Importance of Testing for ROS1 Rearrangements in Non-Small Cell Lung Cancer in the Era of Targeted Therapy in a Latin American Country.

Purpose: Lung cancer is the leading cause of cancer-related deaths worldwide. However, with the optimization of screening strategies and advances in treatment, mortality has been decreasing in recent years. In this study, we describe non-small cell lung cancer patients diagnosed between 2021 and 2022 at a high-complexity hospital in Latin America, as well as the immunohistochemistry techniques used to screen for ROS1 rearrangements, in the context of the recent approval of crizotinib for the treatment of ROS1 rearrangements in non-small cell lung cancer in Colombia. Methods: A descriptive cross-sectional study was conducted. Sociodemographic, clinical, and molecular pathology information from non-small cell lung cancer individuals who underwent immunohistochemistry to detect ROS1 rearrangements between 2021 and 2022 at Fundación Valle del Lili (Cali, Colombia) was recorded. The clinical outcomes of confirmed ROS1 rearrangements in non-small cell lung cancer patients were reported. Results: One hundred and thirty-six patients with non-small cell lung cancer were included. The median age at diagnosis was 69.8 years (interquartile range 61.9-77.7). At diagnosis, 69.8% (n = 95) were at stage IV. ROS1 immunohistochemistry was performed using the monoclonal D4D6 antibody clone in 54.4% (n = 74) of the cases, while 45.6% (n = 62) were done with the monoclonal SP384 antibody clone. Two patients were confirmed to have ROS1 rearrangements in non-small cell lung cancer using next-generation sequencing and received crizotinib. On follow-up at months 5.3 and 7.0, one patient had a partial response, and the other had oligo-progression, respectively. Conclusion: Screening for ROS1 rearrangements in non-small cell lung cancer is imperative, as multiple prospective studies have shown improved clinical outcomes with tyrosine kinase inhibitors. Given the recent approval of crizotinib in Colombia, public health policies must be oriented toward early detection of driver mutations and prompt treatment. Additionally, future approvals of newly tested tyrosine kinase inhibitors should be anticipated.

The microbiota of sexual intercourse and its effect on prostatitis.

It is estimated that microorganisms colonize 90% of the body surface. In some tracts, such as the genitourinary tract, the microbiota varies throughout life, influenced by hormonal stimulation and sexual practices. This study evaluated the semen differences and presence of Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis and Atopobium vaginae in semen samples from patients with symptoms of chronic prostatitis and men asymptomatic for urogenital infections. Fifty-three semen samples were included: 22 samples from men with symptoms of chronic prostatitis and 31 asymptomatic men (control group). In addition to the presence of L. crispatus, L. iners, G. vaginalis and A. vaginae, semen parameters, total antioxidant capacity of seminal plasma, prostatic antigen and some proinflammatory cytokines were evaluated in each semen sample. Volunteers with symptoms of chronic prostatitis presented a lower percentage of sperm morphology (4.3% vs. control group 6.0%, p = 0.004); in the semen samples of volunteers in the group asymptomatic for urogenital infections, microorganisms associated with the vaginal microbiota were detected more frequently. The presence of bacteria in the vaginal microbiota can also benefit male reproductive health, which undergoes various modifications related to lifestyle habits that are susceptible to modification. Microorganisms associated with the vaginal microbiota, such as L. crispatus, L. iners, G. vaginalis and A. vaginae, may have a protective role against the development of male genitourinary diseases such as prostatitis.

Organizing pneumonia as presenting feature of primary Sjögren's syndrome: A case report.

Sjögren's Syndrome (SS) is an autoimmune inflammatory disease, characterized by lymphocytic infiltration of exocrine glands. Approximately 10% of patients with SS have pulmonary involvement as the first manifestation of their disease, the most common being non-specific interstitial pneumonia. We present the case of a 51-year-old man with organizing pneumonia as the presenting feature of primary SS. Pulmonary involvement as the presenting feature of SS is uncommon, especially when the pattern on CT-scan is that of organized pneumonia. Initial management includes steroids and other immunosuppressants agents, with a better response in organized pneumonia secondary SS cases.

Cardiovascular Complications in Coronavirus Disease 2019-Pathogenesis and Management.

