Monica Khunger

Dose Response Relationship Between Physical Activity and Risk of Heart Failure: A Meta-Analysis

Background— Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose–response association between PA and HF risk has not been reported previously. Methods and Results— Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose–response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]–min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67–0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87–0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77–0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58–0.73) the minimum guideline-recommended levels. Conclusions— There is an inverse dose–response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk.

Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials

Background Programmed death 1 (PD‐1) programmed death‐ligand 1 (PD‐L1) inhibitors show significant clinical activity in non‐small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune‐mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD‐1 and PD‐L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. Methods MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian‐Laird random effects models. We compared incidences between PD‐1 and PD‐L1 inhibitors and between treatment naive and previously treated patients. Results Nineteen trials (12 with PD‐1 inhibitors [n = 3,232] and 7 with PD‐L1 inhibitors [n = 1,806]) were identified. PD‐1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD‐L1 inhibitors (3.6%; 95% CI, 2.4%‐4.9% vs 1.3%; 95% CI, 0.8%‐1.9%, respectively; P = .001). PD‐1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%‐1.7% vs 0.4%; 95% CI, 0%‐0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%‐6.3% vs 2.8%; 95% CI, 1.7%‐ 4%; P = .03). Conclusions There was a higher incidence of pneumonitis with use of PD‐1 inhibitors compared with PD‐L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients.

Incidence of pneumonitis with use of PD-1 and PD-L1 inhibitors in non-small cell lung cancer: A Systematic Review and Meta-analysis of trials

Background Programmed death 1 (PD‐1) programmed death‐ligand 1 (PD‐L1) inhibitors show significant clinical activity in non‐small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune‐mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD‐1 and PD‐L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. Methods MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian‐Laird random effects models. We compared incidences between PD‐1 and PD‐L1 inhibitors and between treatment naive and previously treated patients. Results Nineteen trials (12 with PD‐1 inhibitors [n = 3,232] and 7 with PD‐L1 inhibitors [n = 1,806]) were identified. PD‐1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD‐L1 inhibitors (3.6%; 95% CI, 2.4%‐4.9% vs 1.3%; 95% CI, 0.8%‐1.9%, respectively; P = .001). PD‐1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%‐1.7% vs 0.4%; 95% CI, 0%‐0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%‐6.3% vs 2.8%; 95% CI, 1.7%‐ 4%; P = .03). Conclusions There was a higher incidence of pneumonitis with use of PD‐1 inhibitors compared with PD‐L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients.

Efficacy and Safety of Exercise Training in Chronic Pulmonary Hypertension Systematic Review and Meta-Analysis

Background—Exercise training has been shown to improve cardiorespiratory fitness, physical capacity, and quality of life in patients with cardiopulmonary conditions, such as heart failure and chronic obstructive pulmonary disease. However, its role in management of pulmonary hypertension is not well defined. In this study, we aim to evaluate the efficacy and safety of exercise training in patients with pulmonary hypertension. Methods and Results—We included all prospective intervention studies that evaluated the efficacy and safety of exercise training in patients with pulmonary hypertension. Primary outcome of this meta-analysis was a change in 6-minute walk distance. We also assessed the effect of exercise on peak oxygen uptake, resting pulmonary arterial systolic pressure, peak exercise heart rate, and quality of life. A total of 469 exercise-training participants enrolled in 16 separate training studies were included. In the pooled analysis, exercise training was associated with significant improvement in 6-minute walk distance (weighted mean difference, 53.3 m; 95% confidence interval, 39.5–67.2), peak oxygen uptake (weighted mean difference, 1.8 mL/kg per minute; 95% confidence interval, 1.4–2.3), pulmonary arterial systolic pressure (weighted mean difference, −3.7 mm Hg; 95% confidence interval, −5.4 to −1.9), peak exercise heart rate (weighted mean difference, 10 beats per min; 95% confidence interval, 6–15), and quality of life as measured on SF-36 questionnaire subscale scores. Furthermore, exercise training was well tolerated with a low dropout rate, and no major adverse events were related to exercise training. Conclusions—Exercise training in patients with pulmonary hypertension appears safe and is associated with a significant improvement in exercise capacity, pulmonary arterial pressure, and quality of life.

