Synthesis of thiazolidinones and azetidinones from hydrazino thieno [3,2-d]pyrimidines as potential antimicrobial agents

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Interval gangrene complicating superficial femoral artery stent placement

Interval gangrene—necrosis of tissue proximal to a successful distal revascularization procedure—is an exceeding rare complication. To date, only nine cases have been reported in the literature, and all were secondary to traditional open bypass procedures. We report the first case, to our knowledge, of interval gangrene after endovascular stent placement in the superficial femoral artery. We believe that with the increasing utilization of endovascular techniques to treat limb ischemia, the serious complication of interval gangrene must be revisited. Assessment of collateral circulation, precise stent placement, and the appropriate choice of stents and stent grafts will become increasing important as more and more of these lesions are treated with endovascular techniques

A rare case of mixed connective tissue disease presenting with central nervous system glioma, vasculitis and polymyositis

Mixed connective tissue disease (MCTD) was first recognized by Sharp and Colleagues in 1972 among a group of patients with overlapping clinical features of systemic lupus erythematosis (SLE), scleroderma and myositis, with the presence of distinctive antibodies against, what now is known to be U1-ribonucleoprotein (RNP). We report an unusual case of a 23-year old female with MCTD characterized by the coexistence of signs, symptoms and immunological features of 3 defined autoimmune diseases SLE, systemic sclerosis (SSc), polymyositis (PM) and an unusual presence of central nervous system (CNS) Glioma

Effect of Indirect Neural Decompression by Minimally Invasive Oblique Lumbar Interbody Fusion in Adult Degenerative Lumbar Spine Disease and Its Limitations

Objective To study efficacy of minimally invasive oblique lumbar interbody fusion (MIS OLIF) to achieve indirect decompression in degenerative lumbar spine disorders. To find out amount of indirect decompression achieved by assessing clinical and radiological outcomes. To find out limitations of indirect decompression. Methods OLIF was carried out in 60 segments/45 patients having degenerative lumbar spine disorders from May 2016 to April 2018. Patients with infection, trauma, lumbar disc prolapse and listhesis >grade 3 were excluded. 53 segments had posterior and 7 segments had anterior fixation. Auto graft was used in 21 and artificial bone graft in 24 patients. Indirect decompression by MIS OLIF was achieved in all patients. Neuromonitioring was not used. Clinical assessment was done using Modified Macnab’s criteria. Radiological assessment was done on X-rays and MRI. Percentage improvement in foraminal height, disc height, segmental lordosis, spinal canal area and reduction in listhesis were measured. Statistical assessment was done using Paired‘t’ test. Results 60 segments of 45 consecutive patients were operated with 15 of them male and 30 female. Average age was 63 years. Minimum follow-up was for 1 month and maximum follow-up was for 18 months with average of 11 months. Single segment fusion was done in 31, 2 segment fusion in 13 and 3 segment fusion in 1 patient. Clinically 33 (73.33%) had excellent, 11 (24.44%) had good & 1 (2.22%) had fair outcomes. None required direct decompression. Radiologically; foraminal height improved by 26.27%, disc height 92.1%, segmental lordosis 3.4° and listhesis reduction was 6.8°, 41 segments studied on MRI had improvement in spinal canal area of 42.7%. Conclusion Indirect decompression by MIS OLIF is effective in decompressing the spinal canal with good radiological and clinical out comes. Direct decompression is avoidable with help of interbody distraction using OLIF particularly in patients with Schizas grade A, B, and C of lumbar spinal stenosis

Mortality after drug-eluting stents vs. coronary artery bypass grafting for left main coronary artery disease: a meta-analysis of randomized controlled trials.

AIMS: The optimal method of revascularization for patients with left main coronary artery disease (LMCAD) is controversial. Coronary artery bypass graft surgery (CABG) has traditionally been considered the gold standard therapy, and recent randomized trials comparing CABG with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) have reported conflicting outcomes. We, therefore, performed a systematic review and updated meta-analysis comparing CABG to PCI with DES for the treatment of LMCAD. METHODS AND RESULTS: We systematically identified all randomized trials comparing PCI with DES vs. CABG in patients with LMCAD. The primary efficacy endpoint was all-cause mortality. Secondary endpoints included cardiac death, myocardial infarction (MI), stroke, and unplanned revascularization. All analyses were by intention-to-treat. There were five eligible trials in which 4612 patients were randomized. The weighted mean follow-up duration was 67.1 months. There were no significant differences between PCI and CABG for the risk of all-cause mortality [relative risk (RR) 1.03, 95% confidence interval (CI) 0.81-1.32; P = 0.779] or cardiac death (RR 1.03, 95% CI 0.79-1.34; P = 0.817). There were also no significant differences in the risk of stroke (RR 0.74, 95% CI 0.35-1.50; P = 0.400) or MI (RR 1.22, 95% CI 0.96-1.56; P = 0.110). Percutaneous coronary intervention was associated with an increased risk of unplanned revascularization (RR 1.73, 95% CI 1.49-2.02; P < 0.001). CONCLUSION: The totality of randomized clinical trial evidence demonstrated similar long-term mortality after PCI with DES compared with CABG in patients with LMCAD. Nor were there significant differences in cardiac death, stroke, or MI between PCI and CABG. Unplanned revascularization procedures were less common after CABG compared with PCI. These findings may inform clinical decision-making between cardiologists, surgeons, and patients with LMCAD

Complete Revascularization by Percutaneous Coronary Intervention for Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Coronary Artery Disease: An Updated Meta-Analysis of Randomized Trials.

Background For patients with ST-segment-elevation myocardial infarction (STEMI) and multivessel coronary artery disease, the optimal treatment of the non-infarct-related artery has been controversial. This up-to-date meta-analysis focusing on individual clinical end points was performed to further evaluate the benefit of complete revascularization with percutaneous coronary intervention for patients with STEMI and multivessel coronary artery disease. Methods and Results We systematically identified all randomized trials comparing complete revascularization with percutaneous coronary intervention to culprit-only revascularization for multivessel disease in STEMI and performed a random-effects meta-analysis. The primary efficacy end point was cardiovascular death analyzed on an intention-to-treat basis. Secondary end points included all-cause mortality, myocardial infarction, and unplanned revascularization. Ten studies (7542 patients) were included: 3664 patients were randomized to complete revascularization and 3878 to culprit-only revascularization. Across all patients, complete revascularization was superior to culprit-only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47-0.98; P=0.037; I2=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54-0.79; P<0.0001; I2=0.0%). Complete revascularization also significantly reduced the risk of unplanned revascularization (RR, 0.37; 95% CI, 0.28-0.51; P<0.0001; I2=64.7%). The difference in all-cause mortality with percutaneous coronary intervention was not statistically significant (RR, 0.85; 95% CI, 0.69-1.04; P=0.108; I2=0.0%). Conclusions For patients with STEMI and multivessel disease, complete revascularization with percutaneous coronary intervention significantly improves hard clinical outcomes including cardiovascular death and myocardial infarction. These data have implications for clinical practice guidelines regarding recommendations for complete revascularization following STEMI

Use of Intravascular Imaging During Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry

Background: Intravascular imaging can facilitate chronic total occlusion (CTO) percutaneous coronary intervention. Methods and Results: We examined the frequency of use and outcomes of intravascular imaging among 619 CTO percutaneous coronary interventions performed between 2012 and 2015 at 7 US centers. Mean age was 65.4±10 years and 85% of the patients were men. Intravascular imaging was used in 38%: intravascular ultrasound in 36%, optical coherence tomography in 3%, and both in 1.45%. Intravascular imaging was used for stent sizing (26.3%), stent optimization (38.0%), and CTO crossing (35.7%, antegrade in 27.9%, and retrograde in 7.8%). Intravascular imaging to facilitate crossing was used more frequently in lesions with proximal cap ambiguity (49% versus 26%, P<0.0001) and with retrograde as compared with antegrade‐only cases (67% versus 31%, P<0.0001). Despite higher complexity (Japanese CTO score: 2.86±1.19 versus 2.43±1.19, P=0.001), cases in which imaging was used for crossing had similar technical and procedural success (92.8% versus 89.6%, P=0.302 and 90.1% versus 88.3%, P=0.588, respectively) and similar incidence of major cardiac adverse events (2.7% versus 3.2%, P=0.772). Use of intravascular imaging was associated with longer procedure (192 minutes [interquartile range 130, 255] versus 131 minutes [90, 192], P<0.0001) and fluoroscopy (71 minutes [44, 93] versus 39 minutes [25, 69], P<0.0001) time. Conclusions: Intravascular imaging is frequently performed during CTO percutaneous coronary intervention both for crossing and for stent selection/optimization. Despite its use in more complex lesion subsets, intravascular imaging was associated with similar rates of technical and procedural success for CTO percutaneous coronary intervention. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02061436

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions