•Vascular endothelial growth factor.•Pediatric hematopoietic stem cell transplantation.•Real-time Polymerase Chain Reaction.
Vascular endothelial growth factors are proteins that participate in ...processes related to normal physiology, solid tumors and hematologic malignancies; however, their role in hematopoietic stem cell transplantation (HSCT) requires further investigation. To better define the role and changes in vascular endothelial growth factor-A (VEGF-A) in the context of HSCT, we conducted an observational prospective analysis of VEGF-A expression during the early period after HSCT in pediatric patients. Thirty-seven pediatric patients who underwent hematopoietic stem cell transplantation at the Federico Gómez Children's Hospital in Mexico between June 2016 and July 2018 were prospectively enrolled in this study. Ribonucleic acid was isolated from the venous blood of these patents on Days 0, +7, +14, +21, +28, and +35 after transplantation, and TaqMan reverse transcription-polymerase chain reaction was performed using specific primers and a probe for VEGF-A. The concentration of VEGF-A was determined using a complementary deoxyribonucleic acid control. Data were analyzed using one-way ANOVA and Dunnett post hoc tests. Statistical analysis was performed using SPSS version 25. There were significant differences in the concentrations of VEGF-A between Day 0 vs. Day +28 (p = 0.009 95% CI=0.02–0.24), Day 0 vs. Day +35 (p = 0.006; 95% CI=0.03–0.28) and Day 7 vs. Day + 35 (p = 0.006; 95% CI=0.03–0.24) after allogeneic HSCT. We observed significant increases in the VEGF-A concentration during the early period after stem cell transplantation in pediatric patients. Our results provide important insights that should be considered a basis for future clinical trials of pediatric HSCT, including the monitoring of VEGF-A concentrations, proteins and in vitro analysis.
Fecal microbiota transplantation (FMT) is an accepted procedure for the management of recurrent Clostridioides difficile infections. FMT is generally considered safe and well-tolerated - even in ...high-risk patients. Most short-term risks are mild and known to be associated with delivery methods. Long-term side effects have not been established, and no signs of harm have been found to date. However, causality for several microbiome-associated diseases has to be established. Even though FMT is generally considered safe with strict donor screening, serious adverse events have been recently associated with the FMT product from the stool bank, where screening for multi-drug resistant organisms is not included in protocols. Here, we discuss the adverse events associated with FMT and safety issues.
Purpose
Considering the initial treatment of hepatocellular carcinoma (HCC), the best prognostic index for Child–Pugh classes B and C (CP-BC) patients has not been yet established. This study aimed ...to elucidate the risk factors for disease-free survival (DFS) and overall survival (OS) in multicenter patients with a poor liver functional reserve after curative treatment.
Methods
Between April 2000 and April 2014, 212 CP-BC patients who received treatment in five high-volume centers in Japan were included in this study. CP-B and C patients were 206 and 6, respectively. Cox proportional hazard regression analyses for DFS and OS were performed to estimate the risk factors.
Results
The mean observation time was 1132 days. Mean Child–Pugh score and indocyanine green retention rate at 15 min were 7.5 and 31.5%, respectively. Histological chronic hepatitis and liver cirrhosis were observed in 20% and 74% patients, respectively. In the multivariate analysis, the risk factors for DFS were des-gamma-carboxy prothrombin (DCP) hazard ratio (HR), 1.6;
P
= 0.012 and treatment without liver transplantation. Moreover, DCP was identified as an independent risk factor for OS (HR, 1.7;
P
= 0.01). Tumor size, number, tumor thrombus, Milan criteria, liver cirrhosis, and treatment without liver transplantation were not identified as risk factors for OS. The 5-year OS in patients with high serum DCP levels (< 90 mAU/mL) was significantly better than that in those with low serum DCP levels (
P
= 0.003).
Conclusions
Serum DCP value before treatment predicted both DFS and OS in CP-BC patients with HCC.
Thrombocytopenia is among the most common complications following hematopoietic stem cell transplantation and is associated with increased mortality and morbidity with no standard treatment yet. In ...this multicenter and retrospective study, we aim to present our multi-center experience of Eltrombopag treatment in patients with isolated thrombocytopenia following HSCT.
A total of 73 patients from 5 centers who underwent autologous or allogeneic stem cell transplantation, had no primary disease relapse, all of whom had neutrophil engraftment, complete chimerism, and who were diagnosed with Prolonged Isolated Thrombocytopenia (PIT) or Secondary Failure Of Platelet Recovery (SFPR) were included in the study. The patients were initiated on Eltrombopag at a dose of 50–150 mg. Complete response was defined as a platelet count >50×109/L for 7 consecutive days with no transfusion support.
A total of 50.3% of the patients underwent Autologous and 49.7% Allogeneic Stem Cell Transplantation, 54.8% were diagnosed with PIT, and 45.2% were diagnosed with SFPR, and the treatment with 50–150 mg/day Eltrombopag was initiated on the median day +42. Complete response was achieved in 71.2% of these patients on the median day 23 of the treatment. No significant effects of the initial dose (50–150 mg/day) were detected in the Complete Response in the multivariate analysis on response. An insufficient number of Megakaryocytes in the bone marrow before Eltrombopag treatment was determined as an independent risk factor in determining the response (OR 3.57, 95% CI 1.21–10.55). The overall survival of the patients who did not respond to Eltrombopag was found to be significantly worse than that of patients who responded (p=0.022, HR:2.74, 95% CI 1.12–6.54).
