Neutrophils, an emerging new therapeutic platform.

Neutrophils possess unique characteristics that render them indispensable to health, and patients with irregular neutrophil counts or functions suffer from increased morbidity and mortality. As neutrophils are short-lived postmitotic cells, genetic aberrations cannot be corrected directly in neutrophils and must be targeted in their progenitors. Neutrophils are increasingly being contemplated for a range of therapeutic applications, including restoration or modulation of immune function and targeting of solid tumors. This review addresses the state-of-the-art in neutrophil transfusions and their possible applications for infectious disease prevention and treatment. It offers a landscape of the most recent gene therapy approaches to address neutrophil-related genetic diseases. We also discuss how ongoing research could broaden the applicability of neutrophil-based therapies to solid cancer treatments and beyond.

Central ECMO cannulation for severe dihydropyridine calcium channel blocker overdose.

Calcium channel blocker (CCB) toxicity carries a high mortality and is the sixth most fatal drug class reported to US poison centers. Amlodipine overdose is characterized by a life-threatening arterial vasodilation that compromises organ perfusion. The management of CCB intoxication is focused on maintaining adequate organ perfusion. In cases refractory to medical therapies, hemodynamic support with extracorporeal membrane oxygenation (ECMO) is warranted necessitating higher flows than usual to compensate for the vasodilation and requiring central cannulation. We present a case of a 12-year-old with severe dihydropyridine CCB ingestion, refractory to medical management and successfully treated with central ECMO cannulation. The patient was discharged home with no significant disability. Central ECMO cannulation may be helpful to facilitate adequate flows in vasodilatory shock such as CCB overdose.

Kocuria kristinae neuroinfection in an immunocompetent patient: a case report and review of the literature.

Few cases of disease by Kocuria kristinae have been reported, some in immunocompetent patients but mainly in immunocompromised. The current case report describes a 28-year-old female with an initial diagnosis of pituitary macroadenoma. After the initial surgery, the patient was readmitted due to tension pneumocephalus and cerebrospinal fluid (CSF) fistula. Cultures showed K. kristinae in the CSF and Candida albicans in the urine. The patient died after multiple complications. This is the first case of neuroinfection by K. kristinae in the American continent as reviewed. It was not determined as the main cause of death due to the sudden herniation, however, with active infection derived from the identification in two different samples, for this reason, we consider that it could be useful to take it as a cause of disease and a probable cause when the studies for detection of the most common pathogens have been negative.

Neoplasia mucinosa papilar intraductal del páncreas: características clínico-patológicas y supervivencia a largo plazo de pacientes sometidos a pancreatectomía / Intraductal papillary mucinous neoplasm of pancreas: clinicopathological features and long-term survival after surgical resection

Introducción La neoplasia mucinosa papilar intraductal (NMPI) del páncreas puede progresar de displasia de bajo grado a displasia de alto grado y carcinoma invasivo asociado. El objetivo de este trabajo fue describir las características clínico-patológicas y los resultados de seguimiento a largo plazo de pacientes con pancreatectomía por NMPI. Métodos En este estudio retrospectivo de un solo centro, se analizan los resultados de los pacientes sometidos a resección pancreática, con diagnóstico anatomopatológico de NMPI, desde enero del 2009 a diciembre del 2019. Resultados Un total de 31 pacientes tuvieron diagnóstico de NMPI. Nueve pacientes fueron varones y 22 mujeres. La edad media fue de 67 años. Veintisiete pacientes (87%) presentaron síntomas. Los estigmas de alto riesgo se encontraron en 20 pacientes (64,5%) y las características preocupantes («worrisome features») en 10 pacientes (32,2%). Siete pacientes tuvieron NMPI tipo conducto principal, 13 NMPI tipo rama y 11 NMPI tipo mixto. El carcinoma invasivo asociado estuvo presente en 13 pacientes (41,9%), la displasia de alto grado en 4 pacientes (12,9%) y la displasia de bajo grado en 14 pacientes (45,2%). El tiempo de seguimiento fue de 2 a 12 años. La supervivencia media de los pacientes con NMPI y carcinoma invasivo asociado fue de 45,8 meses y la supervivencia libre de enfermedad de estos pacientes fue de 40,8 meses. Conclusiones En nuestros pacientes operados, la NMPI tuvo mayor prevalencia en mujeres, fue predominantemente sintomática y tuvo una elevada incidencia de carcinoma invasivo asociado a las de tipo rama. La supervivencia a 5 años fue buena aun con carcinoma invasivo asociado. (AU)

Introduction Intraductal papillary mucinous neoplasm (IPMN) of pancreas can progress from low grade dysplasia to high grade dysplasia and invasive carcinoma. Methods in this single center retrospective series we analyze the clinicopathological features and long-term follow up of patients who underwent pancreatic resection for IPMN, from January 2009 to December 2019. Results 31 patients were diagnosed with IPMN. Nine males and 22 females. The mean age was 67 years. Twenty-seven patients (87%) were symptomatic. Seven patients had main duct IPMN, 11 branch type IPMN and 13 mixed type IPMN. High-risk stigmata were found in 20 patients (64.5%) and worrisome features in 10 patients (32.2%). Thirteen patients (41.9%) had an associated invasive carcinoma, 4 (12.9%) high-grade dysplasia and 14 (45.2%) low-grade dysplasia. The follow-up was from 2 to 12 years. Median survival for patients with IPMN and associated invasive carcinoma was 45.8 months and disease-free survival was 40.8 months. Conclusions IPMN had higher prevalence in females, mostly symptomatic and high incidence of associated invasive carcinoma with branch type. The 5-year survival was good even with associated invasive carcinoma. (AU)

Genotype and Phenotype Characterization of Patients with Mucopolysaccharidosis IV-A in Chile.

Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children's Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings. Methods: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases. Results: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (n = 10, 41.66%) and p.(Arg386Cys) (n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]. Conclusion: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.

Diagnostic Performance and Safety Profile of Robotic-assisted Bronchoscopy: A Systematic Review and Meta-Analysis.

Rationale: Conventional electromagnetic navigation bronchoscopy and other guided bronchoscopic modalities have a very desirable safety profile, but their diagnostic yield is only 60-70% for pulmonary lesions. Recently, robotic-assisted bronchoscopy (RAB) platforms have been introduced to improve the diagnostic performance of bronchoscopic modalities. Objectives: To determine the diagnostic performance and safety profile of RAB (using shape-sensing and electromagnetic navigation-based platforms) by performing a systematic review and meta-analysis. Methods: The PubMed, Embase, and Google Scholar databases were searched to find studies that reported on the diagnostic performance and/or the safety profile of one of the RAB systems. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was performed using MedCalc version 20.118. Pooled diagnostic yield was calculated using a Freeman-Tukey transformation. We planned to use a random-effects model if the I2 index was >40%. Results: Twenty-five studies were included: 20 including diagnostic and safety analyses and 5 including only safety analyses. The pooled diagnostic yield of RAB (20 studies, 1,779 lesions) was 84.3% (95% confidence interval, 81.1-87.2%). The I2 index was 65.6%. On the basis of our subgroup analyses, the heterogeneity was likely driven by differences in study designs (prospective vs. retrospective) and procedural protocols (such as different RAB systems). Lesion size > 2 cm, the presence of a computed tomography bronchus sign, and concentric radial endobronchial ultrasound view were associated with a statistically significant increase in the odds of diagnosis with RAB. The overall rates of pneumothorax, need for tube thoracostomy, and significant hemorrhage were 2.3%, 1.2%, and 0.5%, respectively. Conclusions: RAB systems have significantly increased the diagnostic yield of navigational bronchoscopy compared with conventional systems such as electromagnetic navigation bronchoscopy, but well-designed prospective studies are needed to better understand the impact of various factors, such as the use of three-dimensional imaging modalities, cryobiopsy, and specific ventilatory protocols, on the diagnostic yield of RAB.

Incidence of Air Leak Syndrome in Pediatric Patients With SARS-COV-2 Pneumonia and Respiratory Failure: A Single-Center Retrospective Study.

Air leak syndrome (ALS) is defined as the extrusion of air from an aerated compartment into an unaerated compartment with associated symptoms of respiratory distress. This syndrome can occur as a consequence of trauma, iatrogenic causes, or spontaneously. Retrospective investigations conducted in the adult population have demonstrated an elevated risk of spontaneous ALS development in patients with coronavirus disease 2019 (COVID-19) pneumonia, along with its correlation with mortality. However, no studies have yet explored this phenomenon within the pediatric population. In light of this knowledge gap, we conducted a retrospective chart review comprising 128 pediatric patients ranging in age from one month to 18 years. The primary objective was to assess the incidence of ALS in two distinct groups: patients diagnosed with COVID-19 pneumonia and those with non-COVID-19 viral pneumonia. The groups were compared using Fisher's exact test for sex, the presence of ALS, the requirement of extracorporeal membrane oxygenation (ECMO), and death. The modified Wald method was used to calculate the 95% confidence interval for the mortality rate in patients with COVID-19 pneumonia in the presence of ALS. Our findings revealed a higher prevalence of ALS in patients with COVID-19 pneumonia compared to the non-COVID-19 viral pneumonia group, with a statistically significant P-value of 0.02 and an odds ratio (OR) of 6.72. In terms of mortality rates, there was a statistically significant difference between the two groups (P = 0.025, OR = 1.083). In addition, in patients with ALS in the presence of COVID-19 pneumonia, the mortality rate was 37.5%. However, the requirement of ECMO was not statistically significant (P = 0.16, OR = 1.04). These results suggest that patients with COVID-19 pneumonia have an increased mortality rate and a heightened risk of developing ALS compared to individuals with other viral pneumonias. Furthermore, the presence of ALS was associated with a high mortality rate in COVID-19 pneumonia patients. However, it is crucial to note that obtaining a larger patient sample and involving multiple institutions would be necessary to obtain more consistent and robust data.

SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling.

SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 is a member of the IL6 family of cytokines. IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease and functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID-19, evidenced altered profibrotic gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID-19 disease.

La obesidad como factor de riesgo de gravedad por la infección de COVID-19

Los nuevos estilos de vida forzados por la pandemia, han mostrado un incremento en la incidencia en los niveles de índice de masa corporal de sobrepeso y obesidad en la población, a su vez estos casos, se visibilizaban más al estar relacionados con casos de gravedad por la enfermedad del COVID-19. Objetivo. Relacionar que el sobrepeso y obesidad, si son factores de riesgo y predicción de situaciones de gravedad por infección del COVID-19. Materiales y métodos. Se realizó un estudio, tipo descriptivo correlacional. Para esta investigación, se tomó muestra poblacional de personal voluntario de 48 personas, principalmente constituido por estudiantes y algunos docentes que pertenecen a la Facultad de Educación de la Universidad Nacional José Faustino Sánchez Carrión. Este personal fue evaluado en dos clínicas ubicadas en ciudades diferentes, la información biométrica y resultados de análisis de sangre, se consultó con personal médico asesor. Luego de un año se realizó una segunda evaluación, mediante una encuesta, para recabar información sobre la respuesta del sistema inmune del personal evaluado, ante una infección COVID-19 si fuera el caso. Se realizó la consulta médica respecto a los resultados obtenidos, sobre la correlación entre la obesidad, como factor de riesgo en el nivel de gravedad de la enfermedad COVID-19. Resultados. Se determinó que 13 personas evaluadas que corresponden: al 27.08% del total, registraron sobrepeso y presentaron clínicas leves o severas ocasionadas por el COVID-19. Conclusiones. Por lo que, este resultado demuestra que en personas con sobrepeso son propensos a padecer diversas enfermedades, esta situación de su comorbilidad, los expone a alto riesgo de llegar a situaciones graves de su salud por la infección del COVID-19.

