Chronic recurrent multifocal osteomyelitis in a patient with selective immunoglobulin M deficiency

Chronic recurrent multifocal osteomyelitis is an unusual inflammatory process of unknown origin involving multiple osseous sites, often recurrently. Selective immunoglobulin M (IgM) deficiency is a rare primary immunodeficiency disease, which can be associated with autoimmune diseases such as systemic lupus erythematosus, Hashimoto’s disease, or hemolytic anemia. Here we report a case of a chronic recurrent multifocal osteomyelitis coexisting with selective IgM deficiency.     

The Dilemma of Chronic Recurrent Multifocal Osteomyelitis

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare idiopathic inflammatory disease that affects mainly children and young adults, resulting in significant morbidity especially if not diagnosed early. The clinical signs and symptoms are nonspecific, with a consequential delay in diagnosis. Radiological and histopathological criteria are important for its definition. Two cases of CRMO are reported, highlighting the diagnostic challenge and demonstrating the importance of timely investigations.     

Role of Testosterone in the Pathogenesis,Progression, Prognosis and Comorbidity of Men With Chronic Kidney Disease

Testosterone deficiency and hypogonadism are common conditions in men with chronic kidney disease (CKD). A disturbed hypothalamic‐pituitary‐gonadal axis due to CKD is thought to contribute to androgen deficiency. Data from experimental studies support the hypothesis that exogenous administration of testosterone may induce the activation of the renin–angiotensin system (RAS), the production of endothelin and the regulation of anti‐ or/and proinflammatory cytokines involved in the pathogenesis of hypertension and kidney damage. On the other hand, low testosterone levels in male patients with CKD are paradoxically associated with a higher risk of morbidity and mortality, possibly explained by anemia, osteoporosis and cardiovascular disease. In this article, we present an overview of clinical and experimental studies of the impact of testosterone on the progression and prognosis of male patients with CKD; even today, this remains a controversial issue.     

Chronic kidney disease,lipids and apolipoproteins,and coronary heart disease: The ARIC Study

Background

Chronic kidney disease (CKD) is associated with elevated apolipoprotein B to A-1 ratio (ApoB/A1). It is not known whether these markers are more strongly associated with the risk of coronary heart disease (CHD) in CKD compared to traditionally measured lipids and lipoprotein cholesterol ratios.

Methods

We studied the association of lipids and apolipoproteins including non-HDL-cholesterol to HDL-cholesterol ratio (NonHDLc/HDLc) and ApoB/A1 with incident CHD in 10,137 individuals free of CHD at baseline (visit four) in the Atherosclerosis Risk in Communities (ARIC) study. An estimated glomerular filtration rate of 15 to <60 ml/min/1.73 m² based on a cystatin C measurement was used to define CKD (Stage 3–4). Cox proportional hazards regression models were used to determine the association of lipids and apolipoprotein measurements with the risk of CHD in those with and without CKD after adjustment for demographic and known clinical cardiovascular risk factors.

Results

CKD was present in 1217 (12%) individuals free of CHD at baseline. The median follow-up time was 11.1 years. A CHD event developed in 498 out of 8920 individuals without CKD (incidence rate: 5.2 events per 1000 person-years) and in 138 out of 1217 individuals with CKD (incidence rate: 12.0 events per 1000 person–years; P < 0.001). Those with CKD had a lower concentration of ApoA1: median (in g/L) and interquartile range (IQR) = 1.40 (1.38–1.42) vs. 1.48 (1.47–1.49) P < 0.001; and a higher ApoB/A1 = 0.75 (0.73–0.77) vs. 0.71 (0.70–0.72) P < 0.001; than those without CKD (eGFR ≥ 60 ml/min/1.73 m²). Among individuals with CKD, ApoB/A1 and NonHDLc/HDLc were both associated with the risk of CHD: hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation increase = 1.22 (1.02–1.46) for ApoB/A1 and 1.30 (1.07–1.57) for NonHDLc/HDLc with no significant differences detected (P for interaction >0.1) when comparing these estimates to those of participants without CKD.

