Cardiopulmonary phenotype in systemic sclerosis associated pulmonary hypertension.

INTRODUCTION: Pulmonary hypertension (PH) associated with systemic sclerosis (SSc) increases morbidity and mortality. Cardiopulmonary comorbidities, as per the 2021 PH consensus, play a role in the choice of therapy between monotherapy and combination therapy. METHODS: A cross-sectional study was conducted in patients with SSc based on the 2013 ACR/EULAR criteria or very early disease (VEDOSS 2011). PH was considered if they met the following criteria: pulmonary artery systolic pressure (PASP)>39mmHg or peak tricuspid regurgitation velocity (PTRV)>3.4m/s, PASP between 33 and 39mmHg or PTRV between 2.9 and 3.4m/s plus two additional findings suggestive of PH. PH was classified as type 2 if LVEF<50% or moderate to severe diastolic dysfunction was present; type 3 if extensive interstitial disease on tomography>20% or forced vital capacity (FVC)<75%; type 4 if abnormalities related to embolism were detected on scintigraphy or tomography. If patients did not meet these criteria, they were classified as type 1 PH. Complete data on cardiopulmonary risk factors and other factors were required. The frequency of these factors in the population and differences between groups based on risk factors were estimated. RESULTS: A total of 228 patients were selected. Three had type 2 PH, 24 had type 3, and 40 had type 1 PH, with the majority (75%) having at least one cardiopulmonary risk factor, and 47.5% having more than one. Mild diastolic dysfunction (25%) and hypertension (35%) were the most prevalent. In the type 1 PH group, those with risk factors experienced an increase in the number of years with Raynaud's phenomenon, anticentromere antibodies, and gastrointestinal symptoms (p<0.05). CONCLUSION: In patients with PH, 75% have one, and 45% have two or more risk factors.

Descripción de las intervenciones broncoscópicas en estenosis traqueales posterior a infección por COVID-19 / Description of Bronchoscopic Interventions in Post-COVID Tracheal Stenosis

Introducción: La infección por SARS-CoV-2 puede presentar síndrome de distrés res-piratorio agudo con requerimiento de ventilación mecánica prolongada y retraso en la realización de traqueostomía. Esto trae como consecuencia un incremento en casos de estenosis traqueal y la necesidad de métodos menos invasivos para su abordaje. Métodos: Estudio descriptivo de corte transversal, desde marzo 2020 hasta diciem-bre 2021 en el Hospital Universitario Nacional de Colombia, en adultos con estenosis traqueal postintubación asociado SARS-CoV-2. Se realizó análisis univariado entre los grupos con infección o no por SARS-CoV-2 como control, y reintervención, grado de estenosis, uso de inyección intramucosa con dexametasona intratraqueal o múltiples estenosis como desenlaces de importancia. Se usó test exacto de Fisher, t Student y Man-Whitney según la naturaleza de variables. Se consideró p estadísticamente significativo menor a 0.05.Resultados: Se identificaron 26 pacientes, 20 tenían COVID-19 y 6 no. Se encontraron diferencias en edad (p=0,002), epilepsia (p=0,007) y estenosis múltiple (p= 0,04). En 85% de los casos se utilizó láser blue más dilatación con balón pulmonar, en 35% inyección intramucosa con dexametasona intratraqueal y reintervención en 35%, sin diferencias significativas entre grupos. Conclusiones: Se observó un incremento tres veces mayor de pacientes con estenosis múltiple en el grupo de infección por COVID-19, así mismo se encontró que el método más utilizado en este grupo para la recanalización fue el uso de láser blue más dilatación con balón pulmonar y la innovación en el uso de inyección intramucosa.

Introduction: SARS-CoV-2 infection can lead to acute respiratory distress syndrome with a prolonged need for mechanical ventilation and delayed tracheostomy, resulting in an increase in cases of tracheal stenosis and the necessity for less invasive approaches.Methods: A descriptive cross-sectional study was conducted from March 2020 to December 2021 at the Hospital Universitario Nacional de Colombia, focusing on adults with post-intubation tracheal stenosis associated with SARS-CoV-2. Univariate analysis was performed between groups with or without SARS-CoV-2 infection as a control, considering reintervention, degree of stenosis, use of intratracheal steroids, or multiple stenoses as important outcomes. Fisher's exact test, Student's t-test, and Mann-Whit-ney test were employed based on the nature of variables. A p-value less than 0.05 was considered statistically significant.Results: A total of 26 patients were included, with 20 having COVID-19 and 6 without. Significant differences were found in age (p=0.002), epilepsy (p=0.007), and multiple stenosis (p=0.04). In 85% of cases, laser blue plus balloon pulmonary dilation was used, intratracheal dexamethasone in 35%, and reintervention in 35%, with no significant differences between groups.Conclusions: A threefold increase in subglottic stenosis was observed during the SARS-CoV-2 pandemic, with more instances of multiple stenosis and predominantly the use of laser blue plus balloon pulmonary dilation as a successful recanalization technique. There was a higher use of intratracheal dexamethasone in this group compared to oth-er pathologies causing tracheal stenosis.

