COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.

A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

Isatuximab-carfilzomib-dexamethasone immediately after failing of the quadruplet Daratumumab-bortezomib-lenalidomide-dexamethasone (Dara-VRD): Striking response with no washout in a newly diagnosed multiple myeloma.

Biochemical evolution of serum IgG-Kappa monoclonal component during the first line with VRD (x1), DARA-VRD (x4), and the second line with ISA-KD (x4).

Pensamiento suicida en médicos residentes con la escala de Plutchik en dos instituciones de salud en Ciudad Obregón, Sonora, México

Objetivo: Evaluar la incidencia y factores asociados al pensamiento suicida en una muestra de médicos residentes de dos instituciones. Materiales y métodos: Se realizó un estudio de tipo descriptivo, observacional, prospectivo y transversal, entre los meses de septiembre a octubre del 2022, para estimar el pensamiento suicida en los médicos residentes de dos hospitales con la escala de Plutchik, además de buscar factores asociados. Se aplicó la estadística descriptiva con medidas de tendencia central y de dispersión, frecuencias relativas y absolutas; las pruebas ji al cuadrado de Pearson y de bondad de ajuste, así como la prueba de Kruskal-Wallis se emplearon para examinar las diferencias entre especialidades, y la prueba post-hoc de Tukey para evaluar la especialidad diferente. Resultados: Se respondió un total de 225 encuestas, de las cuales se eliminaron 20 por inadecuado diligenciamiento, y quedaron 205. El promedio de edad fue de 28,66 años (DS ± 2,360) y el 71,2 % correspondió al sexo femenino. En cuanto a las especialidades, se encontró a pediatría con el 28,8 % y a anestesiología con el 20,5 %. Se evidenció asociación significativa entre especialidades, con un valor de p = 0,0000, y grado académico de p = 0,003 (p ≤ 0,05). Según la especialidad, se encontraron diferencias en cuanto al pensamiento suicida; la prueba de Kruskal-Wallis mostró un valor de p = 0,000 y la prueba post-hoc de Tukey reveló que la especialidad de ginecología fue la diferente. Conclusiones: De acuerdo con los resultados de la muestra, alrededor de una cuarta parte de los médicos residentes manifiesta pensamiento suicida. La prevalencia en dicha muestra no presenta diferencia significativa con respecto a la incidencia a nivel latinoamericano. Se encontró una asociación entre ideas suicidas, especialidades médicas y grado académico. En cuanto a comparación entre las especialidades, ginecología fue la que mostró mayor ideación suicida. Este trabajo presenta algunas limitaciones, por ejemplo, existe una gran heterogeneidad de grupos, no se empleó una técnica de selección probabilística y las pruebas estadísticas empleadas fueron no paramétricas.

Objective: To evaluate the incidence and factors associated with suicidal ideation in a sample of resident physicians from two institutions. Materials and methods: A descriptive, observational, prospective and cross-sectional study was carried out to estimate the suicidal ideation and associated factors with the Plutchik Suicide Risk Scale among resident physicians from two hospitals between September and October 2022. Descriptive statistics were used with measures of central tendency and dispersion, as well as relative and absolute frequencies. In addition, Pearson's chi-square goodness of fit test and Kruskal-Wallis H test were used to examine the differences between specialties, and Tukey's Honest Significant Difference test to determine which specialty was different. Results: A total of 225 surveys were answered, out of which 20 were eliminated due to inadequate completion, leaving 205 complete surveys for analysis. The average age was 28.66 years (SD ± 2.360) and 71.2 % were females. Concerning the specialties, pediatrics was found in 28.8 % of the respondents and anesthesiology in 20.5 %. A significant association between specialties with a value of p = 0.0000 and academic degrees with p = 0.003 (p ≤ 0.05) was evidenced. Differences regarding suicidal ideation were found by specialty: Kruskal-Wallis H test showed a value of p = 0.000 and Tukey's Honest Significant Difference test revealed that the specialty of gynecology was the different one. Conclusions: According to the results of the study sample, approximately one fourth of the resident physicians had suicidal ideation. Its prevalence in this sample showed no significant difference with respect to its incidence in Latin America. An association between suicidal ideation, medical specialties and academic degree was found. As for the comparison between specialties, gynecology was the one with the highest suicidal ideation rate. This work had some limitations; for example, the groups were very heterogeneous, a probabilistic selection technique was not used, and the statistical tests were nonparametric.

Novel Candidate loci and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing.

The familial occurrence of hematological malignancies has been underappreciated. Recent studies suggest that up to 15% of adults with myeloid neoplasms carry germline pathogenic variants in cancer-predisposing genes. This study aimed to identify the underlying germline predisposition variant in patients with a strong family or personal onco-hematological history using whole exome sequencing on sixteen uncharacterized individuals. It was carried out in two groups of patients, one with samples available from two affected relatives (Cohort A) and one with available samples from the index case (Cohort B). In Cohort A, six families were characterized. Two families shared variants in genes associated with DNA damage response and involved in cancer development (CHEK2 and RAD54L). Pathogenic or likely pathogenic germline variants were also found in novel candidate genes (NFATC2 and TC2N). In two families, any relevant pathogenic or likely pathogenic genomic variants were identified. In Cohort B, four additional index cases were analyzed. Three of them harbor clinically relevant variants in genes with a probable role in the development of inherited forms of hematological malignancies (GATA1, MSH4 and PRF1). Overall, whole exome sequencing is a useful approach to achieve a further characterization of these patients and their mutational spectra. Moreover, further investigations may help improve optimization for disease management of affected patients and their families.

Mediación de conflictos, competencia no difundida en médicos en formación: revisión / Conflict mediation, an undisclosed skill among medical students: A review

RESUMEN El ser humano es un ser social por naturaleza, y los desacuerdos y conflictos son situaciones comunes e inherentes a sus diferentes actividades sociales. En esta revisión se pretende describir el origen de los conflictos y las técnicas de mediación en la atención sanitaria. Se sabe de la necesidad de aprender las habilidades para la solución de conflictos, y se reconocen dentro de las prioridades cambiantes de los educandos del profesional sanitario. El desacuerdo y el conflicto son inevitables entre los miembros de los equipos clínicos, así como con los pacientes y sus familias durante el curso de la atención sanitaria. A pesar de la importancia que representa esta competencia, no se ha establecido como una necesidad educacional en los planes de estudio de los profesionales de la salud, no obstante de que los médicos requieren negociar y resolver conflictos de manera continua en los entornos sanitarios. Nuestra función como educadores es la de analizar el contexto profesional empírico cambiante y otorgar a los educandos las herramientas pertinentes para su desarrollo profesional con la mayor posibilidad de éxito en sus actividades cotidianas. Los invitamos a leer, analizar y criticar esta propuesta, que consideramos muy importante para que sea contemplada en los planes de estudio desde el pregrado y posgrado de las diferentes ramas de los profesionales de la salud, que incluyen tanto a médicos de las diferentes especialidades, el personal de enfermería y todos aquellos profesionales que trabajamos con el objetivo común de brindar asistencia sanitaria de calidad.

ABSTRACT Human beings are social beings by nature, and disagreements and conflicts are common situations inherent in their different social activities. This review aims to describe the origin of conflicts and the mediation techniques in healthcare. It is well known that conflict resolution skills are needed to be learned, and such skills are considered within the changing priorities of healthcare students. Disagreement and conflict are inevitable between members of clinical care teams, as well as with patients and their families during healthcare. Despite the importance of these skills, they have not been established as an educational need in healthcare professionals' curricula, even though physicians are required to negotiate and resolve conflicts on an ongoing basis in healthcare settings. Our role as educators is to analyze the changing empirical professional context, and provide our students with the relevant tools with the greatest chance of success for their professional development in their daily activities. We invite you to read, analyze and criticize this proposal, which we consider very important to be included in the undergraduate and graduate curricula of the different fields of healthcare professionals, i.e. specialist physicians, nursing staff and all those professionals who work with the common goal of providing quality healthcare.

