Long-Term Complete Response and Survival in Metastatic Extramammary Paget's Disease Treated With Trastuzumab Plus Paclitaxel: A Case Report.

Extramammary Paget's disease is a rare skin cancer that usually arises from the secretory cells of the apocrine glands. In most cases, an extramammary Paget's tumor occurs as a single intraepithelial form not associated with another cancer, although rarely, it may be associated with other loco-regional or distant cancer. It is generally slow-growing and diagnosed in situ. Most often, surgical excision with wide margins is curative, with the local recurrence rate being lower after the Mohs micrographic surgery technique. Nonetheless, relapses are frequent. In the metastatic setting, there are no treatment guidelines or standard therapies; additionally, the experience is limited to a few individual cases, and the efficacy of conventional chemotherapies is not well-defined. Moreover, chemotherapy can also have serious side effects; therefore, there is a need to identify more effective and less toxic therapies. In this case report, we have observed a long-lasting complete response with anti-HER2 plus paclitaxel.

Early Changes in LIPI Score Predict Immune-Related Adverse Events: A Propensity Score Matched Analysis in Advanced Non-Small Cell Lung Cancer Patients on Immune Checkpoint Blockade.

In advanced cancer patients undergoing immune checkpoint blockade, the burden of immune-related adverse events (irAEs) is high. The need for reliable biomarkers for irAEs remains unfulfilled in this expanding therapeutic field. The lung immune prognostic index (LIPI) is a noninvasive measure of systemic inflammation that has consistently shown a correlation with survival in various cancer types when assessed at baseline. This study sought to determine whether early changes in the LIPI score could discriminate the risk of irAEs and different survival outcomes in advanced non-small cell lung cancer (NSCLC) patients receiving PD-(L)1 blockade-based therapies. We included consecutive patients diagnosed with metastatic NSCLC who received pembrolizumab, nivolumab, or atezolizumab as second-line therapy following platinum-based chemotherapy, or first-line pembrolizumab either alone or in combination with platinum-based chemotherapy. The LIPI score relied on the combined values of derived neutrophil/lymphocyte ratio (dNLR) and lactate dehydrogenase. Their assessment at baseline and after two cycles of treatment allowed us to categorize the population into three subgroups with good (LIPI-0), intermediate (LIPI-1), and poor (LIPI-2) prognosis. Between April 2016 and May 2023, we enrolled a total of 345 eligible patients, 165 (47.8%) and 180 (52.2%) of whom were treated as first- and second-line at our facility, respectively. After applying propensity score matching, we considered 83 relevant patients in each cohort with a homogeneous distribution of all characteristics across the baseline LIPI subgroups. There was a noticeable change in the distribution of LIPI categories due to a significant decrease in dNLR values during treatment. Although no patients shifted to a worse prognosis category, 20 (24.1%) transitioned from LIPI-1 to LIPI-0, and 7 (8.4%) moved from LIPI-2 to LIPI-1 (p < 0.001). Throughout a median observation period of 7.3 (IQR 3.9-15.1) months, a total of 158 irAEs (63.5%) were documented, with 121 (48.6%) and 39 (15.7%) patients experiencing mild to moderate and severe adverse events, respectively. Multivariate logistic regression analysis showed that the classification and changes in the LIPI score while on treatment were independent predictors of irAEs. The LIPI-0 group was found to have significantly increased odds of experiencing irAEs. Following a median follow-up period of 21.1 (95% CI 17.9-25.8) months, the multivariable Cox model confirmed LIPI categorization at any given time point as a significant covariate with influence on overall survival, irrespective of the treatment line. These findings suggest that reassessing the LIPI score after two cycles of treatment could help pinpoint patients particularly prone to immune-related toxicities. Those who maintain a good LIPI score or move from the intermediate to good category would be more likely to develop irAEs. The continuous assessment of LIPI provides prognostic insights and could be useful for predicting the benefit of PD-(L)1 checkpoint inhibitors.

Herpes zoster after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in actively treated cancer patients: a prospective study.

Several concerns have been raised about a causal relationship between COVID-19 mRNA-based vaccines and the development of herpes zoster (HZ). We performed a prospective analysis of the Vax-On-Third-Profile study to investigate the incidence of HZ after the third dose of mRNA-BNT162b2 (tozinameran) and its correlation with immune responses. Patients who had received a booster dose and had been actively treated for at least 8 weeks were eligible. Serologic assessment was performed before the third dose of tozinameran (timepoint-1) and 4 weeks later (timepoint-2). We also assessed the incidence of SARS-CoV-2 breakthrough infections at predefined time points. The current analysis included 310 patients, of whom 109 (35.2%) and 111 (35.8%) were being treated with targeted therapies and cytotoxic chemotherapy, respectively. All participants received a third dose of tozinameran between September 26 and October 30, 2021. After a mean follow-up of 17.3 (IQR 15.1-18.4) months, HZ occurred in 8 recipients, for a cumulative incidence of 2.6%, and an incidence rate of 0.310 per person-year (95% CI 0.267-0.333). All HZ cases occurred within 30 days of booster dosing (range 5-29 days), with a median time to onset of 15 (IQR 9-22) days. Among the 7 patients (2.2%) who also contracted a SARS-CoV-2 infection, all cases preceded COVID-19 outbreaks. No instances of complicated HZ were reported. In multivariate analysis, impaired T helper and T cytotoxic cell counts independently correlated with HZ occurrence. These findings provide the first evidence that cancer patients on active treatment have a not negligible risk of developing HZ within 30 days after the third dose of tozinameran. The favorable clinical outcome of all observed cases confirms that protective effects of boosters in reducing the risk of severe COVID-19 outweigh the potential risk of HZ occurrence.

