Outcomes by Candida spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Reliability, validity and responsiveness of the Kurdish version of the questionnaire Disability of the Arm, Shoulder and Hand in patients with carpal tunnel syndrome.

INTRODUCTION: The Disabilities of Arm, Shoulder and Hand (DASH) questionnaire predicts the amount of the patient's inabilities and symptoms to evaluate the impacts of upper limb conditions in the patient's daily-life activities. This study aims to test the psychometric properties of DASH in Kurdish patients with carpal tunnel syndrome. MATERIALS AND METHODS: 93 patients with diagnosed carpal tunnel syndrome subjected to complete the self-report DASH-KU and patient rated wrist\hand evaluation PRWHEKU questionnaire during two consecutive assessments with a 24-hour interval before any intervention. RESULTS: DASH-KU questionnaire had excellent internal consistency (Cronbach's alpha = 0.99) and test-retest reliability (intra-class correlation coefficient =0.99). A strong correlation between the DASH-KU score and the PRWHE tool (r=0.792) demonstrated acceptable construct validity of DASH-KU. Bland-Altman plot showed good agreement between the two assessments of DASH-KU, and no floor (3%) nor ceiling effects (0%) were observed. Factor analysis showed that the DASH-KU scale had a high acceptable adequacy (adequacy index = 0.700) and a significant sphericity (p<0.001). The analysis showed a major factor that accounted for 40% of the observed variance with an eigenvalue of 13.14. In addition, five items model also explained 81.23% of the DASH-KU scale variance. However, the responsiveness of DASH-KU was suboptimum, which can be linked to the short 24-hour interval between measurements. CONCLUSION: The DASH-KU scale is a reliable, valid, and responsive instrument for assessing disabilities in patients with carpal tunnel syndrome.

Synthesis and antitumor activity of model cyclopentene-[g]annelated isoindigos.

A set of cyclopenten-[g]annelated isoindigos (5a-g) has been prepared and tested for their in vitro antiproliferative activities against MCF-7 and HL60 cells. Among, the N-1-methyl-5'-nitro derivative (5g) displayed the highest activity against HL60 cells (IC50 = 67 nM) and acted as the most potent Flt3 inhibitor. Compounds 5d-g exhibited moderate activity against MCF-7 (IC50 = 50-80 µM).

Healthcare Resource Utilization and Discharge Readiness in Adult Hospitalized Patients With Candidemia or Invasive Candidiasis Who Received an Echinocandin: An Analysis of United States Hospitals.

Background: Scant real-world outcomes data are available among hospitalized patients with candidemia (C) or invasive candidiasis without candidemia (IC) who were treated with an echinocandin and few have assessed if there is an opportunity to accelerate the transition of their care to the outpatient setting. This study described the outcomes associated with echinocandin therapy for C/IC and determined the proportion of patients on an echinocandin at hospital discharge (HD) who were potentially eligible for an earlier HD. Methods: A retrospective, multicenter observational study was performed using the PINC AI Healthcare Database (January 2016-April 2019) of hospitalized adult patients with C/IC who received ≥3 days of an echinocandin. Outcomes included post-index culture hospital costs and discharge location. Patients were considered potentially dischargeable earlier than actual HD day if they met the following 3 criteria prior to their actual HD day: resided on a non-intensive care unit hospital ward until HD, received any oral medications, and had no diagnostic/therapeutic interventions. Results: A total of 1865 patients met study criteria. Mean (standard deviation) post-index culture hospital costs for patients with C and IC were 50 196 (64 630) US dollars and 61 551 (73 080) US dollars, respectively. Of the 1008 patients on an echinocandin near HD and discharged alive, 432 (42.9%) were potentially dischargeable prior to their actual hospital day. Most patients (35.8%) were discharged to a long-term care facility. Conclusions: The findings suggest that a high proportion of hospitalized C/IC patients receiving an echinocandin near the time of HD were potentially dischargeable earlier. Like all studies of this nature, the findings need to be prospectively validated.

Prevalence and associated factors of stunting and thinness among adolescent Sudanese schoolchildren: a cross-sectional study.

BACKGROUND: Malnutrition among adolescents is a considerable health problem worldwide. There are scarce data on undernutrition among adolescents in Sudan. METHODS: A cross­sectional study was conducted to investigate the prevalence and associated factors of stunting and thinness among adolescent schoolchildren in northern Sudan. The questionnaires were used to collect information on sociodemographics. Weights and heights were measured and the height-for-age and body mass index-for-age cut-offs recommended by the WHO were applied, followed by logistic regression analysis. RESULTS: Of 384 enrolled adolescents, 202 (52.6%) were females and 182 (47.4%) were males. The median (IQR) age of these adolescents was 15.1 (14.0‒16.3) y. Seventy-six (19.8%) and 52 (15.4%) adolescents had stunting and thinness, respectively, and 15 (3.9%) had both stunting and thinness. Multivariate analysis showed that increased age (adjusted OR [AOR]=1.30, 95% CI 1.08 to 1.57) and male gender (AOR=5.82, 95% CI 3.11 to 10.91) were associated with stunting. Male gender (AOR=2.08, 95% CI 1.14 to 3.82) and smoking/tobacco snuff (AOR=2.61, 95% CI 1.07 to 6.36) were associated with thinness. CONCLUSIONS: The findings of the current study are that both stunting and thinness are important health problems, especially among boys, older participants and smokers.

Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: pooled data from two prospective randomised controlled trials.

BACKGROUND: Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) or once-a-day intravenous caspofungin (70 mg and 50 mg). Efficacy was evaluated in a pooled modified intent-to-treat (mITT) population. Primary efficacy endpoint was day 30 all-cause mortality (tested for non-inferiority with a pre-specified margin of 20%). Secondary efficacy endpoint was mycological response. Safety was also evaluated. The STRIVE and ReSTORE trials are registered with ClinicalTrials.gov, NCT02734862 and NCT03667690, and both studies are complete. FINDINGS: ReSTORE was conducted from Oct 12, 2018, to Oct 11, 2021, and STRIVE from July 26, 2016, to April 18, 2019. The mITT population, pooling the data from the two trials, comprised 139 patients for rezafungin and 155 patients for caspofungin. Day 30 all-cause mortality rates were comparable between groups (19% [26 of 139] for the rezafungin group and 19% [30 of 155] for the caspofungin group) and the upper bound of the 95% CI for the weighted treatment difference was below 10% (-1·5% [95% CI -10·7 to 7·7]). Mycological eradication occurred by day 5 in 102 (73%) of 139 rezafungin patients and 100 (65%) of 155 caspofungin patients (weighted treatment difference 10·0% [95% CI -0·3 to 20·4]). Safety profiles were similar across groups. INTERPRETATION: Rezafungin was non-inferior to caspofungin for all-cause mortality, with a potential early treatment benefit, possibly reflecting rezafungin's front-loaded dosing regimen. These findings are of clinical importance in fighting active and aggressive infections and reducing the morbidity and mortality caused by candidaemia and invasive candidiasis. FUNDING: Melinta Therapeutics and Cidara Therapeutics.

Variability in indigenous Pakistani tomato lines and worldwide reference collection for Tomato Mosaic Virus (ToMV) and Tomato Yellow Leaf Curl Virus (TYLCV) infection / Variabilidade em linhagens indígenas de tomate do Paquistão e coleção de referência global para infecção por vírus do mosaico do tomateiro (ToMV) e vírus da folha amarela do tomate (TYLCV)

Local and exotic germplasm of tomato remains a major source for genetic improvement. Assessment of such lines for biotic stresses particularly viral diseases are the most important criteria for selection in Pakistan, where Tomato Yellow Leaf Curl Virus (TYLCV) and Tomato Mosaic Virus (ToMV) are the major diseases/viruses. A set of 40 accessions (including indigenous Pakistani lines and exotic germplasm from Europe, the United States, and Asia) were evaluated for their resistance/infection response to ToMV with artificial inoculation under greenhouse conditions. Infection response was quantified through disease scoring and DAS-ELISA test (for ToMV). A subset of 24 lines, was further screened for TYLCV using disease scoring and TAS-ELISA. The tested lines showed significant variability for resistance to ToMV. Only one accession (Acc-17878) was resistant to the ToMV whereas seven accessions i.e. Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352, and CLN-362 expressed resistance to TYLCV. Correlation between phenotypic evaluation was confirmed by the ELISA results in both diseases, although both tools complemented to assess the viral infection status. In future, tomato breeding programs must consider breeding for ToMV and TYLCV resistance (using identified germplasm in our study) so as to deliver virus resistant tomato varieties.

O germoplasma local e exótico do tomate continua sendo uma importante fonte de melhoramento genético. A avaliação de linhagens para estresses bióticos, particularmente as doenças virais, é o critério mais importantes para seleção no Paquistão, onde o vírus da folha amarela do tomate (TYLCV) e o vírus do mosaico do tomateiro (ToMV) são as principais doenças/vírus. Um conjunto de 40 acessos (incluindo linhagens indígenas do Paquistão e germoplasma exótico da Europa, dos Estados Unidos e da Ásia) foi avaliado quanto à resistência/resposta à infecção ao ToMV com inoculação artificial em casa de vegetação. A resposta à infecção foi quantificada por meio de pontuação da doença e de teste DAS-ELISA (para ToMV). Um subconjunto de 24 linhas foi posteriormente rastreado para TYLCV usando pontuação de doença e TAS-ELISA. As linhas testadas apresentaram variabilidade significativa para resistência ao ToMV. Apenas um acesso (Acc-17878) foi resistente ao ToMV, enquanto sete acessos (Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352 e CLN-362) expressaram resistência ao TYLCV. A correlação entre a avaliação fenotípica foi confirmada pelos resultados do ELISA nas duas doenças, embora ambas as ferramentas tenham se complementado para avaliar o estado da infecção viral. No futuro, os programas de melhoramento de tomate devem considerar aperfeiçoamentos para resistência ao ToMV e TYLCV (usando germoplasma identificado em nosso estudo) de modo a fornecer variedades de tomate resistentes a vírus.

Variability in indigenous Pakistani tomato lines and worldwide reference collection for Tomato Mosaic Virus (ToMV) and Tomato Yellow Leaf Curl Virus (TYLCV) infection

Abstract Local and exotic germplasm of tomato remains a major source for genetic improvement. Assessment of such lines for biotic stresses particularly viral diseases are the most important criteria for selection in Pakistan, where Tomato Yellow Leaf Curl Virus (TYLCV) and Tomato Mosaic Virus (ToMV) are the major diseases/viruses. A set of 40 accessions (including indigenous Pakistani lines and exotic germplasm from Europe, the United States, and Asia) were evaluated for their resistance/infection response to ToMV with artificial inoculation under greenhouse conditions. Infection response was quantified through disease scoring and DAS-ELISA test (for ToMV). A subset of 24 lines, was further screened for TYLCV using disease scoring and TAS-ELISA. The tested lines showed significant variability for resistance to ToMV. Only one accession (Acc-17878) was resistant to the ToMV whereas seven accessions i.e. Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352, and CLN-362 expressed resistance to TYLCV. Correlation between phenotypic evaluation was confirmed by the ELISA results in both diseases, although both tools complemented to assess the viral infection status. In future, tomato breeding programs must consider breeding for ToMV and TYLCV resistance (using identified germplasm in our study) so as to deliver virus resistant tomato varieties.

RESUMO O germoplasma local e exótico do tomate continua sendo uma importante fonte de melhoramento genético. A avaliação de linhagens para estresses bióticos, particularmente as doenças virais, é o critério mais importantes para seleção no Paquistão, onde o vírus da folha amarela do tomate (TYLCV) e o vírus do mosaico do tomateiro (ToMV) são as principais doenças/vírus. Um conjunto de 40 acessos (incluindo linhagens indígenas do Paquistão e germoplasma exótico da Europa, dos Estados Unidos e da Ásia) foi avaliado quanto à resistência/resposta à infecção ao ToMV com inoculação artificial em casa de vegetação. A resposta à infecção foi quantificada por meio de pontuação da doença e de teste DAS-ELISA (para ToMV). Um subconjunto de 24 linhas foi posteriormente rastreado para TYLCV usando pontuação de doença e TAS-ELISA. As linhas testadas apresentaram variabilidade significativa para resistência ao ToMV. Apenas um acesso (Acc-17878) foi resistente ao ToMV, enquanto sete acessos (Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352 e CLN-362) expressaram resistência ao TYLCV. A correlação entre a avaliação fenotípica foi confirmada pelos resultados do ELISA nas duas doenças, embora ambas as ferramentas tenham se complementado para avaliar o estado da infecção viral. No futuro, os programas de melhoramento de tomate devem considerar aperfeiçoamentos para resistência ao ToMV e TYLCV (usando germoplasma identificado em nosso estudo) de modo a fornecer variedades de tomate resistentes a vírus.