The coronavirus disease 2019 (COVID-19) pandemic has caused a devastating impact on morbidity and mortality around the world. Severe acute respiratory syndrome-coronavirus-2 has a characteristic tropism for the cardiovascular system by entering the host cells and binding to angiotensin-converting enzyme 2 receptors, which are expressed in different cells, particularly endothelial cells. This endothelial injury is linked by a direct intracellular viral invasion leading to inflammation, microthrombosis, and angiogenesis. COVID-19 has been associated with acute myocarditis, cardiac arrhythmias, new onset or worsening heart failure, ischemic heart disease, stroke, and thromboembolic disease. This review summarizes key relevant literature regarding the epidemiology, diagnosis, treatment, and preventive measures related to cardiovascular complications in the setting of COVID-19.

Validez y fiabilidad de la escala DASH

Introducción: La escala de discapacidades del brazo, el hombro y la mano se utiliza para evaluar los miembros superiores como unidad funcional. Este instrumento se encuentra certificado en diferentes idiomas y permite el estudio de diversas patologías especialmente osteomusculares. Objetivo: Consolidar procesos de validación realizados a la escala DASH en idioma español. Métodos: Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Clinical Key, SciELO, Science Direct, Epistemonikos y Google. Se incluyeron los artículos publicados hasta el 31 de agosto de 2020 sin restringir la fecha de inicio. Desarrollo: En la revisión se incluyeron un total de siete estudios, seis de ellos validaron la versión completa de la escala DASH y uno la versión corta, a partir de los siguientes tipos de validación: contenido, de criterio, de constructo, longitudinal y convergente. Fue utilizada en pacientes con manejo quirúrgico, población con cáncer de mama, patologías osteomusculares y pacientes sanos. Esta escala permite evaluar la evolución y efectividad del tratamiento para determinar el impacto de la enfermedad sobre las estructuras y la función del miembro superior. Conclusión: Se recomienda el uso de la escala DASH para evaluar los miembros superiores porque ha evidenciado buenos resultados de validez y fiabilidad; además es un instrumento útil y de bajo costo que permite su implementación en países con escasos recursos o poca inversión en el sistema de salud.

Introduction: The scale of disabilities of the arm, shoulder and hand is used to evaluate the upper limbs as a functional unit. This instrument is certified in different languages and allows the study of various pathologies, especially musculoskeletal diseases. Objective: To consolidate validation processes implemented to the DASH scale in Spanish. Methods: A literature search was performed in the databases PubMed, Clinical Key, SciELO, Science Direct, Epistemonikos and Google. Articles published up to 31 August 2020 were included without restricting the start date. Development: A total of seven studies were included in the review, six of them validated the full version of the DASH scale and one the short version, based on the following types of validation: content, criterion, construct, longitudinal and convergent. It was used in patients with surgical management, population with breast cancer, musculoskeletal pathologies and healthy patients. This scale allows evaluating the evolution and effectiveness of the treatment to determine the impact of the disease on the structures and function of the upper limb. Conclusion: The use of the DASH scale is recommended to evaluate the upper limbs because it has shown good results of validity and reliability. It is also a useful and low-cost instrument that allows its implementation in countries with scarce resources or little investment in the health system.

Thermodynamic stabilization of von Willebrand factor A1 domain induces protein loss of function.

The von Willebrand disease (vWD) is the most common hereditary bleeding disorder caused by defects of the von Willebrand Factor (vWF), a large extracellular protein in charge of adhering platelets to sites of vascular lesions. vWF performs this essential homeostatic task via specific protein-protein interactions between the vWF A1 domain and the platelet receptor, the glycoprotein Ib alpha (GPIBα). The two naturally occurring vWF A1 domain mutations G1324A and G1324S, near the GPIBα binding site, induce a dramatic decrease in platelet adhesion, resulting in a bleeding disorder classified as type 2M vWD. However, the reason for the drastic phenotypic response induced by these two supposedly minor modifications remains unclear. We addressed this question using a combination of equilibrium-molecular dynamics (MD) and nonequilibrium MD-based free energy simulations. Our data confirms that both mutations maintain the highly stable Rossmann fold of the vWF A1 domain. G1324A and G1324S mutations hardly changed the per-residue flexibility of the A1 domain but induced a global conformational change affecting the region near the binding site to GPIBα. Furthermore, we observed two significant changes in the vWF A1 domain upon mutation, the global redistribution of the internal mechanical stress and the increased thermodynamic stability of the A1 domain. These observations are consistent with previously reported mutations increasing the melting temperature. Overall, our results support the idea of thermodynamic conformational restriction of A1-before the binding to GPIBα-as a crucial factor determining the loss-of-function of the G1324A(S) vWD mutants.

