Impact of PNPLA3 and TM6SF2 polymorphisms on the prognosis of patients with MASLD and type 2 diabetes mellitus.

BACKGROUND/AIMS: Longitudinal studies assessing the impact of genetic polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are scarce. This study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic and extrahepatic outcomes in T2DM-MASLD individuals. METHODS: Patients' polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and CT + TT; combined comparing no mutant allele, one allele G or T or ≥2 alleles G or T. Hierarchical models were built to assess associations between polymorphisms and outcomes, independently of confounding factors. Multivariate logistic regression was used for cirrhosis and its complications and extrahepatic cancer, and Cox regression for cardiovascular events (CVEs) and all-cause mortality. RESULTS: In total, 407 T2DM-MASLD patients (62.1 ± 10.5 years, 67.6% women) were followed for 11 (6-13) years. Having at least one G or T allele independently increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if two or more risk alleles were present (OR 18.48; 95% CI 6.15-55.58; p < .001). Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 CT + TT, also with an even higher risk when two or more risk alleles were present in the combined evaluation (OR 27.20; 95% CI 5.26-140.62; p < .001). There were no associations with CVEs or mortality outcomes. CONCLUSION: In T2DM, PNPLA3 and TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an increased risk of cirrhosis and its complications.

Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis. METHODS: This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs. RESULTS: 161 T2D offspring and 78 controls, 10-46 years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034). CONCLUSIONS: The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.

Psoriasis and steatotic liver disease: Are PNPLA3 and TM6SF2 polymorphisms suitable for the hepato-dermal axis hypothesis?

INTRODUCTION AND OBJECTIVES: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. MATERIALS AND METHODS: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan®, Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP ≥275 dB/m and advanced liver fibrosis as transient elastography ≥10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. RESULTS: One hundred and ninety-nine patients were enrolled (age 54.6 ± 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. CONCLUSIONS: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis.

Ethical regulation of biomedical research in Brazil: a quality improvement initiative.

BACKGROUND: Q-CEP (Qualificação dos Comitês de Ética em Pesquisa que compõem o Sistema CEP/Conep) is a nationwide project resulting from a partnership between the Brazilian National Research Ethics Commission (Conep), the Ministry of Health and Hospital Moinhos de Vento (HMV). It was developed to consolidate policy for ethical review of research with human beings in all members of the CEP/Conep System, Brazil's national system of institutional review boards. The aim of this study was therefore to report on the experience and results of the Q-CEP project. METHODS: An observational, retrospective study includes data from the Q-CEP, obtained from visits to all the institutional research ethics committees (RECs) in the country. The actions implemented by Q-CEP were part of a two-step process: (i) training visits to each REC; (ii) development of distance learning modules on strategic topics pertaining to research ethics evaluation. The data presented herein cover step one (training visits), defined by Q-CEP as the diagnostic stage of the project. For a country with social and economics inequalities such as Brazil, this is a particularly important stage; an accurate picture of reality is needed to inform planning of quality improvement strategies. RESULTS: In 2019-2021, Q-CEP visited 832 RECs and trained 11,197 people. This sample covered almost all active RECs in the country; only 4 (0.5%) were not evaluated. Of the 94 items evaluated, 62% did not reach the target of at least 80% compliance and around 1/4 (26%) were below 50% compliance. The diagnostic stage of the process revealed inadequacies on the part of the RECs in their ethical reviews. The analysis of informed consent forms showed compliance in only 131 RECs (15.74%). The description of pending issues made by RECs in their reports was compliant in 19.33% (n = 161). Administrative and operational aspects were also considered inadequate by more than half of the RECs. CONCLUSIONS: Overall, Brazilian RECs showed poor compliance in several aspects of their operation, both in ethics evaluation and in other processes, which justifies additional training. The Q-CEP project is part of a quality improvement policy promoted by the Brazilian Ministry of Health. The data obtained in the diagnostic step of the project have contributed to the qualification and consolidation of one of the world's largest research ethics evaluation systems.

Adiponectin and leptin gene variants and their effects on body weight trajectories in children from birth to 6 years of age: the PREDI Study.

Excess body weight confers a high risk to human health. Body weight variation between subjects can be partially explained by genetic differences. The aim of the present study was to investigate the association of genetic variants in the ADIPOQ (rs2241766) and LEP (rs7799039) genes with body weight trajectories in children from birth to 6 years of age. This was a prospective cohort (PREDI Study). Socio-economic, biological and anthropometric data were collected at four time points: at birth in the maternity unit; 1-2, 4-5 and 6 years old at the participants' homes. Genotyping was performed by PCR-restriction fragment length polymorphism. Poisson regression and linear mixed-effect regression models were used to address the association of ADIPOQ and LEP genotypes with BMI. Excessive body weight at pre-pregnancy (ß = 0·339, P = 0·01) and excessive gestational weight gain (ß = 0·51, P < 0·001) were associated with children's BMI trajectory from birth to 6 years. The ADIPOQ-rs2241766 TG or GG genotype was associated with a higher risk of excess body weight in the first 6 years of life (both sexes relative risk 1·25, 95 % CI 1·01, 1·56; female relative risk 1·67, 95 % CI 1·20, 2·31). BMI increased over the years according to the presence of the TG or GG genotype (ß = 0·01, 95 % CI 0·01, 0·02), particularly in females (ß = 0·02, 95 % CI 0·01, 0·04). The ADIPOQ-rs2241766 TG and GG genotypes increased the risk of excess body weight in children from birth to 6 years of age and had a positive effect on body weight trajectories in girls. The LEP-rs7799039 genetic variant was not associated with body weight trajectory in children.

Ischemic Stroke and Genetic Variants: In Search of Association with Severity and Recurrence in a Brazilian Population.

OBJECTIVE: The aim of this study was to investigate the relationship between genetic variants in candidate genes and clinical severity and prognosis (recurrence) of ischemic stroke (IS) in a Brazilian population. METHODS: This was a retrospective study based on clinical and demographic data retrieved from the JOINVASC cohort-Epidemiological Study on Cerebrovascular Diseases in Joinville and on respective DNA samples available at the Joinville Stroke Biobank, over the period 2010-2015. Four hundred and thirty-five subjects were included. Patients were divided into large artery atherosclerosis (195 cases) and cardioembolic IS (240 cases) subgroups according to Trial of Org 10172 in the Acute Stroke Treatment standards. The severity of the event was established from the score obtained using the National Institutes of Health Stroke Scale. The genotypic and allelic frequencies of each variant were acquired by Real-Time Polymerase Chain Reaction. The codominance model was considered for the analysis of the genotypes' influence. RESULTS: There was no association between clinical severity and recurrence with variants rs2383207 (CDKN2B-AS1) for atherothrombotic IS and variants rs879324 (ZFHX3), rs966221 (PDE4D), and rs152312 (PDE4D) for cardioembolic IS. The variants rs1396476, rs2910829, rs6843082, and rs2107595 were not in Hardy-Weinberg equilibrium in the evaluated population. CONCLUSIONS: Although this study failed to identify an association between genetic variants and clinical response variability, the need to carry out related studies with larger number of cases covering other populations and genetic variants remains, which would allow the uncovering of hypothetical genetic factors governing stroke outcomes and recurrence.

Association between FTO gene polymorphism and excess body weight in women from before to after pregnancy: A cohort study.

OBJECTIVE: The aim of this study was to examine the influence of the FTO-rs9939609 polymorphism on excess body weight in women during the reproductive transition from pre- to post-pregnancy. METHODS: This was a prospective cohort study covering a period extending from before pregnancy to 2 and 4 years after pregnancy. A total of 435 women were first included in the study and, at last follow-up, 220 of them continued to participate in the study. The FTO-rs9939609 polymorphism was analyzed by the polymerase chain reaction/ restriction fragment length polymorphism (PCR/RFLP) method. RESULTS: The FTO-rs9939609 polymorphism was associated with increasing weight and body mass index (BMI) during the follow-up period. Women carrying at least 1 risk allele (A) were significantly heavier (P < .05, up to 4.24 kg) and had a 1.30 kg/m2 higher BMI. Although the AA genotype was significantly associated with a greater risk compared to the wild-type genotype in the cross-sectional analysis, the results did not differ significantly in the longitudinal analysis (AA genotype, ß = 1.20, 95% CI 0.85-1.68), even after adjustment for pre-pregnancy age, smoking before pregnancy, parity at pregnancy, and gestational weight gain. CONCLUSIONS: The FTO-rs9939609 polymorphism was associated with increased weight and BMI in mothers before and after pregnancy. However, we found no significant effect of the polymorphism on excess body weight of women during the reproductive trajectory.

Alternatives of informed consent for storage and use of human biological material for research purposes: Brazilian regulation.

Informed consent is recognized as a primary ethical requirement to conduct research involving humans. In the investigations with the use of human biological material, informed consent (IC) assumes a differentiated condition on account of the many future possibilities. This work presents suitable alternatives for IC regarding the storage and use of human biological material in research, according to new Brazilian regulations. Both norms - Resolution 441/11 of the National Health Council, approved on 12 May 2011, and Ordinance 2.201 (NATIONAL GUIDELINES FOR BIOREPOSITORIES AND BIOBANKS OF HUMAN BIOLOGICAL MATERIAL FOR RESEARCH PURPOSE) of the Brazil Ministry of Health, approved on 14 September 2011 - state that the consent of subjects for the collection, storage and use of samples stored in Biobanks is necessarily established by means of a Free and Informed Consent Form (ICF). In order to obtain individual and formal statements, this form should contain the following two mutually exclusive options: an explanation about the use of the stored material in each research study, and the need for new consent or the waiver thereof when the material is used for a new study. On the other hand, ICF suitable for Biorepositories must be exclusive and related to specific research. Although Brazilian and international regulations identify the main aspects to be included in the IC, efforts are still necessary to improve the consent process, so that the document will become a bond of trust between subject and researcher.

Exploring the sex-associated differences in molars fused roots.

BACKGROUND: Human sexual dimorphism is associated with many biological characteristics, including dental variables. OBJECTIVES: To investigate if molars fused roots present sex-associated differences. METHODS: Panoramic radiographs were used to investigate the frequency and distribution of permanent molars fused roots. Only patients with all first and second permanent molars were included. Third molars were not investigated. Any molar with roots fused apical to the usual furcal position were considered molar fused roots. Comparisons between males and females were performed using chi-square or Fisher's and Mann-Whitney tests and the established alpha was 5% (p<0.05). Sex-differential liability models were also proposed. RESULTS: A total of 84 males and 86 females were included and 1360 molars were analyzed. Among them, 46 (26.06%) present at least one molar with fused root. Second maxillary molars were the most affected teeth. There was an association between sex and molars with fused roots. Females had a 3.4 higher chance to present fused roots than males (OR=3.4, CI 95% 1.6-6.8; p=0.0008). The female: male ratio of molars with fused roots was 2.5:1. The number of molars with fused roots ranged from 1 to 6 per patient, and the mean number of Females presented more molars with fused roots (mean = 1.01; standard deviation = 1.52) than males (mean = 0.31; standard deviation = 0.85) (p<0.05). CONCLUSIONS: Molar fused root of permanent teeth presents sex-associated differences, in which females are more affected than males. Our results support sex-differential liability models for molars fused roots.

Effects of the Paris System on the Unsatisfactory Category in a Cytohistologic Correlation Study of Patients With Urothelial Carcinoma.

CONTEXT.­: The main objectives of the Paris System are to detect high-grade urothelial carcinoma, to standardize morphologic criteria and the cytopathologic report, to reduce the prevalence of the atypia category, and to improve the malignancy risk stratification. OBJECTIVE.­: To compare the results and sensitivity of cytologic classification before and after reclassification by the Paris System. DESIGN.­: Urinary cytology samples from patients with a histologic diagnosis of urothelial carcinoma were reclassified on the basis of the Paris System categories. The diagnoses before reclassification were divided into 5 categories (A, B, C, D, E) and compared with the Paris System (I, II, III, IV, V). Sensitivity was calculated considering cytohistologic agreement in relation to high-grade urothelial carcinoma. RESULTS.­: A total of 111 urinary cytology samples from patients were analyzed, corresponding to 40 histologic samples; of these, 12 (30%) were high grade and the remaining were low grade. Comparison of the correlated categories showed an increase from 3 (3 of 111; 2.7%) (A) to 31 (31 of 111; 27.9%) (I) in unsatisfactory cases and a decrease from 67 (67 of 111; 60,0%) to 30 (30 of 111; 27.0%) in negative cases, while the atypia category remained unchanged (15 cases [15 of 111; 13.5%]) (C and III). Suspicious cases increased from 5 (5 of 111; 4.5%) (D) to 14 (14 of 111; 12.6%) (IV) and cases of urothelial carcinoma were unchanged (21 cases [21 of 111; 18.9%]) (E and V). Sensitivity was 69% for the previous classification and 90% for the Paris System. CONCLUSIONS.­: The Paris System improved the sensitivity of urinary cytology and the standardization of the unsatisfactory criteria, with an increase of cases in this category and a decrease of cases previously classified as negative among patients with a subsequent histologic diagnosis of urothelial carcinoma.

Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil.

BACKGROUND: The spread of carbapenemase- and extended-spectrum ß-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of ß-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. METHODS: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The ß-lactamase-encoding genes were investigated using polymerase chain reaction. RESULTS: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-ß-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. CONCLUSIONS: C/A and C/T were active against microorganisms with ß-lactam-resistant phenotypes, except when resistance was mediated by metallo-ß-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more ß-lactamase-encoding genes (62.5% and 77.4%, respectively).

Urgent vs. planned peritoneal dialysis initiation: complications and outcomes in the first year of therapy.

INTRODUCTION: Urgent-start peritoneal dialysis (US-PD) has been proposed as a safe modality of renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients with an indication for emergency dialysis initiation. We aimed to compare the characteristics, 30-day complications, and clinical outcomes of US-PD and planned peritoneal dialysis (Plan-PD) patients over the first year of therapy. METHODS: This was a single-center retrospective study that included incident adult patients followed for up to one year. US-PD was considered when incident patients started therapy within 7 days after Tenckhoff catheter implantation. Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Mechanical and infectious complications were compared 30 days from PD initiation. Hospitalization and technique failure during the first 12 months on PD were assessed by Kaplan-Meier curves and the determinants were calculated by Cox regression models. RESULTS: All patients starting PD between October/2016 and November/2019 who fulfilled the inclusion criteria were analyzed. We evaluated 137 patients (70 in the US-PD x 67 Plan-PD). The main complications in the first 30 days were catheter tip migration (7.5% Plan-PD x 4.3% US-PD - p= 0.49) and leakage (4.5% Plan-PD x 5.7% US-PD - p=0.74). Most catheters were placed using the Seldinger technique. The main cause of dropout was death in US-PD patients (15.7%) and transfer to HD in Plan-PD patients (13.4%). The occurrence of complications in the first 30 days was the only risk factor for dropout (OR = 2.9; 95% CI 1.1-7.5, p = 0.03). Hospitalization rates and technique survival were similar in both groups. CONCLUSION: The lack of significant differences in patients' outcomes between groups reinforces that PD is a safe and applicable dialysis method in patients who need immediate dialysis.

Demographic history differences between Hispanics and Brazilians imprint haplotype features.

Admixture is known to greatly impact the genetic landscape of a population and, while genetic variation underlying human phenotypes has been shown to differ among populations, studies on admixed subjects are still scarce. Latin American populations are the result of complex demographic history, such as 2 or 3-way admixing events, bottlenecks and/or expansions, and adaptive events unique to the American continent. To explore the impact of these events on the genetic structure of Latino populations, we evaluated the following haplotype features: linkage disequilibrium, shared identity by descent segments, runs of homozygosity, and extended haplotype homozygosity (integrated haplotype score) in Latinos represented in the 1000 Genome Project along with array data from 171 Brazilians sampled in the South and Southeast regions of Brazil. We found that linkage disequilibrium decay relates to the amount of American and African ancestry. The extent of identity by descent sharing positively correlates with historical effective population sizes, which we found to be steady or growing, except for Puerto Ricans and Colombians. Long runs of homozygosity, a particular instance of autozygosity, was only enriched in Peruvians and Native Americans. We used simulations to account for random sampling and linkage disequilibrium to filter positive selection indexes and found 244 unique markers under selection, 26 of which are common to 2 or more populations. Some markers exhibiting positive selection signals had estimated time to the most recent common ancestor consistent with human adaptation to the American continent. In conclusion, Latino populations present highly divergent haplotype characteristics that impact genetic architecture and underlie complex phenotypes.

ABO blood group system and occurrence of ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a multifactorial disease that presents high rates of morbimortality in Brazil. Several studies proved that there is a link between the ABO blood group system and the occurrence of thrombotic events. Nonetheless, its association with IS is not well established. OBJECTIVE: For that reason, the purpose hereof was to investigate the relation between the ABO blood groups and the occurrence of IS in a Brazilian cohort of cerebrovascular diseases. METHODS: Five hundred and twenty-nine subjects were included over 12 months, from which 275 presented an IS episode and 254 composed the control group. Blood samples were drawn for direct and reverse serotyping. The control and IS groups were compared regarding the traditional risk factors and the distribution of the ABO blood groups. RESULTS: The IS group presented a higher prevalence of systemic arterial hypertension (SAH), diabetes mellitus, smoking habits, family history, cardiopathy, and sedentary lifestyle in comparison with the control group. The AB blood type prevailed among the patients (5.1 vs. 1.6%; p<0.05) and this group had more SAH cases in comparison with the O type group (92.9 vs. 67.3%; p<0.05). CONCLUSIONS: Our results suggest that the occurrence of IS is more frequent among patients of the AB blood type.

Association and interaction of genetic variants with occurrence of ischemic stroke among Brazilian patients.

Ischemic Stroke (IS) is a severe and complex disorder of high morbidity and mortality rates associated with clinical, environmental, and genetic predisposing factors. Despite previous studies have associated genetic variants to stroke, inconsistent results from different populations pointed to the genetic heterogeneity for IS. Therefore, we may hypothesize that an interaction effect among genetic variants could contribute to IS occurrence rather than genetic variants independently. In this context, we investigated the association and interaction between genetic variants and large-artery atherosclerosis IS (LAAS-IS) and cardioembolic IS (CE-IS). We genotyped 435 patients (195 LAAS-IS; 240 CE-IS) and 535 controls from a population of Joinville, Santa Catarina, Brazil. Association and interaction analysis were performed by chi-square test and Multifactor-dimensionality Reduction test. We found an association between rs2383207*A allele, nearby CDKN2B-AS1, and LAAS-IS [OR 2.35 (95% CI = 1.79-3.08); p = 4.66 × 10-10]. We found an interaction among rs2910829, rs966221 and rs152312, with an accuracy of 0.62 (p = 4.3 × 10-5) demonstrating the interaction effect among variants from different genes can contribute to CE-IS risk. Further prediction analysis confirmed that clinical information, such as hypertension and dyslipidemia, presented high accuracy to predict LAAS-IS (86.47%) and CE-IS (90.47%); however, the inclusion of genetic variant information did not increase the accuracy.

Characteristics and predictors of chronic critical illness in the intensive care unit. / Características e preditores de doença crítica crônica na unidade de terapia intensiva.

OBJECTIVE: To characterize patients with chronic critical illness and identify predictors of development of chronic critical illness. METHODS: Prospective data was collected for 1 year in the intensive care unit of a general hospital in Southern Brazil. Three logistic regression models were constructed to identify factors associated with chronic critical illness. RESULTS: Among the 574 subjects admitted to the intensive care unit, 200 were submitted to mechanical ventilation. Of these patients, 85 (43.5%) developed chronic critical illness, composing 14.8% of all the patients admitted to the intensive care unit. The regression model that evaluated the association of chronic critical illness with conditions present prior to intensive care unit admission identified chronic renal failure in patients undergoing hemodialysis (OR 3.57; p = 0.04) and a neurological diagnosis at hospital admission (OR 2.25; p = 0.008) as independent factors. In the model that evaluated the association of chronic critical illness with situations that occurred during intensive care unit stay, muscle weakness (OR 2.86; p = 0.01) and pressure ulcers (OR 9.54; p < 0.001) had the strongest associations. In the global multivariate analysis (that assessed previous factors and situations that occurred in the intensive care unit), hospital admission due to neurological diseases (OR 2.61; p = 0.03) and the development of pressure ulcers (OR 9.08; p < 0.001) had the strongest associations. CONCLUSION: The incidence of chronic critical illness in this study was similar to that observed in other studies and had a strong association with the diagnosis of neurological diseases at hospital admission and chronic renal failure in patients undergoing hemodialysis, as well as complications developed during hospitalization, such as pressure ulcers and muscle weakness.

OBJETIVO: Caracterizar os pacientes com doença crítica crônica e identificar os preditores relacionados à evolução para doença crítica crônica. MÉTODOS: Coleta prospectiva de dados por 1 ano realizada na unidade de terapia intensiva de um hospital geral localizado na Região Sul do país. Construíram-se três modelos de regressão logística para identificar os fatores associados com doença crítica crônica. RESULTADOS: Dentre os 574 pacientes admitidos à unidade de terapia intensiva durante o período do estudo, 200 foram submetidos à ventilação mecânica. Destes, 85 (43,5%) pacientes desenvolveram doença crítica crônica, totalizando 14,8% de todos os pacientes admitidos à unidade de terapia intensiva. O modelo de regressão que avaliou os fatores prévios à admissão à unidade de terapia intensiva associados com doença crítica crônica identificou insuficiência renal crônica submetida à diálise (OR 3,57; p = 0,04) e diagnóstico neurológico quando da admissão ao hospital (OR 2,25; p = 0,008) como fatores independentes. No modelo que avaliou a associação de doença crítica crônica com situações ocorridas durante a permanência na unidade de terapia intensiva, destacaram-se fraqueza muscular (OR 2,86; p = 0,01) e úlceras por pressão (OR 9,54; p < 0,001). Na análise multivariada global (fatores prévios e situações ocorridas durante a permanência na unidade de terapia intensiva), destacaram-se admissão ao hospital por doenças neurológicas (OR 2,61; p = 0,03) e desenvolvimento de úlceras por pressão (OR 9,08; p < 0,001). CONCLUSÃO: A incidência de doença crítica crônica foi similar à observada em outros estudos e teve associação mais forte com o diagnóstico de doenças neurológicas quando da admissão ao hospital e insuficiência renal crônica submetida à hemodiálise, assim como com complicações desenvolvidas durante a hospitalização, como úlceras por pressão e fraqueza muscular.

Earliest identification of New Delhi metallo-ß-lactamase 1 (NDM-1) in Acinetobacter pittii in Brazil.

