Background:

Unnecessary antibiotic use in the community in Canada is not well defined. Our objective was to quantify unnecessary antibiotic prescribing in a Canadian primary care setting.

The article “Effect of Lipoprotein(a) on the Diagnosis of Familial Hypercholesterolemia: Does It Make a Difference in the Clinic?” (Clin Chem 2019;65:1258–66) contained several descriptive errors in the laboratory methods reported on page 1259.

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of ¹⁸F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.

Purpose:

To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease.

Imipenem-relebactam (I-R) is a recently developed carbapenem–beta-lactamase inhibitor combination agent that can overcome carbapenem resistance, which has now emerged in Escherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. To clarify the likely utility of I-R for carbapenem-resistant (CR) E. coli infections in the United States, we characterized 203 recent CR clinical E. coli isolates from across the United States (years 2002 to 2017) for phylogroup, clonal group (including ST131, H30R, and the CTX-M-15-associated H30Rx subset within H30R), relevant beta-lactamase genes, and broth microdilution MICs for I-R and 11 comparator agents. Overall, I-R was highly active (89% susceptible), more so than all comparators except tigecycline and colistin (both 99% susceptible). I-R’s activity varied significantly in relation to phylogroup, clonal background, resistance genotype, and region. It was greatest among phylogroup B2, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive, and northeast U.S. isolates and lowest among phylogroup C, New Delhi metallo-β-lactamase (NDM)-positive, and southeast U.S. isolates. Relebactam improved imipenem’s activity against CR isolates within each phylogroup—especially groups A, B1, and B2—and particularly against isolates containing KPC. I-R remained substantially active against isolates coresistant to comparator agents, albeit somewhat less so than against the corresponding susceptible isolates. These findings suggest that I-R should be useful for treating most CR E. coli infections in the United States, largely independent of coresistance, although this likely will vary in relation to the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1_LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC₅₀) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 x 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution. Cefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2 g every 8 h for intravenous bolus injection or 2 g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO. We established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

Chlorotoxin, a small peptide component of scorpion venom, may help pinpoint glioblastoma cells for destruction when engineered into a chimeric antigen receptor T-cell therapy. The concept has shown efficacy in mice, without off-target toxicity, and will soon be assessed in patients.

Understanding how coronary blood vessels form and regenerate during development and progression of cardiac diseases will shed light on the development of new treatment options targeting coronary artery diseases. Recent studies with the state-of-the-art technologies have identified novel origins of, as well as new, cellular and molecular mechanisms underlying the formation of coronary vessels in the postnatal heart, including collateral artery formation, endocardial-to-endothelial differentiation and mesenchymal-to-endothelial transition. These new mechanisms of coronary vessel formation and regeneration open up new possibilities targeting neovascularization for promoting cardiac repair and regeneration. Here, we highlight some recent studies on cellular mechanisms of coronary vessel formation, and discuss the potential impact and significance of the findings on basic research and clinical application for treating ischemic heart disease.

Background:

Energy balance–related factors, such as body mass index (BMI), diet, and physical activity, may influence colorectal cancer etiology through interconnected metabolic pathways, but their combined influence is less clear.

Background:

Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies.

The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score was developed to establish a simple, standardized scoring system for researchers to quantify adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations and assess its impact on cancer risk and other health-related outcomes. The aim of this commentary is to clarify potential points of ambiguity in its application, focusing on aspects related to specific subscore components (physical activity, fast foods, alcohol, and sugar-sweetened drinks), how to address different data needs due to varied data collection instruments, and future exploratory score approaches. Overall, we encourage researchers to utilize the standardized score to enhance comparability across populations and countries. Researchers who may adapt or augment the 2018 WCRF/AICR Score are strongly encouraged to provide detailed descriptions of their methods to promote transparency and reproducibility.

BACKGROUND AND PURPOSE:

In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population.

SUMMARY:

Polymorphous low-grade neuroepithelial tumors of the young (PLNTYs) are recently described CNS tumors. Classically, PLNTYs are epileptogenic and are a subtype of a heterogeneous group of low-grade neuroepithelial tumors that cause refractory epilepsy, such as angiocentric gliomas, oligodendrogliomas, gangliogliomas, and pleomorphic xanthoastrocytomas. Although they are a relatively new entity, a number of imaging and histologic characteristics of PLNTYs are already known. We present the imaging and pathologic findings of such a tumor as well as the surgical approach and clinical management.

Trước tình trạng bùng phát dịch corona ở nhiều nước trên thế giới, mỗi gia đình cần phải thường xuyên vệ sinh, khử trùng nhà cửa sạch sẽ như một phần của các biện pháp phòng ngừa dịch bệnh.

Thị trường BĐS ở Mỹ vốn đang phục hồi và chuẩn bị có một khởi đầu mạnh mẽ trong mùa Xuân này, cho tới khi virus Corona bùng phát và gây ra những ảnh hưởng không nhỏ.

