Endoscopic ultrasound- versus ERCP-guided primary drainage of inoperable malignant distal biliary obstruction: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: We assessed efficacy and safety of endoscopic ultrasound-guided biliary drainage (EUS-BD) vs. endoscopic retrograde cholangiopancreatography (ERCP) as first-line intervention in malignant distal biliary obstruction (MDBO). METHODS: PubMed/Medline, Embase, and Cochrane databases were searched until 01 /12 /2023 for randomized controlled trials of EUS-BD vs. ERCP for primary biliary drainage in patients with inoperable MDBO. The primary outcome was technical success. Secondary outcomes were clinical success, adverse events, mean procedure time, 1-year stent patency, and overall survival. Relative risk (RR) with 95 %CI were calculated using a random effects model. RESULTS: Five studies (519 patients) were included. RR (95 %CI) for EUS-BD was 1.06 (0.96 to 1.17; P = 0.27) for pooled technical success and 1.02 (0.97 to 1.08; P = 0.45) for clinical success. 1-year stent patency was similar between the groups (RR 1.15, 0.94 to 1.42; P = 0.17), with lower reintervention with EUS-BD (RR 0.58, 0.37 to 0.9; P = 0.01). The RR was 0.85 (0.49 to 1.46; P = 0.55) for adverse events and 0.97 (0.10 to 0.17; P = 0.98) for severe adverse events. On subgroup analysis, EUS-guided placement of lumen-apposing metal stent (LAMS) outperformed ERCP in terms of technical success (RR 1.17, 1.01 to 1.35; P = 0.03). Procedure time was lower with EUS-BD (standardized mean difference -2.36 minutes [-2.68 to -2.05; P < 0.001]). CONCLUSIONS: EUS-BD showed a statistically significant lower reintervention rate than ERCP, but with similar technical success, stent patency, clinical success, and safety. Technical success of EUS-BD with LAMS was better than ERCP.

Predictors of spontaneous passage of ingested foreign bodies in adults: twelve years of experience.

BACKGROUND: Foreign body ingestion in adults is commonly encountered in clinical practice. The therapeutic approach of whether to follow-up or extract is often controversial. AIM: We aimed to explore predictors for spontaneous passage of ingested foreign bodies by focusing on foreign body type, length, and location of impaction. METHODS: We performed a 12-year retrospective single-center study. Logistic regression analysis was done to identify predictors of spontaneous passage. RESULTS: Overall, 365 patients with foreign body ingestion were included. The rate of spontaneous passage was 53.7% in general, while the spontaneous passage rate was 47.9% in food impaction, 44.3% in sharp objects, 88.7% in blunt objects and only 22.2% in long blunt objects (> 6 cm). On regression analysis, esophageal location was associated with a higher impaction rate and lower spontaneous passage vs. stomach and small and large intestine (OR 0.15, 95% CI 0.07-0.31, OR 0.18, 95% CI 0.09-0.37 and OR 0.02, 95% CI 0.003-0.14), respectively. Performing Receiver operating characteristics (ROC) analysis found that the maximal length above which the foreign body will fail to pass spontaneously was 3.5 cm in the stomach and 3 cm in the small intestine, with area under the curve (AUC) of 0.8509 in stomach and 0.8073 in small intestine. CONCLUSION: Endoscopic removal was needed for all esophageal foreign bodies, and all foreign bodies more than 3.5 cm above the duodenum. Spontaneous passage of ingested foreign body in a selected cohort of patients depends on foreign body type, location, and length.

Olive Oil's Attenuating Effects on Lipotoxicity.

Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.

Cytokine Patterns in COVID-19 Patients: Which Cytokines Predict Mortality and Which Protect Against?

(1) Background/Aim: People infected with SARS-CoV-2 may develop COVID-19 in a wide range of clinical severity. Pulmonary fibrosis is characterized by several grades of chronic inflammation and collagen deposition in the interalveolar space. SARS-CoV-2 infection has been demonstrated to cause lung fibrosis without a currently elucidated mechanism. Some studies emphasize the role of proinflammatory cytokines. This research studies the correlation of the released cytokines with mortality or lung injury in COVID-19 patients. (2) Methods: Electronic medical record data from 40 patients diagnosed with COVID-19 in the COVID-19 Department, Galilee Medical Center, Nahariya, Israel, were collected. Epidemiological, clinical, laboratory, and imaging variables were analyzed. The cytokine levels were measured upon admission and discharge. A correlation between cytokine levels and severity and mortality or lung involvement was undertaken. (3) Results: IFN-gamma and IL-10 are the most powerful risk factors for mortality in the COVID-19 patient groups in a multivariate analysis. However, in a univariate analysis, TGF-ß, CXCL-10, IFN gamma, and IL-7 affected mortality in COVID-19 patients. MMP-7 was significantly correlated with a cytokine storm and a high 4-C (severity) score in COVID-19 patients. MMP-7, TGF-ß, IL-10, IL-7, TNF-α, and IL-6 were correlated with high lung involvement in COVID-19 patients. Serum concentrations of IGF-1 were significantly increased upon discharge, but MMP-7 was decreased. (4) Conclusions: Proinflammatory cytokines predict clinical severity, lung fibrosis, and mortality in COVID-19 patients. High concentrations of TGF-ß, CXCL-10, IL-10, IL-6, and TNF-α are correlated to severity and lung injury. However, certain cytokines have protective effects and higher levels of these cytokines increase survival levels and lower lung damage. High levels of INF-γ, IL-7, MMP-7, and IGF-1 have protection probabilities against lung injury and severity.