Discriminación percibida por pacientes en seguimiento por COVID-19. Tajamar Regalado, Ecuador

Fundamento la COVID-19 tuvo repercusión en el estado biopsicosocial de la población. Entre las actitudes y comportamientos, la discriminación se manifestó como una de las respuestas a diferentes niveles de interrelación personal y social. Objetivo describir la discriminación percibida por pacientes en seguimiento por COVID-19. Métodos estudio descriptivo y transversal, realizado en el periodo septiembre de 2021 a febrero de 2022, con todos los pacientes con seguimiento por COVID-19 (N=89) residentes en el barrio de Tajamar Regalado (Tulcán, Ecuador). Mediante la encuesta se obtuvo información sobre las variables: tipo de institución donde recibió seguimiento médico, percepción de discriminación, apoyo social y apoyo comunitario. Resultados el 60,67 % de los pacientes refirió que casi siempre lamentaba haberse contagiado de COVID-19; el 59,55 %, que siempre sintió ser discriminado por haber padecido la enfermedad; el 40,45 %, que casi siempre consideró importante utilizar medidas de protección para evitar más contagios en su comunidad; el 48,31 % planteó que casi siempre recibió consejería por el personal de salud; y el 59,55 % consideró que su salud mental se vio afectada. Casi la mitad de los pacientes expresó haber recibido un apoyo social muy malo, y el 51,68 % un apoyo social malo parte de las autoridades en particular. Conclusiones durante la pandemia de COVID-19 existió un rechazo social a los pacientes contagiados, el cual provocó afectaciones en la salud mental de estos. Se evidenció una falta de apoyo por parte de la comunidad y las autoridades; y una escasa consejería por el personal de salud.

Foundation COVID-19 had an impact on the population' biopsychosocial state. Among attitudes and behaviors, discrimination manifested itself as one of the responses to different levels of personal and social interrelation. Objective to describe the discrimination perceived by patients being monitored for COVID-19. Methods descriptive and cross-sectional study, carried out from September 2021 to February 2022, in all patients monitored for COVID-19 (N=89) who live in Tajamar Regalado neighborhood (Tulcán, Ecuador). Through the survey, information was obtained on the variables: type of institution where they received medical follow-up, perception of discrimination, social support and community support. Results 60.67% of patients reported that they almost always regretted having been infected with COVID-19; 59.55%, who always felt they were discriminated against for having suffered from the disease; 40.45%, who almost always considered it important to use protective measures to avoid further infections in their community; 48.31% stated that they almost always received counseling from health personnel; and 59.55% considered that their mental health was affected. Almost half of the patients expressed having received very bad social support, and 51.68% received bad social support from the authorities in particular. Conclusions during the COVID-19 pandemic, there was social rejection of infected patients, which caused effects on their mental health. A lack of support from the community and authorities was evident; and little counseling by health personnel.

Immune responses and clinical outcomes following the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in advanced breast cancer patients receiving targeted therapies: a prospective study.

Purpose: Metastatic breast cancer patients are the most prevalent oncology population with advanced disease facing COVID-19 pandemic. Immune responses after mRNA-based vaccination during treatment with CDK4/6 inhibitors or HER2-directed agents remain unclear. We conducted a prospective analysis to elucidate changes in antibody titers and lymphocyte counts following full course of mRNA-BNT162b2 (tozinameran) vaccination in recipients undergoing these targeted therapies. Methods: Patients who had received a booster dosing and had been treated for at least 6 months were eligible. Antibody titers against SARS-CoV-2 spike protein were measured at four subsequent time points. Immunophenotyping of circulating lymphocytes was performed before the third dose of tozinameran and four weeks later to quantify the absolute counts of CD3+CD4+ T-helper cells, CD3+CD8+ T-cytotoxic cells, CD19+ B cells, and CD56+CD16+ NK cells. We also assessed the incidence of breakthrough infections and investigated whether immune changes affect time-to-treatment failure (TTF) after booster vaccination. Results: The current analysis included 69 patients, of whom 38 (55%) and 31 (45%) were being treated with CDK4/6 inhibitors and HER2-targeted therapies, respectively. All participants received a third dose of tozinameran between September 23 and October 7, 2021. Multivariate analysis revealed that CDK4/6 inhibition predicted a significantly impaired humoral response after the booster dose. This detrimental effect was also evident for T-helper cell counts before the third immunization, but it disappeared in the subsequent evaluation. After a median follow-up of 22.3 months, we observed 19 (26%) cases of COVID-19 outbreaks, all experiencing favorable clinical outcomes. Univariate analysis showed a significant association between the onset of SARS-CoV-2 infections and the use of CDK4/6 inhibitors, as well as with an impaired antibody and T-helper cell response. Only the last two covariates remained independent predictors after multivariate testing. Dynamic variations in antibody titers and T-helper cell counts did not affect TTF in multivariate regression analysis. Conclusions: Our results confirm that the immune response to tozinameran is impaired by CDK4/6 inhibitors, increasing the odds of breakthrough infections despite the third vaccine dose. Current evidence recommends maintaining efforts to provide booster immunizations to the most vulnerable cancer patients, including those with advanced breast cancer undergoing CDK4/6 inhibition.

