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Abstract: Although Bruton tyrosine kinase inhibitors (BTKis) are generally well tolerated and less toxic than chemotherapy alternatives used to treat lymphoid malignancies, BTKis like ibrutinib have the potential to cause new or worsening hypertension (HTN). Little is known about the optimal treatment of BTKi-associated HTN. Randomly selected patients with lymphoid malignancies on a BTKi and antihypertensive drug(s) and with at least 3 months of follow-up data were sorted into 2 groups: those diagnosed with HTN before BTKi initiation (prior-HTN), and those diagnosed with HTN after BTKi initiation (de novo HTN). Generalized estimating equations assessed associations between time varying mean arterial pressures (MAPs) and individual anti-HTN drug categories. Of 196 patients included in the study, 118 had prior-HTN, and 78 developed de novo HTN. Statistically significant mean MAP reductions were observed in patients with prior-HTN who took β blockers (BBs) with hydrochlorothiazide (HCTZ), (-5.05 mmHg; 95% confidence interval [CI], 10.0 to -0.0596; P = .047), and patients diagnosed with de novo HTN who took either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) with HCTZ (-5.47 mmHg; 95% CI, 10.9 to -0.001; P = .05). These regimens also correlated with the greatest percentages of normotensive MAPs. Treatment of HTN in patients taking a BTKi is challenging and may require multiple antihypertensives. Patients with prior-HTN appear to benefit from combination regimens with BBs and HCTZ, whereas patients with de novo HTN appear to benefit from ACEi/ARBs with HCTZ. These results should be confirmed in prospective studies., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Objective: Magnetic resonance-guided laser-induced thermotherapy (MR-LITT) is a minimally invasive technique that shows promise in neuro-oncology because of its superiority in delivering precise minimally invasive thermal energy with minimal collateral damage. In this analysis, we investigate initial data on the effect of MR-LITT on dural-based lesions., Methods: Five patients were identified with dural-based lesions (4 meningiomas, 1 solitary fibrous tumor) with clear evidence of radiologic progression. In all 5 cases, the tumors were localized to the lateral convexity or paramedian locations in the supratentorial space. All patients received MR-LITT and then a follow-up magnetic resonance imaging scan at 24 hours after treatment, at 1 month, and at each subsequent follow-up visit. Local control of the ablated tumor was evaluated with radiographic follow-up and symptomatic progression-free survival was recorded., Results: Five LITT treatments were performed on 5 patients with an average age of 65.2 years. The average tumor volume was 29.7 cm 3 and ablation dosage was 12.4 W. On average, 80% of the pretreatment lesion volume was ablated. The mean follow-up time was 59.3 weeks. In total, 2 patients (1 with an anaplastic meningioma and 1 with a solitary fibrous tumor) had radiographic evidence of disease progression. In the observed time of the 3 patients with no progression, there was a 52% reduction in tumor volume. There were no major perioperative complications., Conclusions: MR-LITT is a promising technology for dural-based lesion treatment. This initial study demonstrates that MR-LITT is safe and offers several advantages over open surgical treatment. Randomized studies are needed to evaluate its role as a treatment adjunct., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Patients with type-2 diabetes are at risk for treatment- and disease-related complications. Little is known about the interrelation of hypoglycaemia and co-morbid vascular disease (VD), defined as coronary heart disease, stroke and peripheral arterial disease., Hypothesis: Hypoglycaemia is associated with co-morbid VD in diabetic patients., Methods: DiaRegis is a prospective registry that included patients with type-2 diabetes in 2009/2010. Metric variables are displayed as median and quartiles. For the comparison of patients with or without VD Odds Ratios (OR) were determined from univariate analyses and adjusted for differences in patient characteristics (multivariable analysis)., Results: Data on hypoglycaemia and VD within the last 12 months were available for 3741 patients (98.2%) with a median (IQR) age of 65.9 (57.6-72.9) years; 46.7% were female. VD patients (n = 909; 24.3%) were older (70.7 vs 63.9 years; p < 0.0001), less often female (33.6% vs 50.9%; p < 0.0001) and had had diabetes for a longer duration (6.4 vs 5.4 years; p < 0.0001). Mean cholesterol (total, HDL and LDL) was also slightly lower (p < 0.0001). Glycaemic control (HbA1c, fasting and postprandial glucose) was comparable. VD patients received less metformin (80.7 vs 85.2%; p < 0.01) and more sulfonylureas (31.8 vs 27.6%; p < 0.05). There was an increased incidence of symptomatic hypoglycaemia with or without requiring help and with a need for medical assistance. After adjusting a number of baseline variables the rates of symptomatic hypoglycaemias with help remained significantly increased (OR 3.73 (95% CI 1.31-10.65) in patients with VD., Conclusions: As hypothesized there is a strong association between the incidence of hypoglycaemia and vascular disease at comparable glycaemic control, which confirms prior randomized controlled trial data suggesting an interrelationship between hypoglycaemia and vascular disease.

