Showing papers by "Saint Francis University published in 2020"

Initial invasive or conservative strategy for stable coronary disease.

Abstract: Background Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical ther...

ASPEN Consensus Recommendations for Refeeding Syndrome

Abstract: Introduction In the spring of 2017, the American Society for Parenteral and Enteral Nutrition (ASPEN) Parenteral Nutrition Safety Committee and the Clinical Practice Committee convened an interprofessional task force to develop consensus recommendations for identifying patients with or at risk for refeeding syndrome (RS) and for avoiding and managing the condition. This report provides narrative review and consensus recommendations in hospitalized adult and pediatric populations. Methods Because of the variation in definitions and methods reported in the literature, a consensus process was developed. Subgroups of authors investigated specific issues through literature review. Summaries were presented to the entire group for discussion via email and teleconferences. Each section was then compiled into a master document, several revisions of which were reviewed by the committee. Findings/recommendations This group proposes a new clinical definition, and criteria for stratifying risk with treatment and screening strategies. The authors propose that RS diagnostic criteria be stratified as follows: a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by 10%-20% (mild), 20%-30% (moderate), or >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamin deficiency (severe), occurring within 5 days of reintroduction of calories. Conclusions These consensus recommendations are intended to provide guidance regarding recognizing risk and identifying, stratifying, avoiding and managing RS. This consensus definition is additionally intended to be used as a basis for further research into the incidence, consequences, pathophysiology, avoidance, and treatment of RS.

Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial

Abstract: Summary Background Bortezomib, lenalidomide, and dexamethasone (VRd) is a standard therapy for newly diagnosed multiple myeloma. Carfilzomib, a next-generation proteasome inhibitor, in combination with lenalidomide and dexamethasone (KRd), has shown promising efficacy in phase 2 trials and might improve outcomes compared with VRd. We aimed to assess whether the KRd regimen is superior to the VRd regimen in the treatment of newly diagnosed multiple myeloma in patients who were not being considered for immediate autologous stem-cell transplantation (ASCT). Methods In this multicentre, open-label, phase 3, randomised controlled trial (the ENDURANCE trial; E1A11), we recruited patients aged 18 years or older with newly diagnosed multiple myeloma who were ineligible for, or did not intend to have, immediate ASCT. Participants were recruited from 272 community oncology practices or academic medical centres in the USA. Key inclusion criteria were the absence of high-risk multiple myeloma and an Eastern Cooperative Oncology Group performance status of 0–2. Enrolled patients were randomly assigned (1:1) centrally by use of permuted blocks to receive induction therapy with either the VRd regimen or the KRd regimen for 36 weeks. Patients who completed induction therapy were then randomly assigned (1:1) a second time to either indefinite maintenance or 2 years of maintenance with lenalidomide. Randomisation was stratified by intent for ASCT at disease progression for the first randomisation and by the induction therapy received for the second randomisation. Allocation was not masked to investigators or patients. For 12 cycles of 3 weeks, patients in the VRd group received 1·3 mg/m2 of bortezomib subcutaneously or intravenously on days 1, 4, 8, and 11 of cycles 1–8, and day 1 and day 8 of cycles nine to twelve, 25 mg of oral lenalidomide on days 1–14, and 20 mg of oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. For nine cycles of 4 weeks, patients in the KRd group received 36 mg/m2 of intravenous carfilzomib on days 1, 2, 8, 9, 15, and 16, 25 mg of oral lenalidomide on days 1–21, and 40 mg of oral dexamethasone on days 1, 8, 15, and 22. The coprimary endpoints were progression-free survival in the induction phase, and overall survival in the maintenance phase. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who received at least one dose of their assigned treatment. The trial is registered with ClinicalTrials.gov, NCT01863550. Study recruitment is complete, and follow-up of the maintenance phase is ongoing. Findings Between Dec 6, 2013, and Feb 6, 2019, 1087 patients were enrolled and randomly assigned to either the VRd regimen (n=542) or the KRd regimen (n=545). At a median follow-up of 9 months (IQR 5–23), at a second planned interim analysis, the median progression-free survival was 34·6 months (95% CI 28·8–37·8) in the KRd group and 34·4 months (30·1–not estimable) in the VRd group (hazard ratio [HR] 1·04, 95% CI 0·83–1·31; p=0·74). Median overall survival has not been reached in either group. The most common grade 3–4 treatment-related non-haematological adverse events included fatigue (34 [6%] of 527 patients in the VRd group vs 29 [6%] of 526 in the KRd group), hyperglycaemia (23 [4%] vs 34 [6%]), diarrhoea (23 [5%] vs 16 [3%]), peripheral neuropathy (44 [8%] vs four [ Interpretation The KRd regimen did not improve progression-free survival compared with the VRd regimen in patients with newly diagnosed multiple myeloma, and had more toxicity. The VRd triplet regimen remains the standard of care for induction therapy for patients with standard-risk and intermediate-risk newly diagnosed multiple myeloma, and is a suitable treatment backbone for the development of combinations of four drugs. Funding US National Institutes of Health, National Cancer Institute, and Amgen.

Association Between Initiation of Pulmonary Rehabilitation After Hospitalization for COPD and 1-Year Survival Among Medicare Beneficiaries.

Abstract: Importance Meta-analyses have suggested that initiating pulmonary rehabilitation after an exacerbation of chronic obstructive pulmonary disease (COPD) was associated with improved survival, although the number of patients studied was small and heterogeneity was high. Current guidelines recommend that patients enroll in pulmonary rehabilitation after hospital discharge. Objective To determine the association between the initiation of pulmonary rehabilitation within 90 days of hospital discharge and 1-year survival. Design, Setting, and Patients This retrospective, inception cohort study used claims data from fee-for-service Medicare beneficiaries hospitalized for COPD in 2014, at 4446 acute care hospitals in the US. The final date of follow-up was December 31, 2015. Exposures Initiation of pulmonary rehabilitation within 90 days of hospital discharge. Main Outcomes and Measures The primary outcome was all-cause mortality at 1 year. Time from discharge to death was modeled using Cox regression with time-varying exposure to pulmonary rehabilitation, adjusting for mortality and for unbalanced characteristics and propensity to initiate pulmonary rehabilitation. Additional analyses evaluated the association between timing of pulmonary rehabilitation and mortality and between number of sessions completed and mortality. Results Of 197 376 patients (mean age, 76.9 years; 115 690 [58.6%] women), 2721 (1.5%) initiated pulmonary rehabilitation within 90 days of discharge. A total of 38 302 (19.4%) died within 1 year of discharge, including 7.3% of patients who initiated pulmonary rehabilitation within 90 days and 19.6% of patients who initiated pulmonary rehabilitation after 90 days or not at all. Initiation within 90 days was significantly associated with lower risk of death over 1 year (absolute risk difference [ARD], –6.7% [95% CI, –7.9% to –5.6%]; hazard ratio [HR], 0.63 [95% CI, 0.57 to 0.69];P Conclusions and Relevance Among fee-for-service Medicare beneficiaries hospitalized for COPD, initiation of pulmonary rehabilitation within 3 months of discharge was significantly associated with lower risk of mortality at 1 year. These findings support current guideline recommendations for pulmonary rehabilitation after hospitalization for COPD, although the potential for residual confounding exists and further research is needed.

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.

Abstract: Purpose: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. Patients and Methods: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naive patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. Results: Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32–0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5–22.2) vs. 5.6 (95% CI, 3.7–7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07–0.45; P Conclusions: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.

Atorvastatin associated with decreased hazard for death in COVID-19 patients admitted to an ICU: a retrospective cohort study.

