Performance of CHA2DS2-VASc and HAS-BLED in predicting stroke and bleeding in atrial fibrillation and cancer.

Aims: To compare the predictive performance of CHA2DS2-VASc and HAS-BLED scores in atrial fibrillation (AF) patients with and without cancer. Methods and results: Using data from the Clinical Practice Research Datalink in England, we performed a retrospective cohort study of patients with new diagnoses of AF from 2009 to 2019. Cancer was defined as history of breast, prostate, colorectal, lung, or haematological cancer. We calculated the CHA2DS2-VASc and HAS-BLED scores for the 1-year risk of stroke and major bleeding events. Scores performance was estimated by discrimination [area under the receiver operating characteristic curve (AUC)] and calibration plots. Of 141 796 patients with AF, 10.3% had cancer. The CHA2DS2-VASc score had good to modest discrimination in prostate cancer AUC = 0.74 (95% confidence interval: 0.71, 0.77), haematological cancer AUC = 0.71 (0.66, 0.76), colorectal cancer AUC = 0.70 (0.66, 0.75), breast cancer AUC = 0.70 (0.66, 0.74), and lung cancer AUC = 0.69 (0.60, 0.79), compared with no-cancer AUC = 0.73 (0.72, 0.74). HAS-BLED discrimination was poor in prostate cancer AUC = 0.58 (0.55, 0.61), haematological cancer AUC = 0.59 (0.55, 0.64), colorectal cancer AUC = 0.57 (0.53, 0.61), breast cancer AUC = 0.56 (0.52, 0.61), and lung cancer AUC = 0.59 (0.51, 0.67), compared with no-cancer AUC = 0.61 (0.60, 0.62). Both the CHA2DS2-VASc score and HAS-BLED score were well calibrated across all study cohorts. Conclusion: Amongst certain cancer cohorts in the AF population, CHA2DS2-VASc performs similarly in predicting stroke to AF patients without cancer. Our findings highlight the importance of cancer diagnosis during the development of risk scores and opportunities to optimize the HAS-BLED risk score to better serve cancer patients with AF.

Acute Appendicitis Incidence, Diagnostic Markers, and Sequelae; Dallah Hospital-Based Study in Riyadh, Saudi Arabia.

Background: Acute appendicitis is currently considered one of the most common acute surgical diseases of the abdomen and requires emergency surgery. It is also one of the most common abdominal emergencies in both developed and developing countries. The current study is aimed at assessing the specificity and sensitivity of Ultrasound and Computed Tomography in the diagnosis of appendicitis as well as the prevalence of its complications. The association of appendicitis with several laboratory findings will also be evaluated. Methodology: A retrospective study was conducted at Dallah-Namar Hospital, Riyadh City, Saudi Arabia. Results: 720 patients were differentially diagnosed with appendicitis in the study area. Of these, 618 patients had US abdomen/pelvis, with 15 (2.4%) showing positive findings. Amongst the 203 patients noted to have undergone abdominal CT,8 (4.0%) was found to have positive findings. Conclusion: The sensitivity of the US was determined to be relatively low. Also, serum creatinine was found to be elevated among all patients diagnosed with appendicitis. Further research with a larger sample size is needed to be conducted to further support the current findings.

Temporal trends of in-hospital mortality and its determinants following percutaneous coronary intervention in patients with acute coronary syndrome in England and Wales: A population-based study between 2006 and 2021.

BACKGROUND: There is limited data around drivers of changes in mortality over time. We aimed to examine the temporal changes in mortality and understand its determinants over time. METHODS: 743,149 PCI procedures for patients from the British Cardiovascular Intervention Society (BCIS) database who were aged between 18 and 100 years and underwent Percutaneous Coronary Intervention (PCI) for Acute Coronary Syndrome (ACS) in England and Wales between 2006 and 2021 were included. We decomposed the contributing factors to the difference in the observed mortality proportions between 2006 and 2021 using Fairlie decomposition method. Multiple imputation was used to address missing data. RESULTS: Overall, there was an increase in the mortality proportion over time, from 1.7% (95% CI: 1.5% to 1.9%) in 2006 to 3.1% (95% CI: 3.0% to 3.2%) in 2021. 61.2% of this difference was explained by the variables included in the model. ACS subtypes (percentage contribution: 14.67%; 95% CI: 5.76% to 23.59%) and medical history (percentage contribution: 13.50%; 95% CI: 4.33% to 22.67%) were the strongest contributors to the difference in the observed mortality proportions between 2006 and 2021. Also, there were different drivers to mortality changes between different time periods. Specifically, ACS subtypes and severity of presentation were amongst the strongest contributors between 2006 and 2012 while access site and demographics were the strongest contributors between 2012 and 2021. CONCLUSIONS: Patient factors and the move towards ST-elevated myocardial infarction (STEMI) PCI have driven the short-term mortality changes following PCI for ACS the most.

Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome.

Background and aim: The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS). Materials and methods: The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI. Results: Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters. Conclusions: The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

Trichinella spiralis Larval Extract as a Biological Anti-Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma.

Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase-3, TNF-α, Ki-67 and CD31. Additionally, Bcl2 and Bcl2-associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase-3, up-regulation of pro-apoptotic gene, Bax and down-regulation of anti-apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki-67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.

Urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI) and plasmin as novel biomarkers in early diagnosis of lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, with multi systematic affection. Lupus nephritis (LN) is the most frequent cause of renal damage in SLE patients with variable presentations that may progress to end stage renal failure. Coagulation disorders are frequently reported in SLE and LN with higher mortality rates. Renal biopsy is an invasive process, and the existing indicators for LN diagnosis and activity are unreliable. New urinary biomarkers with significant validity, safety, and accuracy are the current focus of most studies. Our study sought to assess the value of urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI), and plasmin as biomarkers for the early identification and detection of LN and its activity. This was a cross-sectional study, included 100 subjects (80 SLE patients, and 20 healthy controls), they were recruited from the Internal Medicine department, Rheumatology and Nephrology units and outpatient's clinics at Assiut University hospital between the period of 2020 and 2022. All patients underwent full history taking, clinical evaluation, and activity scoring calculation and laboratory investigations. The results showed that the best diagnostic accuracy of LN was observed with TFPI (90% accuracy, sensitivity 80% and specificity 95% with p <0.001 at cutoff point of >193.2 ng/ml), followed by uTF (75.4% overall accuracy at cut off point of >12.6 ng/ml, sensitivity 90% and specificity 68% with p < 0.001) and plasmin (70.3% accuracy at cut off point of >30.5 ng/ml, sensitivity 55% and specificity 78% with p < 0.001). Urinary TFPI was the best predictor of LN occurrence with odd ratio of 4.34, (p < 0.001). In conclusion urinary TFPI could be used as a diagnostic marker for LN with high accuracy and an early predictor of LN.

Oral anticoagulant prescribing among patients with cancer and atrial fibrillation in England, 2009-2019.

BACKGROUND: Anticoagulation of patients with atrial fibrillation (AF) and cancer is challenging because of their high risk for stroke and bleeding. Little is known of the variations of oral anticoagulant (OAC) prescribing in patients with AF with and without cancer. METHODS: Patients with first-time AF during 2009-2019 from the Clinical Practice Research Datalink were included. Cancer diagnosis was defined as a history of breast, prostate, colorectal, lung, or hematological cancer. Competing-risk analysis was used to assess the risk of OAC prescribing in patients with AF and cancer adjusted for clinical and sociodemographic factors. RESULTS: Of 177,065 patients with AF, 11.7% had cancer. Compared to patients without cancer, patients with cancer were less likely to receive OAC: prostate cancer (subhazard ratio [SHR], 0.95; 95% CI, 0.91-0.99), breast cancer (SHR, 0.93; 95% CI, 0.89-0.98), colorectal cancer (SHR, 0.93; 95% CI, 0.88-0.99), hematological cancer (SHR, 0.70; 95% CI, 0.65-0.75), and lung cancer (SHR, 0.44; 95% CI, 0.38-0.50). The cumulative incidence function (CIF) of OAC prescribing was lowest for patients with lung cancer and hematological cancer compared with patients without cancer. The difference between the CIF of OAC prescribing in patients with and without cancer becomes narrower in the most deprived areas. Elderly patients (aged ≥85 years) overall had the lowest CIF of OAC prescribing regardless of cancer status. CONCLUSIONS: In patients with AF, underprescribing of OAC is independently associated with certain cancer types. Patients with hematological and lung cancer are the least likely to receive anticoagulation therapy compared with patients without cancer. Underprescribing of OAC in cancer is linked to old age. Further studies of patients with AF and cancer are warranted to assess the net clinical benefit of anticoagulation in certain cancer types.

