Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

The Population Impact of Late Presentation With Advanced HIV Disease and Delayed Antiretroviral Therapy in Adults Receiving HIV Care in Latin America.

Late presentation to care and antiretroviral therapy (ART) initiation with advanced human immunodeficiency virus (HIV) disease are common in Latin America. We estimated the impact of these conditions on mortality in the region. We included adults enrolled during 2001-2014 at HIV care clinics. We estimated the adjusted attributable risk (AR) and population attributable fraction (PAF) for all-cause mortality of presentation to care with advanced HIV disease (advanced LP), ART initiation with advanced HIV disease, and not initiating ART. Advanced HIV disease was defined as CD4 of <200 cells/µL or acquired immune deficiency syndrome. AR and PAF were derived using marginal structural models. Of 9,229 patients, 56% presented with advanced HIV disease. ARs of death for advanced LP were 86%, 71%, and 58%, and PAFs were 78%, 58%, and 43% at 1, 5, and 10 years after enrollment. Among people without advanced LP, ARs of death for delaying ART were 39%, 32%, and 37% at 1, 5, and 10 years post-enrollment and PAFs were 20%, 14%, and 15%. Among people with advanced LP, ART decreased the hazard of death by 63% in the first year after enrollment, but 93% of these started ART; thus universal ART among them would reduce mortality by only 10%. Earlier presentation to care and earlier ART initiation would prevent most HIV deaths in Latin America.

Effectiveness of a prevention program in the incidence of cardiovascular outcomes in a low-income population from Colombia: a real-world propensity score-matched cohort study.

BACKGROUND: Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are among the leading cause of morbidity and mortality in low-and-middle-income countries (LMICs) but evidence in these contexts regarding the effectiveness of primary prevention interventions taking into account patient adherence is scarce. We aimed to evaluate the effectiveness of a cardiovascular risk management program (De Todo Corazón - DTC program) in the incidence of the first cardiovascular outcome (CVO) in a low-income population from the Caribbean region of Colombia using adherence as the main variable of exposure. METHODS: A retrospective propensity score-matched cohort study was conducted. Adult patients with a diagnosis of hypertension (HTA), diabetes mellitus (DM), chronic kidney disease (CKD), or dyslipidemia affiliated to the DTC program between 2013 and 2018 were considered as the study population. Patients with 30 to 76 years, without a history of CVOs, and with more than 6 months of exposure to the program were included. The main outcome of interest was the reduction in the risk of CVOs (stroke, myocardial infarction, or congestive heart failure) based on the adherence to the intervention (attendance to medical appointments with health care professionals and the control of cardiovascular risk factors). Kaplan Meier curves and propensity score-matched Cox regression models were used to evaluate the association between adherence and the incidence of CVOs. RESULTS: A total of 52,507 patients were included. After propensity score matching, a sample of 35,574 patients was analyzed. Mean (SD) exposure time was 1.97 (0.92) years. Being adherent to the program was associated to a 85.4, 71.9, 32.4 and 78.9% risk reduction of in the low (HR 0.14; 95% CI 0.05-0.37; p < 0.001), medium (HR 0.28; 95% CI 0.21-0.36; p < 0.001), high-risk with DM (HR 0.67; 95% CI 0.43-1.04; p = 0.075) and hig-risk without DM (HR 0.21; 95% CI 0.09-0.48; p < 0.001) categories, respectively. CONCLUSIONS: The DTC program is effective in the reduction of the risk of CVOs. Population-based interventions may be an important strategy for the prevention of CVOs in underserved populations in the context of LMICs. A more exhaustive emphasis on the control of diabetes mellitus should be considered in these strategies.

First cardiovascular event in patients with type 2 diabetes mellitus of a cardiovascular risk management program of a poor Colombian population: a cohort study.

BACKGROUND: According to several studies in population of high-income countries (HIC), patients with Type 2 diabetes mellitus (DM) have a considerably higher risk of cardiovascular morbidity and mortality. However, it is not clear if the magnitude of this association can be widespread in other populations. The objective of this study was to determine the independent association between Type 2 DM and first cardiovascular event in Colombian Caribbean poor population with no records of previous cardiovascular events reported. METHODS: We retrospectively reviewed the individual records from the hospitalizations database of 64,668 patients of cardiovascular risk management program from July 2014 to December 2015. We used a propensity score matching cohort analysis for this study. The Kaplan-Meier curves were constructed for the cardiovascular events related endpoints and matched Cox-regression analysis to estimate associations of a history of Type 2 DM with cardiovascular outcomes during 1.5 years of follow-up. A formal sensitivity analysis using The Breslow-Day and Tarone Homogeneity tests was conducted. RESULTS: Out of 56,351 patients with no previous cardiovascular events records, 19,368 (34.4%) patients were found to suffer Type 2 DM. Using propensity scores for Type 2 DM, we gathered a cohort of 18,449 pairs of patients with and without Type 2 DM who were balanced on 22 baseline characteristics. A first cardiovascular event occurred in 650 (3.5%) and 403 (2.1%) matched patients with and without Type 2 DM, respectively, during 1.5 years of follow-up. Type 2 DM was associated with first cardiovascular event (HR 1.69; 95% CI 1.43-2.00; p = 0.000), AMI (HR 1.79; 95% CI 1.45-2.20; p = 0.000) and stroke (HR 1.54; 95% CI 1.18-2.02; p = 0.001). Hazard ratios (95% CIs) for the association of Type 2 DM with all-cause mortality, cardiovascular mortality and all-cause hospitalization were 1.36 (1.21-1.53; p < 0.001), 1.52 (1.12-2.08; p 0.004), and 1.20 (1.21-1.53; p < 0.001), respectively. CONCLUSION: Type 2 DM resulted to be a significant independent risk factor for first cardiovascular event in Colombian Caribbean poor population with no previous records of cardiovascular events.

HIV screening among newly diagnosed TB patients: a cross sectional study in Lima, Peru.

BACKGROUND: Since 2006, the Peruvian National TB program (NTP) recommends voluntary counseling and testing (VCT) for all tuberculosis (TB) patients. Responding to the differential burden of both diseases in Peru, TB is managed in peripheral health facilities while HIV is managed in referral centers. This study aims to determine the coverage of HIV screening among TB patients and the characteristics of persons not screened. METHODS: From March 2010 to December 2011 we enrolled new smear-positive pulmonary TB adults in 34 health facilities in a district in Lima. NTP staff offered VCT to all TB patients. Patients with an HIV positive result were referred for confirmation tests and management. We interviewed patients to collect their demographic and clinical characteristics and registered if patients opted in or out of the screening. RESULTS: Of the 1295 enrolled TB patients, nine had a known HIV diagnosis. Of the remaining, 76.1% (979) were screened for HIV. Among the 23.9% (307) not screened, 38.4% (118) opted out of the screening. TB patients at one of the health care facilities of the higher areas of the district (OR = 3.38, CI 95% 2.17-5.28 for the highest area and OR = 2.82, CI 95% 1.78-4.49 for the high area) as well as those reporting illegal drug consumption (OR = 1.65, CI 95% 1.15-2.37) were more likely not to be screened. Twenty-four were HIV positive (1.9% of all patients 1295, or 2.4% of those screened). Of 15 patients diagnosed with HIV during the TB episode, ten were enrolled in an HIV program. The median time between the result of the HIV screening and the first consultation at the HIV program was 82 days (IQR, 32-414). The median time between the result of the HIV screening and antiretroviral initiation was 148.5 days (IQR 32-500). CONCLUSIONS: An acceptable proportion of TB patients were screened for HIV in Lima. Referral systems of HIV positive patients should be strengthened for timely ART initiation.

Synthesis and evaluation of the anti-proliferative activity of diaryl-3-pyrrolin-2-ones and fused analogs.

Analogs containing a central 3-pyrrolin-2-one core with different methoxyphenyl and/or indole substituents were prepared and tested for anti-proliferative activity in U-937 cells. The most efficacious analogs were non-rigid, (non-fused) contained methoxyaryl groups located at the 4-position, and contained either methoxyaryl or indole groups located at the 3-position. Both the number of methoxy groups contained in the substituents and the particular location of the indole rings with respect to the lactam carbonyl had significant affects on anti-proliferative activity. This work provides a framework to better understand structure-activity relationships for inducing anti-proliferative activity in diaryl heterocyclic scaffolds.

[Non-cirrhotic portal hypertension due to didanosina. A rare case]. / Hipertensión portal no cirrótica por didanosina. Un caso infrecuente.

Liver involvement is usually seen in patients infected with the human immunodeficiency virus (HIV), especially in patients coinfected with hepatitis B or C, in alcohol abuse, etc. However, there is a group of patients who develop liver involvement and portal hypertension of unspecified cause. Non-cirrhotic portal hypertension (NCPH) is a liver disorder recently described, but potentially serious. It has been reported in HIV-infected patients with highly active antiretroviral therapy (HAART), specifically didanosine (DDI). The pathophysiology involves the infectious agent (HIV) and its treatment (HAART), since both generate a pre-hepatic portal venulopathy. Similarly, HIV infection produces a prothrombotic state by protein S deficiency leading to the obliteration of small hepatic venules. It has been postulated that DDI as a cofactor in the pathogenesis of NCPH. All this leads that many of the liver biopsies show nodular regenerative hyperplasia. We present the case of a HIV-infected patient who was treated with a longstanding DDI. She developed upper gastrointestinal bleeding (UGB) and ascites due to NCPH, whose diagnosis was confirmed by biopsy. However, there is no similar study in our country.

Synthesis of Benzo[a]carbazoles and an Indolo[2,3-a]carbazole from 3-Aryltetramic Acids.

A simple and flexible approach to 3-pyrrolin-2-one fused carbazoles is disclosed. The key step involves the BF3-mediated electrophilic substitution of indoles with N-alkyl-substituted 3-aryltetramic acids, which provides access to indole-substituted 3-pyrrolin-2-ones. Scholl-type oxidative cyclizations of these materials led to the formation of the corresponding 3-pyrrolin-2-one-fused benzo[a]carbazoles and indolo[2,3-a]carbazoles. This work represents the first synthesis of the benzo[a]pyrrolo[3,4-c]carbazol-3(8H)-one ring system, while the indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-one ring system is found in a number of biologically active compounds including the protein kinase C (PKC) inhibitor, staurosporine.

Two thousand years of garden urbanism in the Upper Amazon.

A dense system of pre-Hispanic urban centers has been found in the Upano Valley of Amazonian Ecuador, in the eastern foothills of the Andes. Fieldwork and light detection and ranging (LIDAR) analysis have revealed an anthropized landscape with clusters of monumental platforms, plazas, and streets following a specific pattern intertwined with extensive agricultural drainages and terraces as well as wide straight roads running over great distances. Archaeological excavations date the occupation from around 500 BCE to between 300 and 600 CE. The most notable landscape feature is the complex road system extending over tens of kilometers, connecting the different urban centers, thus creating a regional-scale network. Such extensive early development in the Upper Amazon is comparable to similar Maya urban systems recently highlighted in Mexico and Guatemala.

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

INTRODUCTION: Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non-AIDS-related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long-term follow-up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all-cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. METHODS: Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug-based combination therapy and with medical follow-up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T-cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3 ). Primary outcomes included all-cause mortality, AIDS-defining events and non-communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T-cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. RESULTS: In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow-up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T-cell count) and older age were risk factors for all-cause mortality. We also found that older age, male sex and higher baseline CD4 T-cell count were associated with lower CD4 count increase following therapy initiation. CONCLUSIONS: Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow-up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

The impact of earthquakes in Latin America on the continuity of HIV care: A retrospective observational cohort study.

Objectives: As earthquakes occur frequently in Latin America and can cause significant disruptions in HIV care, we sought to analyze patterns of HIV care for adults at Latin American clinical sites experiencing a significant earthquake within the past two decades. Study design: Retrospective clinical cohort study. Methods: Adults receiving HIV care at sites experiencing at least a "moderate intensity" (Modified Mercalli scale) earthquake in the Caribbean, Central and South America network for HIV epidemiology (CCASAnet) contributed data from 2003 to 2017. Interrupted Time Series models were fit with discontinuities at site-specific earthquake dates (Sept. 16, 2015 in Chile; Apr. 18, 2014 and Sept. 19, 2017 in Mexico; and Aug. 15, 2007 in Peru) to assess clinical visit, CD4 measure, viral load lab, and ART initiation rates 3- and 6-months after versus before earthquakes. Results: Comparing post-to pre-earthquake periods, there was a sharp drop in median visit (incidence rate ratio [IRR] = 0.79, 95% confidence interval [CI]: 0.68-0.91) and viral load lab (IRR = 0.78, 95% CI: 0.62-0.99) rates per week, using a 3-month window. CD4 measurement rates also decreased (IRR = 0.43; 95% CI: 0.37-0.51), though only using a 6-month window. Conclusions: Given that earthquakes occur frequently in Latin America, disaster preparedness plans must be more broadly implemented to avoid disruptions in HIV care and attendant poor outcomes.