The new lifestyles forced by the pandemic have shown an increase in the incidence of overweight and obesity body mass index levels in the population, and these cases are more visible because they are related to serious cases of COVID-19 disease. Objective. To relate that overweight and obesity are risk factors and predictors of severity situations due to COVID-19 infection. Materials and methods. A descriptive correlational study was carried out. For this research, a population sample of 48 volunteer personnel was taken, mainly made up of students and some teachers belonging to the Faculty of Education of the Universidad Nacional José Faustino Sánchez Carrión. These personnel were evaluated in two clinics located in different cities; the biometric information and blood test results were consulted with medical advisors. After one year, a second evaluation was carried out by means of a survey to gather information on the response of the immune system of the evaluated personnel to a COVID-19 infection, if applicable. A medical consultation was made regarding the results obtained on the correlation between obesity as a risk factor in the level of severity of COVID-19 disease. Results. It was determined that 13 people evaluated, corresponding to 27.08% of the total, were overweight and presented mild or severe symptoms caused by COVID-19. Conclusions. Therefore, this result shows that overweight people are prone to suffer from various diseases, this situation of their comorbidity, exposes them to high risk of reaching serious health situations due to COVID-19 infection.

Os novos estilos de vida forçados pela pandemia mostraram um aumento na incidência de níveis de índice de massa corporal de sobrepeso e obesidade na população, e esses casos se tornaram mais visíveis por estarem relacionados a casos graves da doença COVID-19. Objetivo. Relacionar que o sobrepeso e a obesidade são fatores de risco e preditores de situações de gravidade devido à infecção por COVID-19. Materiais e métodos. Foi realizado um estudo descritivo correlacional. Para esta pesquisa, foi tomada uma amostra populacional de 48 funcionários voluntários, composta principalmente por estudantes e alguns professores pertencentes à Faculdade de Educação da Universidad Nacional José Faustino Sánchez Carrión. Esses funcionários foram avaliados em duas clínicas localizadas em cidades diferentes, e as informações biométricas e os resultados dos exames de sangue foram consultados com consultores médicos. Após um ano, foi realizada uma segunda avaliação por meio de uma pesquisa para coletar informações sobre a resposta do sistema imunológico do pessoal avaliado a uma infecção por COVID-19, se aplicável. Foi realizada uma consulta médica com relação aos resultados obtidos sobre a correlação entre a obesidade como fator de risco no nível de gravidade da doença COVID-19. Resultados. Foi determinado que 13 pessoas avaliadas, correspondendo a 27,08% do total, estavam acima do peso e apresentavam sintomas leves ou graves causados pela COVID-19. Conclusões. Portanto, esse resultado mostra que as pessoas com sobrepeso são propensas a sofrer de várias doenças, essa situação de comorbidade as expõe a um alto risco de chegar a situações graves de saúde devido à infecção por COVID-19.

Factores asociados a sobrevida a un año en pacientes postoperados de glioblastoma.

OBJECTIVE: To identify factors associated with one-year survival in postoperative glioblastoma patients at a hospital in northeastern Mexico. MATERIAL AND METHODS: Nested case-control study. Patients operated on for glioblastoma between 2016-2019 were included. Information about clinical and surgical factors was obtained, survival was calculated by Kaplan-Meier analysis. Descriptive analysis was performed with medians and ranges, and inferential analysis with χ2, Fisher and Student t test, odds ratio and 95% confidence interval. A value of p < 0.05 was considered significant. RESULTS: Sixty-two patients with glioblastoma were included, 27 (43.5%) women and 35 (56.5%) men, median age 56 years (range: 6-83). Median survival was 3.6 months (1-52), 45 (72.6%) survived less than 12 months. The factors associated with a higher survival were administration of adjuvant treatment (p < 0.001), better functional status (p = 0.001), and absence of post-surgical complications (p = 0.034). CONCLUSIONS: Most patients with glioblastoma survive less than 12 months and the factors most strongly associated with longer survival are administration of adjuvant treatment, better functional status of the patient and absence of post-surgical complications.

OBJETIVO: Identificar los factores asociados a la sobrevida a un año en pacientes postoperados de glioblastoma en un hospital del noreste de México. MATERIAL Y MÉTODOS: Estudio de casos y controles anidado en una cohorte. Se incluyeron pacientes operados de glioblastoma entre 2016 y 2019. Se obtuvo la información sobre factores clínicos y quirúrgicos, se calculó la sobrevida mediante análisis de Kaplan-Meier. El análisis descriptivo se realizó con medianas y rangos, y el inferencial con prueba de χ2, Fisher, t de Student, razón de momios e intervalo de confianza al 95%. Se consideró significativo un valor de p < 0.05. RESULTADOS: Se incluyeron 62 pacientes con glioblastoma, 27 (43.5%) mujeres y 35 (56.5%) hombres, mediana de edad de 56 años (rango: 6-83). La mediana de sobrevida fue de 3.6 meses (1-52), 45 (72.6%) sobrevivieron menos de 12 meses. Los factores asociados a mayor sobrevida fueron: administración de tratamiento adyuvante (p < 0.001), mejor estado funcional (p = 0.001) y ausencia de complicaciones posquirúrgicas (p = 0.034). CONCLUSIONES: La mayoría de los pacientes con glioblastoma sobreviven menos de 12 meses y los factores más fuertemente asociados a mayor sobrevida son administración de tratamiento adyuvante, mejor estado funcional del paciente y ausencia de complicaciones posquirúrgicas.

Current Practices in Airway Stent Management: A National Survey of US Practitioners.

BACKGROUND: Despite a growing number of tracheobronchial stent types and indications, complications remain frequent, and high-quality evidence on practices to prevent stent-related complications is lacking. Understanding current management practice is a first step to designing prospective studies to assess whether specific practices aimed at mitigating stent-related complications improve patient-centered outcomes. OBJECTIVES: In this study, we aimed to understand current management strategies following tracheobronchial stenting. METHOD: We performed a nationwide survey of members of the American Association of Bronchology and Interventional Pulmonology (AABIP) and the General Thoracic Surgical Club (GTSC) who place airway stents. The electronic survey captured data on practitioners' demographics, practice setting, airway stent volume, and standard post-stent practices (if any) including the use of medications, mucus clearance devices, surveillance imaging, and surveillance bronchoscopy. RESULTS: One hundred thirty-eight physicians completed the survey. Respondents were majority male (75.4%) and had diverse training (50.0% completed interventional pulmonary fellowship; 18.1% thoracic surgery; 31.9% other stent training). Post-stent management strategies varied markedly across respondents; 75.4% prescribe at least one medication to prevent post-stent complications, 52.9% perform routine surveillance bronchoscopy in asymptomatic patients, 26.1% prescribe mucus clearance regimens, 16.7% obtain routine computed tomography scans in asymptomatic patients, and 8.3% routinely replace their stents prior to stent failure. CONCLUSIONS: In this national survey of practitioners who place airway stents, there was marked heterogeneity in post-stent management approaches. Further studies are needed to identify which, if any, of these strategies improve patient-centered outcomes.

Candida albicans the main opportunistic pathogenic fungus in humans / Candida albicans el principal hongo patógeno oportunista en humanos

Abstract Candida albicans is a commensal of the mammalian microbiome and the primarypathogenic fungus of humans. It becomes a severe health problem in immunocompromisedpatients and can cause a wide variety of mucosal and systemic infections. The interactionbetween C. albicans and host cells is characterized by the expression of virulence factors suchas adhesins and invasins, the secretion of hydrolytic enzymes, a transition from yeast to fil-amentous hyphae form, and the ability to form biofilms; these features collectively result in cell adhesion, invasion, and damage. This review describes complex commensal interactions of C. albicans with host cells and the cellular events that it triggers in a pathogenic environment. We also review the host immune response induced by C. albicans antigens and the mechanisms developed by this fungus to avoid the action of antifungal agents.

Resumen Candida albicans es un comensal del microbioma de mamíferos y el principal hongopatógeno de humanos. En pacientes inmunocomprometidos se convierte en un grave problemade salud por causar una amplia variedad de infecciones en mucosas y sistémicas. La interacciónentre C. albicans y las células del huésped lleva a la expresión de factores de virulencia, comoadhesinas e invasinas, a la secreción de enzimas hidrolíticas y a la transición de levadura a hifa filamentosa, capaz de para formar biopelículas, lo que genera adherencia, invasión y dano celular. En esta revisión describimos la compleja interacción comensal de C. albicans con la célula huésped y los eventos celulares que ejecuta en un ambiente patogénico. También se revisa la respuesta inmunitaria del huésped inducida por antígenos de C. albicans y los mecanismos desarrollados por este hongo para evitar la acción de agentes antifúngicos.

Safety of Transbronchial Biopsies in Patients with Pulmonary Hypertension: Systematic Review and Meta-Analysis.

Rationale: Transbronchial lung biopsies (TBLBs) are commonly performed by pulmonologists. Most providers consider pulmonary hypertension to be at least a relative contraindication to TBLB. This practice is based primarily on expert opinion, as there are very few patient outcomes data backing it. Objectives: We performed a systematic review and meta-analysis of previously published studies to determine the safety of TBLB in patients with pulmonary hypertension. Methods: The MEDLINE, Embase, Scopus, and Google Scholar databases were searched for pertinent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using MedCalc version 20.118 to calculate the weighted pooled relative risk of complications in patients with pulmonary hypertension. Results: Nine studies with a total of 1,699 patients were included in the meta-analysis. On the basis of the Newcastle-Ottawa Scale, the risk of bias was low in the included studies. The overall weighted relative risk of bleeding with TBLB in patients with pulmonary hypertension was 1.01 (95% confidence interval, 0.71-1.45) compared with patients without pulmonary hypertension. Heterogeneity was low; therefore, the fixed-effects model was used. In a subgroup analysis of three studies, the overall weighted relative risk of significant hypoxia in patients with pulmonary hypertension was 2.06 (95% confidence interval, 1.12-3.76). Conclusions: Our results show that the patients with pulmonary hypertension do not have a significantly elevated risk of bleeding with TBLB compared with control subjects. We hypothesize that significant postbiopsy bleeding might be preferentially originating from bronchial artery circulation as opposed to pulmonary artery circulation, much like episodes of massive spontaneous hemoptysis. This hypothesis can explain our results, as in this scenario, elevated pulmonary arterial pressure would not be expected to have a bearing on the risk of post-TBLB bleeding. Most of the studies in our analysis included patients with mild to moderate pulmonary hypertension and it is not clear if our results can be extrapolated to patients with severe pulmonary hypertension. We noted that the patients with pulmonary hypertension were at a higher risk of developing hypoxia and needing a longer duration of mechanical ventilation with TBLB compared with control subjects. Further studies are needed to better understand the origin and pathophysiology of post-TBLB bleeding.

Biocontrol of Diseases Caused by Phytophthora capsici and P. parasitica in Pepper Plants.

The main objective of this study was to evaluate the ability of Trichoderma aggressivum f. europaeum, T. longibrachiatum, Paecilomyces variotii, and T. saturnisporum as biological control agents (BCAs) against diseases caused by P. capsici and P. parasitica in pepper. For this purpose, their antagonistic activities were evaluated both in vitro and in vivo. We analysed the expression patterns of five defence related genes, CaBGLU, CaRGA1, CaBPR1, CaPTI1, and CaSAR8.2, in leaves. All BCAs showed a high in vitro antagonistic activity, significantly reducing the mycelial growth of P. capsici and P. parasitica. The treatments with T. aggressivum f. europaeum, T. longibrachiatum, and P. variotii substantially reduced the severity of the disease caused by P. capsici by 54, 76, and 70%, respectively, and of the disease caused by P. parasitica by 66, 55, and 64%, respectively. T. saturnisporum had the lowest values of disease reduction. Reinoculation with the four BCAs increased the control of both plant pathogens. Markedly different expression patterns were observed in the genes CaBGLU, CaRGA1, and CaSAR8.2. Based on the results, all four BCAs under study could be used as a biological alternative to chemicals for the control of P. capsici and P. parasitica in pepper with a high success rate.

Analysis of Fifty Years of Severe Malaria Worldwide Research.

This study analyzed fifty years of severe malaria research worldwide. Malaria is a parasitic disease that continues to have a significant impact on global health, particularly in sub-Saharan Africa. Severe malaria, a severe and often fatal form of the disease, is a major public health concern. The study used different bibliometric indicators such as the number of publications, citations, authorship, and keywords to analyze the research trends, patterns, and progress made in the field of severe malaria. The study covers the period from 1974 to 2021 and includes articles from Scopus. The results of the study indicated that there has been a steady increase in the number of publications on severe malaria over the past fifty years, with a particular increase in the last decade. The study also showed that most of the publications are from USA and Europe, while the disease occurs in Africa, South-East Asia, and the Americas. The study also identified the most frequent keywords used in the publications, and the most influential journals and authors in the field. In conclusion, this bibliometric study provides a comprehensive overview of the research trends and patterns in the field of severe malaria over the past fifty years and highlights the areas that need more attention and research efforts.

Statin protects men but not women with HIV against loss of muscle mass, strength, and physical function: a pilot study.

Statins are cholesterol-lowering drugs commonly used among people with HIV, associated with an increased risk of myopathies. Considering that cardiovascular disease, statin therapy, and sarcopenia are independently prevalent in people with HIV, clarity on the potential benefits or harms of statin therapy on muscle health is useful to provide insight into ways to maximize skeletal muscle health and minimize CVD risk in this population. We aimed to study the effects of statin therapy on strength, muscle mass, and physical function parameters in people with HIV. This was a pilot cross-sectional study. People with HIV on continuous statin therapy (n = 52) were paired 1:1 according to age (people with HIV 53.9 ± 8.2 and people with HIV on statins 53.9 ± 8.4 years), sex, body mass index (Body mass index, people with HIV 28.6 ± 5.3 and people with HIV on statins 28.8 ± 6.3 kg/m2), and race with people with HIV not using statin (n = 52). Participants were evaluated for muscle strength (i.e. handgrip strength), lean and fat body mass (using bioelectric impedance analysis), and physical function (i.e. Short Physical Performance Battery-SPPB). Isokinetic strength and appendicular lean mass (using dual-energy X-ray absorptiometry), more accurate strength and body composition measures, were determined in 38% of the participants. Overall, statin usage does not exacerbated loss of muscle strength (32.2 ± 11.5 vs. 30.3 ± 9.6 kg, p > 0.05) muscle mass (7.6 ± 1.8 vs. 7.7 ± 1.1 kg/m2, p > 0.05), and impaired physical performance (10.1 ± 1.8 vs. 9.7 ± 2.1 points, p > 0.05) of PLWH. When analyzed by sex, men living with HIV on statins usage presented higher appendicular muscle mass (28.4 ± 3.1 vs. 26.2 ± 4.9 kg, p < 0.05) handgrip strength (42.1 ± 8.8 vs. 37.1 ± 8.3 kg, p < 0.05) and physical function through SPPB score (10.9 ± 1.3 vs. 9.5 ± 2.1, p < 0.05) than men living with HIV not on statins treatment. The same protection was not observed in women. This data was demonstrated when muscle mass and strength were determined clinically (i.e. handgrip strength and electrical impedance) and when more precise laboratory measurements of muscle mass and strength were conducted (i.e. isokinetic strength and DXA scans). Statin does not exacerbate muscle wasting, strength loss, or muscle dysfunction among people with HIV. Indeed, statins may protect men, but not woman with HIV against HIV and antiretroviral therapy-induced loss of muscle mass and strength.