Ionizing Radiation Exposure in Children with Vesicoureteral Reflux: Should We Be Alarmed? / Exposición a radiacion ionizante en niños con reflujo vesicoureteral: Debemos preocuparnos?

Objectives Ionizing radiation imaging is commonly used for diagnosis and follow up in children with vesicoureteral reflux (VUR). We aim to measure the effective dose (mSv) in patients with VUR. Methods We reviewed our electronic database of patients under 8-years-old with VUR. Primary endpoint was to calculate the effective radiation dose (ED). Absolute frequencies and percentages were reported for global qualitative variables. This study conducted a logistic regression model to calculate the odds ratio for radiation exposure. Analysis was performed using STATA version 14.0 (StataCorp LLC, College Station, TX, EEUU). Results A total of 140 patients were found, 97 were assessed for eligibility. We included 59 patients in the final analysis. Mean age was 20 ± 17.9 months, 66% were females. Most cases of VUR were bilateral (44%) and high grade (93.4%). The lowest number of studies per patient was two, with a minimum radiation of 5.7 mSv. The highest radiation was estimated at 20.7 mSv corresponding to a total of five studies. Logistic regression showed that highest grades of VUR and age of first UTI episode were associated with higher ED (OR, 1.7; 95% CI, 0.87-3.31), (OR 1.02; 95% CI 0.97-1.07) respectively. A mean ED for children with VUR was estimated of 5.5 ± 3 mSv/year. Conclusion In our study, the children with VUR were exposed to 5.5 mSv/year without counting the natural background radiation, which is alarming, and we believe should raise awareness worldwide in how we are unnecessarily diagnosing indolent VUR cases and following patients.

Objetivos La imagenología por radiación ionizante es una herramienta usada frecuentemente para el diagnóstico y seguimiento de pacientes con reflujo vesicoureteral (RVU). El objetivo del presente trabajo es calcular la dosis estimada en milisieverts (mSv) de pacientes con RVU. Métodos Se realizó una revisión retrospectiva de todos los pacientes menores de 8 años con RVU. El objetivo principal fue calcular la dosis de radiación efectiva recibida por los pacientes con base en los estudios imagenológicos realizados hasta el momento de la revisión de la base de datos. Las frecuencias y porcentajes fueron reportados para las variables cualitativas. Se realizó una regresión logística para calcular la asociación de factores de riesgo con la exposición a radiación. El análisis estadístico fue realizado con el programa STATA versión 14.0 (StataCorp LLC, College Station, TX, EEUU). Resultados Se identificaron 140 patientes, de los cuales 97 fueron evaluados para coprobar su elegibilidad. En total, 59 pacientes fueron incluidos para el análisis final. La edad promedio de los pacientes fue de 20 ± 1,.9 meses, y 66% eran mujeres. La mayoría de casos fueron bilaterales (44%) y de alto grado (93,4%). El menor número de estudios realizados por paciente fue 2, con una dosis mínima de radiación acumulada de 5,7 mSv. La máxima radiación acumulada fue de 20,7 mSv, correspondiente a un total de 5 estudios. La regresión logística demostró que altos grados de reflujo y la edad a la cual tuvieron la primera infección se asociaban con mayores dosis de radiación efectiva (razón de probabilidades [RP]: 1.7; intervalo de confianza del 95% [IC95%]: 0,87­3,31), (RP: 1,02; IC95%: 0,97­1,07), respectivamente. Estimamos una dosis efectiva de radiación de 5,5 ± 3 mSv/año en nuestra población. Conclusión Nuestro estudio demuestra que pacientes con reflujo son expuestos a un promedio de 5,5 mSv/año sin contar la radiación de base a la que se exponen todos los humanos anualmente, lo cual resulta alarmante. Esto debe generar introspección al momento de evaluar pacientes con reflujo y evitar efectos a largo y mediano plazos.

Detection of mycobacteria in paraffin-embedded Ziehl-Neelsen-Stained tissues using digital pathology.

INTRODUCTION: Early diagnosis of paucibacillary tuberculosis represents a challenge, even with direct tissue examination. Digital pathology allows the digital analysis of tissues to identify microorganisms. We aim to develop a program to detect and quantify typical and atypical mycobacteria in paraffin-embedded Ziehl-Neelsen-stained tissues. MATERIAL AND METHODS: Program development: The building of the program, named Pat-Scan, included pathology, systems engineering, and scientific applications. The iScan Coreo Au scanner® was used, and 9 variables were adjusted. Ten Ziehl-Neelsen-stained samples were fragmented into 2000 images and analyzed to validate the reproducibility of the bacilli images in the tissue, as detected by the software. RESULTS: Pat-Scan included software and a scanner that were used to detect and quantify bacilli in paraffin-embedded Ziehl-Neelsen-stained tissues. All samples containing mycobacteria were successfully analyzed by the scanner, and the bacilli could be detected; these results were validated by expert pathologists by microscopy examination, and the presence of bacilli was confirmed in all cases. CONCLUSIONS: Pat-Scan allowed the identification and quantification of mycobacteria in paraffin-embedded Ziehl-Neelsen-stained tissues, offering a reproducible diagnostic method that reduces the time for diagnosis and does not affect precision. Further validation is needed for application in the clinical setting.

Doege-Potter Syndrome and Hypoglycemia associated with Solitary Fibrous Tumor of the Pleura: Two Case Reports.

Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal neoplasms that originate from mesenchymal growth in the pleura, tend to be single tumors, usually have an indolent course and show nonspecific symptoms. SFTP can be often diagnosed from an incidental finding of a single mass in the thorax and should be confirmed by biopsy and immunohistochemistry. A minority of cases may present Doege-Potter syndrome (DPS, episodes of refractory hypoglycemia) associated with production of insulin-like growth factor 2 (IGF-2). Both SFTP and DPS are rare occurrences with less than 2000 cases reported worldwide. The curative treatment is tumor resection. Two cases of patients with DPS caused by SFTP are presented below.

First Lung Transplantation in Jehovah's Witness Patient in Latin America.

Lung transplantation is a life-saving alternative for patients with end-stage lung disease. The procedure itself has a high risk of bleeding. Jehovah's Witness patients refuse to accept blood products due to religious beliefs. A 48-year-old Jehovah's Witness woman presented with an 8-year history of cough, dyspnea along with progressive worsening of her functional class and quality of life. A diagnosis of autoimmune interstitial lung disease was made, for which cyclophosphamide was administered without improvement of symptoms, and the patient was accepted as a transplant candidate. Transplantation was performed without complications, nor blood products requirement, intraoperative cell salvage was performed, and pharmacological agents were used preoperatively for bleeding prevention. The patient only developed anemia after administration of immunosuppressor therapy, which was treated with erythropoietin in the outpatient setting.

Unsuspected foreign-body aspiration in adult patient with status asthmaticus: Case report.

INTRODUCTION: Accidental foreign body aspiration can cause severe damage to the airway and threaten the patient's life. This situation requires multidisciplinary and systematic approach from the medical and surgical team, in order to achieve complete resolution maintaining airway permeability. PRESENTATION OF CASE: This is a 49 y/o man who presented with a severe asthma attack, in whom an unsuspected foreign body in the inferior airway was diagnosed, which was possibly the result of aspiration during the initial emergency care, causing worsening of the already critical condition. DISCUSSION: We described the clinical course, radiologic and endoscopic findings, and outcome of the patient, highlighting the importance of considering the possibility of a foreign body in the airway, when there is no improvement in refractory status asthmaticus. This is particularly important in a university hospital. Moreover, the implementation of checklists when invasive procedures are performed can avoid loss of material, preventing iatrogenic aspiration events. CONCLUSION: Foreign body aspirations may remain undetected due to lack of suspicion, especially in adults, in whom they can cause chronic symptoms, or worsen chronic respiratory conditions turning them into more complex diseases. This cause must be considered in the differential diagnosis of refractory status asthmaticus.

Clinical characteristics and PD-L1 expression in primary lung squamous cell carcinoma: A case series.

