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Background and aims Endoscopic enteral stenting (ES) in malignant gastric outlet obstruction (GOO) is limited by high rates of stent obstruction. EUS-guided gastroenterostomy (EUS-GE) is a novel procedure that potentially offers sustained patency without tumor ingrowth/overgrowth. The aim of this study is to compare EUS-GE with ES in terms of (1) symptom recurrence and need for re-intervention, (2) technical success (proper stent positioning as determined via endoscopy and fluoroscopy), (3) clinical success (ability to tolerate oral intake without vomiting), and (4) procedure-related adverse events (AEs). Methods Multicenter retrospective study of all consecutive patients who underwent either EUS-GE at four centers between 2013 and 2015 or ES at one center between 2008 and 2010. Results A total of 82 patients (mean age 66-years ± 13.5 and 40.2% female) were identified: 30 in EUS-GE and 52 in ES. Technical and clinical success was not significantly different: 86.7% EUS-GE versus 94.2% ES ( p  = 0.2) and 83.3% EUS-GE versus 67.3% ES ( p  = 0.12), respectively. Symptom recurrence and need for re-intervention, however, was significantly lower in the EUS-GE group (4.0 vs. 28.6%, ( p  = 0.015). Post-procedure mean length of hospitalization was comparable at 11.3 days ± 6.6 for EUS-GE versus 9.5 days ± 8.3 for ES ( p  = 0.3). Rates and severity of AEs (as per the ASGE lexicon) were also similar (16.7 vs. 11.5%, p  = 0.5). On multivariable analysis, ES was independently associated with need for re-intervention (OR 12.8, p  = 0.027). Conclusion EUS-GE may be ideal for malignant GOO with comparable effectiveness and safety to ES while being associated with fewer symptom recurrence and requirements for re-intervention.

Background and aims Endoscopic placement of enteral self-expandable metallic stents is an alternative to surgical gastrojejunostomy (GJ) for palliation of malignant gastric outlet obstruction (GOO). Factors associated with clinical outcomes are not known. The aims of this study are to compare the overall complication rate and effectiveness (duration of oral intake) between endoscopic stenting (ES) and GJ in patients with GOO and identify predictors of clinical outcomes. Patients and methods This was a retrospective cohort study at a single tertiary academic center. Patients who underwent ES or GJ for treatment of GOO between 1/2001 and 12/2010 were identified using an institutional claims database. The electronic medical records for each patient were reviewed. Univariate and multivariate logistic regression analyses were performed to study the association of treatment outcomes with patient factors and cancer therapy. Results 120 patients had ES while 227 had GJ. Technical success was higher for GJ (99 vs. 96 %, p  = 0.004). Complication rates were higher in the GJ group (22.10 vs. 11.66 %, p  = 0.02). Reintervention was more common with ES [adjusted odds ratio (OR) 9.18, p  < 0.0001]. Mean length of hospital stay (LOHS) was shorter (adjusted p  = 0.005) in the ES compared with the GJ group. However, mean hospital charges, including reinterventions, were greater in the ES group (US $34,250 vs. US $27,599, p  = 0.03). ES and GJ had comparable reintervention-free time in patients who had reintervention (88 vs. 106 days, respectively, p  = 0.79). Chemotherapy [adjusted hazard ratio (HR) 3 > 0.57, p  = 0.04] and radiation therapy (adjusted HR 0.35, p  = 0.03) were associated with significantly longer duration of oral intake after ES or GJ. Conclusion ES is associated with fewer complications, shorter LOHS, but higher reintervention rates and overall charges.

Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment. ClinicalTrials.gov NCT01724580 and NCT02974595. This research was supported by the Intramural Research Program of the NIH, NIAID, and NIAMS. Baricitinib was provided by Eli Lilly and Company, which is the sponsor of the expanded access program for this drug.

Cardiovascular diseases (CVDs) are classed as diseases of aging, which are associated with an increased prevalence of atherosclerotic lesion formation caused by such diseases and is considered as one of the leading causes of death globally, representing a severe health crisis affecting the heart and blood vessels. Atherosclerosis is described as a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease and to date, most pharmacological therapies mainly aim to control risk factors in patients with cardiovascular disease. Advances in transformative therapies and imaging diagnostics agents could shape the clinical applications of such approaches, including nanomedicine, biomaterials, immunotherapy, cell therapy, and gene therapy, which are emerging and likely to significantly impact CVD management in the coming decade. This review summarizes the current anti-atherosclerotic therapies’ major milestones, strengths, and limitations. It provides an overview of the recent discoveries and emerging technologies in nanomedicine, cell therapy, and gene and immune therapeutics that can revolutionize CVD clinical practice by steering it toward precision medicine. CVD-related clinical trials and promising pre-clinical strategies that would significantly impact patients with CVD are discussed. Here, we review these recent advances, highlighting key clinical opportunities in the rapidly emerging field of CVD medicine.

ObjectivesThis study aims to compare the clinical manifestations, laboratory findings, outcomes and overall survival time of patients with COVID-19 with and without comorbidities.DesignRetrospective design.SettingThis study was undertaken at two hospitals in Damascus.ParticipantsA total of 515 Syrian patients met the inclusion criterion, laboratory-confirmed COVID-19 infection following the Centers for Disease Control and Prevention. Exclusion criteria were suspected and probable cases that were not confirmed with a positive reverse transcription-PCR assay, and patients who self-discharged from the hospital against medical advice.Primary and secondary outcome measuresFirst, assess the impacts of comorbidities on COVID-19 infection in four areas (clinical manifestations, laboratory findings, severity and outcomes). Second, calculate the overall survival time for patients with COVID-19 with comorbidities.ResultsOf 515 patients included, 316 (61.4%) were male and 347 (67.4%) had at least one coexisting chronic disease. Patients with comorbidities compared with no comorbidities were more vulnerable to poor outcomes such as severe infection (32.0% vs 9.5%, p<0.001), severe complications (34.6% vs 9.5%, p<0.001), the need for mechanical ventilation (28.8% vs 7.7%, p<0.001) and death (32.0% vs 8.3%, p<0.001). Multiple logistic regression showed that age ≥65 years old, positive smoking history, having ≥2 comorbidities and chronic obstructive pulmonary disease were risk factors linked to severe COVID-19 infection in patients with comorbidities. Overall survival time was lower among patients with comorbidities (vs no comorbidities), patients with ≥2 comorbidities (vs one comorbidity), and patients with hypertension, chronic obstructive pulmonary disease, malignancy or obesity (vs other comorbidities) (p<0.05).ConclusionThis study revealed that COVID-19 infection had poor outcomes among those with comorbidities. Severe complications, mechanical ventilation usage and death were more prevalent among patients with comorbidities compared with those with no comorbidities.

Panton‐Valentine leucocidin toxin‐producing methicillin‐resistant staphylococcus aureus is an important uncommon cause of community‐acquired pneumonia; we describe a case of necrotizing pneumonia presenting as respiratory failure necessitating early initiation of extracorporeal membrane oxygenation, acute kidney injury and rhabdomyolysis, awareness, prompt recognition and appropriate management are crucial due to possible significant pathology. PVL‐toxin‐producing staphylococcal aureus necrotizing pneumonia should be suspected in previously healthy individuals presenting with severe community‐acquired pneumonia with multiorgan dysfunctions including respiratory failure and rhabdomyolysis.