Aggressiveness of Cancer Care at End of Life in Patients with Metastatic Breast Cancer in Jordan.

Background: Contrary to Western societies, more than 15% of patients with breast cancer in Jordan are diagnosed with stage IV disease. In this study, we evaluate the value of early palliative care integration in the end-of-life care of such patients. Methods: All consecutive adult patients who died between 2014 to 2018, while under the care of our institution, with a confirmed diagnosis of breast cancer at the time of death, irrespective of place of death, were retrospectively reviewed. Results: During the study period, a total of 433 patients, median age 51.6 years, were included in the analysis. Among the whole group, 102 (23.6%) were referred to palliative care service early (≥30 days prior to death), 182 (42.0%) had late referral (<30 days from death), while 149 (34.4%) were never referred and were followed up by their medical oncologists. During the last 30 days prior to death, patients who were never referred to palliative care were more likely to visit the Emergency Room (ER) more than once (OR 1.89, 95% CI 1.20-2.99, p = 0.006), more likely to be admitted to the hospital more than once (OR 2.27, 95% CI 1.38-3.73, p = 0.001), and more likely to be admitted to the intensive care unit (ICU) (OR 3.07, 95% CI 1.48-6.38, p = 0.0027). Fewer patients in the "no referral" group died with advance directives compared to those who had early or late referral; 60.8%, 75.0% and 82.5%, respectively, p = 0.0003. Survival of patients followed by medical oncologist was not better than those referred to palliative care, either late or early; median survival was 19.0, 19.1 and 23.8 months, respectively (p = 0.2338). Conclusion: Findings suggest that earlier palliative care referral is associated with less aggressive end-of-life care, leading to less frequent ER visits, hospital and ICU admissions during the last month of life, and does not compromise survival.

Comorbidity clusters and in-hospital outcomes in patients admitted with acute myocardial infarction in the USA: A national population-based study.

BACKGROUND: The prevalence of multimorbidity in patients with acute myocardial infarction (AMI) is increasing. It is unclear whether comorbidities cluster into distinct phenogroups and whether are associated with clinical trajectories. METHODS: Survey-weighted analysis of the United States Nationwide Inpatient Sample (NIS) for patients admitted with a primary diagnosis of AMI in 2018. In-hospital outcomes included mortality, stroke, bleeding, and coronary revascularisation. Latent class analysis of 21 chronic conditions was used to identify comorbidity classes. Multivariable logistic and linear regressions were fitted for associations between comorbidity classes and outcomes. RESULTS: Among 416,655 AMI admissions included in the analysis, mean (±SD) age was 67 (±13) years, 38% were females, and 76% White ethnicity. Overall, hypertension, coronary heart disease (CHD), dyslipidaemia, and diabetes were common comorbidities, but each of the identified five classes (C) included ≥1 predominant comorbidities defining distinct phenogroups: cancer/coagulopathy/liver disease class (C1); least burdened (C2); CHD/dyslipidaemia (largest/referent group, (C3)); pulmonary/valvular/peripheral vascular disease (C4); diabetes/kidney disease/heart failure class (C5). Odds ratio (95% confidence interval [CI]) for mortality ranged between 2.11 (1.89-2.37) in C2 to 5.57 (4.99-6.21) in C1. For major bleeding, OR for C1 was 4.48 (3.78; 5.31); for acute stroke, ORs ranged between 0.75 (0.60; 0.94) in C2 to 2.76 (2.27; 3.35) in C1; for coronary revascularization, ORs ranged between 0.34 (0.32; 0.36) in C1 to 1.41 (1.30; 1.53) in C4. CONCLUSIONS: We identified distinct comorbidity phenogroups that predicted in-hospital outcomes in patients admitted with AMI. Some conditions overlapped across classes, driven by the high comorbidity burden. Our findings demonstrate the predictive value and potential clinical utility of identifying patients with AMI with specific comorbidity clustering.