पंजाब में कोरोना महामारी से बुधवार को दो और लोगों ने दम तोड़ दिया। इसके साथ ही प्रदेश में संक्रमण से मरने वालों की संख्या 27 हो गई।

राजस्थान में शुक्रवार को कोरोना वायरस संक्रमण के 64 नए मामले सामने आए और एक बीमार व्यक्ति की मौत हो गई। अब राज्य में कोरोना की वजह से मौतों का आंकड़ा 100 हो गया है और कुल संक्रमितों की संख्या 3491 हो गई है।

राजस्थान में कोरोना संक्रमण के 57 नए मामले सामने आए, जिससे राज्य में कोरोना वायरस संक्रमितों की कुल संख्या बढ़कर 3,636 हो गई।

देश सेवा हर नागरिक का पहला कर्तव्य होना चाहिए। बहुत कम लोगों को यह मौका मिलता है। देश सेवा में योगदान देकर अच्छा महसूस कर रही हूं।

कश्मीर में शुक्रवार को कोरोना के 30 नए मामले सामने आए। अब प्रदेश में संक्रमितों का आंकड़ा 823 हो चुका है। वहीं 29 मरीजों को ठीक होने पर अस्पताल से छुट्टी दे दी गई।

कोरोना वायरस से लोगों को बचाने के लिए योद्धा के रूप में डेढ़ महीने से कंडी के बीएमओ डॉ. इकबाल मलिक सेवाएं दे रहे हैं। उन्होंने बताया कि उनके परिवार से ज्यादा महत्व उन लोगों का है जिनके लिए वह ड्यूटी देकर सरकार से वेतन लेते हैं।

पंजाब में शनिवार को कोरोना संक्रमण से पीड़ित एक और मरीज की मौत हो गई। इसके साथ ही प्रदेश में महामारी से मृतकों की संख्या 30 पहुंच गई है।

चंडीगढ़ में सेक्टर 32 स्थित जीएमसीएच में शानिवार दोपहर को बापूधाम निवासी कोरोना के संदिग्ध मरीज की मौत हो गई।

छत्तीसगढ़ के कोरबा जिले में तीन और कोरोना संक्रमित मिले हैं। इसी के साथ राज्य में संक्रमितों की संख्या बढ़कर 36 हो गई।

लॉक डाउन का तीसरा चरण शहरियों पर संक्रमण के लिहाज से भारी पड़ा है। महाराष्ट्र और दिल्ली से आए लोग कोरोना संक्रमितों की संख्या बढ़ने का कारण बने। एक मई से सात मई तक सिर्फ पांच दिन में संक्रमितों की संख्या पांच से 17 हो गई।

जिले में बढ़ते कोरोना संक्रमण के बीच राहत की खबर है। शंकरगढ़ के कपारी गांव के दोनों कोरोना पॉजिटिव युवकों की तीसरी बार कराई गई जांच की रिपोर्ट शुक्रवार को निगेटिव आई है। वहीं तेलियरगंज के शंकरघाट निवासी संक्रमित युवक की रिपोर्ट अभी आनी बाकी है...

स्वरूपरानी नेहरू चिकित्सालय में सर्जरी विभाग की पीजी छात्रा प्रथम वर्ष की कोरोना की जांच रिपोर्ट निगेटिव आई है। इसके बाद चिकित्सालय प्रशासन ने राहत की सांस ली है। उधर, ओपीडी में आने वालों में चार लोगों को संदिग्ध मानते हुए भर्ती किया गया है।

दिल्ली-एनसीआर समेत पूरे देश में लॉकडाउन का दूसरा चरण 3 मई को खत्म हो जाएगा और 4 मई से इसका तीसरा चरण शुरू हो जाएगा। लेकिन लॉकडाउन के लंबे दौर के बाद भी कोरोना संक्रमितों के आंकड़े लगातार बढ़ रहे हैंं, पढ़ें दिनभर के अपडेट्स...

गुरुग्राम जिला प्रशासन ने कोरोना वायरस के प्रसार को रोकने के लिए छह और इलाकों को कंटेनमेंट जोन घोषित कर दिया है।

भारतीय महिला हॉकी टीम ने कोविड-19 महामारी के खिलाफ लड़ाई में मदद के लिए 20 लाख रुपये की राशि जुटाई है..

जानलेवा महामारी कोरोना वायरस से संक्रमित बिहार के बिहार शरीफ के रहने वाले महताब आलम संक्रमण से मुक्त हो गए हैं।

बिहार के पूर्णिया जिले में बुधवार को कोरोना संक्रमण का एक नया मामला प्रकाश में आने के साथ प्रदेश में कोविड-19 के मामले अब बढकर 536 हो गए हैं।

बिहार के समस्तीपुर जिले में शुक्रवार को कोरोना वायरस संक्रमण के छह नये मामले सामने आने के बाद प्रदेश में कोविड-19 से संक्रमित लोगों की संख्या बढ़कर 556 हो गई है।