Conclusions

Although CKD is associated with a lower ApoA1 concentration and with a higher ApoB/A1, we found no evidence that these apolipoproteins are more strongly associated with CHD incidence in CKD compared to NonHDLc/HDLc.     

Periodontal Pocket Depth,Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study

Background

No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases.

New Treatment Option for Chronic Obstructive Pulmonary Disease: Two Long-Acting Bronchodilators in a Single Metered-Dose Inhaler

Combination long-acting inhaled bronchodilators are central to the management of patients with moderate to very severe chronic obstructive pulmonary disease. Glycopyrrolate is a long-acting muscarinic antagonist (LAMA), and formoterol fumarate is a long-acting beta₂ agonist (LABA). In randomized controlled trials, this LAMA/LABA combination in a metered-dose inhaler was shown to be effective in improving pulmonary function and quality of life. Clinicians now have the availability of 3 delivery systems for LAMA/LABA therapy, including metered-dose inhaler, dry-powder inhaler, and Soft Mist inhaler. On the basis of numerous patient factors, such as cognitive ability, manual strength/dexterity, and peak inspiratory flow, clinicians may select the most appropriate inhalation device. For each inhalation device, persistent patient education is absolutely essential, including observation of patient use. International evidence-based guidelines stress the critical importance of ensuring correct use of inhalation devices.     

Treatment of Chronic Obstructive Pulmonary Disease with Roflumilast,a New Phosphodiesterase 4 Inhibitor

ABSTRACT

Recent advances in chronic obstructive pulmonary disease (COPD) treatment offer symptom relief, but disease modification remains an unmet goal of pharmacotherapy. Reducing the frequency and severity of COPD exacerbations may help slow disease progression and reduce the morbidity, mortality, and costs associated with these major events. Other desirable characteristics for a COPD treatment include a once-daily dosing schedule, an oral formulation, and a low frequency of systemic side effects. Phosphodiesterase 4 inhibitors have been in clinical development for some years and roflumilast is currently the most advanced of these agents. In this review, the preclinical evidence, clinical safety, and efficacy of roflumilast available in published reports are considered. The data reviewed here suggest that the clinical efficacy of roflumilast occurs through a mechanism unrelated to bronchodilation and may be due to the suppression of lung inflammation. Lung function improved with roflumilast treatment and in some studies, the reduction in exacerbations was substantial and statistically significant. Notably, this effect appeared to be greatest in the subgroup of patients with more severe disease and more severe exacerbations. The evaluation of roflumilast safety largely centers on gastrointestinal adverse events, with diarrhea, nausea, and weight loss occurring more frequently with the drug than placebo. If approved for general use, we expect roflumilast to find its role initially as a substitute for inhaled corticosteroids in the maintenance treatment of severe and very severe disease, particularly in patients who have frequent acute exacerbations, and perhaps as a supplementary drug when symptoms are not adequately controlled by current conventional COPD therapy.     

Chronic Myeloid Leukemia: Current Guidelines for Diagnosis and Management

Over the past two decades advances in the understanding of molecular and biological aspects of chronic myeloid leukemia (CML) have served as one of the cornerstones of progress in the management of leukemias, and more broadly of cancer in general. With the identification of the Philadelphia chromosome and its association with 95% of cases of CML and later with the possible etiologic role of the BCR-ABL fusion gene in the initiation of CML, a new chapter in the understanding of leukemogenesis was entered upon.

Later with the identification of interferons as a therapeutic modality, and demonstration of their role in suppression of the malignant clone and the associated increase in survival, CML was one of the first malignancies in which biologic therapy found an established role.

With advances in allogeneic bone marrow transplantation, it is hoped that more patients would be able to benefit from this curative therapy with less associated toxicity. However, a large proportion of patients are still unable to undergo an allogeneic transplant due to lack of donors and the expected toxicity. Other therapeutic modalities including new forms of interferon, new agents such as Homoharringtonine, and new techniques such as purged autologous transplant with or without immuno-modulation need to be further developed and perfected.

Our current challenges are to stratify CML patients, using the available risk scores in order to assign the most appropriate therapy to the individual, and to continue to improve upon the available therapies.