Mitigation of Sarcopenia after Peritoneovenous Shunt Placement in Patients with Refractory Ascites.

PURPOSE: To evaluate the effect of peritoneonvenous shunt placement on metrics of sarcopenia in patients with refractory ascites. MATERIALS AND METHODS: An institutional review board-approved single-institution retrospective analysis of all patients who underwent peritoneovenous shunt (Denver Shunt; BD, Franklin Lakes, New Jersey) placement (N = 29) and a comparator cohort of patients with cirrhosis who underwent serial paracentesis (N = 42) from 2009 to 2019 with baseline and follow-up cross-sectional imaging of at least 3 months was performed. Axial muscle area measurements (psoas, paraspinal, and total abdominal wall) were performed using free-hand region-of-interest technique. Patient records were reviewed for demographic characteristics, referring indication, laboratory studies, and performance status. Statistical analyses were performed with Student t test, Welch unequal variances, Fisher exact test, and Wilcoxon signed rank test. RESULTS: The most common indications for peritoneovenous shunt placement were metastatic disease or cirrhosis. In the shunt cohort, there were no significant differences in the aggregate psoas muscle area (13.4 vs 14.0 cm2; P = .223) or paraspinal muscle area (43.0 vs 42.2 cm2; P = .471). In the paracentesis cohort, there were significant decreases in aggregate psoas (18.1 vs 15.7 cm2; P < .0001) and erector spinae (43.4 vs 39.9 cm2; P < .0001) muscle area. In addition, there was a significant decrease in serum albumin level (3.2 vs 3.0 g/dL; P = .015) and Eastern Cooperative Oncology Group performance status score (1.0 vs 1.3; P < .0001) in the paracentesis group, compared with no significant changes in the shunt cohort. CONCLUSIONS: In patients with refractory ascites who are not candidates for transjugular intrahepatic portosystemic shunt placement, peritoneovenous shunt mitigates loss of truncal muscle and, in some instances, promotes muscle growth.

Chronic Hepatotoxicity in Patients with Metastatic Neuroendocrine Tumor: Transarterial Chemoembolization versus Transarterial Radioembolization.

PURPOSE: To compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET). MATERIALS AND METHODS: This study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above. RESULTS: Chronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4-5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005). CONCLUSIONS: Delayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.

Radioembolization-Induced Chronic Hepatotoxicity: A Single-Center Cohort Analysis.

PURPOSE: To identify and characterize the delayed effects of transarterial radioembolization (TARE) on the liver. MATERIALS AND METHODS: A single-institution retrospective analysis was undertaken of all patients who received TARE between 2005 and 2014 and survived at least 1 year from the initial TARE (n = 106). Patients were evaluated for the presence or absence of radioembolization-induced chronic hepatotoxicity (RECHT) occurring at least 6 months after TARE. The mean age of patients was 63 years of age, and the malignancy most commonly treated was neuroendocrine tumor (54%). Adjudication of hepatic decompensation to RECHT versus alternative causes was performed by a multidisciplinary panel of specialists from hepatology, radiation oncology, and interventional radiology. RESULTS: Eight patients were excluded from analysis because of liver transplantation (2) or incomplete data (6). RECHT occurred in 13 of 98 patients (13%), and 5 deaths (5%) occurred from hepatic decompensation. There were a total of 69 toxicity events in patients developing RECHT. The most common events were elevation of alkaline phosphatase (10), decrease in serum albumin (10), and development of ascites (9). RECHT patients had a higher intrahepatic tumor volume (P = .021) and a higher number of hepatic comorbidities leading to cirrhosis (P = .015). CONCLUSIONS: Delayed radiation-induced hepatic toxicity occurred in 13% of patients following radioembolization, with 5 fatalities adjudicated to be a result of the treatment. Tumor involvement of greater than 50% of the liver and cirrhosis were predisposing factors for RECHT.

Maturity of nearby faults influences seismic hazard from hydraulic fracturing.

Understanding the causes of human-induced earthquakes is paramount to reducing societal risk. We investigated five cases of seismicity associated with hydraulic fracturing (HF) in Ohio since 2013 that, because of their isolation from other injection activities, provide an ideal setting for studying the relations between high-pressure injection and earthquakes. Our analysis revealed two distinct groups: (i) deeper earthquakes in the Precambrian basement, with larger magnitudes (M > 2), b-values < 1, and many post-shut-in earthquakes, versus (ii) shallower earthquakes in Paleozoic rocks ∼400 m below HF, with smaller magnitudes (M < 1), b-values > 1.5, and few post-shut-in earthquakes. Based on geologic history, laboratory experiments, and fault modeling, we interpret the deep seismicity as slip on more mature faults in older crystalline rocks and the shallow seismicity as slip on immature faults in younger sedimentary rocks. This suggests that HF inducing deeper seismicity may pose higher seismic hazards. Wells inducing deeper seismicity produced more water than wells with shallow seismicity, indicating more extensive hydrologic connections outside the target formation, consistent with pore pressure diffusion influencing seismicity. However, for both groups, the 2 to 3 h between onset of HF and seismicity is too short for typical fluid pressure diffusion rates across distances of ∼1 km and argues for poroelastic stress transfer also having a primary influence on seismicity.

Decision Making: Intra-arterial Therapies for Cholangiocarcinoma-TACE and TARE.

The incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in recent years and now represents the second most common primary hepatic cancer in the United States. The prognosis is dismal without surgical resection. In patients ineligible to receive curative treatments, locoregional therapies represent a diverse array of techniques that can stabilize or reverse tumor progression to improve overall survival and reduce tumor-related symptoms. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) have been demonstrated to be efficacious methods for this patient population. Deciding between these two options is challenging. This article reviews the differences in patient selection, preprocedural evaluation, financial considerations and availability, quality of life, and rates of complications and overall survival.

Effects of intraosseous erythropoietin during hemorrhagic shock in swine.

OBJECTIVE: To determine whether erythropoietin given during hemorrhagic shock (HS) ameliorates organ injury while improving resuscitation and survival. METHODS: Three series of 24 pigs each were studied. In an initial series, 50% of the blood volume (BV) was removed in 30 minutes and normal saline (threefold the blood removed) started at minute 90 infusing each third in 30, 60, and 150 minutes with shed blood reinfused at minute 330 (HS-50BV). In a second series, the same HS-50BV protocol was used but removing an additional 15% of BV from minute 30 to 60 (HS-65BV). In a final series, blood was removed as in HS-65BV and intraosseous vasopressin given from minute 30 (0.04 U/kg min(-1)) until start of shed blood reinfusion at minute 150 (HS-65BV+VP). Normal saline was reduced to half the blood removed and given from minute 90 to 120 in half of the animals. In each series, animals were randomized 1:1 to receive erythropoietin (1,200 U/kg) or control solution intraosseously after removing 10% of the BV. RESULTS: In HS-50BV, O2 consumption remained near baseline yielding minimal lactate increases, 88% resuscitability, and 60% survival at 72 hours. In HS-65BV, O2 consumption was reduced and lactate increased yielding 25% resuscitability. In HS-65BV+VP, vasopressin promoted hemodynamic stability yielding 92% resuscitability and 83% survival at 72 hours. Erythropoietin did not affect resuscitability or subsequent survival in any of the series but increased interleukin-10, attenuated lactate increases, and ameliorated organ injury based on lesser troponin I, AST, and ALT increases and lesser neurological deficits in the HS-65BV+VP series. CONCLUSIONS: Erythropoietin given during HS in swine failed to alter resuscitability and 72 hour survival regardless of HS severity and concomitant treatment with fluids and vasopressin but attenuated acute organ injury. The studies also showed the efficacy of vasopressin and restrictive fluid resuscitation for hemodynamic stabilization and survival.

Investigation to identify a resource-efficient case-control methodology for determining antibiotics associated with Clostridium difficile infection.

