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A letter to the editor is presented about the treatment of diabetes.

Background: Myocardial fibrosis, as diagnosed on cardiac magnetic resonance imaging (cMRI) by late gadolinium enhancement (LGE), is associated with adverse outcomes in adults with hypertrophic cardiomyopathy (HCM), but its prevalence and magnitude in children with HCM have not been established. We investigated: (1) the prevalence and extent of myocardial fibrosis as detected by LGE cMRI; (2) the agreement between echocardiographic and cMRI measurements of cardiac structure; and (3) whether serum concentrations of N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-T are associated with cMRI measurements., Methods: A cross-section of children with HCM from 9 tertiary-care pediatric heart centers in the U.S. and Canada were enrolled in this prospective NHLBI study of cardiac biomarkers in pediatric cardiomyopathy (ClinicalTrials.gov Identifier: NCT01873976). The median age of the 67 participants was 13.8 years (range 1-18 years). Core laboratories analyzed echocardiographic and cMRI measurements, and serum biomarker concentrations., Results: In 52 children with non-obstructive HCM undergoing cMRI, overall low levels of myocardial fibrosis with LGE >2% of left ventricular (LV) mass were detected in 37 (71%) (median %LGE, 9.0%; IQR: 6.0%, 13.0%; range, 0% to 57%). Echocardiographic and cMRI measurements of LV dimensions, LV mass, and interventricular septal thickness showed good agreement using the Bland-Altman method. NT-proBNP concentrations were strongly and positively associated with LV mass and interventricular septal thickness (P < .001), but not LGE., Conclusions: Low levels of myocardial fibrosis are common in pediatric patients with HCM seen at referral centers. Longitudinal studies of myocardial fibrosis and serum biomarkers are warranted to determine their predictive value for adverse outcomes in pediatric patients with HCM., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing ( P =0.005 and P =0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first-degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01873963.

Aging is a multifactorial process accompanied by loss of cell function. Science has been looking for factors responsible for aging for many years. However, despite identifying a number of possible causes, the definite reason for aging has been elusive so far. One of the factors contributing to aging is oxygen free radicals. In this context, beneficial effects of coffee on various organisms, including humans, were investigated, although the results are far from unequivocal. In our research, we used the budding yeast-something of a workhorse in many studies, including the studies of aging. So far, the impact of coffee on the aging of cells in the budding yeast experimental setup has little known about it. Here, we provide strong evidence that coffee compounds, particularly flavonoids, are responsible for scavenging free radicals and longevity in yeast lacking Sod1, Sod2 and Rad52 proteins. In this paper, we compared Arabica and Robusta coffee types. We present an analysis of the concentration of caffeine and flavonoids measured by the High-Performance Liquid Chromatography method. We show that Robusta has a much greater antioxidant capacity than Arabica. We also conclude that coffee infusions significantly extend the chronological lifespan of the Saccharomyces cerevisiae yeast cells by protecting cells against reactive oxygen species, double DNA-strand break and decrease in metabolic activity.

Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time., Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing., Results: With the exception of serum myoglobin, there were no statistical differences or apparent dose-response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P = .0006)., Conclusions: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.

Enrollment of patients in sickle cell intervention trials has been challenging due to difficulty in obtaining consent from a legal guardian and lack of collaboration between emergency medicine and hematology. We utilized education and preconsent in a pediatric multisite sickle cell intervention trial to overcome these challenges. Overall, 48 patients were enrolled after being preconsented. Variable Institutional Review Board policies related to preconsent validity and its allowable duration decreased the advantages of preconsent at some sites. The utility of preconsent for future intervention trials largely depends on local Institutional Review Board policies. Preeducation may also benefit the consent process, regardless of site differences., (© 2016 Wiley Periodicals, Inc.)

There is recent enhanced interest in the potential of medication to produce serious toxicity, and the television media have focused on the serious side effects and drug-drug interactions caused by antibiotics. In fact, a recent hospital study noted that drug-related toxicity was one of the most common causes of death for hospitalized patients. Antibiotic-induced adverse events contribute to host injury diagnostic confusion and excessive medical costs. In addition, however, a "spin-off'' of antibiotic-induced adverse events is the emergence and dissemination of drug-resistant organisms. This chapter will describe the adverse events and drug-drug interactions produced by those antibiotics that are most commonly prescribed to patients to prevent or treat respiratory tract infections. An effort will also be made to focus on those unique settings (the patient with renal insufficiency, the patient receiving immunosuppressive medication, the pregnant patient, the elderly patient, and the HIV-infected patient who is a candidate for primary or secondary prophylaxis for Pneumocystis carinii) that require a knowledge of antibiotic-induced adverse events.