Abstract: To the editor, Since the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) a pandemic, the medical community started a race against time to find effective treatments for this disease [1]. Atorvastatin as adjuvant immunomodulatory therapy is of particular interest given its low cost, known safety profile, and availability. The severe acute respiratory syndrome coronavirus (SARS-CoV) has been shown to interact with Toll-like receptors on the host cell membrane, increasing the expression of the MYD88 gene, ultimately activating NF-κB and triggering inflammatory pathways. Experimental models have demonstrated that statins stabilize MYD88 levels after a pro-inflammatory trigger, and, in a murine model, atorvastatin significantly attenuated NF-κB activation [2]. Furthermore, in the real world, two retrospective cohort studies reported a reduced risk of influenza death among statin users [3, 4]. Therefore, we assessed whether statin users at a dose of 40 mg daily had reduced inpatient mortality hazard from COVID-19. In this retrospective cohort study, we used a deidentified dataset that included 87 adult patients with laboratory-confirmed COVID-19 admitted to our community hospital intensive care unit (ICU) located in Evanston, IL, from March to May 2020. We performed a Cox proportional hazards (PH) regression model to examine the relationship between adjuvant treatments and inpatient mortality. To minimize confounders, we adjusted for age, hypertension, cardiovascular disease, invasive mechanical ventilation, severity according to the National Institutes of Health criteria (respiratory rate > 30, SpO2 < 94%, PaO2/FiO2 < 300 mmHg or lung infiltrates > 50%), number of comorbidities (as a continuous variable), and other adjuvant therapies (including hydroxychloroquine, intravenous steroids, azithromycin, tocilizumab, colchicine, and antibiotics), forcing these variables into the model. We also performed a sensitivity analysis calculating the E value (with the lower confidence limit) as described by VanderWeele et al. [5, 6] for the obtained point estimate. The E value is defined as the minimum strength of association on the risk ratio scale that an unmeasured confounder would need to have with both the exposure and the outcome, conditional on the measured covariates, to explain away a specific exposure-outcome association fully. The median age was 68 years (interquartile range [IQR], 58–75 years), 56 (64.4%) were males, and 50 (57.5%) were skilled nursing facility residents. Of these patients, 39 (44.8%) were ultimately discharged from the hospital, median length of stay 13 days (IQR, 7 to 21 days), and 48 (55.2%) had died, median length of stay 9.5 days (IQR,

Diabetes Prevalence and Its Relationship With Education, Wealth, and BMI in 29 Low- and Middle-Income Countries

Abstract: OBJECTIVE Diabetes is a rapidly growing health problem in low- and middle-income countries (LMICs), but empirical data on its prevalence and relationship to socioeconomic status are scarce. We estimated diabetes prevalence and the subset with undiagnosed diabetes in 29 LMICs and evaluated the relationship of education, household wealth, and BMI with diabetes risk. RESEARCH DESIGN AND METHODS We pooled individual-level data from 29 nationally representative surveys conducted between 2008 and 2016, totaling 588,574 participants aged ≥25 years. Diabetes prevalence and the subset with undiagnosed diabetes was calculated overall and by country, World Bank income group (WBIG), and geographic region. Multivariable Poisson regression models were used to estimate relative risk (RR). RESULTS Overall, prevalence of diabetes in 29 LMICs was 7.5% (95% CI 7.1–8.0) and of undiagnosed diabetes 4.9% (4.6–5.3). Diabetes prevalence increased with increasing WBIG: countries with low-income economies (LICs) 6.7% (5.5–8.1), lower-middle-income economies (LMIs) 7.1% (6.6–7.6), and upper-middle-income economies (UMIs) 8.2% (7.5–9.0). Compared with no formal education, greater educational attainment was associated with an increased risk of diabetes across WBIGs, after adjusting for BMI (LICs RR 1.47 [95% CI 1.22–1.78], LMIs 1.14 [1.06–1.23], and UMIs 1.28 [1.02–1.61]). CONCLUSIONS Among 29 LMICs, diabetes prevalence was substantial and increased with increasing WBIG. In contrast to the association seen in high-income countries, diabetes risk was highest among those with greater educational attainment, independent of BMI. LMICs included in this analysis may be at an advanced stage in the nutrition transition but with no reversal in the socioeconomic gradient of diabetes risk.

Accuracy of computational pressure-fluid dynamics applied to coronary angiography to derive fractional flow reserve: FLASH FFR