Synthesis, biological evaluation, and computational studies of N-benzyl pyridinium-curcumin derivatives as potent AChE inhibitors with antioxidant activity.

A library of N-benzylpyridinium-based compounds, 7a-j and 8a-j, was designed and synthesised as potential acetylcholinesterase) AChE (inhibitors. An in vitro assay for the synthesised compounds showed that most compounds had significant AChE inhibitory activities at the nanomolar and submicromolar levels. The benzyl (8a) and fluoro (8b) derivatives were the most active, with IC50 values ≤56 nM. Compound 7f, which had a benzyl moiety, showed the highest potency among all the target compounds, with an IC50 value of 7.5 ± 0.19 nM against AChE, which was higher than that of the activities of tacrine (IC50 = 30 ± 0.2 nM) and donepezil (IC50 = 14 ± 0.12 nM). Compounds with vanillin moieties exhibited antioxidant activity. Among the tested compounds, four derivatives (7f, 7 g, 8f, and 8 g) exhibited superior AChE inhibitory activity, with Ki values of 6-16 nM, which were potent in the same range as the approved drug, donepezil. These compounds showed moderate antioxidant activities, as indicated by the results of the ABTS assay.

A plain language summary on preventing fungal infections with isavuconazole in people with blood-related conditions.

WHAT IS THIS SUMMARY ABOUT?: People with blood-related conditions have a higher chance of getting invasive fungal infections (IFIs). IFIs are severe fungal infections that can lead to death. Only a few medications, known as antifungals, exist that can be used to prevent IFIs, and sometimes they can cause very bad side effects. Isavuconazole is an antifungal which has been approved to treat IFIs, but it has not been approved to prevent IFIs. In this study, we reviewed published studies that looked at how well isavuconazole prevented IFIs in people who have a higher chance of getting IFIs. WHAT WERE THE RESULTS?: This review showed that isavuconazole could be effective at preventing IFIs in people with blood-related conditions, as well as being a safe medication. WHAT DO THE RESULTS OF THE STUDY MEAN?: Isavuconazole can prevent IFIs in people who have a higher chance of getting IFIs. Guidelines should consider that patients need new antifungals to prevent IFIs, and more research needs to be done to see which medicines work best, and which have fewer side effects. Clinical Trial Registration: Please note that 7 studies included in this review were planned studies (1 prospective, 6 retrospective), 2 were real- world studies, 1 of which was registered as a clinical trial NCT03019939 (ClinicalTrials.gov).

Post-hoc analysis of the safety and efficacy of isavuconazole in older patients with invasive fungal disease from the VITAL and SECURE studies.

Isavuconazole is a triazole with broad-spectrum antifungal activity. In this post-hoc analysis of two prospective clinical trials (VITAL and SECURE), the safety and efficacy of isavuconazole in patients aged ≥ 65 years with invasive fungal diseases were evaluated. Patients were divided into two subgroups (≥ 65 and < 65 years). Adverse events (AEs); all-cause mortality; and overall, clinical, mycological, and radiological response were assessed. A total of 155 patients ≥ 65 years were enrolled in both trials. Most patients reported AEs. In the isavuconazole arm of both studies, serious AEs (SAEs) were greater in patients ≥ 65 versus < 65 years: 76.7% versus 56.9% (VITAL); 61.9% versus 49.0% (SECURE). In SECURE, SAE rates were similar in the ≥ 65 years subgroup of both treatment arms (61.9% vs 58.1%), while in the < 65 years subgroup the SAE rate was lower in the isavuconazole arm (49.0% vs 57.4%). In VITAL, all-cause mortality through day 42 (30.0% vs 13.8%) was higher, and overall response at end of treatment (27.6% vs 46.8%) was lower in patients ≥ 65 years versus < 65 years. In SECURE, all-cause mortality was similar between both subgroups, and isavuconazole (20.6% vs 17.9%) and voriconazole (22.6% vs 19.4%) treatment arms. The overall response was lower in the ≥ 65 years than the < 65 years subgroup in the isavuconazole (23.7% vs 39.0%) and voriconazole (32.0% vs 37.5%) arms. The safety and efficacy of isavuconazole were better in patients < 65 versus ≥ 65 years, and the safety profile was more favorable than that of voriconazole in both subgroups.Clinicaltrials.gov identifier NCT00634049 and NCT00412893.

