Radiation-induced lung injury (RILI) encompasses any lung toxicity induced by radiation therapy (RT) and manifests acutely as radiation pneumonitis and chronically as radiation pulmonary fibrosis. ...Because most patients with thoracic and breast malignancies are expected to undergo RT in their lifetime, many with curative intent, the population at risk is significant. Furthermore, indications for thoracic RT are expanding given the advent of stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) for early-stage lung cancer in nonsurgical candidates as well as oligometastatic pulmonary disease from any solid tumor. Fortunately, the incidence of serious pulmonary complications from RT has decreased secondary to advances in radiation delivery techniques. Understanding the temporal relationship between RT and injury as well as the patient, disease, and radiation factors that help distinguish RILI from other etiologies is necessary to prevent misdiagnosis. Although treatment of acute pneumonitis is dependent on clinical severity and typically responds completely to corticosteroids, accurately diagnosing and identifying patients who may progress to fibrosis is challenging. Current research advances include high-precision radiation techniques, an improved understanding of the molecular basis of RILI, the development of small and large animal models, and the identification of candidate drugs for prevention and treatment.
Abstract Objective Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples. Methods 29 ...UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures). Results Data were available for 7041 UK and 1392 Dutch patients. Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: ‘full’ polysymptomatic (median 8, IQR 7-9 symptoms) 32.8%; ‘pain-only’ (muscle/joint) 20.3%; ‘sore throat/painful lymph node’ 4.5%; and ‘oligosymptomatic’ (median 1, IQR 0-2 symptoms) 4.7%. Two ‘partial’ polysymptomatic phenotypes were similar to the ‘full’ phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data. Conclusions Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments.
Highlights • Multiple organ systems are chronically affected after SJS/TEN. • Chronic complications can severely impact patients’ quality of life. • Preventative care might limit the progression of ...these sequelae.
BACKGROUND AND AIMS
Nonalcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We ...evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD.
APPROACH AND RESULTS
We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between January 1, 2004, and December 31, 2008, with follow‐up through December 31, 2015. We performed competing risk‐adjusted cause‐specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow‐up. At baseline, the mean body mass index was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% had hypertension, and 62.3% had dyslipidemia with substantial overlap among these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared with patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8‐fold higher risk of progression to cirrhosis/HCC (hazard ratio HR = 1.8, 95% confidence interval CI = 1.59‐2.06); the risk was 2.6‐fold higher in patients with diabetes, obesity, dyslipidemia, and hypertension (HR = 2.6, 95% CI = 2.3‐2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort.
CONCLUSIONS
Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Patients with diabetes and coexisting hypertension and obesity may be important targets for secondary prevention.
Objective
Perform a prospective study based on sequential clinical, endoscopic, and histologic evaluations of the foregut late after laparoscopic sleeve gastrectomy (LSG) in obese patients.
Summary
...After LSG, several studies have suggested an increase in the incidence of clinical gastroesophageal reflux (GERD) while others have reported an improvement but based mainly on clinical questionnaires.
Methods
Prospective study of 104 consecutive patients submitted to LSG. Several postoperative endoscopic and histologic evaluations of the esophagogastric junction (EGJ) and the gastric tube (GT) were performed and correlated with symptomatic findings.
Results
According to clinical preoperative findings, patients were divided into non-refluxers (Group I) and refluxers (Group II). Seven patients were unreachable, leaving 97 (93%) for late evaluation. Among Group I, 58.5% developed de novo GERD, while in Group II just 13.6% showed the disappearance of them. Endoscopic evaluations showed progressive deterioration of the EGJ in Group I, with the development of erosive esophagitis (EE), hiatal hernia (HH), and dilated cardia in a large proportion of them. In the GT, the presence of bile was seen in 40%, and an open immobile pylorus was detected in 82%. Short-segment Barrett’s esophagus (BE) appeared in 4%.
Conclusions
Patients submitted to LSG showed a significant and progressive increase in the presence of “de novo” GERD. Also, an increased duodenogastric reflux was seen through an open and immobile pylorus. Therefore, based on these results, it seems like LSG is a “pro-reflux” surgical procedure, which should be continuously evaluated late after surgery.
Objective
To identify predictors of the receipt of medical care, including the receipt of pre‐drug screening, for diagnostically targeted fungal or mycobacterial infections among patients prescribed ...a tumor necrosis factor inhibitor (TNFi).
Methods
We conducted a case–control study using deidentified patient health claims information from a data set representing a commercially insured US population of 15 million patients annually from January 1, 2007 to December 31, 2009. Descriptive statistics as well as a 2‐sample t‐test, chi‐square test of association, Fisher's exact test, and multivariate logistic regression were used for data analysis.
Results
A total of 30,772 patients received a TNFi during the study period. Of these, 158 patients (0.51%) developed targeted fungal and/or mycobacterial infections (cases). The median number of infections per case was 1.0 (interquartile range 1.0–2.0). Tuberculosis was diagnosed in 61% of cases, followed by histoplasmosis in 60%, nontuberculous mycobacterial infections in 11%, coccidioidomycosis in 10%, unspecified fungal infection in 8%, blastomycosis in 4%, cryptococcal infection in 3%, and pneumocystosis in 2%. Compared to controls (n = 474), a higher proportion of cases were prescribed prednisone (55% versus 37%; P < 0.001). Patients who were prescribed prednisone during the study period were twice as likely as those not taking prednisone to seek medical care attributable to a targeted fungal or mycobacterial infection (odds ratio 2.03; P < 0.001).
Conclusion
Development of a targeted fungal or mycobacterial infection among patients taking a TNFi is rare. Concomitant use of prednisone predicted development of such infections.
Summary
Sickle cell trait (SCT) is the carrier state for sickle cell disease that results from the HBB rs334 missense mutation (p.Glu6Val) in the β‐globin chain of haemoglobin. While not associated ...with any impact on life expectancy, it has been established that SCT is associated with an increased risk of both venous thromboembolism (and in particular, pulmonary embolism) and chronic kidney disease. It is largely unknown what short‐ or long‐term effect, if any, pregnancy has upon the risk or outcomes of these disorders. In addition, SCT has been linked with various adverse outcomes in pregnancy, ranging from maternal complications such as elevated risk of bacteriuria to potentially life‐threatening entities such as pre‐eclampsia and prematurity. In these scenarios also, no clear association with SCT has been established. Given the high worldwide prevalence of SCT, further studies addressing these issues are warranted.
Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE ...antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow's milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.
Summary
Use of haematopoietic cell transplantation (HCT) in the treatment of haematologic and neoplastic diseases may lead to life‐threatening complications that cause substantial morbidity and ...mortality if untreated. In addition to patient‐ and disease‐related factors, toxicity associated with HCT puts patients at risk for complications that share a similar pathophysiology involving endothelial cells (ECs). Normally, the endothelium plays a role in maintaining homeostasis, including regulation of coagulation, vascular tone, permeability and inflammatory processes. When activated, ECs acquire cellular features that may lead to phenotypic changes that induce procoagulant, pro‐inflammatory and pro‐apoptotic mediators leading to EC dysfunction and damage. Elevated levels of coagulation factors, cytokines and adhesion molecules are indicative of endothelial dysfunction, and endothelial damage may lead to clinical signs and symptoms of pathological post‐HCT conditions, including veno‐occlusive disease/sinusoidal obstruction syndrome, graft‐versus‐host disease, transplant‐associated thrombotic microangiopathy and idiopathic pneumonia syndrome/diffuse alveolar haemorrhage. The endothelium represents a rational target for preventing and treating HCT complications arising from EC dysfunction and damage. Additionally, markers of endothelial damage may be useful in improving diagnosis of HCT‐related complications and monitoring treatment effect. Continued research to effectively manage EC activation, injury and dysfunction may be important in improving patient outcomes after HCT.
Abstract The pathway leading from beta-amyloid deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer’s disease (AD). However, what drives amyloid ...build-up in sporadic non-genetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (i) GMB taxa with pro- and anti-inflammatory activity, and (ii) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa ( Escherichia/Shigella, Pseudomonas aeruginosa , Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii and Bacteroides fragilis ) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, IL-1β, IL-6, IL-18, IL-8, NLRP3, TNF-α; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n=40, Amy+) and with no brain amyloidosis (n=33, Amy-), and also in a group of controls (n=10, no brain amyloidosis and no cognitive impairment, HC). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3 and IL-1β) compared to both controls and to Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of Eubacterium rectale and higher abundance of Escherichia/Shigella as compared to both HC (Fold Change, FC=-9.6, p<0.001 and FC=+12.8, p<0.001, respectively ) and to Amy- (FC=-7.7, p<0.001 and FC=+7.4, p=0.003 ). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3 and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho=0.60, p<0.001; rho=0.57, p<0.001; and rho=0.30, p=0.007, respectively) and a negative correlation with the anti-inflammatory Eubacterium rectale ( rho=-0.48, p<0.001; rho=-0.25, p=0.024; rho=-0.49, p<0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella , and a reduction in the abundance of an anti-inflammatory taxon, Eubacterium rectale , are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.
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