17ß-estradiol and methylprednisolone association as a therapeutic option to modulate lung inflammation in brain-dead female rats.

Introduction: Brain death (BD) is known to compromise graft quality by causing hemodynamic, metabolic, and hormonal changes. The abrupt reduction of female sex hormones after BD was associated with increased lung inflammation. The use of both corticoids and estradiol independently has presented positive results in modulating BD-induced inflammatory response. However, studies have shown that for females the presence of both estrogen and corticoids is necessary to ensure adequate immune response. In that sense, this study aims to investigate how the association of methylprednisolone (MP) and estradiol (E2) could modulate the lung inflammation triggered by BD in female rats. Methods: Female Wistar rats (8 weeks) were divided into four groups: sham (animals submitted to the surgical process, without induction of BD), BD (animals submitted to BD), MP/E2 (animals submitted to BD that received MP and E2 treatment 3h after BD induction) and MP (animals submitted to BD that received MP treatment 3h after BD induction). Results: Hemodynamics, systemic and local quantification of IL-6, IL-1ß, VEGF, and TNF-α, leukocyte infiltration to the lung parenchyma and airways, and adhesion molecule expression were analyzed. After treatment, MP/E2 association was able to reinstate mean arterial pressure to levels close to Sham animals (p<0.05). BD increased leukocyte infiltration to the airways and MP/E2 was able to reduce the number of cells (p=0.0139). Also, the associated treatment modulated the vasculature by reducing the expression of VEGF (p=0.0616) and maintaining eNOS levels (p=0.004) in lung tissue. Discussion: Data presented in this study show that the association between corticoids and estradiol could represent a better treatment strategy for lung inflammation in the female BD donor by presenting a positive effect in the hemodynamic management of the donor, as well as by reducing infiltrated leukocyte to the airways and release of inflammatory markers in the short and long term.

Effectiveness of dose-intensified salvage regimens versus standard-dose chemotherapy on progression-free survival in early progressed follicular lymphoma before autologous stem cell transplantation: a systematic review protocol.

OBJECTIVE: This review will evaluate the effectiveness of dose-intensified versus standard-dose salvage regimens on progression-free survival in early progressed follicular lymphoma before high-dose chemotherapy and autologous stem cell transplantation. INTRODUCTION: Despite the substantial advances in the management of follicular lymphoma, approximately 20% of patients experience progression of the disease within 2 years of induction therapy. These patients have worse outcomes, and autologous stem cell transplantation is deemed to improve outcomes in this context. Little is known about the optimal salvage regimen. INCLUSION CRITERIA: Studies must include patients ≥18 years old with early progressed follicular lymphoma who were submitted to autologous stem cell transplantation in subsequent remission. Clinical trials and observational studies will be included. METHODS: The search strategy will be carried out in MEDLINE (PubMed), Embase (Periódicos CAPES), Scopus, Web of Science, LiLACS, and the Cochrane Library. No date or language restrictions will be imposed. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis will be used. Studies should score at least 50% in accordance with the critical appraisal tool. Data will be pooled whenever possible using the random effects model. Heterogeneity will be assessed using the standard χ2 and I2 tests. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in the meta-analysis. The GRADE approach will be used to rate certainty of evidence. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022373345.

Ultrasound-Guided Peripheral Venipuncture Decreases the Procedure's Pain and Positively Impacts Patient's Experience: The PRECISE Randomized Clinical Trial.

This study aimed to compare patients' experience of pain during ultrasound (US)-guided peripheral venipuncture versus conventional peripheral venipuncture. This randomized clinical trial was conducted at a public university hospital in 2021. Adult patients with indication for intravenous therapy compatible with peripheral intravenous catheters (PIVCs) were included: intervention group (IG), US peripheral venipuncture executed by specialist nurses; control group (CG), conventional peripheral venipuncture executed by clinical practice nurses. The primary outcome was patient experience of pain during the procedure and patient experience related to the PIVC placement method. Sixty-four patients were included, 32 for each group. The pain experienced was none-to-mild in the IG for 25 patients (78.1%) and moderate-to-severe in the CG for 21 patients (65.7%; P < .001). The overall pain rating was 2 (1-3) in the IG and 4 (3-6) in the CG (P < .001). The recommendation of the procedure in IG (net promoter score [NPS] + 90.6%) versus CG (NPS + 18.8%) was considered excellent and good, respectively (P < .001). Patients had less pain and significantly recommended the US-guided procedure. Patient experience with US-guided PIVC, performed by a specialist nurse, was superior to that of conventional peripheral venipuncture.

COVID-19-Associated Cognitive Biases on Pneumonia Differential Diagnosis.

The coronavirus disease 2019 (COVID-19) pandemic favors cognitive biases such as anchoring and availability biases. The first refers to overvaluing some of the initial information and establishing a diagnosis too early, with resistance to future adjustments. The latter happens when diagnoses more frequently considered are regarded as more common in reality. This case, in which the correct diagnosis was delayed due to these biases, highlights the need to remain aware of them as a means toward timely diagnosis and therapeutic success of pneumonia cases. An 84-year-old woman presented with a mild non-productive cough for two months and fever. She had a history of breast carcinoma treated with radiotherapy in the previous year. Computerized tomography (CT) showed extensive bilateral consolidation foci with ground-glass-opacification areas and bilateral pleural effusion, CO-RADS 3. COVID-19 with bacterial superinfection was suspected and levofloxacin was initiated. Nasopharyngeal swab polymerase chain reaction (PCR) was carried out three times, always negative for SARS-CoV-2. As the patient remained with fever and cough, the antibiotic was escalated to piperacillin/tazobactam and then to meropenem/vancomycin. She underwent bronchofibroscopy and alveolar lavage, with negative SARS-CoV-2 PCR. The re-evaluation CT scan maintained bilateral consolidations, with an aerial bronchogram. The biopsy of pulmonary consolidation allowed the diagnosis of radiation-induced organizing pneumonia. Prednisolone was initiated and achieved clinical remission and radiological improvement. This case highlights the need to remain aware of cognitive biases both when COVID-19 is suspected or ruled out and to consider other diagnoses when there is a lack of therapeutic response.

Factors associated with older adults' cognitive decline 6 months after gamma-variant SARS-CoV-2 infection.

Background: Cognitive deficits are commonly reported after COVID-19 recovery, but little is known in the older population. This study aims to investigate possible cognitive damage in older adults 6 months after contracting COVID-19, as well as individual risk factors. Methods: This cross-sectional study involved 70 participants aged 60-78 with COVID-19 6 months prior and 153 healthy controls. Montreal Cognitive Assessment-Basic (MoCA-B) screened for cognitive impairment; Geriatric Depression Scale and Geriatric Anxiety Inventory screened for depression and anxiety. Data were collected on demographics and self-reports of comorbid conditions. Results: The mean age of participants was 66.97 ± 4.64 years. A higher proportion of individuals in the COVID group complained about cognitive deficits (χ2 = 3.574; p = 0.029) and presented with deficient MoCA-B scores (χ2 = 6.098, p = 0.014) compared to controls. After controlling for multiple variables, all the following factors resulted in greater odds of a deficient MoCA-B: COVID-19 6-months prior (OR, 2.44; p = 0.018), age (OR, 1.15; p < 0.001), lower income (OR, 0.36; p = 0.070), and overweight (OR, 2.83; p = 0.013). Further analysis pointed to individual characteristics in COVID-19-affected patients that could explain the severity of the cognitive decline: age (p = 0.015), lower income (p < 0.001), anxiety (p = 0.049), ageusia (p = 0.054), overweight (p < 0.001), and absence of cognitively stimulating activities (p = 0.062). Conclusion: Our study highlights a profile of cognitive risk aggravation over aging after COVID-19 infection, which is likely mitigated by wealth but worsened in the presence of overweight. Ageusia at the time of acute COVID-19, anxiety, being overweight, and absence of routine intellectual activities are risk factors for more prominent cognitive decline among those infected by COVID-19.

Assessment of myocardial strain patterns in patients with left bundle branch block using cardiac magnetic resonance.

Recently, a classification with four types of septal longitudinal strain patterns was described using echocardiography, suggesting a pathophysiological continuum of left bundle branch block (LBBB)-induced left ventricle (LV) remodeling. The aim of this study was to assess the feasibility of classifying these strain patterns using cardiovascular magnetic resonance (CMR), and to evaluate their association with LV remodeling and myocardial scar. Single center registry included LBBB patients with septal flash (SF) referred to CMR to assess the cause of LV systolic dysfunction. Semi-automated feature-tracking cardiac resonance (FT-CMR) was used to quantify myocardial strain and detect the four strain patterns. A total of 115 patients were studied (age 66 ± 11 years, 57% men, 28% with ischemic heart disease). In longitudinal strain analysis, 23 patients (20%) were classified in stage LBBB-1, 37 (32.1%) in LBBB-2, 25 (21.7%) in LBBB-3, and 30 (26%) in LBBB-4. Patients at higher stages had more prominent septal flash, higher LV volumes, lower LV ejection fraction, and lower absolute strain values (p < 0.05 for all). Late gadolinium enhancement (LGE) was found in 55% of the patients (n = 63). No differences were found between the strain patterns regarding the presence, distribution or location of LGE. Among patients with LBBB, there was a good association between strain patterns assessed by FT-CMR analysis and the degree of LV remodeling and LV dysfunction. This association seems to be independent from the presence and distribution of LGE.

Validation of the SCORE2 risk prediction algorithm in a Portuguese population: A new model to estimate 10-year cardiovascular disease incidence in Europe.

INTRODUCTION AND OBJECTIVES: Subjects without cardiovascular (CV) disease (CVD) may suffer from subclinical atherosclerosis, and are at increased risk for atherosclerotic CV events (ASCVE). The ESC/EAS risk SCORE was updated by SCORE2, which estimates 10-year risk of fatal and non-fatal CVD in European populations aged 40-69 years without established CVD or diabetes. Our aim was to compare the two ESC/EAS risk scores and to validate SCORE2 in our population. METHODS: A total of 1071 individuals (age 57.2±6.1 years; 75.2% male) without CVD or diabetes, from GENEMACOR study controls, were analyzed over 5.4±3.9 years. The population was stratified into risk categories according to the two scores, and the area under the ROC curve (AUC) and Harrell's C-index assessed the scores' performance. Calibration was performed using the goodness-of-fit test, and occurrence of the first event assessed by Cox regression. Kaplan-Meier analysis estimated SCORE2 survival. RESULTS: SCORE stratified subjects into four risk categories: low (7.4%), moderate (46.5%), high (25.3%) and very high (20.8%), and SCORE2 into three: low-to-moderate (24.7%), high (59.0%) and very high (16.2%). SCORE presented good discrimination for CV mortality (AUC=0.838; C-index=0.834, 95% CI: 0.728-0.940), as did SCORE2 for total CV events (AUC=0.744; C-index=0.728, 95% CI: 0.648-0.808). Calibration did not show a disparity between observed and expected ASCVE. The probability of ASCVE was eight times higher in very-high-risk SCORE2 (p=0.001), and three times in the high-risk group (p=0.049). Event-free survival was 99%, 90% and 72% in the low-to-moderate, high and very-high-risk categories, respectively (p<0.0001). CONCLUSIONS: SCORE2 improved population stratification by identifying higher-risk patients, enabling early preventive measures. It showed good discriminative ability for all ASCVE.