Thermodynamic control synthesis of spiro[oxindole-3,3'-pyrrolines] via 1,4-dipolar cycloaddition utilizing imidazo[1,5-a]quinoline.

A series of novel 2-(quinolin-2-yl)-spiro[oxindole-3,3'-pyrrolines] were synthesized by one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 1-phenylimidazo[1,5-a]quinoline and N-alkylisatins in chloroform at ∼60 °C for 24 h. Structures of these new spiro derivatives were deduced from HRMS and NMR spectral data. A plausible mechanism for the observed thermodynamic control pathway is presented herewith. Interestingly, the spiro adduct, derived from 5-chloro-1-methylisatin, exhibited excellent antiproliferative activity on MCF7, A549 and Hela human cell lines (IC50 ≃ 7 µM).

Study of an antifungal medicine isavuconazole used in treatment of mold infections in China: A plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Molds are types of fungus that can cause sickness and death. Mold infections are increasing in China. Until 2022, medicines that can effectively treat all mold infections were still lacking in China. This summary of a study originally published in the journal Infection and Drug Resistance. The study took place in China and tested a medicine called isavuconazole on mold samples to check if isavuconazole can be used to treat mold infections. Isavuconazole became available in China in January 2022 as a capsule (a hard gel-covered pill filled with a dose of medicine) and in June 2022 as an injection or a shot. WHAT WERE THE RESULTS?: Isavuconazole stopped the growth of most molds. Other medicines were needed at higher amounts to stop the growth of molds. WHAT DO THE RESULTS OF THE STUDY MEAN?: Isavuconazole is another option to treat mold infections in China.

8-Amino-7-(aryl/hetaryl)fluoroquinolones. An emerging set of synthetic antibacterial agents.

This study reports the synthesis of seven new 8-amino-7-(aryl/hetaryl)fluoroquinolones and their antibacterial activity against 10 bacteria associated with microbial infections and foodborne illnesses. These fluoroquinolones are prepared via the reactions of selected aryl(hetaryl)boronic acids with ethyl-7chloro-6-fluoro-8-nitroquinolone-3-carboxylate, under Suzuki-Miyaura cross-coupling conditions. Nitro group reduction of the latter resulted in the corresponding 8-aminoquinolone-3-esters which upon hydrolysis formed the respective 8-amino-7-(aryl/hetaryl)-quinolone-3-carboxylic acids. The latter compounds were tested against selected Gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumonia) and Gram-positive bacteria (Enterococcus feacalis, Listeria monocytogenes, Streptococcus agalactiae, Staphylococcus epidermidis, and Staphylococcus aureus). The tested fluoroquinolones showed a significant antimicrobial activity against most of the tested bacterial strains. The antimicrobial activity of some of the tested compounds were comparable to or higher than a wide range of standard antibiotics including ampicillin, ciprofloxacin, and imipenem. The results highlight the new synthesized 8-amino-7-(aryl/hetaryl)fluroquinolones as promising candidates for new antimicrobial drugs to treat bacterial infections. This study highlights that the newly synthetic 8-amino-7-(aryl/hetaryl)fluroquinolones are promising candidates for new antimicrobial drugs to treat human diseases including foodborne illnesses.

Thiophene ring-opening reactions VI. Attempted cyclization towards [fused]-tricyclic system involving a thiolate anion and suitably located electrophilic carbon.

