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BACKGROUND: Polycystic kidney disease (PKD) is the most common hereditary kidney disorder. In most patients, the disease progresses to end stage kidney disease, which is treated preferably by kidney transplantation. In certain clinical circumstances, a pretransplant nephrectomy is indicated. Data regarding long-term outcomes of pretransplant nephrectomy are limited. In this study, we aimed to compare patient and graft survival, as well as other long-term outcomes of kidney transplantation, between patients with PKD who had a pretransplant nephrectomy and those who have not. METHODS: A retrospective analysis of 112 adult kidney transplant recipients with PKD, 36 (32.14%) of which underwent a pretransplant nephrectomy. RESULTS: In a mean follow-up period of 79 and 129 months (for patients who underwent nephrectomy and patients who did not, respectively), no significant differences were found in patient and graft survival, after adjustment to age and donor type. In addition, rate of hospitalizations, urinary tract infections requiring hospitalization, diabetes mellitus, and erythrocytosis post-transplant were similar in both cohorts. CONCLUSIONS: Pretransplant nephrectomy in patients with PKD is not associated with increased risk of mortality and other long-term complications following kidney transplantation.
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Background: Sarcopenia, commonly observed in patients treated with hemodialysis, correlates with low serum phosphate levels. Although normophosphatemia is desired, dietary phosphate restriction is difficult to achieve and may result in undesirable protein restriction. Objective: We aimed to evaluate whether hyperphosphatemia is associated with higher muscle strength in patients receiving hemodialysis treatment. Design: A single-center prospective observational study. Setting: Ambulatory prevalent patients undergoing hemodialysis treatments in a dialysis unit of a tertiary hospital. Patients: Participants included prevalent patients treated with hemodialysis. All patients were above 18 years. Only patients with residual kidney function below 200 mL/24 hours were included to avoid bias. Measurements: Muscle strength was measured by handgrip strength (HGS). Each patient repeated 3 measurements, and the highest value was recorded. Handgrip strength cutoffs for low muscle strength were defined as <27 kg in men and <16 kg in women. Biochemical parameters, including serum phosphate level, were driven from routine monthly blood tests. Hyperphosphatemia was defined as serum phosphate above 4.5 mg/dL. Methods: Handgrip strength results were compared to nutritional, anthropometric, and biochemical parameters-in particular phosphate level. Long-term mortality was recorded. Results: Seventy-four patients were included in the final analysis. Handgrip strength was abnormally low in 33 patients (44.5%). Patients with abnormal HGS were older and more likely to have diabetes mellitus and lower albumin and creatinine levels. There was no correlation between HGS and phosphate level (r = 0.008, P = .945). On multivariable analysis, predictors of higher HGS were body mass index and creatinine. Diabetes mellitus and female sex predicted lower HGS. Hyperphosphatemia correlated with protein catabolic rate, blood urea nitrogen, and creatinine. On multivariable analysis, predictors of hyperphosphatemia were higher creatinine level, normal albumin level, and heart failure. During mean follow-up time of 7.66 ± 3.9 months, 11 patients died. Mortality was significantly higher in patients with abnormally low HGS compared with normal HGS (odds ratio = 9.32, P = .02). Limitations: A single-center study. All measurements were performed at one time point without repeated assessments. Direct dietary intake, degree of physical activity, and medication compliance were not assessed. Conclusion: Hyperphosphatemia correlated with increased protein intake as assessed by protein catabolic rate in patients treated with hemodialysis; however, neither correlated with higher muscle strength as measured by HGS.Trial registration: MOH 202125213.
Contexte: La sarcopénie, qui est fréquemment observée chez les patients traités par hémodialyse, est corrélée à de faibles taux sériques de phosphate. Dans ce contexte, la normophosphatémie est souhaitée, mais la restriction alimentaire en phosphate est difficile à réaliser et peut entraîner une restriction indésirable en protéines. Objectif: Notre objectif était de déterminer si l'hyperphosphatémie est associée à une plus grande force musculaire chez les patients qui reçoivent un traitement par hémodialyse. Conception: Étude observationnelle prospective monocentrique. Cadre: Le service de dialyse d'un hôpital de soins tertiaires. Sujets: Des patients prévalents âgés de plus de 18 ans qui recevaient des traitements d'hémodialyse en ambulatoire dans le service de dialyse de l'hôpital. Afin de limiter les biais, seuls les patients avec une fonction rénale résiduelle inférieure à 200 ml/24 heures ont été inclus. Mesures: La force musculaire a été mesurée par le test de force de préhension (HGS - handgrip strength). Trois mesures ont été faites pour chaque patient et la valeur la plus élevée a été enregistrée. Les seuils de faible force musculaire à l'HGS ont été établis à < 27 kg pour les hommes et à < 16 kg pour les femmes. Les paramètres biochimiques, notamment le taux de phosphate sérique, ont été déterminés à partir des analyses sanguines mensuelles des patients. L'hyperphosphatémie a été définie par une concentration sérique en phosphate supérieure à 4,5 mg/dl. Méthodologie: Les résultats de l'HGS ont été comparés aux paramètres nutritionnels, anthropométriques et biochimiques plus particulièrement au taux de phosphate. La mortalité à long terme a été enregistrée. Résultats: Soixante-quatorze patients ont été inclus dans l'analyse finale. Les résultats de l'HGS étaient anormalement faibles chez 33 patients (44,5 % des sujets). Les patients qui avaient obtenu un résultat anormal à l'HGS étaient plus âgés, plus susceptibles de souffrir de diabète, et présentaient des taux d'albumine et de créatinine plus faibles. Aucune corrélation n'a été observée entre le résultat à l'HGS et le taux sérique de phosphate (r=0.008; p=0.945). Dans l'analyse multivariée, l'indice de masse corporelle et le taux de créatinine étaient des prédicteurs d'un résultat plus élevé à l'HGS, alors que le diabète et le fait d'être une femme étaient prédictifs d'un résultat inférieur à l'HGS. L'hyperphosphatémie a été corrélée au taux de catabolisme des protéines, à l'urée et au taux de créatinine. Dans l'analyse multivariée, un taux de créatinine plus élevé, un taux d'albumine normal et une insuffisance cardiaque étaient des facteurs prédictifs d'une hyperphosphatémie. Au cours de la période moyenne de suivi (7,66 ± 3,9 mois), 11 patients sont décédés. La mortalité était significativement plus élevée chez les patients qui présentaient un résultat anormalement faible à l'HGS par rapport à la normale (RC: 9,32; p = 0,02). Limites: L'étude a été menée dans un seul centre. Toutes les mesures ont été effectuées à un moment donné sans évaluations répétées. L'apport alimentaire direct, le degré d'activité physique et l'observance des médicaments n'ont pas été évalués. Conclusion: Chez des patients traités par hémodialyse, l'hyperphosphatémie est corrélée à une augmentation de l'apport en protéines évalué par le taux de catabolisme des protéines, mais ni l'une ni l'autre n'est corrélée à une plus grande force musculaire mesurée par HGS.
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Introduction: Defining the optimal hydration status in patients with chronic kidney disease (CKD) is challenging, and the quest for an objective accurate method continues. Lung ultrasound (LUS) is a well-validated technique to estimate volume status. Previous studies examining the relationship between LUS and physical examination demonstrated conflicting results. We aimed to evaluate the correlation between LUS results and physical examination for assessing volume status in patients with CKD, and to compare different LUS protocols. Methods: A prospective, single-center trial correlating physical examination findings to LUS results in different CKD groups, including non-dialysis and dialysis patients. Hemodialysis patients were tested twice, before and after dialysis, to compare results with ultrafiltration volume. Different LUS protocols were performed and compared, including 16-, 12-, and 8-zone measurements. Results: We recruited 175 participants. A strong positive correlation was demonstrated between 16- and 12-zone protocols [r = .91 (P < .001)] and between 12- and 8-zone protocols (r = .951, P < .001). Correlation was significant in various CKD groups. While blood pressure did not correlate with LUS score, there was a significant correlation between LUS and other components of the physical examination including lung crackles (OR = 1.15 (95%CI 1.096-1.22), P < .01), pleural effusion (OR = 1.15 (95%CI 1.09-2.13), P < .01) and peripheral edema (r = .24, P < .001). Ultrafiltration volume did not correlate significantly with change in LUS scores pre- and post-dialysis (r = .169, P = .065). Conclusion: Most components of physical examination findings correlated with extravascular lung water assessment on LUS in CKD patients. The use of a simplified pragmatic LUS protocol may facilitate LUS use in clinical practice.
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BACKGROUND: Timely access to quality medical care impacts patient outcomes in inflammatory bowel disease (IBD). In a nationwide study from the epidemiology group of the Israeli IBD research nucleus we aimed to assess the impact of residence and socioeconomic status (SES) on disease outcomes. METHODS: We utilized data from the 4 health maintenance organizations in Israel, representing 98% of the population. Regions were defined as central, northern and southern; SES was graded from lowest to highest (from 1 to 4) as per Israel Central Bureau of Statistics. The primary outcome was steroid dependency, with secondary outcomes of surgeries and biologic therapy use. RESULTS: A total of 28 216 IBD patients were included: 15 818 (56%) Crohn's disease (CD) and 12 398 (44%) ulcerative colitis; 74%, 12% and 14% resided in central, southern, and northern Israel, respectively (SES 1: 21%, SES 4: 12%). Lower SES was associated with steroid dependency (20% in SES 1 vs 12% in SES 4 in CD; P < .001; and 18% vs 12% in ulcerative colitis; P < .001), and higher surgery rates (12% vs 7%; P < .001, and 1.4% vs 0.7%; P = .115, respectively). There were higher steroid dependency and CD surgery rates in peripheral vs central regions. In multivariable models, both SES and peripheral region were independently associated with poorer outcomes. CONCLUSIONS: We found that lower SES and peripheral residence were associated with deleterious outcomes in IBD. This should be considered by policymakers and should encourage strategies for improving outcomes in populations at risk.
In a novel nationwide population study, we found that patients with inflammatory bowel disease living in peripheral regions and those with lower socioeconomic status had significantly worse inflammatory bowel disease outcomes, notably higher corticosteroid dependency, higher surgery rate, and higher repeat surgery rate.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/cirurgia , Baixo Nível Socioeconômico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , EsteroidesRESUMO
Knowing the etiology of cardiac arrest (CA) is important for treatment decisions. Results of previous studies on the diagnostic role of cardiac troponin in patients resuscitated from CA are controversial, few studies were done during the era of high-sensitivity cardiac troponin-I (hs-cTnI), and kinetics of hs-cTnI was not thoroughly investigated. We aimed to explore the diagnostic value of hs-cTnI in patients resuscitated from out-of-hospital CA (OHCA). This retrospective study included 201 consecutive patients after OHCA admitted to the intensive cardiac care unit at Rambam Health Care Campus from 2016 to 2021. Patients were divided into 2 groups according to etiology of CA: group 1-patients with definite acute myocardial infarction (AMI), group 2-patients in whom AMI was excluded. Values of hs-cTnI on admission, peak hs-cTnI, and hs-cTnI upslope were compared between patients with AMI and non-AMI. Peak hs-cTnI and hs-cTnI upslope differed significantly between patients with non-AMI versus AMI CA (median 1,424 vs 32,558 ng/L, p <0.0001 and median 109 vs 2,322 ng/L/h, p <0.0001, respectively). Moreover, peak hs-cTnI and hs-cTnI upslope were found to have good discrimination performance between patients with non-AMI and AMI, with area under the curve receiver operating characteristics (ROC) curves of 0.83 and 0.80, respectively. In conclusion, in patients resuscitated from OHCA values of peak hs-cTnI and hs-cTnI upslope could be helpful in the diagnosis of etiology of CA as adjunct to other diagnostic methods.
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Infarto do Miocárdio , Parada Cardíaca Extra-Hospitalar , Humanos , Troponina I , Estudos Retrospectivos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/etiologia , Biomarcadores , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/complicações , Troponina TRESUMO
BACKGROUND: With the aging of the population, more older patients are being considered for kidney transplantation; therefore, it is crucial to evaluate the risks and benefits of transplantation in this population. This study aimed to assess long-term outcomes of kidney transplantation in a cohort of patients who underwent kidney transplantation at age >70 years, compared with patients aged 60 to 69 years at transplantation. METHODS: Included in the study were 261 consecutive kidney transplant recipients: 52 were aged >70 years, and 209 were aged 60 to 69 years at transplantation. Data were collected retrospectively and analyzed using multivariate logistic regression to identify potential outcome risk factors. RESULTS: The number of transplants in both groups increased during the study period. Mortality after transplantation was strongly correlated to age (hazard ratio [HR] = 1.11; 95% CI, 1.05-1.18; P < .001), deceased donor (HR = 2.0; 95% CI, 1.1-3.8; P = .034), and pretransplant diabetes (HR = 2.9; 95% CI, 1.7-4.9; P = .001). Recipients aged >70 years had an increased risk of death censored graft failure (HR = 2.98; 95% CI, 1.56-5.74; P = .001). In living donor transplants, 3-year survival was 80% in recipients age >70 years, compared with 98% in the 60- to 69-year group. Five-year survival was 71% and 92%, respectively. In deceased donor transplants, 3-year survival was 63% and 78%, and 5-year survival was 58% and 72%, respectively. The risk of malignancy (excluding nonmelanotic skin cancer) was nearly triple in the age >70 years group (HR = 2.96; 95% CI, 1.3-6.8; P = .01). CONCLUSIONS: Patient and graft survival in kidney recipients in the eighth decade is worse compared with recipients in the seventh decade of life. However, it is improved with living kidney donation.
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Transplante de Rim , Humanos , Idoso , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Rejeição de Enxerto/epidemiologia , Doadores de Tecidos , Doadores Vivos , Rim , Sobrevivência de Enxerto , TransplantadosRESUMO
BACKGROUND AND OBJECTIVES: Antileucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis was first described in 2010 and is today the most common type of limbic encephalitis. During the course of the disease, 60%-88% of the patients develop hyponatremia. The etiology of the sodium disorder is unclear, often presumed to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Other electrolyte abnormalities have not been reported in association with anti-LGI1 antibody encephalitis. Due to the presence of hypomagnesemia and hypophosphatemia in our patients, we set out to try to find the expression of LGI1 protein in the kidney as an explanation for these abnormalities. METHODS: We reviewed the medical files of all patients diagnosed with anti-LGI1 antibody encephalitis, at the Department of Neurology in the Tel Aviv Medical Center between January 2011 and December 2020, exploring for electrolyte abnormalities. Using tissue staining, Western blot, mass spectrometry, and RNA expression techniques, we tried to demonstrate the expression of LGI1 protein in the human kidney. RESULTS: We identified 15 patients diagnosed with anti-LGI1 antibody encephalitis. Their average age was 65 years (44-80), and 9 were male individuals. Thirteen of the 15 patients (87%) developed varying degrees of hyponatremia. Laboratory studies demonstrated low serum osmolality, low serum blood urea nitrogen, and low uric acid, with a high urinary sodium and inappropriately high urine osmolality, supporting the presumable diagnosis of SIADH. One patient with hyponatremia that was tested, had high levels of copeptin, supporting the diagnosis of SIADH. In addition to hyponatremia, 7 patients (47%) exhibited other electrolyte abnormalities; 5 patients (33%) had overt hypophosphatemia, 4 patients (27%) had overt hypomagnesemia, and 2 other patients (13%) had borderline low magnesium levels. Western blot analysis of human kidney lysate, mass spectrometry, and qRT-PCR failed to demonstrate the expression of LGI1 protein in the kidney. DISCUSSION: Hyponatremia in patients with anti-LGI1 antibody encephalitis is due to SIADH as previously assumed. Other electrolyte abnormalities such as hypomagnesemia and hypophosphatemia occur in at least 40% of patients and may be another clue for the diagnosis of anti-LGI1 antibody encephalitis. Because we failed to demonstrate LGI1 expression in the kidney, the results of our study suggest that renal losses lead to these disturbances, most probably due to SIADH.
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Encefalite , Hiponatremia , Hipofosfatemia , Síndrome de Secreção Inadequada de HAD , Humanos , Masculino , Idoso , Feminino , Hiponatremia/diagnóstico , Hiponatremia/etiologia , Encefalite/diagnóstico , Anticorpos , Eletrólitos , SódioRESUMO
Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein induced during tissue damage and is not expressed in mature renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. A single Intraperitoneal (IP) injection of folic acid induced AKI in WT and CD24-/- mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis, and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. FA-AKI induced CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24-/- mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. In contrast, renal and systemic IL-33 upregulation were augmented. CD24-/- FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24-/- mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti-CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function as well as the histological injury. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. In conclusion, during AKI, upregulation of CD24 promotes renal inflammation through inhibition of Treg infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove a target for future therapies in AKI.
