeks during which the patients (but not controls) were treated with atorvastatin. RESULTS: Compared with controls, the patients had higher MSNA values (36.0 +/- 6.6 vs. 29.8 +/- 3.7 bursts/minute), mean BP levels (145.1 +/- 10 vs. 124.1 +/- 11.1 mmHg) and total cholesterol concentration (252.6 +/- 22.6 vs. 179.8 +/- 20.7 mg/dl) baseline values. Statin therapy resulted in a decrease of total cholesterol (252.6 +/- 22.0 vs. 173.8 +/- 26.2 mg/dl, p < 0.05) and MSNA (36.0 +/- 6.6 vs. 28.6 +/- 4.8 bursts/min, p < 0.05), whereas BRS values were increased (12.6 +/- 5.6 vs. 18.1 +/- 5.9 ms/mmHg, p < 0.05). Post-treatment BRS was inversely related to post-treatment MSNA (r = -0.73, p < 0.05). In the controls there were no changes in MSNA (29.8 +/- 3.7 vs. 28.9 +/- 2.9 bursts/min), BRS (11.9 +/- 5.0 vs. 13.1 +/- 4.8 ms/mmHg), total cholesterol, BP and heart rate between the first and the second measurement. CONCLUSION: Atorvastatin reduces MSNA and increases BRS in hypertensive and hypercholesterolaemic patients. Decrease in sympathetic activity may be the result of improvement of baroreceptor function by atorvastatin.

The effect of enalapril and telmisartan on clinical and biochemical indices of sympathetic activity in hypertensive patients.

OBJECTIVE: To compare the effect of ARB and ACE inhibitor on sympathetic activity in 32 hypertensives. DESIGN AND METHODS: After a four-week wash-out period, patients were randomized to four weeks of therapy with enalapril or telmisrtan, with crossover to another drug for another four weeks. Blood pressure (BP), NPY, and catecholamine levels and HRV (frequency analysis) were measured during wash-out, in basal condition, and after postural stimulation test (PST). RESULTS: Both drugs significantly reduced BP and NPY as compared to initial values, while no differences in BP and NPY between drugs were observed. Increase in NPY during PST was significantly higher in the enalapril than in the telmisartan group and during the wash-out period. No differences between enalapril and telmisartan in plasma catecholamines were observed. Telmisartan decreased low frequency/high frequency ratio as compared to initial values and enalapril values. CONCLUSIONS: Despite similar BP control, telmisartan attenuated autonomic balance more effectively than enalapril.