Model α-chloro-ß-nitrothieno[2,3-c]pyridazines incorporating N1-(aryl) entity appended with ortho-methoxycarbonyl or trifluoromethyl group were prepared via intramolecular cyclization of their respective N-arylhydrazone precursors. Interaction of these substrates with N'-(p-fluorophenyl)benzothiohydrazide, in the presence of NEt3, furnished the respective 1,3,4-thiadiazoline-pyridazine thiolate hybrids that were S-methylated to produce the corresponding "sulfanyl" derivatives. Their structures were deduced from spectral data, and confirmed by single-crystal X-ray diffraction.

Influenza vaccine effect on risk of stroke occurrence: a systematic review and meta-analysis.

Background: Stroke is a significant global cause of mortality and long-term disability, potentially influenced by infections that heighten systemic inflammation and thrombotic events. The full impact of influenza vaccination on stroke remains uncertain. This systematic review and meta-analysis aimed to investigate the association between influenza immunization and stroke incidence. Methods: We searched for randomized controlled trials (RCTs), case-control, and cohort studies published in PubMed/Medline, Cochrane-Central-Register-of-Controlled-Trials (CENTRAL), and Embase until 5 December 2022, and identified articles investigating the effect of influenza vaccine on stroke occurrence. All articles were screened by two independent reviewers. We performed a meta-analysis to investigate the risk of stroke occurrence in vaccinated vs. unvaccinated individuals. The random-effects model was used in all statistical analyses. Results: Among the 26 articles meeting our criteria, 10 were retrospective cohort studies, 9 were case-control studies, 3 were prospective cohort studies, 3 were RCTs and 1 case-series. Overall, the studies showed a significant decrease in the risk of stroke incidence/hospitalization among vaccinated patients (OR = 0.81, 95% CI [0.77-0.86], p = 0.00001). Furthermore, studies showed flu vaccine decreases the occurrence of mortality among stroke patients (OR = 0.50, 95% CI [0.37-0.68], p = 0.00001). Sub-group analysis revealed significant protective effect for patients with specific comorbidities including atrial fibrillation (OR = 0.68, 95% CI [0.57-0.81], p = 0.0001), diabetes (OR = 0.76, 95% CI [0.66-0.87], p = 0.0001), Chronic obstructive pulmonary disease (OR = 0.70, 95% CI [0.61-0.81], p = 0.00001), and hypertension (OR = 0.76, 95% CI [0.70-83], p = 0.00001). Conclusion: The current meta-analysis further supports prior findings that influenza vaccination reduces stroke risk, particularly in patients with comorbidities. Guidelines should promote vaccination for at-risk individuals.

Rapid Transformation from Face to Face to Virtual Simulation During the SARS-CoV-2 Pandemic: Impact on the Simulation Process during "The Little Room of Horrors".

Objective: 1. To explore the feasibility of a rapid transformation from face to face to virtual simulation and its impact on the simulation process 2. To explore the efficacy of a rapid transformation from face to face to virtual simulation and its impact on the simulation process. Methods: The simulation process (preparation, pre-briefing, simulation, and debriefing) was investigated for feasibility and efficacy from the perspective of the educators and students. This study took place very early in the pandemic, thus highlighting the speed at which it needed to be conducted and acknowledging the limitations of technology at the time. The faculty (n = 3) involved in the virtual simulation experiment and year one medical students(n = 61) were invited to participate in the study voluntarily. The module chosen for this study was the Introduction to the Practice of Medicine, where the students were introduced to the concept of patient safety using simulation-based education. The "Little Room of Horrors" - is a simulation based educational session emphasising the importance of patient safety. Students were taken into a simulated medical ward that demonstrated common hospital-based errors. The learners were timed and asked to identify and document as many patient safety hazards as possible. The semi structured questionnaire was analysed using descriptive statistics and thematic analysis. Results: The Educator's perspective reflected that virtual simulation was technologically dependent and had limitations during debriefing but was also a sustainable and portable standardised process. The student's perspective revealed that the objectives were met, and the session helped them support the theory previously learned. The average rating was 4.09 on a 5-point scale. Innovation: When resources of the simulation center like space, mannikins, and faculty cannot be accessed for reasons like social distancing during a pandemic, virtual simulation was developed and used as a feasible alternative for our students without impacting the learning objectives. Conclusion: This study demonstrates the use of virtual simulation as a valuable option for teaching when face to face simulation is challenging or not possible.

Patient experiences of codesigned rehabilitation interventions in hospitals: a rapid review.

BACKGROUND: Codesign strengthens partnerships between healthcare workers and patients. It also facilitates collaborations supporting the development, design and delivery of healthcare services. Prior rehabilitation reviews have focused mainly on the clinical and organisational outcomes of codesign with less focus on the lived experience of rehabilitation patients. OBJECTIVE: To explore patient experiences of codesigned hospital rehabilitation interventions. DESIGN: Rapid review and evidence synthesis of the literature. DATA SOURCES: CINAHL, MEDLINE, Embase and Cochrane were searched from 1 January 2000 to 25 April 2022. STUDY SELECTION: Studies reporting patient experiences of codesigned rehabilitation interventions in hospitals. RESULTS: 4156 studies were screened, and 38 full-text studies were assessed for eligibility. Seven studies were included in the final rapid review. Five out of the seven studies involved neurological rehabilitation. All eligible studies used qualitative research methods. The main barriers to codesign were related to staffing and dedicated time allocated to face-to-face patient-therapist interactions. High-quality relationships between patients and their therapists were a facilitator of codesign. Thematic synthesis revealed that codesigned rehabilitation interventions can enable a meaningful experience for patients and facilitate tailoring of treatments to align with individual needs. Personalised rehabilitation increases patient involvement in rehabilitation planning, delivery and decision-making. It also promotes positive feelings of empowerment and hope. CONCLUSION: This rapid review supports the implementation of codesigned rehabilitation interventions to improve patient experiences in hospitals. PROSPERO REGISTRATION NUMBER: CRD42021264547.

Targeting Macrophages with CAR T Cells Delays Solid Tumor Progression and Enhances Antitumor Immunity.

Tumor-associated macrophages (TAM) are one of the most abundant cell types in many solid tumors and typically exert protumor effects. This has led to an interest in macrophage-depleting agents for cancer therapy, but approaches developed to date have had limited success in clinical trials. Here, we report the development of a strategy for TAM depletion in mouse solid tumor models using chimeric antigen receptor (CAR) T cells targeting the macrophage marker F4/80 (F4.CAR-T). F4.CAR-T cells effectively killed macrophages in vitro and in vivo without toxicity. When injected into mice bearing orthotopic lung tumors, F4.CAR-T cells infiltrated tumor lesions and delayed tumor growth comparably with PD-1 blockade, and significantly extended mouse survival. Antitumor effects were mediated by F4.CAR-T-produced IFNγ, which promoted upregulation of MHC molecules on cancer cells and tumor-infiltrating myeloid cells. Notably, F4.CAR-T promoted expansion of endogenous CD8 T cells specific for tumor-associated antigen and led to immune editing of highly antigenic tumor cell clones. Antitumor impact was also observed in mouse models of ovarian and pancreatic cancer. These studies provide proof of principle to support CAR T-cell targeting of TAMs as a means to enhance antitumor immunity.

Risk factors in people with mold infections that have spread to different parts of the body: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a study originally published in ClinicoEconomics and Outcomes Research. Mold infections spread from one to other parts of the body and can infect other body parts. We need to understand what makes people more likely to get this type of mold infection (called invasive mold infection). This summary may help doctors to understand the risks that can relate to invasive mold infections. WHAT WERE THE RESULTS?: The main risks in people with invasive aspergillosis (shortened to IA) and invasive mucormycosis (shortened to IM) were: ○diabetes (high blood sugar and associated conditions), ○lung disease (such as tuberculosis, chronic obstructive pulmonary disorder), ○blood-related cancers (such as leukemia, lymphoma), and ○solid organ transplant (removing an organ from one person and placing in another person). WHAT DO THE RESULTS OF THE STUDY MEAN?: People with the risks listed above may be more likely to get invasive mold infections. People with these risks should talk to their doctor about invasive mold infections. Being aware of these risks may help doctors to be aware of which people are at risk of invasive mold infections.