Prolonged-release pirfenidone in patients with pulmonary fibrosis as a phenotype of post-acute sequelae of COVID-19 pneumonia. Safety and efficacy.

INTRODUCTION: One of the major concerns with post-acute sequelae of COVID-19 (PASC) is the development of pulmonary fibrosis, for which no approved pharmacological treatment exists. Therefore, the primary aim of this open-label study was to evaluate the safety and the potential clinical efficacy of a prolonged-release pirfenidone formulation (PR-PFD) in patients having PASC-pulmonary fibrosis. METHODS: Patients with PASC-pulmonary fibrosis received PR-PFD 1800 mg/day (1200 mg in the morning after breakfast and 600 mg in the evening after dinner) for three months. Blood samples were taken to confirm the pharmacokinetics of PR-PFD, and adverse events (AEs) were evaluated monthly using a short questionnaire. Symptoms, dyspnea, and pulmonary function tests (spirometry, diffusing capacity for carbon monoxide, plethysmography, and 6-min walk test [6MWT]) were evaluated at baseline, and one and three months after having started the PR-PFD treatment. RESULTS: Seventy subjects with mild to moderate lung restriction were included. The most common AEs were diarrhea (23%), heartburn (23%), and headache (16%), for which no modifications in the drug study were needed. Two patients died within the first 30 days of enrolment, and three opted not to continue the study, events which were not associate with PR-PFD. Pulmonary function testing, 6MWT, dyspnea, symptoms, and CT scan significantly improved after three months of treatment with PR-PFD. CONCLUSION: In patients with PASC pulmonary fibrosis, three months' treatment with PR-PFD was safe and showed therapeutic efficacy. Still, it remains to be seen whether the pulmonary fibrotic process remains stable, becomes progressive or will improve.

Immediate changes in intra-abdominal pressure and lung indicators in patients undergoing complex ventral hernia repair with the transversus abdominis muscle release, with and without preoperative botulinum toxin.

PURPOSE: The current treatment of complex ventral hernias involves muscle closure with components separation techniques and mesh placement. The purpose of this study is to evaluate the immediate postoperative changes in the intra-abdominal pressure (IAP), and lung indicators after treatment of complex ventral hernias with the transversus abdominis reléase (TAR) technique. METHODS: All patients with complex ventral hernias treated between November 28th, 2016 and October 6th, 2021 were initially included. We excluded patients with lung and/or heart comorbidities. A total of 43 patients were studied, measuring IAP, lung compliance, pulmonary plateau pressure (PPP), and end-tidal CO2 before and after surgical treatment. RESULTS: Median IAP increased from 5 to 9 mmHg (p < 0.0001), and PPP from 11 to 12 mmHg (p = 0.004). Increased body mass index (BMI) was associated to a PPP increase above normal values. Postoperative changes were not different in patients receiving preoperative preparation with botulinum toxin. CONCLUSION: After complex ventral hernia closure, there is an immediate impact on IAP and PPP, the latter more frequent in patients with the highest BMI, and this may not be prevented by the preoperative administration of botulinum toxin.

Luxación tibiofibular proximal diagnóstico y tratamiento / Proximal tibiofibular joint dislocation diagnosis and treatment

Resumen: Introducción: La luxación tibiofibular proximal (LTFP) es una lesión poco frecuente y no diagnosticada. De no ser tratada a tiempo, puede generar una sintomatología crónica de dolor e inestabilidad. La escasa evidencia disponible no entrega un protocolo de enfrentamiento ni consenso respecto a su manejo. Con el objetivo de asistir al enfrentamiento de esta lesión, se presenta una revisión de la literatura de una LTFP con reducción espontánea. Caso clínico: Hombre de 22 años consulta por dolor intenso en su rodilla derecha, posterior a caída en cuatrimoto. Al examen físico con aumento de volumen doloroso en cara lateral de la rodilla y pierna proximal, con movilidad completa y estable. Radiografías son informadas sin alteraciones. Se mantiene la sospecha clínica de LTFP, se continúa estudio con resonancia magnética (RM), la que es sugerente de LTFP. Dentro de las 24 horas de evolución, el paciente indica haber sentido un clank espontáneo en su rodilla afectada con cese completo de sintomatología. Se sigue al paciente por tres meses con RM de control, manteniendo una rodilla asintomática; examen físico y funcionalidad normal. Conclusión: El diagnóstico de las LTFP requiere un adecuado uso de imágenes. Su manejo consiste en una reducción cerrada de urgencia y de no lograrse, una reducción abierta, reparación y fijación interna. El pronóstico de las reducciones espontáneas es incierto, por lo que deben ser seguidas de forma seriada y en caso de recidiva, manejadas quirúrgicamente según el tiempo de evolución.

Abstract: Introduction: Proximal tibiofibular joint dislocations (PTFJD) are uncommon and underdiagnosed injuries. Urgent reduction is mandatory to avoid chronic disfunction. The scarcely available literature does not present a unified management guideline. An acute PTFJD case report with spontaneous reduction and a review of the literature is presented, aiming to assist the diagnosis and management of this pathology. Case report: A 22-years old male presented to the emergency department with high intensity right knee pain after falling in a four-wheel motorcycle. The physical exam revealed a prominent painful mass on the lateral aspect of his knee and proximal leg. His range of motion and knee stability were unremarkable. X-rays were informed negative for musculoskeletal injuries. According to a sustained suspicion of PTFJD, the study was continued with a magnetic resonance imaging (MRI), which suggested PTFJD. During the following 24 hours, the patient referred he was entirely asymptomatic after feeling a loud «clank¼. He has been followed for three months with MRI, and remains asymptomatic with full functions. Conclusion: PTFJD diagnosis requires appropriate images. Urgent close reduction is mandatory; if unsuccessful, open reduction, primary repair and internal fixation are indicated. The prognosis of spontaneous reduction remains uncertain and requires a serial clinical evaluation. In the case of recurrence, the appropriate surgical management is indicated according to the elapsed time from the injury.

[Proximal tibiofibular joint dislocation diagnosis and treatment]. / Luxación tibiofibular proximal diagnóstico y tratamiento.

INTRODUCTION: Proximal tibiofibular joint dislocations (PTFJD) are uncommon and underdiagnosed injuries. Urgent reduction is mandatory to avoid chronic disfunction. The scarcely available literature does not present a unified management guideline. An acute PTFJD case report with spontaneous reduction and a review of the literature is presented, aiming to assist the diagnosis and management of this pathology. CASE REPORT: A 22-years old male presented to the emergency department with high intensity right knee pain after falling in a four-wheel motorcycle. The physical exam revealed a prominent painful mass on the lateral aspect of his knee and proximal leg. His range of motion and knee stability were unremarkable. X-rays were informed negative for musculoskeletal injuries. According to a sustained suspicion of PTFJD, the study was continued with a magnetic resonance imaging (MRI), which suggested PTFJD. During the following 24 hours, the patient referred he was entirely asymptomatic after feeling a loud "clank". He has been followed for three months with MRI, and remains asymptomatic with full functions. CONCLUSION: PTFJD diagnosis requires appropriate images. Urgent close reduction is mandatory; if unsuccessful, open reduction, primary repair and internal fixation are indicated. The prognosis of spontaneous reduction remains uncertain and requires a serial clinical evaluation. In the case of recurrence, the appropriate surgical management is indicated according to the elapsed time from the injury.

INTRODUCCIÓN: La luxación tibiofibular proximal (LTFP) es una lesión poco frecuente y no diagnosticada. De no ser tratada a tiempo, puede generar una sintomatología crónica de dolor e inestabilidad. La escasa evidencia disponible no entrega un protocolo de enfrentamiento ni consenso respecto a su manejo. Con el objetivo de asistir al enfrentamiento de esta lesión, se presenta una revisión de la literatura de una LTFP con reducción espontánea. CASO CLÍNICO: Hombre de 22 años consulta por dolor intenso en su rodilla derecha, posterior a caída en cuatrimoto. Al examen físico con aumento de volumen doloroso en cara lateral de la rodilla y pierna proximal, con movilidad completa y estable. Radiografías son informadas sin alteraciones. Se mantiene la sospecha clínica de LTFP, se continúa estudio con resonancia magnética (RM), la que es sugerente de LTFP. Dentro de las 24 horas de evolución, el paciente indica haber sentido un clank espontáneo en su rodilla afectada con cese completo de sintomatología. Se sigue al paciente por tres meses con RM de control, manteniendo una rodilla asintomática; examen físico y funcionalidad normal. CONCLUSIÓN: El diagnóstico de las LTFP requiere un adecuado uso de imágenes. Su manejo consiste en una reducción cerrada de urgencia y de no lograrse, una reducción abierta, reparación y fijación interna. El pronóstico de las reducciones espontáneas es incierto, por lo que deben ser seguidas de forma seriada y en caso de recidiva, manejadas quirúrgicamente según el tiempo de evolución.

Aerial strategies advance volcanic gas measurements at inaccessible, strongly degassing volcanoes.

Volcanic emissions are a critical pathway in Earth's carbon cycle. Here, we show that aerial measurements of volcanic gases using unoccupied aerial systems (UAS) transform our ability to measure and monitor plumes remotely and to constrain global volatile fluxes from volcanoes. Combining multi-scale measurements from ground-based remote sensing, long-range aerial sampling, and satellites, we present comprehensive gas fluxes-3760 ± [600, 310] tons day-1 CO2 and 5150 ± [730, 340] tons day-1 SO2-for a strong yet previously uncharacterized volcanic emitter: Manam, Papua New Guinea. The CO2/ST ratio of 1.07 ± 0.06 suggests a modest slab sediment contribution to the sub-arc mantle. We find that aerial strategies reduce uncertainties associated with ground-based remote sensing of SO2 flux and enable near-real-time measurements of plume chemistry and carbon isotope composition. Our data emphasize the need to account for time averaging of temporal variability in volcanic gas emissions in global flux estimates.

Global monitoring of volcanic SO2 degassing with unprecedented resolution from TROPOMI onboard Sentinel-5 Precursor.

Over the last four decades, space-based nadir observations of sulfur dioxide (SO2) proved to be a key data source for assessing the environmental impacts of volcanic emissions, for monitoring volcanic activity and early signs of eruptions, and ultimately mitigating related hazards on local populations and aviation. Despite its importance, a detailed picture of global SO2 daily degassing is difficult to produce, notably for lower-tropospheric plumes, due largely to the limited spatial resolution and coverage or lack of sensitivity and selectivity to SO2 of current (and previous) nadir sensors. We report here the first volcanic SO2 measurements from the hyperspectral TROPOspheric Monitoring Instrument (TROPOMI) launched in October 2017 onboard the ESA's Sentinel-5 Precursor platform. Using the operational processing algorithm, we explore the benefit of improved spatial resolution to the monitoring of global volcanic degassing. We find that TROPOMI surpasses any space nadir sensor in its ability to detect weak degassing signals and captures day-to-day changes in SO2 emissions. The detection limit of TROPOMI to SO2 emissions is a factor of 4 better than the heritage Aura/Ozone Monitoring Instrument (OMI). Here we show that TROPOMI SO2 daily observations carry a wealth of information on volcanic activity. Provided with adequate wind speed data, temporally resolved SO2 fluxes can be obtained at hourly time steps or shorter. We anticipate that TROPOMI SO2 data will help to monitor global volcanic daily degassing and better understand volcanic processes and impacts.

Sex disparity persists in the prevention of cardiovascular disease in women on statin therapy compared to that in men.

BACKGROUND AND AIMS: The aim of this study was to assess whether women differ from men with regard to lowering lipid levels, achieving target of optimal lipid levels, and analyzing evidence-based dose and intensity of statin prescription in primary care patients. METHODS AND RESULTS: A multicenter cross-sectional survey was conducted among 1046 patients with dyslipidemia (554 women) who were receiving statin therapy from the Primary Health Care of Andalucía (Spain). A random sample was obtained using data from the electronic health record system. The primary outcomes were the prescription of statin therapy (intensity and dose), lowering lipid levels, and achieving target of optimal lipid levels. Women were less likely to be treated with a more potent statin than men (9.2% vs. 14.4%, p = 0.009), and they received lower doses (45 ± 59 mg/day vs. 56 ± 71 mg/day, p = 0.004) than men. Total cholesterol and LDL-C levels were higher in women than in men (5.7 ± 1.3 mmol/l vs. 5.2 ± 1.2 mmol/l, p < 0.0001 and 3.5 ± 1.2 mmol/l vs. 3.1 ± 1.0 mmol/l, p < 0.0001, respectively). Compliance with established goals for total cholesterol (47.7% vs. 31.3%, p < 0.0001) and LDL-C (39.7% vs. 25.4%, p < 0.0001) was superior in men than in women. In multivariate analysis, adjusted for age, the variables male gender and CVD were associated with a higher compliance with total cholesterol and LDL-C target levels, and the variable diabetes mellitus 2 was associated with a lower compliance with HDL-C and triglycerides target levels. CONCLUSIONS: Women were less likely to be prescribed high-intensity statin to achieve total cholesterol and LDL-C target levels, and mean doses of statin were lower in women than in men. Dyslipidemia is less closely controlled in women than in men.

Validez y confiabilidad de las escalas de evaluación funcional en pacientes críticamente enfermos. Revisión sistemática / Validity of scales for the functional assessment of critically ill patients

The decrease in mortality in critical patient units led to an increase in intensive care unit acquired weakness (ICUAW), which significantly affects the functional performance and quality of life of patients. There are several scales that measure functionality in critical patients. The aim of this systematic review is to determine the criterion validity and reliability of the scales that evaluate functionality in critically ill adult patients. We considered studies in critically ill adult subjects of both genders that determined the psychometric properties of the scales that evaluate functionality. Six minutes' walk test (6MWT), timed up and go (TUG), the Medical Research Council sum score (MRC-SS), grip strength, discharge destination and need for rehabilitation at discharge were considered as gold standards. Three scales were identified: PFIT-s, Perme MS, and DEMMI. PFIT-s has a positive correlation with 6MWT, MRC-SS and grip strength, and a negative correlation with TUG. It also predicts the need for rehabilitation at discharge and discharge to the home. DEMMI has a positive correlation with MRC-SS. the interobserver reliability was evaluated in three articles, demonstrating an almost perfect association. The intraobserver agreement was considered good in one report. With this information, it is not possible to determine which is the instrument with better measurement properties.

Aberrant expression of interleukin-10 in rheumatoid arthritis: Relationship with IL10 haplotypes and autoantibodies.

Interleukin 10 (IL-10) is an immunomodulatory cytokinethat plays a central rolein the pathogenesis of autoimmune diseases. Different studies consistently show increased IL-10 serum levels in rheumatoid arthritis (RA) and it appears to be caused by genetic variants. Three polymorphisms situated at positions -1082, -819 and -592 of IL10 gene and its major haplotypes have been associated with regulating IL10 promoter activity. In this study, we evaluated whether IL10 haplotypes are associated with mRNA expression and IL-10 serum levels as well as susceptibility to RA in a Western Mexican population. A total of 240 RA patients and 240 control subjects (CS) were included. Genotyping of IL10 polymorphisms was performed by PCR and PCR-RFLP, respectively. IL10 mRNA expression was determined by real-time PCR and IL-10 serum levels were measured using an ELISA kit. IL10 mRNA expression was 50-fold higher in RA patients than CS (p<0.001), while IL-10 serum levels did not show differences between groups. However, high IL-10 serum levels were positively related to a higherseropositivityfor rheumatoid factor (FR) and anti-CCP antibodies (p<0.05). No significant differences between the distribution of haplotype frequencies were observed between both study groups, but GCC haplotype was associated with higher IL-10 serum levels compared with the ACC and ATA haplotypes in RA patients (p<0.05). In addition, patients carrying ATA and GCC haplotypes showed higher mRNA expression than ACC (5.4-fold and 8.8-fold, respectively) and surprisingly, this trend was reversed in the controls, although it was not significant. In conclusion, our findings suggest that IL10 (GCC, ACC, and ATA) haplotypes may not be a susceptibility marker for RA in a population from Western Mexico. Nevertheless, independently of the presence of these variants, there is an aberrant overexpression of IL10 gene in RA, and it may play an important role in the pathogenesis of RA.

Factors associated with mixed dementia vs Alzheimer disease in elderly Mexican adults. / Factores asociados a la demencia mixta en comparación con demencia tipo Alzheimer en adultos mayores mexicanos.

INTRODUCTION: Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. MATERIAL AND METHODS: Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. RESULTS: We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004) CONCLUSIONS: DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix.

[Validity of scales for the functional assessment of critically ill patients]. / Validez y confiabilidad de las escalas de evaluación funcional en pacientes críticamente enfermos. Revisión sistemática.

The decrease in mortality in critical patient units led to an increase in intensive care unit acquired weakness (ICUAW), which significantly affects the functional performance and quality of life of patients. There are several scales that measure functionality in critical patients. The aim of this systematic review is to determine the criterion validity and reliability of the scales that evaluate functionality in critically ill adult patients. We considered studies in critically ill adult subjects of both genders that determined the psychometric properties of the scales that evaluate functionality. Six minutes' walk test (6MWT), timed up and go (TUG), the Medical Research Council sum score (MRC-SS), grip strength, discharge destination and need for rehabilitation at discharge were considered as gold standards. Three scales were identified: PFIT-s, Perme MS, and DEMMI. PFIT-s has a positive correlation with 6MWT, MRC-SS and grip strength, and a negative correlation with TUG. It also predicts the need for rehabilitation at discharge and discharge to the home. DEMMI has a positive correlation with MRC-SS. the interobserver reliability was evaluated in three articles, demonstrating an almost perfect association. The intraobserver agreement was considered good in one report. With this information, it is not possible to determine which is the instrument with better measurement properties.

Effects of omapatrilat on blood pressure and insulin sensitivity in an animal model of insulin resistance.

OBJECTIVE: To assess the effects of omapatrilat, fosinopril and placebo on blood pressure, plasma insulin, glucose and triglycerides concentrations in Zucker rats, a model for insulin resistance. DESIGN: Double blind, parallel, prospective trial. METHODS: Forty-two male obese Zucker (falfa) rats (aged 13-18 week) initially weighing 400-600 g were used for the experiments. Omapatrilat (n = 14), placebo (n = 14) or fosinopril (n = 14) were administrated once daily at 10 micromol/kg oral for 15 days. At baseline and at the end of the study, a tail-cuff blood pressure measurement was performed; an oral glucose tolerance test was done at the end of the study. RESULTS: Omapatrilat and fosinopril resulted in significant lower systolic blood pressure compared to the placebo group (p < 0.001). This parameter was significantly lower in the omapatrilat group compared with fosinopril-treated rats (116+/-9 vs 125+/-4 mmHg, p < 0.05). After an overnight fast, there was no difference in the fasting glucose concentrations among treatment groups. The basal and post-glucose challenge insulin concentrations were lower in the omapatrilat group compared to the placebo group. No difference was observed in the fasting triglycerides concentrations between the treatment groups. CONCLUSIONS: Compared to placebo and fosinopril treatment, omapatrilat results in lower arterial blood pressure in an animal model of insulin resistance. The results suggest that omapatrilat may have a positive effect on insulin sensitivity.

[Pneumonia complicated with empyema in children, to operate or not? Risk factors for surgery and review of the literature]. / Neumonía complicada con empiema en niños, operar o no operar? Factores de riesgo para cirugía y revisión de la literatura.

The precise indication for surgery for pleural empyema is still a controversy. With the aim of identifying the risk factors associated with surgery in pediatric patients with empyema post-pneumonia, a retrospective case control study was performed. From 1992 to 1996, 18 children underwent surgery (cases) and 12 did not (controls). The analyzed variables were those mentioned in the literature as risk factors. More than 25 days of evolution, more than three antibiotic schemes, fever, empyema organizing phase, two or more chest tubes lasting more than nine days, multiple loculations, trapped lung and paquipleura were associated with thoracostomy and decortication (p < 0.05). We conclude that a pediatric patient with a late referral to the hospital, empyema organizing phase, and multiple loculations with large purulent collections no longer susceptible to drainage and complications that impair lung expansion will probably require major surgery.

[Sensitivity, specificity, and predictive values of fine-needle biopsy in thyroid cancer]. / Sensibilidad, especificidad y valores predictivos de la biopsia con aguja fina en cáncer de tiroides.

One-hundred and eleven patients were studied with the objective of exploring the diagnostic usefulness of the fine needle aspiration (FNA) biopsy in cases with cancer of the thyroid gland. The mean age of the total sample was 42.4 years, with 89 percent females. A thyroid gland FNA was done in all cases as well as a surgical intervention for the establishment of a definitive diagnosis (i.e., gold standard). The cytologic diagnosis was done by the same expert pathologist in all cases. The diagnostic accuracy was obtained using a 2 x 2 table. Sensitivity was found to be 72 percent and specificity 91 percent, with 85.5 percent of diagnostic accuracy. Taking into account a 30 percent prevalence in our sample, predictive values were found to be 81 percent for positive and 87 percent for negative. It is concluded that FNA is better than the gold standard in the following points: it is easy to do, it has lower risk, and it has lower discomfort and financial cost. FNA showed a better utility to identify the absence of cancer. This is a procedure which is recommended for use in hospitals similar to the General Hospital of Mexico S.S. as part of the presurgical diagnosis in cases with clinical suspicion of thyroid gland malignancy.

Preventive role of atopy in lung cancer.

Incidence of atopic disease, serum and sputum IgE, and sputum IgA levels were studied in lung cancer patients, and compared with those in lung benign disease patients and normal controls. A significantly lower prevalence of personal atopic history was observed in the cancer group in comparison with the other two experimental groups. Patients with lung cancer showed significantly higher serum IgE levels than benign-disease and normal control individuals. At the same time, patients with epidermoid lung carcinoma had significantly increased levels of serum IgE and sputum IgA than those with lung adenocarcinoma.

Diarrea por Escherichia coli enteropatogenea (ECE) en el recien nacido.Su tratamiento compatativo con cefradina vs. cefadroxil. / Diarrhea by enteropathogenic Escherichia coli in newborn infants. Its comparative treatment with cephadine vs cefadroxil

La Escherichia coli enteropatogena (ECE) puede causar una enfermedad muy seria en el recien nacido (Hanson, L.A.). Su mecanismo patogenico aun es oscuro y discutible: sin embargo, estudios recientes indican que la diarrea puede ser causada por dos mecanismos: uno, discreto por Mc.Neish y cols., y el otro por Guerrant y cols.Con objeto de establecer nuestra propia experiencia al respecto, se estudiaron, en secuencia, 200 recien nacidos en las salas de cuna de los hospitales Juarez y Maternidad 2 A del IMSS. Se encontraron, en 60 de los casos, cepas de E. coli enteropatogenea (ECE) 086:B7 y 0126:B 16 y que respondieron satisfactoriamente al tratamiento. Nuestros hallazgos coinciden con los de otros investigadores