Common Cancer Types and Risk of Stroke and Bleeding in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Study in England.

BACKGROUND: The association between cancer and stroke or bleeding outcomes in atrial fibrillation is unclear. We sought to examine how certain types of cancer influence the balance between stroke and bleeding risk in patients with nonvalvular atrial fibrillation (NVAF). METHODS AND RESULTS: We estimated stroke and bleeding risk among adult patients with NVAF and certain types of cancer (breast, prostate, colorectal, lung, and hematological cancer) from 2009 to 2019 based on data from the UK Clinical Practice Research Datalink GOLD and Aurum databases. The control group included patients with NVAF only. Of 177 065 patients with NVAF, 11379 (6.4%) had cancer (1691 breast, 3955 prostate, 1666 colorectal, 2491 hematological, and 1576 lung). Compared with patients without cancer, stroke risk was higher in patients with breast cancer (adjusted hazard ratio [aHR], 1.20 [95% CI, 1.07-1.35) and with prostate cancer (aHR, 1.11 [95% CI, 1.01-1.12) if diagnosed within 6 months before NVAF. The risk of bleeding was increased in subjects with hematological cancer (aHR, 1.55 [95% CI, 1.40-1.71]), lung cancer (aHR, 1.49 [95% CI, 1.25, 1.77]), prostate cancer (aHR, 1.38 [95% CI, 1.28-1.49]), and colorectal cancer (aHR, 1.36 [95% CI, 1.21-1.53]), but not for subjects with breast cancer. The more recent the cancer diagnosis before NVAF diagnosis (within 6 months), the higher the risk of bleeding. CONCLUSIONS: Breast and prostate cancer are associated with increased stroke risk, whereas in some cancer types, the risk of bleeding seemed to exceed stroke risk. In these patients, prescribing of oral anticoagulant should be carefully evaluated to balance bleeding and stroke risk.

Association of strong opioids and antibiotics prescribing with GP burnout: a retrospective cross-sectional study.

BACKGROUND: Prescribing of strong opioids and antibiotics impacts patient safety, yet little is known about the effects GP wellness has on overprescribing of both medications in primary care. AIM: To examine associations between strong opioid and antibiotic prescribing and practice- weighted GP burnout and wellness. DESIGN AND SETTING: A retrospective cross-sectional study was undertaken using prescription data on strong opioids and antibiotics from the Oxford- Royal College of General Practitioners Research and Surveillance Centre linking to a GP wellbeing survey overlaying the same 4-month period from December 2019 to April 2020. METHOD: Patients prescribed strong opioids and antibiotics were the outcomes of interest. RESULTS: Data for 40 227 patients (13 483 strong opioids and 26 744 antibiotics) were linked to 57 practices and 351 GPs. Greater strong opioid prescribing was associated with increased emotional exhaustion (incidence risk ratio [IRR] 1.19, 95% confidence interval [CI] = 1.10 to 1.24), depersonalisation (IRR 1.10, 95% CI = 1.01 to 1.16), job dissatisfaction (IRR 1.25, 95% CI = 1.19 to 1.32), diagnostic uncertainty (IRR 1.12, 95% CI = 1.08 to 1.19), and turnover intention (IRR 1.32, 95% CI = 1.27 to 1.37) in GPs. Greater antibiotic prescribing was associated with increased emotional exhaustion (IRR 1.19, 95% CI = 1.05 to 1.37), depersonalisation (IRR 1.24, 95% CI = 1.08 to 1.49), job dissatisfaction (IRR 1.11, 95% CI = 1.04 to 1.19), sickness-presenteeism (IRR 1.18, 95% CI = 1.11 to 1.25), and turnover intention (IRR 1.38, 95% CI = 1.31 to 1.45) in GPs. Increased strong opioid and antibiotic prescribing was also found in GPs working longer hours (IRR 3.95, 95% CI = 3.39 to 4.61; IRR 5.02, 95% CI = 4.07 to 6.19, respectively) and in practices in the north of England (1.96, 95% CI = 1.61 to 2.33; 1.56, 95% CI = 1.12 to 3.70, respectively). CONCLUSION: This study found higher rates of prescribing of strong opioids and antibiotics in practices with GPs with more burnout symptoms, greater job dissatisfaction, and turnover intentions; working longer hours; and in practices in the north of England serving more deprived populations.

