Sports participation plays a relevant role in the relationship between birth weight and bone mineral content in adolescents.

The Developmental Origins of Health and Disease hypothesis (DOHaD) proposes that growth during the prenatal period might play a critical role in health, affecting the development of diseases, such as osteoporosis. Bone health is particularly affected by human behaviors when sports participation constitutes the main manifestation of physical exercise. The aim of this study is to analyze the relationship between birth weight (BW) and bone mineral content (BMC) among adolescents, as well as to identify if sports participation and maturity can affect this relationship. The sample was composed of adolescents with ages ranging from 11 to 18 years, stratified according to normal birth weight (n = 331), low birth weight (n = 36), and macrosomia (n = 47), extracted from a wider cross-sectional study (ABCD Growth Study). BW was self-reported by the adolescent's parent. Sports participation was assessed by face-to-face interview. BMC was assessed using dual-energy X-ray absorptiometry. In the multivariate models, the relationships between BW and BMC remained non-significant, while sports participation was significantly related to BMC on lower limbs among boys (r = 0.154; p value = .001) and BMC of upper limbs among girls (r = 0.124; p value = .044). APHV was related to BMC of upper limbs among boys (r = 0.137; p value = .001). In conclusion, BMC was not affected by BW, while this phenomenon seems to be significantly affected by the positive impact of sports participation and maturation on it.

Pursuit or discontinuation of anti-PD1 after 2 years of treatment in long-term responder patients with non-small cell lung cancer.

Background: The optimal duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains to be determined. Treatment durations in cornerstone phase 3 clinical trials vary between a fixed 2-year duration and pursuit until disease progression. Clinical practices may thus differ according to the attending physician. Objectives: Here we provide real-world data about treatment decisions at 2 years, with subsequent clinical outcomes. Design and Methods: This multicentric observational study included patients with advanced NSCLC whose disease was controlled after 2 years of pembrolizumab or nivolumab. The primary outcome was the decision to discontinue ICI treatment or not, along with factors motivating this decision. Secondary outcomes included progression-free survival (PFS) (according to treatment continuation or not) and adverse events. Results: A total of 91 patients were included, of which 60 (66%) had been pre-treated. The programmed death-ligand 1 expression level was ⩾50% in 43 patients (47%). In 61 patients (67%), ICI was continued after 2 years of treatment. This decision was significantly associated with the care center (p < 0.001) but neither with the tumor response at 2 years, as evaluated by CT scan or PET scan, nor with clinical status, immune-related adverse events, or previous locally treated oligo-progressive disease under ICI. Two years after the 2-year decision, PFS was 68.5%, [95% confidence interval (CI) (53.3-88.0)] in the 'ICI discontinuation' group and 64.1% [95% CI (51.9-79.2)] in the 'ICI pursuit' group; hazard ratio for relapse was 1.14 [95% CI (0.54-2.30), p = 0.77]. The overall survival rate at 24 months after discontinuation was 89.2% [95% CI (78.4-100)] for the 'discontinuation' group and 93.1% [95% CI (85.8-100)] for the 'pursuit' group. Given insufficient power, overall survival could not be compared. Conclusion: The decision to continue ICI or not after 2 years of treatment depends mainly on the care center and does not seem to impact survival. Larger, randomized data sets are required to confirm this result.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

BACKGROUND: patients hospitalised with covid-19 suffer thrombotic complications. risk factors for poor outcomes are shared with coronary artery disease. Objectives: to investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with covid-19 and coronary disease risk factors. PATIENTS/METHODS: a randomised controlled open-label trial across acute hospitals (uk and brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. primary efficacy and safety outcomes were 30-day mortality and bleeding. the key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. the trial terminated early due to low recruitment. at 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted or 0.73, 95%ci 0.38 to 1.41, p=0.355). significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). using a bayesian markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (or 1.46, 95% cri 0.88 to 95 2.37, pr(beta>0) =93%; adjusted or 1.50, 95% cri 0.91 to 2.45, pr(beta>0) =95%) and median time to discharge home was two days shorter (95% cri -4 to 0, 2% probability that it was worse). CONCLUSIONS: acute coronary syndrome treatment regimen was associated with a 99 reduction in the length of hospital stay without an excess in major bleeding. a larger trial is needed to evaluate mortality.