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Inflammatory bowel diseases are increasing among different ethnic groups. We aimed to compare the clinical characteristics, complications, and outcomes among Arab and Jewish people sharing the same healthcare system. All patients older than 18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between the years 2000 and 2021 were included. Data regarding demographics, disease characteristics, extraintestinal manifestation, treatment, comorbidities, and mortality were retrieved. A total of 1263 (9.8%) Arab CD patients were compared with 11,625 Jewish CD patients, and 1461 (11.8%) Arab UC patients were compared to 10,920 Jewish patients. Arab CD patients were younger at diagnosis, 36.11 ± 16.7 compared to 39.98 ± 19.4 years, p < 0.001, 59.5% males compared to 48.7%, p < 0.001; in addition, Arab CD patients had a higher rate of anal fissure, perianal abscess, erythema nodosum, diabetes mellitus, obesity, liver cirrhosis, and male infertility. Arab CD patients were less frequently treated with azathioprine or mercaptopurine compared with Jewish patients. No significant difference was found in the rate of anti-TNF treatment, but a higher rate of steroids treatment was found. The all-cause mortality of CD patients was lower among Arab patients (8.4% vs. 10.2%, p = 0.039). Significant differences were found regarding disease characteristics, course, comorbidities, and treatment among Arab and Jewish patients with IBD.
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BACKGROUND: Chronic abdominal pain and fatigue are characteristics of Crohn's disease (CD) and contribute to functional impairments. AIMS: To examine whether CD-tailored cognitive-behavioural and mindfulness intervention (COBMINDEX) is effective in reducing abdominal pain and fatigue in patients with CD and whether changes in abdominal pain and fatigue mediate any beneficial effects of COBMINDEX on impairments in work productivity and daily activities. METHODS: This is a secondary analysis of a parallel-group multicentre randomised controlled trial. Patients with mild-to-moderate CD (n = 142) were randomised into either intervention group receiving COBMINDEX, or control group receiving treatment-as-usual for 3 months followed by COBMINDEX. Complete data were collected from 120 patients (34.0 ± 10.7 years, 62.5% female, intervention = 60, control = 60). Analysis of covariance assessed group differences in 3-month follow-up scores, controlling for baseline scores. Multiple parallel mediation analysis assessed the proposed mechanisms for the entire sample. RESULTS: The intervention group demonstrated significantly lower levels of abdominal pain (F = 17.46, p < 0.001, η2 p = 0.13), fatigue (F = 7.26, p = 0.008, η2 p = 0.06) and impairments at work (F = 4.82, p = 0.032, η2 p = 0.07) and daily activities (F = 6.26, p = 0.014, η2 p = 0.05), compared with treatment-as-usual. Moreover, changes in abdominal pain and fatigue significantly mediated the beneficial effects of COBMINDEX on patients' work productivity (b = -9.90, SE = 2.86, 95% CI: -16.11 to -4.94) and daily activities (b = -9.65, SE = 1.91, 95% CI: -13.77 to 6.35), independent of changes in disease activity. CONCLUSIONS: COBMINDEX is effective at reducing abdominal pain and fatigue in patients with CD, which in turn leads to improvement in functioning. Clinicians should incorporate screening for severe abdominal pain and fatigue and consider offering cognitive-behavioural and mindfulness training. CLINICALTRIALS: gov, Number: NCT05085925. Ministry of Health in Israel (https://my.health.gov.il/CliniTrials/Pages/MOH_2020-02-24_008721.aspx).
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Doença de Crohn , Humanos , Feminino , Masculino , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Intervenção Psicossocial , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Fadiga/etiologia , Fadiga/terapia , Israel , Qualidade de VidaRESUMO
Background: Since the outbreak of COVID-19, a significant decline in endoscopic procedures has been observed. Aims: We investigated the change of incidence, clinical characteristics, disease stage and mortality of patients with gastric cancer (GC) or colorectal cancer (CRC) diagnosed in 2020 compared to the pre-pandemic year 2019. Methods: Demographic, clinical and laboratory data on all patients diagnosed with GC or CRC at the Soroka University Medical Center were retrospectively collected and compared. Number of cases, time of diagnosis, clinical presentation, staging at diagnosis and mortality rates were compared. Results: Two hundred sixteen patients were diagnosed with CRC in 2019, whereas only 162 were diagnosed in 2020 (25% reduction), while 36 GC diagnoses were made in 2019 compared to 24 in 2020 (33% reduction). The age-adjusted incidence was calculated to be 24.28 for CRC and 5.0 for GC in 2020 compared to 29.93 and 5.32 in 2019, respectively. CRC patients had a significantly lower rate of rectal bleeding as their presenting symptom in 2020 compared with 2019, 8.1 vs. 19% (p = 0.003), but higher rate of diarrhea as their presenting symptom, 4.3 vs. 1% (p = 0.044). No significant differences regarding other presenting symptoms, comorbidities, surgery or mortality rates were found between the groups diagnosed in 2019 or 2020. Conclusion: A decrease in GC and CRC incidence was observed during the year 2020; lower rate of rectal bleeding and higher rate of diarrhea as presenting symptoms were noted in 2020, but no significant difference was found regarding other presenting symptoms, disease stage, surgery or mortality.
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INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality after kidney transplantation. Metabolic syndrome is common in renal transplant recipients and is associated with increased CVD risk in those patients. Nonalcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of a multi-system disorder, including CVD and metabolic syndrome. The data about prevalence of NAFLD before kidney transplantation and its consequences following transplantation are scarce. METHODS: A retrospective study of metabolic parameters and sonographic evidence of NAFLD, and an analysis of its metabolic outcomes, was performed in 341 consecutive kidney transplant recipients. RESULTS: One-hundred twenty-four (36.4%) kidney recipients had NAFLD before transplantation. The risk of NAFLD before kidney transplantation was independently and significantly related to diabetes (OR = 1.8), male gender (OR = 1.4), older age (every year of age increased the risk by 4%), higher BMI (every increase of 1 kg/m2 increased the risk by 15%), and higher triglycerides level. Mean levels of liver enzymes were similar in patients with and without NAFLD. Recipients with NAFLD before transplantation had a higher prevalence of new onset diabetes, even after adjustment to covariables. In addition, they had a higher increase in liver enzymes, triglycerides, and FIB-4 score, as an indication of liver fibrosis, after transplantation. Furthermore, NAFLD pre-transplantation was independently associated with cardiovascular mortality (HR = 4.4) following kidney transplantation. CONCLUSIONS: Sonographic evidence of NAFLD before kidney transplantation is associated with significant metabolic outcomes including de novo diabetes and cardiovascular mortality following transplantation and should be included as part of the assessment of kidney transplant candidate.
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Doenças Cardiovasculares , Diabetes Mellitus , Transplante de Rim , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Transplante de Rim/efeitos adversos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Estudos Retrospectivos , Fatores de Risco , Diabetes Mellitus/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , TriglicerídeosRESUMO
INTRODUCTION: Kidney transplantation is the treatment of choice for patients with renal failure. It is crucial to select which patients may benefit from renal transplantation and which are at high risk for post-transplant complications. Sarcopenia is associated with poor outcome in various conditions, including in chronic kidney disease patients. The gold standard for measuring sarcopenia is computed tomography (CT) imaging to estimate muscle mass and quality since it is objective, reproducible, and reflects the overall health condition. The data regarding those measurements among kidney transplant recipients are limited, therefore we aimed to describe it in patients before kidney transplantation, assess the parameters associated with sarcopenia, and evaluate the clinical significance of those markers on outcomes following transplantation. METHODS: We retrospectively analyzed 183 kidney transplant recipients who had a CT scan 90 days prior to transplant. Sarcopenia was assessed by measuring the cross-sectional area (CSA) and mean muscle density of the psoas muscle at the third and fourth lumbar vertebrae levels and paravertebral muscles at the 12th thoracic vertebra level. RESULTS: There was a strong linear correlation between muscle size measured as CSA of the psoas muscle at the L3 and L4 vertebral body level and the CSA of the paravertebral muscles at the D12 vertebra level, and a moderate correlation to muscle density at those levels. Age was independently associated with risk of sarcopenia, defined as psoas CSA in the lowest tertile, with every year of age increasing the risk by 5%. CSA at the L3 level had a significant independent association with post kidney transplantation mortality, with an adjusted hazard ratio of 0.86 per cm2. There was a significantly longer hospitalization period postoperation in kidney recipients in the lower tertile of psoas CSA and density. CONCLUSIONS: Sarcopenia as measured by psoas CSA is associated with poor short- and long-term outcomes following kidney transplantation and should be included as part of the assessment of kidney transplantation candidates.
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Transplante de Rim , Sarcopenia , Humanos , Transplante de Rim/efeitos adversos , Modelos de Riscos Proporcionais , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/patologia , Estudos Retrospectivos , Sarcopenia/diagnóstico , Sarcopenia/diagnóstico por imagemRESUMO
BACKGROUND: Most solid organ transplant recipients did not develop an appreciable serologic response after 2 doses of the mRNA SARS-CoV-2 vaccine. METHODS: We analyzed the humoral response after a third dose of the BNT162b2 vaccine in 130 kidney transplant recipients, compared to 48 health care workers, and associated factors, including prevaccine cellular immune response, by evaluating intracellular cytokine production after stimulation of donor's peripheral blood mononuclear cells. RESULTS: After 2 doses, most of the controls (47 out of 48, 98%) and only 40% of kidney recipients (52 of 130) kidney recipients were seropositive (P < .001). Most seronegative recipients developed a serologic response after the booster (47 out 78, 60%), thus bringing the total number of seropositive recipients to 99 out of 130 (76%). After the third dose, there was a significant increase in antibodies titers in both groups. Decreased humoral response was significantly associated with an older age, lower lymphocyte count, and a lower level of antibodies before booster administration. CD4+TNFα+ and CD4+INFγ+ were correlated with mean increase in antibody titers. CONCLUSIONS: A third dose of the BNT162b2 mRNA vaccine in kidney recipients is safe and effectively results in increased IgG anti-S levels, including in individuals who were seronegative after 2 doses. Long-term studies of the length of the immune response and protection are required.
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Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Transplante de Rim , Transplantados , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunização Secundária/efeitos adversos , Imunoglobulina G , Transplante de Rim/efeitos adversos , Leucócitos Mononucleares , RNA Mensageiro , SARS-CoV-2 , Fator de Necrose Tumoral alfa , Vacinas Sintéticas , Vacinas de mRNARESUMO
The use of a bone allograft presents a promising approach for healing nonunion fractures. We have previously reported that parathyroid hormone (PTH) therapy induced allograft integration while modulating angiogenesis at the allograft proximity. Here, we hypothesize that PTH-induced vascular modulation and the osteogenic effect of PTH are both dependent on endothelial PTH receptor-1 (PTHR1) signaling. To evaluate our hypothesis, we used multiple transgenic mouse lines, and their wild-type counterparts as a control. In addition to endothelial-specific PTHR1 knock-out mice, we used mice in which PTHR1 was engineered to be constitutively active in collagen-1α+ osteoblasts, to assess the effect of PTH signaling activation exclusively in osteoprogenitors. To characterize resident cell recruitment and osteogenic activity, mice in which the Luciferase reporter gene is expressed under the Osteocalcin promoter (Oc-Luc) were used. Mice were implanted with calvarial allografts and treated with either PTH or PBS. A micro-computed tomography-based structural analysis indicated that the induction of bone formation by PTH, as observed in wild-type animals, was not maintained when PTHR1 was removed from endothelial cells. Furthermore, the induction of PTH signaling exclusively in osteoblasts resulted in significantly less bone formation compared to systemic PTH treatment, and significantly less osteogenic activity was measured by bioluminescence imaging of the Oc-Luc mice. Deletion of the endothelial PTHR1 significantly decreased the PTH-induced formation of narrow blood vessels, formerly demonstrated in wild-type mice. However, the exclusive activation of PTH signaling in osteoblasts was sufficient to re-establish the observed PTH effect. Collectively, our results show that endothelial PTHR1 signaling plays a key role in PTH-induced osteogenesis and has implications in angiogenesis.
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Células Endoteliais , Hormônio Paratireóideo , Animais , Regeneração Óssea , Camundongos , Hormônio Paratireóideo/farmacologia , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Microtomografia por Raio-XRESUMO
BACKGROUND & AIMS: Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. METHODS: This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. RESULTS: Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). CONCLUSIONS: In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. CLINICALTRIALS: gov ID: NCT01941589.
