Modulation of fungal phosphate homeostasis by the plant hormone strigolactone.

Inter-kingdom communication through small molecules is essential to the coexistence of organisms in an ecosystem. In soil communities, the plant root is a nexus of interactions for a remarkable number of fungi and is a source of small-molecule plant hormones that shape fungal compositions. Although hormone signaling pathways are established in plants, how fungi perceive and respond to molecules is unclear because many plant-associated fungi are recalcitrant to experimentation. Here, we develop an approach using the model fungus, Saccharomyces cerevisiae, to elucidate mechanisms of fungal response to plant hormones. Two plant hormones, strigolactone and methyl jasmonate, produce unique transcript profiles in yeast, affecting phosphate and sugar metabolism, respectively. Genetic analysis in combination with structural studies suggests that SLs require the high-affinity transporter Pho84 to modulate phosphate homeostasis. The ability to study small-molecule plant hormones in a tractable genetic system should have utility in understanding fungal-plant interactions.

On the outside looking in: roles of endogenous and exogenous strigolactones.

A collection of small molecules called strigolactones (SLs) act as both endogenous hormones to control plant development and as ecological communication cues between organisms. SL signalling overlaps with that of a class of smoke-derived compounds, karrikins (KARs), which have distinct yet overlapping developmental effects on plants. Although the roles of SLs in shoot and root development, in the promotion of arbuscular mycorrhizal (AM) fungal branching and in parasitic plant germination have been well characterized, recent data have illustrated broader roles for these compounds in the rhizosphere. Here, we review the known roles of SLs in development, growth of AM fungi and germination of parasitic plants to develop a framework for understanding the use of SLs as molecules of communication in the rhizosphere. It appears, for example, that there are many connections between SLs and phosphate utilization. Low phosphate levels regulate SL metabolism and, in turn, SLs sculpt root and shoot architecture to coordinate growth and optimize phosphate uptake from the environment. Plant-exuded SLs attract fungal symbionts to deliver inorganic phosphate (Pi) to the host. These and other examples suggest the boundary between exogenous and endogenous SL functions can be easily blurred and a more holistic view of these small molecules is likely to be required to fully understand SL biology. Related to this, we summarize and discuss evidence for a primitive role of SLs in moss as a quorum sensing-like molecule, providing a unifying concept of SLs as endogenous and exogenous signalling molecules.

Crystal structure of DRIK1, a stress-responsive receptor-like pseudokinase, reveals the molecular basis for the absence of ATP binding.

BACKGROUND: Plants reprogram metabolism and development to rapidly adapt to biotic and abiotic stress. Protein kinases play a significant role in this process by phosphorylating protein substrates that activate or inactivate signaling cascades that regulate cellular and metabolic adaptations. Despite their importance in plant biology, a notably small fraction of the plant kinomes has been studied to date. RESULTS: In this report, we describe ZmDRIK1, a stress-responsive receptor-like pseudokinase whose expression is downregulated under water restriction. We show the structural features and molecular basis of the absence of ATP binding exhibited by ZmDRIK1. The ZmDRIK1 kinase domain lacks conserved amino acids that are essential for phosphorylation activity. The crystal structure of the ZmDRIK1 kinase domain revealed the presence of a spine formed by the side chain of the triad Leu240, Tyr363, and Leu375 that occludes the ATP binding pocket. Although ZmDRIK1 is unable to bind nucleotides, it does bind the small molecule ENMD-2076 which, in a cocrystal structure, revealed the potential to serve as a ZmDRIK1 inhibitor. CONCLUSION: ZmDRIK1 is a novel receptor-like pseudokinase responsive to biotic and abiotic stress. The absence of ATP binding and consequently, the absence of phosphorylation activity, was proven by the crystal structure of the apo form of the protein kinase domain. The expression profiling of the gene encoding ZmDRIK1 suggests this kinase may play a role in downregulating the expression of stress responsive genes that are not necessary under normal conditions. Under biotic and abiotic stress, ZmDRIK1 is down-regulated to release the expression of these stress-responsive genes.

Use of a special Brazilian red-light emitting railroad worm Luciferase in bioassays of NEK7 protein Kinase and Creatine Kinase.