SanPy: Software for the analysis and visualization of whole-cell current-clamp recordings.

The analysis of action potentials and other membrane voltage fluctuations provides a powerful approach for interrogating the function of excitable cells. However, a major bottleneck in the interpretation of this critical data is the lack of intuitive, agreed-upon software tools for its analysis. Here, we present SanPy, an open-source and freely available software package for the analysis and exploration of whole-cell current-clamp recordings written in Python. SanPy provides a robust computational engine with an application programming interface. Using this, we have developed a cross-platform desktop application with a graphical user interface that does not require programming. SanPy is designed to extract common parameters from action potentials, including threshold time and voltage, peak, half-width, and interval statistics. In addition, several cardiac parameters are measured, including the early diastolic duration and rate. SanPy is built to be fully extensible by providing a plugin architecture for the addition of new file loaders, analysis, and visualizations. A key feature of SanPy is its focus on quality control and data exploration. In the desktop interface, all plots of the data and analysis are linked, allowing simultaneous data visualization from different dimensions with the goal of obtaining ground-truth analysis. We provide documentation for all aspects of SanPy, including several use cases and examples. To test SanPy, we performed analysis on current-clamp recordings from heart and brain cells. Taken together, SanPy is a powerful tool for whole-cell current-clamp analysis and lays the foundation for future extension by the scientific community.

Cytological features of diffuse and circumscribed gliomas.

The current World Health Organization classification of gliomas is based on morphological, genetic, and molecular parameters. In this review, we intend to present the most relevant cytological features of these tumours, with a particular focus on their analysis during intraoperative studies. Rapid diagnosis is required in this context, and at present it is not possible to evaluate the genetic or molecular profile of a tumour intraoperatively. New terminology and diagnostic parameters have been introduced, but the essence of intraoperative recognition remains the same. The main challenge in astrocytoma IDH-mutant, grade 2 is recognising the tissue as neoplastic. Since glioma grades 3 and 4 are assigned based on histological and genetic variables that are not necessarily measurable on cytology, the term high-grade glioma is often used for intraoperative diagnosis. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted shows peculiar cytological findings as well as the common subtypes of glioblastoma IDH-wildtype (giant cell, epithelioid, gliosarcoma and small cell). Many of the paediatric-type-diffuse gliomas have been described very recently and there are no cytological reports of proven cases. Finally, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, and astroblastoma MN1-altered constitute the group of circumscribed astrocytic gliomas. They are remarkable entities that the pathologist must be able to recognise since most are low-grade neoplasms that can show atypical morphological features.

Remodeled connexin 43 hemichannels alter cardiac excitability and promote arrhythmias.

Connexin-43 (Cx43) is the most abundant protein forming gap junction channels (GJCs) in cardiac ventricles. In multiple cardiac pathologies, including hypertrophy and heart failure, Cx43 is found remodeled at the lateral side of the intercalated discs of ventricular cardiomyocytes. Remodeling of Cx43 has been long linked to spontaneous ventricular arrhythmia, yet the mechanisms by which arrhythmias develop are still debated. Using a model of dystrophic cardiomyopathy, we previously showed that remodeled Cx43 function as aberrant hemichannels (non-forming GJCs) that alter cardiomyocyte excitability and, consequently, promote arrhythmias. Here, we aim to evaluate if opening of remodeled Cx43 can serve as a general mechanism to alter cardiac excitability independent of cellular dysfunction associated with a particular cardiomyopathy. To address this issue, we used a genetically modified Cx43 knock-in mouse (S3A) that promotes cardiac remodeling of Cx43 protein without apparent cardiac dysfunction. Importantly, when S3A mice were subjected to cardiac stress using the ß-adrenergic agonist isoproterenol (Iso), they displayed acute and severe arrhythmias, which were not observed in WT mice. Pretreatment of S3A mice with the Cx43 hemichannel blocker, Gap19, prevented Iso-induced abnormal electrocardiographic behavior. At the cellular level, when compared with WT, Iso-treated S3A cardiomyocytes showed increased membrane permeability, greater plasma membrane depolarization, and Ca2+ overload, which likely caused prolonged action potentials, delayed after depolarizations, and triggered activity. All these cellular dysfunctions were also prevented by Cx43 hemichannel blockers. Our results support the notion that opening of remodeled Cx43 hemichannels, regardless of the type of cardiomyopathy, is sufficient to mediate cardiac-stress-induced arrhythmogenicity.

In Silico Mechanical Effort Analysis of the All-On-4 Design Performed With Platform-Switching Distal Short Dental Implants.