Assuntos
Produtos Biológicos , Colite Ulcerativa , Humanos , Feminino , Adulto , Mesalamina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Anti-Inflamatórios não Esteroides/uso terapêutico , Resultado do Tratamento , Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the hypothalamus-pituitary-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) impacts their inflammatory process. METHODS: Circulating inflammatory markers and a wide range of psychological parameters related to stress and well-being were measured in CD patients before and after COBMINDEX. Inflammatory markers in CD patients were also compared to age- and sex-matched healthy controls (HCs). RESULTS: CD patients exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by interconnected inflammatory modules represented by IL-6, TNFα, IL-17, MCP-1 and IL-18. Notably, higher IL-18 levels correlated with higher score of stress and a lower score of wellbeing in CD patients. COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 and IFNα and negatively with those of MCP-1. Furthermore, inflammatory markers of CD patients at baseline predicted COBMINDEX efficacy, as higher levels of distinct cytokines and cortisol at baseline, correlated negatively with changes in disease activity (by Harvey-Bradshaw Index) and psychological distress (global severity index measure) following COBMINDEX. CONCLUSION: CD patients have a characteristic immunological profile that correlates with psychological stress, and disease severity. We suggest that COBMINDEX induces stress resilience in CD patients, which impacts their well-being, and their disease-associated inflammatory process.
RESUMO
BACKGROUND: It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. METHODS: Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan-Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. RESULTS: A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8-9.1] in 2005-2008 vs 0.8 years [0.4-1.5] in 2015-2018; p < 0.001]. Annual rates of surgeries [AAPC -1.3; p = 0.6] and steroid-dependency [AAPC -1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC -1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. CONCLUSION: During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased.
Assuntos
Produtos Biológicos , Colite Ulcerativa , Adulto , Idoso , Produtos Biológicos/uso terapêutico , Criança , Colectomia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Humanos , Estimativa de Kaplan-Meier , EsteroidesRESUMO
BACKGROUND: In recent years, the use of abdominal pelvic computed tomography (APCT) in the emergency department (ED) for patients with Crohn's disease (CD) has risen steadily. Thus, exposing these patients to recurrent radiation, despite studies showing that only 30% to 40% had significant findings in ED APCT. GOAL: Our aim was to find clinical and laboratory variables that can predict substantial findings on ED APCT, which may require invasive intervention. METHODS: We analyzed ED visits of patients with known CD that underwent an emergent APCT for gastrointestinal complaints, over a 10-year period. Patients with positive and negative findings in the APCT were compared in order to evaluate independent effects of different variables, including patients' characteristics, CD history, ED complaints, and laboratory tests. RESULTS: In 44% of 183 ED visits, there were significant findings on ED APCT, however, only 22% of them underwent invasive intervention. Laboratory tests: C-reactive protein >50 mg/L, neutrophil count >75%, platelet count >350×10 9 /L, and ileocolon location at diagnosis were all positive predicting factors. Whereas, smoking or ED complaints of diarrhea/fever reduced the risk for significant findings. CONCLUSIONS: Using the 7 most significant predicting factors, we built an easy to use scoring system-Crohn Assessment Tool for CT upon Hospitalization (CATCH) for ED clinicians. This scoring system could have prevented unnecessary ED APCT from 42% of the patients in our study, without missing those who required invasive intervention.
Assuntos
Doença de Crohn , Doença de Crohn/diagnóstico por imagem , Serviço Hospitalar de Emergência , Humanos , Pelve/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. METHODS: Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. RESULTS: A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9-8.1] years in those diagnosed in 2005-2008 compared with 0.5 [0.2-1.1] years in those diagnosed in 2015-2018; pâ <â 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1-4.6] years compared with 0.2 [0.02-0.9] years; pâ <â 0.001), steroid dependency (1.5 [0.2-5.4] years compared with 0.1 [0.02-0.4] years; pâ <â 0.001), and intestinal surgeries [4.7 [1.6-8.2] years compared with 0.6 [0.2-1.4] years; pâ <â 0.001), but not of perianal surgery (4.2 [1.1-7.7] years compared with 0.6 [0.2-1.4] years; pâ =â 0.2). Outcomes were consistently worse in paediatric onset compared with adults. CONCLUSIONS: The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.