Sexually Transmitted Infections in the Emergency Department.

As the United States faces a worsening epidemic of sexually transmitted infections (STIs), emergency departments (EDs) play a critical role in identifying and treating these infections. The growing health inequities in the distribution and disproportionate impact of STIs add to the urgency of providing high-quality sexual health care through the ED. Changes in population health are reflected in the new Centers for Disease Control recommendations on screening, diagnostic testing, and treatment of STIs. This review covers common, as well as and less common or emerging STIs, and discusses the state-of-the-art guidance on testing paradigms, extragenital sampling, and antimicrobial treatment and prevention of STIs.

Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

Implementing a New Algorithm for Reinterpretation of Ambiguous Variants in Genetic Dilated Cardiomyopathy.

Dilated cardiomyopathy is a heterogeneous entity that leads to heart failure and malignant arrhythmias. Nearly 50% of cases are inherited; therefore, genetic analysis is crucial to unravel the cause and for the early identification of carriers at risk. A large number of variants remain classified as ambiguous, impeding an actionable clinical translation. Our goal was to perform a comprehensive update of variants previously classified with an ambiguous role, applying a new algorithm of already available tools. In a cohort of 65 cases diagnosed with dilated cardiomyopathy, a total of 125 genetic variants were classified as ambiguous. Our reanalysis resulted in the reclassification of 12% of variants from an unknown to likely benign or likely pathogenic role, due to improved population frequencies. For all the remaining ambiguous variants, we used our algorithm; 60.9% showed a potential but not confirmed deleterious role, and 24.5% showed a potential benign role. Periodically updating the population frequencies is a cheap and fast action, making it possible to clarify the role of ambiguous variants. Here, we perform a comprehensive reanalysis to help to clarify the role of most of ambiguous variants. Our specific algorithms facilitate genetic interpretation in dilated cardiomyopathy.

Gut-associated microbes are present and active in the pig nasal cavity.

The nasal microbiota is a key contributor to animal health, and characterizing the nasal microbiota composition is an important step towards elucidating the role of its different members. Efforts to characterize the nasal microbiota composition of domestic pigs and other farm animals frequently report the presence of bacteria that are typically found in the gut, including many anaerobes from the Bacteroidales and Clostridiales orders. However, the in vivo role of these gut-microbiota associated taxa is currently unclear. Here, we tackled this issue by examining the prevalence, origin, and activity of these taxa in the nasal microbiota of piglets. First, analysis of the nasal microbiota of farm piglets sampled in this study, as well as various publicly available data sets, revealed that gut-microbiota associated taxa indeed constitute a substantial fraction of the pig nasal microbiota that is highly variable across individual animals. Second, comparison of herd-matched nasal and rectal samples at amplicon sequencing variant (ASV) level showed that these taxa are largely shared in the nasal and rectal microbiota, suggesting a common origin driven presumably by the transfer of fecal matter. Third, surgical sampling of the inner nasal tract showed that gut-microbiota associated taxa are found throughout the nasal cavity, indicating that these taxa do not stem from contaminations introduced during sampling with conventional nasal swabs. Finally, analysis of cDNA from the 16S rRNA gene in these nasal samples indicated that gut-microbiota associated taxa are indeed active in the pig nasal cavity. This study shows that gut-microbiota associated taxa are not only present, but also active, in the nasal cavity of domestic pigs, and paves the way for future efforts to elucidate the function of these taxa within the nasal microbiota.

INDURG TRIAL PROTOCOL: A RANDOMIZED CONTROLLED TRIAL USING INDOCYANINE GREEN DURING CHOLECYSTECTOMY IN ACUTE CHOLECYSTITIS.

INTRODUCTION: Laparoscopic cholecystectomy is one of the most common gastrointestinal surgeries, and bile duct injury is one of its main complications. The use of real-time indocyanine green fluorescence cholangiography allows the identification of extrahepatic biliary structures, facilitating the procedure and reducing the risk of bile duct lesions. A better visualization of the bile duct may help to reduce the need for conversion to open surgery, and may also shorten operating time. The main objective of this study is to determine whether the use of indocyanine green is associated with a reduction in operating time in emergency cholecystectomies. Secondary outcomes are the postoperative hospital stay, the correct intraoperative visualization of the Calot's Triangle structures with the administration of indocyanine green, and the intraoperative complications, postoperative complications and morbidity according to the Clavien-Dindo classification. METHODS: This is a randomized, prospective, controlled, multicenter trial with patients diagnosed with acute cholecystitis requiring emergency cholecystectomy. The control group will comprise 220 patients undergoing emergency laparoscopic cholecystectomy applying the standard technique. The intervention group will comprise 220 patients also undergoing emergency laparoscopic cholecystectomy for acute cholecystitis with prior administration of indocyanine green. CONCLUSION: Due to the lack of published studies on ICG in emergency laparoscopic cholecystectomy, this study may help to establish procedures for its use in the emergency setting.

