IgG N-glycans are associated with prevalent and incident complications of type 2 diabetes.

AIMS/HYPOTHESIS: Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes. METHODS: In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors. RESULTS: IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex. CONCLUSIONS: We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.

COVID-19 in elderly kidney transplant recipients.

The SARS-Cov-2 infection disease (COVID-19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID-19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti-retroviral and tocilizumab. Short-term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D-dimer, C-reactive protein, and IL-6 at their first tests. COVID-19 is frequent among the elderly KT population and associates a very early and high mortality rate.

COVID-19 in Grade 4-5 Chronic Kidney Disease Patients.

INTRODUCTION: Chronic kidney disease (CKD) increases the risk of mortality during coronavirus disease 2019 (COVID-19) episodes, and some reports have underlined the high incidence and severity of this infection in dialysis patients. Information on COVID-19 in nondialysis CKD patients is not available yet. CASE REPORTS: Here we present 7 patients with grade 4-5 CKD who developed symptomatic COVID-19; they comprise 2.6% of our 267 advanced CKD patients. The estimated GFR was between 12 and 20 mL/min during the month prior to COVID-19. The 3 major symptoms were fever, cough, and dyspnea, and 5 patients showed bilateral pneumonia. Hydroxychloroquine, azithromycin, ceftriaxone, and steroids were the most frequently prescribed drugs. Two patients needed noninvasive mechanical ventilation. All patients showed minimal to moderate kidney function deterioration during admission, with an eGFR decline below 5 mL/min in 6 cases. No patient required acute dialysis. Six patients were discharged alive and remained dialysis free athe t the time of reporting, and one 76-year-old patient died. CONCLUSIONS: COVID-19 affects grade 4-5 CKD patients, but prognosis may be acceptable if prompt supportive measures are applied. These findings should be confirmed in larger cohorts, and further observations will be needed to understand the full spectrum of clinical features and the optimal approach to COVID-19 in patients with advanced CKD.

Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome.

AIMS: The clinical implications of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in patients with post-transplant lymphoproliferative disorders are largely unknown, and its association with Epstein-Barr virus (EBV) status and PD-L1 copy number alterations (CNAs) has not been thoroughly studied. METHODS AND RESULTS: PD1/PD-L1 expression was studied in 50 adult post-transplant lymphoproliferative disorders, and the correlations with PD-L1 CNAs, EBV, clinicopathological features and outcome were evaluated. Thirty-seven (74%) cases were classified as diffuse large B-cell lymphoma (DLBCL), nine (18%) cases were classified as polymorphic, and four (8%) cases were classified as classic Hodgkin lymphoma. Thirty-four cases were EBV-positive, with 29 of 34 (85%) having latency II or III, and 15 of 34 (44%) having viral replication. PD-L1 expression in tumour cells and tumour-associated macrophages was observed in 30 (60%) and 37 (74%) cases, respectively. PD1 positivity was seen in 16 (32%) cases. PD-L1 expression was associated with EBV with latency II or III (P = 0.001) and organ rejection (P = 0.04), and, in DLBCL, with non-germinal centre type DLBCL (P < 0.001). Cases with PD-L1-positive tumour cells showed a higher number of PD-L1 CNAs than PD-L1-negative cases (P = 0.001). Patients with EBV/latency III/replication and simultaneous PD-L1 expression showed the worst overall survival (P < 0.001). CONCLUSIONS: The PD1/PD-L1 axis is deregulated in post-transplant lymphoproliferative disorders, with frequent PD-L1 expression and PD1 negativity. PD-L1 expression is associated with EBV latency II or III and PD-L1 CNAs, and probably reflects a proinflammatory tumour microenvironment. The combined analysis of EBV status and PD-L1 expression may help to identify deeply immunosuppressed patients who can benefit from immune reconstitution approaches.

CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions.

BACKGROUND: Squamous intraepithelial lesions/cervical intraepithelial neoplasias (SIL/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL/CIN2-3) or low grade (LSIL/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL/CIN lesions. DESIGN: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL/CIN1, 30 HSIL/CIN2, 60 HSIL/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. RESULTS: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1/8) of normal samples, 31.5% (6/19) of LSIL/CIN1, 83.3% (25/30) of HSIL/CIN2, 81.6% (49/60) of HSIL/CIN3 and 100% (14/14) of CC (p < 0.001). The sensitivity and specificity for HSIL/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL/CIN2-3 and CC, respectively. CONCLUSIONS: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL/CIN.

Impact of Recurrent Acute Kidney Injury on Patient Outcomes.

BACKGROUND/AIMS: Recurrent acute kidney injury (AKI) is common among patients after a first hospitalized AKI. However, little is known about the prognosis of recurrent AKI episodes in chronic kidney disease (CKD) development, cardiovascular events and mortality. METHODS: A retrospective study included patients admitted to our Hospital from 2000 to 2010. AKI was defined according to the Acute Dialysis Quality Initiative criteria. In the follow-up period after the first AKI episode, clinical, laboratory data and the number of repeated AKI episodes, etiology and severity were recorded. RESULTS: Among the 359 AKI survivor patients included, 250 new AKI episodes were observed in 122 patients (34%). Variables independently associated to new episodes were: type 2 DM [OR 1.2, 95%CI 1.2-3.8, p=0.001], ischemic heart disease [OR 1.9; 95%CI 1.1-3.6, p=0.012], and SCr at the first AKI event>2,6 mg/dl [OR 1.2; 95%CI 1.03-1.42, p=0.02]. Development of CKD during four years follow-up was more frequent in patients with recurrent AKI, HR [2.2 (95% CI: 1.09-4.3, p=0.003)] and 44% of recurrent AKI patients who developed CKD occurred during the first 6 months after the initial event. Cardiovascular events were more frequent among patients with recurrent AKI patients than in those with one AKI episode (47.2% vs 24%, p=0.001). Mortality at 4 years was higher in the patient subgroup with several episodes of AKI as compared with those with a single episode [HR: 4.5 (95% CI 2.7-7.5) p<0.001]. CONCLUSION: Episodes of recurrent AKI have a high potential to be associated with relevant complications such as cardiovascular events, mortality and CKD development.

Short- and long-term outcomes after non-severe acute kidney injury.

BACKGROUND: Severe acute kidney injury (AKI) is associated with chronic kidney disease (CKD), cardiovascular events and increased mortality. However, little is known about the prognosis in hospitalized population suffering from non-severe AKI episodes. The aim of this study is to determine the impact of non-severe AKI episodes in cardiovascular events, mortality and CKD, on short and long term. METHODS: Retrospective cohort study to 360 patients who met the criteria for diagnosis of AKI according ADQI guidelines with full recovery of renal function after the AKI episode, admitted between January 2000 and December 2010 in our hospital. Follow-up was 4 years after the diagnosis of AKI. Covariates included demographic variables, baseline creatinine and diagnosis of comorbidities. RESULTS: 360 AKI survivor patients were included. Twenty five of them (6.7%) had developed CKD after 1-year follow-up. Hypertension (OR 1.62; 95% CI 1.2-2.6, p < 0.05) and serum creatinine >2.6 mg/dL in AKI (OR 1.7; 95% CI 1.2-3.7, p < 0.05) were independent risk factors. After 4-year follow-up, 40 patients (18.3%) had developed CKD; age >66 years was an independent risk factor (OR 1.03, 95% CI 1.03-1.06, p < 0.05). Mortality rate at 4 years was 25.3% and was significantly higher in CKD patients (OR 4.3, 95% CI 1.13-4.90, p < 0.05) and patients >66 years (OR 1.12, 95% CI 1.02-1.06, p < 0.05). The incidence of cardiovascular events also was higher in CKD patients than in non-CKD patients (62.7 vs. 21.7%, p < 0.05). CONCLUSION: Even after fully recovered non-severe AKI episodes, some patients develop CKD and those have an increase in the incidence of cardiovascular events and long-term mortality.

Role of Human Papillomavirus in Vulvar Cancer.

Human papillomavirus (HPV) is involved in one of the at least 2 pathways leading to vulvar squamous cell carcinoma (VSCC). Inactivation of p53 and retinoblastoma by the viral products E6 and E7 is involved in malignant transformation. The percentage of HPV-positive VSCCs ranges from 18% to 75%, depending on the geographical area. HPV-associated tumors affect relatively young women and arise from high-grade intraepithelial lesions, identical to other HPV-associated premalignant lesions of the anogenital tract. HPV-independent tumors tend to affect older women and usually arise in a background of inflammatory skin disorders and a subtle variant of in situ lesion called differentiated vulvar intraepithelial neoplasia. HPV-positive tumors tend to be of basaloid or warty types, whereas HPV-independent tumors tend to be of keratinizing type, but there is frequent overlap between histologic types. There is no conclusive evidence yet on the best strategy in terms of determining HPV attribution. HPV DNA detection is generally considered the gold standard although there is some concern about misclassification when using this technique alone. p16 immunostaining has shown to be an excellent surrogate marker of HPV infection. Positive results for both techniques are considered the best evidence for HPV-association. The prognostic role of HPV in VSCC is still contradictory, but increasing evidence suggests that HPV-associated tumors are less aggressive. Currently, there are no differences in treatment between HPV-associated and HPV-independent VSCC, but novel immunological strategies based on anti-HPV antigens are being evaluated in clinical trials.

Ceramide levels regulated by carnitine palmitoyltransferase 1C control dendritic spine maturation and cognition.

The brain-specific isoform carnitine palmitoyltransferase 1C (CPT1C) has been implicated in the hypothalamic regulation of food intake and energy homeostasis. Nevertheless, its molecular function is not completely understood, and its role in other brain areas is unknown. We demonstrate that CPT1C is expressed in pyramidal neurons of the hippocampus and is located in the endoplasmic reticulum throughout the neuron, even inside dendritic spines. We used molecular, cellular, and behavioral approaches to determine CPT1C function. First, we analyzed the implication of CPT1C in ceramide metabolism. CPT1C overexpression in primary hippocampal cultured neurons increased ceramide levels, whereas in CPT1C-deficient neurons, ceramide levels were diminished. Correspondingly, CPT1C knock-out (KO) mice showed reduced ceramide levels in the hippocampus. At the cellular level, CPT1C deficiency altered dendritic spine morphology by increasing immature filopodia and reducing mature mushroom and stubby spines. Total protrusion density and spine head area in mature spines were unaffected. Treatment of cultured neurons with exogenous ceramide reverted the KO phenotype, as did ectopic overexpression of CPT1C, indicating that CPT1C regulation of spine maturation is mediated by ceramide. To study the repercussions of the KO phenotype on cognition, we performed the hippocampus-dependent Morris water maze test on mice. Results show that CPT1C deficiency strongly impairs spatial learning. All of these results demonstrate that CPT1C regulates the levels of ceramide in the endoplasmic reticulum of hippocampal neurons, and this is a relevant mechanism for the correct maturation of dendritic spines and for proper spatial learning.

The GenoDiabMar Registry: A Collaborative Research Platform of Type 2 Diabetes Patients.

The GenoDiabMar registry is a prospective study that aims to provide data on demographic, biochemical, and clinical changes in type 2 diabetic (T2D) patients attending real medical outpatient consultations. This registry is also used to find new biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. With this purpose, longitudinal serum and urine samples, DNA banking, and data on 227 metabolomics profiles, 77 immunoglobulin G glycomics traits, and other emerging biomarkers were recorded in this cohort. In this study, we show a detailed longitudinal description of the clinical and analytical parameters of this registry, with a special focus on the progress of renal function and cardiovascular events. The main objective is to analyze whether there are differential risk factors for renal function deterioration between sexes, as well as to analyze cardiovascular events and mortality in this population. In total, 650 patients with a median age of 69 (14) with different grades of chronic kidney disease­G1−G2 (eGFR > 90−60 mL/min/1.73 m2) 50.3%, G3 (eGFR; 59−30 mL/min/1.73 m2) 31.4%, G4 (eGFR; 29−15 mL/min/1.73 m2) 10.8%, and G5 (eGFR < 15 mL/min/1.73 m2) 7.5%­were followed up for 4.7 (0.65) years. Regardless of albuminuria, women lost 0.93 (0.40−1.46) fewer glomerular filtration units per year than men. A total of 17% of the participants experienced rapid deterioration of renal function, 75.2% of whom were men, with differential risk factors between sexes­severe macroalbuminuria > 300 mg/g for men OR [IQ] 2.40 [1.29:4.44] and concomitant peripheral vascular disease 3.32 [1.10:9.57] for women. Overall mortality of 23% was detected (38% of which was due to cardiovascular etiology). We showed that kidney function declined faster in men, with different risk factors compared to women. Patients with T2D and kidney involvement have very high mortality and an important cardiovascular burden. This cohort is proposed as a great tool for scientific collaboration for studies, whether they are focused on T2D, or whether they are interested in comparing differential markers between diabetic and non-diabetic populations.