BACKGROUND: Antimicrobial exposure remains an important risk factor for developing Clostridium difficile infection (CDI). Efficient method to identify antibiotics associated with CDI is important for formulating strategies to curtail their use. As a prelude to a more extensive Agency for Healthcare Research and Quality-funded project (Evaluation & Research on Antimicrobial Stewardship's Effect on Clostridium difficile), we undertook an exploratory evaluation to determine a resource-efficient method for identifying antibiotic targets for antimicrobial stewardship interventions. METHODS: The study compared a series of 6 focused case-control studies. Cases consisted of patients with laboratory-confirmed CDI admitted from July-October 2009. Controls were selected from patients without CDI hospitalized during the same period. Five groups of controls were matched to cases (2:1 ratio) using group-specific matching criteria, including admission date, age, type of admission, length of stay (LOS) to discharge, and/or LOS to CDI diagnosis. The final control group was selected from patients who received antibiotics during hospitalization. Data, including demographics and antibiotic usage, were compared between case and control groups. RESULTS: A total of 126 cases were matched to 6 groups of 252 controls. For control groups 1-5, the use of piperacillin and tazobactam, ceftriaxone or cefepime, ciprofloxacin or moxifloxacin, intravenous vancomycin, azithromycin, and antibiotics of last resort were significantly more frequent in case than control patients. For the final control group, the associations between ceftriaxone or cefepime, and ciprofloxacin or moxifloxacin use and CDI no longer persisted. This could in part be explained by differences in comorbidities between case and control patients even with stringent matching criteria. CONCLUSION: Use of a simple matching strategy to conduct case-control studies is an efficient and feasible compromise strategy, especially in resource-limited settings, to identify high-risk antibiotics associated with CDI.

Changing the research landscape: the New York City Clinical Data Research Network.

The New York City Clinical Data Research Network (NYC-CDRN), funded by the Patient-Centered Outcomes Research Institute (PCORI), brings together 22 organizations including seven independent health systems to enable patient-centered clinical research, support a national network, and facilitate learning healthcare systems. The NYC-CDRN includes a robust, collaborative governance and organizational infrastructure, which takes advantage of its participants' experience, expertise, and history of collaboration. The technical design will employ an information model to document and manage the collection and transformation of clinical data, local institutional staging areas to transform and validate data, a centralized data processing facility to aggregate and share data, and use of common standards and tools. We strive to ensure that our project is patient-centered; nurtures collaboration among all stakeholders; develops scalable solutions facilitating growth and connections; chooses simple, elegant solutions wherever possible; and explores ways to streamline the administrative and regulatory approval process across sites.

Sck1 negatively regulates Gpa2-mediated glucose signaling in Schizosaccharomyces pombe.

Schizosaccharomyces pombe detects extracellular glucose via a G protein-mediated cyclic AMP (cAMP)-signaling pathway activating protein kinase A (PKA) and regulating transcription of genes involved in metabolism and sexual development. In this pathway, Gpa2 Gα binds to and activates adenylyl cyclase in response to glucose detection by the Git3 G protein-coupled receptor. Using a two-hybrid screen to identify extrinsic regulators of Gpa2, we isolated a clone that expresses codons 471 to 696 of the Sck1 kinase, which appears to display a higher affinity for Gpa2(K270E)-activated Gα relative to Gpa2(+) Gα. Deletion of sck1(+) or mutational inactivation of the Sck1 kinase produces phenotypes reflecting increased PKA activity in strains expressing Gpa2(+) or Gpa2(K270E), suggesting that Sck1 negatively regulates PKA activation through Gpa2. In contrast to the Gpa2(K270E) GDP-GTP exchange rate mutant, GTPase-defective Gpa2(R176H) weakly binds Sck1 in the two-hybrid screen and a deletion of sck1(+) in a Gpa2(R176H) strain confers phenotypes consistent with a slight reduction in PKA activity. Finally, deleting sck1(+) in a gpa2Δ strain results in phenotypes consistent with a second role for Sck1 acting in parallel with PKA. In addition to this parallel role with PKA, our data suggest that Sck1 negatively regulates Gpa2, possibly targeting the nucleotide-free form of the protein that may expose the one and only AKT/PKB consensus site in Gpa2 for Sck1 to bind. This dual role for Sck1 may allow S. pombe to produce distinct biological responses to glucose and nitrogen starvation signals that both activate the Wis1-Spc1/StyI stress-activated protein kinase (SAPK) pathway.

Pay for performance improves quality across demographic groups.

