Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.

BACKGROUND: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. MATERIAL AND METHODS: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. RESULTS: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. CONCLUSIONS: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Tobacco Use, Quitting, and Service Access for Northern California Arab Americans: A Participatory Study.

BACKGROUND: Cigarette smoking rates have decreased in the United States, particularly in California. Despite representing a large population in the United States and particularly in California, Arab Americans are not typically assessed in tobacco-related health studies. Disparately high smoking rates have been found in community samples of Arab Americans. In a formative participatory research study, we aimed to assess experiences with tobacco products and access to cessation and prevention services for Arab Americans who use commercial tobacco products. METHODS: In partnership with a community advisory board, we conducted a brief survey of adult Northern California Arab Americans who use tobacco products, both men and women (n = 101), followed by assets mapping to identify services, and focus groups with a subset of survey participants (n = 30), to assess tobacco product use, readiness to quit, and access to culturally appropriate cessation services. RESULTS: The majority of people who smoked did so daily. Waterpipe use was as common as cigarette smoking, and more so for women. Intent to quit was offset by highly normative tobacco use in the social environment, and limited access to culturally appropriate cessation services. CONCLUSIONS: Improvement in outreach and services specific to Arab Americans may support prevention and cessation of commercial tobacco products.

Comparing the Efficacy of Local Corticosteroid Injection, Platelet-Rich Plasma, and Extracorporeal Shockwave Therapy in the Treatment of Pes Anserine Bursitis: A Prospective, Randomized, Comparative Study.

Background: Pes anserine bursitis (PAB) is one of the most common causes of painful knee syndromes. This study aimed at examining the efficacy of local corticosteroid injection, platelet-rich plasma (PRP) injection, and extracorporeal shock wave therapy (ESWT) as different modalities to alleviate pain and enhance function in patients with pes anserine bursitis (PAB). Methods: A prospective, randomized, comparative study was conducted on 180 patients diagnosed with chronic PAB. They were equally divided into three groups as follows: Group I received a local corticosteroid injection of 40 mg of methylprednisolone acetate/1 ml; Group II received a PRP injection; and in Group III, ESWT was used. Outcome measures included the visual analog scale (VAS), Western Ontario and McMaster Universities (WOMAC) pain score, WOMAC physical function score, and Ritchie articular index (RAI) for tenderness, which were recorded at the baseline, after 1 week, and after 8 weeks. Results: Before the application of procedures, there was a statistically significant increase in the WOMAC pain score in the local corticosteroid group compared to the PRP group and the ESWT group (P < 0.001). After the application of procedures, there was a statistically significant improvement in the 1-week and 8-week WOMAC pain score, WOMAC physical function score, and VAS in the local corticosteroid group in comparison to the PRP group and the ESWT group. (P < 0.001). Moreover, RAI for tenderness shows statistically significant improvement at 8 weeks in the local corticosteroid groups compared to the PRP groups (P < 0.001) and ESWT groups (P < 0.001). Similarly, a statistically significant difference was found between the PRP and ESWT groups (P=0.023). Conclusion: Our data suggest that in patients with PAB, local corticosteroid injection is more efficient than PRP injection and ESWT for reducing pain and enhancing function.

Peripartum veno-venous extracorporeal membrane oxygenation in patients with severe CoViD-19-related-ARDS.

We describe a case series of five pregnant or postpartum women with severe CoViD-19-related ARDS requiring VV ECMO at our centre between Jan 1 and Sep 30, 2021. All patients were cannulated at the referring hospitals by our team before transferring to our centre. None of the women were vaccinated against CoViD-19. All had severe ARDS with Murray's Lung Injury Score of 3-4 and met the severity threshold for ECMO initiation that was used in the EOLIA study. All patients were discharged alive to home, acute rehabilitation, or lung transplant centre. One patient suffered intrauterine death before ECMO initiation and another while on ECMO. VV ECMO for refractory CoViD-19 related ARDS in the peripartum period is safe, and in this small series, it was associated with good maternal survival rates.

The Value of Combining Carbon Dioxide Gap and Oxygen-Derived Variables with Lactate Clearance in Predicting Mortality after Resuscitation of Septic Shock Patients.

