Enhancement of Streptomyces thinghirensis WAE1 for production of bioactive metabolites under different optimization strategies.

Isolation of novel bioactive metabolites from Streptomyces strains is a promising source for drug discovery. However, conventional screening approaches have limitations in identifying new leads due to redundant discoveries. Optimization of culture conditions is important but traditionally optimized one factor at a time, failing to consider interactions. This study addressed these gaps by enhancing metabolite production from Streptomyces thinghirensis WAE1 through statistical optimization. Various chemical and physical factors impacting metabolite production were identified. Response surface methodology with a central composite design was applied to optimize significant factors like carbon source, nitrogen source, inoculum size, pH, temperature and incubation period. This optimized production against Streptococcus pneumoniae, increasing antibacterial activity by 74.92%. Gas chromatography-mass spectrometry revealed 19 bioactive compounds, including 1,25-dihydroxyvitamin D3 inhibiting cell wall development. This highlights S. thinghirensis WAE1's potential as a bioresource and emphasizes studying metabolite production from novel Streptomyces strains to discover new antibacterial drugs.

Magnetic resonance imaging of pilonidal sinus disease: interobserver agreement and practical MRI reporting tips.

OBJECTIVE: To evaluate the interobserver agreement for the features of natal cleft pilonidal sinus disease (PSD) on magnetic resonance imaging (MRI) and propose a standardized checklist for reporting PSD on MRI. MATERIALS AND METHODS: Forty MRI studies of 39 discrete patients with PSD were retrospectively evaluated by five independent radiologists using a standardized checklist. Fleiss' Kappa (k) coefficients of agreement were used to test the agreement between categorical variables. The MRI features of the natal cleft sepsis associated with PSD were classified into four main categories: morphology, branching and extensions, external skin openings, and the relationship of the PSD to the coccyx. A survey was created and disseminated online among general surgeons who treat patients with PSD to assess the relevance of the MRI features proposed in the standardized checklist. RESULTS: The overall agreement regarding the identification of morphology of the natal cleft sepsis was moderate (k = 0.59). Lateral and caudal extensions interobserver agreement was substantial (k = 0.64 and 0.71, respectively). However, the overall agreement regarding the individual parts of anal sphincter involved was moderate (k = 0.47). Substantial interobserver agreement was found in assessing the proximity of the PSD to the coccyx (k = 0.62). CONCLUSION: Preoperative MRI can delineate the extensions and branching of PSD with substantial agreement. MRI is superior in describing the deep extensions of PSD with better reliability than assessing the number and locations of the external openings. Expert consensus agreement is needed to establish the MRI features necessary for optimal reporting of PSD. CLINICAL RELEVANCE STATEMENT: MRI can offer valuable information about the extent of sepsis associated with pilonidal sinus disease, particularly in cases with involvement of critical anatomical structures such as the coccyx and anal triangle. MRI can potentially contribute to more accurate patient stratification and surgical planning. KEY POINTS: • The interobserver agreement for assessing PSD's lateral and caudal extension on MRI is substantial. • MRI can describe deep extensions and branching of PSD with superior reliability than assessing the number and site of external openings. • Reporting the relationship between natal cleft sepsis in PSD and the anal region may influence the surgical approach and postoperative healing.

Mental health literacy and help-seeking behaviour among Egyptian undergraduates: a cross-sectional national study.