OBJECTIVE: To evaluate quality and the effect of pay for performance among minority patient groups, during a pay-for-performance program in 22 primary care practice sites. METHODS: Data were collected on 26 standardized measures of care for 2 measurement cycles. Proportions of recommended care received across 5 composite quality domains were analyzed by demographic group. Regression models including significant covariates were constructed. Adjusted odds ratios (ORs) were derived to assess the effect of pay of performance within demographic groups. RESULTS: Improvements were observed from 2007 to 2009 for all patients in each of 5 composite quality domains of diabetes, coronary artery disease, heart failure, screening and prevention, and all care. With the exception of heart failure care for Hispanic/Latino and Spanish language-preferring patients, improvement was observed in all domains for African American/black race, Hispanic/Latino ethnicity, and Spanish language-preferred groups. Following adjustment for covariates, pay for performance was associated with significant improvement in all-patient diabetes care (adjusted OR = 1.15; [95% confidence interval [CI], 1.09-1.22), screening and prevention (adjusted OR = 1.55; 95% CI, 1.41-1.69), and all care (adjusted OR = 1.27; 95% CI, 1.20-1.35). Significant improvements were also observed within the minority demographic groups noted earlier. CONCLUSIONS: Pay-for-performance programs structured as additional incentive monies for providers improved care for all patients and among minority groups, in whom disparities have historically been observed.

Investigation of inpatient probiotic use at an academic medical center.

OBJECTIVES: Despite the widespread use of probiotics, there are limited data regarding their safety. The aims of this study were to characterize inpatient probiotic use and to determine the incidence of probiotic-related bloodstream infections due to Lactobacillus acidophilus/Lactobacillus bulgaricus. METHODS: This study was a two-part retrospective study conducted at a large academic medical center. The first part was the characterization of probiotic use during 2007-2008, which included the type of prescribing provider, choice of probiotic prescribed, indications for use, and presence of potential risk factors for probiotic infection among recipients; the second part was the determination of the incidence of probiotic-related bloodstream infections due to L. acidophilus/L. bulgaricus for September 2000-August 2008. RESULTS: Probiotic use was uncommon (0.4%). Ninety-six percent of patients received Lactobacillus-based compounds. Use was common in patients at theoretical risk for probiotic infection. The maximum estimated incidence of probiotic-related bacteremia due to L. acidophilus/L. bulgaricus during the 8-year period was 0.2%. CONCLUSIONS: L. acidophilus/L. bulgaricus probiotic use at our institution appeared to be associated with a minimal risk of probiotic-related infection, even though it was used at a high frequency among inpatients who could be considered at high theoretical risk for probiotic-related bloodstream infection.

Large-diameter burrows of the Triassic Ischigualasto Basin, NW Argentina: paleoecological and paleoenvironmental implications.

Large-diameter ichnofossils comprising three morphotypes have been identified in the Upper Triassic Ischigualasto and Los Colorados formations of northwestern Argentina. These burrows add to the global record of the early appearance of fossorial behavior during early Mesozoic time. Morphotypes 1 and 2 are characterized by a network of tunnels and shafts that can be assigned to tetrapod burrows given similarities with previously described forms. However, differences in diameter, overall morphology, and stratigraphic occurrence allow their independent classification. Morphotype 3 forms a complex network of straight branches that intersect at oblique angles. Their calcareous composition and surface morphology indicate these structures have a composite biogenic origin likely developed due to combined plant/animal interactions. The association of Morphotypes 1 and 2 with fluvial overbank lithologies deposited under an extremely seasonal arid climate confirms interpretations that the early appearance of burrowing behavior was employed by vertebrates in response to both temperature and moisture-stress associated with seasonally or perpetually dry Pangean paleoclimates. Comparisons of burrow morphology and biomechanical attributes of the abundant paleovertebrate fauna preserved in both formations permit interpretations regarding the possible burrow architects for Morphotypes 1 and 2. In the case of the Morphotype 1, the burrow constructor could be one of the small carnivorous cynodonts, Ecteninion or Probelesodon. Assigning an architect for Morphotype 2 is more problematic due to mismatches between the observed burrow morphology and the size of the known Los Colorados vertebrates.

Is primary prevention of Clostridium difficile infection possible with specific probiotics?

