Real-world pan-cancer landscape of frameshift mutations and their role in predicting responses to immune checkpoint inhibitors in cancers with low tumor mutational burden.

Background: Pembrolizumab is FDA approved for tumors with tumor mutational burden (TMB) of ≥10 mutations/megabase (mut/Mb). However, the response to immune checkpoint inhibitors (ICI) varies significantly among cancer histologies. We describe the landscape of frameshift mutations (FSs) and evaluated their role as a predictive biomarker to ICI in a clinical cohort of patients.

Bacterial and Viral Infections in Atopic Dermatitis: a Comprehensive Review.

Atopic dermatitis (AD) is the most common allergic skin disease in the general population. It is a chronic inflammatory skin disease complicated by recurrent bacterial and viral infections that, when left untreated, can lead to significant complications. The current article will review immunologic and molecular mechanisms underlying the propensity of AD patients to microbial infections.

Altered sensitization patterns to sweet food stimuli in patients recovered from anorexia and bulimia nervosa.

Recent studies show that higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa (AN) and overeating in bulimia nervosa (BN). The purpose of this study was to determine whether sensitization effects might underlie pathologic eating behavior when a taste stimulus is administered repeatedly. Recovered AN (RAN, n=14) and BN (RBN, n=15) subjects were studied in order to avoid the confounding effects of altered nutritional state.

Caring for 'Very Important Patients'--Ethical Dilemmas and Suggestions for Practical Management.

The care of Very Important Patients (VIPs) is different from other patients because they may receive greater access, attention, and resources from health care staff. Although the term VIP is used regularly in the medical literature and is implicitly understood, in practice it constitutes a wide and heterogeneous group of patients that have a strong effect on health care providers. We define a VIP as a very influential patient whose individual attributes and characteristics (eg, social status, occupation, position), coupled with their behavior, have the potential to significantly influence a clinician's judgment or behavior.

Three-minute method for amino acid analysis by UHPLC and high-resolution quadrupole orbitrap mass spectrometry.

Amino acid analysis is a powerful bioanalytical technique for many biomedical research endeavors, including cancer, emergency medicine, nutrition and neuroscience research. In the present study, we present a 3 min analytical method for underivatized amino acid analysis that employs ultra high-performance liquid chromatography and high-resolution quadrupole orbitrap mass spectrometry. This method has demonstrated linearity (mM to nM range), reproducibility (intra-day <5 %, inter-day <20 %), sensitivity (low fmol) and selectivity.

Maintenance of Certification Part IV Quality-Improvement Project for Hypertension Control: A Preliminary Retrospective Analysis.

Fifty-two American Board of Family Medicine and 19 American Board of Internal Medicine certified physicians completed projects to increase the percentage of hypertensive patients on their patient panels who had controlled blood pressure. Mean panel blood pressure control improved from 79.49% to 84.

Self-reported sleep quality and acute exacerbations of chronic obstructive pulmonary disease.

Background: Many patients with chronic obstructive pulmonary disease (COPD) suffer from poor sleep quality. We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients.

Methods: This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment.

Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.

Background: Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD.

Study Design: Cohort study.

Aberrant chloride intracellular channel 4 expression contributes to endothelial dysfunction in pulmonary arterial hypertension.

Background: Chloride intracellular channel 4 (CLIC4) is highly expressed in the endothelium of remodeled pulmonary vessels and plexiform lesions of patients with pulmonary arterial hypertension. CLIC4 regulates vasculogenesis through endothelial tube formation. Aberrant CLIC4 expression may contribute to the vascular pathology of pulmonary arterial hypertension.

Fetal diagnostic indications for second and third trimester outpatient pregnancy termination.

Objective: To determine the frequency of diagnostic indications among women seeking to terminate pregnancies for reasons of fetal abnormality, spontaneous fetal demise, or a genetic disorder in a private outpatient clinic specializing in late outpatient abortion procedures.

Method: A total of 1005 women requested termination of pregnancy for reasons of genetic disorder, fetal anomaly, or fetal demise over 20 years (1992-2012). Gestational ages ranged from 12 to 39 weeks.

Effects of solution conditions on methionine oxidation in albinterferon alfa-2b and the role of oxidation in its conformation and aggregation.

Physical and chemical degradation of therapeutic proteins can occur simultaneously. In this study, our first objective was to investigate how solution conditions that impact conformational stability of albinterferon alfa-2b, a recombinant fusion protein, modulate rates of methionine (Met) oxidation. Another objective of this work was to determine whether oxidation affects conformation and rate of aggregation of the protein.