BACKGROUND: Mental health literacy (MHL) and help-seeking behaviors are pivotal in managing mental well-being, especially among Egyptian undergraduates. Despite the importance and prevalent psychological distress in this group, limited research has addressed MHL and associated behaviors in Egypt. This study aimed to assess the levels of MHL and help-seeking behavior among Egyptian university students. METHODS: A cross-sectional study was conducted across ten Egyptian universities during the academic year 2022-2023. A convenience sample of 1740 students was obtained through online questionnaires distributed via social media platforms. The survey comprised demographic characteristics, the Mental Health Literacy Scale (MHLS), and the General Help Seeking Behavior Questionnaire (GHSPQ). RESULTS: Among 1740 Egyptian undergraduates, medical students scored higher in recognizing disorders (p < 0.05), while non-medical students excelled in attitudes (p < 0.05). A strong correlation was observed between attitudes toward mental illness and total mental health literacy (coefficients of 0.664 and 0.657). Univariate analysis indicated a significant association with professional help-seeking (OR = 1.023). Females, individuals aged 21 or above, and non-medical students were more likely to seek mental health information (OR = 1.42, 1.82, 1.55 respectively). Help-seeking behavior for emotional problems was more inclined towards intimate partners, whereas suicidal thoughts prompted seeking professional help. CONCLUSION: The findings advocate for comprehensive mental health education, particularly in rural areas, and emphasis on the role of personal relationships in mental well-being. Implementing these insights could foster improved mental health outcomes and reduce related stigma in Egypt.

In situ evaluation of the impact of metformin or verapamil coadministration with vildagliptin on its regional absorption from the rabbit's intestine.

This research aims to identify regional differences in vildagliptin absorption across the intestinal membrane. Furthermore, it was to investigate the effect of verapamil or metformin on vildagliptin absorptive clearance. The study utilized an in situ rabbit intestinal perfusion technique to determine vildagliptin oral absorption from duodenum, jejunum, ileum, and ascending colon. This was conducted both with and without perfusion of metformin or verapamil. The findings revealed that the vildagliptin absorptive clearance per unit length varied by site and was in the order as follows: ileum < jejunum < duodenum < ascending colon, implying that P-gp is significant in the reduction of vildagliptin absorption. Also, the arrangement cannot reverse intestinal P-gp, but the observations suggest that P-gp is significant in reducing vildagliptin absorption. Verapamil co-perfusion significantly increased the vildagliptin absorptive clearance by 2.4 and 3.2 fold through the jejunum and ileum, respectively. Metformin co-administration showed a non-significant decrease in vildagliptin absorptive clearance through all tested segments. Vildagliptin absorption was site-dependent and may be related to the intestinal P-glycoprotein content. This may aid in understanding the important elements that influence vildagliptin absorption, besides drug-drug interactions that can occur in type 2 diabetic patients taking vildagliptin in conjunction with other drugs that can modify the P-glycoprotein level.

Graft function and incidence of cardiac allograft vasculopathy in donation after circulatory-determined death heart transplant recipients.

Experience in donation after circulatory-determined death (DCD) heart transplantation (HTx) is expanding. There is limited information on the functional outcomes of DCD HTx recipients. We sought to evaluate functional outcomes in our cohort of DCD recipients. We performed a single-center, retrospective, observational cohort study comparing outcomes in consecutive DCD and donation after brain death (DBD) HTx recipients between 2015 and 2019. Primary outcome was allograft function by echocardiography at 12 and 24 months. Secondary outcomes included incidence of cardiac allograft vasculopathy, treated rejection, renal function, and survival. Seventy-seven DCD and 153 DBD recipients were included. There was no difference in left ventricular ejection fraction at 12 months (59% vs 59%, P = .57) and 24 months (58% vs 58%, P = .87). There was no significant difference in right ventricular function at 12 and 24 months. Unadjusted survival between DCD and DBD recipients at 5 years (85.7% DCD and 81% DBD recipients; P = .45) was similar. There were no significant differences in incidence of cardiac allograft vasculopathy (odds ratio 1.59, P = .21, 95% confidence interval 0.77-3.3) or treated rejection (odds ratio 0.60, P = .12, 95% confidence interval 0.32-1.15) between DBD and DCD recipients. Post-transplant renal function was similar at 1 and 2 years. In conclusion, cardiac allografts from DCD donors perform similarly to a contemporary population of DBD allografts in the medium term.

Mortality and morbidity following initiation of anticoagulant or antiplatelet treatment for blunt cerebrovascular injury.

