Renal Disease in Metabolic Syndrome: the Hidden Role of Intrarenal Ischemia.

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project. Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m2; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease. Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) (P = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P < 0.05). These vascular changes were independent of differences in age. Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health.

Predicting Cellular Rejection of Renal Allograft Based on the Serum Proteomic Fingerprint.

Kidney transplantation is an essential medical procedure that significantly enhances the survival rates and quality of life for patients with end-stage kidney disease. However, despite advancements in immunosuppressive therapies, allograft rejection remains a leading cause of organ loss. Notably, predictions of cellular rejection processes primarily rely on biopsy analysis, which is not routinely performed due to its invasive nature. The present work evaluates if the serum proteomic fingerprint, as acquired by Fourier Transform Infrared (FTIR) spectroscopy, can predict cellular rejection processes. We analyzed 28 serum samples, corresponding to 17 without cellular rejection processes and 11 associated with cellular rejection processes, as based on biopsy analyses. The leave-one-out-cross validation procedure of a Naïve Bayes model enabled the prediction of cellular rejection processes with high sensitivity and specificity (AUC > 0.984). The serum proteomic profile was obtained in a high-throughput mode and based on a simple, rapid, and economical procedure, making it suitable for routine analyses and large-scale studies. Consequently, the current method presents a high potential to predict cellular rejection processes translatable to clinical scenarios, and that should continue to be explored.

Activation of a Rhythmic Lower Limb Movement Pattern during the Use of a Multimodal Brain-Computer Interface: A Case Study of a Clinically Complete Spinal Cord Injury.

Brain-computer interfaces (BCIs) that integrate virtual reality with tactile feedback are increasingly relevant for neurorehabilitation in spinal cord injury (SCI). In our previous case study employing a BCI-based virtual reality neurorehabilitation protocol, a patient with complete T4 SCI experienced reduced pain and emergence of non-spastic lower limb movements after 10 sessions. However, it is still unclear whether these effects can be sustained, enhanced, and replicated, as well as the neural mechanisms that underlie them. The present report outlines the outcomes of extending the previous protocol with 24 more sessions (14 months, in total). Clinical, behavioral, and neurophysiological data were analyzed. The protocol maintained or reduced pain levels, increased self-reported quality of life, and was frequently associated with the appearance of non-spastic lower limb movements when the patient was engaged and not experiencing stressful events. Neural activity analysis revealed that changes in pain were encoded in the theta frequency band by the left frontal electrode F3. Examination of the lower limbs revealed alternating movements resembling a gait pattern. These results suggest that sustained use of this BCI protocol leads to enhanced quality of life, reduced and stable pain levels, and may result in the emergence of rhythmic patterns of lower limb muscle activity reminiscent of gait.

Localized APP expression results in progressive network dysfunction by disorganizing spike timing.

Progressive cognitive decline in Alzheimer's disease could either be caused by a spreading molecular pathology or by an initially focal pathology that causes aberrant neuronal activity in a larger network. To distinguish between these possibilities, we generated a mouse model with expression of mutant human amyloid precursor protein (APP) in only hippocampal CA3 cells. We found that performance in a hippocampus-dependent memory task was impaired in young adult and aged mutant mice. In both age groups, we then recorded from the CA1 region, which receives inputs from APP-expressing CA3 cells. We observed that theta oscillation frequency in CA1 was reduced along with disrupted relative timing of principal cells. Highly localized pathology limited to the presynaptic CA3 cells is thus sufficient to cause aberrant firing patterns in postsynaptic neuronal networks, which indicates that disease progression is not only from spreading pathology but also mediated by progressively advancing physiological dysfunction.

A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study.

INTRODUCTION: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. METHODS: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. RESULTS: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. CONCLUSION: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Adenovirus Infection in a Kidney-Pancreatic Transplant Recipient: Case Report.