Allergic reactions, adverse effects, and drug interactions are an inevitable part of antimicrobial prescribing. A working knowledge of these issues remains paramount, especially when administering such agents to patients who are pregnant, infected with HIV, or who have renal insufficiency. The discussion also includes antibiotic-OTC drug interactions and antibiotic hypersensitivity.

Background: Nosocomial infections affect more than 2 million patients annually in the United States at a cost of $4.5 billion. The aim of this study is to identify the role of the APACHE II score and the Injury Severity Scale (ISS) as independent predictors of nosocomial infections in trauma patients admitted to the intensive care unit (ICU)., Methods: A retrospective chart review of 113 trauma patients admitted to the ICU was conducted by an infectious disease physician. Demographic data and incidence of nosocomial infections were recorded. Multivariate logistic regression analysis was used to determine variables that are predictive of the occurrence of nosocomial infections., Results: Presence or absence of intubation, ICU length of stay, APACHE II score, and ISS were related to the presence of infections; however, only the ICU length of stay was an independent predictor of a nosocomial infection, with an odds ratio of 1.81. By linear regression, 17% of the variance in the ICU duration of stay was a result of the APACHE II score in patients with a score >/=5., Conclusion: APACHE II score and ISS score were not good predictors of the incidence of nosocomial infections in trauma patients admitted to the ICU, but the APACHE II score has a modest correlation with the duration of stay in the ICU. A stratified cohort study could identify the subset of patients for which the APACHE II score predicts a prolonged stay in the ICU, thus an increased risk of infection.

Study Objective: To study the epidemiology of Stenotrophomonas maltophilia infections in the intensive care units (ICUs) of community general hospitals., Design: Retrospective chart review of 143 patients with cultures positive for S. maltophilia over a 2-year period., Setting: Intensive care units of 2 community general hospitals., Results: Patients with S. maltophilia infection or colonization were elderly (mean age 62.4 years), intubated for a mean of 11.8 days, and had a mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 16.6. A tracheostomy was present in 22.4%, and underlying chronic respiratory disease and malignancy were found in 25.9% and 15.4%, respectively. Only 2 patients (1.4%) were neutropenic. Most isolates (89.5%) were from the respiratory tract and were part of a polymicrobial culture in 52. 5% of patients. Only a slightly higher APACHE II score (mean = 18.0, SD 7.8 vs mean = 15.6, SD 6.2, P = 0.052) differentiated patients with infection from those with colonization. All but 2 patients were exposed to antibiotics before their positive culture. Crude mortality rate was 41.3% overall and was significantly higher in those with an APACHE II score of 15 or more (48.8% vs 30.5%, P = 0. 028)., Conclusion: S. maltophilia is emerging as an important cause of nosocomial infection, especially pneumonia, in ICUs of community general hospitals. Patients tend to be elderly, intubated for a mean of about 12 days, have high APACHE II scores, and frequently have a tracheostomy or underlying chronic respiratory disease. In contrast to earlier reports, neutropenia and underlying malignancy are uncommon in our ICU population. We found prior antibiotic exposure was almost universal and similar to previous reports, but use of imipenem was much less common in our community hospital patients. Patients with a high APACHE II score should be considered infected rather than colonized, but differentiation of infection from colonization remains problematic. Isolation of S. maltophilia from a patient carries a crude mortality rate of 41.3%, and patients with an APACHE II score of 15 or more have a significantly higher mortality rate than those with lesser scores, approaching 50%. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the drug of choice for infections caused by S. maltophilia.

Infectious arthritis in renal transplant patients may be a commonly diagnosed condition with traditional bacterial organisms isolated. However, since nontuberculous mycobacteria are ubiquitous in the environment, immunocompromised individuals may suffer from infections with these organisms. Concomitant gout and Mycobacterium avium intracellulare septic arthritis is described for the first time in this clinical setting. Appropriate cultures should be performed even in the setting of crystal arthritis in posttransplant patients when clinically indicated.