Pediatric overuse injuries in sports.

Overuse injuries in the pediatric and adolescent population are a growing problem in the United States as more children participate in recreational and organized sports. It is not uncommon for children and adolescents to play on multiple teams simultaneously or to be involved in sports year-round. Without adequate rest, the demands of exercise can exceed the body's ability to repair tissues, leading to repetitive microtrauma and overuse injury.

Physical stability of albinterferon-α(2b) in aqueous solution: effects of conformational stability and colloidal stability on aggregation.

Controlling aggregation in protein therapeutics is a significant challenge. In this study, the aggregation behavior of albinterferon-α(2b) , a genetic fusion protein combining human serum albumin and α-interferon, was examined as a function of solution conditions. The stability was monitored during agitation and during storage at elevated temperature, where the extent of aggregation was determined using size-exclusion chromatography.

A "high-risk" epithelioid hemangioendothelioma presenting as a solitary, ulcerated, subcutaneous tumor.

So-called "high-risk" epithelioid hemangioendotheliomas are uncommon neoplasms that demonstrate classic histopathologic features of epithelioid hemangioendotheliomas and a size larger than 3 cm or >3 mitotic figures per 50 high power fields. These neoplasms show an increased rate of metastasis (25% of cases) and are associated with a poor 5-year survival (59%). They may pose a diagnostic challenge for dermatopathologists as they mimic metastatic carcinoma, malignant mixed tumor, melanocytic neoplasms, epithelioid sarcoma, and epithelioid angiosarcoma.

Azithromycin for prevention of exacerbations of COPD.

Background: Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.

Methods: We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.

DITPA, a thyroid hormone analog, reduces infarct size and attenuates the inflammatory response following myocardial ischemia.

Background: Thyroid hormone can have positive effects on the cardiovascular system but its therapeutic potential is limited secondary to its adverse effects. DITPA (3,5-diiodothyroproprionic acid) is a synthetic thyroid hormone analog with positive inotropic effects similar to thyroid hormone but with minimal systemic effects. DITPA has previously been shown to reduce pathologic remodeling and improve cardiac output following myocardial infarction; however, few studies have examined the role of DITPA in determining infarct size or the early inflammatory response following myocardial ischemia.

Balance in children with bilateral cochlear implants.

Objective: To determine whether unilateral or bilateral cochlear implantation affects the functional balance of children when compared with children with severe-to-profound bilateral hearing loss without a cochlear implant.

Designs: An observational case control study.

Methods: Three cohorts of children aged 4 to 17 years were studied: those with unilateral cochlear implants, those with bilateral cochlear implants, and nonimplanted children with severe-to-profound bilateral hearing loss.

Kyphectomy improves sitting and skin problems in patients with myelomeningocele.

Background: Progressive kyphosis occurs in up to 20% of patients with myelomeningocele. Severely affected patients can develop recurrent skin breakdown, osteomyelitis, sitting imbalance, and poor cosmetic appearance.

Questions/purposes: We (1) assessed the ability of kyphectomy to restore an intact skin envelope and allow comfortable seating in a wheelchair; (2) reviewed the complications of kyphectomy and spinal fusion in myelomeningocele; and (3) determined whether patients requiring unexpected reoperation had worse correction or more ulceration compared with those patients treated with a single surgery.

Long-term outcomes in children with pulmonary arterial hypertension treated with bosentan in real-world clinical settings.

Treatment algorithms in pediatric pulmonary arterial hypertension (PAH) are derived from clinical trials in adult populations and from clinical practice, but experience in children is limited. In this retrospective cohort study, we analyzed outcomes in a previously identified cohort of 86 consecutive children with PAH treated with bosentan as part of their treatment regimen. All children with idiopathic PAH or heritable PAH and PAH associated with congenital heart disease or connective tissue disease who started bosentan treatment from May 2001 to April 2003 in 2 tertiary pediatric referral centers were followed, with data collection ending August 2006.

Not all rickets is vitamin D deficiency.

Although vitamin D deficiency is a common cause of rickets, other types of rickets, including hereditary forms, must be considered in the differential diagnosis. The patient described here presented for evaluation of bowing of his lower extremities, and was ultimately diagnosed with X-linked hypophosphatemic rickets, a disorder caused by renal wasting of phosphate that occurs as a result of a mutation in the PHEX gene.