Regen-COV-2 Antibody Cocktail Mediated Clearance of SARS-COV-2 in an Immunocompromised Patient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) affects different people in different ways. Most infected people develop mild to moderate illness and recover without hospitalization. This case report presents a patient who had difficulty eradicating the corona virus due to being treated with rituximab, which depletes B lymphocytes and therefore disables the production of neutralizing antibodies. The regen-COV-2 antibody cocktail consists of two monoclonal antibodies, casirivimab and imdevimab. This cocktail successfully helped the patient's immune system eradicate the virus without auto specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production. In vitro studies confirm that eradication of the intact the virus. This case report emphases the importance of providing external antiviral antibodies regularly, like the regen-COV-2 antibody cocktail, as post- and even pre- SARS-CoV-2 infection prophylaxis in patients treated with rituximab.

Clearance of the SARS-CoV-2 Virus in an Immunocompromised Patient Mediated by Convalescent Plasma without B-Cell Recovery.

Coronavirus disease (COVID-19) is a contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This case report presents a patient who had difficulty eradicating the corona virus due to being treated with Rituximab, which depletes B lymphocyte cells and therefore disables the production of neutralizing antibodies. The combined use of external anti-viral agents like convalescent plasma, IVIG and Remdesivir successfully helped the patient's immune system to eradicate the virus without B-cell population recovery. In vitro studies showed that convalescent plasma is the main agent that helped in eradicating the virus.

Isolation and expansion of high yield of pure mesenchymal stromal cells from fresh and cryopreserved placental tissues.

The injection of placental stromal cells isolated from fetal human tissues (f-hPSC) was reported to indirectly induce tissue regeneration in different animal models. A procedure of f-hPSC isolation from fragments of both selected fresh or cryopreserved bulk placental neonate tissues is proposed, based on their high migratory potential,. The fragments of the desired fetal placental tissues are adhered to a culture dish by traces of diluted fibrin and covered with culture medium. Spontaneous migration of pure f-hPSC from the tissue fragments to the cell culture dishes is followed by their rapid expansion by numerous passages. The isolated f-hPSC express typical mesenchymal surface antigens, including CD29, CD105, CD166 and CD146, with negative expression of white blood cell lineage and endothelial cells markers. Optimal yields of f-hPSC cultures can also be obtained from tissue samples cryopreserved in medium composed of 10% dimethyl sulfoxide (M2SO) and 50% fetal calf serum. Slightly better yields are obtained with media supplemented with 1% human albumin. Medium with 5% M2SO and/or 0.25 mg/ml PEG yielded inferior results. The f-hPSC from fresh or cryopreserved tissues express similar cell markers and growth kinetics. The proposed isolation protocol may also be applied for high yield isolation of stromal cells from fresh and cryopreserved tissue of other organs.

The hemodynamic response to constant dobutamine infusion: the effect of ADRB1 389 polymorphism and sex.