OBJECTIVE: Cerebrovascular accidents (CVA) are potential sequelae of blunt cerebrovascular injuries (BCVI). To minimize their risk, medical therapy is used commonly. It is unclear if anticoagulant or antiplatelet medications are superior for decreasing CVA risk. It is also unclear as to which confer fewer undesirable side effects specifically in patients with BCVI. The aim of this study was to compare outcomes between nonsurgical patients with BCVI with hospital admission records who were treated with anticoagulant medications and those who were treated with antiplatelet medications. METHODS: We performed a 5-year (2016-2020) analysis of the Nationwide Readmission Database. We identified all adult trauma patients who were diagnosed with BCVI and treated with either anticoagulant or antiplatelet agents. Patients who were diagnosed with index admission CVA, intracranial injury, hypercoagulable states, atrial fibrillation, and or moderate to severe liver disease were excluded. Those who underwent vascular procedures (open and/or endovascular approaches) and or neurosurgical treatment were also excluded. Propensity score matching (1:2 ratio) was performed to control for demographics, injury parameters, and comorbidities. Index admission and 6-month readmission outcomes were examined. RESULTS: We identified 2133 patients with BCVI who were treated with medical therapy; 1091 patients remained after applying the exclusion criteria. A matched cohort of 461 patients (anticoagulant, 159; antiplatelet, 302) was obtained. The median patient age was 72 years (interquartile range [IQR], 56-82 years), 46.2% of patients were female, falls were the mechanism of injury in 57.2% of cases, and the median New Injury Severity Scale score was 21 (IQR, 9-34). Index outcomes with respect to (1) anticoagulant treatments followed by (2) antiplatelet treatments and (3) P values are as follows: mortality (1.3%, 2.6%, 0.51), median length of stay (6 days, 5 days; P < .001), and median total charge (109,736 USD, 80,280 USD, 0.12). The 6-month readmission outcomes are as follows: readmission (25.8%, 16.2%, <0.05), mortality (4.4%, 4.6%, 0.91), ischemic CVA (4.9%, 4.1%, P = not significant [NS]), gastrointestinal hemorrhage (4.9%, 10.2%, 0.45), hemorrhagic CVA (0%, 0.41%, P = NS), and blood loss anemia (19.5%, 12.2%, P = NS). CONCLUSIONS: Anticoagulants are associated with a significantly increased readmission rate within 6 months. Neither medical therapy is superior to one another in the reduction of the following: index mortality, 6-month mortality, and 6-month readmission with CVA. Notably, antiplatelet agents seem to be associated with increased hemorrhagic CVA and gastrointestinal hemorrhage on readmission, although neither association is statistically significant. Still, these associations underscore the need for further prospective studies of large sample sizes to investigate the optimal medical therapy for nonsurgical patients with BCVI with hospital admission records.

Racial diversity and Black vascular surgeons in vascular surgery workforce.

OBJECTIVES: The precise number of actively practicing vascular surgeons who self-identify as Black American and the historical race composition trends within the overall profession of vascular surgery are unknown. Limited demographic data have been collected and maintained at the societal or national board level. Vascular surgery societal reports suggest that less than 2% of vascular surgeons identify as Black American. Black Americans comprise 13.4% of the U.S. population yet for disorders such as peripheral artery disease and end-stage renal disease, Black communities are disproportionately impacted, and the prevalence of disease is greater on an age-adjusted basis. A significant body of research shows that clinical outcomes such as medication adherence, shared decision-making, and research trial participation are positively impacted by racial concordance especially for communities in whom distrust is high as a consequence of historic experiences. This survey aims to characterize practice and career variables within a network of Black American vascular surgeons. METHODS: A cross-sectional survey was conducted via a questionnaire sent to all participants of the Society of Black Vascular Surgeons that began to convene monthly during the COVID-19 pandemic and experienced subsequent organic growth. The survey included 20 questions with variables quantified including the surgeon's demographics, clinical experience, practice setting, patient demographics, and professional society engagement. RESULTS: Fifty-nine percent of the Society of Black Vascular Surgeons members completed the survey. Males comprised 81% of the responding vascular surgeons. The majority (62%) of respondents were involved in academic practice. Less than 25% of the total medical staff were Black American in 77% of the respondents' current work practice. The patient racial composition within their respective practice settings was as follows: White (47%), Black (34%), Hispanic (13%), Asian (3%), Middle Eastern or North African (2%), and American Indian and Alaskan Natives (0.4%). Forty-three percent of respondents had a current active membership in the Society for Vascular Surgery, and 24% had a regional society membership. Fifty-eight percent of respondents reported that they experienced a workplace event that they felt was racially or ethically driven in the 12 months before the survey. CONCLUSIONS: This survey describes an under-represented in medicine vascular surgeon subgroup that has not heretofore been characterized. Racial and ethnic demographic data are essential to better understand the current demographic makeup of our specialty and to develop benchmark goals of race composition that mirrors our society at large. The patients of this group of Black American vascular surgeons were more likely to represent a racial minority. Efforts to increase race diversity in vascular surgery have the potential benefit of enhancing care of patients with vascular disease.