Short dental implants with platform matching connection have been used for the rehabilitation of atrophic jaws whenever standard-length dental implants cannot be placed without prior bone augmentation. Yet, there remains a lack of data regarding the risk of technical failures when the all-on-4 configuration is performed in atrophic jaws with platform-switching distal short dental implants. Thus, the current study used the finite element method to evaluate the mechanical behavior at the level of the prosthetic components of the all-on-4 concept performed in atrophic mandible using short-length distal implants with platform switching (PSW) connection. Three models of the all-on-4 configuration were generated in human atrophic mandibles. The geometric models consisted of PSW connection tilted standard (AO4T; θ = 30 deg; 11 mm-length), straight standard (AO4S; θ = 0 deg; 11 mm-length) and straight short (AO4Sh; θ = 0 deg; 8 mm-length) distal implants. A resultant force of 300 N was performed obliquely in the left side and posterior region of the prosthetic bar. The von Mises equivalent stress (σvm) and maximum and minimum principal stresses (σmax and σmin) were performed at level of the prosthetic components/implants and peri-implant bone crest, respectively. The general displacement of the models was also evaluated. The stress analysis was performed on the side of load application. The AO4S configuration showed the lowest values of σvm in the mesial left (ML) and distal left (DL) abutments (37.53 MPa and 232.77 MPa, respectively) and dental implants (91.53 MPa and 231.21 MPa, respectively). The AO4Sh configuration showed the highest values of σvm in the bar screw (102.36 MPa), abutment (117.56 MPa), and dental implant (293.73 MPa) of the ML area. Among the models, the highest values of σmax and σmin were noticed in the peri-implant bone crest of the AO4T design (131.48 MPa and 195.31 MPa, respectively). All models showed similar values of general displacements, which were concentrated in the mandible symphysis. The all-on-4 configurations designed with PSW connection and tilted standard (AO4T; θ = 30 deg; 11 mm-length), straight standard (AO4S; θ = 0 deg; 11 mm-length) or straight short (AO4Sh; θ = 0 deg; 8 mm-length) distal implants were not associated with higher odds of technical failures. The AO4Sh design may be a promising option for the prosthetic rehabilitation of atrophic jaws.

SanPy: A whole-cell electrophysiology analysis pipeline.

The analysis of action potentials and other membrane voltage fluctuations provide a powerful approach for interrogating the function of excitable cells. Yet, a major bottleneck in the interpretation of this critical data is the lack of intuitive, agreed upon software tools for its analysis. Here, we present SanPy, a Python-based open-source and freely available software pipeline for the analysis and exploration of whole-cell current-clamp recordings. SanPy provides a robust computational engine with an application programming interface. Using this, we have developed a cross-platform graphical user interface that does not require programming. SanPy is designed to extract common parameters from action potentials including threshold time and voltage, peak, half-width, and interval statistics. In addition, several cardiac parameters are measured including the early diastolic duration and rate. SanPy is built to be fully extensible by providing a plugin architecture for the addition of new file loaders, analysis, and visualizations. A key feature of SanPy is its focus on quality control and data exploration. In the desktop interface, all plots of the data and analysis are linked allowing simultaneous data visualization from different dimensions with the goal of obtaining ground truth analysis. We provide documentation for all aspects of SanPy including several use cases and examples. To test SanPy, we have performed analysis on current-clamp recordings from heart and brain cells. Taken together, SanPy is a powerful tool for whole-cell current-clamp analysis and lays the foundation for future extension by the scientific community.

Current status of musculoskeletal ultrasound in Colombian rheumatology

Introduction: Ultrasound is very useful in the management of rheumatological pathology today. Despite this, in Colombia, progress towards its implementation is limited and entails great difficulties. This deficit is also related to the difficulties in training new human talent. In Colombia, there is no study that identifies the current status of ultrasound among rheumatologists in the country. Methods: This is a descriptive cross-sectional study where medical specialists in Rheumatology practising in Colombia were surveyed through an online form. They were asked about general aspects and for their opinion regarding ultrasound in rheumatology and, if they practiced it, they were asked about specific aspects of its application in clinical practice. Additionally, questions were asked of the rheumatologists who are part of the specialist training processes in the country. Closed multiple-choice or Likert scale assessment questions were presented as required. The main objective was to describe the current use and opinion of musculoskeletal ultrasound in Colombian rheumatologists, as well as the limitations for its implementation. Frequency measurements were performed of the categorical variables of nominal type and ordinal type. The intention was to survey all rheumatologists in the country, who according to Colombian Society of Rheumatology data for the end of 2019 totalled 186. Results: Taking into account the number of rheumatologists of the Colombian Association of Rheumatology (Asoreuma) for 2019 totalling 186, a participation of 139 specialists (74.7%) was obtained, of which 22 of the respondents performed ultrasound in their daily practice (15.8%) the majority in this group being trained in Colombian territory (80.6%). Of the 139 respondents, 64.7% have received some type of training in ultrasound, generally pre-congress courses (22.5%), EULAR courses (16.7%) and training included in their residency curriculum outside the rheumatology service (9.8%). The acceptance of ultrasound is high among rheumatologists practicing in Colombia, 75.5% consider it important or very important and 84.9% indicated that for a comprehensive rheumatology service it is important or very important to have ultrasound. From the responses, however, they consider that its use could change their behaviour frequently, and very frequently in less than half of the cases at 46.7%. Regarding the opinion on the use of ultrasound in specific pathologies, rheumatoid arthritis (77.7%) and crystal arthropathies (72.7%) were considered the highest and most important, as well as in the performance of procedures at 87%. For decision-making in the inflammatory pathology study, 60.4% would consider performing ultrasound compared to 28.8% who responded MRI. Regarding the limitations for implementation, the lack of training in the country (25.6%), followed by the lack of resources to procure equipment (17.9%) and ignorance and lack of interest on the part of the health entities (17.1%) were the most recognized. Conclusion: Musculoskeletal ultrasound is only practiced by a minority of rheumatologists practicing in Colombia, even though the majority consider it important. Its importance lies in its use to treat patients with rheumatoid arthritis, crystal arthropathies and psoriatic arthropathy, as well as for the performance of procedures. More than half of the rheumatologists have received some type of training in ultrasound, usually very few hours' education and without practical or informal training, this being the main problem for its implementation.

