Peliosis Hepatis With Intrahepatic Hemorrhage: Successful Embolization of the Hepatic Artery

Peliosis hepatis is defined as the appearance of blood filled lakes in the hepatic parenchyma. It has been associated with various pharmacological agents and infections. Treatment has been primarily symptomatic and includes discontinuation of offending medications, partial hepatectomy or occasionally liver transplantation. We report a 58 year old white female on hormone replacement therapy who developed symptomatic peliosis hepatis and underwent successful superselective hepatic artery embolization with control of bleeding

Grootschalige landbouw in een kleinschalig landschap : oplossingsrichtingen voor toekomstgerichte grootschalige melkveehouderij uitgewerkt voor het kleinschalige, open veenweidelandschap van Laag Holland

Schaalvergroting wordt door de meeste veehouderijbedrijven gezien als een belangrijke mogelijkheid om de kostprijs te verlagen. Maar vooral in kleinschalige gebieden lopen grotere bedrijven tegen de grenzen van hun omgeving aan. Vanuit de maatschappij klinkt immers de roep om een mooier landschap en hogere natuurwaarden. In de brochure 'Grootschalige landbouw in een kleinschalig landschap' zijn oplossingsrichtingen voor toekomstgerichte grootschalige melkveehouderij uitgewerkt voor het kleinschalige, open veenweidelandschap van Laag Holland

Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.

BackgroundCabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts.Patients and methodsEligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily. After an initial 12-week cabozantinib treatment period, patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 were randomized to cabozantinib or placebo. The primary endpoint of the lead-in stage was objective response rate (ORR) at week 12, and the primary endpoint of the randomized stage was progression-free survival (PFS).ResultsAmong the 41 HCC patients enrolled, the week 12 ORR was 5%, with 2 patients achieving a confirmed partial response (PR). The week 12 disease control rate (PR or SD) was 66% (Asian subgroup: 73%). Of patients with ≥1 post-baseline scan, 78% had tumor regression, with no apparent relationship to prior sorafenib therapy. Alpha-fetoprotein (AFP) response (>50% reduction from baseline) occurred in 9 of the 26 (35%) patients with elevated baseline AFP and ≥1 post-baseline measurement. Twenty-two patients with SD at week 12 were randomized. Median PFS after randomization was 2.5 months with cabozantinib and 1.4 months with placebo, although this difference was not statistically significant. Median PFS and overall survival from Day 1 in all patients were 5.2 and 11.5 months, respectively. The most common grade 3/4 adverse events, regardless of attribution, were diarrhea (20%), hand-foot syndrome (15%), and thrombocytopenia (15%). Dose reductions were utilized in 59% of patients.ConclusionsCabozantinib has clinical activity in HCC patients, including objective tumor responses, disease stabilization, and reductions in AFP. Adverse events were managed with dose reductions.Trial registration numberNCT00940225

Linguistic diversity, multilingualism, and cognitive skills: A study of disadvantaged children in India

Multilingualism and linguistic diversity are the norm in India. Although studies have shown a relation between bilingualism and cognitive gains, linguistic diversity has so far been ignored as a potential factor affecting cognitive skills. This study aims to fill this gap by examining how cognitive skills—as measured by the n-back and Raven’s Colored Progressive Matrices tasks—are affected by multilingualism and/or sociolinguistic diversity in a large cohort of socioeconomically disadvantaged primary school children in two urban sites of India: Delhi and Hyderabad. We present a questionnaire estimating sociolinguistic diversity and show that this measure assesses a distinct construct, as compared to a child’s multilingualism. Children were classified as growing up monolingually or bilingually, depending on whether they grew up with one or more languages in the home. Regarding cognitive performance, bilinguals were found to outperform monolinguals on the n-back task, as well as on the Raven’s task. In addition, a socially and linguistically diverse environment seems to enhance cognitive performance for children who are not multilingual themselves. Finally, several contextual factors such as city were found to influence cognitive performance. Overall, this shows that cognitive tasks are subject to contextual effects and that bilingualism and linguistic diversity can enhance cognitive performance of children in disadvantaged contexts.</jats:p

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of &gt;2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (&gt;2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

Effects of mother tongue education and multilingualism on reading skills in the regional language and English in India

In a highly multilingual country like India, challenges and opportunities arise in education and language policy. Although multilingualism is often associated with developmental advantages, Indian primary school children generally show low learning outcomes, specifically on literacy. Here we examine the influence of mother tongue education and multilingualism on the reading skills and reading comprehension of 1272 Indian primary school children from low SES homes. The children performed the ASER literacy task in both the regional, majority language and in English, which was followed by newly developed reading comprehension questions. The results show that minority language speakers from monolingual households—who do not receive mother tongue education—underperform compared to majority language speakers when reading in the majority language. When reading in English, growing up in a multilingual household improves children\u27s performance. Finally, in sites which have a larger proportion of mother tongue-educated children, children perform better in literacy in the regional language and worse in English. Overall, these results provide insight into the influence of mother tongue education and multilingualism on reading abilities and show that more support is needed for minority language speakers to develop literacy in the majority language, and for all children to develop literacy in English

Deletion of nuoG from the Vaccine Candidate Mycobacterium bovis BCG ΔureC::hly Improves Protection against Tuberculosis

The current tuberculosis (TB) vaccine, Mycobacterium bovis Bacillus Calmette-Guàérin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene nuoG, encoding NADH dehydrogenase 1 subunit G, from BCG ΔureC::hly. In vitro, deletion of nuoG unexpectedly led to strongly increased recruitment of the autophagosome marker LC3 to the engulfed vaccine, suggesting that nuoG also affects xenophagic pathways. In mice, BCG ΔureC::hly ΔnuoG vaccination was safer than BCG and improved protection over that of parental BCG ΔureC::hly, significantly reducing TB load in murine lungs, ameliorating pulmonary pathology, and enhancing immune responses. Transcriptome analysis of draining lymph nodes after vaccination with either BCG ΔureC::hly or BCG ΔureC::hly ΔnuoG demonstrated earlier and stronger induction of immune responses than that with BCG SSI and suggested upregulation of inflammasome activation and interferon-induced GTPases. In summary, BCG ΔureC::hly ΔnuoG is a promising next-generation TB vaccine candidate with excellent efficacy and safety

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3&nbsp;years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6&nbsp;months (median). The median age was 72&nbsp;years, and the baseline median prostate-specific antigen level was 15.0&nbsp;ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7&nbsp;months (95% confidence interval [CI], 28.6-32.2&nbsp;months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7&nbsp;months (95% CI, 39.4-46.2&nbsp;months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings