Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation.

Introduction: We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Methods: Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n = 71) or MN diagnosed de novo after KT (n = 4). Results: Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18; P = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. Conclusions: One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.

Association of severe preeclampsia and vascular damage assessed by noninvasive markers of arterial stiffness.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with high maternal and fetal morbidity and mortality and increased future risk of cardiovascular complications. OBJECTIVE: To analyze whether women who have had PE with severe features in their pregnancy have higher arterial stiffness (AS) parameters than those whose PE course was without signs of severity. METHODS: Sixty-five women who developed PE during their gestation were evaluated, divided into two groups: PE group without severe features or non-severe PE (n=30) and PE group with severe features or severe PE (n=35). Carotid-femoral pulse wave velocity (cfPWV), central augmentation index corrected to a heart rate of 75 beats per minute (AIxc75) and central augmentation pressure (cAP) were determined one month and six months postpartum. Comparison of proportions was carried out using the chi-square test, comparison of means between groups using the Student's t-test or the Mann-Whitney test, and comparison of means of the same group at different evolutionary moments, using the t-test or the Wilcoxon test. Correlation, with and between hemodynamic parameters, was carried out with Spearman's correlation coefficient and the association between demographic variables, personal history and hemodynamic parameters, and altered arterial stiffness parameters was carried out using linear and logistic regression models. RESULTS: Women with severe PE presented, both at 1 and 6 months postpartum, higher values of blood pressure, both central and peripheral, as well as AR and pulse amplification parameters, than those women whose PE was not severe. Central augmentation index (cAIx) values at 1 month and 6 months postpartum were higher, although not significantly, in the severe PE group compared to the non-severe PE group (24.0 (16.5-34.3) vs. 19.0% (14-29) and 24.0 (14.0-30.0) vs. 20.0% (12.3-26.8), respectively). Carotid-femoral pulse wave velocity (cfPWV) was significantly higher at both 1 and 6 months postpartum in the severe PE group compared to the non-severe PE group (10.2 (8.8-10.7) vs. 8.8m/s (8.3-9.6) and 10.0 (8.8-10.6) vs. 8.8m/s (8.3-9.3), respectively). Central systolic pressure and central pulse pressure amplification were also higher, although not significantly, in the severe PE group in comparison with the non-severe PE group. CONCLUSIONS: Women who have had severe PE have more pronounced arterial stiffness parameters than those in whom PE was not particularly severe. The determination of cAIx and cfPWV, as a strategy for the assessment of cardiovascular risk, should be evaluated among women who have had PE.

Meat Intake, Cooking Methods, Doneness Preferences and Risk of Gastric Adenocarcinoma in the MCC-Spain Study.

BACKGROUND: The association of meat intake with gastric adenocarcinoma is controversial. We examined the relation between white, red, and processed meat intake and gastric adenocarcinoma, considering doneness preference and cooking methods, by histological subtype and anatomical subsite. METHODS: MCC-Spain is a multicase-control study that included 286 incident gastric adenocarcinoma cases and 2993 controls who answered a food-frequency questionnaire. The association of gastric adenocarcinoma with meat intake, doneness preference and cooking methods was assessed using binary multivariate logistic regression mixed models and a possible interaction with sex was considered. Multinomial logistic regression models were used to estimate risk by tumor subsite (cardia vs. non-cardia) and subtype (intestinal vs. diffuse). Sensitivity analyses were conducted comparing models with and without data on Helicobacter pylori infection. RESULTS: The intake of red and processed meat increased gastric adenocarcinoma risk (OR for one serving/week increase (95% CI) = 1.11 (1.02;1.20) and 1.04 (1.00;1.08), respectively), specifically among men and for non-cardia and intestinal gastric adenocarcinoma. Those who consume well done white or red meat showed higher risk of non-cardia (white: RRR = 1.57 (1.14;2.16); red: RRR = 1.42 (1.00;2.02)) and intestinal tumors (white: RRR = 1.69 (1.10;2.59); red: RRR = 1.61 (1.02;2.53)) than those with a preference for rare/medium doneness. Stewing and griddling/barbequing red and white meat, and oven baking white meat, seemed to be the cooking methods with the greatest effect over gastric adenocarcinoma. The reported associations remained similar after considering Helicobacter pylori seropositivity. CONCLUSIONS: Reducing red and processed meat intake could decrease gastric adenocarcinoma risk, especially for intestinal and non-cardia tumors. Meat cooking practices could modify the risk of some gastric cancer subtypes.

Immunosuppression with Calcineurin Inhibitor after Renal Transplant Failure Inhibits Allosensitization.

Immunosuppression withdrawal after graft failure seems to favor sensitization. A high percentage of calculated panel-reactive antibody (cPRA) and the development of de novo donor specific antibodies (dnDSA) indicate human leukocyte antigen (HLA) sensitization and may hinder the option of retransplantation. There are no established protocols on the immunosuppressive treatment that should be maintained after transplant failure. A retrospective analysis including 77 patients who lost their first renal graft between 1 January 2006-31 December 2015 was performed. Two sera were selected per patient, one immediately prior to graft loss and another one after graft failure. cPRA was calculated by Single Antigen in all patients. It was possible to analyze the development of dnDSA in 73 patients. By multivariate logistic regression analysis, the absence of calcineurin inhibitor (CNI) at 6 months after graft failure was related to cPRA > 75% (OR 4.8, CI 95% 1.5-15.0, p = 0.006). The absence of calcineurin inhibitor (CNI) at 6 months after graft loss was significantly associated with dnDSA development (OR 23.2, CI 95% 5.3-100.6, p < 0.001). Our results suggest that the absence of CNI at the sixth month after graft loss is a risk factor for sensitization. Therefore, maintenance of an immunosuppressive regimen based on CNI after transplant failure should be considered when a new transplant is planned, since it seems to prevent HLA allosensitization.

Growth Differentiation Factor 15: A Biomarker with High Clinical Potential in the Evaluation of Kidney Transplant Candidates.

Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49-16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2-8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65-11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates.

Síndrome de Ehlers-Danlos em paciente com dor crônica. Relato de caso / Ehlers-Danlos syndrome in chronic pain patient. Case report

RESUMO JUSTIFICATIVA E OBJETIVOS: A síndrome de Ehlers-Danlos é uma doença do tecido conjuntivo que em alguns casos torna-se incapacitante. O objetivo deste estudo foi apresentar um caso raro diagnosticado no Ambulatório de Controle de Sintomas e Cuidados Paliativos com quadro doloroso importante. RELATO DO CASO: Paciente do gênero masculino, 17 anos, apresentou-se ao ambulatório com queixa de dor no corpo generalizada havia 4 anos. Referia história de hipermobilidade articular notada desde a infância. CONCLUSÃO: Neste caso realizou-se o diagnóstico de Síndrome de Ehlers-Danlos, tipo hipermobilidade, com base na história clínica e no exame físico, além dos critérios de Brighton. A adesão ao tratamento multidisciplinar mostrou impactante melhora na qualidade de vida do paciente.

ABSTRACT BACKGROUND AND OBJECTIVES: Ehlers-Danlos Syndrome is a connective tissue disease which becomes disabling in some cases. This study aimed at presenting a rare case diagnosed in the Ambulatory of Symptoms Control and Palliative Care with severe pain. CASE REPORT: Male patient, 17 years old, who came to the ambulatory complaining of widespread pain for 4 years. He referred history of joint hypermobility noticed since childhood. CONCLUSION: Based on clinical history and physical evaluation, in addition to Brighton criteria, patient was diagnosed as having hypermobility-type Ehlers-Danlos Syndrome.

Stenosis in laparoscopic gastric bypass: management by endoscopic dilation without fluoroscopic guidance.

OBJECTIVES: gastric bypass is the surgical procedure that is carried out most frequently in the treatment of morbid obesity. Stenosis of the gastro-jejunal anastomosis is a relatively frequent complication that requires endoscopic management. However, the optimal dilation technique is yet to be determined. The purpose of this study was to evaluate the safety and efficacy of dilation with a hydrostatic balloon (CRE) without radioscopic guidance in morbidly obese patients treated by laparoscopic bypass. MATERIAL AND METHODS: retrospective review of the data elicited from 525 patients treated against morbid obesity with laparoscopic gastric bypass from January, 2006 to November, 2010. RESULTS: a total of 22/525 patients (4.1%) developed stenosis of the anastomosis [20 women (91%), 2 men (9%)]. In four patients (18.2%), there was an associated anastomotic ulcer, and in one case, there was a history of bleeding of an ulcer treated with sclerosis one month earlier. The diagnosis of stenosis was done in most patient during the first 90 days after the bypass. All cases were resolved by means of endoscopic dilation without adioscopic guidance, 15 cases (68.1%) required a single session, 6 cases (27.2%) two sessions, and 1 case (4.5%) required four sessions. This last case had an associated anastomotic ulcer. The diameter of the balloons ranged from 12 to 20 mm, generally using diameters of 12-15 mm in the first session, and increasing them in the following sessions according to the previous result. One patient treated with a 20 mm balloon presented with a small tear, without showing any evidence of leak of contrast medium in the radioscopic guidance, and was thus managed conservatively. In the follow-up, no re-stenoses were detected. CONCLUSIONS: in our experience, stenosis of the anastomosis in the laparoscopic gastric bypass is an infrequent complication. When it happens, dilation with a hydrostatic balloon is an effective and safe treatment. Radioscopic guidance during dilation is not strictly necessary if norms of progressive dilation are followed.

Efeito do priming na redução da latência do pipecurônio, novo bloqueador neuromuscular não-despolarizante / Effect of priming in shortening onset of pipecuronium, a new nondepolarizing neuromuscular blocker

JUSTIFICATIVA E OBJETIVOS: Uma das mais importantes propriedades dos bloqueadores neuromusculares é o rápido início de ação, possibilitando intubação traqueal precoce. A administração de pequena dose de bloqueador não-despolarizante antes da dose plena é sabidamente redutora da latência da maioria dos bloqueadores neuromusculares utilizados. O brometo de pipecurônio é um agente aminoesteróide de longa duração com grande estabilidade cardiovascular, porém, com início de ação tardio. O objetivo desse estudo foi avaliar o efeito do priming do pipecurônio em pacientes adultos submetidos a cirurgias eletivas sob anestesia geral. MÉTODO: Foram estudados 33 pacientes adultos de ambos os sexos, com idade entre 20 e 65 anos, estado físico ASA I ou II, submetidos a cirurgias eletivas sob anestesia geral. Foram excluídos do estudo pacientes com insuficiência renal ou hepática, neuromiopatia, uso concomitante de drogas que influenciem a sua farmacocinética ou pacientes com histórico familiar de hipertermia maligna. Foram divididos em dois grupos: Grupo 1 onde foi utilizado o priming com 0,01 mg.kg-1 e três minutos depois completada a dose de 0,08 mg.kg-1 e o Grupo 2, sem dose priming (Grupo Controle). O relaxamento neuromuscular foi controlado pela aceleromiografia (Aparelho TOF-Guard) e no momento em que T1 < 10 por cento era realizada a laringoscopia. A análise estatística foi feita pelos testes T para amostras independentes e a normalidade pelo Shapiro Wilks. RESULTADOS: Os grupos foram homogêneos e observou-se que o tempo para T1 < 10 por cento no Grupo 1 foi de 161,4 ± 13,7 segundos e no Grupo 2 foi 217,8 ± 23,4 segundos, com p < 0,001, havendo diferença estatística significativa entre os grupos. CONCLUSÕES: Os resultados do estudo mostraram diferença estatística significativa entre os grupos com e sem priming, indicando que o pipecurônio também tem latência reduzida, assim como os demais bloqueadores neuromusculares conhecidos.

Effect of priming in shortening onset of pipecuronium, a new nondepolarizing neuromuscular blocker.

BACKGROUND AND OBJECTIVES: One of the most important neuromuscular blockers property is short onset, allowing early tracheal intubation. Low nondepolarizing blocker dose before the full dose is known to decrease the onset of most neuromuscular blockers. Pipecuronium bromide is a long-lasting aminosteroid with major cardiovascular stability, however, with late onset. This study aimed at evaluating pipecuronium priming effect in adult patients submitted to elective surgeries under general anesthesia. METHODS: Participated in this study 33 adult patients of both genders, aged 20 to 65 years, physical status ASA I or II, to be submitted to elective surgeries under general anesthesia. Exclusion criteria were patients with kidney or liver failure, neuromuscular diseases, in concurrent use of drugs influencing pipecuronium pharmacokinetics, and patients with family history of malignant hyperthermia. Patients were divided in 2 groups: Group 1 = priming with 0.01 mg kg(-1) and 3 minutes later the remaining 0.07 mg kg(-1) (total 0.08 mg kg(-1)); Group 2 = no priming dose (group control). Neuromuscular relaxation was controlled by acceleromyography (TOF-Guard device) and laryngoscopy was accomplished when T1 < 10%. T test for independent samples was used for statistical analysis and Shapiro Wilks was used to test normality. RESULTS: Groups were homogeneous. Time for T1 < 10% was 161.4 +/- 13.7 seconds for Group 1 and 217.8 +/- 23.4 seconds for Group 2, with p < 0.001 and statistically significant differences between groups. CONCLUSIONS: Our results have shown statistically significant differences between groups with and without priming, indicating that pipecuronium also has its onset decreased, similarly to other known neuromuscular blockers.