Effects of Acetaminophen Exposure on Outcomes of Patients Receiving Immune Checkpoint Inhibitors for Advanced Non-Small-Cell Lung Cancer: A Propensity Score-Matched Analysis.

(1) Background: Several studies have investigated potential interactions between immune checkpoint inhibitors (ICIs) and commonly prescribed medications. Although acetaminophen (APAP) has not been considered susceptible to interaction with ICIs, recent research has shown that detectable plasma levels of this drug can hinder the efficacy of PD-1/PD-L1 blockade therapies. A reliable assessment of the potential interaction between APAP and ICIs in advanced non-small cell lung cancer (NSCLC) patients would be worthwhile since it is often prescribed in this condition. We sought to evaluate the impact of the concomitant use of APAP in patients with advanced NSCLC on PD-1/PD-L1 blockade using real-world evidence. (2) Methods: This study included consecutive patients with histologically proven stage IV NSCLC who underwent first-line therapy with pembrolizumab as a single agent or in combination with platinum-based chemotherapy, or second-line therapy with pembrolizumab, nivolumab, or atezolizumab. The intensity of APAP exposure was classified as low (therapeutic intake lasting less than 24 h or a cumulative intake lower than 60 doses of 1000 mg) or high (therapeutic intake lasting more than 24 h or a total intake exceeding 60 doses of 1000 mg). The favorable outcome of anti-PD-1/PD-L1 therapies was defined by durable clinical benefit (DCB). Progression-free survival (PFS) and overall survival (OS) were relevant to our efficacy analysis. Propensity score matching (PSM) methods were applied to adjust for differences between the APAP exposure subgroups. (3) Results: Over the course of April 2018 to October 2022, 80 patients were treated with first-line pembrolizumab either as single-agent therapy or in combination with platinum-based chemotherapy. During the period from June 2015 to November 2022, 145 patients were given anti-PD-1/PD-L1 blockade therapy as second-line treatment. Subsequent efficacy analyses relied on adjusted PSM populations in both treatment settings. Multivariate testing revealed that only the level of APAP and corticosteroid intake had an independent effect on DCB in both treatment lines. Multivariate Cox regression analysis confirmed high exposure to APAP and immunosuppressive corticosteroid therapy as independent predictors of shorter PFS and OS in both treatment settings. (4) Conclusions: Our findings would strengthen the available evidence that concomitant intake of APAP blunts the efficacy of ICIs in patients with advanced NSCLC. The detrimental effects appear to depend on the cumulative dose and duration of exposure to APAP. The inherent shortcomings of the current research warrant confirmation in larger independent series.

Changes in Peripheral Immune Cells after the Third Dose of SARS-CoV-2 mRNA-BNT162b2 Vaccine and Disease Outcomes in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Prospective Analysis of the Vax-on-Third-Profile Study.

BACKGROUND: Anti-SARS-CoV-2 mRNA vaccines can deeply affect cell-mediated immune responses in immunocompromised recipients, including cancer patients receiving active treatments. The clinical implications of changes in peripheral blood lymphocyte subsets following the third dose of mRNA-BNT162b2 vaccination (tozinameran) in patients on immune checkpoint blockade are not fully understood. We conducted a prospective analysis of the Vax-On-Third-Profile study to evaluate the impact of circulating lymphocyte dynamics on disease outcomes in this subgroup of patients. METHODS: Recipients of booster dosing who had received before vaccination at least one course of an anti-PD-1/PD-L1 treatment for an advanced solid tumor were eligible. Immunophenotyping of peripheral blood was performed before the third dose of tozinameran (timepoint-1) and four weeks later (timepoint-2) to quantify the absolute counts of lymphocyte subpopulations, including CD3+CD4+ T cells, CD3+CD8+ T cells, B cells, and NK cells. Logistic regression was used to analyze the relationship between lymphocyte subsets and durable clinical benefit (DCB). The log-rank test and Cox regression model were applied to evaluate the relationship between lymphocyte subpopulations and both vaccine-related time-to-treatment failure (V-TTF) and overall survival (OS). RESULTS: We included a total of 56 patients with metastatic disease who were given a third dose of tozinameran between 23 September and 7 October 2021 (median age: 66 years; male: 71%). Most recipients had a diagnosis of lung cancer and were being treated with pembrolizumab or nivolumab. Compared to baseline, the third immunization resulted in an incremental change in the median counts of all lymphocyte subpopulations, which was statistically significant only for NK cells (p < 0.001). A significant correlation was found between NK cell counts and DCB at timepoint-2 (p < 0.001). Multivariate logistic regression analysis of DCB confirmed the predictive significance of high-level NK cell counts (p = 0.020). In multivariate Cox regression analysis, high-level NK cell counts independently predicted longer V-TTF [HR 0.34 (95% CI 0.14-0.80), p = 0.014] and OS [HR 0.36 (95% CI 0.15-0.89), p = 0.027]. CONCLUSIONS: Our data suggest expansion of NK cell counts as the most noteworthy change in circulating lymphocytes after the third dose of tozinameran in cancer patients receiving PD-1/PD-L1-targeted agents. This change correlated with enhanced therapeutic efficacy, improving the rate of disease control, and prolonging survival outcomes. Similar findings have not been previously reported, implying that they have proof-of-concept value and warrant further confirmation.