A One Health approach revealed the long-term role of Mycobacterium caprae as the hidden cause of human tuberculosis in a region of Spain, 2003 to 2022.

IntroductionMycobacterium caprae is a member of the Mycobacterium tuberculosis complex (MTBC) not routinely identified to species level. It lacks specific clinical features of presentation and may therefore not be identified as the causative agent of tuberculosis. Use of whole genome sequencing (WGS) in the investigation of a family microepidemic of tuberculosis in Almería, Spain, unexpectedly identified the involvement of M. caprae.AimWe aimed to evaluate the presence of additional unidentified M. caprae cases and to determine the magnitude of this occurrence.MethodsFirst-line characterisation of the MTBC isolates was done by MIRU-VNTR, followed by WGS. Human and animal M. caprae isolates were integrated in the analysis.ResultsA comprehensive One Health strategy allowed us to (i) detect other 11 M. caprae infections in humans in a period of 18 years, (ii) systematically analyse M. caprae infections on an epidemiologically related goat farm and (iii) geographically expand the study by including 16 M. caprae isolates from other provinces. Integrative genomic analysis of 41 human and animal M. caprae isolates showed a high diversity of strains. The animal isolates' diversity was compatible with long-term infection, and close genomic relationships existed between isolates from goats on the farm and recent cases of M. caprae infection in humans.DiscussionZoonotic circulation of M. caprae strains had gone unnoticed for 18 years. Systematic characterisation of MTBC at species level and/or extended investigation of the possible sources of exposure in all tuberculosis cases would minimise the risk of overlooking similar zoonotic events.

Intraductal papillary mucinous neoplasm of pancreas: Clinicopathological features and long-term survival after surgical resection.

INTRODUCTION: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas can progress from low-grade dysplasia to high-grade dysplasia and invasive carcinoma. METHODS: In this single-center retrospective series, we analyze the clinicopathological features and long-term follow up of patients who underwent pancreatic resection for IPMN, from January 2009 to December 2019. RESULTS: 31 patients were diagnosed with IPMN: 9 males and 22 females. Mean age was 67 years. Twenty-seven patients (87%) were symptomatic. Seven patients had main duct IPMN, 11 branch-type IPMN and 13 mixed-type IPMN. High-risk stigmata were found in 20 patients (64.5%) and worrisome features in 10 patients (32.2%). Thirteen patients (41.9%) had an associated invasive carcinoma, 4 (12.9%) high-grade dysplasia and 14 (45.2%) low-grade dysplasia. The follow-up was from 2 to 12 years. Median survival for patients with IPMN and associated invasive carcinoma was 45.8 months, and disease-free survival was 40.8 months. CONCLUSIONS: IPMN had a higher prevalence in females, mostly symptomatic and high incidence of associated invasive carcinoma with branch type. The 5-year survival was good even with associated invasive carcinoma.

Candida albicans the main opportunistic pathogenic fungus in humans.

Candida albicans is a commensal of the mammalian microbiome and the primary pathogenic fungus of humans. It becomes a severe health problem in immunocompromised patients and can cause a wide variety of mucosal and systemic infections. The interaction between C. albicans and host cells is characterized by the expression of virulence factors such as adhesins and invasins, the secretion of hydrolytic enzymes, a transition from yeast to filamentous hyphae form, and the ability to form biofilms; these features collectively result in cell adhesion, invasion, and damage. This review describes complex commensal interactions of C. albicans with host cells and the cellular events that it triggers in a pathogenic environment. We also review the host immune response induced by C. albicans antigens and the mechanisms developed by this fungus to avoid the action of antifungal agents.