Patient exposure during videofluoroscopic swallowing studies performed by speech-language pathologists.

Videofluoroscopic swallowing studies (VFSSs) are fluoroscopic examinations performed by speech and language pathologists (SLPs), for the evaluation of the oral and pharyngeal phases of swallowing, in patients who are diagnosed with symptoms like dysphagia and speech impairment. The study was focused on the evaluation of the patient doses from VFSS performed at Hamad Medical Corporation hospitals. Data on the patient exposure and examination parameters were extracted from the Radiation Dose Monitoring system, statistically analysed and compared with literature. For adult patients, the mean (median) values for fluoroscopy time and kerma-air product were 2.8 (2.7) min and 181 (144) cGycm2, respectively. For children, the respective mean (median) values were 2.6 (2.4) min and 15.3 (9.2) cGycm2. The results of the study indicate that the VFSS are performed by well-trained health professionals, and as a result, image quality sufficient for a confident diagnosis is obtained at relatively low dose levels.

Longevity of Immunoglobulin-G Antibody Response Against Nucleocapsid Protein Against SARS-CoV-2 Among Healthcare Workers.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the latest pandemic and the most significant challenge in public health worldwide. Studying the longevity of naturally developed antibodies is highly important clinically and epidemiologically. This paper assesses the longevity of antibodies developed against nucleocapsid protein amongst our health-care workers. Methods: This longitudinal cohort study was conducted at a tertiary hospital, Saudi Arabia. Anti-SARSsCoV-2 antibodies were tested among health-care workers at three-point intervals (baseline, eight weeks, and 16 weeks). Results: Of the 648 participants, 112 (17.2%) tested positive for Coronavirus (COVID-19) by PCR before the study. Of all participants, 87 (13.4%) tested positive for anti-SARS-CoV-2 antibodies, including 17 (2.6%) participants who never tested positive for COVID-19 using rt-PCR. Out of the 87 positive IgG participants at baseline, only 12 (13.7%) had remained positive for anti-SARS-CoV-2 antibodies by the end of the study. The IgG titer showed a significant reduction in values over time, where the median time for the confirmed positive rt-PCR subgroup from infection to the last positive antibody test was 70 (95% CI: 33.4-106.5) days. Conclusion: Health-care workers are at high risk of exposure to the SARS-CoV-2 virus, and contracting an asymptomatic infection is not unlikely. Developing and sustaining natural immunity differs from one person to another, while the rate of positive IgG anti-SARS-CoV-2 wanes over time. Clinicaltrialsgov Identifier: NCT04469647, July 14, 2020.

Surfactant vesicles for enhanced antitoxoplasmic effect of norfloxacin: In vitro and in vivo evaluations.

The goal was to scrutinize niosomes as potential carriers for enhanced efficacy of norfloxacin against Toxoplasma gondii RH strain. This was assessed in vitro and in vivo. Standard niosomes of Span 60 and cholesterol were prepared. Gelucire 48/16 or Tween 80 was incorporated as hydrophilic fluidizer. The prepared vesicles were characterized for shape, size, viscosity and norfloxacin release. The in vitro anti-Toxoplasma was assessed by monitoring tachyzoites viability after incubation with niosomes. In vivo efficacy of niosomes encapsulated norfloxacin was evaluated on infected mice. Transmission electron micrographs showed nano-sized spherical vesicles. Norfloxacin release varied with niosomal composition to show faster liberation in presence of fluidizing agent. The half maximum effective concentration of norfloxacin against tachyzoites (EC50) was significantly reduced after niosomal encapsulation compared with simple drug solution with no significant difference between vesicular formulations. Tachyzoite count in the peritoneal fluid of infected mice was reduced by 45.2, 90.8, 88.3 and 84% after treatment with simple drug dispersion, standard niosomes, Gelucire containing and Tween containing vesicles, respectively compared to infected untreated mice. These results correlate with the in vitro data and reflects the efficacy of niosomes. The study introduced surfactant vesicles as a tool for enhanced efficacy of norfloxacin against toxoplasma.

Examining non-linearity in the association between age and reported opioid use in different socioeconomic strata: cohort study using Health Survey for England waves from 1997 to 2014.

BACKGROUND: Age and socioeconomic status (SES) predict several health-related outcomes, including prescription opioid use. Contrasting findings from previous literature found higher prevalence of opioid use in both people over 65 years old and the working-age population of 35-55 years old. This study aimed to analyse if the association between age and opioid use is non-linear and differs in adults with different SES levels. METHODS: This cohort study used the Health Survey for England waves 1997-2014 data to investigate the shape of the correlation between reported opioid use and income decile, employment status and educational level. A semiparametric Generalised Additive Model was employed, so that linearity of correlation was not assumed. The shape of the relationship was assessed using the effective degrees of freedom (EDF). RESULTS: Positive correlation between age and reported opioid use, more linear in people in the highest income decile (EDF: 1.01, p<0.001) and higher education (EDF: 2.03, p<0.001) was observed. In people on lower income and with lower levels of education, the highes probability of reported opioid use was at around 40-60 years old and slowly decreased after that. Higher income decile and higher levels of education were predictors of a lower probability of reported opioid use (OR: 0.27, 95% CI: 0.21 to 0.36 and OR: 0.48, 95% CI: 0.41 to 0.57, respectively). There was no statistically significant difference in opioid use between employed and unemployed people. CONCLUSION: The relationship between age and the probability of prescribed opioid use varies greatly across different income and educations strata, highlighting different drivers in opioid prescribing across population groups. More research is needed into exploring patterns in opioid use in older people, particularly from disadvantaged socioeconomic backgrounds.

The synergetic potential of Lactobacillus delbrueckii and Lactobacillus fermentum probiotics in alleviating the outcome of acute toxoplasmosis in mice.

Toxoplasmosis is an immunologically complex disease, particularly in immunocompromised patients. Although there are several therapeutic regimens for such disease, the majority of them have many drawbacks. Therefore, it is of utmost importance to improve the current regimen in an effort to achieve a well-tolerated therapy while also enhancing the host immune response. Famous for their immunomodulatory effect, Lactobacillus delbrueckii and Lactobacillus fermentum probiotics were chosen to be evaluated in this study as an adjuvant therapy against the virulent RH Toxoplasma gondii (T. gondii) strain. Experimental mice were divided into control and treated groups. The control group was further subdivided into two groups: group I: 10 uninfected mice and group II: 20 infected untreated mice. The treated experimental group was subdivided into three groups (20 mice each); group III: sulfamethoxazole-trimethoprim (SMZ-TMP) treated, group IV: probiotics treated, and group V: SMZ-TMP combined with probiotics. The results obtained revealed that combined therapy increased survival rate and time up to 95% and 16 days, respectively, with an 82% reduction of tachyzoites and marked distortion, as detected by the scanning electron microscope (SEM). Additionally, combined therapy alleviated the severity and the extent of the inflammatory cells' infiltration, thereby reducing hepatocyte degeneration. Intriguingly, serum IF-γ level showed a significant increase to 155.92 ± 10.12 ng/L with combined therapy, reflecting the immunological role of the combined therapy. The current results revealed that probiotics have a high adjuvant potential in alleviating the impact of toxoplasmosis. Using probiotics as a synergistic treatment to modulate conventional therapy in systemic toxoplasmosis may gain popularity due to their low cost and current availability.

The effects of L-citrulline adjunctive treatment of Toxoplasma gondii RH strain infection in a mouse model.

