Biopsy‐proven adenoviral diarrhea responding to low‐dose cidofovir

Abstract: We present a case of diarrhea secondary to biopsy‐proven adenovirus (ADV) infection after autologous peripheral hematopoietic stem cell transplant for multiple myeloma. The patient had a negative plasma polymerase chain reaction for ADV and a dramatic clinical response to low‐dose cidofovir. To our knowledge, this is the first report in an adult hematopoietic stem cell recipient of the use of low‐dose cidofovir to treat proven ADV gastrointestinal infection.     

Long‐term follow‐up of interferon‐alpha induction and low‐dose maintenance therapy in hairy cell leukemia

Objective: Interferon‐α (IFNα) was the first effective pharmacologic treatment of hairy cell leukemia (HCL). Since 1990 purine analogs replaced IFNα because of higher rates of complete remission and an invariable disease recurrence after cessation of IFNα. However, there are only limited data about long‐term maintenance treatment with IFNα and none about dose finding in this phase. Patients and methods: Fifty‐two consecutive patients treated at our institution for HCL are included in this retrospective analysis. Forty (77%) patients received IFNα and 35 patients continue on long‐term IFNα maintenance therapy. The initial dose of IFNα was 3 Mio IU three times per week and was tapered 6 months after initiation to doses as low as 3 Mio IU/12 wk. Dose adaptation was performed by repeated measurement of soluble Interleukin 2 receptor (sIL2R) together with peripheral blood values. Results: The median follow‐up of patients in the long‐term IFNα group was 13.6 ± 7.5 yr. Long‐term IFNα was in general well tolerated and only in six (17%) patients the treatment had to be changed to purine analogs in the long‐term IFNα group because of side effects. There are no deaths directly related to HCL. Conclusions: IFNα is still an effective and well tolerated therapeutic option. By repeated measurements of sIL2R together with the peripheral blood values, IFNα doses can be tapered to the minimal effective dose. The advantages and disadvantage of IFNα in regards to the standard treatment in HCL patients are discussed.     

Safety and feasibility of low‐dose ticagrelor in patients with ST‐segment elevation myocardial infarction

BackgroundPrevious studies have confirmed the safety and feasibility of half‐dose ticagrelor in Chinese patients with acute coronary syndrome, but currently there is no plan for the use of ticagrelor for Chinese ST‐segment elevation myocardial infarction (STEMI) patients.HypothesisIt is safe and feasible of low‐dose ticagrelor in patients with STEMI.MethodsThe STEMI patients who were undergoing emergency intervention and taking ticagrelor were enrolled. Patients whose level of platelet aggregation rate (PAR) less than 30% after 7‐day treatment with standard‐dose ticagrelor were randomly divided into low‐dose group (LD group, 45 mg twice daily) and standard‐dose group (SD group, 90 mg twice daily). The changes of levels of platelet parameters were compared between the two groups. The incidence of major adverse cardiac events (MACE), bleeding events were compared between the two groups within 6 months of follow‐up.ResultsThe levels of PAR in the SD group decreased compared with baseline, and was lower than those of LD group at the same time point. The levels of platelet distribution width in both groups decreased from the baseline values (all p < .05) at 1, 3, and 6 months after grouping treatment, but there was no significant difference between the two groups. The incidence of MACE was similar between the two groups of patients. There were decreasing trends in the incidences of minimal bleeding event, minor bleeding event, dyspnea, and gout in the LD group.ConclusionIt is safe and feasible of low‐dose ticagrelor for patients with STEMI based on the monitoring of PAR.     

Prevalence of erosive esophagitis among Japanese patients taking low‐dose aspirin

Background and Aim: The risk for erosive esophagitis (EE) with low‐dose aspirin (ASA) remains unknown, especially among Japanese patients. We conducted the present study to compare the risk of EE with that of gastroduodenal mucosal injury among Japanese patients taking ASA. Methods: From 5555 patients undergoing upper gastrointestinal endoscopy from January 2005 to December 2006 at Teikyo University Hospital, Tokyo, Japan, 159 patients (76 males and 83 females, mean age: 69.3 ± 11 years) fulfilling the following conditions were selected: (i) taking ASA (less than 100 mg/day) continuously; (ii) not taking acid suppressants; and (iii) no history of gastrointestinal tract surgery, malignancies, severe cardiac failure, or liver cirrhosis. Age‐ and sex‐matched patients not taking aspirin were randomly chosen as controls (n = 159). Two well‐experienced endoscopic examiners evaluated endoscopic records to determine the presence or absence of esophageal hiatal hernia, EE, and gastroduodenal ulcers. Results: The prevalence of EE in patients taking aspirin (9.4%) was not different from that of the controls (6.3%, odds ratio [OR]: 1.5, 95% confidence interval [CI]: 0.7–3.2), whereas peptic ulcers were found more frequently in the aspirin group (14%) than in the control group (4%, OR: 3.6, 95% CI: 1.5–8.8). Conclusion: In Japanese patients taking ASA, EE was not as common as peptic ulcers.     

