Journal of Investigative Medicine

Non-cardiac critically ill patients with type II myocardial infarction (MI) have a high risk of mortality. There are no evidence-based interventions to mitigate this risk. We systematically reviewed the literature regarding the use of medications known to reduce mortality in patients with cardiac troponin (cTn) elevation due to type I MI (β blockers, statin, and aspirin) in studies of critically ill patients without Type I MI. All PubMed publications between 1976–2/19/16 were reviewed. Search terms included: β blocker or aspirin or statin and intensive care unit (ICU) or critically ill or sepsis; 497 primary references were obtained. Inclusion criteria were as follows: (1) study population consisted of critically ill patients in the ICU with non-cardiovascular illnesses, (2) mortality end point, (3) severity of illness (or injury) was measured, and (4) the antiplatelet agent was primarily aspirin. Retrospective investigations, prospective observational studies, meta-analysis, systematic review, and randomized controlled trials were included; case reports were excluded. 25 primary references were obtained. The data were extracted and tabulated using data collection headings as follows: article title, first author/year/reference number, study type/design, population studied, outcome and intervention, and study question addressed. Evidence was not graded as the majority of studies were non-randomized (low-to-moderate quality). 11 studies were found through bibliography reviews for a total of 36 references. In conclusion, β blockers, statins, and aspirin may play a role in reducing mortality in non-cardiac critically ill patients. Benefit appears to be related to severity of illness, for which cTn may be a marker.

The use of immune checkpoint inhibitors to treat malignant tumors with microsatellite instability is an emerging new modality. This is based on the observations that these tumors may have a high mutation rate—thus a potential source of tumor-specific neoantigens—and harbor infiltrating cytotoxic T cells in response, suggesting that they may be particularly susceptible to immune checkpoint therapy. PUBMED and ASCO library were systematically reviewed to identify all relevant data that involved the use of immune checkpoint inhibitors in the treatment of cancers with microsatellite instability. The manual search retrieved a total of 3 relevant articles and 1 abstract published between 2015 and 2016. A total of 61 patients with colorectal, 3 with ampullary/cholangiocarcinoma, 2 with endometrial carcinomas, 3 with small bowel cancers, 2 with glioblastoma multiforme, and 1 with bladder cancer with reported efficacy results were reviewed. All the patients had stage IV cancer and were treated with immune checkpoint inhibitors until progression of disease or intolerable side effects emerged. The range of objective response rate was 25–71%. Responses were also durable with progression-free survival at 20 weeks of around 67–78% and to 46% at 1 year. The use of immune checkpoint inhibitors is effective in cancers that express microsatellite instability.

The value of nasogastric (NG) tube placement in patients with upper gastrointestinal tract bleeding (UGIB) is unclear. We therefore aimed to determine the usefulness of NG tube placement in patients with UGIB. The study was a single-blind, randomized, prospective, non-inferiority study comparing NG placement (with aspiration and lavage) to no NG placement (control). The primary outcome was the probability that physicians could predict the presence of a high-risk lesion (ie, requiring endoscopic therapy). 140 patients in each arm were included; baseline clinical features were similar in each group. The probability that there would be a high-risk lesion in the control arm was predicted to be 35% compared with 39% in the NG arm (after NG placement)—a probability difference of −4% (95% CI −12% to 3%), which confirmed non-inferiority of the 2 arms (p=0.002). All patients underwent endoscopy and all patients with high-risk lesions had endoscopic therapy. Physicians predicted the specific culprit lesion in 38% (53/140) and 39% (55/140) of patients in the control and NG (after NG placement) groups, respectively. The presence of coffee grounds or red blood in the NG aspirate did not change physician assessments. Pain, nasal bleeding, or failure of NG occurred in 47/140 (34%) patients. There were no differences in rebleeding rates or mortality. In patients with acute UGIB, the ability of physicians to predict culprit bleeding lesions and/or the presence of high-risk lesions was poor. Routine NG placement did not improve physician's predictive ability, did not affect outcomes, and was complicated in one-third of patients.

The high cost associated with antiviral treatment for chronic hepatitis C virus (HCV) infection mandates further investigation in the context of preventing complications such as type 2 diabetes mellitus (DM2). We determined the cumulative incidence of DM2 in subjects with chronic HCV infection who received concomitant pegylated interferon (Peg-IFN) and ribavirin. We conducted a retrospective analysis of data obtained from Veterans Administrations Informatics and Computing Infrastructure (VINCI) to identify an adult cohort of patients without diabetes with chronic HCV infection who received Peg-IFN-based therapy between October 2001 and December 2011. Patients with history of HIV, hepatitis B infection, hepatocellular cancer (HCC), non-HCC cancers, and history of transplantation were excluded. Sustained virological response (SVR) was defined as negative HCV RNA 3 months after completion of therapy. Using Cox proportional hazards regression for multivariable analysis, we determined that patients who achieved SVR were at a significantly less risk of developing DM2. Adjusted survival rates showed that the responders' group was significantly less likely to develop DM2 over time (HR 0.60, CI 0.48 to 0.74, p<0.001). Peg-IFN-based therapy in chronic HCV patients that resulted in SVR significantly decreased the risk of developing DM2 and independently predicts the development of new onset disease after controlling for correlates of metabolic syndrome.