Adenovirus infection in transplant recipients may present from asymptomatic viremia to multisystemic involvement. Most frequently, it occurs in the first year after a kidney transplant, and it is secondary to the reactivation of latent disease. However, primary infection may occur, and disseminated disease is more common when related to primary infection. Kidney involvement may be confirmed by biopsy, although diagnosis may be presumptive. Reduction of immunosuppression and supportive care are important components of therapy. CASE DESCRIPTION: A 41-year-old female renal-pancreatic recipient 12 years before with chronic renal graft dysfunction and a functional pancreatic graft had a history of cytomegalovirus and polyoma virus infection 2 years after transplantation. She was taking tacrolimus, mycophenolate mofetil, and prednisolone. The patient was admitted after persistent uncharacteristic diarrhea 3 weeks before hospitalization without any relevant epidemiologic context. She was dehydrated, and the lab results showed worsened kidney function and leucocytosis. The viral culture revealed adenovirus. Vigorous hydration was implemented, and the mycophenolate mofetil dose was reduced. The patient was discharged, and renal function returned to previous values. DISCUSSION AND CONCLUSION: Adenovirus infection has a wide clinical presentation, and multisystemic involvement may occur in transplant recipients. Supportive care is paramount. The clinical features and viral culture confirm the diagnosis, although tissue samples and quantitative polymerase chain reaction may be required in more severe cases.

Neurophysiological correlates of tactile width discrimination in humans.

Introduction: Tactile information processing requires the integration of sensory, motor, and cognitive information. Width discrimination has been extensively studied in rodents, but not in humans. Methods: Here, we describe Electroencephalography (EEG) signals in humans performing a tactile width discrimination task. The first goal of this study was to describe changes in neural activity occurring during the discrimination and the response periods. The second goal was to relate specific changes in neural activity to the performance in the task. Results: Comparison of changes in power between two different periods of the task, corresponding to the discrimination of the tactile stimulus and the motor response, revealed the engagement of an asymmetrical network associated with fronto-temporo-parieto-occipital electrodes and across multiple frequency bands. Analysis of ratios of higher [Ratio 1: (0.5-20 Hz)/(0.5-45 Hz)] or lower frequencies [Ratio 2: (0.5-4.5 Hz)/(0.5-9 Hz)], during the discrimination period revealed that activity recorded from frontal-parietal electrodes was correlated to tactile width discrimination performance between-subjects, independently of task difficulty. Meanwhile, the dynamics in parieto-occipital electrodes were correlated to the changes in performance within-subjects (i.e., between the first and the second blocks) independently of task difficulty. In addition, analysis of information transfer, using Granger causality, further demonstrated that improvements in performance between blocks were characterized by an overall reduction in information transfer to the ipsilateral parietal electrode (P4) and an increase in information transfer to the contralateral parietal electrode (P3). Discussion: The main finding of this study is that fronto-parietal electrodes encoded between-subjects' performances while parieto-occipital electrodes encoded within-subjects' performances, supporting the notion that tactile width discrimination processing is associated with a complex asymmetrical network involving fronto-parieto-occipital electrodes.

Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease.

BACKGROUND: High levels of FGF23 associate with adverse events in CKD. The urinary fractional excretion of phosphate (FePi) might modify this association, although data are limited in moderate and advanced CKD. We investigated the association of combined FePi and serum FGF23 with incident heart failure, cardiovascular events and mortality in patients with CKD stages 2-4. METHODS: Patients from the Chronic Renal Insufficiency Cohort were divided into four groups according to the median of FePi and FGF23: low-FePi/low-FGF23, reference group; high-FePi/low-FGF23; low-FePi/high-FGF23; high-FePi/high-FGF23. Primary outcomes were: the composite of cardiovascular death or hospitalization for heart failure; cardiovascular death; hospitalization for heart failure; and death from any cause. Survival analysis and adjusted regression analyses were performed. RESULTS: We analyzed 3684 patients with a mean age of 58 ± 11 years of whom 45% were male. Mean eGFR was 44 ± 15 ml/min/1.73 m2. The median time of follow-up was 12 (IQR 7-13) years. The risk of the composite of cardiovascular death or hospitalization for heart failure was increased in the low-FePi/high-FGF23 group (HR 1.35; 95%CI 1.09-1.67) and in the high-FePi/high-FGF23 group (HR 1.50; 95%CI 1.20-1.86), compared to the low-FePi/low-FGF23 group. Cardiovascular death and hospitalization for heart failure were also increased in both groups with high FGF23. Death from any cause was increased in the low-FePi/high-FGF23 group (HR 1.56 (95%CI 1.30-1.89) and in the high-FePi/high-FGF23 (HR 1.57 (95%CI 1.29-1.90)). CONCLUSIONS: High FGF23 was associated with heart failure and cardiovascular death in patients with low FePi and high FePi with moderate to advanced CKD. This contrasts with reports in mild CKD.

Embodiment Comfort Levels During Motor Imagery Training Combined With Immersive Virtual Reality in a Spinal Cord Injury Patient.

Brain-machine interfaces combining visual, auditory, and tactile feedback have been previously used to generate embodiment experiences during spinal cord injury (SCI) rehabilitation. It is not known if adding temperature to these modalities can result in discomfort with embodiment experiences. Here, comfort levels with the embodiment experiences were investigated in an intervention that required a chronic pain SCI patient to generate lower limb motor imagery commands in an immersive environment combining visual (virtual reality -VR), auditory, tactile, and thermal feedback. Assessments were made pre-/ post-, throughout the intervention (Weeks 0-5), and at 7 weeks follow up. Overall, high levels of embodiment in the adapted three-domain scale of embodiment were found throughout the sessions. No significant adverse effects of VR were reported. Although sessions induced only a modest reduction in pain levels, an overall reduction occurred in all pain scales (Faces, Intensity, and Verbal) at follow up. A high degree of comfort in the comfort scale for the thermal-tactile sleeve, in both the thermal and tactile feedback components of the sleeve was reported. This study supports the feasibility of combining multimodal stimulation involving visual (VR), auditory, tactile, and thermal feedback to generate embodiment experiences in neurorehabilitation programs.

Horizontal Gaze Palsy and Progressive Scoliosis in Dizygotic Twins.

Horizontal gaze palsy and progressive scoliosis (HGPPS) is a rare autosomal recessive disorder caused by mutations in the ROBO3 gene. Clinical presentation consists of impairment of conjugate horizontal eye movements together with a progressive scoliosis beginning in childhood. We report dizygotic twins with HGPPS that had absence of conjugate horizontal eye movements combined with divergent strabismus and synergistic divergence. One of them also had a congenital palpebral ptosis and vertical strabismus of the right eye. Onset of scoliosis occurred in childhood with rapid progression in the second decade of life. Brain imaging showed characteristic features of the disease such as hypoplasia of the pons and a midline cleft of the brainstem with a butterfly-like bifid appearance. Genetic analysis revealed a pathogenic homozygous mutation on the ROBO3 gene. These siblings and a previous report of two other individuals with the same disorder from the same small geographical region with less than 38000 inhabitants, likely represent a founder effect.

[The problem of overutilization of resources and the Choosing Wisely Portugal program - Judicious Choices in Health]. / O problema da sobreutilização de recursos e o projeto Choosing Wisely Portugal - Escolhas Criteriosas em Saúde.

The variation of clinical practice is a well-described phenomenon in which patients with similar diagnoses, prognoses and demographic status receive different levels of care depending on when, where and by whom they are treated, despite agreed and documented evidence of best practice. The overutilization of health resources is also known to have a negative risk-benefit ratio. Unfortunately, both phenomena occur in several countries, especially in developed countries. In the light of this, the American Board of Internal Medicine launched the Choosing Wisely campaign, which has subsequently been implemented in several countries, including Portugal.