OBJECTIVES: Prolonged activation of the ß-1 adrenergic receptor (ADRB1) is associated with receptor desensitization. This process has been suggested to have important pathophysiological and clinical implications in conditions such as congestive heart failure. The contribution of genetic factors to this process is a subject of ongoing research. We have previously shown that the ADRB1 389 polymorphism affects the response to incremental dose infusion of the ADRB agonist dobutamine. The aim of the current study was to determine whether the ADRB1 389 polymorphism affects the hemodynamic response to constant dose infusion of dobutamine in healthy patients. PATIENTS AND METHODS: Healthy patients were recruited according to their ADRB1 49 and 389 genotypes [15 Arg389Arg, 10 Gly389Arg, and 10 Gly389Gly patients (all Ser49Ser), 21 men and 14 women]. Following a standardized protocol of dose increase, 6 mcg/kg/min dobutamine was infused over 2 h. Heart rate (HR), blood pressure (BP), and active plasma renin (PR) were measured. Standardized exercise (1 min) was performed at three time points during infusion. RESULTS: In all patients, resting systolic BP was significantly decreased during infusion [144.4±11.5 vs. 140.3±12.2 mmHg (mean±SD), P=0.007]. There was no change in HR, and PR following 120 min of dobutamine infusion. ADRB1 389 genotypes were not associated with HR, systolic BP, and PR changes during dobutamine infusion (all P>0.05, repeated measures analysis of variance). Sex was associated with response to dobutamine. Among women, but not in men, resting HR significantly increased, and diastolic blood pressure (DBP) significantly decreased during dobutamine infusion [HR: 76.0±7.3 to 86.3±17.5 beats per minute (P=0.023), and DBP 78.5±8.49 mmHg to 72.36±6.16 (P=0.041) (repeated measures analysis of variance)]. CONCLUSION: In healthy patients, the ADRB1 389 genotype was not associated with hemodynamic changes during constant dobutamine infusion. In women, but not in men, HR significantly increased and DBP decreased during 2 h of infusion.

Effects of sex and the common ADRB1 389 genetic polymorphism on the hemodynamic response to dobutamine.

INTRODUCTION: The ADRB1 389 polymorphism affects responses to the ß-1 adrenergic receptor (ß1AR) agonist in vitro. Previous studies on its effect on the response to dobutamine stress echocardiography were conflicting. In addition, sex differences in the response to dobutamine have been suggested. The aim of this study was to determine whether the ADRB1 389 polymorphism affects the hemodynamic response to dobutamine in healthy individuals including men and women. PARTICIPANTS AND METHODS: Healthy individuals were recruited according to their ADRB1 49 and 389 genotypes [15 Arg389Arg, 10 Gly389Arg, and 10 Gly389Gly individuals, (all Ser49Ser), 21 men and 14 women]. Dobutamine was infused at 2, 4, and 6 mcg/kg/min. Standardized exercise was performed during the last minute of each infusion. RESULTS: Resting heart rate (HR) response to 6 mcg/kg/min dobutamine (ΔHR) was 4.7-fold larger in Arg389Arg than in Gly389Gly [(mean ± SD) 12.95 ± 6.99, 2.75 ± 1.65 bpm, respectively, PANOVA=0.012]. Renin response to dobutamine (ΔRenin) was 3.9-fold greater in Arg389Arg than in Gly389Gly (PANOVA=0.032). Among Arg389Gly heterozygotes, ΔHR and ΔRenin were not significantly different from either homozygote group. In multivariate analysis for ΔHR variance, significant contributions were observed for genotype (P=0.011), baseline HR (P=0.011), and borderline effect for sex (P=0.049). CONCLUSION: In healthy individuals, HR and renin responses to dobutamine were more than three-fold greater among ADRB1 Arg389 compared with Gly389 homozygotes. Future studies on the effect of the ADRB1 389 polymorphism on dobutamine stress echocardiography should compare Arg389 and Gly389 homozygotes.

Yield of alarm features in predicting significant endoscopic findings among hospitalized patients with dyspepsia.

BACKGROUND: Dyspepsia is a very prevalent upper gastrointestinal tract symptoms complex. Some of these symptoms might arise from serious underlying diseases, so the promotion of evidence-based guidelines could potentially better align evaluation and treatment. AIM: To determine the value of alarm features as a predictive factor for significant endoscopic findings (SEFs) among hospitalized patients presenting with dyspepsia. METHODS: We conducted a retrospective case-control study including information about 6208 endoscopic procedures performed for hospitalized patients. Patients were divided into two groups, with and without SEFs, and compared to elucidate the ability of the different alarm features to predict SEFs. RESULTS: During the study, 605 patients fulfilled the inclusion criteria. When the demographics and clinical characteristics of the two groups were compared, tachycardia (P < 0.05), normocytic anemia, (P < 0.05), leukocytosis (P < 0.05), and hypoalbuminemia (P < 0.05) documented on admission prior to endoscopy were strong predictors of SEFs. Among the alarm features, upper gastrointestinal bleeding, persistent vomiting, odynophagia [odds ratio (OR) = 3.81, P < 0.05; OR = 1.75, P = 0.03; and OR = 7.81, P = 0.07, respectively] were associated with SEFs. Unexplained weight loss was strongly associated with malignancy as an endoscopic finding (OR = 2.05; P < 0.05). In addition, long-term use of anti-aggregate medications other than aspirin (P < 0.05) was correlated to SEFs. CONCLUSION: Novel predictors of SEFs were elucidated in this study. These parameters could be used as an adjunctive in decision making regarding performing upper endoscopy in hospitalized patients with dyspepsia.