Introducción: En la actualidad, la ecografía es de gran utilidad en el manejo de la patología reumatológica. A pesar de esto, en Colombia, los avances para su implementación son escasos y han enfrentado grandes dificultades. Este déficit también se encuentra relacionado con las complicaciones para la formación del nuevo talento humano. En Colombia no se dispone de ningún estudio en el que se identifique el estado actual de la ecografía entre los reumatólogos del país. Métodos: Se trata de un estudio descriptivo de carácter transversal en el cual se encuestó, por medio de un formulario on-line, a médicos especialistas en reumatología que hacen su práctica en el territorio colombiano. Se les preguntó acerca de los aspectos generales y su opinión sobre la ecografía en la reumatología, si la practicaban, como también en torno a los aspectos específicos de su aplicación en la práctica clínica. De manera adicional, se formularon preguntas dirigidas a aquellos reumatólogos que hacen parte de los procesos de capacitación de especialistas en el país; se presentaron preguntas cerradas de opción múltiple o de valoración por escala de Likert según se requirió. El objetivo principal fue describir el uso y la opinión actual sobre la ecografía musculoesquelética en reumatólogos colombianos, así como las limitantes para su implementación. A las variables categóricas de tipo nominal y de tipo ordinal se les hicieron medidas de frecuencia. Se pretendía encuestar a la totalidad de los reumatólogos en el país, los cuales, según información de la Asociación Colombiana de Reumatología (Asoreuma) de finales del 2019, eran 186. Resultados: De acuerdo con el número de reumatólogos proporcionado por la Asoreuma, de 186 especialistas en el año 2019, se obtuvo una participación de 139 de estos (74,7%), de los cuales 22 realizaban ecografía en su práctica diaria (15,8%), siendo este grupo en su mayoría formado en Colombia (80,6%). De los 139 encuestados, el 64,7% había recibido algún tipo de estudios en ecografía, generalmente cursos precongreso (22,5%), cursos de la Liga Europea Contra el Reumatismo (EULAR) (16,7%) y formación incluida en el pensum de su residencia fuera del servicio de reumatología (9,8%). La aceptación de la ecografía es alta entre los reumatólogos que ejercen en Colombia, el 75,5% la consideraron importante o muy importante. Asimismo, el 84,9% indicó que para un servicio de reumatología integral es importante o muy importante contar con ecografía. Sin embargo, los encuestados consideraron que su uso podría llegar a cambiar su conducta de manera frecuente, y muy frecuentemente en menos de la mitad de los casos (46,7%). Con respecto a la opinión sobre el uso de la ecografía en patologías específicas, se consideró con importancia y mucha importancia en artritis reumatoide (77,7%) y artropatías por cristales (72,7%), que fueron las más altas, así como para la realizaron de procedimientos (87%). Para la toma de decisiones en estudio de patología inflamatoria, el 60,4% consideraría realizar ecografía, comparado con 28,8% que se inclina por la resonancia. En relación con las limitaciones para la implementación, la falta de entrenamiento en el país (25,6%), seguida de la carencia de recursos para la consecución del equipo (17,9%) y el desconocimiento y la falta de interés por parte de los entes de salud (17,1%) fueron las más reconocidas. Conclusiones: La ecografía musculoesquelética solamente es practicada por una minoría de los reumatólogos que ejercen en Colombia, a pesar de que la mayoría la considera importante. Su relevancia radica en su uso para tratar a los pacientes con artritis reumatoide, artropatías por cristales y por artropatía psoriásica, así como para la realización de procedimientos. Más de la mitad de los reumatólogos ha recibido algún tipo de formación en ecografía, la mayoría de las veces educación de muy pocas horas o sin entrenamiento práctico, o no formal, lo cual constituye el principal problema para su implementación.

