Peruvian Patients Research Articles

Factors associated with preferences for ambience and human resources among adult patients during dental office care: A logistic regression study

Aim: Focussing on adult patients, this study evaluated the factors associated with preferences for ambience and human resources when receiving care at dental offices in Peru. Materials and Methods: We conducted an observational, retrospective, and analytical analysis of data previously obtained through an anonymous survey among Peruvian patients (n = 618) who visited an American Dental Center in Lima, Peru between 2018 and 2020. The statistical analyses were conducted using the frequencies and percentages of each preference, whereas a χ2 test and logistic regression were used to identify the factors associated with patient preferences (significance determined at P < 0.05). Results: Preferences were expressed at a rate of 80.9%, with the highest frequencies found for appointment time (91.7%), the delegation of certain functions to assistant personnel (89%), and environmental privacy (89%). Further, the logistic regression model showed that only age influenced the day of the week on which respondents preferred to receive care (odds ratio = 0.97, confidence interval: 0.95–0.98, P < 0.001). Conclusion: Respondents reported strong preferences for several elements related to ambience and human resources while receiving care at dental offices, including the professional ratings/genders of service providers and available amenities.

Neuropsychiatric Symptoms in Patients With Alzheimer's Disease During SARS-COV-2 Pandemic in Peru.

To evaluate neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and their association with cognition and functionality during lockdown of the COVID-19's first wave. We included 91 patients and caregivers of people with AD from a memory clinic. The RUDAS, M@T, and CDR were administered to patients and NPI/ADCS-ADL to caregivers. Baseline and lockdown measurements scales were analyzed to compare the frequencies at baseline versus lockdown and conditional Odds Ratio (ORc) was calculated for the neuropsychiatric symptoms. During the pandemic, significant increase in the number of cases was observed in depression (23%), agitation (36.8%), aberrant motor activity (12%), sleep disorders (26.3%), and appetite change (12.1%). In worsening of pre-existing symptoms, the most frequent were delusions (75%), followed by sleep disorders (71.7%). Lockdown induces a rapid increase of neuropsychiatric symptoms affecting cognitive symptoms and functionality of Peruvian patients with AD.

Clinicopathologic Comparison of Plasmablastic Lymphoma Patients According HIV-Status: Peruvian Experience

Background:Plasmablastic lymphoma (PBL) is an aggressive lymphoma associated mainly to HIV infection, although cases in immunocompetent patients are described as well. Objective:To describe the clinicopathologic features and determine the overall survival of lymphoma patients according human immunodeficiency virus (HIV) status in Peruvian patients. Methods:We reviewed the pathology databases of 2 cancer centers and a general hospital from Peru. Forty cases were documented between 2005 and 2020. Categorical variables were compared using Fisher's exact test. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Statistical analysis was based on SPSS Program version 23. All cases were reviewed by two pathologists. Results:32 patients (80%) were HIV-positive. The median age for the whole cohort was 40 years (range, 22-86). The median age for HIV-positive and HIV-negative PBL patients were 37 years (range 22-67 years) and 57 years (range 27-86 years), respectively. The proportion of patients ≥60 years was lower in HIV-positive than in HIV-negative patients (8% and 37%, respectively; p= 0.046). 80% of patients in the whole cohort were female, and 84% and 62% in the HIV-positive and HIV-negative group, respectively. Extra-oral primary sites were the most frequent primary sites in both groups (66% and 88%, respectively). There were no statistically significant differences in Ann Arbor stage, Ki-67 expression, LDH levels, IPI scores, albumin levels, and neutrophil/lymphocyte ratio between HIV-positive and HIV-negative patients. All cases showed large lymphoid cells, of plasmablastic morphology with expression of at least one plasma cell marker (CD138, CD38, MUM1), CD45 positivity, variable expression of EMA, CD79 and CD30 and absence of expression of CD20, CD3, CD68 and LMP1; the proliferative index Ki67 varied between 60 and 90%. A small proportion of patients (18%) did not receive chemotherapy because of poor performance status or a personal decision. DA-EPOCH regimen was used in 52% and 25% of HIV+ and HIV- patients, respectively and CHOP/CHOEP regimen in 48 % and 75%, respectively. The overall response rate was 68% and 57% in HIV+ and HIV- patients with complete response (CR) in 32% and 14%, respectively. In the HIV-positive group, 66% of patients were antiretroviral therapy (ART)-naïve. The median progression-free survival (PFS) was 38 months and 7 months for HIV+ and HIV- patients, and the 1-year PFS was 74% and 0%, respectively. The median overall survival (OS) was 43 months (range 0.2-86.5) in HIV-positive patients and 10 months (range 0.5-19.0 months) in HIV-negative patients and the 1-year OS were 59% y 38%, respectively (p=0.27). Conclusions: PBL is a rare lymphoma, specially, if not related to HIV infection. In this study, 60 years or older was the only variable that showed significant difference. In our cohort, HIV-positive patients had better prognosis than HIV-negative PBL patients. Disclosures No relevant conflicts of interest to declare.