Abstract: Aims Conventional fractional flow reserve (FFR) is measured invasively using a coronary guidewire equipped with a pressure sensor. A non-invasive derived FFR would eliminate risk of coronary injury, minimize technical limitations, and potentially increase adoption. We aimed to evaluate the diagnostic performance of a computational pressure-flow dynamics derived FFR (caFFR), applied to coronary angiography, compared to invasive FFR. Methods and results The FLASH FFR study was a prospective, multicentre, single-arm study conducted at six centres in China. Eligible patients had native coronary artery target lesions with visually estimated diameter stenosis of 30-90% and diagnosis of stable or unstable angina pectoris. Using computational pressure-fluid dynamics, in conjunction with thrombolysis in myocardial infarction (TIMI) frame count, applied to coronary angiography, caFFR was measured online in real-time and compared blind to conventional invasive FFR by an independent core laboratory. The primary endpoint was the agreement between caFFR and FFR, with a pre-specified performance goal of 84%. Between June and December 2018, matched caFFR and FFR measurements were performed in 328 coronary arteries. Total operational time for caFFR was 4.54 ± 1.48 min. caFFR was highly correlated to FFR (R = 0.89, P = 0.76) with a mean bias of -0.002 ± 0.049 (95% limits of agreement -0.098 to 0.093). The diagnostic performance of caFFR vs. FFR was diagnostic accuracy 95.7%, sensitivity 90.4%, specificity 98.6%, positive predictive value 97.2%, negative predictive value 95.0%, and area under the receiver operating characteristic curve of 0.979. Conclusions Using wire-based FFR as the reference, caFFR has high accuracy, sensitivity, and specificity. caFFR could eliminate the need of a pressure wire, technical error and potentially increase adoption of physiological assessment of coronary artery stenosis severity. Clinical trial registration URL: http://www.chictr.org.cn Unique Identifier: ChiCTR1800019522.

Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with Coronavirus Disease 2019.

Abstract: Coronavirus disease 2019 has markedly varied clinical presentations, with most patients being asymptomatic or having mild symptoms. However, severe acute respiratory disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is common and associated with mortality in patients who require hospitalization. The etiology of susceptibility to severe lung injury remains unclear. Angiotensin II, converted by angiotensin-converting enzyme (ACE) from angiotensin I and metabolized by ACE 2 (ACE2), plays a pivotal role in the pathogenesis of lung injury. ACE2 is identified as an essential receptor for SARS-CoV-2 to enter the cell. The binding of ACE2 and SARS-CoV-2 leads to the exhaustion and down-regulation of ACE2. The interaction and imbalance between ACE and ACE2 result in an unopposed angiotensin II. Considering that the ACE insertion (I)/deletion (D) gene polymorphism contributes to the ACE level variability in general population, in which mean ACE level in DD carriers is approximately twice that in II carriers, we propose a hypothesis of genetic predisposition to severe lung injury in patients with coronavirus disease 2019. It is plausible that the ACE inhibitors and ACE receptor blockers may have the potential to prevent and to treat the acute lung injury after SARS-CoV-2 infection, especially for those with the ACE genotype associated with high ACE level.

Endotheliitis and endothelial dysfunction in patients with COVID-19: Its role in thrombosis and adverse outcomes

Abstract: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerging in Wuhan, China and developing into a pandemic with rapidly emerging cardiovascular manifestations [...].

Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure.

Abstract: While torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared with furosemide remain unclear. We performed a systematic review and meta-analysis, including all published studies that compared torsemide and furosemide use in heart failure patients from January 1996 through August 2019. Nineteen studies (9 randomized control trials (RCTs) and 10 observational studies) with a total of 19,280 patients were included. During a mean follow-up duration of 15 months, torsemide was associated with a numerically lower risk of hospitalization due to heart failure (10.6% vs. 18.4%; odds ratio (OR) 0.72, 95% confidence interval (CI) (0.51, 1.03), p=0.07, I2=18%; number needed to treat (NNT) =23) compared with furosemide. Torsemide was associated with statistically significant more improvement in functional status from New York Heart Association (NYHA) class III/IV to I/II (72.5% vs. 58%; OR 2.32, 95% CI (1.32, 4.1), p=0.004, I2=27%; NNT=5) and lower risk of cardiac mortality (1.5% vs. 4.4%; OR 0.37, 95% CI (0.20, 0.66), p

Deformation of organic matter and its effect on pores in mud rocks

Abstract: Pores within organic matter (OM) are strongly linked to hydrocarbon generation and primary migration in fine-grained source rocks and are very important for evaluating hydrocarbon storage and flow in shale reservoirs. Thus, it is critical to clarify the features of OM-hosted pores and their evolution in organic-rich mud rocks. The OM in mud rocks, including kerogen and bitumen, is deformed when the original equilibrium stress conditions are altered. The OM deformation at the nano- or microscale has rarely been discussed because of the lack of unequivocal evidence. This research begins with examining the subsurface evolution of kerogen and bitumen, with emphasis on various features of pores hosted by bitumen. Evidence of OM deformation is documented in scanning electron microscope images of seven overmature samples from the lower Silurian Longmaxi Shale, Sichuan Basin. To aid in the understanding and analysis, OM deformation is classified into three types: type I deformation induced by one additional force, type II deformation induced by two additional forces acting on two locations of single OM particles, and type III deformation induced by three or more deforming forces acting at three or more locations of single OM particles. Thus, type I deformation is generally less complex than type II and III deformation. The OM particles subjected to type I deformation were analyzed quantitatively for parameters such as pore size, geometry, and long-axis orientation of elliptical pores. Deformation of OM enhances the robust heterogeneity of OM-hosted pores.