BACKGROUND: Squamous cell lung carcinoma(SCLC), accounts for 20% of lung cancer(LC). The binding of programmed cell death 1(PD-1) to its ligand PD-L1 is a key checkpoint regulator of immune response, and overexpression of the latter leads to immune surveillance escape. This might represent an important oncogenic mechanism, as well as a predictor for immunotherapy treatment success in SCLC. METHODS: A retrospective series of 24 patients with SCLC was included(2009-2013). These patients presented with a single pulmonary lesion and no history of previous cancer. Expression of PD-L1 was evaluated on tumoral biopsies with immunohistochemistry. PD-L1 tumor proportion score(TPS) was considered high when ≥50%. Clinical characteristics regarding diagnosis were reviewed and recorded. Data were analysed in STATA v.14®. RESULTS: Twenty four patients were included in this series. Mean age was 67 + 14 years, and 62.5% were men. Smoking status was positive in 54%. Cancer stage IV was present in 54%. PD-L1 was positive in 13(54%). (+)PD-L1 was more frequent in smokers than in non-smokers(11 vs 2)(p = 0.001), as well as in COPD patients(p = 0.006). General overall survival was 21.8% at 5 years. Overall survival at one year in PD-L1(+) was 30.7% and 72.7% for PD-L1(-) patients. Survival median for PD-L1(+) patients was 10.5mo, as well as for the whole series. CONCLUSION: Patients with primary SCLC who have a high PD-L1 TPS, had a worse overall survival than their counterparts. PD-L1 expression in SCLC in a Colombian sample lies between the one found in the literature.

Tracheobronchopathia Osteochondroplastica-Clinical, Radiological, and Endoscopic Correlation: Case Series and Literature Review.

Tracheobronchopathia osteochondroplastica (TO) is a rare idiopathic and benign disease that is often underdiagnosed. TO is characterized by multiple submucosal cartilaginous and osseous tracheobronchial nodules that spare the posterior wall. It usually affects the elderly, developing when the person is around 60 years old without gender preference and has a reported incidence of 0.11%. TO can be symptomatic and should be considered in patients with chronic cough, dyspnea, and recurrent pulmonary infections. Diagnosis is usually incidental by computed tomography or bronchoscopy, the latter being the gold standard diagnostic test for TO. Many thoracic imagers are not well acquainted with TO; thus, these patients are often underdiagnosed or misdiagnosed. We came across 5 patients in our institution who were incidentally diagnosed with TO, inspiring us to review the available literature on this disease. A total of 33 patients diagnosed with TO between 2009 and 2019 were identified by our retrospective review. Clinical and imaging data were collected on these patients. We also included the clinical, radiological, and endoscopic data of our 5 cases. TO should be considered in patients with chronic cough, dyspnea, and recurrent pulmonary infections. Our experience is that both computed tomography and bronchoscopy can be used to make a reliable diagnosis. It is crucial for physicians, especially radiologists and pulmonologists, to be aware of the existence of TO in order to ensure proper diagnosis.

Endobronchial ultrasound-guided transbronchial needle aspirate for diagnosis of anaplastic large cell lymphoma of unusual presentation: A case report.

Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma (NHL) originated from mature post thymic T cells. They represent 1-3% of NHL. Different subtypes have been described: Anaplastic lymphoma kinase (ALK)-negative ALCL, ALK-positive ALCL and breast implant-associated ALCL. ALK-positive ALCL affects mainly the young and has better prognosis. We present a case report of an adult woman with AKL-positive ALCL, diagnosed by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA). A 59-year-old women with no history of breast implants, was admitted for a four-month low back pain. Initially, the patient was treated for a spondyloarthropathy, but due to persistence of the symptoms, a lumbosacral MRI was performed, showing changes in morphology and signal intensity in the vertebral body of L3, along with edema and a paravertebral collection that affected the left psoas muscle, suggesting granulomatous spondylodiscitis. Chest CT-scan showed mild left pleural effusion, subcarinal and right hiliar adenomegalies. An EBUS-TBNA with ROSE (rapid on-site evaluation) was performed showing positive findings for malignancy, suggestive of hematolymphoid neoplasia. Pathology analysis showed an AKL-positive ALCL. Additionally, a biopsy of paravertebral tissue biopsy was obtained, which was consistent with the nodal sample. Chemotherapy was initiated with the CHOP protocol: cyclophosphamide, hydroxydaunorubicin, vincristine sulfate and prednisone. EBUS-TBNA is a minimally invasive and safe technique for obtaining mediastinal samples. Collaboration with a cytopathologist trained to perform ROSE improves the diagnostic performance.