Clinical inertia in newly diagnosed type 2 diabetes mellitus among patients attending selected healthcare institutions in Colombia.

BACKGROUND: The burden of disease of diabetes in Colombia have increased in the last decades. Secondary prevention is crucial for diabetes control. Many patients already treated remain with poor glycemic control and without timely and appropriate treatment intensification. This has been called in the literature as Clinical Inertia. Updated information regarding clinical inertia based on the Colombian diabetes treatment guidelines is needed. OBJECTIVE: To measure the prevalence of clinical inertia in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients in healthcare institutions in Colombia, based on the recommendations of the current official guidelines. METHODS: An observational and retrospective cohort study based on databases of two Health Medical Organizations (HMOs) in Colombia (one from subsidized regimen and one from contributory regimen) was conducted. Descriptive analysis was performed to summarize demographic and clinical information. Chi-square tests were used to assess associations between variables of interest. RESULTS: A total of 616 patients with T2DM (308 for each regimen) were included. Median age was 61 years. Overall clinical inertia was 93.5% (87.0% in contributory regimen and 100% in subsidized regimen). Patients with Hb1Ac ≥ 8% in the subsidized regimen were more likely to receive monotherapy than patients in the contributory regimen (OR 2.33; 95% CI 1.41-3.86). CONCLUSIONS: In this study, the prevalence of overall clinical inertia was higher in the subsidized regime than in the contributory regime (100% vs 87%). Great efforts have been made to equalize the coverage between the two systems, but this finding is worrisome with respect to the difference in quality of the health care provided to these two populations. This information may help payers and clinicians to streamline strategies for reducing clinical inertia and improve patient outcomes.

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial.

PURPOSE: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS: Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

Socio-Demographic, Clinical, and Mortality Differences between HIV-Infected and HIV/HTLV-1 Co-Infected Patients in Peru.

BACKGROUND AND AIMS: In Peru, the estimated prevalence of human immunodeficiency virus (HIV) and human T-lymphotropic virus-1 (HTLV-1) co-infection has been reported to be as high as 18%. Despite the endemicity of HTLV-1 in Peru, few studies have assessed the impact of HIV/HTLV-1 co-infection. Our study compared socio-demographic and clinical characteristics, and mortality rates between HIV-infected and HIV/HTLV-1 co-infected patients. METHODS: We reviewed the medical records of patients aged 18 years and older belonging to the HIV and HTLV-1 cohorts in Lima during a 30-year period: 1989-2019. Each HIV/HTLV-1 co-infected patient was randomly matched with two HIV-infected patients with similar characteristics (same sex, age ± 5 years, and same year of HIV diagnosis). Allegedly co-infected patients without a confirmatory diagnosis of HIV and HTLV-1 were excluded. Most of the patients in the HIV-infected group did not have a negative test result for HTLV-1 infection, so we used two probabilistic sensitivity analysis models to correct for potential HTLV-1 exposure misclassification bias in the group of HIV-infected patients. RESULTS: Of 162 patients enrolled, 54 were HIV/HTLV-1 co-infected and 108 were HIV-infected. The median age was 42 years (IQR = 34-51 years) and the majority were male (61.1%), single (44.4%), heterosexual (71%), born in Lima (58%), educated at the secondary school level (55.6%), and receiving antiretroviral treatment (91.4%). HIV/HTLV-1 co-infection was associated with an increased risk of death (HR: 11.8; 95% CI: 1.55-89.00; p = 0.017) while antiretroviral treatment was associated with a decreased risk of death (HR: 0.03; 95% CI: 0.003-0.25; p = 0.001). The overall mortality rate was 13.6 per 100 persons and the survival time for co-infected patients (median = 14.19 years) was significantly shorter than that of HIV-infected patients (median = 23.83 years) (p < 0.001). CONCLUSIONS: HIV/HTLV-1 co-infected patients had a significantly shorter survival time compared to HIV-infected patients, suggesting that the immune alterations caused by HTLV-1 in CD4 cell count may have contributed to late initiation of antiretroviral treatment and prophylaxis against opportunistic infections over the decades, and thus reducing their benefits in these patients.

Non-timely referral of women aged 40 to 69 to preventive medicine for breast cancer detection and its association with the BI-RADS classification.

Purpose: In the first level of health care, the timely detection of breast cancer is essential to prevent the progression of the disease, obtain optimal treatment and improve the prognosis and survival of patients. The objective of this study was to analyze the opportunity in referral to the Preventive Medicine Modules offered to women aged 40 to 69 years of the Family Medicine Unit 1, of the Mexican Social Security Institute, Decentralized Administrative Operation Body, Aguascalientes, Mexico, by their family physician, and its impact in the findings of mammographic screening according to the BI-RADS classification. Methods This was a cross-sectional comparative study of 412 mammograms performed on women aged 40 to 69, who were treated in the preventive medicine modules from January 2019 to June 2021. Data collection was carried out by simple random sampling using a checklist. Multiple logistic regression models adjusted for age were applied. Results: A total of 90.29% of the patients who underwent screening mammography were not referred in a timely manner to the preventive medicine modules by the family physician, this delay in diagnosis and treatment increased by 3.01 times the probability of having a classification BI-RADS suspected of malignancy compared to those women whose referral was timely (OR adj = 3.01, 95% CI 1.04-8.72, p = 0.041). Conclusion: The untimely referral of women aged 40-69 to preventive medicine modules for the detection of breast cancer increases the risk of finding a malignant lesión.

Long-term impact on cardiopulmonary function and quality of life among patients recovered from SARS-CoV-2 infection in a 6-month follow-up period in Lima, Peru: FUNCTION cohort study protocol.

INTRODUCTION: The sequelae of COVID-19 have been described as a multisystemic condition, with a great impact on the cardiovascular and pulmonary systems with abnormalities in pulmonary function tests, such as lower diffusing capacity of the lung for carbon monoxide (DLco) levels and pathological patterns in spirometry; persistence of radiological lesions; cardiac involvement such as myocarditis and pericarditis; and an increase in mental disorders such as anxiety and depression. Several factors, such as infection severity during the acute phase as well as vaccination status, have shown some variable effects on these post-COVID-19 conditions, mainly at a clinical level such as symptoms persistence. Longitudinal assessments and reversibility of changes across the spectrum of disease severity are required to understand the long-term impact of COVID-19. METHODS AND ANALYSIS: A prospective cohort study aims to assess the impact of SARS-CoV-2 infection on cardiopulmonary function and quality of life after the acute phase of the disease over a 6-month follow-up period. Sample size was calculated to recruit 200 participants with confirmatory COVID-19 tests who will be subsequently classified according to infection severity. Four follow-up visits at baseline, month 1, month 3 and month 6 after discharge from the acute phase of the infection will be scheduled as well as procedures such as spirometry, DLco test, 6-minute walk test, chest CT scan, echocardiogram, ECG, N-terminal pro-B-type natriuretic peptide measurement and RAND-36 scale. Primary outcomes are defined as abnormal pulmonary function test considered as DLco <80%, abnormal cardiovascular function considered as left ventricular ejection fraction <50% and abnormal quality of life considered as a <40 score for each sphere in the RAND-36-Item Short Form Health Survey. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Ethics Committee of the Universidad Peruana Cayetano Heredia (SIDISI 203725) and the Ethics Committee of the Hospital Cayetano Heredia (042-2021). Protocol details were uploaded in ClinicalTrials.gov. Findings will be disseminated through peer-reviewed journals, scientific conferences and open-access social media platforms. TRIAL REGISTRATION NUMBER: NCT05386485.

Burden of COVID-19 in Córdoba, A Department of Colombia: Results of Disability-Adjusted Life-Years: Carga de COVID-19 en Córdoba, un Departamento de Colombia: Resultados de los Años de Vida Ajustados por Discapacidad.

OBJECTIVES: This study aimed to estimate the burden of acute COVID-19 in Córdoba, one of the most affected departments (states) in Colombia, through the estimation of disability-adjusted life-years (DALYs). METHODS: DALYs were estimated based on the number of cases of severe acute respiratory syndrome coronavirus 2 infection cases reported by official Colombian sources. A transition probability matrix among severity states was calculated using data obtained from a retrospective cohort that included 1736 COVID-19 confirmed subjects living in Córdoba. RESULTS: Córdoba had 120.23 deaths per 100 000 habitants during the study period (March 2020 to April 2021). Estimated total DALYs were 49 243 (2692 DALYs per 100 000 inhabitants), mostly attributed to fatal cases (99.7%). On average, 25 years of life were lost because of death by this infection. A relevant proportion of years of life lost because of COVID-19 (46.6%) was attributable to people < 60 years old and was greater in men. People ≥ 60 years old showed greater risk of progression to critical state than people between the age of 35 and 60 years (hazard ratio 2.5; 95% confidence interval 2.5-12.5) and younger than 35 years (9.1; 95% confidence interval 4.0-20.6). CONCLUSION: In Córdoba, premature mortality because of COVID-19 was substantially represented by people < 60 years old and was greater in males. Our data may be representative of Latin American populations with great infection spread during the first year of the pandemic and contribute to novel methodological aspects and parameter estimations that may be useful to measure COVID-19 burden in other countries of the region.

First case report of gastric outlet obstruction due to aortofemoral bypass Dacron graft erosion of the duodenum treated with neo aortoiliac system procedure.

INTRODUCTION: Gastric outlet obstruction is an uncommon complication of surgical treatment of aortoiliac occlusive disease with aortofemoral bypass. The most frequent presenting feature of duodenal erosion due to aortic synthetic graft is upper gastrointestinal bleeding, which can range from a minor "herald" bleed to exsanguinating hemorrhage. CASE PRESENTATION: A 64-year-old male patient with an aortofemoral Dacron bypass due to aortoiliac occlusive disease TASC II D with a chronic graft infection required emergency resection of the right limb of the Dacron graft two years ago. The patient developed abdominal pain, postprandial vomiting and progressive weight loss with an upper gastrointestinal endoscopy that showed Dacron graft material eroding into the fourth portion of the duodenum generating a gastric outlet obstruction without aortoenteric fistula and ulceration in the duodenal mucosa. CLINICAL DISCUSSION: The treatment goals of aortoenteric fistula are to control hemorrhage, treat infection, maintain adequate distal perfusion, graft explantation and aortic reconstructions like in this case. Traditional treatment of aortoenteric fistula is graft excision and establishing an anatomic autologous or an extra-anatomic synthetic bypass. Neo aortoiliac system procedure has shown to be the most effective and safest emerging technique today. CONCLUSION: Aortoenteric fistula is a life-threatening condition associated with high morbidity and mortality and it can also pose a diagnostic dilemma. There are many presentations of aortoenteric fistula including gastric outlet obstruction syndrome. The neo aortoiliac system procedure is the ideal curative surgical approach in stable patients.

Clinical situation of Venezuelan migrants living with HIV in a hospital in Lima, Peru.

Due to a huge crisis extensive to health services many Venezuelan people living with HIV (PLWH) had migrated abroad, including Peru where favorable laws were in place until June 2019. We describe the health status and epidemiological trends of PLWH from Venezuela at an HIV program in Lima. We analyzed baseline and follow-up data of all Venezuelan PLWH enrolled in our HIV program from January 2017 to December 2019. A cross-sectional study in a subsample served to describe ARV adherence and context of migration. Between 2017-2019 our HIV Program registered 398 Venezuelan PLWH, representing 20% of the 2018 annual enrollments; numbers decreased since mid-2019. The median age was 30 years (IQR 26;37) and 90.5% were men. Between 2017 and 2019, the proportion with diagnosis in Peru increased from 14.3% to 60.9%; of AIDS stage at entry, from 8.8% to 27.2%. By December 2019, 182/250 (72.8%) were still in care, and 43 (10.8%) had not started ART. Viral suppression evaluated in 195, was achieved in 71.8%. From 2017 to 2019, migrant PLWH arrived in worsened clinical conditions, with increasing diagnosis in Peru; the flow of migrant PLWH entering care diminished with less favorable laws. Viral suppression rates were suboptimal.