Efficacy and Safety of Exercise Training in Chronic Pulmonary HypertensionCLINICAL PERSPECTIVE

Background—Exercise training has been shown to improve cardiorespiratory fitness, physical capacity, and quality of life in patients with cardiopulmonary conditions, such as heart failure and chronic obstructive pulmonary disease. However, its role in management of pulmonary hypertension is not well defined. In this study, we aim to evaluate the efficacy and safety of exercise training in patients with pulmonary hypertension. Methods and Results—We included all prospective intervention studies that evaluated the efficacy and safety of exercise training in patients with pulmonary hypertension. Primary outcome of this meta-analysis was a change in 6-minute walk distance. We also assessed the effect of exercise on peak oxygen uptake, resting pulmonary arterial systolic pressure, peak exercise heart rate, and quality of life. A total of 469 exercise-training participants enrolled in 16 separate training studies were included. In the pooled analysis, exercise training was associated with significant improvement in 6-minute walk distance (weighted mean difference, 53.3 m; 95% confidence interval, 39.5–67.2), peak oxygen uptake (weighted mean difference, 1.8 mL/kg per minute; 95% confidence interval, 1.4–2.3), pulmonary arterial systolic pressure (weighted mean difference, −3.7 mm Hg; 95% confidence interval, −5.4 to −1.9), peak exercise heart rate (weighted mean difference, 10 beats per min; 95% confidence interval, 6–15), and quality of life as measured on SF-36 questionnaire subscale scores. Furthermore, exercise training was well tolerated with a low dropout rate, and no major adverse events were related to exercise training. Conclusions—Exercise training in patients with pulmonary hypertension appears safe and is associated with a significant improvement in exercise capacity, pulmonary arterial pressure, and quality of life.

Optimal management of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), also known by the eponym Osler–Weber–Rendu syndrome, is a group of related disorders inherited in an autosomal dominant fashion and characterized by the development of arteriovenous malformations (AVM) in the skin, mucous membranes, and/or internal organs such as brain, lungs, and liver. Its prevalence is currently estimated at one in 5,000 to 8,000. Most cases are due to mutations in the endoglin (HHT1) or ACVRLK1 (HHT2) genes. Telangiectasias in nasal and gastrointestinal mucosa generally present with recurrent/chronic bleeding and iron deficiency anemia. Larger AVMs occur in lungs (~40%–60% of affected individuals), liver (~40%–70%), brain (~10%), and spine (~1%). Due to the devastating and potentially fatal complications of some of these lesions (for example, strokes and brain abscesses with pulmonary AVMs), presymptomatic screening and treatment are of utmost importance. However, due to the rarity of this condition, many providers lack an appreciation for the whole gamut of its manifestations and complications, age-dependent penetrance, and marked intrafamilial variation. As a result, HHT remains frequently underdiagnosed and many families do not receive the appropriate screening and treatments. This article provides an overview of the clinical features of HHT, discusses the clinical and genetic diagnostic strategies, and presents an up-to-date review of literature and detailed considerations regarding screening for visceral AVMs, preventive modalities, and treatment options.

Infection in autoimmune bullous diseases: A retrospective comparative study

Certain autoimmune bullous diseases (AIBD), including pemphigoid and pemphigus, confer increased infection risk. Infections have not been systematically studied in these conditions, however. Little is known about infection risk in these conditions, particularly dermatitis herpetiformis (DH). We aimed to characterize and compare infection patterns and risk factors in patients with pemphigoid, pemphigus, and DH. We retrospectively studied the medical records of Olmsted County, Minnesota, residents who had a diagnosis of AIBD between 1 January 1998 and 1 January 2011. Of 81 patients studied, 54 (67%) had pemphigoid, 11 (14%) had pemphigus and 16 (20%) had DH. Most patients studied developed at least one localized infection (72%) or one systemic infection (83%). Almost one‐third of patients (31%) developed infections requiring hospitalization or contributing to death. All patients taking systemic corticosteroids experienced a localized or systemic infection during the follow‐up period. Systemic infections were significantly less frequent in patients with DH than those with pemphigoid or pemphigus (P = 0.03), as were systemic infections requiring hospitalization or contributing to death (P = 0.002). Patients with DH were significantly less likely to require systemic corticosteroids (P < 0.001) and significantly more likely to receive dapsone (P = 0.002). The study design was retrospective and a limited number of patients met the inclusion criteria. Patients with AIBD frequently developed localized and systemic infections, a substantial portion of which contributed to hospitalization or death. Patients with DH experienced infections of lesser severity than patients with pemphigoid or pemphigus.

Evaluation of CROSS technique with 100% TCA in the management of ice pick acne scars in darker skin types

Background  Acne scars are difficult to treat. Chemical reconstruction of skin scars (CROSS) is a technique using high strength trichloroacetic acid (TCA) focally on the atrophic acne scars to induce collagenization and cosmetic improvement.

Subcision for Depressed Facial Scars Made Easy Using a Simple Modification

Subcision is a surgical technique for the treatment of depressed scars. Although Spangler reported the use of a Bowmen’s iris needle to cut the fibrous strands beneath deeply depressed facial scars in 1957, Orentreich and Orentreich gave the technique the name ‘‘subcutaneous incisionless surgery’’ or subcision in 1995. In this technique, a sharp needle is introduced into the skin beneath the scar, acting like a scalpel, causing incision of the fibrous bands that cause depression of the scar. The scar surface is released from the underlying fibrous attachments with the incising effect of the needle, which lifts up the scar. This injury also induces connective tissue formation beneath the scar, without injury to the skin surface. In atrophic acne scars, subcision is mainly useful for rolling scars that are distensible with gentle sloping edges. It is not a very effective technique for ice pick or crateriform scars with steep edges. Subcision is performed using a tribevelled needle, triangular Nokor needle, or hypodermic 18 to 27 G needle. As traditionally described, the skin is pinched up or flattened, and the straight needle is inserted 1 to 2 mm away from the target scar with the bevel upward. It is first moved in a linear back-and-forth motion and then turned horizontally in a fanning motion to cut the fibrous tissue at the edges. Care has to be taken that the needle is nearly parallel to the skin surface into the dermis to avoid injury to the underlying vessels and nerves, although it is sometimes difficult to maintain the same plane, and the needle may go deeper or pierce the skin superficially during the movement of the needle. To obviate this complication, a slight modification is described that makes the technique safer, quicker, and easier.

Programmed Cell Death 1 (PD-1) Ligand (PD-L1) Expression in Solid Tumors As a Predictive Biomarker of Benefit From PD-1/PD-L1 Axis Inhibitors: A Systematic Review and Meta-Analysis

PurposeDrugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway show significant clinical activity across several tumor types. However, a majority of patients do not respond to these agents. Use of biomarker assays to predict response to these agents is an active area of research; however, the predictive value of PD-L1 immunohistochemistry (IHC) assays is largely inconsistent across clinical trials. In this meta-analysis of clinical trials of PD-1/PD-L1–targeted agents, we evaluate the predictive value of a tumor and tumor-infiltrating immune cell PD-L1 IHC assay as a biomarker for objective response to PD-1/PD-L1 inhibitors.MethodsWe searched databases (PubMed, Medline, ASCO abstracts, European Society for Medical Oncology abstracts, and Scopus) up until December 2016 for clinical trials using PD-1/PD-L1 inhibitors with reported PD-L1 biomarker data. Objective response rates (primary end point) from all phase I to III trials investigating nivolumab, pembrolizumab,...