BACKGROUND: Achieving hemodynamic stabilization does not prevent progressive tissue hypoperfusion and organ dysfunction during resuscitation of septic shock patients. Many indicators have been proposed to judge the optimization of oxygen delivery to meet tissue oxygen consumption. METHODS: A prospective observational study was conducted to evaluate and validate combining CO2 gap and oxygen-derived variables with lactate clearance during early hours of resuscitation of adults presenting with septic shock. RESULTS: Our study included 456 adults with a mean age of 63.2 ± 6.9 years, with 71.9% being males. Respiratory and urinary infections were the origin of about 75% of sepsis. Mortality occurred in 164 (35.9%) patients. The APACHE II score was 18.2 ± 3.7 versus 34.3 ± 6.8 (p < 0.001), the initial SOFA score was 5.8 ± 3.1 versus 7.3 ± 1.4 (p=0.001), while the SOFA score after 48 hours was 4.2 ± 1.8 versus 9.4 ± 3.1 (p < 0.001) in the survivors and nonsurvivors, respectively. Hospital mortality was independently predicted by hyperlactatemia (OR: 2.47; 95% CI: 1.63-6.82, p=0.004), PvaCO2 gap (OR: 2.62; 95% CI: 1.28-6.74, p=0.026), PvaCO2/CavO2 ratio (OR: 2.16; 95% CI: 1.49-5.74, p=0.006), and increased SOFA score after 48 hours of admission (OR: 1.86; 95% CI: 1.36-8.13, p=0.02). A blood lactate cutoff of 40 mg/dl at the 6th hour of resuscitation (T6) had a 92.7% sensitivity and 75.3% specificity for predicting hospital mortality (AUROC = 0.902) with 81.6% accuracy. Combining the lactate cutoff of 40 mg/dl and PvaCO2/CavO2 ratio cutoff of 1.4 increased the specificity to 93.2% with a sensitivity of 75.6% in predicting mortality and with 86.8% accuracy. Combining the lactate cutoff of 40 mg/dl and PvaCO2 gap of 6 mmHg increased the sensitivity to 93% and increased the specificity to 98% in predicting mortality with 91% accuracy. CONCLUSION: Combining the carbon dioxide gap and arteriovenous oxygen difference with lactate clearance during early hours of resuscitation of septic shock patients helps to predict hospital mortality more accurately.

Price and volatility spillovers between global equity, gold, and energy markets prior to and during the COVID-19 pandemic.

This study sets out to provide fresh evidence on the dynamic interrelationships, at both return and volatility levels, between global equity, gold, and energy markets prior to and during the outbreak of the novel coronavirus. We undertake our analysis within a bivariate GARCH(p, q) framework, after orthogonalizing raw returns with respect to a rich set of relevant universal factors. Under the COVID-19 regime, we find bidirectional return spillover effects between equity and gold markets, and unidirectional mean spillovers from energy markets to the equity and gold counterparts. The results also suggest the presence of large reciprocal shock spillovers between equity and both of energy and gold markets, and cross-shock spillovers from energy to gold markets. Most probably driven by the recent oil price collapse, energy markets appear to have a substantial cross-volatility spillover impact on the others. Our results offer implications for policymakers and investors.

Bilateral subdural hygromas after endovascular coiling for ruptured aneurysmal subarachnoid hemorrhage: an unusual and rare complication.

Subarachnoid hemorrhage (SAH) with subdural hygroma (SH) was rarely reported after endovascular coiling. A 60-year-old male presented with impaired consciousness and convulsions due to SAH from a ruptured aneurysm. It was managed by endovascular coiling 20 h after the onset of symptoms. Serial brain imaging for 2 weeks revealed progressive bilateral SHs, more on contralateral side of leaking aneurysm. Management of SH was discussed in a multidisciplinary setting to be conservative as there was neither significant mass effect nor hydrocephalus. The patient recovered neurologically except for mild dysarthria. The SH persisted for 2 months and then cleared gradually. We concluded that SH may arise and become symptomatic as an unusual sequela of post-coiling of a ruptured intracranial aneurysm, in which the SH can complicate the clinical course of SAH. However, the symptomatic SH may resolve spontaneously and completely without any intervention, but needs meticulous neurological assessment and follow-up.