Factors Associated with Good Patient Outcomes Following Convalescent Plasma in COVID-19: A Prospective Phase II Clinical Trial.

Abstract: Coronavirus disease 2019 (COVID-19) is a viral respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This novel virus was discovered in Wuhan City, Hubei Province, China, in December 2019. As of September 6, 2020, confirmed cases have risen to more than 27,000,000 worldwide and more than 885,000 people have died. Currently, no cure or standard treatment for COVID-19 exists. We conducted a prospective single-arm open-label phase II clinical trial assessing the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19. Convalescent plasma with sufficient total anti-SARS-CoV-2 IgG titer (1:320) obtained from recovered donors was administered to adult patients with either severe or critical COVID-19 illness. Primary outcomes were adverse events in association with plasma administration, and hospital mortality. Secondary outcomes included disease progression, recovery, length of stay, and hospital discharge. Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged, and 14 (37%) died. Patients who received convalescent plasma early in the disease course (severe illness group) as compared to the patients that received convalescent plasma later in the disease progression (critical illness group) had significantly lower hospital mortality 13% vs 55% (p < 0.02) and shorter mean hospital length of stay 15.4 vs 33 days (p < 0.01). One patient experienced a transient transfusion reaction. No other adverse effects of convalescent plasma infusion were observed. Our results suggest that convalescent plasma with adequate anti-SARS-CoV-2 antibody titer is safe and has the potential for positive impact on clinical outcomes including recovery and survival if given to patients early in the course of COVID-19 disease. ClinicalTrials.gov. Identifier, NCT04343261, IND #19805.

Development and upgrading of public primary healthcare facilities with essential surgical services infrastructure: a strategy towards achieving universal health coverage in Tanzania

Abstract: Infrastructure development and upgrading to support safe surgical services in primary health care facilities is an important step in the journey towards achieving Universal Health Coverage (UHC). Quality health service provision together with equitable geographic access and service delivery are important components that constitute UHC. Tanzania has been investing in infrastructure development to offer essential safe surgery close to communities at affordable costs while ensuring better outcomes. This study aimed to understand the public sector’s efforts to improve the infrastructure of primary health facilities between 2005 and 2019. We assessed the construction rates, geographic coverage, and physical status of each facility, surgical safety and services rendered in public primary health facilities. Data was collected from existing policy reports, the Services Availability and Readiness Assessment (SARA) tool (physical status), the Health Facility Registry (HFR), implementation reports on infrastructure development from the 26 regions and 185 district councils across the country (covering assessment of physical infrastructure, waste management systems and inventories for ambulances) and Comprehensive Emergence Obstetric Care (CEMONC) signal functions assessment tool. Data was descriptively analyzed so as to understand the distribution of primary health care facilities and their status (old, new, upgraded, under construction, renovated and equipped), and the service provided, including essential surgical services. Of 5072 (518 are Health Centers and 4554 are Dispensaries) existing public primary health care facilities, the majority (46%) had a physical status of A (good state), 33% (1693) had physical status of B (minor renovation needed) and the remaining facilities had physical status of C up to F (needing major renovation). About 33% (1673) of all health facilities had piped water and 5.1% had landline telecommunication system. Between 2015 and August 2019, a total of 419 (8.3%) health facilities (Consisting of 350 health centers and 69 District Council Hospitals) were either renovated or constructed and equipped to offer safe surgery services. Of all Health Centers only 115 (22.2%) were offering the CEMONC services. Of these 115 health facilities, only 20 (17.4%) were offering the CEMONC services with all 9 - signal functions and only 17.4% had facilities that are offering safe blood transfusion services. This study indicates that between 2015 and 2019 there has been improvement in physical status of primary health facilities as a result constructions, upgrading and equipping the facilities to offer safe surgery and related diagnostic services. Despite the achievements, still there is a high demand for good physical statuses and functioning of primary health facilities with capacity to offer essential and safe surgical services in the country also as an important strategy towards achieving UHC. This is also inline with the National Surgical, Obstetrics and Anesthesia plan (NSOAP).