Frequency of IKZF1 Deletions in a Peruvian Population with B-Cell Acute Lymphoblastic Leukemia

Frequency of IKZF1 Deletions in a Peruvian Population with B-cell Acute Lymphoblastic Leukemia Background: B-cell Acute Lymphoblastic Leukemia (B-ALL) is an aggressive disease with worse outcomes in older patients, and latino ethnicity. Additionally, Latino populations are at higher risk of developing B-ALL.IKZF1is an essential lymphoid transcription factor with deletions (ΔIKZF1)implicated in treatment failure and relapses. We aimed to evaluate the frequency ofIKZF1deletions in a cohort of Peruvian patients with newly diagnosed B-ALL. Methods: We collected diagnostic bone marrow samples from 41 consecutive patients with B-ALL diagnosed between 2015-2019 at Instituto Nacional de Enfermedades Neoplasicas (INEN; Lima, Peru). Bone marrow samples were cryopreserved prior to induction treatment. DNA was extracted using High Pure PCR Template Preparation Kit (Roche) at INEN. Samples with adequate DNA were screened forΔIKZF1by multiplex endpoint PCR covering four main deletions - dominant negative Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 IKZF1 deletions at UCL Cancer Insitute (London, UK) using the primers described by Caye et. al. We analyzed outcomes byIKZF1status. Results: Forty-one cases were enrolled during the study period. Clinical characteristics are presented in Table 1. Median age was 20 years[1-63]. Fifteen∆IKZF1cases (37%) were detected (67%BCR-ABL1 negand 33%BCR-ABL1pos).Cases withΔIKZF1were older than those with wild-typeIKZF1(median age 31 vs 13 years, p=0.002). Median presenting white blood count (WBC) was 48 x109/L [R:2-218], with a higher WBC inΔIKZF1compared to wild-type (87 vs 24 x109/L, p=0.001). The most frequent deletion was ∆4-7 (sevenBCR-ABL1 negand threeBCR-ABL1 pos) additional deletions are described in table 2. All patients received intensive 'pediatric-based' treatment, 21 with BFM-2009 and 19 with the CALGB 10403 protocol. CR rates after induction were 67% and 92% for∆IKZF1and wild-type cases, respectively. Eleven (73%) of patients with∆IKZF1subjects (73%) were MRD positive by flow cytometry after induction compared to 11 (44%) among wild-type. At a median follow-up of 2 years EFS was 38% in the∆IKZF1group and 58% in the wild type group, correspond OS was 38% and 58%, respectively. Conclusion: A high frequency of IKZF1 deletions was found in a Peruvian population with B-ALL and was associated with older age and higher presenting white blood counts. Prospective studies with larger Latino population are warranted to confirm this finding. Disclosures No relevant conflicts of interest to declare.

Impact of Mutated Genes By Next Generation Sequencing on Overall Survival in a Cohort of Peruvian Patients with AML/MDS

Background Acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) represents a broad and complex group of diseases characterized by involvement of the myeloid lineage on hematopoiesis with remarkable variability on clinical presentation, genes mutations, karyotype and molecular abnormalities. Precise characterization on AML/MDS biology is important and the identification of the pathogenic mutated genes is relevant for risk stratification and therapy strategy, mainly for those patients in which targeted therapies is a must. Among pathogenic mutated genes in AML/MDS; TP53 is associated with lower response and high mortality rates. The cumulated number of mutated genes is associated with bad clinical outcomes as well. Aims To explore the frequency and impact of mutated genes on clinical outcomes in a cohort of Peruvian patients diagnosed with AML/MDS studied at diagnosis. Methods In this report we showed 31 consecutive AML/MDS cases treated at three medical centers in Lima (Clínica Delgado, Clínica Anglo Americana and INEN) from January 2016 until July 2020. Information available at diagnosis was: clinical, karyotype, molecular PCR panel, Illumina TruSight Myeloid Sequencing (TSM) panel which include 53 genes involved on oncogenesis, therapy regimen, response to treatment and overall survival (OS). Results A total of 31 cases were studied. F/M ratio 0.55 (11/20), median age 62 years (range 16-87), number of cases by disease were AML=23 and MDS=8. Among the 26 available karyotypes, the abnormal vs diploid karyotype ratio was 0.18 (4/22). Ad hoc PCR panel were positive in just 5 cases among 30 studies available, for FLT3-ITD(n=2), CBFB-MYH11(n=1), NPM1(n=1) and AML-ETO (n=1). In the TSM analysis, median number of pathogenic mutated genes was 3 (range 0-15). Most common (≥18%) pathogenic mutated genes wereBCOR (n=11; 35,5%), CUX1 (n=7; 22,6%) , DNMT3 (n=7; 22,6%), RAD21(n=6; 19,4%), and STAG2 (n=6; 19,4%)with different rates compare with other series (figure 1). Response rate were as follow: 58,1% complete (18/31), 9,7% partial (3/31), 19,3% non-response (6/31) and 12,9% non-evaluable (4/31). The estimated median OS was 36,67 months for the entire cohort, the 1 and 3-years OS rates were 69,9% and 62,2% respectively. For AML and MDS cases median OS was not reached, 1-year OS rates were 68,6% and 72,9% respectively, 3-years OS rates were 54,9% and 72,9% respectively (Log Rank 0,071 p=0,79). MutatedTP53was detected in 5 cases (MDS=3 and AML=2) with no therapy response in 4 and all of them had already dead; median OS for mutatedTP53cases was 3,53±0,43 months; 1-year OS rates for non-mutated vs mutatedTP53cases were 80,2% and 20% respectively, 3-year OS rates for cases with non-mutated vs mutatedTP53were 70,2% and 20% respectively (Log Rank 14,6 p&amp;lt;0,0001) (figure 2). The median OS for mutatedBCORwas not reached; 1-year OS rates for non-mutated vs mutatedBCORwere 77,4% and 52,6% respectively; 3-year OS rates for non-mutated vs mutatedBCORwere 64,5% and 52,6% respectively (Log Rank 0,09 p=0,76). The medians OS were not reached for &amp;lt;3 and ≥3 pathogenic mutated genes cases, 1-year OS rates were 92,3% and 53,5% respectively and 3-years OS rates were 73,8% and 53,5% respectively (Log Rank 1,98 p=0,159). The median OS for ≥4 pathogenic mutated genes cases was 11,93±2,5 months, 1-year OS for &amp;lt;4 and ≥4 were 88,9% and 42,4% respectively and 3-years OS for &amp;lt;4 and ≥4 were 71,1% and 42,4% respectively (Log Rank 3,293 p=0,07). Ad-hoc composite analysis for cases of &amp;lt;4 vs ≥4±mutated-TP53showed medians OS not reached and 9,87±2,9 months respectively; 1-year OS rates were 100% and 40,8% and 3-years OS were 75,0% and 40,8% respectively (Log Rank 9,10 p=0,003)(figure 3). Conclusion NGS for LMA/MDS is an important tool for diagnosis, assessment and risk stratification in our serie of cases. Only 5 over 53 genes were detected in ≥ 18% of casesBCOR, CUX1, DNMT3, RAD, and STAG. TP53 was related with a high therapy failure response and short OS. Number of pathogenic mutated genes ≥3 or ≥4 by TSM showed tendencies for shorter OS. A composite analysis for patients with 4 mutated genes with or without mutated-TP53showed significant shorter OS. Further studies with mature data and more cases are warrant to propose genetics characterization and risk stratification by NGS in Peruvian AML/MDS cases. Disclosures No relevant conflicts of interest to declare.

Evaluation of germline RET proto-oncogene variants in Peruvian patients with medullary thyroid carcinoma

Evaluation of germline RET proto-oncogene variants in Peruvian patients with medullary thyroid carcinoma

Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019

Introduction: In patients with HIV in antiretroviral treatment (ART) and virological failure to the first-line regimen, establishing a therapeutic regimen after having identified the M184V mutation, which confers ART resistance, represents a dilemma. Objective: To compare the virological response of the therapeutic regimens prescribed to patients with HIV who presented the M184V mutation in two national hospitals in Lima, Peru, during the years 2008 to 2019, and to determine the risk factors associated with poor virological response. Methods: A retrospective cohort study was developed based on the information of the HIV program participants with the M184V mutation. Results: A total of 175 participants were eligible for the study. The male sex predominated (75.4%), the current median age was 41 years [interquartile range (IQR) 35.84-47.47], and the time on ART was 89 months (IQR 57.7-124.53). The median initial viral load (VL) was 4.5 log10 copies/mL (IQR 3.97-5.09) and the time between genotyping and the change of therapy was 2 months (IQR 0-3.56). The most used antiretroviral regimen was protease inhibitor plus two nucleoside reverse transcriptase inhibitors (55.4%). With the protease inhibitor plus integrase inhibitor (PI + INI) ART, 69% less risk of poor virological response was obtained [p = .019 (confidence interval 95% 0.117-0.825)]. Conclusions: In patients with HIV and the M184V mutation, the PI + INI ART has shown a greater decrease in control VL and, thus, a good virological response. The risk factors associated with a poor virological response were the delay between genotyping and change of therapy, high levels of initial VL, and poor adherence among the participants.

Antimicrobial Resistance of Helicobacter pylori in Gastric Biopsy Samples from Lima/Peru.

Background: Helicobacter pylori prevalence and gastric cancer rates are remarkably high in Peru. Effective antimicrobial regimens are essential for successful H. pylori eradication. We aimed at assessing antimicrobial resistance rates to first- and second-line therapeutic agents in H. pylori strains detected in gastric biopsy samples. Materials and Methods: Gastric biopsy samples (antrum and corpus) were collected from therapy-naive patients (n = 154). H. pylori presence in the samples was confirmed by histopathology. Genotypic resistance to clarithromycin and quinolones was determined by real-time PCR. Results: Histology results were 100% concordant with PCR results (97/154; 63% H. pylori-positive in both). In 6% (6/97) of the patients, we found discordant results of H. pylori infection in antrum and corpus samples from the same patient. Resistance rates to clarithromycin and quinolone were 34% (33/97) and 68% (56/82), respectively. Antimicrobial resistance to both antimicrobials was 30% (25/82). Conclusion: Antimicrobial resistance rates of H. pylori to clarithromycin and quinolones are very high in Lima, Peru. Many first- and second-line, empiric eradication regimens may not be recommended for Peruvian patients.

AML-164: Next-Generation Sequencing (NGS) Profile by Illumina Trusight Myeloid Sequencing Panel (TSM) in a Cohort of Peruvian Patients with AML/MDS

Precise identification of AML/MDS biology and the identification of pathogenic mutated genes is relevant for risk stratification and therapy strategy, mainly for cases where targeted therapies is a must. Here, we describe the main pathogenic mutated genes and clinical outcomes in a cohort of Peruvian patients diagnosed with AML/MDS studied at diagnosis with the Illumina TruSight Myeloid Sequencing Panel (TSM), which includes 54 genes. In this report, we showed 20 consecutive AML/MDS cases treated in 2 different medical centers in Lima from January 2016 until March 2020. F/M ratio 1/4, median age 64 years (range, 16-87), number of cases were AML=12 and MDS=8. Abnormal vs diploid karyotype ratio was 1/4 (only four cases with abnormal karyotype). Median number of pathogenic mutated genes was 3 (range, 0-15). Most common (≥20%) pathogenic mutated genes expressed were BCOR, CUX1, ETV6/DEL, KMT2A, NOTCH1, NRAS, RAD21, STAG2, and TP53. Response rates were as follows: 45% complete (9/20), 15% partial (3/20), 25% non-response (5/20), and 15% non-evaluable (3/20). At a median follow-up of 12.0 months, the median overall survival (OS) was 32.88 ± 4.75 months for the entire cohort; for the AML and MDS cases, mean OS were 26.7 ± 4.4 and 32.8 ± 7.2 months, respectively (Log Rank 0.001; p=0.969). Mutated TP53 was detected in 5 AML/MDS cases with no therapy response in 4 that had already died with a median OS of 3.1 months (range, 0.8-36.6). We analyzed if ≥4 or ≥3 mutated genes impact on OS. We found a trend (non-significant) of longer OS for cases with < 4 vs ≥4 pathogenic mutated genes (37.7 ± 5.2 vs 26.0 ± 6.7; Log Rank 1.64; p=0.2) and longer OS for cases with <3 vs ≥3 pathogenic mutated genes (37.7 ± 5.2 vs 29.1 ± 6.0; Log Rank 0.834; p=0.36). NGS for AML/MDS is an important tool at diagnostic, assessment, and risk stratification in our series of cases. Only 9 over 53 genes were detected in ≥20% of cases. TP53 was related with a high therapy failure response and short OS for AML/MDS cases. Number of pathogenic mutated genes ≥4 or ≥3 by TSM showed a tendency for lower OS. Precise identification of AML/MDS biology and the identification of pathogenic mutated genes is relevant for risk stratification and therapy strategy, mainly for cases where targeted therapies is a must. Here, we describe the main pathogenic mutated genes and clinical outcomes in a cohort of Peruvian patients diagnosed with AML/MDS studied at diagnosis with the Illumina TruSight Myeloid Sequencing Panel (TSM), which includes 54 genes. In this report, we showed 20 consecutive AML/MDS cases treated in 2 different medical centers in Lima from January 2016 until March 2020. F/M ratio 1/4, median age 64 years (range, 16-87), number of cases were AML=12 and MDS=8. Abnormal vs diploid karyotype ratio was 1/4 (only four cases with abnormal karyotype). Median number of pathogenic mutated genes was 3 (range, 0-15). Most common (≥20%) pathogenic mutated genes expressed were BCOR, CUX1, ETV6/DEL, KMT2A, NOTCH1, NRAS, RAD21, STAG2, and TP53. Response rates were as follows: 45% complete (9/20), 15% partial (3/20), 25% non-response (5/20), and 15% non-evaluable (3/20). At a median follow-up of 12.0 months, the median overall survival (OS) was 32.88 ± 4.75 months for the entire cohort; for the AML and MDS cases, mean OS were 26.7 ± 4.4 and 32.8 ± 7.2 months, respectively (Log Rank 0.001; p=0.969). Mutated TP53 was detected in 5 AML/MDS cases with no therapy response in 4 that had already died with a median OS of 3.1 months (range, 0.8-36.6). We analyzed if ≥4 or ≥3 mutated genes impact on OS. We found a trend (non-significant) of longer OS for cases with < 4 vs ≥4 pathogenic mutated genes (37.7 ± 5.2 vs 26.0 ± 6.7; Log Rank 1.64; p=0.2) and longer OS for cases with <3 vs ≥3 pathogenic mutated genes (37.7 ± 5.2 vs 29.1 ± 6.0; Log Rank 0.834; p=0.36). NGS for AML/MDS is an important tool at diagnostic, assessment, and risk stratification in our series of cases. Only 9 over 53 genes were detected in ≥20% of cases. TP53 was related with a high therapy failure response and short OS for AML/MDS cases. Number of pathogenic mutated genes ≥4 or ≥3 by TSM showed a tendency for lower OS.

Triple-negative breast cancer in Peru: 2000 patients and 15 years of experience

BackgroundEpidemiological studies commonly identify the clinical characteristics and survival outcomes of patients with breast cancer at five years. Our study aims to describe the sociodemographic, clinicopathological characteristics and determine the long-term event-free survival (EFS) and overall survival (OS) of a Peruvian population with triple-negative breast cancer.MethodsWe reviewed the medical records of new cases treated at a single institution in the period 2000–2014. The survival analysis included patients with stages I-IV. Survival estimates at 10 years were calculated with the Kaplan-Meier method and compared with the Log-rank test. We further used multivariate Cox regression analysis to calculate prognostic factors of recurrence and mortality.ResultsAmong the 2007 patients included, the median age at diagnosis was 49 years (19–95 years). Most patients presented histologic grade III (68.7%), tumor stage II (34.2%), and III (51.0%) at diagnosis. Local and distant relapse was present in 31.9 and 51.4% of the patients, respectively. The most frequent sites of metastasis were the lungs (14.5%), followed by bone (9.7%), brain (9.6%), and liver (7.9%). The median follow-up was 153 months. At 3, 5, and 10 years, the EFS of the population was 55%, 49%, and 41%, respectively, while the OS was 64%, 56%, and 47%, respectively. Moreover, an N3 lymph node status was the most important prognostic factor for both disease relapse (HR: 2.54, 95% CI: 2.05–3.15) and mortality (HR: 2.51, 95% CI: 2.01–3.14) at ten years. An older age and higher T staging were associated with a worse OS, while patients who received radiotherapy and adjuvant chemotherapy had better survival rates.ConclusionThe sociodemographic features of Peruvian patients with TNBC are similar to those of other populations. However, our population was diagnosed at more advanced clinical stages, and thus, EFS and OS were lower than international reports while prognostic factors were similar to previous studies.

Linfoma difuso de células B grandes, NOS. Estudio clínico-patológico en una cohorte de pacientes peruanos

Objetivo. Evaluar las características clinicopatológicas del linfoma de células B grandes difuso, sin otra especificación (LCBGD, NOS), en una cohorte de pacientes peruanos. Métodos. Se estudiaron 72 casos con diagnóstico de LCBGD, NOS, en el INEN. Se evaluaron características clinicopatológicas, sobrevida global (SG) y otros parámetros clínicos de acuerdo con la célula de origen, la infección por virus Epstein-Barr (EBER) y la expresión inmunohistoquímica (IHQ) de MYC y BCL2. Resultados. Hubo 54 % de mujeres y 46 % de hombres, con edad promedio de 65 años. El 76 % fueron ganglionares, la mayoría de ubicación cervical y el 24 % extraganglionares, siendo el estómago el más afectado. Los estadios más frecuentes fueron II (35 %) y III (29 %), la mayoría con IPI medio-alto y alto. Histológicamente, casi todos los casos tuvieron morfología centroblástica e inmunoblástica. Hubo proporción similar de casos con subtipos centro germinal (GCB) y no centro germinal (no-GCB). Los GCB y EBER+ tuvieron mejor SG que los no-GCB y los EBER-, respectivamente. Asimismo, los casos con IHQ negativa para MYC y BCL2 tuvieron mejor SG y mayor porcentaje en estadios tempranos. Estos hallazgos no tuvieron significación estadística. Conclusión. Nuestros casos presentan características similares a lo descrito en la literatura, aunque con mayor porcentaje asociados al EBV y de casos no-GCB. El poco número de casos evaluados con IHQ para determinar subtipos y biomarcadores puede haber limitado el análisis estadístico en esta cohorte de casos.

Encefalitis aguda en pacientes COVID-19: primer reporte de casos en Perú.

En el contexto de la pandemia de COVID-19, se han descrito formas clínicas atípicas, en las que predominan síntomas extrar-respiratorios; entre ellos han sido reportados casos de manifestaciones neurológicas concurrentes. En base a la identificación de coronavirus en el sistema nervioso central en el brote SARS-CoV del 2002, se ha planteado un potencial neurotropismo del SARS-CoV-2. En la literatura mundial se han descrito escasos pacientes con encefalitis aguda asociada a SARS-CoV-2. En este reporte les presentamos dos casos de pacientes peruanos con encefalitis aguda concurrente a COVID-19, revisamos la literatura y discutimos los posibles mecanismos de neurotropismo y neuro-invasión.

Accidente cerebrovascular isquémico asociado a COVID-19: primer reporte de casos en Perú

La enfermedad causada por el coronavirus 2 asociado al síndrome respiratorio agudo grave (SARS-CoV-2) se conoce como Coronavirus Disease-2019 (COVID-19). Su afectación es principalmente respiratoria, pero se han descrito diversas manifestaciones neurológicas. El neurotropismo y potencial rol neuropatógeno del SARS-CoV-2, se plantea en base a modelos en animales y casos de afección neurológica descritos en otros coronavirus, así como por reportes recientes de síndromes neurológicos específicos relacionados a COVID-19, incluido el accidente cerebrovascular (ACV).La sociedad española de neurología (SEN) describió a losACV isquémicos como la segunda manifestación neurológica más frecuente en pacientes con COVID-19. Se reconoce que el estado de hiperinflamación e hipercoagulabilidad sanguínea desencadenada por el COVID-19 incrementaría el riesgo de eventos protrombóticos.Reportamos 3 casos de pacientes peruanos que presentaron ACV isquémico asociado a COVID-19: describimos el cuadro clínico, exámenes paraclínicos y revisamos la literatura mundial.

Abstract PR05: A genetic variant at 6q25 associated with estrogen receptor-negative breast cancer subtypes in Peruvian breast cancer patients

Abstract Background: We have previously identified a genetic variant, rs140068132, which has a strong protective effect on breast cancer risk. This variant is located near the estrogen receptor 1 gene (ESR1) on chromosome 6q25, a locus which has been repeatedly implicated in breast cancer risk. Women who carry two copies of the protective variant (GG) have 60-70% reduction in risk of developing breast cancer compared to women with none. The G variant has relatively high frequency in Latin American women (up to 23% in the 1000 Genomes Project Peruvians); it is only common in people of Indigenous American ancestry and almost absent in all other populations. We investigated whether the rs140068132-A/G polymorphism is associated with a specific breast cancer subtype among Peruvian women with breast cancer. Methods: Blood samples and clinical data were collected from 441 women with breast cancer at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru. Genotypic profiles were generated using the Affymetrix Precision Medicine Research Array. Four major breast cancer subtypes were identified based on immunohistochemical markers (luminal A, luminal B, triple-negative, and human epidermal growth factor receptor 2 (HER2) overexpressing). Quality control of the genotyped data was performed in PLINK. Genetic ancestry was determined for each individual using ADMIXTURE. ANOVAs were performed on the proportion of genetic ancestry and disease subtype. PLINK was used to perform a binary logistic regression on the rs140068132 variant and ER status (ER-negative versus-ER positive), with age and genetic ancestry as covariates. Results: The breast cancer patients analyzed have the following average ancestry proportions: 77.3% Indigenous American, 17.4% European, 3.8% African and 1.5% East Asian. The frequency of the G allele in the Peruvian breast cancer patients is 14% (compared to 23% in healthy individuals from the 1000 Genomes Project). We found that the G allele of rs140068132 was associated with ER-negative status among cases (OR = 0.6443, P = 0.086) for both HER2 overexpressing and triple-negative. We also examined the proportions of ancestry in relation to subtypes of disease. The proportion of Indigenous American ancestry was associated with the HER2 overexpressing subtype (P = 0.06), with an average Indigenous American ancestry among these patients of 83.1% compared to 77.3% among all patients. The proportion of African ancestry was higher in women with the triple-negative subtype, with an average African ancestry of 4.8% among patients with the triple-negative subtype compared to a 3.8% average among all patients, but this trend was not statistically significant (P = 0.21). Conclusions: The lower frequency of the variant in Peruvian breast cancer cases is consistent with a protective effect in this population. We have confirmed that the protective effect of the rs140068132 variant is stronger for ER-negative subtypes. Additional analyses are under way in a larger sample of Peruvian breast cancer patients. This abstract is also being presented as Poster C051. Citation Format: K.M. Marker, T. Vidaurre, L.I. Tamayo, J.N. Vásquez, R. Meza Florez, S. Casavilca, M. Calderon, J.E. Abugattas, H.L. Gómez, H.A. Fuentes, C.L. Monge Pimentel, S. Song, D. Cherry, S. Huntsman, D. Hu, E. Ziv, L. Fejerman. A genetic variant at 6q25 associated with estrogen receptor-negative breast cancer subtypes in Peruvian breast cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr PR05.

2261-PUB: Type 2 Diabetes Mellitus Debut in Peru: The DDPeru Study

Objective: To describe the clinical and metabolic characteristics of debut type 2 diabetes mellitus (T2D) Peruvian patients and to evaluate if there are any differences between the different geographical regions. To describe the initial pharmacological treatment of these patients. Methods: Case series study that took place in different regions of Peru, from July 2016 to November 2017. The inclusion criteria were: patient older than 20 years old, ambulatory setting, first time diagnosis of T2D through: fasting glycemia ≥ 126 mg/dl or random glycemia ≥ 200 mg/dl with symptoms, or oral glucose tolerance test (OGTT) ≥ 200 mg/dl on the 2 hour sample. Also, a description of their initial treatment was registered. Results: Five hundred eighty-one patients were identified, from which two hundred eighty-four (48.9%) were women. The average age of diagnosis was 53.2 ± 12.8 years old. Average weight was 77.3 +/- 16.6 kg, from which 228 patients (39.2%) were over weighted and 178 (30.6%) had type I obesity. Average glycemia was 249.4 mg/dl and average HbA1c was 8.9 %. In those who had abdominal ultrasonography (US), 56.7% had fatty liver. Most of the patients that were from Lima or the northern region of the country, had higher levels of glycemia and HbA1c. The T2D patients that were from high altitude presented more often fatty liver in the US, and lower levels of total cholesterol and LDL-c than those patients from the coast. The younger the patient, more cardiometabolic risk factors were present. Sixty percent of the patients received monotherapy, being metformin the preferred drug. Conclusions: Patients with T2D debut from Lima and the northern region of Peru, and also the younger patients, have more cardiometabolic risk factors than their counterparts from the rest of the country and the older ones. We didn’t find any clinical difference between patients from the coast or from high altitude. Metformin was the most prescribed drug to treat these patients. Disclosure J. Rocca: Consultant; Self; Merck KGaA. Other Relationship; Self; Novo Nordisk A/S. M. Calderon: None. A. Whittembury: None. V. Ulloa: Employee; Self; Novo Nordisk A/S. Funding Novo Nordisk Peru S.A.C.

Abstract B080: Assessment of the molecular mechanisms of a protective variant for breast cancer in Latinas

Abstract The incidence of breast cancer is lower in women of Latin American origin in the U.S. compared to European American and African American women. Among Latinas, the rs140068132A&amp;gt;G variant, which is common in women with IAA, has been associated to a lower risk of breast cancer. The frequency of the G allele is 0% for non-Latinos while 12% in Latinos, being highest in the Peruvian population (23%). This variant is located on chromosome 6 near the Estrogen Receptor 1 gene (ESR1) and even though experimental evidence suggests that this variant might be functional, the molecular mechanisms that explain its protective effect are unknown. We hypothesize that the rs140068132-G variant decreases ESR1 expression, which affects the expression or function of genes involved in associated pathways. We aim to test the association of the rs140068132 variant and gene expression in breast cancer tumors from patients with high IAA. We collected 47 breast tumors and blood samples from the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. These patients were genotyped for IAA estimation and determination of the rs140068132 genotype. Total RNA was extracted from tumor samples and used for a paired-end sequencing (2 × 75bp paired-end,100 million reads per sample) in the Illumina NextSeq500. Differential gene expression between genotypes was performed by DEseq2 R package and statistical significance was determined using FDR&amp;lt;0.05 for samples with at least log2 1.5-fold change. Differentially expressed isoforms were detected by EBseq R package using FDR&amp;lt;0.05. Tumor intrinsic subtypes were obtained using PAM50 as implemented in the genefu R package. The average IAA for the 47 Peruvian patients was 77% (SD=0.17). Twenty-seven patients were homozygous AA, 19 heterozygous AG and 1 GG for the rs140068132 variant. According to PAM50 classification, 10 tumors were Luminal A, 12 Luminal B, 15 HER2+ and 10 Basal. Among luminal tumors there was a suggestive trend towards lower expression of the ESR1 gene in patients carrying the protective allele (p=0.16). Including all subtypes, 27 genes were differentially expressed according to the rs140068132 genotype. Four of these genes are ER dependent or associated with ER status. The expression of the top gene, which is a transcriptional target of ER, is lost in patients with the protective allele. This association is mainly driven by its expression in luminal tumors and remained significant after adjusting for IAA. ESR1 isoforms were not differentially expressed by genotype, however significant differences were detected in the expression of isoforms for 115 genes, of which 18% have been reported to be transcriptional targets of ER or functionally related. Our preliminary results suggest that the rs140068132 variant decreases ER expression and affects the expression of functionally associated genes in luminal tumors. Further allele-specific expression analysis will elucidate if this variant is part of a cis-regulatory module. Note: This abstract was not presented at the conference. Citation Format: Valentina A. Zavala, Tatiana Vidaurre, Katie Marker, Sandro Casavilca, Lizeth Tamayo, Carlos Castañeda, Jeannie Vásquez, Fernando Valencia, Zaida Morante, M. Calderon, J. Abugattas, H. Gomez, H. Fuentes, C. Monge-Pimentel, Silvia Neciosup, Jovanny Zabaleta, Laura Fejerman. Assessment of the molecular mechanisms of a protective variant for breast cancer in Latinas [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B080.

Factores asociados al funcionamiento global en pacientes con esquizofrenia de un hospital general del Perú

ObjectiveTo evaluate the influence of the factors associated with overall functioning in patients with schizophrenia who attended the outpatient clinic of the Hospital Nacional de la Policía [National Police Hospital] “Luis Nicasio Saenz” in 2018-2019. MethodologyNon-experimental quantitative study of a descriptive cross-sectional correlational type. Convenience sampling was carried out, and consisted of 53 patients with schizophrenia. Functioning Assessment Short Test (FAST) was used to assess overall functioning, the Screen for Cognitive Impairment in Psychiatry (SCIP) for cognitive functioning, and a data collection sheet with sociodemographic data and a history of the disease. ResultsIt was found that 34 (62.2%) patients were male; 52 (98.1%), single; 39, (73.6%) without a current job. We found worse overall functioning in patients with a lower educational level (p=0.005) and without a current job (p=0.004). The total FAST was correlated with the time of the disease (ρ=0.334, p <0.05), the number of previous psychotic episodes (ρ=0.354, p <0.01), the total SCIP score (ρ=0.542, p <0.01) and their working memory dimension (VMT) (ρ=-0.523, p <0.05). In the multiple linear regression model, it was found that the variables that most influenced the FAST were the total SCIP score (Beta=-0.528) and the number of previous psychotic episodes (Beta=0.278). ConclusionThe associated factors that most influence overall functioning in this sample of Peruvian patients with schizophrenia are cognitive functioning and the number of previous psychotic episodes.

Safety of immunotherapy in Peruvian patients with diverse type of malignancies: Experience at a private center.

e19258 Background: Immunotherapy has changed the landscape of cancer treatment. The aim of this work was to describe the adverse events related to immunotherapy treatment in diverse type of malignant tumors using real-world data. Methods: This is a retrospective review of patients with diverse type of advanced malignancies treated with immunotherapy at Oncosalud-AUNA (Lima-Peru) during the period 2016-2018. We present a descriptive analysis of the clinicopathological and treatment features of the patients, as well as data of safety of immunotherapeutic agents. Results: In total, 37 patients were included in the study. The median age was 67 years (38 to 84 years); 64.9% of patients were male; 54.1% were smoker/former smoker and 45.9% non-smokers. Regarding to the primary tumor, 75.7% were lung cancers (82.1%, adenocarcinomas and 17.9%, squamous cell carcinomas), 16.2% were melanomas, 5.4, head and neck cancers and 2.7%, were bladder cancers. Central nervous system metastases were present in 29.7% of patients. Immunotherapy was given after a first line in 43.2% of cases, 40.5% after the second line and 16.2%, after the third line of treatment. The types of immunotherapy were prembrolizumab in 54.1%, nivolumab in 40.5%, atezolizumab in 2.7% and avelumab in 2.7%. 27% of cases had combination of immuno with chemotherapy. Finally, regarding to adverse events, 94.6% had any adverse event; 48.6% fatigue and asthenia; 35.1%, nausea; 32.4, pruritus/rash; 27.7%, decreased appetite; 18.9%, hypo/hyperthyroidism; 13.5%, diarrhea/colitis; 10.8%, pneumonitis and 5.4%, infusion-related reactions. Conclusions: During the study period we had a slightly higher incidence of adverse events than reported by other works. It could be probably due to the age of patients and several prior lines of treatment.

T68. RELATIONSHIP BETWEEN GLOBAL AND COGNITIVE FUNCTIONING IN PATIENTS WITH SCHIZOPHRENIA IN A GENERAL HOSPITAL IN PERU

BackgroundSchizophrenia is a chronic mental disorder, which produces high costs and has a substantial impact on health care budgets globally. This is mainly due to poor global and cognitive functioning in these patients. The objective of this study was to relate global functioning and cognitive functioning in patients with schizophrenia who attend the outpatient clinic of a general hospital in Peru during the years 2018–2019.MethodsNon-experimental quantitative study of descriptive cross-sectional correlational type. The sample was for convenience, and consisted of 53 patients with schizophrenia from the “Hospital Nacional de la PNP”. Functioning Assessment Short Test (FAST) was used to assess global functioning, the Screen for Cognitive Impairment (SCIP), cognitive functioning, and a data collection sheets with the history of the disease.The relationship between FAST and SCIP with the qualitative variables was evaluated by the Mann-Whitney U test or Student’s t test depending on whether they met the normality assumptions. The linear correlation between the FAST, the SCIP and the other quantitative variables was evaluated using Spearman’s Rho.A multiple linear regression model was constructed in which all variables other than the total FAST result are considered using the forward method.ResultsIt was found that 34 (62.2%) were male; 52 (98.1%), single; 39, (73.6%) without a current job. We found worse overall functioning in patients with lower educational level (p = 0.005) and without a current job (p = 0.004). The total FAST was correlated with the time of the disease (ρ = 0.334, p <0.05) and with the number of previous psychotic episodes (ρ = 0.354, p <0.01). We found worse cognitive functioning in patients with lower educational level (p = 0.000) and without a current job (p = 0.017). The SCIP total was correlated to the FAST (ρ = 0.542, p <0.01).The multiple linear regression analysis with the total FAST score as the explained variable evidenced the existence of a relationship between variables that is explained by the equation:Y = 57.032 + (-0.521) X1 + (1.896) X2Where Y is the total FAST score, X1 the total SCIP and X2 the number of previous psychotic episodes. The coefficient of determination was 0.392 and the mean square error of 161.46. The Durbin-Watson statistic was 1,529.DiscussionThis is the first exploratory pilot analysis of the factors associated with global functioning, with special emphasis on cognitive functioning and the history of the disease, in Peruvian patients with schizophrenia.Patients with higher educational level and those who have a current job showed a better global and cognitive functioning. It was found an indirect and significant relationship of moderate intensity between cognitive functioning and its subtest with global functioning, that is, a lower level of cognitive functioning is related to greater difficulties in the daily functioning of patients with schizophrenia. Both the bivariate analysis and the linear regression model found a relationship between global and cognitive functioning. In the multiple linear regression model, it was found that the total SCIP was the one that had the most influence on global functioning (Beta = -0.528), that is, lower levels of cognitive functioning are related to high levels of poor global functioning.Taking these results into account, we recommend implementing functional and cognitive evaluation programs in patients with schizophrenia at the “Hospital Nacional de la PNP”. Future longitudinal studies should be performed on samples from larger patients, especially with a first psychotic episode, with the purpose of seeking a cause-effect relationship between global and cognitive functioning in patients with schizophrenia.

Delays to diagnosis and barriers to care for breast cancer in Mexico and Peru: a cross sectional study

BackgroundDelays to breast cancer diagnosis and treatment initiation are associated with worsened outcomes. However, population-based screening is impractical in many low-income and middle-income countries (LMICs) because of resource constraints and a lack of capacity to effectively diagnose and treat screen-detected disease. Mexico and Peru have similar mortality-to-incidence ratios for breast cancer. Unlike Peru, Mexico has attempted to implement mammography screening, although it remains opportunistic with low (20%) national coverage rates. The aim of this study was to compare delays and describe barriers to care among breast cancer patients in Mexico and Peru. MethodsThis international cross-sectional study included breast cancer patients interviewed at four public cancer hospitals in Mexico City between 2009 and 2011, and a federally-funded regional cancer institute in Trujillo, Peru in 2015. A Breast Cancer Delays Questionnaire, developed and validated in Mexico and modified for Peru, was administered to breast cancer patients during routine hospital visits at each location. Patient-related, diagnostic, and treatment delays were quantified, and barriers to care identified. FindingsWe included data from 597 Mexican women and 113 Peruvian women. Age at diagnosis did not differ between countries (53 years [Mexico] vs 54 years [Peru], p=0·266). Most women in both countries had breast cancer detected by symptoms (84% [Mexico] vs 93% [Peru]; p<0·001), although more women in Mexico were diagnosed by mammography screening (12% vs 6%) and screening clinical breast examination (4% vs 1%). Of patients with available stage information, the majority of disease was AJCC stage II or III at diagnosis (76% [n=597, Mexico] vs 91% [93, Peru]; p=0·014). More women in Mexico were diagnosed at an early stage (AJCC stage 0 or I) (14% [Mexico] vs 4% [Peru]). Total delay (symptom discovery or screening to initiation of treatment) did not differ between the two countries (median 210 days [IQR 128–415; n=597] Mexico vs 201 days [82–442; n=74] Peru; [p=0·71]). Diagnostic delay (first medical consultation to diagnosis) was the greatest contributor to overall delay (113 days [59–250; n=597, Mexico] vs 174 days [40–396; n=95, Peru]; p=0·105). Approximately 60% of all patients had diagnostic delays greater than 3 months. Less than half (44%) of Mexican patients visited more than two health-care facilities before the cancer centre, compared with 71% of Peruvian patients (p<0·001). Patients in both countries reported that barriers to prompt arrival at the cancer centre were: not knowing where to go, lack of money, spread out appointments, and diagnostic errors. InterpretationImproved diagnostic and referral systems are necessary to reduce delays to breast cancer care in Mexico and Peru. Such improvements are prerequisites to the establishment of maximally effective mammography screening programmes in LMICs. FundingNIH Research Training Grant 3R25TW009345 awarded to the Northern Pacific Global Health Fellows Program by the Fogarty International Center and Institutes at the NIH; the Fulbright Scholar Program, a program of the United States Department of State Bureau of Educational and Cultural Affairs; and the Mexican National Council of Science and Technology (grant CONACYT/SSA/IMSS/ISSSTE SALUD-2007-C01-69,439).