Recurrent ulcer after successful treatment with cimetidine or antacid

This study was designed to compare the rates of duodenal ulcer healing and recurrence after treatment with cimetidine or antacid. Patients with endoscopically documented duodenal ulcer received cimetidine, 1200 mg daily, or Mylanta II, 7 oz daily, in a randomized, double-blind trial. For the 69 patients in each group who completed the healing phase of the trial, endoscopic ulcer healing was almost identical. At 2, 4, and 6 wk, the cumulative percent healed on antacid was 33%, 64%, and 80%, and on cimetidine it was 25%, 62%, and 86%. The 114 patients with healed ulcer were observed on no therapy and underwent additional endoscopy to detect recurrences when symptomatic or at 3, 6, and 12 mo. There was no difference in the frequency of recurrences between treatments. At 3 and 6 mo, the cumulative percentages of patients with recurrence were 29% and 56% after antacid therapy and 36% and 55% after cimetidine therapy. Some patient variables were associated with delayed ulcer healing or ulcer recurrence. These included sex, pain frequency, smoking, disease duration, and acid secretion.     

Fatal upper and lower gastrointestinal cytomegalovirus disease following autologous peripheral blood stem cell transplantation

Although the life-threatening cytomegalovirus (CMV) disease is a well known complication following allogeneic hematopoietic stem cell transplantation (HSCT), it has been considered infrequent after autologous peripheral blood stem cell transplantation (PBSCT). On the other hand, the massive involvement of the gastrointestinal (GI) tract as the primary site of fatal CMV disease is particularly rare after autologous PBSCT. We present the case of a woman who suffered from CMV disease after high-dose busulphan/melphalan/thiotepa (BuMelTT) and autologous PBSCT. The primary site of infection was the GI tract, which was extensively affected. During the fifth week post-transplant the patient started with epigastralgia, diarrhea, fever, GI bleeding, and thrombocytopenia, and she died on day +52. Another case of fatal CMV disease among the few patients treated with BuMelTT has been recently reported, which suggests that the immunodeficiency associated with that regimen can be as intense as that occurring after allogeneic BMT.     

Distribución de fenotipos clínicos en pacientes con enfermedad pulmonar obstructiva crónica por humo de biomasa y por tabaco

Introduction

Exposure to biomass smoke is a risk factor for chronic obstructive pulmonary disease (COPD). It is unknown whether COPD caused by biomass smoke has different characteristics to COPD caused by tobacco smoke.

Objective

To determine clinical differences between these two types of the disease.

Methods

Retrospective observational study of 499 patients with a diagnosis of COPD due to biomass or tobacco smoke. The clinical variables of both groups were compared.

Results

There were 122 subjects (24.4%) in the biomass smoke group and 377 (75.5%) in the tobacco smoke group. In the tobacco group, the percentage of males was higher (91.2% vs 41.8%, P < .0001) and the age was lower (70.6 vs 76.2 years, P < .0001). Body mass index and FEV₁% values were higher in the biomass group (29.4 ± 5.7 vs 28.0 ± 5.1, P = .01, and 55.6 ± 15.6 vs 47.1 ± 17.1, P < .0001, respectively). The mixed COPD-asthma phenotype was more common in the biomass group (21.3% vs 5%, P < .0001), although this difference disappeared when corrected for gender. The emphysema phenotype was more common in the tobacco group (45.9% vs 31.9%, P = .009). The prevalence of the chronic bronchitis and exacerbator phenotypes, the comorbidity burden and the rate of hospital admissions were the same in both groups.

Conclusion

Differences were observed between COPD caused by biomass and COPD caused by tobacco smoke, although these may be attributed in part to uneven gender distribution between the groups.     

Efficacy of Glutamine in the Prevention of Acute Radiation Enteritis

Background: Acute radiation enteritis is a common adverse effect related to radiotherapy (RT). Glutamine is an immune modulator and antioxidant amino acid that can exert a protective role in patients receiving abdominal or pelvic radiation. The aim of this study was to test if glutamine prevents radiation enteritis during RT. Materials and Methods: Double‐blind, randomized, controlled trial including 69 patients who needed RT because of pelvic or abdominal malignancies and received glutamine (30 g/d) or placebo (casein, 30 g/d). Enteritis was evaluated according to the Radiation Therapy Oncology Group scale, intestinal inflammation using fecal calprotectin, and gut integrity with citrulline. The incidence of enteritis was analyzed by Kaplan‐Meier curves, and the hazard ratio (HR) was calculated using Cox regression. Results: Patients were predominantly male (65.2%), with an average (SD) age of 66.6 (9.9) years, with urologic (44.9%), rectal (24.6%), or gynecological cancer (23.1%). More patients developed enteritis with glutamine than with the placebo (55.9% vs 22.0%; P = .002), with an HR of 1.59 (95% confidence interval, 0.62–4.05). There were no differences in final calprotectin levels (glutamine, 57.9 [85.8] mg/kg vs placebo, 54.0 [57.7] mg/kg; P = .182) or the number of patients with values >50 mg/kg (glutamine, 58.1% vs placebo, 54.6%; P = .777). Final citrulline levels were similar between groups (glutamine, 26.31 [10.29] mmol/L vs placebo, 27.69 [12.31] mmol/L; P = .639), without differences in the number of patients with <20 mmol/L (glutamine, 24.1% vs placebo, 25.0%; P = .938). Citrulline concentration was reduced during RT with placebo but remained unchanged with glutamine. Conclusion: Glutamine does not prevent the development of enteritis during RT.     

Rasch analysis of clinical outcome measures in spinal muscular atrophy

Introduction: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. Muscle Nerve 49 :422–430, 2014     

Prognostic relevance of early AKI according to pRIFLE criteria in children undergoing cardiac surgery

Background

Acute renal injury increases risk of death after cardiac surgery. The objective of the study was to evaluate the ability of the pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) criteria to characterize the development of postoperative renal damage in children after cardiopulmonary bypass (CPB) and to evaluate the relationship between the severity of kidney injury and mortality, pediatric intensive care unit (PICU) length of stay, and the duration of mechanical ventilation (MV).

Methods

In this retrospective study including children undergoing CPB surgery during a 3-year period in the PICU of a tertiary hospital, demographic, clinical, surgery-related, and postoperative clinical data were collected. Kidney damage was assessed with pRIFLE criteria.

Results

Four hundred and nine patients were included. Early acute kidney injury (AKI) was found in 82 patients (achieving categories Risk 44; Injury 16; Failure 22). Early AKI was associated with younger age (P?=?0.010), longer CPB, deep hypothermic circulatory arrest (DHCA) use, ICU stay >12 days, MV >4 days, and death (P?<?0.001). Controlling the effect of age, CPB, DHCA use, previous cardiac surgeries, and Risk Adjustment in Congenital Heart Surgery Surgical Severity Score (RACHS-1), early AKI development proved to predict ICU stay >12 days [odds ratio (OR) 3.5; 95 % confidence interval (CI) 1.9–6.5, P?<?0.001)] and need of MV >4 days (OR 5.1; 95 % CI 2.6–10.2, P?<?0.001).

Conclusions

Early AKI when evaluated with the pRIFLE criteria can predict prolonged ICU stay, need of prolonged MV, and mortality.     

Transient regional osteoporosis

Transient regional osteoporosis (TRO) is a disease that predisposes to fragility fracture in weight bearing joints of mid-life women and men. Pregnant women may also suffer the process, usually at the hip. The prevalence of TRO is lower than the systemic form, associated with postmenopause and advanced age, but may be falsely diminished by under-diagnosis. The disease may be uni- or bilateral, and may migrate to distinct joints. One main feature of TRO is spontaneous recovery. Pain and progressive limitation in the functionality of the affected joint(s) are key symptoms. In the case of the form associated with pregnancy, difficulties in diagnosis derive from the relatively young age at presentation and from the clinical overlapping with the frequent aches during gestation. Densitometric osteoporosis in the affected region is not always present, but bone marrow edema, with or without joint effusion, is detected by magnetic resonance. There are not treatment guidelines, but the association of antiresorptives to symptomatic treatment seems to be beneficial. Surgery or other orthopedic interventions can be required for specific indications, like hip fracture, intra-medullary decompression, or other.     

Spanish Menopause Society position statement: Use of denosumab in postmenopausal women

Denosumab is a new drug developed for the treatment of osteoporosis. Moreover, increasing evidences link denosumab with benefits in cancer, an area of interest for those in charge of the postmenopausal health. Denosumab has shown efficacy in the control of bone loss associated with hypogonadic states created by chemotherapy in breast and other cancers. Moreover, some studies reveal efficacy in reducing the progression of metastases. A panel of experts from the Spanish Menopause Society has met to develop usage recommendations based on the best available evidence.     

Systems Medicine: from molecular features and models to the clinic in COPD

Background and hypothesis

Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice.

Objective and method

Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework.

Results

In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice.

Conclusions

The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models. Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them.