BACKGROUND: The efficacy of probiotics for the prevention of Clostridium difficile infection (CDI) is highly controversial, particularly with regard to the prevention of recurrent CDI. We hypothesize that primary prevention of CDI among patients receiving antibiotics might be a more achievable goal for probiotics than prevention in patients with previous CDI where the host flora is markedly altered. METHODS: We conducted a literature search for randomized, placebo-controlled efficacy studies of probiotic use among adults receiving antibiotics, in which CDI was one of the outcomes measured. In addition, we conducted meta-analyses of probiotics that were included in more than one randomized trial. RESULTS: Eleven studies were identified; most were seriously underpowered to determine the efficacy of probiotics in the prevention of CDI. Two showed significantly lower rates of CDI among the probiotic recipients. A meta-analysis of three studies that used the probiotic combination Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R and a combined analysis of those studies with four studies that used Saccharomyces boulardii, showed lower CDI rates in recipients of probiotics compared with recipients of placebo (risk ratio=0.39; 95% confidence interval 0.19-0.79). CONCLUSIONS: While potential flaws in study design were identified, a review of the available literature suggests that the primary prevention of CDI with specific probiotic agents may be achievable. Additional studies of sufficient size and with rigorous design are needed to confirm these findings.

Standardizing race, ethnicity, and preferred language data collection in hospital information systems: results and implications for healthcare delivery and policy.

The Institute of Medicine has identified the need for healthcare organizations to collect standardized demographic data as a step toward reducing healthcare disparities. This observational study of patients discharged from a large academic medical center between 2005 and 2009, evaluates an organizational effort to standardize demographic data collection, characterizes limitations of the implementation, and assesses its utility in quality improvement and disparity reduction efforts. Primary measures include percentages of inpatient discharges with unknown race, ethnicity, and language data. Secondary measures include "ideal" cardiovascular care and readmission rates. From 2005 to 2009, the proportion of discharges with unknown race, ethnicity, or preferred language data decreased significantly. Among discharges with known ethnicity in 2009, Hispanic/Latino patients were significantly more likely to decline to specify their race or designate their race as a "Multiracial: Other Combination." No significant differences in ideal cardiovascular care were observed across demographic groups. Differences in readmission rates were observed among some groups. A provider organization can effectively standardize demographic data collection practices for use in quality improvement efforts. Current federal race categories are of limited utility for persons of Hispanic/Latino ethnicity, and performance measurement approaches that exclude demographic variables may fail to address healthcare disparities.

Developing a multidisciplinary model of comparative effectiveness research within a clinical and translational science award.

The Clinical and Translational Science Awards (CTSAs) were initiated to improve the conduct and impact of the National Institutes of Health's research portfolio, transforming training programs and research infrastructure at academic institutions and creating a nationwide consortium. They provide a model for translating research across disciplines and offer an efficient and powerful platform for comparative effectiveness research (CER), an effort that has long struggled but enjoys renewed hope under health care reform. CTSAs include study design and methods expertise, informatics, and regulatory support; programs in education, training, and career development in domains central to CER; and programs in community engagement.Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center have entered a formal partnership that places their CTSA at a critical intersection for clinical and translational research. Their CTSA leaders were asked to develop a strategy for enhancing CER activities, and in 2010 they developed a model that encompasses four broadly defined "compartments" of research strength that must be coordinated for this enterprise to succeed: evaluation and health services research, biobehavioral research and prevention, efficacy studies and clinical trials, and social science and implementation research.This article provides historical context for CER, elucidates Einstein-Montefiore's CER model and strategic planning efforts, and illustrates how a CTSA can provide vision, leadership, coordination, and services to support an academic health center's collaborative efforts to develop a robust CER portfolio and thus contribute to the national effort to improve health and health care.

A basal dinosaur from the dawn of the dinosaur era in southwestern Pangaea.

Upper Triassic rocks in northwestern Argentina preserve the most complete record of dinosaurs before their rise to dominance in the Early Jurassic. Here, we describe a previously unidentified basal theropod, reassess its contemporary Eoraptor as a basal sauropodomorph, divide the faunal record of the Ischigualasto Formation with biozones, and bracket the formation with (40)Ar/(39)Ar ages. Some 230 million years ago in the Late Triassic (mid Carnian), the earliest dinosaurs were the dominant terrestrial carnivores and small herbivores in southwestern Pangaea. The extinction of nondinosaurian herbivores is sequential and is not linked to an increase in dinosaurian diversity, which weakens the predominant scenario for dinosaurian ascendancy as opportunistic replacement.