CD200 is a novel immune-effective molecule, existing in a cell membrane-bound form, as well as in a soluble form in serum, which performs to modulate inflammatory and acquired immune responses. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of large renal cysts and progressive loss of renal function. As defects in cell cycle arrest and apoptosis of renal tubular epithelial cells occur in ADPKD, we asked whether serum soluble CD200 might underlie and effect on ADPKD. Serum soluble CD200 levels were measured in 44 patients with ADPKD and 24 healthy volunteers. Concentrations of soluble CD200 in the serum samples were quantified using an ELISA kit. The mean serum soluble CD200 levels were higher in patients with ADPKD than in the control group (71.4±29.2 and 21.4±5.6 pg/mL, p<0.001). Positive correlation was detected between serum soluble CD200 levels and glomerular filtration rate (r=0.772, p<0.001), and serum albumin level (r=0.466, p=0.001). Negative correlation was detected between serum soluble CD200 levels and serum creatinine levels (r=−0.761, p<0.001), and C reactive protein levels (r=−0.364, p=0.015). In the ADPKD patients group, serum soluble CD200 levels were lower in patients with stage 5 chronic kidney disease (CKD) than in patients with stages 1–2 (p<0.001), 3 (p=0.005) and 4 CKD (p=0.006). Serum soluble CD200 levels were similar in patients with stages 1–2, 3, and 4 CKD (p>0.05). Our results show that patients with ADPKD have activated soluble CD200 levels which were related to renal function and inflammation.

Metastatic spinal cord compression (MSCC) is one of the most dreaded complications of cancer. A Nationwide Inpatient Sample (NIS) from 2000 to 2011 was used to extract data for all in-hospital stays of patients with MSCC using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The usage and timing of radiation therapy and surgical interventions were identified using ICD-9-M codes. These interventions were defined as ‘early intervention’ if they were provided within the first 48 hours of hospitalization. Multivariable logistic regression was used to examine the factors associated with delays in ‘early intervention’. We also examined whether delays in treatment led to worse outcomes in terms of mortality and morbidity. 13 457 patients were admitted with MSCC from 2000 to 2011 who received one or more modalities of treatment. Of these, 5035 (37%) received early intervention. Female gender, private-for-profit hospitals and higher comorbidity index were associated with lower rate of early intervention. In-hospital mortality was lower in the early intervention group (5.0% vs 6.9%, p=0.04). Patients receiving early intervention were discharged home more often (44.2% vs 36.4%, p<0.001) along with lower need of home health services (14.6% vs 18.8%, p=0.004). The length of stay (LOS) was significantly shorter and hospital charges lower in those who received early intervention (LOS: median 6 vs 11 days, p<0.001; charges: $34 354 vs $50 062; p<0.001). The rate of care delivery by early intervention in MSCC is suboptimal. Early treatment results in lower mortality, shorter LOS and higher rates of discharges to home along with lower hospital charges and decreased usage of home healthcare.

Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke. This study included 298 patients with ischemic stroke and 258 age-matched and sex-matched controls. MMP-2 promoter methylation levels were measured by pyrosequencing at eight potential cytosine-guanine (CpG) sites. Multivariate regression analysis was used to adjust for general stroke risk factors, and the specific effects of sex and stroke subtype were analysed. The methylation levels of MMP-2 in the peripheral blood of the patients with stroke were lower than controls in all eight CpG sites, especially at site 1, site 5, site 7, and site 8 (adjusted p=0.036, 0.002, 0.021, and 0.041, respectively). In subgroup analysis by sex, a significant association was found only in men but not in women. When the stroke subtype was considered, men with small-vessel stroke had significantly lower methylation levels at all MMP-2 CpG sites than the controls (3.01% vs 3.65%, adjusted p=0.018). Although men with large-artery atherosclerosis stroke also had lower MMP-2 methylation levels, no significant difference was found (3.25% vs 3.65%, adjusted p=0.253). Demethylation of the MMP-2 promoter in patients with ischemic stroke was in a sex and stroke subtype-specific manners. These findings may add to the understanding of epigenetic modification of MMP-2 on ischemic stroke.

Pneumocystis jirovecii can colonize patients with chronic obstructive pulmonary disease. To determine if colonization occurs in asthma patients, sputum samples from 10 patients with mild asthma, who were not receiving oral corticosteroids, were evaluated by a sensitive real-time PCR assay that targets a multicopy gene of P. jirovecii. 2 patients (20%) had Pneumocystis DNA detected; 1 patient had 3 positive samples over an 11-day period. Thus, Pneumocystis colonization occurs in asthma patients, and further studies are warranted to evaluate its role in airways disease.

To analyze visits to and admissions from the emergency department (ED) in children with a primary diagnosis of functional abdominal pain (FAP). This was a cross-sectional study using data from the Nationwide Emergency Department Sample (HCUP-NEDS 2008–2012). FAP-related ED visits were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The most frequent secondary diagnoses associated with FAP-related ED visits were also extracted. In 2012, a total of 796,665 children presented to the ED with a primary diagnosis of FAP. This correlated to a rate of 11.5 ED visits/1000 population. The highest incidence of ED visits was observed for children in the 10–14-year age group; median (IQR) age of 11 (8) years. In analyzing the temporal trends associated with FAP-related ED visits, we observed an increase in both the overall number of visits (14.0%) as well as the population-adjusted incidence (16.0%) during the period 2008–2012. This coincided with a decreasing trend in hospital admissions from the ED; from 1.4% in 2008 to 1.0% in 2012 (−28.5%). The overwhelming majority (96.7%) of patients with FAP who presented to the ED were treated and released. On multivariate analysis, the leading factor associated with an increased likelihood of admission from the ED was teaching hospital status (aOR 2.07; 95% CI 1.97 to 2.18). The secondary diagnosis most commonly associated with FAP-related ED visits was nausea and/or emesis (19.8%). Pediatric FAP-related ED visits increased significantly from the period 2008 to 2012. However, the incidence of hospital admissions from the ED declined during the same period.