Risk factors for readmission after open abdominal aortic aneurysms repair and its outcome in chronic kidney disease patients.

OBJECTIVE: Readmission after vascular procedures is a burden to hospitals and the Medicare system. Therefore, identifying risk factors leading to readmission is vital. We examined the frequency of and risk factors for 30-day readmission after open aneurysm repair (OAR) and explored post-operative outcomes with special attention for those with preexisting chronic kidney disease (CKD). METHODS: Patients who underwent OAR were identified in the National Readmission Database (2016-2018). Demographic information and comorbidities were collected. Patients readmitted within 30 days after their index hospitalization were identified and compared to patients without readmission records. RESULTS: A total of 5090 patients underwent OAR during the study timeframe with 488 patients (9.6%) were readmitted within 30 days. Females were more readmitted than males (F = 11.1% vs M = 9.0%, P < 0.001). Readmitted patients had more comorbidities (median ECI 12, P < 0.05), were on Medicare (73.7%, P < 0.001), had higher surgery admission cost ($146,844, P < 0.001), longer length of stay (8 days, P < 0.001), and were discharged to a lower level care facility (62.7%, P < 0.001). Comorbidities that predisposed patients for readmission include: peripheral arterial disease (OR 2.15, P < 0.01), asthma (OR 1.87, P < 0.01), chronic heart failure (OR 1.74, P < 0.05). On readmission visit, acute renal failure (23.8%) was the most common diagnosis, while intestinal surgery (13.7%) was the most common procedure. Patients with CKD (n = 968, 18.9% of total population) had double the mortality rate compared to non-CKD patients on surgery admission (10.4%, P < 0.001) and readmission (10.1%, P < 0.001). CONCLUSION: Certain factors were noted to increase readmission rate, special attention need to be paid when dealing with such group of patients requiring OAR. Vascular surgeons should meticulously weigh benefits and risks when considering OAR in patients with CKD who are not a candidate for endovascular repair, and optimize their kidney function before considering such approach.

The relationship between lower extremity amputation and body mass index.

OBJECTIVES: Non-traumatic lower extremity amputation (LEA) is associated with significant morbidity and mortality. Diabetes mellitus (DM) and peripheral vascular disease (PVD) are associated with increased risk for LEA. As such, DM and PVD account for 54% of all LEA's, performed in the United States annually. As obesity is highly associated with both DM and PVD, our study sought to explore the relationship between LEA and obesity defined by BMI. METHODS: Using the National Inpatient Sample (NIS) database, a retrospective review of patients who underwent non-traumatic LEA (LEA) between 2008 and 2014 was performed. The International Classification of Diseases 9th edition (ICD-9) codes were utilized to determine the diagnoses, comorbidities, and procedures. Patient BMIs were classified as follows: Non-obese [BMI <30], Obesity class I [BMI 30-34.9], Obesity class II [BMI 35-39.9], and Obesity class III [BMI ≥40]. Predictors for LEA were compared between groups using chi-square test and binary logistic regression to identify possible underlying factors associated with LEA. We also conducted a multivariate analysis to measure the effect of multiple variables on LEA. RESULTS: We identified 16,259 patients with non-traumatic LEA and a mean age of 59.9 years. Rate of amputation in females was lower than males at 0.35% vs 0.87% respectively (p < 0.001). Of patients that underwent amputation there was a V-shape trend based on BMI, with 30.4% in non-obese patients, 18.2% in obesity class I, 17.3% in obesity class II, and 34.1% in obesity class III. The incidence of diabetes increased with obesity class, while the incidence of PVD decreased. Interestingly, of those with DM there was an inverse relationship between amputation rate and BMI class, with LEA rates in non-obese versus obesity class III patients were 1.63% vs 0.98% respectively (p < 0.001). Similarly, patients who had both diabetes and PVD showed a downward trend in LEA rate as obesity class increased; non-obese patients had a LEA rate of 8.01%, while obesity class III had 4.65% (p < 0.001). Patients in higher income bracket have lower odds of LEA (OR 0.77, p < 0.001) compared to the lowest income patients. Also, patients with comorbidities such as PVD (OR 10.78), diabetes (OR 5.02), renal failure (OR 1.41), and hypertension (OR 1.36) had higher odds to get an LEA (p < 0.001). Individuals with obesity class III are almost at half the odds (OR 0.52) to get an LEA compared to non-obese (p < 0.001). CONCLUSIONS: Higher BMI and female gender are protective factors against lower extremity amputation. Factors that predisposing to LEA include lower household income and certain comorbidities such as PVD, diabetes, renal failure, and hypertension. These findings warrant further research to identify patients at high risk for LEA and help develop management guidelines for targeted populations.

Studies of surface plasmon resonance of silver nanoparticles reduced by aqueous extract of shortleaf spikesedge and their catalytic activity.

This study describes the synthesis of silver nanoparticles (AgNPs) using shortleaf spikesedge extract (SSE) to reduce AgNO3. Visual observation, in addition to analyses of UV-vis, EDX, XRD, FTIR, and TEM was employed to monitor the formation of AgNPs. The effects of SSE concentration, AgNO3 concentration, reaction time, pH, and temperature on the synthesis of AgNPs were studied based on the surface plasmon resonance (SPR) band. From the TEM image, highly-scattered AgNPs of quasi-spherical shape with an average particle size of 17.64 nm, were observed. For the catalytic study, the reduction of methylene blue (MB) was evaluated using two systems. A detailed batch study of the removal efficiency (%RE) and kinetics was done at an ambient temperature, various MB initial concentrations, and varying reaction time. Employing the electron relay effect in System 2, the batch study clearly highlighted the significant role of AgNPs in boosting the catalytic activity for MB removal. At 30-100 mg/L initial concentrations, MB was reduced by 100% in a very short reaction time between 1.5 and 5.0 mins. The kinetic data best fitted the pseudo-first-order model with a maximum reaction rate of 2.5715 min-1. These findings suggest the promising application of AgNPs in dye wastewater treatment.The SSE-driven AgNPs were prepared using unwanted dried biomass of shortleaf spikesedge extract (SSE) as a reducing as well as stabilizing agent. Employing the electron relay effect, the batch study clearly highlighted the significant role of SSE-driven AgNPs in boosting the catalytic activity for MB removal. At 30-100 mg/L initial concentrations, MB was reduced by 100% in a very short reaction time between 1.5 and 5.0 mins. In this sense, SSE-driven AgNPs acted as an electron relay point that behaves alternatively as acceptor and donor of electrons. The findings revealed the good catalytic performance of SSE-driven AgNPS, proving their viability for dye wastewater treatment.

Adult heart procurement following circulatory determined death from a donor on venous-venous extracorporeal membrane oxygenation: A case report.

Donation after circulatory death in the context of heart transplants is attracting interest and becoming popular in clinical practice. Activity is growing in the United Kingdom, Australia, and the United States. We believe that a prolonged warm ischemic time (time from asystole to reperfusion of the heart on an ex vivo perfusion system) is a primary indicator of adverse outcomes. However, 1.5 liters of blood must be retrieved from the right atrium following sternotomy prolonging warm ischemic time. The patient in the following case report was supported by veno-venous extra-corporeal membrane oxygenation following drowning, further complicated by aspiration-related lung failure. Following circulatory death and a mandatory five-minute stand-off period, 1.5 liters of blood was drained from the circuit as sternotomy began. Surgeons then proceeded to direct procurement of the heart, aiming for least functional warm ischemic time. Following standard implantation, the patient's postoperative recovery has been unremarkable to date.