Validation of a Non-Laboratory Based Screening Tool for Predicting Non-Alcoholic Fatty Liver Disease in an Egyptian Setting.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disorder in more than 20% of the general population worldwide.  Several combinations of non-invasive factors and scoring models were investigated as indicators of NAFLD. This study aimed to validate and adapt an established fatty liver score, which allows the identification of NAFLD based on routinely available clinical and laboratory data. MATERIALS AND METHODS: The study cohort comprised 190 adults seeking health check-up at the out-patient clinic of a tertiary care hospital in Alexandria, Egypt. Anthropometric, clinical, and laboratory data were recorded and the status of fatty liver was diagnosed by abdominal ultrasound. A logistic regression model was built to determine the predictors of NAFLD. The performance of the derived risk scores was compared to other existing models. RESULTS: Obesity (60.0%), metabolic syndrome (42.6%), and NAFLD (56.8%) were predominant features among the study population. Smoking [OR (95% CI) = 4.4 (0.9-21.4)], obesity [OR (95% CI) = 4.0 (1.7-9.7)], hypertension [OR (95% CI) = 2.4 (1.03-5.5)], elevated serum total cholesterol [OR (95% CI) = 4.8 (1.8-13.1)], triglycerides [OR (95% CI) = 11.8 (2.3-661.02)], and ALT [OR (95% CI) = 4.8 (1.8-13.1)] were multivariate predictors of NAFLD. A NAFLD screening questionnaire with values applicable for Egyptians was adapted from an existing model after validation. A total score ≥7 was suggestive of NAFLD [AUC = 0.810 (0.749-0.871); sensitivity = 87.0%; specificity = 62.2%; PPV = 75.2%; NPV = 78.5%]. CONCLUSIONS: NAFLD can be sufficiently predicted among apparently healthy Egyptians by a tempted simple and non-invasive scoring index although external validation is warranted.

Acute neurological complications in adult patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation support.

BACKGROUND: Extracorporeal life support has markedly progressed over the recent years to support patients with severe cardiac and pulmonary dysfunction refractory to conventional management. Many patients developed acute neurological complications while being supported with extracorporeal membrane oxygenation (ECMO). Our objectives were to study the frequencies and outcomes of CNS complications in adult patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and to study the risk factors of these CNS complications. We conducted a retrospective study including adult patients admitted to the cardiac critical care unit with cardiopulmonary instability and supported with VA-ECMO from January 2016 until December 2018 in a tertiary care hospital. RESULTS: After reviewing 231 patients with ECMO, 67 patients with cardiogenic shock supported with VA-ECMO were included. About 65.7% of the studied patients were supported after cardiothoracic surgeries. About 56.7% of the patients developed acute CNS events. According to brain CT imaging, ischaemic stroke was diagnosed in 14.9% and intracerebral haemorrhage (ICH) was diagnosed in 11.9% of patients while 16.4% of patients with CNS events had negative brain CT imaging. The SOFA score was significantly higher in the group with CNS events at ICU admission and after 48 hours . As compared to patients with ischaemic strokes, patients with ICH were younger with lesser BMI, had higher SOFA scores at admission and at 48 hours of ICU admission, had longer cardiopulmonary bypass and aortic cross clamping times and had more support with central than peripheral VA-ECMO. AF was more frequent in the group with CNS events especially in the ischaemic stroke subgroup. Presence of intracardiac thrombi was more frequent in the ischaemic stroke subgroup. There was no statistically significant difference between both groups regarding ECMO circuit thrombi. The use of IABP and presence of DM were more frequent in the ischaemic stroke subgroup. Patients with neurological events had hypoalbuminaemia and higher blood glucose and serum creatinine levels compared to those without CNS events. The peak lactate level and lactate after 24 hours of ECMO support were significantly higher in those with CNS events. Patients with ICH had significant thrombocytopenia and higher INR with more prolonged aPTT and PTT ratio than those with ischaemic stroke. Patients with neurological events had significant hospital mortality, more mechanical ventilation days and tracheostomy, AKI and haemodialysis compared to those without CNS events, but there were no significant differences between both groups regarding ECMO duration, ICU or post ICU stays nor 1 year mortality. CONCLUSION: Acute neurological events are frequent in patients supported with VA-ECMO and associated with significant morbidity and hospital mortality. As compared to ischaemic stroke, ICH is more frequent in younger patients with lesser BMI, central VA-ECMO after cardiothoracic surgeries, thrombocytopenia, and coagulopathy. Our findings may have major implications for the care of patients requiring VA-ECMO.

Incidence and predictors of radial artery occlusion after transradial coronary catheterization.