BACKGROUND: Luciferases, enzymes that catalyze bioluminescent reactions in different organisms, have been extensively used for bioanalytical purposes. The most well studied bioluminescent system is that of firefly and other beetles, which depends on a luciferase, a benzothiazolic luciferin and ATP, and it is being widely used as a bioanalytical reagent to quantify ATP. Protein kinases are proteins that modify other proteins by transferring phosphate groups from a nucleoside triphosphate, usually ATP. METHODS: Here, we used a red-light emitting luciferase from Phrixotrix hirtus railroad worm to determine the activity of kinases in a coupled assay, based on luminescence that is generated when luciferase is in the presence of its substrate, the luciferin, and ATP. RESULTS: In this work we used, after several optimization reactions, creatine kinase isoforms as well as NEK7 protein kinase in the absence or presence of ATP analogous inhibitors  to validate this new luminescence method. CONCLUSION: With this new approach we validated a luminescence method to quantify kinase activity, with different substrates and inhibition screening tests, using a novel red-light emitting luciferase as a reporter enzyme.

King Ghidorah technique for a trifurcation lesion in a very high-risk NSTEMI.

A 66-year-old male Jehovah's Witness arrived at the emergency room having experienced typical persistent angina.

Transcatheter aortic valve replacement planning with cardiac computed tomography in quadricuspid aortic valve stenosis: a case series.

Background: The presence of severe aortic stenosis in quadricuspid aortic valve (QAV) is an extremely rare combination, and it is unknown whether transcatheter aortic valve replacement (TAVR) is a safe option due to the low incidence. Case summary: We present two patients diagnosed with severe aortic stenosis with QAV morphology type 1 (Nakamura classification). All patients presented to our hospital for evaluation because of worsening functional class, dyspnoea, or syncope. During tomographic planning, the aortic annulus was measured at the level of the deepest sinus for the selection of the number of devices. Due to the presence of four cusps, the smallest cusp was excluded, and three sinuses were virtualized for placement of the pigtail catheter during the procedure. Without complications, a 23 mm Edwards SAPIEN 3 was deployed through the femoral artery in both patients. Control aortography showed no valve leakage or regurgitation. Discussion: In patients with QAV and aortic stenosis undergoing TAVR, similar to the tricuspid valve, tomographic planning can be used to ensure the success of the procedure. However, unlike the tricuspid valve, where the selection of the device number is based on the measurements of the aortic annulus at the level of the non-coronary sinus, in these QAV cases, we perform the measurements at the level of the deepest aortic sinus (right coronary sinus).

High risk of coronary artery obstruction during TAVR, how to avoid it?

BACKGROUND: Coronary artery obstruction after percutaneous aortic replacement is a complication with high short-term mortality secondary to the lack of timely treatment. There are various predictors of coronary obstruction prior to valve placement such as the distance from the ostia, the degree of calcification, the distance from the sinuses; In such a situation some measures must be taken to prevent and treat coronary obstruction. CASE PRESENTATION: An 84-year-old male, with severe aortic stenosis and high surgical risk, who was treated with TAVR. However, during the deployment of the valve he presented hemodynamic instability secondary to LMCA obstruction. The intravascular image showed obstruction of the ostium secondary to the displacement of calcium that he was successfully treated with a chimney stent technique. CONCLUSIONS: The high degree of calcification and the left ostium near the annulus are conditions for obstruction of the ostium at the time of valve release; In this context, provisional stenting prior to TAVR in patients at high risk of obstruction should be considered as a safe prevention strategy to achieve the success of the procedure.

Transcatheter aortic valve replacement before to breast cancer management: case report and literature review.

Background: The coexistence of aortic stenosis (AS) and neoplastic pathology are common due to shared risk factors with atherosclerotic disease, such as diabetes, inflammatory conditions, and smoking. Severe AS in patients with cancer requires careful assessment in order to select the appropriate therapeutic choices and their timing (i.e. valve treatment first vs. cancer treatment first). Case summary: A 66-year-old woman with a history of smoking was admitted to our centre due to heart failure (HF). During her hospitalization, severe AS with severe ventricular dysfunction and cancer were documented. Because of her severe heart disease, she was unable to receive antineoplastic treatment. Therefore, she underwent percutaneous surgery to treat the aortic valve. After that, the management of cancer became possible, which included bilateral radical mastectomy and chemotherapy.We are presenting a case of cancer coexisting with aortic stenosis and reduced left ventricle ejection fraction. In this case, we performed Transcatheter Aortic Valve Replacement (TAVR) with the aim of improving the ejection fraction, followed by chemotherapy. Discussion: Cancer patients may be further disadvantaged by AS if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and HF. Clinical trials and guidelines on TAVR exclude cohorts with limited life expectancy. Hence, the correct and optimal care for cancer patients with severe AS is complex. The TAVR, for cancer patients with severe AS, can more frequently be the best clinical choice by avoiding cardiopulmonary bypass, minimal invasiveness, and therefore, shorter recovery time.

Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis.

To conduct a systematic review and meta-analysis of studies assessing the association between serum vitamin D status and mortality in patients with COVID- 19. We searched PubMed and Embase for studies addressing the association of serum vitamin D levels and COVID-19 mortality published until April 24, 2022. Risk ratios (RRs) and 95% confidence interval (CIs) were pooled using fixed or random effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. The meta-analysis included 21 studies that measured serum vitamin D levels close to the date of admission, of which 2 were case-control and 19 were cohort studies. Vitamin D deficiency was associated with COVID-19 mortality in the overall analysis but not when the analysis was adjusted to vitamin D cutoff levels < 10 or < 12 ng/mL (RR 1.60, 95% CI 0.93-2.27, I2 60.2%). Similarly, analyses including only studies that adjusted measures of effect for confounders showed no association between vitamin D status and death. However, when the analysis included studies without adjustments for confounding factors, the RR was 1.51 (95% CI 1.28-1.74, I2 0.0%), suggesting that confounders may have led to many observational studies incorrectly estimating the association between vitamin D status and mortality in patients with COVID-19. Deficient vitamin D levels were not associated with increased mortality rate in patients with COVID-19 when the analysis included studies with adjustments for confounders. Randomized clinical trials are needed to assess this association.

Percutaneous mitral and tricuspid edge-to-edge repair as a bridge therapy to heart transplantation in advanced heart failure secondary to human immunodeficiency virus: a case report.

Background: Patients with end-stage heart failure (HF) and severe pulmonary hypertension (PH) are not eligible for heart transplant due to high mortality risk. Percutaneous interventions as edge-to-edge repair of the mitral/tricuspid valves are a safe and effective therapy as a bridge for transplantation in patients who have contraindications to heart transplantations (HTs). Case summary: A 44-year-old man with a previous diagnosis of infection by human immunodeficiency virus (HIV) was admitted at the emergency room for exertional dyspnoea. He was diagnosed with a decompensated heart failure with reduced ejection fraction (HFrEF), severe mitral and tricuspid regurgitation, and high probability of PH. He presented poor response to guided medical treatment, even after implantable cardiac resynchronization therapy defibrillator (CRT-D). He was listed for a cardiac transplant, but after right catheterization, he was not an ideal candidate for transplantation, so it was decided to undergo percutaneous mitral and tricuspid edge-to-edge repair as a bridge to transplantation. The post-operative course was uneventful, with significant improvement in New York Heart Association functional class. The patient underwent a successful heart transplant 10 months after the procedure. Discussion: In patients with advanced HF due to HIV, HT is an adequate treatment option. When there are functional mitral and tricuspid regurgitation and severe PH, despite optimal treatment according to current guidelines, percutaneous mitral and tricuspid repair therapy appears to be safe and effective for control of severe PH as a bridge measure for cardiac transplantation.

Valve-in-valve as a rescue treatment in retrograde migration of the transcatheter aortic valve to the left ventricle: a case report.

Background: The treatment of choice for patients with severe symptomatic pure native aortic valve regurgitation (PNAVR) is surgical aortic valve replacement (SAVR). However, not all patients are candidates for surgery because of comorbidities or are deemed high risk for surgery. In such cases, transcatheter aortic valve replacement (TAVR) has proved to be better than medical treatment. Case summary: A 78-year-old male with a history of ankylosing spondylitis was admitted with New York Heart Association III heart failure. The echocardiogram showed severe aortic regurgitation and a left ventricular ejection fraction of 52%. Because of high surgical risk and being refractory to medical RX, he was accepted for TAVR. The tomography of anatomical characteristics reported the absence of calcium and dilation of the aortic ring and aortic root. During the TAVR procedure, the patient experienced valve migration, but it was autonomously repositioned in the aortic annulus. As a rescue measure, a second valve was placed. Here, we present a case of valve migration to the left ventricle treated with a valve-in-valve procedure without the need for surgical treatment. Discussion: The absence of annulus calcification in PNAVR increases the risk of post-TAVR paravalvular leak and device embolization. Valve migration generally requires valve recovery and conversion to SAVR.

Complete revascularization with PCI in STEMI patients with multivessel disease, when is the appropriate time? / Revascularización completa mediante ICP en pacientes con STEMI y enfermedad coronaria multivaso, ¿cuál es el momento adecuado?

Objective: The purpose was to compare the outcomes of patients with ST-elevation myocardial infarction and multivessel coronary artery disease undergoing one-time multivessel revascularization (OTMVR) versus in-hospital staged complete revascularization with percutaneous coronary intervention. Methods: This was a single-center, retrospective, observational, and cohort study, including data from January 2013 to April 2019. A total of 634 patients were included in the study. Comparisons were made between patients who underwent in-hospital staged complete revascularization versus OTMVR. The primary endpoint was all-cause in-hospital mortality, secondary endpoints included cardiovascular complications, all-cause new hospitalization, and mortality evaluated at 30 days and 1 year. In addition, we constructed a logistic regression model for determining the risk factors that predicted mortality. Results: Of the 634 patients, 328 were treated with staged revascularization and 306 with OTMVR. About 76.7% were men, with a mean age of 63.3 years. Less complex coronary lesions and a higher proportion of the left anterior descending artery as the culprit vessel were found in the OTMVR group. Compared with staged revascularization, the primary and secondary endpoints occurred less frequently with OTMVR strategy. Conclusions: OTMVR did not generate more complications and demonstrate better clinical outcomes than in-hospital staged revascularization.

Objetivo: El propósito fue comparar resultados de pacientes con infarto agudo de miocardio con elevación del segmento ST y enfermedad coronaria multivaso sometidos a revascularización completa de un solo momento frente a revascularización completa por etapas mediante intervención coronaria percutánea. Métodos: Estudio cohorte observacional, retrospectivo, unicéntrico, con datos de enero de 2013 a abril de 2019, incluyendo 634 pacientes. Se compararon resultados entre pacientes sometidos a revascularización completa por etapas frente a revascularización completa en un solo momento. El objetivo primario fue valorar mortalidad intrahospitalaria por cualquier causa y como objetivos secundarios se evaluaron a 30 días y 1 año las complicaciones cardiovasculares, hospitalizaciones y mortalidad. Se construyó un modelo de regresión logística para determinar los factores de riesgo que predijeron mortalidad. Resultados: De 634 pacientes, 328 fueron tratados con revascularización por etapas y 306 con revascularización en una intervención. El 76.7% fueron hombres, con una media de edad de 63.3 años. En el grupo de revascularización de un solo tiempo se encontraron lesiones coronarias menos complejas y una mayor proporción de la arteria descendente anterior como vaso culpable. Comparado con el grupo de revascularización por etapas, los objetivos primarios y secundarios ocurrieron con menos frecuencia en el grupo de revascularización en un solo tiempo. Conclusiones: Comparada con la revascularización intrahospitalaria por etapas, la revascularización en una intervención lleva a mejores desenlaces clínicos sin generar más complicaciones.

COVID-19 vaccines: Update of the vaccines in use and under development.

The ongoing COVID-19 pandemic has imposed a series of challenges on the scientific community. One of the biggest was the development of safe and effective vaccines in record time, which could be achieved through a global effort. A topic of great discussion has been the technology surrounding these vaccines: ranging from the well-known inactivated virus vaccines to the latest RNA vaccines. As vaccines became available, another point also came into question: their efficacy and effectiveness against the original Wuhan strain and its variants. Among the numerous variants, 5 of them (Alpha, Beta, Gamma, Delta and, more recently, Omicron) gained greater prominence due to their epidemiological relevance. In this scenario, with numerous variants and several vaccine options, scientific information can often be mismatched. This review aims to provide an overview of the efficacy, effectiveness, and safety of 11 vaccines in use or under development against the original Wuhan strain and the variants of concern identified by the World Health Organisation (WHO). Simultaneously, we aim to explore possible scenarios that can be expected shortly regarding new variants and vaccines. Overall, COVID-19 vaccines have satisfactory efficacy and loss of effectiveness against SARS-CoV-2 variants, especially the Omicron strain.