Unravelling the Mechanisms Behind Exercise Intolerance and Recovery in Long COVID.

BACKGROUND: Patients suffering from long COVID may exhibit autonomic dysregulation. However, the association between autonomic dysregulation and exercise intolerance and the impact of therapeutic interventions on its modulation remain unclear. This study investigated the relationship between heart rate recovery at the first minute (HRR1), a proxy for autonomic imbalance, and exercise intolerance in patients with long COVID. Additionally, the study aimed to assess the effects of a 12-week home-based inspiratory muscle training program on autonomic modulation in this patient population. METHODS: This study is a post hoc subanalysis of a randomized trial in which 26 patients with long COVID were randomly assigned to receive either a 12-week inspiratory muscle training program or usual care alone (NCT05279430). The data were analyzed using Pearson's correlation and linear mixed regression analysis. RESULTS: The mean age was 50.4±12.2 years, and 11 (42.3%) were women. Baseline HRR1 was significantly correlated with maximal functional capacity (peakVO2) (r=0.402, p=0.041). Patients with lower baseline HRR1 (≤ 22 bpm) exhibited higher resting heart rates and lower peakVO2. Inspiratory muscle training led to a more substantial increase in peakVO2 in patients with lower HRR1 at baseline (p=0.019). Additionally, a significant improvement in HRR1 was observed in the IMT group compared to the usual care group after 12-week (Δ +9.39, 95% CI=2.4-16.4, p=0.010). CONCLUSION: Lower baseline HRR1 is associated with exercise intolerance in long COVID patients and may serve as a valuable criterion for identifying individuals likely to benefit more from a home-based inspiratory muscle training program.

Aerobiological and clinical study in the semidesertic area of the Southeastern of Spain.

Aerobiological studies constitute a relevant tool to predict the most influential parameters over the pollen seasons with significant clinical relevance in the allergic populations. The aim of this study was to describe the aerobiological behaviour of the most relevant allergenic sources in the semi-arid area of southeast of Spain (Almería) and to investigate the correlation with meteorological factors and clinical symptoms of allergic patients. Daily pollen count and meteorological parameters of Almería, Spain, were compiled for ten years. The clinical symptoms of 248 allergic patients were also recorded. Descriptive statistics and correlations between variables were assessed. Multivariate analyses were performed to predict the influence of meteorological factors on pollen concentration and the risk of suffer respiratory symptoms. Eight pollen families were identified as the most relevant allergenic sources. Temperature correlated with main pollen season evolution of all taxa whereas rainfall and relative humidity only correlated in Oleaceae, Pinaceae, Amaranthaceae, Asteraceae and Urticaceae. Rainfall and relative humidity were the most influential predictors of pollen concentration, except in Amaranthaceaea and Poaceae families, while temperature only influenced on Cupressaceae and Urticaceae pollen concentrations. A significant positive influence was observed between maximum temperature and rainfall with the appearance of allergic symptoms in patients sensitized to grasses, Parietaria sp. and Olea sp. This study, highlight the main aerobiological features in the region and establish a suitable tool for clinical follow-up and management of allergic patients. Further studies are needed to establish an accurate measurement aimed to control and prevent pollinosis in sensitized patients.

Resistencia antibiótica y aspectos clínicos de Neisseria gonorrhoeae anorrectal en un hospital de CABA, Argentina / Antimicrobial resistance and clinical aspects in anorectal Neisseria gonorrhoeae in a hospital in CABA, Argentina