Immune-related adverse events and disease outcomes after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients receiving immune checkpoint inhibitors.

BACKGROUND: The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. METHODS: Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible. RESULTS: The current analysis included 56 patients with metastatic disease (median age: 66 years; male: 71%), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 486 BAU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 486 BAU/mL) or high-responders (High-R, ≥ 486 BAU/mL). After a median follow-up time of 226 days, 21.4% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but an increase in the cumulative incidence of immuno-related thyroiditis was observed within the High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. CONCLUSIONS: Our findings would strengthen the recommendation not to change anti-PD-1/PD-L1 treatment plans based on current or future immunization schedules, implying that all these patients should be closely monitored.

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study.

(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population. (2) Methods: We enrolled 230 cancer patients who were on active treatment for advanced disease and had received booster dosing of an mRNA-BNT162b2 vaccine as part of the Vax-On-Third trial between September 2021 and October 2021. Four weeks after the third immunization, IgG antibodies against the spike receptor domain of SARS-CoV-2 were tested in all patients. We prospectively evaluated the incidence of breakthrough infections and disease outcomes. The coprimary endpoints were the effects of antibody titers on the development of breakthrough infections and the impact of COVID-19 outbreaks on cancer treatment failure. (3) Results: At a median follow-up of 16.3 months (95% CI 14.5-17.0), 85 (37%) patients developed SARS-CoV-2 infection. Hospitalization was required in 11 patients (12.9%) and only 2 (2.3%) deaths related to COVID-19 outbreaks were observed. Median antibody titers were significantly lower in breakthrough cases than in non-cases (291 BAU/mL (95% CI 210-505) vs. 2798 BAU/mL (95% CI 2323-3613), p < 0.001). A serological titer cut-off below 803 BAU/mL was predictive of breakthrough infection. In multivariate testing, antibody titers and cytotoxic chemotherapy were independently associated with an increased risk of outbreaks. Time-to-treatment failure after booster dosing was significantly shorter in patients who contracted SARS-CoV-2 infection (3.1 months (95% CI 2.3-3.6) vs. 16.2 months (95% CI 14.3-17.0), p < 0.001) and had an antibody level below the cut-off (3.6 months (95% CI 3.0-4.5) vs. 14.6 months (95% CI 11.9-16.3), p < 0.001). A multivariate Cox regression model confirmed that both covariates independently had a worsening effect on time-to-treatment failure. (4) Conclusions: These data support the role of vaccine boosters in preventing the incidence and severity of COVID-19 outbreaks. Enhanced humoral immunity after the third vaccination significantly correlates with protection against breakthrough infections. Strategies aimed at restraining SARS-CoV-2 transmission in advanced cancer patients undergoing active treatment should be prioritized to mitigate the impact on disease outcomes.

Transcriptional Activation of a Pro-Inflammatory Response (NF-κB, AP-1, IL-1ß) by the Vibrio cholerae Cytotoxin (VCC) Monomer through the MAPK Signaling Pathway in the THP-1 Human Macrophage Cell Line.

This study describes, to some extent, the VCC contribution as an early stimulation of the macrophage lineage. Regarding the onset of the innate immune response caused by infection, the ß form of IL-1 is the most important interleukin involved in the onset of the inflammatory innate response. Activated macrophages treated in vitro with VCC induced the activation of the MAPK signaling pathway in a one-hour period, with the activation of transcriptional regulators for a surviving and pro-inflammatory response, suggesting an explanation inspired and supported by the inflammasome physiology. The mechanism of IL-1ß production induced by VCC has been gracefully outlined in murine models, using bacterial knockdown mutants and purified molecules; nevertheless, the knowledge of this mechanism in the human immune system is still under study. This work shows the soluble form of 65 kDa of the Vibrio cholerae cytotoxin (also known as hemolysin), as it is secreted by the bacteria, inducing the production of IL-1ß in the human macrophage cell line THP-1. The mechanism involves triggering the early activation of the signaling pathway MAPKs pERK and p38, with the subsequent activation of (p50) NF-κB and AP-1 (cJun and cFos), determined by real-time quantitation. The evidence shown here supports that the monomeric soluble form of the VCC in the macrophage acts as a modulator of the innate immune response, which is consistent with the assembly of the NLRP3 inflammasome actively releasing IL-1ß.