We report the occurrence in Brazil of the bla NDM-1 gene in Acinetobacter pittii, prior to the previously described first reports regarding the species Providencia rettgeri and Enterobacter hormaechei. Clinical isolates were investigated by polymerase chain reaction followed by bidirectional sequencing, and species was confirmed by 16S rDNA sequencing and matrix-assisted laser desorption-ionization time-of-flight spectrometry. A. pittii carrying bla NDM-1 was confirmed in a patient with no national or international travel history, or transfer from another hospital. The findings warn of the possibility of silent spread of bla NDM-1 to the community.

Cohorting to prevent acquisition of multidrug-resistant bacteria: An interrupted time series study.

BACKGROUND: Grouping patients who acquired resistant microorganisms within a single area (cohorting) has been used to prevent cross-transmission. We aimed to assess cohorting effectiveness in the absence of an outbreak. METHODS: An interrupted time series study was performed in a general hospital considering patients admitted to wards. In the first year, patients who acquired multidrug-resistant (MDR) bacteria were isolated without physical transfer. In the second year, cohorting was implemented, and patients with mixed MDR bacteria were transferred to individual rooms in a specific isolation unit. Cultures were requested upon clinician orders, and surveillance or routine cultures were not performed. The effect of cohorting on the incidence density of MDR bacteria acquisition was assessed using segmented regression analysis. RESULTS: In the first and second years, 2.0 and 2.8 cases per 1,000 patient-days acquired MDR bacteria. The length of hospitalization and mortality rate were similar between phases. There was a linear increase of the monthly incidence densities of MDR bacteria acquisition in the first year (ß1: 0.11; 95% confidence interval [CI]: -0.02 to 0.24), though without an immediate impact of cohorting (ß2: -1.32; 95% CI: -3.81 to 1.16) or a change in the temporal trend (ß3: 0.04; 95% CI: -0.14 to 0.23) from the first to second phase. CONCLUSION: Cohorting may not reduce the incidence density of MDR bacteria acquisition in the absence of an outbreak.

Accuracy of Intraoperative Examination in Central Nervous System Lesions: A Study of 133 Cases.

OBJECTIVE: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions. STUDY DESIGN: Retrospective analysis of intraoperative examination of CNS lesions and their final diagnosis obtained during 16 consecutive years. All diagnoses were reviewed and classified according to World Health Organization (WHO) grading for CNS tumors. Squash was performed in 119 cases, while frozen section and both methods were done in 7 cases each. RESULTS: Among the 133 intraoperative examinations considered, 114 (85.7%) presented concordance and 19 (14.3%) diagnostic disagreement when compared with subsequent histopathological examinations. The sensitivity and specificity for the detection of neoplasia in intraoperative examination was 98 and 94%, respectively. The positive and negative predictive values were 99 and 88%, respectively. The accuracy for neoplastic and nonneoplastic disease was 85.7%. Disagreements were more frequent among low-grade (WHO grades I and II) neoplasms and nonmalignant cases. CONCLUSIONS: Our results showed good accuracy of the intraoperative assessments for diagnosis of CNS lesions, particularly in high-grade (grades III and IV) lesions and metastatic neoplasms.

Prevalence of atrial fibrillation without diagnosis or treatment in Primary Health Care in Joinville, Brazil

Introduction: Estimation of the prevalence of undiagnosed or untreated atrial fibrillation (AF) is crucial for the prevention of AF-related ischemic stroke. Objective: To assess the prevalence of undiagnosed or untreated AF in primary care. Methods: We conducted a prospective cross-sectional non-randomized study in Joinville, Brazil, among elderly individuals in primary care units (PCUs). Results: One thousand individuals were included, with a mean age of 69±7 years, and 57% women. Prevalence of AF was 3%, with 50% of AF patients being previously undiagnosed and 33% of previously diagnosed AF patients not receiving oral anticoagulation despite clinical indication. Using agestandardized prevalences, we estimated 68 and 27,342 strokes per year due to untreated or undiagnosed AF in Joinville and Brazil, respectively. Conclusion: The observation that two out of three AF patients were either undiagnosed or untreated is very alarming. Screening strategies to uncover this population are urgently needed.