Patterns of use of biological and genetic markers for chronic lymphocytic leukemia and acute myeloid leukemia in Puerto Rico.

BACKGROUND: The use of markers has stimulated the development of more appropriate targeted therapies for chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). We assessed the use and prevalence of biological and genetic markers of CLL and AML in the homogeneous Hispanic population of Puerto Rico. METHODS: We used the Puerto Rico CLL/AML Population-Based Registry, which combines information from linked databases. Logistic regression models were used to examine factors associated with biological and genetic testing. RESULTS: A total of 926 patients 18 years or older diagnosed with CLL (n = 518) and AML (n = 408) during 2011-2015 were included in this analysis. Cytogenetic testing (FISH) was reported for 441 (85.1%) of the CLL patients; of those, 24.0% had the presence of trisomy 12, 9.5% carried deletion 11q, 50.3% carried deletion 13q, and 6.3% carried deletion 17p. Regarding AML, patients with cytogenetics and molecular tests were considered to determine the risk category (254 patients), of which 39.8% showed poor or adverse risk. Older age and having more comorbidities among patients with CLL were associated with a lower likelihood of receiving a FISH test. CONCLUSIONS: Although prognostic genetic testing is required for treatment decisions, the amount of testing in this Hispanic cohort is far from ideal. Furthermore, some tests were not homogeneously distributed in the population, which requires further exploration and monitoring. This study contributes to the field by informing the medical community about the use and prevalence of biological and genetic markers of CLL and AML. Similarly, it has the potential to improve the management of CLL and AML through benchmarking.

Diagnostic role of DOG-1, GFAP and B-catenin in Basal cell Adenoma and Cellular Pleomorphic Adenoma of the Salivary Gland.

BACKGROUND: Pleomorphic Adenoma (PA) and Basal cell adenoma (BCA) are benign salivary gland tumors that may pose a diagnostic challenge if typical features are not present. Due to the increased relapse and malignant transformation rate of the former, a correct diagnosis carries relevant prognostic information. Even though immunohistochemistry (IHC) plays a limited role in the diagnosis of these tumors, the use of IHC panels could increase diagnostic accuracy. In the present work, we aimed to demonstrate that the use of an IHC panel consisting of Glial Fibrillary Acid Protein (GFAP), B-Catenin and Discovered On GIST 1 (DOG-1) can aid in the differential diagnosis between PA and BCA. METHODS: We analyzed 18 cases of benign salivary gland tumors (Pleomorphic adenomas and Basal cell adenomas) with overlapping histologic features. First, a head and neck pathologist diagnosed the cases relying on morphology alone. Afterwards, cases were re-evaluated considering the IHC panel results. Inter-observer IHC scoring concordance was evaluated with pre-defined marker cut-off points using Cohen's Kappa scores. RESULTS: Based on morphology alone, 9 cases were classified as PA while the remaining tumors were considered to be BCA. Five out of nine BCA cases showed GFAP staining and absent nuclear B-catenin and DOG-1 positivity. Conversely, 2 PA cases showed absent GFAP and positive nuclear B-catenin with concurrent DOG-1 expression. Therefore, after IHC evaluation, up to 40% of morphologic diagnoses were reconsidered. Overall, the inter-observer concordance for IHC evaluation was good (resulting Kappa Scores between 0.78 and 1). CONCLUSION: Our work supports the use of a concise IHC panel to improve the diagnostic accuracy of benign salivary gland tumors with overlapping histologic features.

Adenylyl cyclase isoform 1 contributes to sinoatrial node automaticity via functional microdomains.

Sinoatrial node (SAN) cells are the heart's primary pacemaker. Their activity is tightly regulated by ß-adrenergic receptor (ß-AR) signaling. Adenylyl cyclase (AC) is a key enzyme in the ß-AR pathway that catalyzes the production of cAMP. There are current gaps in our knowledge regarding the dominant AC isoforms and the specific roles of Ca2+-activated ACs in the SAN. The current study tests the hypothesis that distinct AC isoforms are preferentially expressed in the SAN and compartmentalize within microdomains to orchestrate heart rate regulation during ß-AR signaling. In contrast to atrial and ventricular myocytes, SAN cells express a diverse repertoire of ACs, with ACI as the predominant Ca2+-activated isoform. Although ACI-KO (ACI-/-) mice exhibit normal cardiac systolic or diastolic function, they experience SAN dysfunction. Similarly, SAN-specific CRISPR/Cas9-mediated gene silencing of ACI results in sinus node dysfunction. Mechanistically, hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) channels form functional microdomains almost exclusively with ACI, while ryanodine receptor and L-type Ca2+ channels likely compartmentalize with ACI and other AC isoforms. In contrast, there were no significant differences in T-type Ca2+ and Na+ currents at baseline or after ß-AR stimulation between WT and ACI-/- SAN cells. Due to its central characteristic feature as a Ca2+-activated isoform, ACI plays a unique role in sustaining the rise of local cAMP and heart rates during ß-AR stimulation. The findings provide insights into the critical roles of the Ca2+-activated isoform of AC in sustaining SAN automaticity that is distinct from contractile cardiomyocytes.

Induction Therapy and Survival for Acute Myeloid Leukemia in Hispanic Adults from Puerto Rico.

BACKGROUND: Acute myeloid leukemia (AML) is the most common type of leukemia in adults. There are no previous studies evaluating AML treatment patterns in Puerto Rico. We describe the first-line therapy patterns and survival of patients diagnosed with AML in Puerto Rico using the Puerto Rico Central Cancer Registry Health Insurance Linkage Database (2011-2015). METHODS: We describe patient characteristics according to intensive, non-intensive, and non-treatment status. We used Cox proportional hazard models to evaluate the factors associated with the risk of death stratified by intensive and non-intensive therapy. For this study, 385 patients with AML were included. RESULTS: The mean age was 67 years old and 50.1% were female. Nearly half of AML patients (46.8%) received intensive treatment, 23.6% received non-intensive treatment, and 26.2% did not receive treatment. The overall 3-year survival rate was 17.9%. Among those who received intensive therapy, the risk of death among females was lower than males (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.44-0.93). Patients 60 years or older who received intensive treatment had a higher risk of death than younger patients (HR: 1.67, 95% CI: 1.09-2.55). Patients with poor/adverse risk receiving intensive (HR: 3.43, 95% CI: 1.76-6.69) or non-intensive (HR: 4.32, 95% CI: 1.66-11.28) treatment had a higher risk of death than patients with a favorable risk category. CONCLUSION: Our findings are the first step to monitor the quality of care of patients with AML in Puerto Rico, particularly related to the administration of appropriate induction therapies, which is one of the most important predictors of AML survival.

Impact of ultrasound on the perception of health quality in adult patients with rheumatoid arthritis / Impacto de la ecografía en la percepción de la calidad en salud de pacientes adultos con artritis reumatoide

ABSTRACT Introduction: Ultrasound has shown its usefulness in multiple aspects in the management of inflammatory joint disease and in particular of rheumatoid arthritis (RA). The evidence using patient outcomes and its aspects related to quality of health care is scarce. The aim of this study is to determine the level of satisfaction in the perception of the quality of health care in a group of patients with RA who underwent ultrasound during the consultation, and whether it is higher than those who did not have the ultrasound. Methods: An observational, cross-sectional descriptive study was performed. Patients older than 18 years with a diagnosis of RA using the ACR/EULAR classification criteria were included. One group underwent skeletal muscle ultrasound to study RA during the out-patient medical consultation, as decided by the attending physician. After the completion of the medical action according to prior verbal acceptance by the patient, the Servqhos questionnaire and an ultrasound questionnaire were completed. A satisfied patient was defined as one who had 70% or more in the responses in the Servqhos questionnaire greater than or equal to 4, and a score of 5 in this questionnaire was defined as maximum satisfaction. There were no significant differences between the number of satisfied patients in the two groups. Univariate analysis was performed according to the distribution in the ultrasound or non-performing groups. Subsequently, a bivariate analysis of the different questions was carried out according to the distribution in the satisfaction and very high satisfaction groups. It was established if there was any degree of association using the Chi squared test for categorical variables, and the parametric tests (Mann Whitney U) or non-parametric tests (Kruskal-Wallis test) for the numerical variables were performed according to the distribution. Results: A total of 126 patients were obtained, of whom 62 corresponded to the group of patients who underwent ultrasound during the consultation and 62 to the control group in whom no ultrasound was performed. The majority were women (91%). Ultrasound was mostly performed to study joint disease (93%), with a third of the time to assess more than one aspect. In those on whom the ultrasound was performed, the number of satisfied patients was 56 (90%) and for the control group it was 48 (77%). The difference in the proportion of satisfied patients (13%) was statistically significant (P = .05). A difference was found between the groups in the number of patients with the highest level of satisfaction in the questions regarding presentation of staff and technology (P < .05). The vast majority of patients considered that ultrasound was useful during the consultation (93%), and that it generates greater confidence in the treatments and the doctor (93%). Conclusions: Performing skeletal muscle ultrasound during consultation in patients with RA improves satisfaction rates of health care, perception of the doctor, and treatments.

RESUMEN Introducción: La ecografía ha mostrado su utilidad en múltiples aspectos del manejo de la enfermedad articular inflamatoria, particularmente en la artritis reumatoide (AR). Su utilidad usando desenlaces derivados de pacientes y relacionados con aspectos de la calidad de la atención en salud es escasa. El objetivo del estudio es determinar si el grado de satisfacción de la calidad de la atención en un grupo de pacientes con AR, en quienes se realizó ecografía durante la consulta, es superior al de un grupo en los que esta no se llevó a cabo. Métodos: Se realizó un estudio observacional, descriptivo transversal. Se incluyeron pacientes mayores de 18 años con diagnóstico de AR por criterios clasificatorios ACR/EULAR que posteriormente a la finalización del acto médico respondieron las preguntas del cuestionario Servqhos. Quienes se sometieron a ecografía musculoesquelética para estudio de AR durante la consulta ambulatoria, según decisión del médico tratante, respondieron adicionalmente el cuestionario de ecografía. Se define paciente satisfecho como aquel que tiene un 70% o más en las respuestas del cuestionario Servqhos con un puntaje mayor o igual a 4, y se define como la máxima satisfacción al puntaje de 5 en una pregunta de dicho cuestionario. Se determinó si había diferencias significativas entre las proporciones de pacientes satisfechos en los dos grupos con y sin ecografía. Se realizó un análisis univariado según la distribución en los grupos, y posteriormente se hizo un análisis bivariado de las diferentes preguntas según la distribución en los grupos de satisfacción y muy alta satisfacción. Se estableció si había algún grado de asociación con las pruebas de chi-cuadrado para las variables categóricas, en tanto que para las variables numéricas se llevaron a cabo pruebas paramétricas (U de Mann Whitnney) y no paramétricas (test de Kruskal-Wallis), según la distribución. Resultados: Se obtuvo un total de 126 pacientes, de los cuales 62 corresponden al grupo de aquellos en quienes se realizó ecografía durante la consulta, mientras que otros 62 hacen parte del grupo control, en quienes no se realizó ecografía. La mayoría eran mujeres (91%). En quienes se hizo la ecografía, el número de pacientes satisfechos fue de 56 (90%), en tanto que para el grupo control fue de 48 (77%). La diferencia en la proporción de pacientes satisfechos entre los grupos fue del 13%, siendo estadísticamente significativa (p = 0,05). Se encontró diferencia entre los grupos en las preguntas referentes a presentación del personal y la tecnología de los equipos (p < 0,05). La gran mayoría de los pacientes consideró que la ecografía fue útil durante la consulta (93%) y que genera mayor seguridad en los tratamientos y en el criterio médico (93%). Conclusiones: La realización de ecografía musculoesquelética durante la consulta en pacientes con AR mejora los índices de satisfacción de atención en salud, así como la percepción del criterio médico y de los tratamientos.

Strontium-loaded titanium-15molybdenum surface improves physicochemical and biological propertiesin vitro.

The titanium alloy composition and microdesign affect the dynamic interplay between the bone cells and titanium surface in the osseointegration process. The current study aimed to evaluate the surface physicochemical properties, electrochemical stability, and the metabolic response of the MC3T3-E1 cells (pre-osteoblast cell line) cultured onto titanium-15molybdenum (Ti-15Mo) discs treated with phosphoric acid (H3PO4) and sodium hydroxide (NaOH) and/or strontium-loading by the hydrothermal method. The x-ray dispersive energy spectroscopy (EDS) and x-ray diffraction (XRD) analysis showed no trace of impurities and the possible formation of hydrated strontium oxide (H2O2Sr), respectively. The confocal laser microscopy (CLSM) analysis indicated that titanium samples treated with strontium (Sr) showed greater surface roughness. The acid/alkali treatment prior to the hydrothermal Sr deposition improved the surface free energy and resistance to corrosion of the Ti-15Mo alloy. The acid/alkali treatment also provided greater retention of the Sr particles on the Ti-15Mo surfaces accordingly with inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. The AlamarBlue and fluorescence analysis indicated noncytotoxic effects against the MC3T3-E1 cells, which allowed cells' adhesion and proliferation, with greater cells' spreading in the Sr-loaded Ti-15Mo samples. These findings suggest that Sr deposition by the hydrothermal method has the potential to enhance the physicochemical properties of the Ti-15Mo previously etched with H3PO4and NaOH, and also improve the initial events related to cell-mediated bone deposition.

Biological noise is a key determinant of the reproducibility and adaptability of cardiac pacemaking and EC coupling.

