Barriers and facilitators to tuberculosis diagnosis in Lima, Peru: a mixed methods study.

BACKGROUND: Tuberculosis (TB) infectiousness decreases significantly with only a few days of treatment, but delayed diagnosis often leads to late treatment initiation. We conducted a sequential explanatory mixed methods study to understand the barriers and facilitators to prompt diagnosis among people with TB. METHODS: We enrolled 100 adults who started TB treatment in the Carabayllo district of Lima, Peru, between November 2020 and February 2022 and administered a survey about their symptoms and healthcare encounters. We calculated total diagnostic delay as time from symptom onset to diagnosis. We conducted semi-structured interviews of 26 participants who had a range of delays investigating their experience navigating the health system. Interview transcripts were inductively coded for concepts related to diagnostic barriers and facilitators. RESULTS: Overall, 38% of participants sought care first from public facilities and 42% from the private sector. Only 14% reported being diagnosed with TB on their first visit, and participants visited a median of 3 (interquartile range [IQR] health facilities before diagnosis. The median total diagnostic delay was 9 weeks (interquartile range [IQR] 4-22), with a median of 4 weeks (IQR 0-9) before contact with the health system and of 3 weeks (IQR 0-9) after. Barriers to prompt diagnosis included participants attributing their symptoms to an alternative cause or having misconceptions about TB, and leading them to postpone seeking care. Once connected to care, variations in clinical management, health facility resource limitations, and lack of formal referral processes contributed to the need for multiple healthcare visits before obtaining a diagnosis. Facilitators to prompt diagnosis included knowing someone with TB, supportive friends and family, referral documents, and seeing a pulmonologist. CONCLUSIONS: Misinformation about TB among people with TB and providers, poor accessibility of health services, and the need for multiple encounters to obtain diagnostic tests were major factors leading to delays. Extending the hours of operation of public health facilities, improving community awareness and provider training, and creating a formal referral process between the public and private sectors should be priorities in the efforts to combat TB.

The impact of the COVID-19 pandemic on patients' experiences obtaining a tuberculosis diagnosis in Peru: a mixed-methods study.

BACKGROUND: The COVID-19 pandemic disrupted TB services worldwide, leading to diagnostic delays. There have been few published reports describing how the pandemic affected people's pathway to diagnosis from their own perspectives. We sought to evaluate the impact on the pandemic on people's experiences obtaining a TB diagnosis. METHODS: We performed a mixed-methods study, enrolling newly diagnosed TB patients from 12 health centers in Lima, Peru. We used structured surveys to quantify diagnostic delay, defined as the time between symptom onset and diagnosis, and in-depth interviews to understand the ways in which the pandemic affected the pathway to care. We compared diagnostic delay between patients enrolled during the first year of the pandemic to those diagnosed after using a Wilcoxon rank-sum test. We used an inductive content analysis approach to analyze interview content related to the pandemic. RESULTS: We enrolled 51 patients during November 2020-April 2021 (during the first year of the pandemic) and 49 patients during October 2021-February 2022. Median diagnostic delay was longer for patients diagnosed during the first year of the pandemic (median 15 [IQR 5-26] weeks compared to 6 [IQR 3-18] weeks, p = 0.027). Qualitative analysis of 26 interviews revealed that the pandemic affected participants' care-seeking behavior and their ability to access to TB diagnostic services, particularly for those diagnosed in the first year of the pandemic. Many participants initially had their symptoms attributed to COVID-19, resulting in delayed TB evaluation and additional costs for COVID-19 treatment. CONCLUSIONS: The COVID-19 pandemic impacted multiple steps in the pathway to care for TB patients in Lima, causing delays in TB diagnosis. These findings demonstrate how the shifting of health care resources to prioritize COVID-19 can lead to collateral damage for people with TB and other conditions.

Improved survival in patients with thyroid function test abnormalities secondary to immune-checkpoint inhibitors.

Immune-checkpoint inhibitors (ICI) are monoclonal antibodies which target molecules to enhance antitumor response. Several adverse events have been described and the major ICI-related endocrinopathies are thyroid dysfunction and hypophysitis. Its occurrence has been associated with improved outcomes, but it is still to be proven. We performed a retrospective study of patients treated with ICI between 2014 and 2019 at an oncologic center to characterize thyroid function test abnormalities (TFTA) and to evaluate clinical outcomes. We excluded patients without regular monitoring of thyroid function, with previous thyroid or pituitary disease, previous head/neck radiotherapy and who performed only one ICI cycle. We included 161 of 205 patients treated with pembrolizumab, nivolumab or ipilimumab for several neoplasms, with a median duration of 18.9 weeks (9.1-42.6) of ICI treatment and 49.4 weeks (26.5-75.8) of follow-up. New-onset TFTA was diagnosed in 18% of patients (n = 29), in median at 10.6 weeks (6.1-31.1) of ICI therapy. On the whole, 8.7% had primary hypothyroidism, 4.3% central hypothyroidism, 2.5% biphasic thyroiditis and 2.5% thyrotoxicosis. Patients who experienced primary or central thyroid dysfunction had a significantly improved overall response rate (58.6% vs 34.2%, p = 0.015) and overall survival (3.27 vs 1.76 years, p = 0.030), compared to the control group. The risk of mortality was two times higher for control group (adjusted HR = 2.43, 95% CI 1.13-5.23, p = 0.023). This study recognizes that primary and central thyroid dysfunction can be a predictive clinical biomarker of a better response to ICI across several neoplasms.

Surveillance of succinate dehydrogenase gene mutation carriers: Insights from a nationwide cohort.

OBJECTIVE: Mutations in the genes coding for succinate dehydrogenase (SDHx) are the most frequent germline alterations in pheochromocytomas and paragangliomas. Evidence for the advantages associated with presymptomatic screening for SDHx mutation carriers is scarce. This study describes a nationwide cohort of these mutation carriers and aims to compare patients with clinical manifestations of the disease and those diagnosed through genetic screening. DESIGN: Cross-sectional study. PATIENTS: SDHx mutation carriers (n = 118) followed through the Portuguese Oncology referral centres: 41 probands and 77 nonprobands. MEASUREMENTS: All participants were subjected to biochemical and body imaging examinations for a complete assessment of the extent and spread of disease. Clinical data obtained this way were further analysed. RESULTS: The mean age of this cohort was 44.5 ± 17.4 years, and more than half carried the same founder SDHB mutation. About 50.8% of the mutation carriers developed pheochromocytomas or paragangliomas. Compared to patients diagnosed through genetic screening, those diagnosed clinically were characterized by larger tumours (P < .001), more frequent metastases (P = .024), were more frequently subjected to surgery (P = .011) and radiotherapy (P = .013), and had worse outcomes, such as macroscopic positive margins (P = .034). Persistent and/or unresectable disease and disease-related mortality were also more frequent in symptomatic patients compared to those diagnosed through genetic screening (P = .014). CONCLUSIONS: In this nationwide cohort study, a large proportion of mutation carriers were found to develop SDHx-related neoplasia. Genetic testing and subsequent follow-up resulted in the diagnosis of smaller and nonmetastatic tumours, fewer treatment procedures, fewer complications and greater number of disease-free patients.

Potential clinical use of azithromycin against gastroenteritis-causing pathogens other than Campylobacter.

The activity of azithromycin against enteritis-producing agents other than Campylobacter spp. was studied. The susceptibility to azithromycin, through gradient test, of 88 clinical isolates (51 Salmonella spp., 23 Aeromonas spp., 10 Shigella sonnei and 4 Yersinia enterocolitica) for one year was studied prospectively. The results were compared with the activity of ampicillin, trimethoprim-sulfamethoxazole and ciprofloxacin by microdilution. For azithromycin, the minimum inhibitory concentration (MIC) 50 and MIC90 were 4 and 12 mg/l, respectively. Six (6.8%) isolates were simultaneously resistant to ampicillin, trimethoprim- sulfamethoxazole and ciprofloxacin, and 3 (50%) of them presented a MIC >256 mg/l. Azithromycin may be a good empirical therapeutic option for the treatment of bacterial enteritis.

Novel Peptidomic Approach for Identification of Low and High Molecular Weight Tauopathy Peptides Following Calpain Digestion, and Primary Culture Neurotoxic Challenges.

Tauopathy is a class of a neurodegenerative disorder linked with tau hyperphosphorylation, proteolysis, and aggregation. Tau can be subjected to proteolysis upon calpain activation in Alzheimer disease (AD), and traumatic brain injury (TBI). We and others have extensively researched calpain-mediated tau breakdown products (Tau-BDP; 45K, 35K, and 17K). Tau proteolysis might also generate low molecular weight (LMW ≤10K) proteolytic peptides after neurodegenerative damage. In this study, we have subjected purified tau protein (phospho and non-phospho) and mouse brain lysate to calpain-1 digestion to characterize the LMW generated by nano-liquid chromatography coupled to electrospray ionization to tandem mass spectrometry (nano-LC-ESI-MS/MS). We have also challenged differentiated primary cerebrocortical neuronal cultures (CTX) with neurotoxic agents (calcium ionophore calcimycin (A23187), staurosporine (STS), N-methyl-D-aspartate (NMDA), and Maitotoxin (MTX)) that mimic neurodegeneration to investigate the peptidome released into the conditioned cell media. We used a simple workflow in which we fractionate LMW calpain-mediated tau peptides by ultrafiltration (molecular weight cut-off value (MWCO) of 10K) and subject filtrate fractions to nano-LC-MS/MS analysis. The high molecular weight (HMW) peptides and intact proteins retained on the filter were analyzed separately by western blotting using total and phospho-specific tau antibodies. We have identified several novel proteolytic tau peptides (phosphorylated and non-phosphorylated) that are only present in samples treated with calpain or cell-based calpain activation model (particularly N- and C-terminal peptides). Our findings can help in developing future research strategies emphasizing on the suppression of tau proteolysis as a target.

[Association between the functional impact of osteoarthritis and body mass index in women]. / El índice de masa corporal como fenotipo en el perfil clínico y funcional en mujeres con osteoartritis de rodilla.

BACKGROUND: Obesity is associated with pain, reduction of function and quality of life in patients with osteoarthritis (OA). AIM: To describe the clinical profile of women with knee OA according to their body mass index (BMI). MATERIAL AND METHODS: Observational study in 308 women with knee OA. According to their BMI, they were classified as normal-weight, overweight and obese. The primary outcome measure was functionality evaluated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes were sleep quality evaluated using the Pittsburgh Sleep Quality Index (PSQI) and quality of life assessed with the European Quality of Life Five Dimension (EuroQol-5D). RESULTS: WOMAC, PSQI and EuroQol-5D scores were significantly higher in obese women. CONCLUSIONS: Overweight and obese women with OA have more sleep disorders, reduction on functionality and quality of life compared to their normal weight counterparts.

Effect of homogenisation in formation of thermally induced aggregates in a non- and low- fat milk model system with microparticulated whey proteins.

The objective of the research presented in this paper was to investigate how different characteristics of whey protein microparticles (MWP) added to milk as fat replacers influence intermolecular interactions occurring with other milk proteins during homogenisation and heating. These interactions are responsible for the formation of heat-induced aggregates that influence the texture and sensory characteristics of the final product. The formation of heat-induced complexes was studied in non- and low-fat milk model systems, where microparticulated whey protein (MWP) was used as fat replacer. Five MWP types with different particle characteristics were utilised and three heat treatments used: 85 °C for 15 min, 90 °C for 5 min and 95 °C for 2 min. Surface characteristics of the protein aggregates were expressed as the number of available thiol groups and the surface net charge. Intermolecular interactions involved in the formation of protein aggregates were studied by polyacrylamide gel electrophoresis and the final complexes visualised by darkfield microscopy. Homogenisation of non-fat milk systems led to partial adsorption of caseins onto microparticles, independently of the type of microparticle. On the contrary, homogenisation of low-fat milk resulted in preferential adsorption of caseins onto fat globules, rather than onto microparticles. Further heating of the milk, led to the formation of heat induced complexes with different sizes and characteristics depending on the type of MWP and the presence or not of fat. The results highlight the importance of controlling homogenisation and heat processing in yoghurt manufacture in order to induce desired changes in the surface reactivity of the microparticles and thereby promote effective protein interactions.

Effects of an Exercise Intervention in Frail Older Patients with Chronic Obstructive Pulmonary Disease Hospitalized due to an Exacerbation: A Randomized Controlled Trial.

The objective of this study was to determine whether an exercise intervention using a pedal exerciser is able to reduce disability in frail older patients with chronic obstructive pulmonary disease (COPD) during hospitalization due to an acute exacerbation. This study was a randomized, single-blind clinical trial. Fifty-eight frail older patients admitted to hospital due to an acute exacerbation of COPD (AECOPD) were included in this study. All patients received standard medical and pharmacological care. Patients assigned to the intervention group also received an exercise intervention. The main outcome measures were balance, muscle strength, and exercise capacity. Significant between-group differences were found in muscle strength (p = 0.028) and balance (p = 0.013) after the intervention. All the variables improved significantly (p < 0.05) in the exercise intervention group. In the intervention group, the mean difference in muscle strength between baseline and discharge was 10.47 N. Balance also improved, showing a mean difference of 7.56 seconds on the right leg and 6.57 seconds on the left leg. Exercise capacity improved as well, with a difference of 4.97 stands between baseline and discharge. All the variables showed impairment in the control group. In conclusion, an exercise intervention using a pedal exerciser during the hospital stay of frail elderly patients with an AECOPD improves muscle strength, balance, and exercise capacity.

The Arf family G protein Arl1 is required for secretory granule biogenesis in Drosophila.

The small G protein Arf like 1 (Arl1) is found at the Golgi complex, and its GTP-bound form recruits several effectors to the Golgi including GRIP-domain-containing coiled-coil proteins, and the Arf1 exchange factors Big1 and Big2. To investigate the role of Arl1, we have characterised a loss-of-function mutant of the Drosophila Arl1 orthologue. The gene is essential, and examination of clones of cells lacking Arl1 shows that it is required for recruitment of three of the four GRIP domain golgins to the Golgi, with Drosophila GCC185 being less dependent on Arl1. At a functional level, Arl1 is essential for formation of secretory granules in the larval salivary gland. When Arl1 is missing, Golgi are still present but there is a dispersal of adaptor protein 1 (AP-1), a clathrin adaptor that requires Arf1 for its membrane recruitment and which is known to be required for secretory granule biogenesis. Arl1 does not appear to be required for AP-1 recruitment in all tissues, suggesting that it is crucially required to enhance Arf1 activation at the trans-Golgi in particular tissues.

Evaluation of a novel procedure for rapid detection of carbapenemase-producing Enterobacteriaceae (CPE) using the LightMix® modular carbapenemase kits.

OBJECTIVES: Evaluation of the LightMix® modular carbapenemase kits for the rapid detection of carbapenemase-producing Enterobacteriaceae (CPE) and the application of these kits to the direct detection of colonized patients and bacteraemias. METHODS: The modular multiplex PCR kits targeting blaKPC, blaNDM, blaVIM, blaIMP and blaOXA-48-like carbapenem resistance genes were evaluated in terms of sensitivity and specificity for carbapenemase resistance in a set of 118 labelled clinical isolates. Among these, 96 were CPE genotypically characterized by PCR and sequencing. The limits of detection were calculated for the different carbapenem resistance genes in terms of cfu/mL. In addition, the kits were used to evaluate colonization of patients by CPE by comparing this assay with the Xpert® Carba-R Kit on 127 rectal, perirectal and pharyngeal samples. Blood cultures from bacteraemias (4) and spiked blood cultures (23) with genotypically characterized isolates were also evaluated. RESULTS: The overall sensitivity and specificity of the multiplex PCR assay was 99% and 100%, respectively. The limit of detection for blaKPC, blaVIM, blaIMP and blaOXA-48-like is 60 cfu/mL and for blaNDM 500 cfu/mL. The colonization and bacteraemia studies revealed a 100% agreement between the results obtained by this assay and the ones obtained by GeneXpert®. CONCLUSIONS: The LightMix® modular carbapenemase kits are highly reliable and utilizable assays for both colonized and septic patients, and can help in the improvement of infection control. Their modular design facilitates cost-effective detection of CPE in hospital settings.

Results of a Multimodal Program During Hospitalization in Obese COPD Exacerbated Patients.

The objective of this study was to analyze the results of a multimodal therapeutic program during hospitalization in obese AECOPD patients. This was a randomized, single-blind clinical trial conducted at two university hospitals in Granada, Spain. Forty-nine patients hospitalized due to AECOPD were randomly allocated to a control group (CG), in which patients received standard care, or to an intervention group (IG), in which patients were included in a multimodal therapeutic program, added to the standard care. The main outcome measures were pulmonary, physical (strength and exercise capacity) and perceived (dyspnea, quality of life and psychological distress) variables. Within-group significant improvements (p < 0.05) were found in physical and perceived variables in the IG after the treatment. In the CG, a significant decrease was found in lower limb strength and a significant improvement in dyspnea and in three subscales of the EuroQol-5D questionnaire. The between-groups analysis showed significant differences after the treatment on lower limb strength and exercise capacity values (p < 0.05), in three of the EuroQol-5D subscales, and in the total score and the depression subscale of the Hospital Anxiety and Depression Scale. A multimodal therapeutic program has a beneficial effect on physical functioning and perceived variables in hospitalized obese patients with AECOPD.

Changes in Cognitive Status in COPD Patients Across Clinical Stages.

Chronic obstructive pulmonary disease (COPD) is a progressive disease, its prevalence increases with age. COPD is frequently associated with co-morbidities such as cognitive impairment, and their clinical relevance has risen in the recent past. Cognitive function may fluctuate with the variable components of COPD like hypoxaemia, hypercapnia, lung function, exacerbations or severity of the disease. The objectives of this study were to examine whether the cognitive status of COPD patients is different across clinical stages (exacerbation, at discharge and stable COPD) and also if there are cognitive areas that have more potential to change than others. Prospective observational clinical study: 62 patients admitted to hospital due to acute exacerbation of COPD were evaluated at hospital admission; 61 at discharge; and finally, 48 patients with stable COPD completed the study and were included in the analysis. Cognitive status was assessed with the Montreal Cognitive Assessment (MoCA). Our results show that all clinical variables improved from exacerbation to discharge COPD. MoCA total score, visuoconstructional, attention, language, abstraction, delayed recall and orientation subscores improved significantly from exacerbation to discharge COPD (p < 0.05). MoCA total score, visuoconstructional and naming subscores worsened significantly from discharge to stable COPD (p < 0.05). Finally, from exacerbation to stable COPD all the clinical variables improved; MoCA total score and naming, attention, language, abstraction and delayed recall subscores have shown significant differences (p < 0.05). Cognitive status of COPD patients is different across clinical stages, and there are cognitive areas with more potential to change than others.

Unveiling the Rarity: A Case of a Mixed Neuroendocrine-Non-Neuroendocrine Tumor of the Gastroesophageal Junction.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are a rare group of heterogeneous tumors, consisting of an endocrine and a nonendocrine component, which can develop throughout the gastrointestinal (GI) tract. This case presents a 70-year-old man with a complex medical history who initially presented with an upper GI bleed. After being stabilized, he underwent an esophagogastroduodenoscopy (EGD) that revealed a suspicious gastroesophageal junction (GEJ) mass. Histopathological studies paired with immunohistochemical investigations of the mass confirmed the rare diagnosis of MiNENs. He then underwent an endoscopic submucosal dissection (ESD) with subsequent chemotherapy and adjunct radiotherapy, with no recurrence noted on post-treatment surveillance. This case highlights the need for an EGD, histopathological examination, and immunohistochemical staining for detecting the underlying etiology of an upper GI bleed.

Exploring the Role of the Private Sector in Tuberculosis Detection and Management in Lima, Peru: A Mixed-Methods Patient Pathway Analysis.

In Latin America, little is known about the involvement of private health-care providers in tuberculosis (TB) detection and management. We sought to gain a better understanding of current and potential roles of the private sector in delivering TB services in Peru. We conducted a mixed-methods study in North Lima, Peru. The quantitative component comprised a patient pathway analysis assessing the alignment of TB services with patient care-seeking behavior. The qualitative component comprised in-depth interviews with 18 private health-care providers and 5 key informants. We estimated that 77% of patients sought care initially at a facility with TB diagnostic capacity and 59% at a facility with TB treatment capacity. Among private facilities, 43% offered smear microscopy, 13% offered radiography, and none provided TB treatment. Among public-sector facilities, 100% offered smear microscopy, 26% offered radiography, and 99% provided TB treatment. Private providers believed they offered shorter wait times and a faster diagnosis, but they struggled with a lack of referral systems and communication with the public sector. Nonrecognition of private-sector tests by the public sector led to duplicate testing of referred patients. Although expressing willingness to collaborate with public-sector programs for diagnosis and referral, private providers had limited interest in treating TB. This study highlights the role of private providers in Peru as an entry point for TB care. Public-private collaboration is necessary to harness the potential of the private sector as an ally for early diagnosis.

Effects of aerobic exercise on components of the metabolic syndrome in older adults with type 2 diabetes mellitus: systematic review and meta-analysis. / Efectos del ejercicio aeróbico sobre los componentes del síndrome metabólico en adultos mayores con diabetes mellitus tipo 2: revisión sistemática y metaanálisis.

OBJECTIVE.: To determine the effects of aerobic exercise on the components of the metabolic syndrome in older adult diabetic patients by means of a systematic review with meta-analysis. MATERIALS AND METHODS.: We used the PubMed/Medline, Scopus, Cochrane library, Web of Science databases and the Google Scholar search engine. Randomized controlled trials (RCTs) were selected according to the inclusion criteria. Two reviewers independently determined whether studies met the inclusion criteria, extracted data, and used the Cochrane risk of bias tool (RoB 2). Quantitative analyses were performed in R v 4.0.5, using random effects. RESULTS.: We identified 8697 studies, of which 7 RCTs were included in the qualitative synthesis. Most studies were assessed as having a high or low RoB in at least three domains. Meta-analysis showed that aerobic exercise was effective in improving glucose levels (standardized mean difference [SMD]: -1.04; 95% confidence interval [95% CI] -1.27, -0.81), systolic blood pressure (SMD: -0.79; 95% CI: -1.02, -0.56), diastolic blood pressure (SMD: -0.75; 95% CI: -0.98, -0.52), glycosylated hemoglobin (SMD: -0.57, 95% CI: -0.77, -0.37), HDL (SMD: 0.35, 95% CI: 0.15, 0.55), triglycerides (SMD: -0.26, 95% CI: -0.47, -0.06). No significant adverse effects were reported. The level of certainty of the results was low for fasting glucose, moderate for systolic and diastolic blood pressure, and very low for the other outcomes, in addition to few adverse effects. However, these results should be interpreted with caution due to the use of surrogate markers. CONCLUSIONS.: Aerobic exercise was shown to have a significant improvement in the components of the metabolic syndrome in older diabetic adults, and no major adverse effects were reported. However, we recommend more RCTs with longer intervention time to establish the impact on symptoms and complications.Motivation for the study. The motivation for this research arises from the high prevalence of metabolic syndrome and diabetes mellitus around the world. Despite their impact, there is a gap in knowledge regarding non-pharmacological interventions in older adults aimed at improving the metabolic profile of these patients. Main findings. Our results show a significant improvement in glucose, blood pressure, glycosylated hemoglobin, HDL, and triglyceride levels after the aerobic exercise intervention. In addition, no significant adverse effects were observed. Public health implications. Physical exercise is an affordable and globally available strategy. It improves the metabolic profile of older adult patients with metabolic syndrome.

Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis.

INTRODUCTION: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer. METHODS AND ANALYSIS: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis. ETHICS AND DISCLOSURE: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235163.

Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights.

BACKGROUND: Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. METHODS: We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. RESULTS: At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. CONCLUSIONS: Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

Endometriosis: A Comprehensive Analysis of the Pathophysiology, Treatment, and Nutritional Aspects, and Its Repercussions on the Quality of Life of Patients.

Endometriosis is a chronic proinflammatory pathology characterized by the growth of tissue similar to the endometrium outside the uterus, affecting approximately 5 to 15% of women worldwide. Suffering from endometriosis entails a complex pathophysiological process, significantly impacting the quality of life and reproductive function of affected women; therefore, it must be addressed in a personalized and comprehensive manner, as its management requires a multidisciplinary approach. This article aims to conduct a comprehensive literature review of endometriosis, not only as a pathophysiological condition but also as a significant factor impacting the social, nutritional, and mental well-being of those who experience it. Emphasis is placed on the importance of understanding and assessing the impact of the pathology to provide a better and more comprehensive approach, integrating various alternatives and strategic treatments for the factors involved in its development. The aim is to provide a complete overview of endometriosis, from its pathophysiology to its impact on the quality of life of patients, as well as a review of current treatment options, both pharmacological and alternative, in order to broaden the perspective on the pathology to improve the care of patients with this disease.