Peripherally Inserted Central Catheter Versus Centrally Inserted Central Catheter for In-Hospital Infusion Therapy: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the comparative effectiveness and cost-effectiveness of peripherally inserted central catheters (PICCs) compared with centrally inserted central catheters (CICCs). METHODS: Prospective cohort study was followed by an economic analysis over a 30-day time horizon. Propensity score matching was used to select hospitalized adults with similar indications for PICC or CICC. The composite outcome was device removal or replacement because of complications before the end of treatment. The economic evaluation was based on a decision tree model for cost-effectiveness analysis, with calculation of the incremental cost-effectiveness ratio (ICER) per catheter removal avoided. All costs are presented in Brazilian reais (BRL) (1 BRL = 0.1870 US dollar). RESULTS: A total of 217 patients were followed in each group; 172 (79.3%) of those receiving a PICC and 135 (62.2%) of those receiving a CICC had no device-related complication, respectively. When comparing the events leading to device removal, the risk of composite endpoint was significantly higher in the CICC group (hazard ratio 0.20; 95% CI 0.11-0.35). The cost of PICC placement was BRL 1290.98 versus BRL 467.16 for a CICC. In the base case, the ICER for placing a PICC instead of a CICC was BRL 3349.91 per removal or replacement avoided. On univariate sensitivity analyses, the model proved to be robust within an ICER range of 2500.00 to 4800.00 BRL. CONCLUSIONS: PICC placement was associated with a lower risk of complications than CICC placement. Although the cost of a PICC is higher, its use avoided complications and need for catheter replacement before the end of treatment.

Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction.

AIMS: Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2). METHODS AND RESULTS: In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events' predictive and discriminative ability through Harrell's C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories. CONCLUSION: In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

Our study highlights the impact of including coronary artery calcium score (CACS) and genetic risk score (GRS) alongside Systematic Coronary Risk Evaluation 2 (SCORE2) for enhancing cardiovascular (CV) risk assessment in primary prevention. In our population, adding CACS to SCORE2 exhibited a superior discriminative capacity for CV events compared with GRS alone in terms of risk prediction, discrimination, and reclassification. Our results emphasize the potential clinical relevance of using all three scores to identify high-risk individuals who would benefit from earlier and more stringent cardiovascular risk management strategies to prevent future cardiovascular events.

Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP. METHODS: Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart-lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1ß levels. Leukocyte infiltration, myeloperoxidase presence, IL-1ß gene expression, and long-term release in lung culture (explant) were evaluated. RESULTS: Brain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1ß levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile. CONCLUSION: In this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.

As there is a shortage of viable lungs for transplantation, methods of lung preservation, such as ex vivo perfusion, are important. This method is a good alternative, as it will not only preserve the lungs, but also enable lung function assessment and treatment of the organs. Studies have showed that lungs from donors of the female sex have greater risk of being rejected, when transplanted to male receptors. However, it's not certain if sex differences in anatomy, physiology and specially in immune response could interfere with the transplant result. Females do present a greater and more efficient immune response to any hazard, however after brain death this control is lost, producing a great inflammatory response as a result. Therefore, in this study we have investigated in more detail the influence of sex on the effects of brain death followed by the preservation method. Thus, we performed a brain death model in males and females rats and placed their lungs in an ex vivo lung perfusion machine. At the end of the experiment, we analyzed lung ventilation, gas exchange, and inflammatory parameters. The obtained data indicated that overall the lung ventilation and gas exchange is maintained by the ex vivo perfusion machine. Also, that lung inflammation is influenced by the sex of the donor; where the lungs from females present greater inflammation compared to the lungs from males.

Human health risk assessment of metals in soil samples of a Brazilian city with a historic contamination complex.

Rio Grande is a city located on a narrow industrialized and urbanized Brazilian peninsula, characterized by wetlands. Due to population growth, numerous urban backfilled regions were built to expand the territorial area of the city. Currently, more than 60% of the central area of the city comes from the grounding of wetlands. The material used for the expansion of the territory had a history of contamination from metals from the tannery and textile industries (mainly Hg) and urban solid waste. In addition to past sources, the city has an active industrial complex with fertilizer, petrochemical, and grain industries. This study evaluated the risks to human health caused by metals (Hg, Fe, Ni, Cr, Cu, Pb, and Zn) in original soils and backfills, considering the oral, inhalation, and dermal routes of exposure for children and adults using the tool human health risk assessment (HHRA) proposed methodology by USEPA. A total of 63.81% of the original soil samples and 57.14% of the backfill soil samples showed a non-carcinogenic risk (HInc>1) for at least one evaluated metal. Still, approximately 10% of the samples presented carcinogenic risk when the Cr was considered in the hexavalent form. The dermal (Hg, Ni, and Cr) and oral (Fe, Cu, and Zn) exposure routes had the greatest contribution to the total risk. The non-carcinogenic risk for Hg, Cr(VI), and Pb was heterogeneously distributed between the original soils and backfills and associated with the proximity to some pollution sources. Given the complexity of historical occupation in the municipality and the increasing industrialization, both the original areas and the backfills should be included in the risk management strategy to minimize risks.

Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket.

To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography.

Dificuldades alimentares em pré-escolares de uma escola de educação infantil / Feeding difficulties in preschool children at an early childhood education school

Dificuldade alimentar é todo problema que afeta negativamente o processo dos pais ou cuidadores de suprirem alimento ou nutrientes à criança. O objetivo deste trabalho foi investigar as dificuldades alimentares em pré-escolares de uma escola municipal de educação infantil de Uruguaiana/RS. O estudo foi aprovado pelo Comitê de Ética em Pesquisa e realizado entre outubro e novembro de 2022. Foram convidadas a participar da pesquisa todos os pais ou responsáveis das crianças (n=70) que frequentavam a escola, na faixa etária de 4-5 anos. Todos receberam o Termo de Consentimento Livre e Esclarecido, bem como o questionário de pesquisa. O instrumento utilizado foi a Escala Brasileira de Alimentação Infantil (EBAI), que possui 14 perguntas referentes à alimentação das crianças. Foi realizada estatística descritiva, em termos de frequência e realizada análise de variância (ANOVA) para comparações entre os sexos (p<0,05). Foram obtidas 31 respostas dos pais relativas à alimentação das crianças. Os dados revelaram que 9,68% (n=3) possuíam algum grau de dificuldade alimentar, sendo 3,33% (n=1) com grau severo e 6,45% (n=2) com grau moderado. As demais crianças (n=28) também apresentaram comportamentos relacionados às dificuldades alimentares, porém, sem pontuação suficiente para serem classificadas com dificuldade alimentar. Os comportamentos mais frequentemente descritos foram: o responsável usar distrações ou ir atrás da criança para que ela coma, tempo de a alimentação em torno de 31-60min ou mais, criança que nauseia, cospe ou vomita com algum tipo de alimento e a influência negativa da alimentação nas relações familiares. Desta forma, observou-se um baixo percentual de dificuldades alimentares na população estudada, de acordo com a literatura estudada.

Feeding difficulties are any problem that negatively affects the process of parents or caregivers providing food or nutrients to the child. The objective of this work was to investigate eating difficulties in preschool children at a municipal early childhood education school in Uruguaiana/RS. The study was approved by the Research Ethics Committee and carried out between October and November 2022. All parents or guardians of children (n=70) who attended school, aged 4-5 years, were invited to participate in the research. Everyone received the Free and Informed Consent Form, as well as the research questionnaire. The instrument used was the Brazilian Infant Feeding Scale (EBAI), which has 14 questions regarding children's nutrition. Descriptive statistics were performed in terms of frequency and analysis of variance (ANOVA) was performed for comparisons between sexes (p<0.05). 31 responses were obtained from parents regarding children's nutrition. The data revealed that 9.68% (n=3) had some degree of feeding difficulty, 3.33% (n=1) with a severe degree and 6.45% (n=2) with a moderate degree. The remaining children (n=28) also presented behaviors related to feeding difficulties, however, without enough scores to be classified as having feeding difficulties. The most frequently described behaviors were: the caregiver using distractions or going after the child to make them eat, feeding time around 31-60 minutes or more, child who nauseates, spits or vomits with some type of food and the negative influence of food in family relationships. Thus, a low percentage of feeding difficulties was observed in the studied population, in accordance with the literature studied.

Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients / Impacto do risco de desnutrição pré-transplante no desfecho clínico e na sobrevida do enxerto de pacientes transplantados renais

ABSTRACT Background: The prevalence of malnourished patients before transplantation and the influence of malnutrition on graft and patient outcomes remain underestimated, despite being associated with higher postoperative morbidity and mortality. This study aimed to develop an easy nutritional screening tool and evaluate the impact of nutritional status on clinical outcome, graft survival (GS) and mortality risk in kidney transplant patients (KTP). Methods: In this retrospective cohort study including 451 KTP, we developed a score by using anthropometric, clinical, and laboratory measures performed in the pretransplant evaluation. The patients were stratified into 3 groups according to the final score: G1 (0 or 1 point)=low risk, G2 (2 to 4 points)=moderate risk, and G3 (>5 points)=high risk of malnutrition. The patients were monitored after transplantation at least 1 to 10 years. Results: Stratifying the 451 patients based on the pretransplant risk score, G1, G2, and G3 were composed of 90, 292, and 69 patients, respectively. Patients from G1 maintained the lowest serum creatinine levels at hospital discharge when compared with others (p = 0.012). The incidence of infection in the patients from G3 was higher than patients from G1 and G2 (p = 0.030). G3 recipients showed worse GS than G1 patients (p = 0.044). G3 patients showed almost threefold higher risk for graft loss (HR 2.94, 95% CI 1.084-7.996). Conclusions: KTP with higher malnutrition risk score were associated with worse outcomes and GS. The nutritional screening tool is easy to be used in clinical practice to evaluate the patient in preparation for kidney transplant.

RESUMO Antecedentes: A prevalência de pacientes desnutridos antes do transplante e a influência da desnutrição nos desfechos do enxerto e do paciente permanecem subestimadas, embora estejam associadas a maior morbimortalidade pós-operatória. Este estudo buscou desenvolver uma ferramenta simples de triagem nutricional e avaliar o impacto do estado nutricional no desfecho clínico, sobrevida do enxerto (SE) e risco de mortalidade em pacientes transplantados renais (PTR). Métodos: Neste estudo de coorte retrospectivo incluindo 451 PTR, desenvolvemos um escore usando medidas antropométricas, clínicas e laboratoriais tomadas na avaliação pré-transplante. Os pacientes foram estratificados em 3 grupos segundo a pontuação final: G1 (0-1 ponto) = baixo risco, G2 (2-4 pontos) = risco moderado e G3 (>5 pontos) = alto risco de desnutrição. Eles foram monitorados por pelo menos 1 a 10 anos após o transplante. Resultados: Os 451 pacientes foram estratificados em G1, G2 e G3, que consistiram em 90, 292 e 69 pacientes, respectivamente. Os pacientes do G1 mantiveram os menores níveis de creatinina sérica na alta hospitalar em relação aos demais (p = 0,012). A incidência de infecção nos pacientes do G3 foi maior que nos pacientes do G1 e G2 (p = 0,030). Os pacientes do G3 apresentaram SE pior do que os pacientes do G1 (p = 0,044) e um risco quase três vezes maior de perda do enxerto (HR 2,94; IC 95% 1,084-7,996). Conclusões: PTR com maior escore de risco de desnutrição foram associados a piores desfechos e menor SE. A ferramenta de triagem nutricional é fácil de usar na prática clínica para avaliar pacientes em preparação para transplante renal.

Effects of kidney perfusion on renal stiffness and tissue fluidity measured with tomoelastography in an MRI-compatible ex vivo model.

Stiffness plays a vital role in diagnosing renal fibrosis. However, perfusion influences renal stiffness in various chronic kidney diseases. Therefore, we aimed to characterize the effect of tissue perfusion on renal stiffness and tissue fluidity measured by tomoelastography based on multifrequency magnetic resonance elastography in an ex vivo model. Five porcine kidneys were perfused ex vivo in an MRI-compatible normothermic machine perfusion setup with adjusted blood pressure in the 50/10-160/120 mmHg range. Simultaneously, renal cortical and medullary stiffness and fluidity were obtained by tomoelastography. For the cortex, a statistically significant (p < 0.001) strong positive correlation was observed between both perfusion parameters (blood pressure and resulting flow) and stiffness (r = 0.95, 0.91), as well as fluidity (r = 0.96, 0.92). For the medulla, such significant (p < 0.001) correlations were solely observed between the perfusion parameters and stiffness (r = 0.88, 0.71). Our findings demonstrate a strong perfusion dependency of renal stiffness and fluidity in an ex vivo setup. Moreover, changes in perfusion are rapidly followed by changes in renal mechanical properties-highlighting the sensitivity of tomoelastography to fluid pressure and the potential need for correcting mechanics-derived imaging biomarkers when addressing solid structures in renal tissue.

Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.

Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study.

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.

Use of the ADHERE Risk Model as a Predictor of Risk of in-Hospital Worsening Heart Failure in a Cohort. / Uso do Modelo de Risco ADHERE como Preditor de Piora Intra-Hospitalar de Insuficiência Cardíaca em uma Coorte.

BACKGROUND: Patients admitted with acute decompensated heart failure (HF) are subject to developing worsening episodes that require more complex interventions. The Acute Decompensated Heart Failure National Registry (ADHERE) risk model was developed in the United States to predict the risk of in-hospital worsening HF. OBJECTIVE: To use the ADHERE risk model in the assessment of risk of in-hospital worsening HF and to determine its sensitivity and specificity in hospitalized patients. METHODS: This cohort study was conducted at a Brazilian public university hospital, and data from 2013 to 2020 were retrospectively collected. P values < 0.05 were considered statistically significant. RESULTS: A total of 890 patients with a mean age of 74 ± 8 years were included. The model showed that, in the group of 490 patients at risk, 254 (51.8%) developed in-hospital worsening HF. In the group of 400 patients not at risk, only 109 (27.2%) experienced worsening HF. The results demonstrated a statistically significant curve (area under the curve = 0.665; standard error = 0.018; P < 0.01; confidence interval = 0.609 to 0.701), indicating good accuracy. The model had a sensitivity of 69.9% and a specificity of 55.2%, with a positive predictive value of 52% and a negative predictive value of 72.7%. CONCLUSIONS: In this cohort, we showed that the ADHERE risk model was able to discriminate patients who in fact developed worsening HF during the admission period, from those who did not.

FUNDAMENTO: Pacientes hospitalizados com insuficiência cardíaca (IC) aguda descompensada estão sujeitos a desenvolver episódios de piora que requerem intervenções mais complexas. O modelo de predição de risco "Acute Decompensated Heart Failure National Registry" (ADHERE) foi desenvolvido nos Estados Unidos para prever o risco de piora intra-hospitalar da IC. OBJETIVO: Utilizar o modelo de predição de risco ADHERE para avaliar o risco de piora intra-hospitalar da IC e determinar a sua sensibilidade e especificidade em pacientes hospitalizados. MÉTODOS: O presente estudo de coorte foi realizado em um hospital universitário público brasileiro e os dados de 2013 a 2020 foram coletados retrospectivamente. Foram considerados estatisticamente significativos valores de p < 0,05. RESULTADOS: Foram incluídos 890 pacientes com idade média de 74 ± 8 anos. O modelo mostrou que no grupo de 490 pacientes de risco, 254 (51,8%) desenvolveram piora intra-hospitalar da IC. No grupo de 400 pacientes sem risco, apenas 109 (27,2%) apresentaram piora da IC. Os resultados demonstraram uma curva estatisticamente significativa (área sob a curva = 0,665; erro padrão = 0,018; p < 0,01; intervalo de confiança = 0,609 a 0,701), indicando boa precisão. O modelo apresentou sensibilidade de 69,9% e especificidade de 55,2%, com valor preditivo positivo de 52% e valor preditivo negativo de 72,7%. CONCLUSÕES: Na presente coorte, demonstramos que o modelo de predição de risco ADHERE foi capaz de discriminar pacientes que, de fato, desenvolveram piora da IC durante o período de internação daqueles que não desenvolveram.

Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients.

BACKGROUND: The prevalence of malnourished patients before transplantation and the influence of malnutrition on graft and patient outcomes remain underestimated, despite being associated with higher postoperative morbidity and mortality. This study aimed to develop an easy nutritional screening tool and evaluate the impact of nutritional status on clinical outcome, graft survival (GS) and mortality risk in kidney transplant patients (KTP). METHODS: In this retrospective cohort study including 451 KTP, we developed a score by using anthropometric, clinical, and laboratory measures performed in the pretransplant evaluation. The patients were stratified into 3 groups according to the final score: G1 (0 or 1 point)=low risk, G2 (2 to 4 points)=moderate risk, and G3 (>5 points)=high risk of malnutrition. The patients were monitored after transplantation at least 1 to 10 years. RESULTS: Stratifying the 451 patients based on the pretransplant risk score, G1, G2, and G3 were composed of 90, 292, and 69 patients, respectively. Patients from G1 maintained the lowest serum creatinine levels at hospital discharge when compared with others (p = 0.012). The incidence of infection in the patients from G3 was higher than patients from G1 and G2 (p = 0.030). G3 recipients showed worse GS than G1 patients (p = 0.044). G3 patients showed almost threefold higher risk for graft loss (HR 2.94, 95% CI 1.084-7.996). CONCLUSIONS: KTP with higher malnutrition risk score were associated with worse outcomes and GS. The nutritional screening tool is easy to be used in clinical practice to evaluate the patient in preparation for kidney transplant.

Transcription factor 21 gene and prognosis in a coronary population.

INTRODUCTION AND OBJECTIVES: Transcription factor 21 (TCF21) is a member of the basic helix-loop-helix (bHLH) transcription factor family, and is critical for embryogenesis of the heart. It regulates differentiation of epicardium-derived cells into smooth muscle cell (SMC) and fibroblast lineages. The biological role of TCF21 in the progression of atherosclerosis is the subject of debate. The aim of this study was to investigate the impact of the TCF21 rs12190287 gene variant on the prognosis of coronary artery disease (CAD) in a Portuguese population from Madeira island. METHODS: We analyzed major adverse cardiovascular events (MACE) in 1713 CAD patients, mean age 53.3±7.8, 78.7% male, for 5.0±4.3 years. Genotype and allele distribution between groups with and without MACE was determined. The dominant genetic model (heterozygous GC plus homozygous CC) was used and compared with the wild GG to assess survival probability. Cox regression with risk factors and genetic models assessed variables associated with MACE. Kaplan-Meier analysis was used to estimate survival. RESULTS: The wild homozygous GG, heterozygous GC and risk CC genotypes were found in 9.5%, 43.2% and 47.3% of the population, respectively. The dominant genetic model remained in the equation as an independent risk factor for MACE (HR 1.41; p=0.033), together with multivessel disease, chronic kidney disease, low physical activity and type 2 diabetes. The C allele in the dominant genetic model showed worse survival (22.5% vs. 44.3%) at 15 years of follow-up. CONCLUSION: The TCF21 rs12190287 variant is a risk factor for CAD events. This gene may influence fundamental SMC processes in response to vascular stress, accelerating atherosclerosis progression, and may represent a target for future therapies.