Application of Design of Experiment in the Optimization of Apixaban-Loaded Solid Lipid Nanoparticles: In Vitro and In Vivo Evaluation.

Solid lipid nanoparticles (SLnPs) are usually utilized as lipid-based formulations for enhancing oral bioavailability of BCS class IV drugs. Accordingly, the objective of this work was to investigate the effect of formulation and processing variables on the properties of the developed SLnPs for oral delivery of apixaban. Randomized full factorial design (24) was employed for optimization of SLnPs. With two levels for each independent variable, four factors comprising both formulations and processing factors were chosen: the GMS content (A), the Tween 80 content (B), the homogenization time (C), and the content of poloxamer 188 used (D). The modified hot homogenization and sonication method was employed in the formulation of solid lipid nanoparticles loaded with apixaban (APX-SLnPs). The size of APX-SLnPs formulations was measured to lie between 116.7 and 1866 nm, polydispersity index ranged from 0.385 to 1, and zeta potential was discovered to be in the range of - 12.6 to - 38.6 mV. The entrapping efficiency of APX-SLnPs formulations was found to be in the range of 22.8 to 96.7%. The optimized formulation was evaluated in vivo after oral administration to rats. Oral administration of APX-SLnPs resulted in significant prolongation in bleeding time compared with both positive and negative control. This indicates the ability of this system to enhance drug therapeutic effect either by increasing intestinal absorption or trans-lymphatic transport. So, this study highlighted the capability of SLnPs to boost the pharmacological effect of apixaban.

Three common sampling techniques in Pleistocene coral reefs of the Red Sea: a comparison.

Line Intercept Transects (LIT), Point Intercept Transects (PIT), and Photoquadrats (PQ) are the most common quantitative sampling techniques in modern and fossil coral reefs. Data from coral reefs obtained by the different methods are generally compared between various reef ages and localities. Quaternary reefs from warmer interglacial periods, which represent climate scenarios projected for the future, are particularly interesting for comparisons with modern reefs. Importantly, fossil reefs differ from modern reefs because they are diagenetically altered and time averaged. While several studies have compared different quantitative methods in modern reefs, very few have dealt with the comparability among fossil and between fossil and modern reefs. Here, we compare LIT, PIT at 10, 20 and 50 cm intervals, and PQ in two Pleistocene reef localities in Egypt. We find that alpha diversity, reef cover and community composition are dependent on the method. Results gained with plotless methods (LIT, PIT) differ strongly from results gained with plot methods (PQ). However, coral cover results are similar between LIT and PIT, and community composition is indistinguishable between the two, but alpha diversity depends on the interval used for PIT. We discuss the implications of our findings for comparing coral reefs of various ages and localities. We recommend surveying Pleistocene reefs with PIT at 20 cm intervals. This is because A) alpha diversity is well captured, B) the amount of time averaging recorded by PIT is reduced compared to PQ, C) the PIT results can be directly compared to reefs analyzed by LIT, and D) the method is less time consuming than LIT and PQ.

Imbalance of Follicular Helper and Follicular Regulatory T Cells in Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Data regarding the imbalance in follicular helper T (Tfh) and follicular regulatory T (Tfr) cell responses in patients having chronic rhinosinusitis with nasal polyps (CRSwNP) is so far limited. Thus, we aimed to assess the changes in circulating Tfh and Tfr in CRSwNP patients. METHODS: This case-control study included 21 patients having CRSwNP and 20 age and sex-matched healthy blood donors as a control group. Lund-Mackay staging system was used for radiologic scoring of chronic rhinosinusitis. Two milliliters of peripheral blood samples were collected from all participants into EDTA-containing vacutainer tubes to assess the levels of Tfh and Tfr cells using flow cytometry. RESULTS: Patients having CRSwNP did not show significant differences in the percentages of CD4+ T cells and total CD4+CXCR5+ T cells from healthy controls. Meanwhile, levels of both activated circulating Tfh and Tfr showed a marked rise in patients than controls. In addition, a positive correlation was observed between the levels of both activated Tfh and Tfr cells. CONCLUSION: An imbalance in circulating Tfh/Tfr levels was detected in patients having CRSwNP. A significant rise in the levels of Tfh and Tfr was detected in patients proposing a possible role of this imbalance in disease pathogenesis.