BACKGROUND: Radial artery occlusion (RAO) is considered the most common and devastating complication of transradial approach (TRA). It has been described as the "Achilles' heel" of the transradial technique. Our aim was to assess the incidence and predictors of radial artery occlusion after transradial coronary catheterization. RESULTS: This was a prospective study enrolling 164 patients undergoing percutaneous coronary interventions (PCI) via the transradial approach (TRA) using 6-F catheters. Doppler ultrasonography assessment of the radial artery (RA) was conducted on day 1 and 6 months following the procedure. The studied group included 104 male (63.4%) and 60 female (36.6%) patients with a mean age of 57.7 ± 8.8 years and a mean RA diameter of 2.8 ± 0.5 mm. On day 1, Doppler examination revealed RAO in 54 patients (32.9%). After 6 months, RAO was detected in 49 patients (29.9%). Interestingly, only 1 new case (0.9%) of RAO was noted, and 6 patients (11.1%) had regained their RA patency. On multivariate analysis, female gender, age, manual compression, and RA diameter emerged as independent predictors of RAO. Using TR band for hemostasis for only 2 h was recognized as a potent independent predictor of RA patency on day 1 and 6 months after the procedure (n = 2, 3.7% in the RAO group, vs. n = 23, 20.9% in the non-RAO group, p = 0.004). CONCLUSION: RAO, although clinically a silent issue, has been the main complication following TRA. In patients with high predictors of RAO, careful management and close follow-up are required to ensure radial artery long-term patency.

Left ventricular scar impact on left ventricular synchronization parameters and outcomes of cardiac resynchronization therapy.

BACKGROUND: Left ventricular scar, including global scar and lateral wall, plays an important role in predicting response to cardiac resynchronization therapy (CRT). MATERIALS AND METHODS: Thirty patients underwent CRT implantation. Assessment of left ventricular (LV) dyssynchrony was done through Gated SPECT LV phase analysis. Pre-implantation cardiac magnetic resonance (CMR) with late gadolinium enhancement technique to examine LV scar burden. Echocardiographic examination of LV end-systolic volume (LVES) prior to CRT and 6 months later. RESULTS: Thirty patients received CRT (mean age 58.7±9.0, 24 males). Reverse LV remodeling (decline ≥15% from baseline VES) was documented in 19 patients. Temporal changes in LV dyssynchrony parameters were correlated to LV reverse remodeling. Applying ROC for predicting CRT non-response showed a cutoff 36.5% of global LV scar burden had a sensitivity of 81.8% and specificity of 68.4%. A cutoff for lateral wall scar burden 40.5% of whole lateral wall had a sensitivity of 72.7% and specificity of 68.4%. CONCLUSION: Reverse LV remodeling is associated with temporal improvements in LV dyssynchrony parameters. LV scar had an unfavorable impact on CRT response. Both global and lateral wall scar burden could predict CRT nonresponse status.

Long-term mortality of patients surviving firearm violence.

OBJECTIVE: We aim to calculate the 5-year mortality after surviving to hospital discharge after a firearm injury and estimate the association of firearm injury with later mortality. METHODS: We performed a retrospective cohort study of patients from an urban emergency department (ED) and trauma centre in Oakland, California, USA, in 2007. We created three cohorts of patients presenting for (1) gunshot wound (GSW), (2) MVC and (3) assault without a firearm. Demographic and clinical information was obtained from the clinical chart, and the California Department of Public Health Vital Statistics and Social Security Death Master File (2007-2012) were queried to identify patients who died. RESULTS: We analysed 516 GSW patients, 992 MVC patients and 695 non-GSW assault patients. Of the GSW patients, 86.4% were alive at 5 years. All-cause 5-year mortality among GSW victims surviving to discharge after injury was 5.1%. Compared with MVC patients, both GSW and non-GSW assault patients have higher risk of death at 5 years (HR 2.54 (95% CI 1.41 to 4.59) and HR 1.64 (95% CI 1.01 to 2.68), respectively), adjusting for age, sex and race. Risk of death was higher in the first year for the GSW cohort (HR 6.14 (95% CI 2.35 to 16.08) and HR 5.06 (95% CI 1.88 to 13.63) as compared with MVC and non-GSW assault cohorts, respectively). Homicide was the cause of death in 79.2% of GSW patients who died after surviving the index injury. CONCLUSION: Among individuals presenting to the ED after injury or assault and surviving to discharge, firearm injury exposure is an important predictor of death within 5 years and most pronounced in the first year after injury.

Effect of galantamine on adjuvant-induced arthritis in rats.

Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF-α, IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis.