[Association between high vitamin B12 levels and one year mortality in older people admitted to the hospital]. / Asociación entre niveles de vitamina B-12 y mortalidad en pacientes hospitalizados adultos mayores.

BACKGROUND: Supplementation of vitamin B12 in older adults is a common practice to avoid vitamin B12 insufficiency. However, there is a paucity of information about the effects of cobalamin excess. AIM: To asses any potential effects of high levels vitamin B12 on mortality on adults aged ≥ 65 years admitted to an internal medicine service. MATERIAL AND METHODS: We Prospectively studied patients admitted to an internal medicine service of an academic hospital from September 2017 to September 2018, who were able to give their consent and answer questionnaires. We tabulated age, gender, medical history, comorbidity index (Charlson), frailty score (Fried scale), admission diagnosis and blood tests performed within 48 hours of admission. The primary outcome was death by any cause in less of 30 days or after one of year follow up, determined according to death certificates. RESULTS: We included 93 patients aged 65 to 94 years (53% males). Fifteen patients died during the year of follow up (five within 30 days of admission). Those who died had higher cobalamin levels than survivors (1080.07 ± 788.09 and 656.68 ± 497.33 pg/mL respectively, p = 0.02). Patients who died had also a significantly lower corrected serum calcium, sodium (p = 0.04) and a medical history of chronic liver disease (p = 0.03). In the multivariable analysis, only vitamin B12 preserved the association with mortality (p = 0.009). CONCLUSIONS: There was a significant association between high levels of cobalamin and all-cause mortality in this group of patients aged ≥ 65 years-old.

European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.

Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.

Association between cardiovascular mortality and STOP-Bang questionnaire scores in a cohort of hospitalized patients: a prospective study.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with an increased risk of mortality and cardiometabolic diseases. The STOP-Bang questionnaire is a tool to screen populations at risk of OSA and prioritize complementary studies. Our objective was to evaluate the clinical utility of this questionnaire in identifying patients at an increased risk of mortality after discharge in a cohort of hospitalized patients. METHODS: This was a prospective cohort study involving consecutive patients admitted to an internal medicine unit between May and June of 2017 who were reevaluated three years after discharge. At baseline, we collected data on comorbidities (hypertension, obesity, diabetes, and fasting lipid profile) and calculated STOP-Bang scores, defining the risk of OSA (0-2 score, no risk; ≥ 3 score, risk of OSA; and ≥ 5 score, risk of moderate-to-severe OSA), which determined the study groups. We also recorded data regarding all-cause and cardiovascular mortality at the end of the follow-up period. RESULTS: The sample comprised 435 patients. Of those, 352 (80.9%) and 182 (41.8%) had STOP-Bang scores ≥ 3 and ≥ 5, respectively. When compared with the group with STOP-Bang scores of 0-2, the two groups showed higher prevalences of obesity, hypertension, diabetes, and dyslipidemia. Multivariate analysis showed an independent association between cardiovascular mortality and STOP-Bang score ≥ 5 (adjusted hazard ratio = 3.12 [95% CI, 1.39-7.03]; p = 0.01). Additionally, previous coronary heart disease was also associated with cardiovascular mortality. CONCLUSIONS: In this cohort of hospitalized patients, STOP-Bang scores ≥ 5 were able to identify patients at an increased risk of cardiovascular mortality three years after discharge.

Prevalence of STOP BANG questionnaire and association with major cardiovascular events in hospitalized population: is it enough with currently used cardiovascular risk measurements?

Cardiovascular risk (CR) is associated with obstructive sleep apnea hypopnea syndrome (OSAHS). This association enhances the risk of major adverse cardiovascular events (MACE); nevertheless, data from hospitalized populations and interactions among these conditions remain unclear. PURPOSE: To evaluate the risk of MACE in the population with risk of OSAHS using the STOP-BANG questionnaire. METHODS: We performed a prospective study in an academic hospital from 2017 to 2018. Data included demography, admissions, STOP-BANG score and CR using AHA scores. The primary outcome was risk of MACE in participants with low risk of OSAHS (STOP-BANG 0-2 points), risk of OSAHS (≥3 points) and risk of moderate/severe OSAHS (≥5 points). Risk of MACE was evaluated using odds ratios (OR), and average CR was evaluated using the t-test. RESULTS: A total of 441 participants were included. The cumulative prevalence of STOP BANG ≥3 points was 80.9%, and that of ≥5 points was 41.6%. OR of MACE ≥3 points was 3.93 (CI 2.08-7.24) (p < 0.001) compared with <3 points, and Average CR was 10.91% (SD ± 2.13) at <3 points versus 24.3% (SD ± 1.24) for ≥3 points for ≥5 points OR of MACE was 1.72 (CI 1.18-2.59) (p = 0.005) and average CR was 26.14% (SD ± 1.63). However, after multivariable analysis, gender differences and previous heart failure were independently associated to MACE. CONCLUSION: The risk of OSAHS in the hospitalized population is high. This population has a higher risk of MACE and higher CRs than do low-risk participants. Conversely, gender and heart failure are potential cofounders.

Results of a pilot trial of immunotherapy with dendritic cells pulsed with autologous tumor lysates in patients with advanced cancer.

AIMS AND BACKGROUND: The purpose of the study was to test the immunological and clinical effects of infusions of dendritic cells pulsed with autologous tumor lysate in patients with advanced cancer. PATIENTS AND METHODS: Peripheral blood mononuclear cells from 15 patients with metastatic cancer (melanoma in 10, lung cancer in 2, renal cell carcinoma in 1, sarcoma in 1, breast cancer in 1) were harvested by leukapheresis after mobilization with GM-CSF (5 microg/kg/day s.c. for 4 days). Mononuclear cells were separated and cultured in GM-CSF (1000 U/ml) and interleukin-4 (1000 U/ml) for 7 days. Phenotype was assessed by 2-color flow cytometry and immunocytochemistry. On day 6, dendritic cells were pulsed with 1 g of fresh autologous tumor lysate for 24 h and infused intravenously. Interleukin-2 (6 million IU), interferon a (4 million IU) and GM-CSF (400 microg) were injected s.c. daily for 10 days beginning on the day of dendritic cell infusion. Treatment was repeated every 21 days for 3 courses. RESULTS: The morphology, immunocytochemistry and phenotype of cultured cells was consistent with dendritic cells: intense positivity for HLA-DR and CD86, with negativity for markers of other lineages, including CD3, CD4, CD8 and CD14. More than 5 x 10(7) dendritic cells were injected in all patients. Nine patients developed >5 mm delayed type cutaneous hypersensitivity reactions to tumor lysate+/-GM-CSF after the first immunization (larger than GM-CSF in all cases). Median delayed type cutaneous hypersensitivity to lysate +/- GM-CSF was 3 cm after the third immunization. One melanoma patient with skin, liver, lung and bone metastases had a partial response lasting 8 months (followed by progression in the brain). Seven patients had stable disease for >3 months, and 7 had progression. CONCLUSIONS: Infusion of tumor lysate-pulsed dendritic cells induces a strong cell-mediated antitumor immune reaction in patients with advanced cancer and has some clinical activity.

Association between cardiovascular mortality and STOP-Bang questionnaire scores in a cohort of hospitalized patients: a prospective study / Associação entre mortalidade cardiovascular e pontuação do questionário STOP-Bang em uma coorte de pacientes hospitalizados: um estudo prospectivo

ABSTRACT Objective: Obstructive sleep apnea (OSA) is associated with an increased risk of mortality and cardiometabolic diseases. The STOP-Bang questionnaire is a tool to screen populations at risk of OSA and prioritize complementary studies. Our objective was to evaluate the clinical utility of this questionnaire in identifying patients at an increased risk of mortality after discharge in a cohort of hospitalized patients. Methods: This was a prospective cohort study involving consecutive patients admitted to an internal medicine unit between May and June of 2017 who were reevaluated three years after discharge. At baseline, we collected data on comorbidities (hypertension, obesity, diabetes, and fasting lipid profile) and calculated STOP-Bang scores, defining the risk of OSA (0-2 score, no risk; ≥ 3 score, risk of OSA; and ≥ 5 score, risk of moderate-to-severe OSA), which determined the study groups. We also recorded data regarding all-cause and cardiovascular mortality at the end of the follow-up period. Results: The sample comprised 435 patients. Of those, 352 (80.9%) and 182 (41.8%) had STOP-Bang scores ≥ 3 and ≥ 5, respectively. When compared with the group with STOP-Bang scores of 0-2, the two groups showed higher prevalences of obesity, hypertension, diabetes, and dyslipidemia. Multivariate analysis showed an independent association between cardiovascular mortality and STOP-Bang score ≥ 5 (adjusted hazard ratio = 3.12 [95% CI, 1.39-7.03]; p = 0.01). Additionally, previous coronary heart disease was also associated with cardiovascular mortality. Conclusions: In this cohort of hospitalized patients, STOP-Bang scores ≥ 5 were able to identify patients at an increased risk of cardiovascular mortality three years after discharge.