Medical labour under neoliberalism: an ethnographic study in Colombia.

OBJECTIVES: In order to increase the knowledge about the impacts of neoliberal market forces on physician's labour, this article's objectives are to analyse how and why the labour of physicians is transformed by neoliberalism, and the implications of these transformations for patient care. METHODS: Ethnographic investigation is carried out through semi-structured interviews with 20 general practitioners at public and private facilities in Colombia. The interviews were contrasted with national studies of physician's labour since the 1960s. A "mock" job search was also simulated. The analysis was guided by Marxian frameworks. The study was approved by a Human Research Ethics Committee, and informed consent was obtained from all participants. RESULTS: The overpowering for-profit administration of the Colombian healthcare system imposes productivity mechanisms on physicians as a result of a deregulated labour market characterized by low salaries, reduced and self-funded social security benefits, and job insecurity. Overworked physicians with reduced autonomy become frustrated for not being able to provide the care their patients need according to clinical standards. CONCLUSIONS: Under neoliberal conditions, medical labour becomes exploitable and directly productive through its formal and real subsumption to Capital. The negative consequences of a progressive loss in physician's autonomy unveil the incompatibility between neoliberal health systems and people's health.

[Underlying conditions on the southern border between Colombia and Venezuela to face the COVID-19 pandemic]. / Condiciones en la frontera sur entre Colombia y Venezuela ante la pandemia de COVID-19.

OBJECTIVES: To size human migration on the southern border between Colombia and Venezuela (Guainía department), and characterize the social, access and health care conditions relevant to the COVID-19 pandemic. METHODS: Mixed epidemiological and ethnographic study. Rate of Venezuelan migrants was calculated according to Migration Colombia data until December 31st, 2019, also effective access to medical care, and provision of health posts were calculated, with information from each Guainía health post collected from June 2017 to June 2019, through semi-structured interviews, participant observations, Google Earth™ and Wikiloc™. Stata™ was used to calculate and graph median times of effective access. Cultural dynamics and health care conditions were described by the field work information and a permanent documentary review. RESULTS: Guainía is the 23rd department, according to the total number of Venezuelans, but the fourth in Venezuelans density (14,4%). In the Guainía river, the median times to the real reference health institution were 8,7 hours in winter and 12,3 in summer, and complex cases require air referrals. In the Inírida river, the median times to the real reference health institution were 11,9 hours in winter and 16,1 in summer. Only 57% of the health posts had supplies for acute respiratory infections. CONCLUSIONS: Facing COVID-19 in south border territories, it is necessary to immediately strengthen medical and public health services to avoid high fatality rates.

Consumption of Alcohol, Tobacco and Psychoactive Substances in Adolescents from an Indigenous Territory in the Colombian Amazon. / Consumo de alcohol, tabaco y sustancias psicoactivas de los adolescentes de un territorio indígena en la Amazonía colombiana.

INTRODUCTION: There are very few studies on the consumption of psychoactive substances (PAS) among young people from indigenous territories and evening or blended learning students. In Inírida, a municipality in the Colombian Amazon, there were concerns about a possible consumption issue that had never been characterised before. OBJECTIVE: To characterise the consumption of alcohol, tobacco and PAS in Inírida among teenage evening and blended learning students. METHODS: The Inter-American Uniform Drug Use Data System (SIDUC) survey developed by the Inter-American Drug Abuse Control Commission (CICAD) was adapted to the cultural context and carried out on 95% of 284 evening and blended learning students (262). Descriptive statistics and multiple correspondence analyses were used. RESULTS: Currently, 59% consume alcohol; 28% tobacco; 21% marijuana; 3% cocaine paste; 1% ecstasy (MDMA); 1% cocaine; and 1% inhalants. Also, 61% believe that drugs are available inside and around the vicinity of their school, and that marijuana (62%) and cocaine paste (35%) are easily acquired. Drugs are most commonly offered in neighbourhoods (56%) and at parties (30%). Those offering the highest quantity of drugs are acquaintances (35%) and friends (29%). And 51% stated that they had participated in preventive activities related to consumption. CONCLUSIONS: The population has a higher consumption of the substances studied in comparison with the national reference, that of Orinoquía and Amazonía, with the exception of cocaine and inhalants. The consumption situation was confirmed, so participatory actions are proposed.