Metabolic potentials of archaeal lineages resolved from metagenomes of deep Costa Rica sediments.

Abstract: Numerous archaeal lineages are known to inhabit marine subsurface sediments, although their distributions, metabolic capacities, and interspecies interactions are still not well understood. Abundant and diverse archaea were recently reported in Costa Rica (CR) margin subseafloor sediments recovered during IODP Expedition 334. Here, we recover metagenome-assembled genomes (MAGs) of archaea from the CR margin and compare them to their relatives from shallower settings. We describe 31 MAGs of six different archaeal lineages (Lokiarchaeota, Thorarchaeota, Heimdallarchaeota, Bathyarcheota, Thermoplasmatales, and Hadesarchaea) and thoroughly analyze representative MAGs from the phyla Lokiarchaeota and Bathyarchaeota. Our analysis suggests the potential capability of Lokiarchaeota members to anaerobically degrade aliphatic and aromatic hydrocarbons. We show it is genetically possible and energetically feasible for Lokiarchaeota to degrade benzoate if they associate with organisms using nitrate, nitrite, and sulfite as electron acceptors, which suggests a possibility of syntrophic relationships between Lokiarchaeota and nitrite and sulfite reducing bacteria. The novel Bathyarchaeota lineage possesses an incomplete methanogenesis pathway lacking the methyl coenzyme M reductase complex and encodes a noncanonical acetogenic pathway potentially coupling methylotrophy to acetogenesis via the methyl branch of Wood–Ljungdahl pathway. These metabolic characteristics suggest the potential of this Bathyarchaeota lineage to be a transition between methanogenic and acetogenic Bathyarchaeota lineages. This work expands our knowledge about the metabolic functional repertoire of marine benthic archaea.

Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial.

Abstract: LBA3Background: Bortezomib (btz) combined with lenalidomide (len) and dexamethasone (dex) (VRd) is a standard initial therapy for NDMM. Carfilzomib (cfz), a next-generation proteasome inhibitor, in...

Hormesis: A potential strategic approach to the treatment of neurodegenerative disease.

Abstract: This review describes neuroprotective effects mediated by pre- and post-conditioning-induced processes that act via the quantitative features of the hormetic dose response. These lead to the development of acquired resilience that can protect neuronal systems from endogenous and exogenous stresses and insult. Particular attention is directed to issues of dose optimization, inter-individual variation, and potential ways to further study and employ hormetic-based preconditioning approaches in medical and public health efforts to treat and prevent neurodegenerative disease.

Assembly of Gold Nanowires on Gold Nanostripe Arrays: Simulation and Experiment

Abstract: Nanowires (NWs) have a large aspect ratio and large available surface area, which have made them a potential platform for applications in biosensors as well as electronic/optic and power storage de...

Assessing health system responsiveness in primary health care facilities in Tanzania

Abstract: Health system performance is one of the important components of the health care delivery; its achievement depends on the quality of services rendered and the health system responsiveness of its beneficiaries. Health system responsiveness is a multi-dimensional concept and is usually measured through several domains. Health system responsiveness (HSR) remains to be a key indicator for evaluation of health system performance in any settings. This study aimed at assessing the situation of health system responsiveness in primary health facilities in Tanzania prior to introduction of the Direct Health Facility Financing (DHFF) program. This was a cross sectional study conducted between January and February in 2018. We collected data from 42 primary health facilities (14 health centers and 28 dispensaries) where a questionnaire was administered to a total of 422 participants. The questionnaire collected information on attention, respect to dignity, clear communication, autonomy, access to care, respect to confidentiality and basic amenities. Descriptive analysis was done to determine the distribution of the variables whereas ANOVA and linear regression analysis was employed to discern the association between variables. More than 67% of participants had visited the same health facility more than 5 times. Sixty seven percent of the patients were residing within 5kms from the public primary health care facilities. The geographical access to health care scored the lowest (43.5% for Dispensaries and 36% for Health center) mean as compared to other domains of health system responsiveness. The highest score was in respect to confidentiality (86.7%) followed by respect to dignity (81.4%). Linear regression analysis revealed no statistical association between any of the social demographic features with the overall HSR performances. However, in post hoc analysis, Pwani and Shinyanga regions didn’t differ significantly in terms of their performances whereas those two regions differ from all other regions. Based on the study findings health system responsiveness domains has performed relatively poor in many regions except for respect of dignity and confidentiality scored high of all the domains. Shinyanga and Pwani regions scored relatively well in all domains this could have been due to the effect of Results Based financing (RBF) in the respective regions. All in all the Government and other stakeholders in the health sector they should deliberately invest on the access to care domain as seem to be a challenge as compared to others.

Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study.

Abstract: Author(s): Brenner, Andrew J; Peters, Katherine B; Vredenburgh, James; Bokstein, Felix; Blumenthal, Deborah T; Yust-Katz, Shlomit; Peretz, Idit; Oberman, Bernice; Freedman, Laurence S; Ellingson, Benjamin M; Cloughesy, Timothy F; Sher, Naamit; Cohen, Yael C; Lowenton-Spier, Noa; Rachmilewitz Minei, Tamar; Yakov, Niva; Mendel, Itzhak; Breitbart, Eyal; Wen, Patrick Y | Abstract: BackgroundVB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).MethodsPatients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).ResultsVB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.ConclusionsPatients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.

Real world validation of the nonhyperemic index of coronary artery stenosis severity-Resting full-cycle ratio-RE-VALIDATE.

Abstract: OBJECTIVE The primary objective was to demonstrate diagnostic equivalence between RFR and iFR in clinical practice. BACKGROUND The instantaneous wave-free ratio (iFR), a nonhyperemic pressure ratio (NHPR), has been shown to be noninferior to fractional flow reserve (FFR) in determining coronary artery stenosis severity in intermediate lesions. However, iFR has a number of inherent limitations, including sensitive landmarking of the pressure waveform and the assumption that maximal flow and minimal microcirculatory resistance occur during a fixed period within diastole. The resting full-cycle ratio (RFR) is a novel NHPR which evaluates the entire cardiac cycle independent of the ECG, landmark identification, and timing within the cardiac cycle. METHODS RE-VALIDATE RFR was designed to determine the diagnostic utility of RFR for the physiological assessment of coronary artery disease in clinical practice compared to iFR. RFR was also tested for equivalence (1% margin), diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), areas under the receiver operated characteristic curve (AUC), and correlations compared to calculated iFR (iFRcalc ). RESULTS From two centers, 501 blinded rest- and hyperemic pressure recordings from 431 patients were suitable for analysis according to a core laboratory. The mean FFR, RFR, and iFRcalc were 0.80 ± 0.09, 0.90 ± 0.08, and 0.90 ± 0.08, respectively. Based on a binary cut-off approach (RFR/iFR ≤0.89), RFR demonstrated equivalence with iFRcalc (95% confidence interval: 0.025-0.019) with overall diagnostic accuracy 97.8%, sensitivity 97.8%, specificity 97.8%, PPV 96.2%, NPV 98.7%, and AUC 0.96 (0.94-0.97, p < .001). RFR had a mean bias 0.003 (95% limits of agreement: 0.019, -0.025). CONCLUSIONS RFR was equivalent to iFR in clinical practice. RFR is an alternative NHPR, avoiding the need for hyperemic agents, thus potentially reducing side effects, procedural time and cost compared to FFR.

Three‐year outcomes with brentuximab vedotin plus bendamustine as first salvage therapy in relapsed or refractory Hodgkin lymphoma

Abstract: F., Wilson, R.K., Ley, T.J. & Ding, L. (2014) Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nature Medicine, 20, 1472–1478. Yuan, X.Q., Chen, P., Du, Y.X., Zhu, K.W., Zhang, D.Y., Yan, H., Liu, H., Liu, Y.L., Cao, S., Zhou, G., Zeng, H., Chen, S.P., Zhao, X.L., Yang, J., Zeng, W.J. & Chen, X.P. (2019) Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients. Journal of Translational Medicine, 17, 220.

Influence of reservoir properties on the methane adsorption capacity and fractal features of coal and shale in the upper Permian coal measures of the South Sichuan coalfield, China:

Abstract: Pore structure plays an essential role in the reservoir heterogeneity and methane adsorption capacity. Significant progress has been made in the pore structure classification of porous materials (s...

Patella fractures treated with cannulated lag screws and fiberwire® have a high union rate and low rate of implant removal

Abstract: Objectives The purpose of this study is to report the results of open reduction internal fixation of patella fractures (OTA 34 A-C) using cannulated lag screws and FiberWire® (Arthrex, Naples, FL, USA) with regard to union and symptomatic implant removal. Design Retrospective review of prospectively collected database. Setting Urban Level 1 trauma center and Level 2 trauma center Methods All displaced intra-articular patella fractures (OTA 34 A-C) treated with ORIF by cannulated lag screws and FiberWire® tension band/cerclage between January 1, 2009 and August 1, 2018. Three hundred and eighty seven consecutive patients were identified. Fifty fractures were included in the final analysis. Main Outcome Measurement All patients were followed to clinical and radiographic union. Nonunion was defined as lack of clinical and radiographic union, fracture displacement, and/or return to OR for revision surgery. Rate of symptomatic implant removal was recorded. Results Average age was 57.7 years (range 21–86). Average follow up was 20.6 months (range 6–98 months). Average time to clinical and radiographic union was 3.1 months (range 3–7 months). Four fractures were open. There was a 96% (48/50) rate of primary union, with one patients requiring revision surgery to achieve union, and one developing an asymptomatic radiographic nonunion. The rate of symptomatic implant removal was 8% (4/50). Only 1 of the 4 was operated for a prominent suture knot, and the remaining 3 were for prominent screw removal. Knee range of motion averaged 0.37° extension to 119° flexion (range, 0–150°). Conclusion Patella fractures can be treated with cannulated lag screws and FiberWire® with a high rate of primary union (96%) and a low rate of symptomatic implant removal (8%). The implant removal rate compares favorably with alternative constructs, with an equivalent rate of fracture union.

Idiopathic Granulomatous Mastitis-A Mystery Yet to be Unraveled: A Case Series and Review of Literature.

Abstract: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast, the etiology of which, has still not been elucidated. There have been several mechanisms proposed to explain the pathogenesis. Since the first description of the disease, it has proved itself to be a great diagnostic and therapeutic challenge. It is very often misdiagnosed as cancer, resulting in myriad workup by the physician and great distress to the patient. Clear guidelines as to the management have still not been described. Here, we describe two patients who presented with IGM and have been successfully treated. The first patient was treated with a combination of steroids and antibiotics. The second patient achieved remission of the disease with antibiotics alone. We also propose an algorithm for the management of IGM.

Sociodemographic inequities associated with participation in leisure-time physical activity in sub-Saharan Africa: an individual participant data meta-analysis

Abstract: Leisure-time physical activity (LTPA) is an important contributor to total physical activity and the focus of many interventions promoting activity in high-income populations. Little is known about LTPA in sub-Saharan Africa (SSA), and with expected declines in physical activity due to rapid urbanisation and lifestyle changes we aimed to assess the sociodemographic differences in the prevalence of LTPA in the adult populations of this region to identify potential barriers for equitable participation. A two-step individual participant data meta-analysis was conducted using data collected in SSA through 10 population health surveys that included the Global Physical Activity Questionnaire. For each sociodemographic characteristic, the pooled adjusted prevalence and risk ratios (RRs) for participation in LTPA were calculated using the random effects method. Between-study heterogeneity was explored through meta-regression analyses and tests for interaction. Across the 10 populations (N = 26,022), 18.9% (95%CI: 14.3, 24.1; I2 = 99.0%) of adults (≥ 18 years) participated in LTPA. Men were more likely to participate in LTPA compared with women (RR for women: 0.43; 95%CI: 0.32, 0.60; P < 0.001; I2 = 97.5%), while age was inversely associated with participation. Higher levels of education were associated with increased LTPA participation (RR: 1.30; 95%CI: 1.09, 1.55; P = 0.004; I2 = 98.1%), with those living in rural areas or self-employed less likely to participate in LTPA. These associations remained after adjusting for time spent physically active at work or through active travel. In these populations, participation in LTPA was low, and strongly associated with sex, age, education, self-employment and urban residence. Identifying the potential barriers that reduce participation in these groups is necessary to enable equitable access to the health and social benefits associated with LTPA.