RESUMO Objetivo: A apneia obstrutiva do sono (AOS) está associada a um risco maior de mortalidade e doenças cardiometabólicas. O questionário STOP-Bang é uma ferramenta para rastrear populações em risco de AOS e assim priorizar estudos complementares. Nosso objetivo foi avaliar a utilidade clínica desse questionário na identificação de pacientes com risco aumentado de mortalidade após a alta em uma coorte de pacientes hospitalizados. Métodos: Estudo de coorte prospectivo com pacientes consecutivos internados em uma unidade de medicina interna entre maio e junho de 2017 que foram reavaliados três anos após a alta. No momento basal, coletamos dados sobre comorbidades (hipertensão, obesidade, diabetes e perfil lipídico em jejum) e calculamos as pontuações no STOP-Bang, definindo o risco de OSA (pontuação 0-2, sem risco; pontuação ≥ 3, risco de AOS; e pontuação ≥ 5, risco de AOS moderada a grave), que determinou os grupos de estudo. Também registramos dados sobre mortalidade por todas as causas e mortalidade cardiovascular ao final do período de acompanhamento. Resultados: Foram incluídos 435 pacientes. Desses, 352 (80,9%) e 182 (41,8%) apresentaram pontuações no STOP-Bang ≥ 3 e ≥ 5, respectivamente. Quando comparados com o grupo com pontuação no STOP-Bang de 0-2, os outros dois grupos apresentaram prevalências mais elevadas de obesidade, hipertensão, diabetes e dislipidemia. A análise multivariada mostrou uma associação independente entre mortalidade cardiovascular e pontuação no STOP-Bang ≥ 5 (razão de risco ajustada = 3,12 [IC95%, 1,39-7,03]; p = 0,01). Além disso, doença coronariana prévia também foi associada à mortalidade cardiovascular. Conclusões: Nesta coorte de pacientes hospitalizados, pontuações no STOP-Bang ≥ 5 foram capazes de identificar pacientes com risco aumentado de mortalidade cardiovascular três anos após a alta.

Asociación entre niveles de vitamina B-12 y mortalidad en pacientes hospitalizados adultos mayores / Association between high vitamin B12 levels and one year mortality in older people admitted to the hospital

Background: Supplementation of vitamin B12 in older adults is a common practice to avoid vitamin B12 insufficiency. However, there is a paucity of information about the effects of cobalamin excess. Aim: To asses any potential effects of high levels vitamin B12 on mortality on adults aged ≥ 65 years admitted to an internal medicine service. Material and Methods: We Prospectively studied patients admitted to an internal medicine service of an academic hospital from September 2017 to September 2018, who were able to give their consent and answer questionnaires. We tabulated age, gender, medical history, comorbidity index (Charlson), frailty score (Fried scale), admission diagnosis and blood tests performed within 48 hours of admission. The primary outcome was death by any cause in less of 30 days or after one of year follow up, determined according to death certificates. Results: We included 93 patients aged 65 to 94 years (53% males). Fifteen patients died during the year of follow up (five within 30 days of admission). Those who died had higher cobalamin levels than survivors (1080.07 ± 788.09 and 656.68 ± 497.33 pg/mL respectively, p = 0.02). Patients who died had also a significantly lower corrected serum calcium, sodium (p = 0.04) and a medical history of chronic liver disease (p = 0.03). In the multivariable analysis, only vitamin B12 preserved the association with mortality (p = 0.009). Conclusions: There was a significant association between high levels of cobalamin and all-cause mortality in this group of patients aged ≥ 65 years-old.

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.

Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).