Fever is common among HIV-infected patients. Because it may signal a serious, potentially fatal underlying infection, a thorough investigation is merited. Where does evaluation begin and end? Drs Gleckman and Czachor discuss a diagnostic approach for primary care physicians that emphasizes rapid identification of the source of fever.

Various water-borne bacteria can cause significant illness. Illness most often results from ingestion of contaminated water or seafood, with gastrointestinal entry of pathogens or their byproducts. The skin and soft tissues are also common entry points, either through trauma in or near the water, or by seawater contamination of an existing wound or break in the skin. Clinically significant water-borne illnesses are still rare. However, because humans are increasingly exposed to contaminated water sources through recreation or habitat, the rate of water-borne illnesses can be expected to increase. In patients who present with gastrointestinal illness or infections that do not respond to conventional therapy, water-borne pathogens should be considered in the differential diagnosis. A complete history, with attention to seafood ingestion and exposure to marine or freshwater life-forms, in conjunction with a high index of suspicion (especially in immunocompromised patients), will increase diagnostic accuracy in patients with water-borne illnesses.

Aztreonam is a synthetic, monobactam antibiotic structurally related to the beta-lactam class of drugs. It has inhibitory activity against many aerobic gram-negative bacteria, although it does not inhibit gram-positive or anaerobic bacteria. Administration of aztreonam occasionally is associated with minimal and transient adverse effects. This case report describes a patient we believe experienced bone marrow suppression approximately ten days after aztreonam was given for treatment of pneumonia caused by Pseudomonas aeruginosa. This untoward effect primarily was manifested as neutropenia, although normochromic, normocytic anemia and thrombocytopenia were noted as well. One week after aztreonam was discontinued, the patient's bone marrow suppression resolved spontaneously. Although the mechanism responsible for myelosuppression is unclear, aztreonam may be implicated as the offending agent based on the temporal relationship between the development of neutropenia and its administration, and the resolution of neutropenia upon its discontinuation.

As the elderly segment of our population expands, physicians will be prescribing medications more frequently for this age group. Physiologic changes, drug-drug interactions, and untoward adverse reactions are more common in the elderly. In addition, therapeutic decisions regarding antimicrobial agents for infectious disease in the aged are also complicated by the burgeoning number of compounds available to clinicians. A thorough knowledge of various antibiotic interactions, potential toxicities, and pharmacokinetics is necessary to safely and effectively prescribe these agents for elderly patients.

The elevated serum glucose levels of diabetics affect traditional host defenses, predisposing these individuals to infectious processes. The elderly diabetic patient is also faced with senescence of the immune system which can alter host defense mechanisms and increase the risk of infection. Infections in elderly diabetics can be severe and life-threatening, and only through the prompt recognition and treatment of these disorders can morbidity and mortality be avoided. Broad-spectrum antimicrobial agents, in conjunction with surgical intervention, are often necessary to eradicate these infections. Common sites of involvement include the skin, biliary tract, urinary tract, and the soft tissues and bones of the feet.

Third-generation cephalosporins are indicated for treatment of sexually transmitted diseases, resistant salmonellosis, and infections in the febrile leukopenic host. The practicing physician must weigh the expanding role of these agents against their limitations. Some potential problems include bleeding (confined to the use of moxalactam [Moxam] or cefoperazone [Cefobid]), a reaction like that to disulfiram (Antabuse) when combined with alcohol (also confined to the use of moxalactam or cefoperazone), and superinfection. A prolonged course of treatment entails significant expense. Further evaluation and clinical experience is necessary before use of third-generation cephalosporins for some of the newer indications (eg, late stages of Lyme disease, neurosyphilis) becomes routine medical practice.

A case of postoperative anaerobic mediastinitis after coronary artery bypass grafting is reviewed. One of the causative organisms, Bacteroides oralis, has never previously been described as a pathogen causing mediastinitis after median sternotomy incision. There was associated Bacteroides fragilis bacteremia. Only three cases of Bacteroides species mediastinitis after open heart surgery have been reported. This anaerobic bacterium remains a rare pathogen in median sternotomy infections despite the increasing number of cases of mediastinitis seen in association with the burgeoning number of patients undergoing cardiac surgery. Multiple risk factors may contribute to mediastinal infections, which occur in about 2% of patients undergoing coronary artery surgery. When infection occurs, aerobic and anaerobic wound cultures should be made and appropriate antimicrobial and surgical therapy instituted.