Toxoplasma gondii is a zoonotic intracellular protozoan parasite and its therapeutic limitations are one of its major problems. L-citrulline is an organic compound that has beneficial effects on many diseases. The purpose of this study was to assess the impact of L-citrulline, alone or in combination with sulfamethoxazole-trimethoprim (SMZ-TMP) on acute toxoplasmosis caused by Toxoplasma gondii RH virulent strain. In our study, 60 Swiss albino mice were divided into two main groups; the control group and the infected treated group, which was subdivided into group IIa: infected treated with L-citrulline, group IIb: infected treated with SMZ-TMP, and group IIc: infected treated with L-citrulline combined with SMZ-TMP. The effects of treatment were assessed by parasitological study, electron microscopic study of tachyzoites, and histopathological study of the liver. Moreover, ELISA measurement of the serum level of Interferon-gamma, Interleukin 10, Nitric oxide, and apoptotic markers was used. It was noticed that L-citrulline combined with SMZ-TMP significantly increased the survival time of infected mice with a significant decrease in the number of tachyzoites compared to the other groups. Moreover, it increased the levels of measured cytokines and serum anti-apoptotic proteins Bcl-2 and improved the extent of liver cell damage associated with a decrease in inflammatory infiltration. In conclusion, L-citrulline supplementation was found to be effective against acute toxoplasmosis, especially when combined with SMZ-TMP as it has multifactorial mechanisms; nitric oxide production, anti-inflammatory, anti-apoptotic, and immune stimulator.

Optimization of Bacillus subtilis growth parameters for biosynthesis of silver nanoparticles by using response surface methodology.

Silver nanoparticles (AgNPs) are among the most widely biosynthesized and used nanomaterials. They have different unique properties and a wide range of applications. This study is concerned with optimization of the growth conditions of Bacillus subtilis NRC1 for the biosynthesis of AgNPs using two designs of response surface methodology (RSM) statistical analysis. The data obtained from Plackett-Burman design (PBD) followed by central composite design (CCD), showed a good agreement between the experimental and predicted values of AgNPs biosynthesis. The optimum conditions were 0.7% (w/v) casein hydrolysate, 5% dextrin (w/v), pH 7.5 and 57 × 106 CFU/ml inoculum size. The model was highly valid and could be applied with a confidence factor of 99.47%. Minimal inhibitory concentration (MIC) of these AgNPs synthesized using the extracellular filtrate after growth of Bacillus subtilis NRC1 in the optimized medium was found to be 41-43µg/ml for all tested microorganisms with exception of Pseudomonas aeruginosa where MIC was 169 µg/ml.

Allogeneic Hematopoietic Stem Cell Transplantation in the Outpatient Setting: The Mayo Clinic Experience.

Hematopoietic stem cell transplantations (HSCT) are intensive and potentially curative modalities available for a variety of hematological diseases. Although alloHSCTs are typically performed in an inpatient setting, there has been increasing interest in moving them to the outpatient setting. AlloHSCTs are associated with a median length of hospital stay of 30 days. AlloHSCTs in the inpatient setting may increase patient exposure to nosocomial infections, drug-resistant organisms, rapid deconditioning with time spent in hospital beds, and loss of muscle mass. In this study, we aim to share outcomes of 856 consecutive alloHSCTs done in our institute over the past 2 decades. This is a single-center retrospective chart review encompassing 856 patients who underwent outpatient alloHSCTs between 2000 and 2017. Reduced-intensity conditioning, stem cell infusion, and much of the immediate follow-up in the early alloHSCT period was performed on an outpatient basis with daily evaluation, laboratory assessment, and intervention as needed. Rate of non-routine hospital admission was our primary outcome of interest. We also looked at various secondary outcomes, including causes of admission, median length of stay, and in-hospital mortality rate. Data analysis was performed using STATA statistical software Version 15. Descriptive statistics were used to summarize baseline demographic data and outcomes. Logistic regression modeling was used to identify predictors of hospital admission. We observed that about one third of our cohort never required admission to the hospital throughout the first 100 days after HSCT. Among those admitted, 6.6% experienced a direct admission to the intensive care unit, and the overall in hospital mortality was low at 5%. Furthermore, the median length of stay was noted to be decreased at 6 days compared to a median reported 30 days in existing literature. Overall, we observed favorable safety profile and outcomes with outpatient management of HSCTs.