Each heartbeat begins with the generation of an action potential in pacemaking cells in the sinoatrial node. This signal triggers contraction of cardiac muscle through a process termed excitation-contraction (EC) coupling. EC coupling is initiated in dyadic structures of cardiac myocytes, where ryanodine receptors in the junctional sarcoplasmic reticulum come into close apposition with clusters of CaV1.2 channels in invaginations of the sarcolemma. Cooperative activation of CaV1.2 channels within these clusters causes a local increase in intracellular Ca2+ that activates the juxtaposed ryanodine receptors. A salient feature of healthy cardiac function is the reliable and precise beat-to-beat pacemaking and amplitude of Ca2+ transients during EC coupling. In this review, we discuss recent discoveries suggesting that the exquisite reproducibility of this system emerges, paradoxically, from high variability at subcellular, cellular, and network levels. This variability is attributable to stochastic fluctuations in ion channel trafficking, clustering, and gating, as well as dyadic structure, which increase intracellular Ca2+ variance during EC coupling. Although the effects of these large, local fluctuations in function and organization are sometimes negligible at the macroscopic level owing to spatial-temporal summation within and across cells in the tissue, recent work suggests that the "noisiness" of these intracellular Ca2+ events may either enhance or counterintuitively reduce variability in a context-dependent manner. Indeed, these noisy events may represent distinct regulatory features in the tuning of cardiac contractility. Collectively, these observations support the importance of incorporating experimentally determined values of Ca2+ variance in all EC coupling models. The high reproducibility of cardiac contraction is a paradoxical outcome of high Ca2+ signaling variability at subcellular, cellular, and network levels caused by stochastic fluctuations in multiple processes in time and space. This underlying stochasticity, which counterintuitively manifests as reliable, consistent Ca2+ transients during EC coupling, also allows for rapid changes in cardiac rhythmicity and contractility in health and disease.

A tree-based machine learning model to approach morphologic assessment of malignant salivary gland tumors.

Malignant salivary gland tumors represent a challenge for pathologists due to their low frequency and morphologic overlap. In recent years machine learning techniques have been applied to the field of pathology to improve diagnostic performance. In the present work, we fitted a machine learning algorithm to approach the diagnosis of malignant salivary gland tumors. Twelve morphologic variables were scored across 115 samples representing the most commonly encountered malignant salivary gland tumors. The sample was randomly split into a discovery and validation set. A recursive partitioning algorithm was used to systematically screen and organize candidate variables into a classification tree using the discovery set. A cross-validation strategy was used to tune the algorithm hyperparameters. Inter-observer concordance was calculated by independent evaluation of 26 randomly selected cases. The five-tiered tree built, required the evaluation of 6 morphological variables. Basaloid appearance, presence of mucous cells, necrosis, cribriform pattern, clear cells and keratinization were selected by the algorithm to build the tree. This diagnostic tool correctly classified 89.9% and 84.6% of the samples in the discovery and validation sets respectively. Misclassification pattern was consistent between both sets. Misclassified tumors belonged to one of three histologic types: epithelial-myoepithelial, polymorphous and mucoepidermoid carcinomas. Other histotypes demonstrated perfect recall in both the discovery and validation sets. Overall inter-observer concordance was good, with median kappa scores between the expert evaluator and training pathologists being 0.81. Overall, our classification tool developed using a recursive partitioning algorithm can effectively guide the morphological approach to malignant salivary gland tumors.

Serum chemerin in a cohort of Colombian patients with primary osteoarthritis.

BACKGROUND AND PURPOSE: Osteoarthritis (OA) is considered the most common degenerative joint pathology in the adult population, being an important cause of disability worldwide, and its prevalence is increasingly associated with different factors, including obesity. Obesity together with metabolic syndrome have been associated with a pro-inflammatory state due to the release of cytokines that induce changes in cartilage metabolism. Chemerin is an adipokine secreted mainly by adipocytes and its final action is to increase the production of IL-6, IL-8, IL-1b, TNF-a and metalloproteinases by macrophages, dendritic cells and chondrocytes, which are responsible for damage to the articular cartilage. This is one of the reasons that obesity and inflammation have been linked to OA. The main objective of this study is to determine whether the serum chemerin concentrations of a group of patients with primary OA are higher when compared with control individuals. A further purpose of the study is to determine the relationship between the presence of obesity/overweight with the severity of the disease measured by a radiological scale. PATIENTS AND METHODS: An analytical cross-sectional study was carried out where serum chemerin levels were quantified by enzyme-linked immunoadsorption assay (ELISA), in patients with primary OA of the hip, knee and hand with criteria from the ACR (American College Of Rheumatology) and controls. Radiological studies of patients and controls were analysed to determine the severity of joint involvement using the Kellgren and Lawrence (KL) classification system. The statistical significance of the difference in serum chemerin values between the two groups was verified and the correlation between the variables of body mass index (BMI) with radiological severity, number of joint regions and serum chemerin levels was analysed. RESULTS: During the period from July 2015 to July 2016, serum samples and radiographs of compromised joints were collected from 40 patients with primary OA who met the inclusion criteria, as well as serum samples from 20 controls. The average concentration of chemerin was higher in the group of patients with OA compared to that of the control group, being 373ng / ml and 175.55ng / ml respectively (p<2.2×10-16). No significant associations were found between the different degrees of disease severity measured by the KL radiological scale, such as the number of involved joint regions and BMI. CONCLUSIONS: In a group of patients with primary OA of the hand, knee or hip, the values of chemerin were higher than those found in controls, without significant association with the severity of the disease established radiologically by K/L scale, the number of involved joint regions, and the BMI.