Clinical Profiles in Renal Patients with COVID-19.

The COVID-19 pandemic has led to frequent referrals to the emergency department on suspicion of this infection in maintenance hemodialysis (MHD) and kidney transplant (KT) patients. We aimed to describe their clinical features comparing confirmed and suspected non-confirmed COVID-19 cases during the Spanish epidemic peak. Confirmed COVID-19 ((+)COVID-19) corresponds to patient with positive RT-PCR SARS-CoV-2 assay. Non-confirmed COVID-19 ((-)COVID-19) corresponds to patients with negative RT-PCR. COVID-19 was suspected in 61 patients (40/803 KT (4.9%), 21/220 MHD (9.5%)). Prevalence of (+)COVID-19 was 3.2% in KT and 3.6% in MHD patients. Thirty-four (26 KT and 8 MHD) were (+)COVID-19 and 27 (14 KT and 13 MHD) (-)COVID-19. In comparison with (-)COVID-19 patients, (+)COVID-19 showed higher frequency of typical viral symptoms (cough, dyspnea, asthenia and myalgias), pneumonia (88.2% vs. 14.3%) and LDH and CRP while lower phosphate levels, need of hospital admission (100% vs. 63%), use of non-invasive mechanical ventilation (36% vs. 11%) and mortality (38% vs. 0%) (p < 0.001). Time from symptoms onset to admission was longer in patients who finally died than in survivors (8.5 vs. 3.8, p = 0.007). In KT and MHD patients, (+)COVID-19 shows more clinical severity than suspected non-confirmed cases. Prompt RT-PCR is mandatory to confirm COVID-19 diagnosis.

Usefulness of the KDPI in Spain: A comparison with donor age and definition of standard/expanded criteria donor.

INTRODUCTION: Kidney donor shortage requires expanding donor selection criteria, as well as use of objective tools to minimize the percentage of discarded organs. Some donor pre-transplant variables such as age, standard/expanded criteria donor (SCD/ECD) definition and calculation of the Kidney Donor Profile Index (KDPI), have demonstrated correlations with patient and graft outcomes. We aimed to establish the accuracy of the three models to determine the prognostic value of kidney transplantation (KT) major outcomes. MATERIAL AND METHODS: We performed a retrospective study in deceased donor KTs at our institution. Unadjusted Cox and Kaplan-Meier survival, and multivariate Cox analyses were fitted to analyze the impact of donor age, SCD/ECD and KDPI on outcomes. RESULTS: 389 KTs were included. Mean donor age was 53.6±15.2 years; 163 (41.9%) came from ECD; mean KDPI was 69.4±23.4%. Median follow-up was 51.9 months. The unadjusted Cox and Kaplan-Meier showed that the three prognostic variables of interest were related to increased risk of patient death, graft failure and death-censored graft failure. However, in the multivariate analysis only KDPI was related to a higher risk of graft failure (HR 1.03 [95% CI 1.01-1.05]; p=0.014). CONCLUSIONS: SCD/ECD classification did not provide significant prognostic information about patient and graft outcomes. KDPI was linearly related to a higher risk of graft failure, providing a better assessment. More studies are needed before using KDPI as a tool to discard or accept kidneys for transplantation.

Value of HPV 16/18 Genotyping and p16/Ki-67 Dual Staining to Predict Progression to HSIL/CIN2+ in Negative Cytologies From a Colposcopy Referral Population.

OBJECTIVES: To assess the prognostic value of human papillomavirus (HPV) 16/18 genotyping and p16/Ki-67 dual staining cytology in high-risk HPV (hrHPV)-positive women with no lesion or minor abnormalities. METHODS: We evaluated progression to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grades 2 to 3 or cervical cancer (HSIL/CIN2+), persistence/regression of hrHPV infection in women referred to colposcopy showing hrHPV infection, histology diagnosis different from HSIL/CIN2+, and negative cytology. HPV 16/18 genotyping and dual staining were performed in liquid-based cytologic specimens obtained on the first visit. RESULTS: Progression was observed in 16 (8.0%) of 200 women. Those with HPV 16/18 infection had an increased risk of progression compared with women infected by other hrHPV types, and they also showed more persistence. However, no association was observed between progression or persistence and the result of the dual staining. CONCLUSIONS: HPV 16/18-positive women with no lesions or minor abnormalities are at high risk of progression to HSIL/CIN2+ and hrHPV persistence.

Mortalidad por cáncer de cuello uterino en la amazonia de Colombia / Cervical cancer mortality in the Colombian Amazon

Resumen OBJETIVO: Analizar el pico de mortalidad por cáncer de cuello uterino registrado en 2018 en Guainía, Colombia. MATERIALES Y MÉTODOS: Estudio ecológico basado en los datos de todas las instituciones con información de la morbilidad y mortalidad y atenciones relacionadas con el cáncer de cuello uterino en Colombia, entre enero de 2009 y diciembre de 2019. Se incluyeron todos los datos disponibles para Guainía. Se excluyeron las bases sin datos entre 2016 y 2018. Se analizaron la morbilidad y mortalidad, atenciones y procedimientos, y se compararon con el comportamiento en 2018 respecto de los demás años. RESULTADOS: Las personas atendidas, las atenciones y los procedimientos relacionados con cáncer de cuello uterino disminuyeron en 2016 y 2017. La concentración de atenciones por persona más baja del periodo se dio en 2017. En 2019, aumentó la cantidad de personas con diagnóstico de infección por papilomavirus. CONCLUSIONES: La reducción en el tamiz, las atenciones y los procedimientos relacionados con el cáncer de cuello uterino, en un territorio, puede ocasionar aumentos en la mortalidad por este tipo de cáncer. Es fundamental sostener en el tiempo las acciones de prevención, diagnóstico y tratamiento, para evitar esta mortalidad.

Abstract OBJECTIVE: To analyze the cervical cancer mortality peak, in Guainía, in 2018. MATERIALS AND METHODS: Ecological study. Data from all institutions with cervical cancer morbidity, mortality and attention information in Colombia, between January/2009 and December/2019, were analyzed. All available data for Guainía were included. The databases with no data between 2016 and 2018 were excluded. Morbidity, mortality, attention, and procedures were analyzed, comparing the behavior in 2018 to the other years. RESULTS: Cervical cancer-related patients, care and procedures decreased in 2016 and 2017. The lowest concentration of care per person in the period was in 2017. In 2019, the number of people diagnosed with papillomavirus infection increased. CONCLUSIONS: The reduction in screenings, care and procedures related to cervical cancer, in a territory, can lead to increases in mortality from this type of cancer. It is essential to sustain prevention, diagnosis, and treatment actions over time to avoid this mortality.

Guillain-Barré syndrome in patients with a recent history of Zika in Cúcuta, Colombia: A descriptive case series of 19 patients from December 2015 to March 2016.

PURPOSE: Zika virus (ZIKV) infection is an emerging global threat and a public health problem in the Americas. Guillain-Barré syndrome (GBS) has been recently associated to ZIKV. This report presents a case series of GBS possibly associated to ZIKV. METHODS: Clinical and demographic data from patients with GBS treated in 5 intensive care units and with recent history of ZIKV in Cúcuta, Colombia were collected from December 1 2015 to April 30 2016. Electrophysiological examination, lumbar puncture, and reverse transcriptase-polymerase chain reaction for ZIKV were performed in 14, 10, and 1 patients, respectively. RESULTS: Nineteen patients with GBS and a recent history of acute viral syndrome compatible with ZIKV infection were studied (mean age, 44 years; range, 17-78). Neurologic symptoms developed at a median of 10 days after the onset of the viral symptoms. Albuminocytological dissociation was found in 8 cases. Electrophysiological criteria for acute motor axonal neuropathy were found in all patients tested. Five patients met level 1, 8 patients level 2, and 6 patients level 3 of diagnostic certainty for GBS in the Brighton classification. Fifteen patients required respiratory assistance, 16 received intravenous immunoglobulins, and 3 had plasmapheresis. Seventy-nine percent of patients were in Hughes GBS disability scale 4 to 5 at discharge and no patients died during the observation period. Acute ZIKV infection, confirmed by reverse transcriptase-polymerase chain reaction, was observed for 1 patient. CONCLUSIONS: All cases of this GBS outbreak had a recent history ZIKV infection, reinforcing existing evidence for the association between GBS and ZIKV. Future genetic and immunologic studies are warranted to further investigate the cause of the outbreak in detail.

Estrategia educativa intercultural para la prevención del cáncer de cuello cérvico uterino en el resguardo de Paujil, Amazonia Colombiana / Intercultural educational strategy for the prevention of cervical cancer in Paujil Resguardo Amazonía colombiana

RESUMEN Los pueblos indígenas siguen sufriendo inequidades, a pesar de los avances relacionados con la protección de la diversidad étnica y cultural, siendo las mujeres uno de los grupos de mayor riesgo, sobre todo, en lo referente a la salud sexual y reproductiva, situación contemplada como un compromiso de acción en los objetivos de desarrollo sostenible. En ese contexto, esta investigación acción participativa buscó construir una estrategia educativa intercultural, sostenible y segura culturalmente que, a propósito de la prevención del cáncer de cuello uterino, aportará al empoderamiento y la conservación de la salud de las mujeres habitantes del resguardo de Paujil -Colombia. La iniciativa surgió de mujeres indígenas preocupadas por mejorar la salud de sus congéneres y un grupo de investigadores. La construcción de una estrategia educativa intercultural representa un reto, pues la pedagogía occidental no necesariamente corresponde a las concepciones de enseñanza aprendizaje de las indígenas del resguardo. Hay dificultades lingüísticas, pues cada etnia tiene su propia lengua. Las indígenas lideresas se convirtieron en las facilitadoras del proceso que se centró más en el uso de la oralidad y encuentros entre mujeres, que se conocen entre sí. Las mujeres prefieren estrategias didácticas basadas en compartir experiencias y el uso de cartillas y videos. El trabajo permitió concluir que cualquier estrategia educativa intercultural que se proponga debe ser específica y acorde a las necesidades de las comunidades.

ABSTRACT Despite the advances related to the protection of ethnic and cultural diversity, indigenous people continue to suffer inequities, with women being one of the groups most at risk, especially concerning sexual and reproductive health, a situation considered as a problem, a commitment to action in the sustainable development goals. In this context, this Participatory action research searched to build an intercultural educational strategy, sustainable and culturally safe, which, concerning the prevention of cervical cancer, would contribute to the empowerment and conservation of the health of the women who live in the Paujil reservation-Colombia. The initiative arose from indigenous women concerned about improving the health of their peers, and a group of researchers. The construction of an intercultural educational strategy represents a challenge since western pedagogy does not necessarily correspond to the teaching-learning conceptions of the indigenous people of the reservation. There are linguistic difficulties because each ethnic group has its language. The indigenous leaders became the facilitators of the process that focused more on the use of orality and meetings between women who know each other. Women prefer a didactic strategy based on sharing experiences, and the use of primers, and videos. The work allowed to conclude that any proposed of intercultural educational strategy must be specific and according to the needs of the communities.

Renal graft survival according to Banff 2013 classification in indication biopsies. / Supervivencia del injerto renal según la categoría de Banff 2013 en biopsia por indicación.

INTRODUCTION: The impact of acute rejection in kidney graft survival is well known, but the prognosis of other diagnoses is uncertain. We evaluated the frequency and impact on graft survival of different diagnostic categories according to the Banff 2013 classification in a cohort of renal transplant recipients. MATERIAL AND METHODS: Retrospective study of 495 renal biopsies by indication in 322 patients from 1990-2014. Two independent observers reviewed the histological reports, reclassifying according to the Banff 2013 classification. RESULTS: Of 495 biopsies, 28 (5.7%) were not diagnostic. Of the remaining 467, 10.3% were «normal¼ (category 1), 19.6% antibody-mediated changes (category 2), 5.9% «borderline¼ changes (category 3), 8.7% T-cell-mediated rejection (category 4), 23.4% interstitial fibrosis/tubular atrophy (IFTA) (category 5) and 26.5% with other diagnoses (category 6). As time after transplantation increases, diagnoses of categories 1, 3 and 4 decrease, while categories 5 and 2 increase. Worse graft survival with category 2 diagnosis was observed (45% at 7.5 years, HR 4.29 graft loss [95% CI, 2.39-7.73]; P≤.001, compared to category 1). Grafts with «unfavourable histology¼ (chronic antibody-mediated rejection, moderate-severe IFTA) presented worse survival that grafts with «favourable histology¼ (normal, acute tubular necrosis, mild IFTA). CONCLUSIONS: The Banff 2013 classification facilitates a histological diagnosis in 95% of indication biopsies. While diagnostic category 6 is the most common, a change in the predominant histopathology was observed according to time elapsed since transplantation. Antibody-mediated changes are associated with worse graft survival.