GVHD prophylaxis using low‐dose cyclosporine improves survival in leukaemic recipients of HLA‐identical sibling transplants

Graft‐versus‐host disease (GVHD) prophylaxis of short duration (6 months) with low‐dose cyclosporine A (CsA) starting at 1 mg/kg per day i.v. and four doses of methotrexate (MTX) were given to 171 consecutive leukaemic recipients of HLA‐identical sibling transplants. In contrast, apart from MTX, retrospective controls received high‐dose CsA, starting at 5–7.5 mg/kg per day i.v. and discontinued 1 yr post‐transplant. In the low‐dose CsA group, the probability of acute GVHD grades I–II (70% vs. 53%, P < 0.01), and chronic GVHD were increased (58% vs. 25%, P < 0.01), whereas the incidences of acute GVHD grades III–IV (9% vs. 5%, P = 0.62), and non‐relapse mortality (20% vs. 22%, P = 0.58) were similar. Moreover, the probability of relapse was decreased (31% vs. 54%, P < 0.01), and both relapse‐free (56% vs. 38%, P = 0.04) and overall survival (61% vs. 40%, P = 0.04) were markedly improved using the low‐dose CsA regimen. In multivariate analyses, low‐dose CsA was strongly associated with chronic GVHD [relative hazard (RH) 2.56, P < 0.01], which decreased the risk of relapse (RH 0.46, P < 0.01) and improved the probability of survival (RH 1.84, P < 0.01). In conclusion, a low‐dose CsA regimen in leukaemic recipients of HLA‐identical sibling transplants increases the rate of chronic GVHD, which seems to attenuate the risk of relapse, thereby improving patient survival owing to enhanced graft‐versus‐leukaemia effect.     

Cardiac resynchronization therapy for low‐flow,low‐gradient aortic stenosis

Low‐flow, low‐gradient aortic stenosis is a heterogeneous entity that encompasses truly severe aortic stenosis as well as mild‐to‐moderate aortic stenosis in which aortic valve orifice area is severely reduced primarily due to left ventricular (LV) contractile dysfunction. Under such circumstances the capacity of the LV to generate stroke‐work is severely compromised. In this case report, we describe a patient with severe LV dysfunction and ventricular dyssynchrony due to right ventricular pacing who presented with decompensated heart failure in the setting of low‐flow, low‐gradient aortic stenosis. We discuss the management of this high‐operative‐risk patient, who ultimately underwent upgrading of his dual chamber pacemaker to a biventricular pacemaker with significant echocardiographic, haemodynamic, and clinical improvement.     

Clarithromycin (Biaxin)‐lenalidomide‐low‐dose dexamethasone (BiRd) versus lenalidomide‐low‐dose dexamethasone (Rd) for newly diagnosed myeloma

The objective of this case‐matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low‐dose dexamethasone (BiRd) vs. lenalidomide/low‐dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital‐Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention‐to‐treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very‐good‐partial‐response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time‐to‐progression (median 48.3 vs. 27.5 months, P = 0.071), and progression‐free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3‐year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3–4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case‐matchedanalysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Complications of low‐dose,echo‐guided alcohol septal ablation

Background : Alcohol septal ablation (ASA) is a catheter‐based intervention that has been used as an alternative to surgical myectomy in highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods : This retrospective study was designed to evaluate the incidence of major complications in the mid‐term follow‐up of low‐dose (1–2.5 ml of ethanol), echo‐guided alcohol septal ablation. Results : A total of 101 consecutive patients (56 ± 15 years) with highly symptomatic HOCM were enrolled. At 6 months, there was a significant decrease in resting outflow gradient accompanied by reduction in basal septal diameter and improvement in symptoms (P < 0.01). Two patients (2%) experienced procedural ventricular tachycardias terminated by electrical cardioversion. A total of 87 patients (86%) underwent an uneventful postprocedural hospital stay. The postprocedural complete heart block occurred in 10 patients (10%), and subsequent permanent pacemaker was implanted in four cases (4%). Sustained ventricular arrhythmias requiring electrical cardioversion occurred in four patients (4%) within postprocedural hospital stay. Subsequently, ICD was not implanted in any of these cases. The patients were repeatedly examined by Holter ECG monitoring, and in the mid‐term follow‐up (6–50 months), they stayed asymptomatic and without any ventricular arrhythmias. Conclusion : This study demonstrates the same early incidence of complete heart block requiring permanent pacemaker implantation (4%) and sustained ventricular arrhythmias following low‐dose, echo‐guided ASA. © 2009 Wiley‐Liss, Inc.     

Maintenance of long‐term blood pressure control and vascular health by low‐dose amiloride‐based therapy in hyperaldosteronism

Whether aldosterone itself contributes directly to macro‐ or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long‐term single‐practice experience in an unusual group of five patients with chronic hyperaldosteronism (HA, including three with glucocorticoid‐remediable aldosteronism, GRA) treated with low‐dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5‐10 (mean 7) mg daily for 14‐28 (mean 20) years. Except for one GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normalized within 1‐4 weeks after starting amiloride and office BP’s remained well controlled throughout the next two decades. 24‐hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, reflection magnitude), regional pulse wave velocities, pulse stiffening ratio, ankle‐brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio were measured after a mean of 18 years; all of these indicators were essentially normal. Over two additional years of observation (100 patient‐years total), no cardiovascular or renal event occurred. We conclude that long‐term ENaC blockade with amiloride can normalize BP and protect macro‐ and microvascular function in patients with HA. This suggests that either (a) putative vasculopathic effects of aldosterone are mediated via ENaC or (b) aldosterone may not play a direct role in age‐dependent vasculopathic changes in humans independent of blood pressure. These findings, coupled with our literature review in both animal and human results, underscore the need for additional studies.