Insatisfacción con la atención de salud en los usuarios del Centro de Salud Tajamar, Ecuador

Introducción: La OMS atribuye entre 5,7 y 8,4 millones de muertes anuales a la atención de calidad deficiente en los países de ingresos bajos y medianos, lo que representa hasta el 15 % de las muertes en esos países; es decir, que a nivel general existe un alto nivel de insatisfacción sobre todo en los países tercermundistas. Objetivo: Evaluar el grado de insatisfacción de la atención de salud en los usuarios del Centro de Salud Tajamar, Ecuador. Método: Se realizó un estudio cuantitativo observacional, descriptivo, de corte transversal en el centro de salud Tajamar de Ecuador durante el año 2022. Se trabajó con 215 usuarios por el método aleatorio simple, se utilizó los métodos científicos de observación, análisis y síntesis, empírico de encuesta. Las respuestas de la encuesta permitieron dar un grado de consecución en: muy adecuado, adecuado, poco adecuado e inadecuado, además de siempre, casi siempre y nunca. Se tuvo en cuenta criterios de inclusión y exclusión. Resultados: El 51,2 % consideró muy adecuado el trato por parte del personal de salud, solo el 32,6 % encontró adecuado el estado general de la infraestructura, el 44,2 estuvo de acuerdo con el medicamento recetado. En cuanto a la información brindada el 37,7 % siempre lo halló correcto y entendible. El 69 % alegó volvería al centro nuevamente. En sentido general el 37 % y el 29 % de los usuarios calificaron de neutra y negativa la calidad de la atención en los servicios de salud prestados. Conclusiones: Se logró evidenciar la insatisfacción de la atención en salud en los usuarios del Centro de Salud Tajamar. Se recomienda realizar intervención para mejorar la calidad de atención en dicha unidad de salud.

Introduction: WHO attributes between 5.7 and 8.4 million deaths annually to poor-quality care in low- and middle-income countries, accounting for up to 15% of deaths in these countries; That is to say, at a general level there is a high level of dissatisfaction, especially in third world countries. Objective: To evaluate the degree of dissatisfaction with health care in users of the Tajamar Health Center, Ecuador. Method: A quantitative observational, descriptive, cross-sectional study was carried out at the Tajamar health center in Ecuador during the year 2022. We worked with 215 users using the simple random method, using scientific methods of observation, analysis and synthesis. empirical survey. The survey responses made it possible to give a degree of achievement in: very adequate, adequate, slightly adequate and inadequate, as well as always, almost always and never. Inclusion and exclusion criteria were taken into account. Results: 51.2% considered the treatment by health personnel to be very adequate, only 32.6% found the general state of the infrastructure adequate, 44.2% agreed with the prescribed medication. Regarding the information provided, 37.7% always found it correct and understandable. 69% said they would return to the center again. In general, 37% and 29% of users described the quality of care in the health services provided as neutral and negative. Conclusions: Dissatisfaction with health care among users of the Tajamar Health Center was evident. It is recommended to carry out an intervention to improve the quality of care in said health unit.

Introdução: A OMS atribui anualmente entre 5,7 e 8,4 milhões de mortes a cuidados de má qualidade em países de baixo e médio rendimento, sendo responsáveis por até 15% das mortes nestes países; Isto é, a nível geral existe um elevado nível de insatisfação, especialmente nos países do terceiro mundo. Objetivo: Avaliar o grau de insatisfação com os cuidados de saúde em usuários do Centro de Saúde Tajamar, Equador. Método: Foi realizado um estudo quantitativo observacional, descritivo e transversal no centro de saúde Tajamar, no Equador, durante o ano de 2022. Trabalhamos com 215 usuários através do método aleatório simples, utilizando métodos científicos de observação, análise e síntese. As respostas ao inquérito permitiram atribuir um grau de realização em: muito adequado, adequado, pouco adequado e inadequado, bem como sempre, quase sempre e nunca. Critérios de inclusão e exclusão foram levados em consideração. Resultados: 51,2% consideraram o tratamento do pessoal de saúde muito adequado, apenas 32,6% consideraram adequado o estado geral da infraestrutura, 44,2% concordaram com a medicação prescrita. Quanto às informações prestadas, 37,7% consideraram-nas sempre corretas e compreensíveis. 69% disseram que voltariam ao centro novamente. Em geral, 37% e 29% dos utentes descreveram a qualidade dos cuidados nos serviços de saúde prestados como neutra e negativa. Conclusões: Ficou evidente a insatisfação com a assistência à saúde entre os usuários do Centro de Saúde Tajamar. Recomenda-se a realização de uma intervenção para melhorar a qualidade do atendimento na referida unidade de saúde.

Dynamic changes in peripheral lymphocytes and antibody response following a third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients.

The aim of this study was to evaluate the association of circulating lymphocytes profiling with antibody response in cancer patients receiving the third dose of COVID-19 mRNA-BNT162b2 vaccine. Immunophenotyping of peripheral blood was used to determine absolute counts of lymphocyte subsets, alongside detection of IgG antibodies against receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein (S1) before booster dosing (timepoint-1) and four weeks afterward (timepoint-2). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. An IgG titer ≥ 4446 AU/mL was assumed as a correlate of 50% vaccine efficacy against symptomatic infections. A total of 258 patients on active treatment within the previous six months were enrolled between September 23 and October 7, 2021. The third dose resulted in an exponential increase in median anti-RBD-S1 IgG titer (P < 0.001), seroconversion rates (P < 0.001), and 50% vaccine efficacy rates (P < 0.001). According to ROC curve analysis, T helper and B cells were significantly associated with seroconversion responses at timepoint-1, whereas only B cells were relevant to 50% vaccine efficacy rates at timepoint-2. A positive linear correlation was shown between anti-RBD-S1 IgG titers and these lymphocyte subset counts. Multivariate analysis ruled out a potential role of T helper cells but confirmed a significant interaction between higher B cell levels and improved antibody response. These findings suggest that peripheral counts of B cells correlate with humoral response to the third dose of mRNA-BNT162b2 vaccine in actively treated cancer patients and could provide insights into a more comprehensive assessment of vaccination efficacy.

Caracterización de lesiones cutáneas asociadas al uso de equipos de protección individual e infecciones por Staphylococcus aureus en personal sanitario en la lucha contra el Covid-19 / Characterization of skin lesions associated with the use of personal protective equipment and Staphylococcus aureus infections in health personnel in the fight against Covid-19

La pandemia por Covid-19 ha marcado cambio en paradigma de la atención médica, generando la necesidad del uso de equipo de protección individual (EPI), para salvaguardar la salud. Lo que ha originado manifestaciones cutáneas secundarias asociadas al uso de los mismos. Se realizó una investigación descriptiva de corte transversal con el objetivo de caracterizar las lesiones cutáneas asociadas al uso de EPI e infecciones por Staphylococcusaureus en 283 enfermeros, el diagnóstico dermatológico fue realizado por especialistas; el cultivo bacteriológico se realizó a partir de hisopados de algodón estériles o frotis de aposición sobre la lesión de piel. Para el aislamiento del género Staphylococcus, las muestras se sembraron en agar salino manitol rojo de fenol, incubándose de 24 a 48 horas a 37°C. La identificación de S. aureus se efectúo por la fermentación del manitol en el agar selectivo, la reacción positiva de la prueba de la coagulasa. El S. aureus se diferenció del Staphylococcus coagulasa negativo con el empleo de la prueba de la Dnasa. Se precisó LC-EPI en 75,618% de los enfermeros, de los cuales 92,523% presentaron síntomas sugestivos a infección bacteriana secundaria, ratificada en su totalidad por cultivo microbiológico, identificando a S. aureus. Se estimó que más del 60% de las LC-EPI eran de presentación única catalogada grado I, afectando mayormente las regiones: orbitaria, temporal, nasal, infraorbitaria y frontal, asociándose con el uso de lentes/protectores faciales, gorros y mascarillas como causantes de las lesiones. Se recomienda la definición de protocolos de prevención de LC-EPI(AU)

The Covid-19 pandemic has marked a paradigm shift in medical care, generating the need for the use of personal protective equipment (PPE) to safeguard health. This has caused secondary skin manifestations associated with their use. A descriptive cross-sectional investigation was carried out with the objective of characterizing the skin lesions associated with the use of PPE and Staphylococcus aureus infections in 283 nurses. The dermatological diagnosis was made by specialists; the bacteriological culture was performed using sterile cotton swabs or apposition smears on the skin lesion. For the isolation of the genus Staphylococcus, the samples were seeded in phenol red mannitol saline agar, incubating for 24 to 48 hours at 37°C. The identification of S. aureus was carried out by the fermentation of mannitol in the selective agar, the positive reaction of the coagulase test. S. aureus was differentiated from coagulase-negative Staphylococcus using the DNase test. LC-EPI was required in 75.618% of the nurses, of which 92.523% presented symptoms suggestive of secondary bacterial infection, fully confirmed by microbiological culture, identifying S. aureus. It was estimated that more than 60% of the LC-EPI were of a single presentation classified as grade I, mainly affecting the regions: orbital, temporal, nasal, infraorbital, and frontal, associated with the use of glasses/face protectors, hats, and masks as causes of the injuries. The definition of LC-EPI prevention protocols is recommended(AU)

Real-Life Experience of the Prognostic Significance of the Primary Tumor Location on the Timing of Colorectal Liver Metastases: A Retrospective Analysis.

Background Numerous research studies have looked into how the primary tumor location (PTL) affects patients' prognosis for colorectal cancer (CRC). Our research aimed to investigate the prognostic effects of PTL in patients with synchronous (SM) and metachronous (MM) colorectal cancer liver metastases (CRCLM). Material and methods From 2016 to 2021, we looked back at the records of patients at our institute who were affected by CRCLM. Results 109 patients were included, of whom 21.1% received CRCLM resection (R0=73.9%), with 57.7% having left-sided colon cancer (LCC) and 42.2% having right-sided colon cancer (RCC). SM predominated (69.7%). The median duration of follow-up was 21,3 months (95%CI=15,4-25,2). ≥5 hepatic metastases prevailed in the SM group (N=61; 83.5%). 21% of all patients underwent CRCLM resection (R0=78.2%). We observed a double rate of patients unresponsive to standard systemic antineoplastic treatments in the SM group (35.8% vs. 17.9% of the MM group) (p=0.27). We found a significantly longer median overall survival (OS) in patients with MM-LCC compared with the other groups (27.7 months; HR=0.3797; 95%CI=0.19-0.74; p=0.0205). The median OS, regardless of PTL, was higher in the MM group (16,5 months vs. 16,1 months; HR=0,29; 95%CI=0,13-0,67; p=0.0038) as well as progression-free survival (PFS) (11 months vs. 10,2 months; HR=0,61; 95%CI=0,33-1,12; p=0.11). Finally, in patients undergoing liver surgery, a noteworthy median OS was shown to be significantly in favor of patients with metachronous liver metastases from the primary left tumor (37.0 months; HR=0.47; 95%CI=0.11-1.96; p=0.0041). Conclusions Our real-life study demonstrated that patients with LCC, particularly MM-LCC, have the highest survival and that the timing of CRCLM should be a prognostic factor.

Acute kidney injury associated to sulfamethoxazole urine crystal: The importance of clinical suspicion.

Management of acute kidney injury (AKI) associated with drug-induced crystal nephropathy can be difficult, and timely diagnosis is critical to resolve this condition. We present the case of a 55-year-old woman with history of systemic lupus erythematosus (SLE), who, after treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for suspected Pneumocystis jirovecii pneumonia, developed severe AKI. Automated urinary sediment initially reported hematuria, leukocyturia and "uric acid crystals". She did not have allergic symptoms, clinical manifestations of active SLE nor hyperuricemia. AKI persisted despite volume expansion with crystalloids. Due to SMX exposure, it was suspected that "uric acid crystals" could be in reality "SMX crystals", and were a possible cause of crystal nephropathy. TMP/SMX was withheld and urinary alkalization was performed, with subsequent resolution of AKI. SMX urine crystals were posteriorly confirmed by Fourier transform infrared spectroscopy.

Dynamic Changes of Peripheral NK Cells Predict Outcome in Patients with PD-L1 Positive Non-small-cell Lung Cancer Undergoing Immune Checkpoint Inhibitors as Second-line Therapy.

We evaluated immune cell frequencies in peripheral blood samples of 41 NSCLC patients before and after second-line therapy with anti-PD-1/PD-L1 agents. Changes in lymphocyte subsets and their correlation with clinical response, progression-free survival (PFS), and overall survival (OS) were analyzed. We observed an increase in median values of all lymphocyte subsets, being significant only for NK cells. A correlation was retrieved between higher post-treatment NK cell level and clinical benefit. On multivariate analysis, PD-L1 tumor proportion score ≥1% and higher post-treatment NK cell counts were predictive of longer PFS and OS. Co-presence of these factors was characterized by longer survival.

Immune-related Thyroid Dysfunction (irTD) in Non-small Cell Lung Cancer (NSCLC) Correlates With Response and Survival.

Background: There is no clear information on the proportion of patients who need therapy for immune-related thyroid dysfunction (irTD) or who need to delay, omit, or discontinue immunotherapy. Furthermore, it is not well known whether irTD correlates with better outcomes or not. Patients and Methods: We conducted a retrospective study in patients with metastatic non-small cell lung cancer (NSCLC) treated with anti-PD1 or anti-PD-L1. Results: Our study enrolled 75 patients, 25.3% of them developed immune-related thyroid dysfunction. Three patients delayed a course of immunotherapy due to irTD, 2 patients omitted a course and 1 patient permanently discontinued. In patients with irTD compared with those without irTD the ORR was 42.1% vs. 7.1% (p<0.001), DCR was 78.9% vs. 32.1% (p<0.001); mPFS was 15.7 vs. 3.6 months (p<0.001) and mOS was 18.6 months vs. 5.1 months (p<0.001). Conclusion: Immune-related thyroid dysfunction has a mild impact on the immunotherapy treatment program. The occurrence of irTD correlates with more favorable response and survival.

Efectividad de la educación sanitaria para la prevención de enfermedades diarreicas agudas / Effectiveness of health education for the prevention of acute diarrheal diseases

En investigaciones similares se ha reportado un grado de desconocimiento respecto a las enfermedades diarreicas agudas en los padres de grupos de riesgo. Varias investigaciones han abordado el tema de la educación sanitaria como factor determinante en la prevención de enfermedades. Las políticas de salud, están obligadas a mantener vigentes las estrategias de prevención efectivas y proponer una búsqueda continua y exhaustiva de nuevas políticas que ayuden a desterrar la EDA de las principales causas de morbilidad en grupos vulnerables. El desafío actual es atenuar los determinantes sociales y atender a la población con factores de riesgo. En esta revisión se evaluó y sistematizó publicaciones en busca de pruebas de la efectividad de la educación sanitaria en la prevención de la enfermedad diarreica aguda(AU)

Similar investigations have reported a degree of ignorance regarding acute diarrheal diseases in parents of risk groups. Several investigations have addressed the issue of health education as a determining factor in disease prevention. Health policies are obliged to keep effective prevention strategies in force and propose a continuous and exhaustive search for new policies that help banish ADD from the main causes of morbidity in vulnerable groups. The current challenge is to mitigate the social determinants and care for the population with risk factors. In this review, we evaluated and systematized publications looking for evidence of the effectiveness of health education in the prevention of acute diarrheal disease(AU)

Factores de riesgo de infección por VPH en estudiantes universitarios de Guayaquil / Risk factors for HPV infection in university students in Guayaquil

La infección por VPH constituye un grave problema de salud pública a nivel mundial. Aunque las investigaciones sobre VPH han girado en torno del diagnóstico, el tratamiento y la prevención de las infecciones en las mujeres, se ha reportado que la mayor parte de los estudiantes universitarios desconoce con certeza la clínica, manejo y tratamiento de esta infección y prácticas de prevención contra el VPH e, incluso, la mayoría de las universitarias nunca se realizado la prueba de Papanicolaou. Se evaluaron los factores de riesgo de infección por VPH (virus del papiloma humano) en estudiantes universitarios de Guayaquil. El estudio reveló que la prevalencia de infección por VPH en los estudiantes que reportaron no poseer información sobre la infección por VPH fue significativamente mayor ya que permanecen en un estado de baja percepción de riesgo de contagio(AU)

HPV infection is a serious public health problem worldwide. Although research on HPV has revolved around the diagnosis, treatment, and prevention of infections in women, it has been reported that most university students are unaware of the clinical signs, management, and treatment of this infection, and of health practices. prevention against HPV and even the majority of university students have never had a Pap smear. Risk factors for HPV (human papillomavirus) infection in university students from Guayaquil were evaluated. The study revealed that the prevalence of HPV infection in students who reported not having information about HPV infection was significantly higher since they remain in a state of low perception of risk of contagion(AU)

Leishmaniasis cutánea americana: Índices epidemiológicos en Valle Hermoso de la provincia Santo Domingo de Los Tsachilas / American cutaneous leishmaniasis: Epidemiological indices in Valle Hermoso, Santo Domingo de Los Tsachilas province

Las leishmaniasis son causadas por aproximadamente 15 especies de protozoos del género Leishmania. Prevalecen en áreas tropicales y subtropicales del Viejo y Nuevo Mundo, la movilidad humana también los convierte en un problema médico en áreas no endémicas. Las manifestaciones clínicas pueden comprender formas cutáneas que pueden ser localizadas. El diagnóstico y el tratamiento varían según las manifestaciones clínicas, el área geográfica y la especie involucrada. Este artículo destaca aspectos epidemiológicos y clínicos en la provincia de Santo Domingo de los Tsachilas, Ecuador. Se utilizaron fichas clínicas y epidemiológicas de pacientes que presentaron lesiones ulceradas o no, con un tiempo de evolución igual o mayor a 2 semanas. El mayor número de casos están entre los grupos sucesivos de adolescentes de 11 a 19 años y los adultos jóvenes entre 20 y 39 años. El 81,79% de los positivos procedían de áreas rurales o periurbanas. Dos terceras partes de los pacientes eran masculinos. Hubo predominio de lesiones únicas (87,79%); ubicadas en cuello y región cervical, y extremidades inferiores (24,84 y 24,20%, respectivamente). Cerca del 88% de los pacientes no presentaron ningún tipo de sintomatología asociada a la infección parasitaria. El 97,86% de los diagnósticos de laboratorio fueron por observación microscópica directa. 81,80% obtuvieron cura total de las lesiones y el 22% de los pacientes abandonaron la terapia antiparasitaria. Se requieren pruebas rápidas y accesibles que puedan definir las especies de Leishmania, ya que la discriminación tiene una importancia significativa para el pronóstico y tratamientos específicos de la especie(AU)

Leishmaniases are caused by approximately 15 species of protozoa of the genus Leishmania. They prevail in tropical and subtropical areas of the Old and New World human mobility also makes them a medical problem in nonendemic areas. Clinical manifestations may comprise cutaneous forms that may be localized. Diagnosis and treatment vary according to the clinical manifestations, geographic area, and species involved. This article highlights epidemiological and clinical aspects in the province of Santo Domingo de los Tsachilas, Ecuador. Clinical and epidemiological records of patients who presented ulcerated lesions or not, with an evolution time equal to or greater than 2 weeks were used. The largest numbers of cases are between the successive groups of adolescents from 11 to 19 years old and young adults between 20 and 39 years old. 81.79% of the positives came from rural or peri-urban areas. Two thirds of the patients were male. There was a predominance of single lesions (87.79%); located in the neck and cervical region, and lower extremities (24.84 and 24.20%, respectively). About 88% of the patients did not present any type of symptomatology associated with the parasitic infection. 97.86% of laboratory diagnoses were by direct microscopic observation. 81.80% obtained complete cure of the lesions and 22% of the patients abandoned antiparasitic therapy. Rapid and accessible tests that can define Leishmania species are required, as discrimination is of significant importance for species-specific prognosis and treatment(AU)