Cambios ventilatorios después de una traqueotomía en neumonía por COVID-19 / Ventilatory changes after a tracheostomy in COVID-19 pneumonia

Introducción: existe aún una controversia sobre los efectos en los parámetros ventilatorios en pacientes sometidos a una traqueotomía, y los estudios en casos de pacientes con SARS-CoV-2 son escasos. Objetivo: describir los cambios en los parámetros ventilatorios en pacientes operados de traqueotomía por SARS-CoV-2 en la unidad de cuidados intensivos (UCI). Métodos: se realizó un estudio retrospectivo, descriptivo y longitudinal en el que se incluyeron las variables como edad, sexo, comorbilidades, tiempo de intubación, parámetros ventilatorios, gasométricos y el índice de Kirby. Se utilizó estadística descriptiva con medidas de tendencia central y medidas de dispersión. Resultados: se recibieron 493 casos con COVID-19, 133 (26,35 %) ingresaron, 21 fueron operados en la UCI; el género masculino fue 76 % y edad de 56 años; la obesidad y la hipertensión fueron las comorbilidades más comunes, todos con PCR positivo; los parámetros ventilatorios preoperatorios fueron presión positiva al final de la espiración (PEEP) de 7,61 y fracción inspirada de oxígeno (FiO2) de 41,42, la gasometría fue pH de 7,42, presión parcial de oxígeno (pO2) de 95,04, presión parcial de dióxido de carbono (pCO2) de 41,47, bicarbonato (HCO3) de 29,14, saturación de oxígeno (SatO2) de 94,7 %, el índice de Kirby x = 235; y los posoperatorios (PEEP de 7,19 y FiO2 de 40,6), la gasometría fue de pH de 7.44, pO2 de 43,7, pCO2 de 87,7, HCO3 de 27,4, SatO2 de 95,23 %. Fallecieron tres pacientes, dos pacientes complicados con sangrado y un caso con decanulación accidental. El tiempo promedio de ventilación mecánica de fue de 5,7 días. Conclusiones: la traqueotomía generó cambios muy sutiles en los parámetros ventilatorios y gasométricos; sin embargo, la liberación de la ventilación mecánica fue en promedio menor a una semana, desocupando espacio en la UCI.

Introduction: Controversy continues to exist regarding the effects on ventilatory parameters in patients undergoing tracheostomy, and studies in cases with SARS-CoV-2 are scarce. Objective: To describe changes in ventilatory parameters in patients undergoing tracheostomy for SARS-CoV-2 in the intensive care unit. Methods: A retrospective, descriptive, longitudinal study was carried out. Variables such as age, sex, comorbidities, time of IOT, ventilatory parameters, blood gases and the Kirby index were included. Descriptive statistics with measures of central tendency and measures of dispersion were used. Results: n = 493 COVID-19 cases were received, n = 133 (26.35%) were admitted, 21 were operated on in the ICU, male gender was 76%, age 56 years, obesity and hypertension were the most common comorbidities, all With CRP +, the preoperative ventilatory parameters x (PEEP 7.61) and (FiO2 41.42), the blood gas was (pH 7.42), (pO2 95.04), (pCO2 41.47), ( HCO3 29.14), (Saturation O2 94.7%) and the Kirby index x = 235 and postoperative x (PEEP 7.19) and (FiO2 40.6), the blood gas was (pH 7.44), (pO2 43.7), (pCO2 87.7), (HCO3 27.4), (Saturation O2 95.23%). n = 3 died, two patients with bleeding complications and one case with accidental decannulation. The mean time of mechanical ventilation was n = 5.7 days. Conclusions: The tracheostomy generated very subtle changes in the ventilatory and gasometric parameters, however, the release of mechanical ventilation was on average less than one week, emptying space in the ICU.

Tuberculosis laríngea secundaria a foco pulmonar primario inadvertido: caso clínico / Laryngeal tuberculosis secondary to an inadvertent primary pulmonary focus: clinical case

Introducción: La tuberculosis laríngea es una entidad sumamente rara en países del primer mundo, sin embargo, en nuestro medio no es extraño, como país latinoamericano, sospechar esta patología como una de las causas de disfonía y lesiones granulomatosas en la actualidad. La tuberculosis laríngea debe considerarse dentro de las patologías en pacientes con disfonía de larga evolución que no responden al tratamiento común, esta entidad puede ser confundida con neoplasias. Reporte de caso: Se presenta el caso de una mujer en la cuarta década de la vida con disfonía crónica de 6 meses de evolución, que fue remitida para laringoscopia. Se localizaron neoformaciones granulomatosas acompañadas de edema en ambas cuerdas vocales, sometidas a biopsia, con resultados con la tinción de hematoxilina-eosina de células gigantes multinucleadas de Langhans y la tinción Zielh-Nielsen fue positiva para bacilo alcohol ácido resistente. La radiografía de tórax mostró lesiones reticulonodulares sugestivas de tuberculosis pulmonar. Conclusión: Un alto nivel de sospecha y un diagnóstico temprano pueden limitar las complicaciones y facilitar un manejo oportuno de estos casos. Es necesario sospechar de tuberculosis laríngea en pacientes que presentan disfonía crónica, especialmente cuando se asocia con síntomas constitucionales, aunque no siempre los presentan, por otro lado, en algunos casos, no existe asociación con inmunodeficiencia.

Introduction: Laryngeal tuberculosis is an extremely rare entity in first world countries, however, it is not strange in our environment as a Latin American country to suspect this pathology as one of the causes of dysphonia and granulomatous lesions today. Laryngeal tuberculosis should be considered within the pathologies in patients with long-standing dysphonia that do not respond to common treatment, this entity can be confused with neoplasms. Case report: We present the case of a female in the fourth decade of life with chronic dysphonia of six months of evolution, who was referred for laryngoscopy, granulomatous neoformations accompanied by edema in both vocal cords were located, subjected to biopsy with results with hematoxylin staining. Langhans multinucleated giant cell eosin and Zielh-Nielsen staining were positive for acid-fast bacillus. Chest X-ray showed reticule-nodular lesions suggestive of pulmonary tuberculosis. Conclusion: A high level of suspicion and an early diagnosis can limit complications and facilitate timely management of these cases. It is necessary to suspect laryngeal tuberculosis in patients with chronic dysphonia, especially when associated with constitutional symptoms, although they do not always present them; on the other hand, in some cases, there is no association with immunodeficiency

Influence of ruthenium doping on UV- and visible-light photoelectrocatalytic color removal from dye solutions using a TiO2 nanotube array photoanode.

The photocatalytic activity of TiO2 anodes was enhanced by synthesizing Ru-doped Ti|TiO2 nanotube arrays. Such photoanodes were fabricated via Ti anodization followed by Ru impregnation and annealing. The X-ray diffractograms revealed that anatase was the main TiO2 phase, while rutile was slightly present in all samples. Scanning electron microscopy evidenced a uniform morphology in all samples, with nanotube diameter ranging from 60 to 120 nm. The bias potential for the photoelectrochemical (PEC) treatment was selected from the electrochemical characterization of each electrode, made via linear sweep voltammetry. All the Ru-doped TiO2 nanotube array photoanodes showed a peak photocurrent (PP) and a saturation photocurrent (SP) upon their illumination with UV or visible light. In contrast, the undoped TiO2 nanotubes only showed the SP, which was higher than that reached with the Ru-doped photoanodes using UV light. An exception was the Ru(0.15 wt%)-doped TiO2, whose SP was comparable under visible light. Using that anode, the activity enhancement during the PEC treatment of a Terasil Blue dye solution at Ebias(PP) was much higher than that attained at Ebias(SP). The percentage of color removal at 120 min with the Ru(0.15 wt%)-doped TiO2 was 98% and 55% in PEC with UV and visible light, respectively, being much greater than 82% and 28% achieved in photocatalysis. The moderate visible-light photoactivity of the Ru-doped TiO2 nanotube arrays suggests their convenience to work under solar PEC conditions, aiming at using a large portion of the solar spectrum.

A new regulatory mechanism of protein phosphatase 2A activity via SET in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although novel emerging drugs are available, the overall prognosis remains poor and new therapeutic approaches are required. PP2A phosphatase is a key regulator of cell homeostasis and is recurrently inactivated in AML. The anticancer activity of several PP2A-activating drugs (e.g., FTY720) depends on their interaction with the SET oncoprotein, an endogenous PP2A inhibitor that is overexpressed in 30% of AML cases. Elucidation of SET regulatory mechanisms may therefore provide novel targeted therapies for SET-overexpressing AMLs. Here, we show that upregulation of protein kinase p38ß is a common event in AML. We provide evidence that p38ß potentiates SET-mediated PP2A inactivation by two mechanisms: facilitating SET cytoplasmic translocation through CK2 phosphorylation, and directly binding to and stabilizing the SET protein. We demonstrate the importance of this new regulatory mechanism in primary AML cells from patients and in zebrafish xenograft models. Accordingly, combination of the CK2 inhibitor CX-4945, which retains SET in the nucleus, and FTY720, which disrupts the SET-PP2A binding in the cytoplasm, significantly reduces the viability and migration of AML cells. In conclusion, we show that the p38ß/CK2/SET axis represents a new potential therapeutic pathway in AML patients with SET-dependent PP2A inactivation.

A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity.

Acute myeloid leukemia (AML) is an aggressive disease associated with very poor prognosis. Most patients are older than 60 years, and in this group only 5-15% of cases survive over 5 years. Therefore, it is urgent to develop more effective targeted therapies. Inactivation of protein phosphatase 2 A (PP2A) is a recurrent event in AML, and overexpression of its endogenous inhibitor SET is detected in ~30% of patients. The PP2A activating drug FTY720 has potent anti-leukemic effects; nevertheless, FTY720 induces cardiotoxicity at the anti-neoplastic dose. Here, we have developed a series of non-phosphorylable FTY720 analogues as a new therapeutic strategy for AML. Our results show that the lead compound CM-1231 re-activates PP2A by targeting SET-PP2A interaction, inhibiting cell proliferation and promoting apoptosis in AML cell lines and primary patient samples. Notably, CM-1231 did not induce cardiac toxicity, unlike FTY720, in zebrafish models, and reduced the invasion and aggressiveness of AML cells more than FTY720 in zebrafish xenograft models. In conclusion, CM-1231 is safer and more effective than FTY720; therefore, this compound could represent a novel and promising approach for treating AML patients with SET overexpression.

Allocation to Matched Related or Unrelated Donor Results in Similar Clinical Outcomes without Increased Risk of Failure to Proceed to Transplant among Patients with Acute Myeloid Leukemia: A Retrospective Analysis from the Time of Transplant Approval.

Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p < .001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; p = .63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; p = .001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (p = .54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; p = .83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant.

Dolor postoperatorio: frecuencia y caracterización del manejo / Postoperative pain: frequency and management characterization

Abstract Introduction: Acute postoperative pain is a usual symptom and a surgical challenge. Objective: To determine the frequency of pain in the postoperative period of patients undergoing elective surgery and to characterize pain management at a second-level public hospital. Material and methods: A cross-section study of 175 postop patients was conducted, analyzing variables such as level of pain 24 hours after surgery according to the visual analog scale, type of surgery, use of analgesics, and anesthetic technique. Results: The findings indicate that the frequency of moderate, severe, and excruciating pain is 66.3%. In all cases, the analgesia treatment was prescribed by the treating service, and 2 to 3 nonsteroidal anti-inflammatory drugs were used in 86.4% of the cases, with a minimal use of opioids in 13% of the patients. The anesthetic techniques used included balanced general anesthesia, neuro-axial block, and a mixed technique; the latter improved pain control. Conclusion: The frequency of postoperative pain is similar to the level reported in other trials (30%-70%), pointing to the need to review our current management, with more extensive participation and training of the staff involved in pain control.

Resumen Introducción: El dolor agudo postoperatorio es un síntoma frecuente, el cual representa un reto en el ámbito quirúrgico. Objetivo: determinar la frecuencia de dolor en el paciente postoperado de cirugía electiva y caracterizar el manejo del mismo en un hospital público de segundo nivel de atención. Material y métodos: se realizó un estudio transversal en 175 pacientes postoperados, analizando las variables de grado de dolor a las 24 horas del postoperatorio con la escala visual análoga, tipo de cirugía, uso de analgésicos, técnica anestésica. Resultados: Se encontró que la frecuencia de dolor moderado, severo o insoportable es del 66.3%. El tratamiento analgésico en todos los casos fue prescrito por el servicio tratante y en el 86.4% de los casos se emplearon AINE'S, en número de uno a tres. Con un uso mínimo de opioides en el 13% de los pacientes. Las técnicas anestésicas usadas fueron AGB, BNA y técnica mixta; con mejoría en el grado de dolor con la técnica mixta. Conclusión: Existe una frecuencia de dolor postoperatorio similar a lo reportado en otros estudios (30-70%), reflejando la necesidad de revisión del manejo actual, mayor participación y capacitación del personal involucrado en su manejo.