Validation of predicted heart mass equations by measurement of donor heart mass at time of heart transplantation.

Predicted heart mass (PHM) equations may be used in donor-recipient size matching in heart transplantation. We compared PHM and actual heart mass in 25 consecutive DBD heart transplants. There was a moderate positive correlation between actual heart mass and PHM. There was a similar moderate correlation between actual heart mass and donor weight or donor body surface area but not donor height. PHM was lower than actual heart mass for all donor hearts. Bland-Altman analysis showed a systematic bias between PHM and actual heart mass, with a mean difference of 190.9 ± 66.4 g. The utility of PHM equations is likely to be part of a multi-parametric assessment of the relative differences between donor and recipient, so the absolute difference is likely to be unimportant.

Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan.

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic, stigmatizing skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (ClinicalTrials.gov: NCT02894008) was an open-label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration, 30 months; range, 6-180 months). Patients received a single intramuscular vaccination of 1 × 1010 viral particles (v.p.; adults only) or 7.5 × 1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42-120 days follow-up. AmBisome was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole-blood transcriptomics and ELISpot. 7/23 patients (30.4%) monitored to study completion showed >90% clinical improvement, and 5/23 (21.7%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomized controlled trial to determine whether these clinical responses were vaccine-related and whether ChAd63-KH vaccine has clinical utility is underway.

Intravenous thrombolysis before mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion; should we cross that bridge? A systematic review and meta-analysis of 36,123 patients.

BACKGROUND: The use of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a debatable subject in the field of neuro-interventional surgery. We conducted this systematic review and meta-analysis to synthesize evidence from published studies on the outcomes of IVT + MT compared with MT alone in AIS-LVO patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to January 2022 for relevant clinical trials and observational studies. Eligible studies were identified, and all relevant outcomes were pooled in the meta-analysis DerSimonian-Liard random-effects model. RESULTS: Forty-nine studies, with a total of 36,123 patients, were included in this meta-analysis. IVT + MT was significantly superior to MT alone in terms of successful recanalization (RR 1.06, 95% CI 1.03 to 1.09), mortality (RR 0.75, 95% CI 0.68-0.82), favorable functional outcome (RR 1.21, 95% CI 1.13 to 1.29), and complete recanalization (RR 1.06, 95% CI 1.00 to 1.11). There were no significant differences between the two groups in terms of improvement of the National Institute of Health Stroke Scale (NIHSS) score at 24 h or at discharge (p > 0.05). Complications including symptomatic intracranial hemorrhage, symptomatic intracerebral hemorrhage (sICH), procedure-related complications, and parenchymal hematoma were comparable between the two groups (p > 0.05). CONCLUSION: For AIS-LVO, IVT + MT is associated with slightly better rates of survival, successful and complete recanalization, and favorable functional outcome as compared with MT alone. Further clinical trials are needed to corroborate such benefits of bridging IVT.

A comparison of revascularization methods for peripheral arterial disease in diabetics: Changing trends in lower extremity revascularization from 2008 to 2014.