Background: We aimed to identify predictors of anamnestic hypoglycaemia in type-2 diabetic patients on oral mono- or dual oral combination antidiabetic pharmacotherapy., Methods: DiaRegis is a prospective registry in type-2 diabetic patients in primary care. Odds ratios (OR) with 95% confidence intervals were determined from univariate logistic regression. Using multivariate logistic regression analysis with stepwise backward selection at an alpha of 0.05 independent predictors of hypoglycaemia were determined., Results: 3,808 patients had data on hypoglycaemia available (median age 65.9 years, 46.6% female). 10.8% had at least one anamnestic hypoglycaemic episode within the previous 12 months. Patients with hypoglycaemia received more sulfonylureas (OR 2.16; 95%CI 1.75-2.67) and less metformin (OR 0.64; 95%CI 0.50-0.82). On top of metformin, patients with thiazolidine (OR 0.50; 95%CI 0.28-0.89) and DPP-4 inhibitor use (OR 0.34; 95%CI 0.16-0.70) had a decreased risk for hypoglycaemia while it was again increased with sulfonylureas (OR 2.08; 95%CI 1.44-2.99). Age < 65 years was an independent predictor of a reduced hypoglycaemia incidence (OR 0.76; 95%CI 0.59-0.96), low HbA1c (OR 1.68; 95%CI 1.31-2.14), stroke/TIA (OR 1.72; 95%CI 1.08-2.72), heart failure (OR 1.77; 95%CI 1.28-2.45), and the use of sulfonylureas (OR 2.58; 95%CI 2.03-3.29) were independent predictors of increased risk., Conclusions: The results indicate that the risk of hypoglycaemia might be substantially reduced by carefully selecting antidiabetic pharmacotherapy in patients with type-2 diabets in primary care.

Background: Patients with type 2 diabetes are at an increased risk for disease and treatment related complications after the initial approach of oral mono/dual antidiabetic therapy has failed. Data from clinical practice with respect to this patient group are however scarce. Therefore we set up a registry in primary care documenting the course and outcomes of this patient group., Methods: Diabetes Treatment Patterns and Goal Achievement in Primary Diabetes Care (DiaRegis) is a prospective, observational, German, multicenter registry including patients with type-2 diabetes in which oral mono/dual antidiabetic therapy has failed. Data were recorded at baseline and will be prospectively documented during visits at 6 ± 1, 12 ± 2 and 24 ± 2 months. The primary objective is to estimate the proportion of patients with at least 1 episode of severe hypoglycemia within one year., Results: 313 primary care offices included 4,048 patients between June 2009 and March 2010 of which 3,810 patients fulfilled the in- and exclusion criteria. 46.7% of patients were female; patients had a median diabetes duration of 5.5 years and most were obese with respect to BMI or waist circumference. HbA1c at baseline was 7.4%, fasting plasma glucose 142 mg/dl and postprandial glucose 185 mg/dl. Co-morbidity in this patient population was substantial with 17.9% having coronary artery disease, 14.4% peripheral neuropathy, 9.9% heart failure and 6.0% peripheral arterial disease. 68.6% of patients received oral monotherapy, 31.4% dual oral combination therapy. The most frequent antidiabetic agent used as monotherapy was metformin (79.0%) followed by sulfonylureas (14.8%)., Conclusions: DiaRegis is a large, prospective registry in primary diabetes care to document the course and outcomes of patients with type-2 diabetes in which the initial approach of oral mono/dual antidiabetic therapy has failed. The two year follow-up will allow for a prospective evaluation of these patients during multiple adjustments of therapy.

During the course of malaria several organs develop pathology. Frequently also signs of hepatocyte damage are found. In the present work we studied the mechanisms leading to liver pathology during the erythrocyte stage of Plasmodium berghei malaria. During infection, mice developed an inflammation of the liver, associated with infiltration of T cells, although only little tissue damage could be observed. Histological analysis revealed the presence of CTL-associated antigen-4 (CTLA-4)-positive T cells in the liver parenchyma. To study the influence of CTLA-4 expression on liver inflammation, mice were treated with an antibody against CTLA-4. Treated mice suffered from a dramatically increased liver pathology. Using cytokine-deficient mice we found that pathology was dependent on the presence of IL-12 and IFN-gamma. To further study the mechanisms that lead to an enhanced pathology, we analyzed cytokine production from liver-derived T cells. In infected mice the frequency of IFN-gamma-producing cells in the liver was low. In contrast, in anti-CTLA-4-treated mice larger numbers of IFN-gamma-producing cells were detectable. Our results indicate that activated T cells during the erythrocyte stage of malaria can induce pathology due to secretion of pro-inflammatory cytokines. Moreover, these results provide evidence that CTLA-4 expression can restrict T cell function in inflamed organs and might therefore prevent pathology.