Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties

When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch’s bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required.     

Effects of thyroidectomy alone or followed by radioiodine ablation of thyroid remnants on the outcome of graves' ophthalmopathy.

Fifty-five patients with Graves' disease (GD) and mild to moderate Graves' ophthalmopathy (GO) underwent near-total thyroidectomy (Tx). In 16 patients this was followed by a standard ablative dose of (131)I because of the hystologic evidence of differentiated thyroid carcinoma. We retrospectively evaluated whether or not GO activity could be affected by thyroid surgery alone or followed by complete ablation of thyroid tissue. Accordingly, on the basis of clinical activity score (CAS) values prior to thyroidectomy, we identified two groups: group A with active GO (CAS > or = 3; n = 31) and group B with inactive GO (CAS < or = 2; n = 24). CAS values were then recorded at 6, 12, and 24 months after surgery/(131)I ablation. Over the course of the follow-up period, GO became inactive in approximately 70% of group A patients (CAS 4.2 +/- 0.8 at baseline, 2.1 +/- 2.0 at 24 months, p < 0.0001) and became active in 37.5% patients from group B. When we examined GO activity according to the type of treatment used (Tx or Tx and (131)I), the prevalence of inactive GO both short- and long-term, was significantly higher in the group of patients who underwent Tx and (131)I ablation. Therefore, this seems to be a more effective means of inducing and maintaining inactive GO.     

Endothelins and markers of renal damage in recently diagnosed hypertensive patients

Endothelin has been identified as a potent vasoconstrictor. The aim of this study was to evaluate urinary endothelins and their relation to other markers of renal damage, such as microalbuminuria, creatinine, and N-acetyl-beta-glucosaminidase (NAG), in a group of recently diagnosed (less than 1 year) hypertensive subjects and a control group. We selected 50 subjects and divided them into two groups: 27 hypertensive patients (15 females and 12 males) without previous pharmacologic therapy, and 23 healthy, normotensive subjects (12 females and 11 males). All patients underwent a history and physical examination, chest x-ray, electrocardiography, funduscopy, and hematologic and biochemical analyses. Endothelins, microalbuminuria, creatinine, and NAG values were also determined in 24-hour urine samples. Creatinine, microalbuminuria, and NAG values were found to be higher in hypertensive than in normotensive subjects. The hypertensive group showed a nonsignificant elevation of total endothelin. In conclusion, the determination of elevated urinary endothelin does not appear to be an early marker of organ damage in hypertensive subjects. The urinary excretion of protein, creatinine, and NAG was higher in hypertensive subjects. A positive correlation was found between the urinary excretion of endothelins and markers of renal damage, microalbuminuria and NAG values. The relationship between endothelins and hypertension was without statistical significance.     

HIV-1 matrix protein p17 enhances the proliferative activity of natural killer cells and increases their ability to secrete proinflammatory cytokines

We investigated the effects of human immunodeficiency type-1 virus (HIV-1) matrix protein p17 on freshly isolated and purified human natural killer (NK) cells. HIV-1 p17 increased the cytokines interleukin (IL) 2, IL-12 and IL-15, and induced natural killer cell proliferation, but not cytotoxicity. This effect was specific because it was abrogated by anti-p17 monoclonal antibody. Moreover, HIV-1 p17 enhanced the cytokine-induced production of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma by NK cells. IL-4 downregulated IFN-gamma and TNF-alpha secretion in IL-2- and IL-15-treated NK cells. HIV-1 p17 restored the ability of NK cells to produce both cytokines when added to the cultures simultaneously with IL-4. The property of p17 to increase the production of TNF-alpha and IFN-gamma might be a mechanism used by HIV-1 to modulate the immune system to support its replication and spreading.     

Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.     

Successful kidney transplantation in leprosy and transitory recurrence of the disease

A 40-year-old woman on chronic hemodialysis had been diagnosed as having lepromatous leprosy at the age of 17 and treated for 15 years with sulfones. She remained clinically free of leprosy during 19 months of hemodialysis and then underwent successful renal transplantation. Fourteen months after surgery, recurrence of leprosy was observed. In spite of immunosuppression, the skin lesions healed with sulfone treatment. Renal transplantation is a useful treatment in patients with leprosy and chronic renal failure.     

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.     

Huesca and Teruel survey on hemodialysis management

A cross sectional study was performed in order to evaluate the treatment conditions and medical outcomes among 131 prevalent hemodialysis patients (57% males; mean age 66 +/- 12 years) in Huesca and Teruel. Data were collected at 5 hemodialysis units in Huesca and Teruel. Diabetes mellitus, at 30 percent, was the most common cause of renal insufficiency. The mean (+/- SD) urea-reduction ratio (URR) was 66.0 +/- 8.8%. We observed that 56.5% of the population reached an URR higher than 65%. The duration of dialysis session was 220 +/- 24 minutes, with a rate of blood flow 297 +/- 47 ml/min. 36% of patients used high-flux membranes. The patterns of vascular access were: 69% arteriovenous fistula, 5% synthetic graft and 26% catheter. Eighty nine percent of patients were treated with erythropoietin. The mean dose of erythropoietin was 109 +/- 62 UI/Kg weight/week. Thirty nine percent of patients had haemoglobin below 11.0 g/dl (mean 11.2 +/- 1.4 g/dl). Ferritin levels were below 100 ng/ml in 24% of the patients and 25% showed a transferrin saturation index below 20%. Fifty percent of patients were receiving vitamin D. Serum calcium 9.3 +/- 0.8 mg/dl; phosphorous 5.5 +/- 1.5 mg/dl; calcium-phosphorous product 51.5 +/- 14.3 mg/dl; PTHi 433 +/- 459 pg/ml; and aluminium 26.8 +/- 14.5 mcg/l were the mean of main biochemical markers of mineral metabolism. Sixty eight percent of patients had phosphorous levels below 6.0 mg/dl. Thirty seven percent of patients had aluminium levels lower than 20 mcg/l. The mean serum albumin was 3.4 +/- 0.4 g/dl. Forty five percent of patients had albumin below 3.5 g/dl.