La pandemia de COVID-19 en curso ha impuesto una serie de dificultades a la comunidad científica. Una de las mayores ha sido el desarrollo de vacunas seguras y efectivas en tiempo récord, lo cual ha podido lograrse mediante un esfuerzo global. Una cuestión objeto de gran discusión ha sido la tecnología que rodea a estas vacunas, que fluctúa entre las bien conocidas que contienen virus inactivados, a las últimas vacunas basadas en ARN. A medida que se fue disponiendo de vacunas, también surgió otro punto en cuestión: su eficacia y efectividad contra la cepa originaria de Wuhan y sus variantes. Entre estas, cinco de ellas (Alfa, Beta, Gama, Delta y, más recientemente Ómicron) ganaron mayor importancia debido a su relevancia epidemiológica. En este escenario, con numerosas variantes y diversas opciones de vacunas, la información científica puede verse a menudo desfasada. El objetivo de esta revisión fue aportar una visión general sobre la eficacia, efectividad y seguridad de once vacunas en uso o en desarrollo contra la cepa originaria de Wuhan y las variantes preocupantes identificadas por la Organización Mundial de la Salud (OMS). De manera simultánea, otro objetivo es explorar los posibles escenarios que pueden preverse a corto plazo en cuanto a las nuevas variantes y vacunas. En general, las vacunas contra la COVID-19 tienen una eficacia y una pérdida de efectividad satisfactorias contra las variantes del SARS-CoV-2, especialmente la cepa Ómicron.

Use of hydroxychloroquine and chloroquine in patients with COVID-19: a meta-analysis of randomized clinical trials.

COVID-19 has quickly become a public health problem worldwide, and treatment for this new disease is needed. Hydroxychloroquine is an antimalarial that in vitro studies have shown action against SARS-CoV-2, which is why it has been the target of clinical studies with conflicting results. Therefore, the aim of this systematic review was to assess the association of hydroxychloroquine use with the virological cure, clinical recovery, mortality, and development of adverse effects in patients with COVID-19. PubMed, Cochrane Library, and Lilacs were searched until 7 January 2021, for randomized clinical trials with COVID-19 patients treated with hydroxychloroquine or chloroquine. Of the 130 studies found, 12 met the inclusion criteria. Compared to the patient's control group, the risk ratio (RR) for the virological cure and clinical recovery with hydroxychloroquine or chloroquine use was 1.04 (95%CI 0.91-1.17) and 1.03 (95%CI 0.92-1.13), respectively. Hydroxychloroquine (with or without azithromycin) was also not associated with mortality (RR = 1.09, 95%CI 0.98-1.20). Treatment with hydroxychloroquine was associated with any adverse effects (RR = 1.50, 95%CI 1.18-1.81). Hydroxychloroquine or chloroquine use did not have a significant effect on virological cure, the time of clinical recovery, and improvement in survival in COVID-19 patients. However, patients who used hydroxychloroquine showed an increase in adverse effects.

Reliability, validity, interpretability and responsiveness of the DEMMI mobility index for Brazilian older hospitalized patients.

AIM: To translate and adapt cross-culturally the De Morton Mobility Index from English to Brazilian Portuguese. Furthermore, to test the content validity, reliability, construct validity, interpretability and responsiveness for older hospitalized patients. METHODS: After we carried out the translation and the cross-cultural adaptation of the De Morton Mobility Index and its administration instructions according to international guidelines, the content validity of De Morton Mobility Index was tested by experienced physiotherapists. In the sequence, the reliability, construct validity, interpretability and responsiveness were tested in a test-retest design with 93 older patients hospitalized in ward for clinical reasons. The reliability was tested by Cronbach's alpha coefficient (internal consistency), standard error measurement (agreement), and interclass correlation coefficients (intra and inter-examiner reliability). The construct validity was tested by Pearson's correlation between the De Morton Mobility Index score and the number of steps. Interpretability was analyzed by determining the minimum detectable change and the floor and ceiling effects (frequency of maximum and minimum scoring). Responsiveness was analyzed by effect size. RESULTS: The Brazilian version of the De Morton Mobility Index was made and adapted. The internal consistency (α = 0.89), reliability intra-(ICC = 0.94) and inter-examiners (ICC = 0.82), agreement were all adequate. The De Morton Mobility Index is validity when correlated with number of steps (r = 0.46). Floor or ceiling effects (<15%) were not observed and the responsiveness was high (ES = 3.65). CONCLUSION: The De Morton Mobility Index has shown adequate reliability, validity, interpretability and responsiveness for the evaluation of the mobility of older hospitalized patients.

Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: Respiratory illnesses is the most common manifestation of Coronavirus disease 2019 (COVID-19); however, myocardial injury has recently emerged as a frequent complication. METHODS: An observational, longitudinal, prospective, and multicenter study of hospitalized Mexican patients was made. We assessed the prevalence of myocardial injury and its relationship with complications and mortality. RESULTS: 254 COVID-19 patients were included. Their average age was 53.8 years old, 167 (65.7%) were male and 87 (34.3%) female. According to troponin levels, two populations were generated, those with and without myocardial injury. There was no difference in gender or age between both groups. However, there was a greater proportion of obesity and hypertension in myocardial injury group. Multivariate logistic regression analysis revealed that obesity (OR 2.029, 95% CI 1.039-3.961; p = 0.038), arterial oxygen saturation <90% (OR 2.250, 95% CI 1.216-3.560; p = 0.025), and systolic blood pressure <90 mmHg (OR 2.636, 95% CI 1.530-4.343; p = 0.042), were directly related to higher levels of troponins. Multivariate cox proportional hazards analysis showed that primary endpoint (mortality) was determined by overweight/obesity (OR 1.290, 95% CI 0.115-0.730; p = 0.009), ferritin levels (OR 1.001, 95% CI 1.000-1.001; p < 0.001), myocardial injury (OR 3.764, 95% CI 1.307-10.838; p = 0.014), septic shock (OR 4.104, 95% CI 1.142-14.132; p = 0.024), acute respiratory distress syndrome (OR 3.001, 95% CI 1.008-10.165; p = 0.040), and treatment with Hydroxychloroquine/Azithromycin (OR 0.357, 95% IC 0.133-0.955; p = 0.040). Secondary endpoint (Mechanical ventilation risk) was associated to the same factors. CONCLUSIONS: Myocardial injury represents an increased risk of complications and death in Mexican hospitalized patients with COVID-19.

Physiotherapist advice to older inpatients about the importance of staying physically active during hospitalisation reduces sedentary time, increases daily steps and preserves mobility: a randomised trial.

QUESTIONS: Does advice from a physiotherapist about the importance of staying physically active during hospitalisation improve activity, mobility, strength, length of stay, and complications in older inpatients? What barriers to physical activity during hospitalisation do older inpatients perceive? DESIGN: Randomised controlled trial with concealed allocation, intention-to-treat analysis, and blinded assessment. PARTICIPANTS: Sixty-eight people who were aged > 60 years and admitted to a university hospital ward. INTERVENTION: In addition to usual hospital care, the experimental group received a booklet with content about the deleterious effects of hospitalisation and the importance of staying active during hospitalisation. The control group received usual hospital care only. OUTCOME MEASURES: The amount of physical activity was measured via accelerometry during the hospital admission. Mobility was assessed using the de Morton Mobility Index (DEMMI), and muscle strength was assessed using a handgrip dynamometer. Length of stay and complications were extracted from hospital records. The barriers to staying active during hospitalisation were investigated via a questionnaire. RESULTS: Accelerometry showed a mean between-group difference of 974 steps/day (95% CI 28 to 1919) in favour of the experimental group. The intervention also increased moderate-intensity physical activity and reduced sedentary time, although these effects might be trivially small. Experimental group participants were about one-fifth as likely to lose mobility during their hospital admission (two of 33) than control group participants (10 of 35), relative risk 0.21 (95% CI 0.05 to 0.90). Effects of the intervention were unclear regarding muscle strength, length of stay and incidence of complications between the groups. Patients reported that the main barriers to remaining active during hospitalisation were dyspnoea, lack of space, and fear of contracting infection. CONCLUSION: In older inpatients, the addition of advice from a physiotherapist about maintaining activity during hospitalisation increases the level of physical activity and prevents loss of mobility. REGISTRATION: ClinicalTrials.govNCT03297567.

Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis

ABSTRACT To conduct a systematic review and meta-analysis of studies assessing the association between serum vitamin D status and mortality in patients with COVID- 19. We searched PubMed and Embase for studies addressing the association of serum vitamin D levels and COVID-19 mortality published until April 24, 2022. Risk ratios (RRs) and 95% confidence interval (CIs) were pooled using fixed or random effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. The meta-analysis included 21 studies that measured serum vitamin D levels close to the date of admission, of which 2 were case- control and 19 were cohort studies. Vitamin D deficiency was associated with COVID-19 mortality in the overall analysis but not when the analysis was adjusted to vitamin D cutoff levels < 10 or < 12 ng/mL (RR 1.60, 95% CI 0.93-2.27, I2 60.2%). Similarly, analyses including only studies that adjusted measures of effect for confounders showed no association between vitamin D status and death. However, when the analysis included studies without adjustments for confounding factors, the RR was 1.51 (95% CI 1.28-1.74, I2 0.0%), suggesting that confounders may have led to many observational studies incorrectly estimating the association between vitamin D status and mortality in patients with COVID-19. Deficient vitamin D levels were not associated with increased mortality rate in patients with COVID-19 when the analysis included studies with adjustments for confounders. Randomized clinical trials are needed to assess this association.