La infección por Neisseria gonorrhoeae (NG) es considerada de alta prioridad en salud pública, por su capacidad para desarrollar resistencia a la mayoría de los antibióticos empleados para tratarla. La presentación anorrectal suele ser asintomática y frecuente en hombres que tienen sexo con hombres (HSH). En Argentina, se recomienda terapia antibiótica dual (ceftriaxona+azitromicina/doxiciclina) como primera línea empírica. Este estudio observacional y retrospectivo se realizó para evaluar el porcentaje de positividad de NG anorrectal, el perfil de sensibilidad a penicilina, tetraciclina, ciprofloxacina, ceftriaxona, cefixima y azitromicina, así como los aspectos clínicos-epidemiológicos de los pacientes atendidos entre 20/10/2015 y 20/03/2020 en consultorios coloproctológicos de un hospital público. Se detectaron 55/436 hisopados rectales positivos para NG (13%). El 95% era HSH y 71%, VIH+. En 18/55 NG fue la única infección. Las co-infecciones más frecuentes: HPV (38%) y C. trachomatis (35%). La sensibilidad a cefalosporinas de espectro extendido (CEE) y a azitromicina fueron 100% y 98%, respectivamente. Se observó la emergencia local de los primeros cinco aislamientos de NG anorrectal con sensibilidad reducida (SR) a CEE, el primer aislamiento con categoría no-sensible a azitromicina y otro con SR a azitromicina concomitantemente con SR a CEE. Aunque el uso de terapia empírica dual sigue siendo adecuado para nuestra institución, se observó la emergencia de aislamientos con SR y NS a las drogas de primera línea, evidenciando la importancia de la vigilancia epidemiológica a nivel local para definir los tratamientos empíricos.

Neisseria gonorrhoeae (NG) infection is considered a high public health priority because of its ability to develop resistance to most of the antibiotics used to treat it.The anorectal presentation is generally asymptomatic and frequent in men who have sex with men (MSM). In Argentina, dual therapy (ceftriaxone+azithromycin/doxycycline) is recommended as first line empiric therapy.This observational and retrospective study was conducted to evaluate the percentage of anorectal NG positivity, the susceptibility profile to penicillin, tetracycline, ciprofloxacin, ceftriaxone, cefixime and azithromycin, as well as the clinical-epidemiological aspects of patients attended between 20/10/2015 and 20/03/2020 in coloproctology of a public hospital.We detected 55/436 positive rectal swabs for NG (13%). 95% were MSM and 71% were PLHIV. In 18/55 NG was the only infection. The most frequent co-infections: HPV (38%) and C. trachomatis (35%).Susceptibility to extended-spectrum cephalosporins (ESCs) and azithromycin was 100% and 98%, respectively. Local emergence of the first five anorectal NG isolates with decreased susceptibility (DS) to ESCs, the first isolate with nonsusceptible category to azithromycin and another with DS to azithromycin concomitantly with DS to ESCs were observed.Although the use of dual empirical therapy continues to be adequate for our institution, the emergence of isolates with DS and NS to first-line drugs was observed, evidencing the importance of epidemiological surveillance at the local level to define empirical treatments

Risk factors for shunt-dependent hydrocephalus after spontaneous subarachnoid hemorrhage.

INTRODUCTION: Subarachnoid haemorrhage (SAH) is one of the most frequent neurosurgical emergencies, most of them due to intracranial aneurysm rupture. Hydrocephalus is a prevalent complication with a high rate of complications. The aims of this study are to identify predictors of shunt-dependent hydrocephalus following aneurysmal SAH and to quantify the complications arising from ventriculoperitoneal shunts. METHODS: This study is about an observational retrospective analytic study of the patients with spontaneous SAH admitted to Miguel Servet Universitary Hospital between 2017 and 2022. Patients' clinical and radiological characteristics, type of treatment, diagnoses and treatment of hydrocephalus, complications of ventriculoperitoneal shunts and mortality are some of the data achieved in this study. A descriptive study of these variables has been done and, subsequently, the most relevant variables have been statistically analysed to identify patients with increasing risk of shunting for hydrocephalus. This study was authorized by the Ethics Committee prior to its elaboration. RESULTS: A total of 359 patients with spontaneous SAH were admitted to Miguel Servet Universitary Hospital between 2017 and 2022, with an intrahospitalary death rate of 25.3%. 66.3% of the total of patients with SAH were due to intracranial aneurysm rupture (n = 238). 45.3% of the patients with aneurysmal SAH required an external ventricular drain (EVD) to treat acute hydrocephalus. 11.7% (n = 28) developed a shunt-dependent hydrocephalus. Statistical significance was found between shunt-dependent hydrocephalus and the following: high score in modified Fisher scale and placement of EVD. The mean interval from EVD to ventriculoperitoneal shunt placement was 26.1 days. The mean rate of reoperation of patients after shunt was 17.7%, mostly due to infection. CONCLUSIONS: The most significant risk factor for shunt-dependent hydrocephalus after aneurysmal SAH was high Fisher grade and previous need of EVD. Shunt infections is the main cause of shunt reoperation. Early shunt placement in selected patients might reduce the rate of infectious complications.

Venous congestive encephalopathy secondary to arteriovenous fistula aggravated by cerebrospinal fluid shunt.

We present a unique clinical case of venous congestive encephalopathy in the context of a cerebral arteriovenous fistula with clinical worsening secondary to valvular overdrainage. ICP monitoring, the different pressure settings of the programable CSF shunt and the detailed clinical description that is carried out offer us enough data to understand that this case provides important pathophysiological knowledge to a little-known disease.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases.

Mutations in NR2E3, a gene encoding an orphan nuclear transcription factor, cause two retinal dystrophies with a distinct phenotype, but the precise role of NR2E3 in rod and cone transcriptional networks remains unclear. To dissect NR2E3 function, we performed scRNA-seq in the retinas of wildtype and two different Nr2e3 mouse models that show phenotypes similar to patients carrying NR2E3 mutations. Our results reveal that rod and cone populations are not homogeneous and can be separated into different sub-classes. We identify a previously unreported cone pathway that generates hybrid cones co-expressing both cone- and rod-related genes. In mutant retinas, this hybrid cone subpopulation is more abundant and includes a subpopulation of rods transitioning towards a cone cell fate. Hybrid photoreceptors with high misexpression of cone- and rod-related genes are prone to regulated necrosis. Overall, our results shed light on the role of NR2E3 in modulating photoreceptor differentiation towards cone and rod fates and explain how different mutations in NR2E3 lead to distinct visual disorders in humans.

ompA Sequencing and Multilocus Sequence Typing of Lymphogranuloma Venereum Cases in Buenos Aires Reveal New Chlamydia trachomatis Genotypes.

Since the Lymphogranuloma venereum (LGV) outbreak was first described in Buenos Aires in 2017, the detected strains presented peculiar characteristics. Our goal was to increase the understanding of the strains involved in the LGV outbreak in Argentina. We characterized the ompA gene sequences, using Sanger sequencing, of 88 LGV strains from 239 symptomatic patients in Buenos Aires enrolled between 2017 and 2019, and selected 20 C. trachomatis strains for further characterization using Multilocus Sequence Typing (MLST). Following the ompA gene analysis of the 88 LGV strains, we detected 43% L2b, 31% L1-like, and 26% L2. Among the 38 L2b samples analyzed, there were 7 distinct sequences, 3 of them not previously reported (L2bv12, L2bv13, and L2bv14). Additionally, we detected a strain with a new mutation (AM884176.1:g.59122A>T) found in the position defining L2 or L2b, proposed as L2i. Using MLST, five different sequence types (STs) were detected, including the ST2 (corresponding to the L1-like strains) and a new one (ST60). ST58 was associated with the concomitant presence of another STI and HIV. A high genetic diversity in C. trachomatis LGV strains in Argentina was observed in a short period of time, with a relatively low number of samples from a limited geographical area.

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

OBJECTIVES: Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT. METHODS: We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy. RESULTS: One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13 mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients. CONCLUSIONS: Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

Bacteremia associated with non-tunneled central venous catheters in children undergoing chronic hemodialysis. / Bacteriemia asociada a catéteres venosos centrales no tunelizados en niños en hemodiálisis crónica.

Introduction. Central venous catheter (CVC)-related infection is the main complication observed in patients undergoing hemodialysis with this type of venous access. Objective. To estimate the incidence of non-tunneled CVC-related bacteremia, analyze the frequency of causative agents, and explore associated risk factors in children undergoing hemodialysis. Population and methods. Retrospective study in children receiving hemodialysis via a non-tunneled CVC between June 1st, 2015 and June 30th, 2019. A logistic regression was carried out to assess risk factors that were predictors of CVC-related bacteremia. Independent risk factors were described as odds ratios with their corresponding 95% confidence interval (CI). A value of p < 0.05 was considered statistically significant. Results. A total of 121 non-tunneled CVCs were included in this study. The incidence of bacteremia was 3.15 per 1000 catheter-days. The most commonly isolated microorganism was Staphylococcus epidermidis (16 cases, 51.5%). Prior catheter infection was the only independent risk factor for the development of bacteremia associated with non-tunneled CVC (OR: 2.84, 95% CI: 1.01-7.96, p = 0.04). Conclusions. Prolonged use of non-tunneled CVCs for chronic hemodialysis was associated with a low incidence of bacteremia. Gram-positive microorganisms prevailed among causative agents. A prior CVC infection almost trebled the risk for CVC-related bacteremia in our pediatric population receiving hemodialysis.