OBJECTIVES: This study examined the current demographic and outcome trends regarding endovascular and open revascularization for people with diabetes. METHODS: The National Inpatient Sample database was utilized to identify diabetic patients who underwent lower extremity revascularization and amputation procedures between 2008 and 2014. International Classification of Diseases 9th edition codes were used to identify the procedures, diagnoses, and comorbidities. RESULTS: We identified 38,143 diabetic patients who underwent endovascular revascularization and 25,415 who underwent open revascularization between 2008 and 2014. The number of endovascular and open revascularization procedures decreased steadily by 17.5% and 12.43% during the study period, respectively. The total charges for the endovascular procedure were greater than the open procedure ($98,761 vs. $80,782, p ≤ 0.001) despite similar median length of stay (5 days (inner quartile range (IQR) = 1-10) vs. 5 days (IQR = 3-10), p ≤ 0.001). Compared to open, the in-patient amputation rate for endovascular patients has been increasing faster for both minor (11.75% vs. 0.37%) and major amputations (3.08% vs. 0.19%). Although the post-procedure amputation rates between endovascular and open procedures were increased for endovascular patients (odds ratio [OR] = 1.71, confidence interval [CI] = 1.35-2.18, p ≤ 0.001) in 2008, by 2014 the risk of major amputation was doubled in endovascular patients (OR = 2.88, CI = 2.27-3.64, p ≤ 0.001). African Americans were more likely to undergo minor amputation than Whites (p ≤ 0.001). Lastly, diabetic patients with uncontrolled diabetes, systemic infection, weight loss, congestive heart failure, gangrene, and end-stage renal disease were more likely to undergo endovascular repair. CONCLUSIONS: As more medically complex patients undergo endovascular revascularization, endovascular revascularization for diabetic patients is becoming associated with higher total cost despite similar length of stay, minor amputation, and major amputation rates. Further studies are needed to continuously evaluate the post-procedural outcomes and cost effectiveness of this trend.

Machine learning prediction of diabetic foot ulcers in the inpatient population.

BACKGROUND: The objective of this study was to create an algorithm that could predict diabetic foot ulcer (DFU) incidence in the in-patient population. MATERIALS AND METHODS: The Nationwide Inpatient Sample datasets were examined from 2008 to 2014. The International Classification of Diseases 9th Edition Clinical Modification (ICD-9-CM) and the Agency for Healthcare Research and Quality comorbidity codes were used to assist in the data collection. Chi-square testing was conducted, using variables that positively correlated with DFUs. For descriptive statistics, the Student T-test, Wilcoxon rank sum test, and chi-square test were used. There were six predictive variables that were identified. A decision tree model CTREE was utilized to help develop an algorithm. RESULTS: 326,853 patients were noted to have DFU. The major variables that contributed to this diagnosis (both with p < 0.001) were cellulitis (OR 63.87, 95% CI [63.87-64.49]) and Charcot joint (OR 25.64, 95% CI [25.09-26.20]). The model performance of the six-variable testing data was 79.5% (80.6% sensitivity and 78.3% specificity). The area under the curve (AUC) for the 6-variable model was 0.88. CONCLUSION: We developed an algorithm with a 79.8% accuracy that could predict the likelihood of developing a DFU.

Influence of piperine and omeprazole on the regional absorption of Daclatasvir from rabbit intestine.

The study assessed the site dependent intestinal absorption of Daclatasvir and investigated the effects of piperine and omeprazole on such absorption utilizing in situ rabbit intestinal perfusion technique. The intestinal absorption of Daclatasvir was assessed in four segments: duodenum, jejunum, ileum, and colon. The effect of co-perfusion with omeprazole was monitored through the tested anatomical sites. The effect of piperine, a P-glycoprotein (P-gp) inhibitor on Daclatasvir absorption from jejunum and ileum was tested. The results showed that Daclatasvir was incompletely absorbed from the rabbit small and large intestine. The absorptive clearance per unit length (PeA/L) was site dependent and was ranked as colon > duodenum > jejunum > ileum. This rank is the opposite of the rank of P-gp intestinal content suggesting possible influence for P-gp. Co-perfusion with omeprazole increased PeA/L and this was evidenced also with reduced the L95% of Daclatasvir from both small and large intestinal segments. Significant enhancement in Daclatasvir absorption through jejunum and ileum was shown in presence of piperine. Daclatasvir showed site dependent intestinal absorption in a manner suggesting its affection by P-gp efflux. This effect was inhibited by piperine. Co-administration of Daclatasvir with omeprazole can enhance intestinal absorption a phenomenon which requires extension to human pharmacokinetic investigation.