Relationship of Objectively Measured Physical Activity, Sedentary Behavior and Sleep Time with Cardiovascular and Mtabolic Outcomes in Adolescents (A Pilot Study): ABCD Growth Study.

STUDY OBJECTIVE: Different behaviors are considered important factors that may influence a healthy lifestyle. Given this fact, we aim to analyze the relationship between moderate-vigorous physical activity (MVPA), sleep time, and sedentary time, with cardiometabolic outcomes in adolescents. METHODS: Cross-sectional study, with 152 eutrophic and healthy adolescents. The behavioral variables were collected objectively and the arterial thickness was measured through ultrasound. Blood variables (LDL, TG, HDL, glucose, and insulin) were collected in a private laboratory. To analyze the data, the Student t test and Kruskal-Wallis test were used to compare the groups. All analyses adopted p < 0.05. RESULTS: Girls who demonstrated better combined behaviors, presented significant results for TG (p = 0.045), BP (p = 0.016), and cardiovascular score (p = 0.049) when compared to their peers. Furthermore, the practice of physical activity combined with sufficient sleep time was associated with lower values of arterial thickening (p = 0.017). CONCLUSIONS: In view of the results presented, it is possible to state that the aggregation of behaviors was more consistent in females and that the practice of physical activity and adequate sleep time can reflect on cardiovascular health.

Estimating the causal effect of treatment with direct-acting antivirals on kidney function among individuals with hepatitis C virus infection.

BACKGROUND: Direct-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated. METHODS: We analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m2), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m2) under each intervention. For patients with baseline CKD Stages 2-4 (15

Herb-Induced Liver Injury-A Challenging Diagnosis.

Herb-induced liver injury (HILI) can be caused by supplements containing herbs, natural products, and products used in traditional medicine. Herbal products' most common adverse reaction is hepatotoxicity. Almost every plant part can be used to make herbal products, and these products can come in many different forms, such as teas, powders, oils, creams, capsules, and injectables. HILI incidence and prevalence are hard to estimate and vary from study to study because of insufficient large-scale prospective studies. The diagnosis of HILI is a challenging process that requires not only insight but also a high degree of suspicion by the clinician. HILI presents with unspecific symptoms and is a diagnosis of exclusion. For diagnosis, it is necessary to make a causality assessment; the Council for International Organizations of Medical Sciences assessment is the preferred method worldwide. The most effective treatment is the suspension of the use of the suspected herbal product and close monitoring of liver function. The objective of this review is to highlight the necessary steps for the clinician to follow to reach a correct diagnosis of herb-induced liver injury. Further studies of HILI are needed to better understand its complexity and prevent increased morbidity and mortality.

Colonic Epithelial Angiotensin-Converting Enzyme 2 (ACE2) Expression in Blacks and Whites: Potential Implications for Pathogenesis Covid-19 Racial Disparities.

BACKGROUND: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. "cytokine storm"). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites. METHODS: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent neoplasia or inflammation were used for this study. Total mRNA was isolated and subjected to real-time polymerase chain reaction for ACE2, and TMPRSS2 was assessed from non-Hispanic Blacks (n = 45) and non-Hispanic Whites (n = 38). GAPDH and beta-actin were used for normalization. Multivariable analysis was performed using Analyse-IT software. RESULTS: ACE2 and TMPRSS2 levels were not altered by gender, BMI, or age. ACE2 levels were lower in Blacks than Whites achieving statistical significance in multivariable (0.51-fold, p = 0.03) but not quite in univariable (p = 0.07) analysis. This downregulation was mirrored in TMRPSS2 in both univariable (p = 0.03) and multivariable analyses (0.41-fold, p = 0.02). Moreover, there was a strong correlation between ACE2 and TMPRSS2 levels (r-squared = 0.78). CONCLUSIONS: To our knowledge, this is the first report on racial differences inACE2 and TMPRSS2 mucosal expression. This may provide potential biological underpinnings for the disproportionately higher mortality of Covid-19 in Blacks and should spur future studies.

Pharmacist-Managed Helicobacter pylori Treatment Service Within a Gastroenterology Clinic: Workflow and Real-World Experiences.

BACKGROUND: Treatment eradication rates of Helicobacter pylori, a gastrointestinal infection, are 70% to 90% in clinical studies but lower in real-world settings. Potential barriers include multidrug regimen complexity or prescribing/administration errors. A pharmacist-managed H pylori treatment service was implemented to address these barriers and optimize treatment outcomes. The clinical pharmacist provided 2 services: (1) treatment education and monitoring for treatment-naïve patients and (2) treatment initiation, education, and monitoring for treatment-experienced patients. OBJECTIVE: We aimed to evaluate the impact of a pharmacist-managed H pylori treatment service within a gastroenterology clinic. METHODS: We conducted a retrospective observational cohort study of all patients referred to and seen in the pharmacist-managed H pylori treatment service from July 10, 2019, to December 31, 2020. Patient demographics, prior treatment history, course(s) of treatment prescribed, frequency of follow-ups, and outcomes posttreatment were collected. RESULTS: The clinical pharmacist managed 60 referrals for 55 unique patients over a mean of 5 ± 2 visits. Five patients failed H pylori treatment and were re-referred. Identified barriers included prescribing/dispensing and administration errors. Posttreatment, 38 referrals tested for H pylori eradication, of which 100% of treatment-naïve patients and 69% of treatment-experienced patients were cured, and 13 (22%) referrals were lost to follow-up. CONCLUSION AND RELEVANCE: This study described and assessed the impact of a pharmacist-managed H pylori treatment service in a gastroenterology clinic, in which various barriers were effectively addressed to optimize treatment outcomes. Future studies should focus on long-term outcome, impact on health care costs, and patient satisfaction with this service.

Drug Induced Liver Injury: Perspective of the Adverse Drug Reaction Reports to the Portuguese Pharmacovigilance System from 2010 to 2019.

BACKGROUND: Drug induced liver injury (DILI) is an adverse drug reaction that causes liver damage in a predictable (dose-dependent) or an unpredictable (idiosyncratic) fashion. We performed an assessment of DILI in Portugal, by analyzing the reports, sent to the Portuguese Pharmacovigilance System (PPS). METHODS: A search was performed on the PPS database, in a 10-year time frame, from 1 January 2010 to 31 December 2019. RESULTS: There was not a prevalence of either sex in any age group. Most reports (n = 1120, 55.0%) belonged to patients in the age group 19-64 years old. Hepatitis (n = 626, 26.7%) was the most common adverse drug reaction in our study. Hepatotoxicity (n = 362, 15.5%) and hepatitis (n = 333, 14.2%) were more frequent in age group 19-64 years old. Cholestasis was more prevalent in adults independently of age. Hepatic fibrosis and encephalopathy were more common in the elderly. Most patients consumed between one and four suspected drugs (n = 1867, 92%). Most patients in our study evolved to "cure" (n = 796; 39%). Hepatotoxicity (n = 23; 13.8%) and hepatitis (n = 610; 25.9%) had a female predominancy while choluria (n = 8; 4.8%) and splenomegaly (n = 8; 4.8%) were of male predominance. CONCLUSIONS: DILI is rare but can be fatal. As such, an active search of DILI is necessary.

Autoimmune Gastrointestinal Dysmotility in a Patient With HIV Treated With Methylprednisolone and Pyridostigmine.

Primary autoimmune gastrointestinal dysmotility is a limited form of autoimmune dysautonomia, driven by antiganglionic autoantibodies (AGAs) against enteric neurons. AGAs are observed in other autoimmune diseases, such as Guillain-Barré syndrome, before the development onset of gastrointestinal symptoms. Here, we report a case of a 57-year-old woman with human immunodeficiency virus, who previously developed Guillain-Barré syndrome, presenting with 6 months of intestinal dysmotility. Diagnosis was made by detecting AGAs to ganglionic acetylcholine receptor, alpha-3 subunit, radiographic evidence of duodenal dysmotility, and exclusion of other causes. The patient received high-dose methylprednisolone with low-dose pyridostigmine, which led to significant improvement of symptoms.

Alcohol Consumption and Hepatitis C Virus (HCV) RNA Levels in HIV/HCV Coinfected Patients.

BACKGROUND: The impact of Hepatitis C virus (HCV) RNA levels on the evolution of chronic HCV infection-related liver damage is controversial. Heavy alcohol use is believed to have a deleterious impact on the course of HCV disease, but current knowledge about the possible effect of alcohol use on HCV RNA levels in HIV/HCV coinfected patients is limited. METHODS: We examined 107 HIV/HCV-infected individuals with current or past unhealthy alcohol use to assess the association between alcohol consumption (any drinking vs. abstinent) and HCV RNA levels. RESULTS: Participants were 75% male, with a mean age of 43 years, and 63% were on antiretroviral therapy. Mean (SD) log HIV RNA was 3.1 (1.4) and mean (SD) log HCV RNA was 6.1 (0.8). Past-month alcohol use was present in 38% of participants. In a multivariable linear regression analysis we found no significant differences in mean log HCV RNA levels between those reporting alcohol use and those who were abstinent [ß (95%CI): -0.04 (-0.34, 0.26), p = 0.79)]. There was no significant association between any heavy drinking day and HCV RNA level (0.07, 95% CI: (-0.24, 0.38), p = 0.66). CONCLUSIONS: We did not detect significant associations between alcohol use and HCV RNA levels among HIV/HCV coinfected patients.

Quantification of gastric mucosal microcirculation as a surrogate marker of portal hypertension by spatially resolved subdiffuse reflectance spectroscopy in diagnosis of cirrhosis: a proof-of-concept study.

BACKGROUND AND AIMS: Portal pressure can be used to identify patients with chronic liver disease who have progressed to cirrhosis. Portal pressure can also provide accurate prognostication for patients with cirrhosis. However, there are no practical means for assessment of portal pressure. Although it is well established that the gastric mucosal blood supply increases in patients with cirrhosis, this has been difficult to quantify reproducibly. Our group has developed a novel spectroscopic technology called spatially resolved subdiffuse reflectance spectroscopy (SRSRS), which enables quantification of mucosal microcirculation. We aim to ascertain if quantification of the gastric mucosal microcirculation with SRSRS correlates with clinical evidence of portal hypertension. METHODS: Patients undergoing EGD for clinical indications had 10 measurements taken in the endoscopically normal gastric fundus via SRSRS probe to assess the microcirculation. Cases were defined as patients with cirrhosis (n = 18), and controls were those without evidence of liver disease (n = 18); this was corroborated with transient elastography. RESULTS: The blood volume fraction (P = .06) and subdiffuse reflectance (P = .02) from a shallow depth in the gastric fundus were higher in patients with cirrhosis than those without. These markers were combined to yield an overall optical marker that can differentiate patients with cirrhosis from controls with a sensitivity of 72% and specificity of 94% (area under receiver operating curve, 0.82). CONCLUSIONS: Spectroscopic quantification of gastric fundal mucosal microcirculation is a promising surrogate of clinical correlates of portal hypertension. This approach may represent a less-intrusive surrogate biomarker for liver disease prognostication and potentially response to therapy.

Correlação de diferentes métodos de imagem em pacientes submetidos a angioplastia com stent dedicado para bifurcação / Correlation of different imaging methods in patients undergoing dedicated bifurcation stent angioplasty

INTRODUÇÃO: Cerca de 20% das intervenções percutâneas envolvem bifurcação, sendo um assunto de interesse devido a menor taxa de sucesso do procedimento (< 90%) e taxas relativamente elevadas de recorrências no seguimento tardio. A compreensão dos mecanismos de falência são fundamentais para o aprimoramento da intervenção coronária percutânea (ICP). Os métodos de imagem invasivos como ultrassom intracoronário (USIC) e tomografia de coerência ótica (TCO) são utilizados para avaliar a eficácia e segurança tardia de dispositivos coronários. O nosso objetivo foi avaliar a correlação destes métodos à angiografia coronária quantitativa (ACQ) em lesões de bifurcação coronária tratadas com stents dedicados a bifurcação. MÉTODOS: Estudo prospectivo, não-randomizado, de braço único, envolvendo um centro clinico que avaliou a correlação entre diferentes métodos de avaliação de imagem (ACQ, USIC e TCO) na avaliação tardia (9 meses) de pacientes com lesões de bifurcação tratados com o stent farmacológico liberador de sirolimus dedicado BiOSS. Foram incluídos 35 pacientes (36 lesões) tratadas entre Jan/16 a Fev/17. RESULTADOS: A maior parte das lesões (69%) envolveram bifurcação na artéria descendente anterior. Em relação ao envolvimento dos segmentos da bifurcação, 42.2% foram classificadas como lesões verdadeiras (Medina 111 11.1%, 011 22.8%, e 101 8.3%). Em relação a técnica de tratamento, a estratégia provisional foi planejada na totalidade dos casos, sendo necessário o implante de stent no ramo lateral em 25% dos casos. No reestudo protocolar aos 9 meses, realizado em 100% dos casos, a perda tardia do lumen (PTL) no vaso principal e no ramo lateral foram, respectivamente, 0,29 mm e 0,18 mm. Considerando os subsegmentos intra-stent proximal, carina e intra-stent distal no vaso principal, a PTL foi 0,23 mm, 0,29 mm e 0,33 mm, respectivamente; ja a área mínima do lúmen (AML) pelo TCO e USIC foram, respectivamente, 8,60 mm2 e 5,68 mm2, 8,18 mm2 e 5,32 mm2, e 6,29 mm2 e 3,99 mm2. Pelo método de Pearson, a TCO e o USIC demonstraram elevada correlação para as medidas de AML (r = 0,75; p < 0,05) no segmento intra-stent e área mínima do stent (r = 0,79). Já a ACQ não demonstrou correlação significativa com os métodos invasivos. CONCLUSÕES: Nesta investigação, os métodos de imagem invasivos (TCO e USIC) demonstraram alta correlação em termos de AML e área mínima do stent em lesões de bifurcação tratadas com stent farmacológico dedicado. (AU)

Improved Antibody Response to Three Additional Hepatitis B Vaccine Doses Following Primary Vaccination Failure in Patients with Inflammatory Bowel Disease.

BACKGROUND: Studies have shown the efficacy of hepatitis B (HBV) vaccination in patients with inflammatory bowel disease (IBD) is impaired, but few data exist regarding the effectiveness of revaccination strategies following primary vaccination failure. Our aim was to analyze the association between administration of additional vaccine doses and hepatitis B surface antibody (HBsAb) seroconversion. METHODS: This is a retrospective cohort study. Inclusion criteria are as follows: age ≥ 18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), inadequate HBsAb < 10 IU/L following initial HBV vaccination series, subsequent administration of 1-3 additional doses of HBV vaccine with follow-up serum HBsAb measurements. Patients were stratified into groups of ≤ 2 or 3 doses received. Primary outcome was achieving HBsAb > 10 IU/L. Outcomes were stratified by age ≥ or < 40 years. We performed logistic and linear multivariable regression analyses for categorical and continuous data. RESULTS: The study cohort consists of (n = 149) 54.4% women; 77.9% white; 72.6% with CD, with mean age: 46.2. Patients of all ages and age ≥ 40 years, who received 3 additional doses of vaccine, were more likely to achieve seroprotective HBsAb levels than patients who received 1 or 2 doses (OR 1.77, P = 0.01; OR 1.9, P = 0.03, respectively, after adjusting for age, sex, race, immunosuppressive medication exposure, time between vaccine/titer). CONCLUSIONS: Following initial HBV vaccination failure, patients with IBD of all ages are more likely to develop seroprotective levels of HBsAb following 3 additional vaccine doses, rather than 1 or 2 alone. In patients who fail primary HBV vaccination, providers should consider a more aggressive revaccination strategy with an additional 3-dose series.

Sustained Improvement in Type 2 Diabetes Mellitus is Common After Treatment of Hepatitis C Virus With Direct-acting Antiviral Therapy.

GOALS: To determine whether diabetic patients with hepatitis C virus (HCV) treated with direct-acting antiviral agents have improved diabetes, accounting for change in both hemoglobin A1c (HbA1c) and diabetes medications, and whether any improvement was sustained. BACKGROUND: HCV infection is associated with an increased risk of diabetes, with improvement in glycemic control after eradication. There remains uncertainty about the durability and magnitude of this effect. STUDY: HbA1c and diabetes medications were recorded at 6-month intervals for 1.5 years pretreatment and posttreatment for 122 patients. Subjects were classified as having improved diabetes if there was a decrease in HbA1c≥0.5% with no increase in diabetes medications or a decrease in diabetes medications with a stable HbA1c. RESULTS: HbA1c at the nearest time point before treatment was 8.4%±1.9%, compared with 7.8%±1.7% after treatment, a mean difference of 0.6% [95% CI (0.2, 0.9), P<0.01]. A linear mixed effects model incorporating each subject's repeated measurements over time also demonstrated a reduction after treatment of 0.5% [95% CI, (0.3, 0.8), P<0.001]. Accounting for both HbA1c and diabetes medications, 42 of 122 (34%) had an improvement in diabetes after HCV treatment, and 20 of 28 (71%) of these subjects sustained improvement at 1.5 years follow-up. Prescription of insulin was associated with improved diabetes. CONCLUSIONS: Treatment of HCV with direct-acting antiviral agents was associated with improved diabetes in a significant portion of patients with an average reduction in HbA1c of clinically significant magnitude. Among responders, this effect was sustained over 1.5 years of follow-up.

Intensive Pharmacy Care Improves Outcomes of Hepatitis C Treatment in a Vulnerable Patient Population at a Safety-Net Hospital.

BACKGROUND: Treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) regimens has resulted in high rates of sustained virologic response (SVR). Treatment of vulnerable populations may be improved by incorporating an on-site intensive specialty pharmacy (ON-ISP). AIMS: To describe outcomes of HCV treatment at a safety-net hospital and proportion of subjects achieving SVR for those using the ON-ISP compared to an off-site pharmacy (OFF-SP). METHODS: A retrospective cohort study of 219 subjects treated for HCV with DAA at Boston Medical Center was conducted. Subject characteristics, virologic response, and pharmacy services used were recorded. We used multivariable logistic regression to test the association between ON-ISP and SVR after adjusting for covariates. RESULTS: SVR occurred in 71% of subjects by intention-to-treat (73% among ON-ISP users vs 57% among OFF-SP users) and 95% completing treatment per-protocol (96% among ON-ISP users vs 87% among OFF-SP users). Adjustment for age, sex, ethnicity, insurance, fibrosis, prior treatment, and MELD revealed an increased likelihood of SVR among users of ON-ISP: OR 6.0 (95% CI 1.18-31.0). No significant difference in treatment delay or adverse events was seen among users of either pharmacy type. CONCLUSIONS: HCV treatment with DAA was well tolerated, but the rate of SVR was low (71%) compared to trials. This was due to loss to follow-up, as the per-protocol rate of SVR was much higher (95%). Use of ON-ISP was associated with an increase in SVR and may be valuable for improving care for vulnerable populations.

Correction: Biophotonic detection of high order chromatin alterations in field carcinogenesis predicts risk of future hepatocellular carcinoma: A pilot study.

[This corrects the article DOI: 10.1371/journal.pone.0197427.].

Biophotonic detection of high order chromatin alterations in field carcinogenesis predicts risk of future hepatocellular carcinoma: A pilot study.

PURPOSE: Hepatocellular carcinoma (HCC) results from chronic inflammation/cirrhosis. Unfortunately, despite use of radiological/serological screening techniques, HCC ranks as a leading cause of cancer deaths. Our group has used alterations in high order chromatin as a marker for field carcinogenesis and hence risk for a variety of cancers (including colon, lung, prostate, ovarian, esophageal). In this study we wanted to address whether these chromatin alterations occur in HCC and if it could be used for risk stratification. EXPERIMENTAL DESIGN: A case control study was performed in patients with cirrhosis who went on to develop HCC and patients with cirrhosis who did not develop cancer. We performed partial wave spectroscopic microscopy (PWS) which measures nanoscale alterations on formalin fixed deparaffinized liver biopsy specimens, 17 progressors and 26 non-progressors. Follow up was 2089 and 2892 days, respectively. RESULTS: PWS parameter disorder strength Ld were notably higher for the progressors (Ld = 1.47 ± 0.76) than the non-progressors (Ld = 1.00 ± 0.27) (p = 0.024). Overall, the Cohen's d effect size was 0.907 (90.7%). AUROC analysis yielded an area of 0.70. There was no evidence of confounding by gender, age, BMI, smoking status and race. CONCLUSIONS: High order chromatin alterations, as detected by PWS, is altered in pre-malignant hepatocytes with cirrhosis and may predict future risk of HCC.

Hepatitis C virus infection in kidney transplantation-changing paradigms with novel agents.

Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha-based therapies that were difficult to tolerate and were associated with adverse side-effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side-effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon-based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct-acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation.