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Genetic and environmental cues shape the evolution of the B cell Ig repertoire. Activation-induced cytidine deaminase (AID) is essential to generating Ig diversity through isotype class switching and somatic mutations, which then directly influence clonal selection. Impaired B cell development in AID-knockout mice has made it difficult to study Ig diversification in an aging repertoire. Therefore, in this report, we used a novel inducible AID-knockout mouse model and discovered that deleting AID in adult mice caused spontaneous germinal center formation. Deep sequencing of the IgH repertoire revealed that Ab diversification begins early in life and evolves over time. Our data suggest that activated B cells form germinal centers at steady state and facilitate continuous diversification of the B cell repertoire. In support, we identified shared B cell lineages that were class switched and showed age-dependent rates of mutation. Our data provide novel context to the genesis of the B cell repertoire that may benefit the understanding of autoimmunity and the strength of an immune response to infection.

Senecavirus A (SVA) infection in pigs causes vesicular disease and results in a short viremia and transient shedding of the virus, mainly in oral fluids and feces. Here we describe the consistent prolonged shedding of SVA in the semen of 2 boars, and persistence of SVA within the tonsils and testes of 3 adult boars. Two SVA-infected boars that were identified on a Minnesota sow farm in 2017 shed SVA RNA in semen for >3 mo after an outbreak of vesicular disease had occurred on the farm. SVA was isolated from 1 semen sample collected 9 d after clinical disease began on the farm. The third SVA-infected boar was identified on an Indiana sow farm in 2020. All boars had SVA RNA detected in the testes and tonsils by RT-rtPCR, with lower Ct values obtained for the testes than from the tonsils. All boars had multifocal lymphocytic orchitis with segmental degeneration and atrophy of the germinal epithelium within the seminiferous tubules. One boar also had areas of seminiferous tubule collapse and interstitial fibrosis within the testes. In all boars, in situ hybridization demonstrated the presence of SVA mRNA within cells located basally in the seminiferous tubules of the testes, and within the basal surface epithelial cells, crypt epithelial cells, and subepithelial and parafollicular lymphocytes and histiocytes of the tonsil.

Objetivo: Describir las características académicas e institucionales de estudiantes que rindieron el Examen Nacional de Internado Médico (ENIM) del Seguro Social de Salud (EsSalud) y explorar su asociación con el puntaje obtenido. Materiales y métodos: Estudio transversal analítico de una base de datos secundaria de estudiantes de medicina que rindieron el ENIM del EsSalud en Perú el 27 de diciembre del 2022. Evaluamos los factores asociados al puntaje del ENIM mediante regresión lineal. Resultados: Evaluamos a 1228 estudiantes de medicina que rindieron el ENIM. La mediana de puntaje en el ENIM fue de 12,2 (rango 10,2 a 13,8), el 35,9% de los estudiantes aprobó el examen y solo el 26,5% proviene de una Universidad que cuenta con el programa de medicina ya licenciado. En el modelo ajustado, el puntaje en el ENIM fue mayor en estudiantes que pertenecían a una universidad con el programa de medicina ya licenciado (β 0,5; IC 95%: 0,2 a 0,8) y aquellos con un promedio ponderado universitario mayor o igual a 13. Y el puntaje fue menor en estudiantes de universidades societarias (β -1,2; -1,6 a -0,8) o asociativa (β -2,0; -2,4 a -1,6) con respecto a estudiantes de universidades nacionales. Conclusión: Los estudiantes de medicina provenientes de universidades nacionales, universidades con programa de medicina licenciados y promedio ponderado universitario mayor o igual a 13 tuvieron un mejor desempeño en el examen nacional de internado médico de EsSalud.

We evaluated neutralizing antibody (NAbs) levels as a protective factor against vaccine breakthrough infection (VBI) in healthcare workers (HCWs) during the third COVID-19 wave in Peru. This retrospective cohort study employed the information from a private laboratory in Lima (Peru) of HCW who received only two BBIBP-CorV vaccines or (additionally) a heterologous booster with BNT162b2. We evaluated the association between the VBI and the levels of NAbs at 21, 90, 180, and 210 days after the BBIBP-CorV second dose. NAbs were calculated with the cPass™ SARS-CoV-2 Neutralization Antibody Detection kit (surrogate virus neutralization test (sVNT)) and the Elecsys® anti-SARS-CoV-2 S Test. Of the 435 HCW evaluated, 31.72% had an infection previous to vaccination, 68.28% received a booster dose, and 23.21% had a VBI during the third wave. The variables associated with a lower risk of VBI were male sex (aRR: 0.43) and those who had (180 days after BBIBP-CorV inoculation) NAbs levels ≥ 60% (aRR: 0.58) and ≥90% (aRR: 0.59) on cPass™, and ≥500 with Elecsys® (aRR: 0.58). HCW whose NAbs persisted at higher levels six months after the BBIBP-CorV showed a lower risk of suffering from a VBI during the third COVID-19 wave.

Interspecies transmission of influenza A virus (IAV) between pigs and people represents a threat to both animal and public health. To better understand the risks of influenza transmission at the human-animal interface, we evaluated 1) the rate of IAV detection in swine farmworkers before and after work during two human influenza seasons, 2) assessed risk factors associated with IAV detection in farmworkers and 3) characterized the genetic sequences of IAV detected in both workers and pigs. Of 58 workers providing nasal passage samples during 8-week periods during the 2017/18 and 2018/19 influenza seasons, 33 (57%) tested positive by rRT-PCR at least once. Sixteen (27%) workers tested positive before work and 24 (41%) after work. At the sample level, 58 of 1,785 nasal swabs (3.2%) tested rRT-PCR positive, of which 20 of 898 (2.2%) were collected prior to work and 38 of 887 (4.3%) after work. Although farmworkers were more likely to test positive at the end of the working day (OR = 1.98, 95% CI 1.14-3.41), there were no influenza-like illness (ILI) symptoms, or other risk indicators, associated with IAV detection before or after reporting to work. Direct whole-genome sequencing from samples obtained from worker nasal passages indicated evidence of infection of a worker with pandemic 2009 H1N1 of human-origin IAV (H1-pdm 1A 3.3.2) when reporting to work, and exposure of several workers to a swine-origin IAV (H1-alpha 1A 1.1) circulating in the pigs on the farm where they were employed. Our study provides evidence of 1) risk of IAV transmission between pigs and people, 2) pandemic H1N1 IAV infected workers reporting to work and 3) workers exposed to swine harbouring swine-origin IAV in their nasal passages temporarily. Overall, our results emphasize the need to implement surveillance and transmission preventive protocols at the pig/human interface.

The use of processing fluids to monitor the breeding herd's porcine reproductive and respiratory syndrome (PRRS) status has gained industry acceptance. However, little is known about PRRS virus RT-qPCR detection dynamics in processing fluids and factors that may contribute to maintain PRRS virus in the herd after an outbreak. This study aimed to describe weekly RT-qPCR processing fluid results in breeding herds after an outbreak and to evaluate the proportion of RT-qPCR positive results among parity groups. Processing tissues of 15 first parity (P1), 15 second parity (P2), and 15 third parity or higher (P3+) litters (parity groups) were collected weekly for between 19 and 46 weeks in nine breeding herds. Processing fluids were aggregated, and RT-qPCR tested by parity group weekly. Additionally, a subset of 743 processing fluid samples of litters that formed 50 parity groups, as previously described, were RT-qPCR tested individually at the litter level. The agreement between RT-qPCR results of processing fluid samples of parity groups (15 litters) and results based on individual litter testing was assessed using overall percent of agreement, Kappa statistic, and McNemar test. The association between RT-qPCR results and the parity group was evaluated using a generalized estimating equations model, after accounting for the effects of sampling week, breeding herd PRRS control strategy (i.e., open to replacements v/s closed) and herd. An autoregressive correlation structure was used to account for the repeated samplings within a herd in time. The overall agreement was 98 %, and Kappa statistic 0.955 (McNemar p = 1.0). Sensitivity of parity group processing fluid samples was estimated at 100 % (95 % CI 89-100 %), while specificity was estimated at 94 % (95 % CI 71-100 %). Although P1 aggregated litters had on average a higher proportion of RT-qPCR positive results from outbreak week 25 onwards, the proportion was not significantly different to the one observed for P2 and P3+ aggregated litters (p > 0.13). Additionally, herds that interrupted gilt entry had lower odds of PRRS RT-qPCR positivity than herds that continued entering gilts (OR = 0.35, 95 % CI 0.16-0.78). PRRS virus persistence in processing fluids was not affected by the sow parity effect in most of the breeding herds studied. No evidence of disagreement between RT-qPCR results of an aggregated sample of 15 litters and those of individual litters was observed. This level of litter aggregation testing strategy may be of particular use at the last stages of an elimination program under low PRRS virus prevalence. info:eu-repo/semantics/acceptedVersion

Sow mortality has become a growing concern in the pig production industry over the past decade. Therefore, we aimed to describe sow mortality and associated factors in a production system in the midwestern USA.Mortality records from 2009 to 2018 for four farrow-to-wean farms were described. Environmental, farm- and individual-level factors associated with weekly mortality and individual risk of dying throughout a sow's lifetime were assessed.Deaths occurred at a median of 116 days from last service, or 26 days postpartum. The median parity upon death was two. Overall, the main reasons for death were locomotion (27%) and reproduction (24%). A higher weekly number of deaths was associated with spring (incidence rate ratio [IRR] 1.27, compared to winter). Sows had a higher mortality when they were exposed to at least one porcine reproductive and respiratory syndrome (PRRS) outbreak during their lifetime (IRR 1.55) and when housed in groups (pens) during gestation (IRR 1.32). Conversely, they had a lower mortality when housed in filtered farms (IRR 0.76), accounting for an interaction term between parity at removal and PRRS outbreak exposure.Issues with data completion and information accuracy were present, and prospective data collection throughout sows' lifetimes is still needed.Efforts to reduce infectious diseases within the herd and manage environmental stressors should help reduce mortality.

To describe the clinical, laboratory and treatment characteristics of COVID-19 patients and to determine the factors associated with mortality during hospital stay. Materials and Methods: Retrospective cohort study of adult COVID-19 inpatients. The clinical, laboratory and treatment data were obtained from the medical records of patients from the Hospital Nivel III Daniel Alcides Carrión in Tacna. For the survival analysis we used the Cox proportional hazards model, and we calculated crude and adjusted hazard ratios (HR) with 95% confidence intervals (95% CI).We evaluated 351 patients; 74.1% of them were men. The most common comorbidities were obesity (31.6%), hypertension (27.1%) and diabetes mellitus (24.5%). The median time of hospitalization was 8 days (IQR: 4-15). From the total of patients, 32.9% died during follow-up. The multivariate analysis showed an increased risk of dying associated with the following: age ≥65 years, HR = 3.55 (95% CI: 1.70-7.40); increase in lactate dehydrogenase720 U/L, HR = 2.08 (95% CI: 1.34-3.22); and oxygen saturation less than 90%, mainly when it was less than 80%, HR = 4.07 (95% CI: 2.10-7.88). In addition, the use of colchicine during treatment showed a protective effect, HR = 0.46 (95% CI: 0.23-0.91).Risk factors for mortality due to COVID-19 included being older than 65 years, having oxygen saturation less than 90%, and elevated lactate dehydrogenase720 U/L; colchicine treatment could improve the prognosis of patients.Describir las características demográficas, clínicas, laboratoriales y de tratamiento de pacientes hospitalizados por la COVID-19 y determinar los factores asociados a la mortalidad hospitalaria.Estudio de cohorte retrospectivo de pacientes adultos hospitalizados por la COVID-19. Se extrajeron datos demográficos, clínicos, laboratoriales y de tratamiento de las historias clínicas de pacientes que ingresaron al Hospital III Daniel Alcides Carrión de Tacna. Para el análisis de supervivencia se empleó el modelo de riesgos proporcionales de Cox y se calcularon los cocientes de riesgo instantáneos (HR) crudos y ajustados con sus respectivos intervalos de confianza al 95% (IC 95%).Se evaluó a 351 pacientes, el 74,1% eran hombres; las comorbilidades más comunes fueron obesidad (31,6%), hipertensión (27,1%) y diabetes mellitus (24,5%). La mediana de tiempo de hospitalización fue 8 días (RIC: 4-15). El 32,9% falleció durante el seguimiento. El análisis multivariado mostró un aumento del riesgo de morir asociado a la edad ≥65 años, HR = 3,55 (IC 95%: 1,70-7,40); al incremento de lactato deshidrogenasa720 U/L, HR = 2,08 (IC 95%: 1,34-3,22); y a la saturación de oxígeno por debajo del 90%, principalmente cuando fue menor al 80%, HR = 4,07 (IC 95%: 2,10-7,88). Además, el uso de colchicina en el tratamiento tuvo un efecto protector, HR = 0,46 (IC 95%: 0,23-0,91).Los factores asociados a muerte por la COVID-19 incluyeron ser mayor de 65 años, tener saturación de oxígeno menor de 90% y elevación del lactato deshidrogenasa720 U/L; el tratamiento con colchicina podría mejorar el pronóstico de los pacientes.

The COVID-19 pandemic circumstances have varied the pathogens related to acute respiratory infections (ARI), and most specialists have ignored them due to SARS-CoV-2’s similar symptomatology. We identify respiratory pathogens with multiplex PCR in samples with presumptive SARS-CoV-2 but negative RT-qPCR results. We performed a retrospective transversal study employing clinical data and nasopharyngeal swab samples from patients with suspected clinical SARS-CoV-2 infection and a negative PCR result in a private laboratory in Lima, Peru. The samples were analyzed using the FilmArray™ respiratory panel. Of 342 samples, we detected at least one pathogen in 50% of the samples. The main ones were rhinovirus (54.38%), influenza A(H3N2) (22.80%), and respiratory syncytial virus (RSV) (14.04%). The clinical characteristics were sore throat (70.18%), cough (58.48%), nasal congestion (56.43%), and fever (40.06%). Only 41.46% and 48.78% of patients with influenza met the definition of influenza-like illness (ILI) by the World Health Organization (WHO) (characterized by cough and fever) and the Centers for Disease Control and Prevention (CDC) (characterized by fever and cough and sore throat), respectively. A higher prevalence of influenza was associated with ILI by WHO (aPR: 2.331) and ILI by CDC (aPR: 1.892), which was not observed with other respiratory viruses. The clinical characteristic associated with the increased prevalence of rhinovirus was nasal congestion (aPR: 1.84). For patients with ARI and negative PCR results, the leading respiratory pathogens detected were rhinovirus, influenza, and RSV. Less than half of patients with influenza presented ILI, although its presence was specific to the disease.

Reducing neonatal mortality is a global challenge. This study’s objective was to determine the predictors of mortality in patients with neonatal sepsis. The study was a retrospective cohort study in a Peruvian hospital from January 2014 to April 2022. Neonates diagnosed with sepsis were included. To find predictors of mortality, we used Cox proportional regression models. We evaluated 288 neonates with sepsis; the median birth weight and hospitalization time were 3270 g and seven days, respectively. During follow-up, 18.4% did not survive, and the most common complications were jaundice (35.42%), respiratory distress syndrome (29.51%), and septic shock (12.5%). The most isolated bacteria were Klebsiella pneumoniae. The risk factors associated with higher mortality were prematurity (aHR = 13.92; 95% CI: 1.71–113.51), platelets

Since the arrival of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, elimination and control programmes have had partial success. The dynamics of its spread are hard to quantify, though previous work has shown that local transmission and the transfer of pigs within production systems are most associated with the spread of PEDV. Our work relies on the history of PEDV infections in a region of the southeastern United States. This infection data is complemented by farm-level features and extensive industry data on the movement of both pigs and vehicles. We implement a discrete-time survival model and evaluate different approaches to modelling the local-transmission and network effects. We find strong evidence in that the local-transmission and pig-movement effects are associated with the spread of PEDV, even while controlling for seasonality, farm-level features and the possible spread of disease by vehicles. Our fully Bayesian model permits full uncertainty quantification of these effects. Our farm-level out-of-sample predictions have a receiver-operating characteristic area under the curve (AUC) of 0.779 and a precision-recall AUC of 0.097. The quantification of these effects in a comprehensive model allows stakeholders to make more informed decisions about disease prevention efforts.

Background and objectives: Sleep disorders are a common public health problem among college students. The objective of this study was to evaluate sleep quality and its associated factors in medical students during the COVID-19 pandemic. Materials and Methods: Cross-sectional analytical study—we conducted a secondary analysis of the survey “Nomophobia in medical students in Peru” database between 2020 and 2021. Sleep disturbances were assessed using the Pittsburgh Sleep Quality Index (PSQI). To evaluate associated factors, crude and adjusted prevalence ratios (aPR) and their 95% confidence intervals (95% CI) were calculated. Results: We analyzed data from 3139 participants from 18 cities in Peru (61.1% were women, median age: 22 years). 43.4% had a quality of sleep that could require medical attention; the PSQI dimension with the highest score was daytime dysfunction. The poor sleep quality was associated with symptoms of anxiety (aPR: 1.48; 95% CI: 1.27–1.72), depression (aPR: 2.03; 1.72–2.39), or nomophobia (aPR: 1.28; 1.09–1.51). Conclusions: Sleep disorders were a common problem among Peruvian medical students and were associated with anxiety, depression, or nomophobia symptoms.

Due to close contact with death, medical students may question their own and their patients’ dying process, especially with the impact of the COVID-19 pandemic on the increase in deaths. This situation provokes fear and negative attitudes towards dealing with patients and their environment. This study aimed to assess the level of fear of death and associated factors in medical students at a Peruvian university. A cross-sectional analytical study was conducted during March 2021 in human medicine students from the first to the seventh year. A validated survey including the Collet–Lester fear-of-death scale was applied. Factors associated with the fear-of-death score were evaluated by calculating linear regression coefficients (β). A total of 284 students were included. The median age was 22 years, and 58.1% were female. The mean Collet–Lester scale score was 2.79, and it was higher in the dimensions related to the death of others. Adjusted analysis showed that the score on this scale was lower in students aged 24–40 years compared to 17–21 years (β: −0.25; 95% CI: −0.46 to −0.04) and those who had no religious beliefs (β: −0.29; 95% CI: −0.53 to −0.04). In conclusion, fear of death was lower than reported in other investigations despite the COVID-19 situation, being much lower among older students and those without religious beliefs.

Introducción: La pandemia de la COVID-19 ha cobrado más de dos millones de muertes, generando el colapso de los sistemas de salud en todo el mundo, especialmente en países de bajos recursos. A medida que la pandemia fue avanzando, el desequilibrio entre la oferta y la demanda de recursos médicos creó dilemas éticos relacionados con la mejor manera de asignar los recursos disponibles. Discusión: El Perú no contaba con los recursos necesarios para enfrentar una pandemia como la del COVID-19, es por ello que su sistema sanitario colapsó, mostrando la tasa de mortalidad más alta a nivel mundial durante la primera ola. Ante la saturación de los servicios hospitalarios, el dilema que se presentó fue: ¿cuándo, cómo y a quién se le debe asignar los pocos recursos médicos disponibles? Desde un punto de vista bioético, los profesionales de la salud deben buscar salvar la mayor cantidad de vidas, dando prioridad a los pacientes con mejor pronóstico y a quienes podrían contribuir a este fin, como el personal sanitario. Conclusión: La identificación de los dilemas éticos que surgen por la pandemia ayudará a los médicos a tomar decisiones cercanas a lo que se considere adecuado para el grupo, no solo de trabajadores de salud, sino también de pacientes y familiares. Las recomendaciones aquí descritas podrían ayudar a la toma de estas decisiones.

Objetivo: Determinar la percepción del uso de dióxido de cloro (CDS) y el grado de conocimiento sobre la COVID-19 en estudiantes de Medicina de una universidad peruana. Material y métodos: Estudio observacional de corte transversal. Se realizó una encuesta virtual a 158 estudiantes de Medicina de la Universidad Nacional Jorge Basadre Grohmann, del 15 al 18 de agosto del 2020. El instrumento utilizado se dividió en tres secciones: características sociodemográficas, nivel de conocimientos sobre la COVID-19 y actitudes frente al uso del CDS. El análisis bivariado se realizó utilizando la prueba exacta de Fisher. Resultados: De los 158 estudiantes de Medicina encuestados, el 53 % fueron mujeres, la edad media fue de 21 (RIC: 19-23) años. El 22 % considera que si un médico o personal de salud recomienda el uso de dióxido de cloro, es porque tiene alguna utilidad para tratar la COVID-19, y el 39 % tiene un conocimiento bajo sobre la enfermedad. Existe diferencia entre la percepción frente al uso de dióxido de cloro y el nivel de conocimientos sobre la COVID-19 (p

Information on the effects of a heterologous booster in adult patients first vaccinated with the BBIBP-CorV vaccine is limited. This prospective cohort study evaluated the humoral response of 152 healthcare workers (HCWs) from a private laboratory in Lima (Peru) before and after receiving the BNT162b2 vaccine, with a seven-month interval since the BBIBP-CorV doses. We employed the Elecsys® anti-SARS-CoV-2 S and the cPass™ SARS-CoV-2 Neutralization Antibody (NAbs) assays to evaluate anti-S-RBD IgG and NAbs, respectively. Of the 152 HCWs, 79 (51.98%) were previously infected (PI) with SARS-CoV-2 and 73 (48.02%) were not previously infected (NPI). The proportion of HCWs with positive NAbs, seven months after the BBIBP-CorV immunization, was 49.31% in NPI and 92.40% in PI. After the booster, this ratio increased to 100% in both groups. The anti-S-RBD IgG and NAbs in the HCWs’ NPI increased by 32.7 and 3.95 times more, respectively. In HCWs’ PI, this increment was 5 and 1.42 times more, respectively. There was no statistical association between the history of previous SARS-CoV-2 infection and the titer of anti-S-RBD IgG and NAbs after the booster. The humoral immunity presented a robust increase after receiving the BNT162b2 booster and was more pronounced in NPI.

Insufficient data have been reported about the effect of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) on the humoral response through time in healthcare workers (HCW). This retrospective cohort studied the information of 252 HCW from a private laboratory, comparing the antibody-mediated response provoked by BBIBP-CorV between HCW previously infected with SARS-CoV-2 (PI) and not previously infected (NPI), employing the Elecsys® anti-SARS-CoV-2 S and the cPass™ SARS-CoV-2 Neutralization Antibody Detection kit at intervals of 21, 90, and 180 days after vaccination. The presence of neutralizing antibodies in HCW 21 days after full vaccination was 100% in PI and 91.60% in NPI. We observed a progressive decrease in antibody levels over time in both groups. Comparing HCW PI with NPI, PI had a 10.9, 14.3, and 8.6-fold higher antibody titer with the Elecsys® anti-SARS-CoV-2 S at 21 (p < 0.001), 90 (p< 0.001) and 180 days (p < 0.001) respectively, compared to NPI. Using the percent of signal inhibition (PSI) of the antibody neutralization cPass™, HCW PI showed a level of 1.3, 2.0, and 3.1 times more antibodies, at 21 (p < 0.001), 90 (p < 0.001), and 180 days (p < 0.001) respectively, compared to NPI. We determined a progressive decrease in humoral immunity over time, particularly higher in those NPI.

Background The rapid spread of SARS-CoV-2 has created a shortage of supplies of reagents for its detection throughout the world, especially in Latin America. The pooling of samples consists of combining individual patient samples in a block and analyzing the group as a particular sample. This strategy has been shown to reduce the burden of laboratory material and logistical resources by up to 80%. Therefore, we aimed to evaluate the diagnostic performance of the pool of samples analyzed by RT-PCR to detect SARS-CoV-2. Methods A cross-sectional study of diagnostic tests was carried out. We individually evaluated 420 samples, and 42 clusters were formed, each one with ten samples. These clusters could contain 0, 1 or 2 positive samples to simulate a positivity of 0, 10 and 20%, respectively. RT-PCR analyzed the groups for the detection of SARS-CoV-2. The area under the ROC curve (AUC), the Youden index, the global and subgroup sensitivity and specificity were calculated according to their Ct values that were classified as high (H: ≤ 25), moderate (M: 26–30) and low (L: 31–35) concentration of viral RNA. Results From a total of 42 pools, 41 (97.6%) obtained the same result as the samples they contained (positive or negative). The AUC for pooling, Youden index, sensitivity, and specificity were 0.98 (95% CI, 0.95–1); 0.97 (95% CI, 0.90–1.03); 96.67% (95% CI; 88.58–100%) and 100% (95% CI; 95.83–100%) respectively. In the stratified analysis of the pools containing samples with Ct ≤ 25, the sensitivity was 100% (95% CI; 90–100%), while with the pools containing samples with Ct ≥ 31, the sensitivity was 80% (95% CI, 34.94–100%). Finally, a higher median was observed in the Ct of the clusters, with respect to the individual samples (p Conclusions The strategy of pooling nasopharyngeal swab samples for analysis by SARS-CoV-2 RT-PCR showed high diagnostic performance.

Introduction Acute respiratory distress syndrome (ARDS) due to Coronavirus Disease 2019 (COVID-19) causes high mortality. The objective of this study is to determine whether the arterial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2) 24 h after invasive mechanical ventilation (IMV) and the difference between PaO2/FiO2 at 24 h after IMV and PaO2/FiO2 before admission to IMV (ΔPaO2/FiO2 24 h) are predictors of survival in patients with ARDS due to COVID-19. Methods A retrospective cohort study was conducted that included patients with ARDS due to COVID-19 in IMV admitted to the intensive care unit (ICU) of a hospital in southern Peru from April 2020 to April 2021. The ROC curves and the Youden index were used to establish the cut-off point for PaO2/FiO2 at 24 h of IMV and ΔPaO2/FiO2 at 24 h associated with mortality. The association with mortality was determined by Cox regression, calculating the crude (cHR) and adjusted (aHR) risk ratios, with their respective 95% confidence intervals (95% CI). Results Two hundred patients were analyzed. The average age was 54.29 years, 79% were men, and 25.5% (n = 51) died. The cut-off point calculated for PaO2/FiO2 24 h after IMV and ΔPaO2/FiO2 24 h was 222.5 and 109.5, respectively. Those participants with a value below the cut-off point of ΔPaO2/FiO2 24 h and PaO2/FiO2 24 h after IMV had higher mortality, aHR = 3.32 (CI 95% [1.82–6.07]) and aHR = 2.87 (CI 95% [1.48–5.57]) respectively. Conclusion PaO2/FiO2 24 h after IMV and ΔPaO2/FiO2 24 h in patients diagnosed with ARDS due to COVID-19 on IMV were associated with higher hospital mortality. These findings are helpful to identify those patients with a higher risk of dying on admission to the ICU.

The role of transportation vehicles, pig movement between farms, proximity to infected premises, and feed deliveries has not been fully considered in the dissemination dynamics of porcine epidemic diarrhea virus (PEDV). This has limited efforts for disease prevention, control and elimination restricting the development of risk-based resource allocation to the most relevant modes of PEDV dissemination. Here, we modeled nine pathways of between-farm transmission represented by a contact network of pig movements between sites, farm-to-farm proximity (local transmission), four distinct contact networks of transportation vehicles (trucks that transport pigs from farm-to-farm and farm-to-markets, as well as trucks transporting feed and staff), the volume of animal by-products in feed diets (e.g., fat and meat-and-bone-meal) to reproduce PEDV transmission dynamics. The model was calibrated in space and time with weekly PEDV outbreaks. We investigated the model performance to identify outbreak locations and the contribution of each route in the dissemination of PEDV. The model estimated that 42.7% of the infections in sow farms were related to vehicles transporting feed, 34.5% of infected nurseries were associated with vehicles transporting pigs between farms, and for both farm types, local transmission or pig movements were the next most relevant transmission routes. On the other hand, finishers were most often (31.4%) infected via local transmission, followed by the vehicles transporting feed and pigs between farms. Feed ingredients did not significantly improve model calibration metrics, sensitivity, and specificity; therefore, it was considered to have a negligible contribution in the dissemination of PEDV. The proposed modeling framework provides an evaluation of PEDV transmission dynamics, ranking the most important routes of PEDV dissemination and granting the swine industry valuable information to focus efforts and resources on the most important transmission routes.