Introducción. La infección asociada a catéter venoso central (CVC) es la principal complicación que presentan los pacientes en hemodiálisis en los que se usa este tipo de acceso. Objetivo. Estimar la incidencia de bacteriemia asociada a CVC no tunelizado, analizar la frecuencia de agentes causales y explorar factores de riesgo asociados en niños en hemodiálisis. Población y métodos. Estudio retrospectivo realizado en niños en hemodiálisis por CVC no tunelizado entre el 1 junio de 2015 y el 30 de junio de 2019. Para evaluar factores de riesgo predictores de bacteriemia asociada a CVC, se realizó regresión logística. Los factores de riesgo independiente se expresaron con odds ratio con sus respectivos intervalos de confianza del 95 %. Se consideró estadísticamente significativo un valor de p <0,05. Resultados. En este estudio se incluyeron 121 CVC no tunelizados. La incidencia de bacteriemia fue de 3,15 por 1000 días de catéter. El microorganismo aislado con mayor frecuencia fue Staphylococcus epidermidis (16 casos, 51,5 %). La infección previa del catéter fue el único factor de riesgo independiente encontrado para el desarrollo de bacteriemia asociada a CVC no tunelizado (OR: 2,84; IC95%: 1,017,96; p =0,04). Conclusiones. El uso prolongado de los CVC no tunelizados para hemodiálisis crónica se asoció con una incidencia baja de bacteriemia. Los gérmenes grampositivos predominaron como agentes causales. La presencia de infección previa del CVC aumentó en casi 3 veces el riesgo de bacteriemia asociada a CVC en nuestra población pediátrica en hemodiálisis.

Association between Post-Hospitalization Psychological Distress, Exercise Capacity, Physical Function and Health Status in COVID-19 Survivors.

This study aims to determine whether post-hospitalization psychological distress is associated with exercise capacity, physical function and health status in COVID-19 survivors. In this observational study, hospitalized COVID patients were included and divided into two groups according to the mental component summary subscale of the 12-item Short-Form Health Survey. Patients with a score ≤ 45 were included in the psychological distress group, and patients with a score > 45 were included in the non-psychological distress group. The main variables were exercise capacity, physical function, and health status. Patients were evaluated at discharge, 3 months, and at 6 months follow-up. Finally, a total of 60 patients were included in the study. Significant differences were found in exercise capacity, physical function, and health status (p < 0.05), with worse results in the group with psychological distress at discharge and 3 months follow-up. At 6 months after discharge, COVID patients with psychological distress exhibited worse results in exercise capacity, physical function, and health status, being significant exercise capacity and physical function (p < 0.05). It can be concluded that COVID patients with psychological distress at hospital discharge reported worse exercise capacity, physical function and health status at hospital discharge, 3 months and 6 months follow-up.

Efficacy and Safety of Ripretinib in Advanced Gastrointestinal Stromal Tumors within an Expanded Access Program: A Cohort Study.

Ripretinib, a novel tyrosine kinase inhibitor used in advanced gastrointestinal stromal tumors (GIST) resistant to standard therapies, was assessed in the United Kingdom (UK) within an Expanded Access Program (EAP). A retrospective review of patients treated between January 2020 and October 2021 within the ripretinib EAP in our Institution was conducted. Clinician-documented and mRECIST 1.1 assessments were collected. The primary endpoints were progression-free survival (PFS) and time to treatment discontinuation (TTD). Treatment beyond progression (TBP), overall survival (OS), objective response rates and safety data were also analyzed. Survival curves were constructed using the Kaplan-Meier method, and univariate and multivariate Cox regression analyses were performed. All analyses were performed with R software. Overall, forty-five patients were included. After a median follow-up of 24.2 (95% CI 19.7-29.7) months, the median PFS of the group receiving 150 mg ripretinib once daily (OD) was 7.9 (95% CI 5.6-19.3) months. In the cohort of 22 patients with dose escalation upon tumor progression to 150 mg ripretinib twice daily (BD), the median PFS from BD was 5.4 (95% CI 2.8-9.3) months. Overall, median PFS and OS values for patients on ripretinib were 9.7 (95% CI 8.3-18.1) and 14.0 (95% CI 9.9-NA) months, respectively. TTD was similar to PFS. TBP was observed in about one third of all patients. Objective responses to ripretinib OD and BD treatments were observed in 16.7% and 10.0% of the patients, respectively. No new safety signals were identified. In conclusion, patients with advanced GIST receiving ripretinib in the UK within the EAP reported prolonged benefits, in line with the recent phase III clinical trials.