As a result of the present study, Eltrombopag treatment was found to be effective and safe in thrombocytopenia that develops following hematopoietic stem cell transplantation. It was concluded that its use may be more effective in patients with sufficient bone marrow megakaryocytes before the treatment and an initial dose of 50 mg/day may be appropriate in terms of cost, effectiveness, and toxicity. Large-scale randomized and controlled prospective studies are needed to determine the roles of Eltrombopag treatment in patients with post-transplant PIT and SFPR.
Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool ...consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients. Clin Endosc 2021;54:152-156
Oxalate overproduction in Primary Hyperoxaluria type I (PH1) leads to progressive renal failure and systemic oxalate deposition. In severe infantile forms of PH1 (IPH1), end-stage renal disease ...(ESRD) occurs in the first years of life. Usually, the management of these infantile forms is challenging and consists in an intensive dialysis regimen followed by a liver-kidney transplantation (combined or sequential).
Medical records of all infants with IPH1 reaching ESRD within the first year of life, diagnosed and followed between 2005 and 2018 in two pediatric nephrology departments in Brussels and Paris, have been reviewed.
Seven patients were included. They reached ESRD at a median age of 3.5 (2-7) months. Dialysis was started at a median age of 4 (2-10 months). Peritoneal dialysis (PD) was the initial treatment for 6 patients and hemodialysis (HD) for one patient. Liver transplantation (LT) was performed in all patients and kidney transplantation (KT) in six of them. A sequential strategy has been chosen in 5 patients, a combined in one. The kidney transplanted as part of the combined strategy was lost. Median age at LT and KT was 25 (10-41) months and 32.5 (26-75) months, respectively. No death occurred in the series. At the end of a median follow-up of 3 years, mean eGFR was 64 ± 29 ml/min/1.73 m
. All patients presented retinal and bone lesions and five patients presented bones fractures.
Despite encouraging survival figures, the morbidity in IPH1 patients remains extremely heavy and its management presents a huge challenge. Thanks to the newly developed RNA-interference drug, the future holds brighter prospects.
Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and ...diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a ‘chamber of secrets’, particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.
Aim: To evaluate the cardiovascular system functions biochemically and echocardiographically in renal transplant recipients before and after transplantation. Materials and Methods: Patients who were ...followed up in Gazi University Faculty of Medicine, Department of Pediatric Nephrology and diagnosed with CRF, and underwent renal transplantation before the age of 18 were included in the study. A control group was formed from healthy volunteers. BMI, biochemical values, echocardiographic findings, and CIMT measurements of these patients before and after transplantation were compared. Tissue Doppler imaging and BNP values performed after transplantation were compared with the control group. Results: Data from 64 subjects (patient group;32, healthy control group;32) were evaluated. Values of the patients before and after renal transplantation were compared. BMI values increased significantly after transplantation compared to pre-transplantation (p
Amaç: Renal transplantasyon hastalarında transplantasyon öncesi ve sonrası kardiyovasküler sistem fonksiyonlarını biyokimyasal ve ekokardiyografik açıdan değerlendirmek. Gereç ve Yöntemler: Gazi Üniversitesi Tıp Fakültesi Çocuk Nefroloji Bölümü’nde takip edilen KBY tanısı alıp 18 yaşından önce renal transplantasyon yapılan hastalar çalışmaya dahil edildi. Araştırma kriterlerine uygun sağlıklı gönüllülerden kontrol grubu oluşturuldu. Bu hastaların transplantasyon öncesi ve sonrası vücut kitle indeksleri, biyokimyasal değerleri, ekokardiyografi bulguları, CİMT ölçümleri karşılaştırıldı. Hastalara transplantasyon sonrası bakılan doku Doppler görüntüleme ile BNP değerleri kontrol grubu ile karşılaştırıldı. Bulgular: Toplam 64 veri (hasta grubu;32, sağlıklı kontrol grubu;32) değerlendirildi. Hastaların renal transplantasyon öncesi ve sonrası değerleri karşılaştırıldı. VKİ değerlerinin nakil sonrasında nakil öncesine göre istatistiksel açıdan anlamlı derecede arttığı(p
Newer coexisting conditions should be identified in order to modify newer risk factors. Aim was to identify patients with non-classical or less common coexisting conditions in patients infected of ...COVID 19.
Single centred study from June 2020 to May 2021 at a tertiary centre in North India. A preformed questionnaire was used to record clinical and laboratory parameters and to identify cases which are in addition to CDC list and Indian data.
0.67% (46) cases out of 6832 patients were identified to have non-classical coexisting illness. It was divided into 2 groups-infections A (60.1%) and non-infections B (39.9%). Group A included-tuberculosis- pulmonary (14.3%) & extra pulmonary (32.9%), bacterial (25.0%) viral infections dengue, hepatitis B & C (14.3%), HIV disease (10.7%) and malaria (3.6%). Group B included- organ transplant (27.8%), autoimmune myasthenia gravis, polymyositis, psoriasis (22.6%), haematologic Haemophilia, ITP, Aplastic anaemia, APML, CML (27.8%), uncommon malignancies disseminated sacral chordoma and GTN (11.1%) and snakebite (11.1%). Serum Procalcitonin was not helpful for diagnosis of bacterial infection in COVID-19 disease. Group A had significantly longer duration of illness, hepatitis and elevated CRP. The mortality in group A & B were 32.1% and 43.8% respectively. Death in non-severe COVID cases was in tetanus and snakebite. 30.7% death among tuberculosis patients. More than 70% of deaths were attributable to COVID 19 in both the groups.
In Indian settings, comorbidities like tuberculosis and bacterial infections can precipitate severe COVID 19 unlike other parts of the world where tuberculosis is relatively uncommon.
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