Se realizó un estudio descriptivo en el que se evaluaron las características clínicas y laboratoriales en la evolución de pacientes con diagnóstico de síndrome de distrés respiratorio agudo (SDRA) secundario a infección por SARS-CoV-2 y que recibieron Tocilizumab. Veinticuatro pacientes recibieron Tocilizumab, la mayoría eran varones (95,8 %), la comorbilidad más frecuente fue obesidad (33,3 %), al momento de recibir Tocilizumab la mediana de PaO2/FiO2 fue 159,5 (RIC 114,5-255,3). Veintiún (87,5 %) pacientes presentaron mejoría clínica y 3 (12,5 %) fallecieron. Quince pacientes (62,5 %) desarrollaron hepatotoxicidad, la mayoría de grado 3 (33,3 %) y tres (12,5 %) pacientes presentaron injuria hepática grado 4. Once pacientes (45,8 %) presentaron sobreinfección bacteriana, siendo el germen más frecuente Acinetobacter baumannii. Luego de la administración de Tocilizumab más de la mitad de los pacientes presentó una reacción adversa, a pesar de ello la mortalidad fue baja y la mayoría tuvo una mejora clínica.

Objective: To describe the clinical, laboratory and treatment characteristics of COVID-19 patients and to determine the factors associated with mortality during hospital stay. Materials and Methods: Retrospective cohort study of adult COVID-19 inpatients. The clinical, laboratory and treatment data were obtained from the medical records of patients from the Hospital Nivel III Daniel Alcides Carrión in Tacna. For the survival analysis we used the Cox proportional hazards model, and we calculated crude and adjusted hazard ratios (HR) with 95% confidence intervals (95% CI). Results: We evaluated 351 patients; 74.1% of them were men. The most common comorbidities were obesity (31.6%), hypertension (27.1%) and diabetes mellitus (24.5%). The median time of hospitalization was 8 days (IQR: 4-15). From the total of patients, 32.9% died during follow-up. The multivariate analysis showed an increased risk of dying associated with the following: age ≥65 years, HR = 3.55 (95% CI: 1.70-7.40); increase in lactate dehydrogenase 720 U/L, HR = 2.08 (95% CI: 1.34-3.22); and oxygen saturation less than 90%, mainly when it was less than 80%, HR = 4.07 (95% CI: 2.10-7.88). In addition, the use of colchicine during treatment showed a protective effect, HR = 0.46 (95% CI: 0.23-0.91). Conclusions: Risk factors for mortality due to COVID-19 included being older than 65 years, having oxygen saturation less than 90%, and elevated lactate dehydrogenase 720 U/L; colchicine treatment could improve the prognosis of patients. Objetivo: Describir las características demográficas, clínicas, laboratoriales y de tratamiento de pacientes hospitalizados por la COVID-19 y determinar los factores de riesgo de mortalidad hospitalaria. Materiales y métodos: Estudio de cohorte retrospectivo de pacientes adultos hospitalizados por la COVID-19. Se extrajeron datos demográficos, clínicos, laboratoriales y de tratamiento de las historias clínicas de pacientes que ingresaron al Hospital III Daniel Alcides Carrión de Tacna. Para el análisis de supervivencia se empleó el modelo de riesgos proporcionales de Cox y se calcularon los cocientes de riesgo instantáneos (HR) crudos y ajustados con sus respectivos intervalos de confianza al 95% (IC 95%). Resultados: Se evaluó a 351 pacientes, el 74,1% eran hombres; las comorbilidades más comunes fueron obesidad (31,6%), hipertensión (27,1%) y diabetes mellitus (24,5%). La mediana de tiempo de hospitalización fue 8 días (RIC: 4-15). El 32,9% falleció durante el seguimiento. El análisis multivariado mostró un aumento del riesgo de morir asociado a la edad ≥65 años, HR = 3,55 (IC 95%: 1,70-7,40); al incremento de lactato deshidrogenasa 720 U/L, HR = 2,08 (IC 95%: 1,34-3,22); y a la saturación de oxígeno por debajo del 90%, principalmente cuando fue menor al 80%, HR = 4,07 (IC 95%: 2,10-7,88). Además, el uso de colchicina en el tratamiento tuvo un efecto protector, HR = 0,46 (IC 95%: 0,23-0,91). Conclusiones: Los factores de riesgo de muerte por la COVID-19 incluyeron ser mayor de 65 años, tener saturación de oxígeno menor de 90% y elevación del lactato deshidrogenasa 720 U/L; el tratamiento con colchicina podría mejorar el pronóstico de los pacientes.

Overuse of antibiotics during the Coronavirus Disease 2019 (COVID-19) pandemic could increase the selection of extensively resistant bacteria (XDR). However, it is unknown what impact they could have on the evolution of patients, particularly critically ill patients. This study aimed to evaluate the characteristics and impact of ICU-acquired infections in patients with COVID-19. A retrospective cohort study was conducted, evaluating all patients with critical COVID-19 admitted to the intensive care unit (ICU) of a hospital in Southern Peru from 28 March 2020 to 1 March 2021. Of the 124 patients evaluated, 50 (40.32%) developed a healthcare-associated infection (HAI), which occurred at a median of 8 days (IQR 6–17) after ICU admission. The proportion of patients with HAI that required ceftriaxone was significantly higher, the same was true for the use of dexamethasone. Forty bacteria isolations (80%) were classified as XDR to antibiotics, with the most common organisms being Acinetobacter baumannii (54%) and Pseudomonas aeruginosa (22%), 33% (41/124) died at the ICU during the follow-up. In the adjusted analysis, healthcare-associated infection was associated with an increased risk of mortality (aHR= 2.7, 95% CI: 1.33–5.60) and of developing acute renal failure (aRR = 3.1, 95% CI: 1.42–6.72). The incidence of healthcare infection mainly by XDR pathogens is high in critically ill patients with COVID-19 and is associated with an increased risk of complications or death.

Iodinated contrast substances may cause different adverse events, most frequently renal involvement and hypersensitivity reactions. Transient cortical blindness and global amnesia are rarely described neurological complications after the administration of contrast substances. We report the case of a 63-year old patient with high blood pressure who presented with cyanosis and cold sensation affecting the second and third digits of his left hand. The patient underwent an arteriography of the left arm, where 50-mL of iopamidol was used as a contrast substance, and he immediately developed occipital headache associated to bilateral blurred vision that rapidly progressed to blindness. A cerebral computed tomography (CT) scan showed occipital subarachnoid hypodense areas, with no mass effect. Eighteen hours after the event, the patient showed retrograde amnesia with persistent amaurosis. His control cerebral CT scan did now show any focal disorder. The patient had a good progression, both bilateral amaurosis and headache subsided thirty hours after the event, and the patient was uneventfully discharged after ten days.

The dysregulation of multiple signaling pathways, including those through endosomal Toll-like receptors (TLRs), Fc gamma receptors (FcγR), and antigen receptors in B cells (BCR), promote an autoinflammatory loop in systemic lupus erythematosus (SLE). Here, we used selective small-molecule inhibitors to assess the regulatory roles of interleukin-1 receptor (IL-1R)-associated kinase 4 (IRAK4) and Bruton's tyrosine kinase (BTK) in these pathways. The inhibition of IRAK4 repressed SLE immune complex- and TLR7-mediated activation of human plasmacytoid dendritic cells (pDCs). Correspondingly, the expression of interferon (IFN)-responsive genes (IRGs) in cells and in mice was positively regulated by the kinase activity of IRAK4. Both IRAK4 and BTK inhibition reduced the TLR7-mediated differentiation of human memory B cells into plasmablasts. TLR7-dependent inflammatory responses were differentially regulated by IRAK4 and BTK by cell type: In pDCs, IRAK4 positively regulated NF-κB and MAPK signaling, whereas in B cells, NF-κB and MAPK pathways were regulated by both BTK and IRAK4. In the pristane-induced lupus mouse model, inhibition of IRAK4 reduced the expression of IRGs during disease onset. Mice engineered to express kinase-deficient IRAK4 were protected from both chemical (pristane-induced) and genetic (NZB/W_F1 hybrid) models of lupus development. Our findings suggest that kinase inhibitors of IRAK4 might be a therapeutic in patients with SLE.

La pandemia del COVID-19 plantea nuevos retos, pero también propone un nuevo enfoque de la educación médica en pregrado.

Colony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34 and CSF1 at homeostasis or in the context of inflammatory diseases or cancer in wild-type mice have not been clarified in vivo. By neutralizing CSF1 and/or IL34 in adult mice, we identified that they play important roles in macrophage differentiation, specifically in steady-state microglia, Langerhans cells, and kidney macrophages. In several inflammatory models, neutralization of both CSF1 and IL34 contributed to maximal disease protection. However, in a myeloid cell-rich tumor model, CSF1 but not IL34 was required for tumor-associated macrophage accumulation and immune homeostasis. Analysis of human inflammatory conditions reveals IL34 upregulation that may account for the protection requirement of IL34 blockade. Furthermore, evaluation of IL34 and CSF1 blockade treatment during Listeria infection reveals no substantial safety concerns. Thus, IL34 and CSF1 play non-redundant roles in macrophage differentiation, and therapeutic intervention targeting IL34 and/or CSF1 may provide an effective treatment in macrophage-driven immune-pathologies.