A variação da prática clínica é um fenómeno que se encontra bem descrito e que se caracteriza por uma prática clínica utilizando testes diagnósticos e esquemas terapêuticos diversos, em doentes semelhantes na patologia que apresentam e no seu risco basal. A sobreutilização de recursos em saúde caracteriza-se por apresentar um benefício-risco negativo. Infelizmente ambos os fenómenos se verificam em diversos países, em particular países desenvolvidos. Neste contexto, o American Board of Internal Medicine lançou a campanha Choosing Wisely, a qual foi, entretanto, implementada em diversos países incluindo Portugal.

Does Symptom Recognition Improve Self-Care in Patients with Heart Failure? A Pilot Study Randomised Controlled Trial.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognition of symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate the longitudinal effect of a nursing-led complex intervention on self-care management and quality-of-life changes in patients with heart failure and assessed by a pilot study performed on sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p < 0.001) and emergency admission (IRR 4.24; p < 0.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (ßSlope. Assignment_group = -0.881; p < 0.001) and in the quality of life (ßSlope. Assignment_group = 1.739; p < 0.001). This study supports that a nurse-led programme on symptom recognition and fluid restriction can positively impact self-care behaviours and quality of life in patients with heart failure. This randomised controlled trial was retrospectively registered (NCT04892004).

O problema da sobreutilização de recursos e o projeto Choosing Wisely Portugal - Escolhas Criteriosas em Saúde / The problem of overutilization of resources and the Choosing Wisely Portugal program - Judicious Choices in Health

Resumo A variação da prática clínica é um fenómeno que se encontra bem descrito e que se caracteriza por uma prática clínica utilizando testes diagnósticos e esquemas terapêuticos diversos, em doentes semelhantes na patologia que apresentam e no seu risco basal. A sobreutilização de recursos em saúde caracteriza-se por apresentar um benefício-risco negativo. Infelizmente ambos os fenómenos se verificam em diversos países, em particular países desenvolvidos. Neste contexto, o American Board of Internal Medicine lançou a campanha Choosing Wisely, a qual foi, entretanto, implementada em diversos países incluindo Portugal.

Abstract The variation of clinical practice is a well-described phenomenon in which patients with similar diagnoses, prognoses and demographic status receive different levels of care depending on when, where and by whom they are treated, despite agreed and documented evidence of best practice. The overutilization of health resources is also known to have a negative risk-benefit ratio. Unfortunately, both phenomena occur in several countries, especially in developed countries. In the light of this, the American Board of Internal Medicine launched the Choosing Wisely campaign, which has subsequently been implemented in several countries, including Portugal.

A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement.

The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care.Trial Registration ClinicalTrials.gov Identifier: NCT00930735 and ClinicalTrials.gov Identifier: NCT01755936.

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease.

INTRODUCTION: The clinical-histologic correlation in diabetic nephropathy is not completely known. METHODS: We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). RESULTS: Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m2). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%; P = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III. CONCLUSIONS: Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes.

Translation and Cross-Cultural Adaptation of Quality of Life Scale in Patients with Onychomycosis.

(1) Background: Onychomycosis (OM) is a fungal nail infection, considered a risk factor for diabetic foot ulcers. It is associated with changes in quality of life, in terms of pain, self-confidence and self-esteem. The aim was to translate and adapt the OM quality of life questionnaire "OnyCOE-tTM-Quality Of Life Questionnaire Onychomycosis (Nail Fungal Condition)". (2) Methods: This study followed the guidelines proposed by Beaton et al. (2000), where two English to Portuguese translations were performed and, after an expert consensus, a common version was obtained. This was followed by two back-translations. The expert committee achieved semantic equivalence, idioms and concepts. The pre-test was applied to 49 people. The final version and processed data were sent to the authors. (3) Results: We adapted terms semantically, modified statements syntactically, altering items from interrogative to affirmative. (4) Conclusions: The translated version of the "Quality of life-Onychomycosis" questionnaire suggested that it can be used for further studies to test validity and reliability in this population.