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Transplantation Reviews (Orlando, Fla.) Dec 2021Portal vein obstruction (PVO) is a significant vascular complication after liver transplantation (LT) in pediatric patients. Current treatment strategies include... (Review)
Review
INTRODUCTION
Portal vein obstruction (PVO) is a significant vascular complication after liver transplantation (LT) in pediatric patients. Current treatment strategies include percutaneous transluminal angioplasty (PTA), with or without stent placement, mesorex bypass (MRB), splenorenal shunt, mesocaval shunt, endovascular recanalization (EVR), splenic artery embolization and splenectomy. However, specific characteristics of patients undergoing intervention and selection of individual treatment and its efficacy have remained unclear. This review systematically analyzed biochemical and clinical characteristics, selection of treatment, efficacy, and post-procedural complications.
METHODS
We systematically searched PubMed and Embase between January 1995 and March 2021 for studies on the management of PVO after LT. We analyzed the reports for biochemical and clinical characteristics at the timing of the intervention in different patients, selection of treatment, and reported efficacies.
RESULTS
We found 22 cohort studies with 362 patients who had the following characteristics: biliary atresia (83%), living-donor LT (85%), thrombocytopenia (73%), splenomegaly (40%), ascites (16%), or gastrointestinal bleeding (26%). The 3-year primary patency of PTA without stent placement was similar to that with stent placement (70%-80% and 43%-94%, respectively). MRB was used as an initial treatment with a 3-year patency of 75% to 100%. One study showed that 5-year primary patency of EVR was 80%. Secondary patency was 90% to 100% after 3 years in all studies with PTA alone, PTA/stent placement, and stent placement alone.
CONCLUSION
This is the first review of all treatment protocols in PVO after pediatric LT. We showed that an important group of patients has severe symptoms of portal hypertension. Efficacy of all treatment modalities was high in the included studies which make them important modalities for these patients.
Topics: Angioplasty; Child; Humans; Liver Transplantation; Portal Vein; Stents; Vascular Patency
PubMed: 34107368
DOI: 10.1016/j.trre.2021.100630 -
The Cochrane Database of Systematic... Mar 2015Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence.
OBJECTIVES
To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014.
SELECTION CRITERIA
All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the risk of bias in the included studies, and extracted relevant data.
MAIN RESULTS
Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously untreated individuals with type 1 Gaucher disease. Two studies investigated maintenance enzyme replacement therapy in people with stable type 1 Gaucher disease previously treated for at least two years. One study compared substrate reduction therapy, enzyme replacement therapy and a combination thereof as maintenance therapy in people with type 1 Gaucher disease previously treated with enzyme replacement therapy. One study examined substrate reduction therapy in people with chronic neuronopathic (type 3) Gaucher disease who continued to receive enzyme replacement therapy.Treatment-naïve participants had similar increases in haemoglobin when comparing those receiving imiglucerase or alglucerase at 60 units/kg, imiglucerase or velaglucerase alfa at 60 U/kg, taliglucerase alfa at 30 units/kg or 60 units/kg, and velaglucerase alfa at 45 units/g or 60 units/kg. For platelet count response in participants with intact spleens, a benefit for imiglucerase over velaglucerase alfa at 60 units/kg was observed, mean difference -79.87 (95% confidence interval -137.57 to -22.17). There were no other significant differences in platelet count response when comparing different doses of velaglucerase alfa and of taliglucerase alfa, and when comparing imiglucerase to alglucerase. Spleen and liver volume reductions were not significantly different in any enzyme replacement therapy product or dose comparison study. Although a dose effect on serum biomarkers was not seen after nine months, a significantly greater reduction with higher dose was reported after 12 months in the velaglucerase study, mean difference 16.70 (95% confidence intervaI 1.51 to 31.89). In the two enzyme replacement therapy maintenance studies comparing infusions every two weeks and every four weeks, there were no significant differences in haemoglobin concentration, platelet count, and spleen and liver volumes over a 6 to 12 month period when participants were treated with the same cumulative dose.A total of 25 serious adverse events were reported, nearly all deemed unrelated to treatment.There are, as yet, no randomized trials of substrate reduction therapy in treatment-naïve patients that can be evaluated. Miglustat monotherapy appeared as effective as continued enzyme replacement therapy for maintenance of hematological, organ and biomarker responses in people with type 1 Gaucher disease previously treated with imiglucerase for at least two years. In those with neuronopathic Gaucher disease, no significant improvements in haemoglobin concentration, platelet count or organ volumes occurred when enzyme replacement therapy was augmented with miglustat.One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review.
AUTHORS' CONCLUSIONS
The results reflect the limitations of analysing evidence restricted to prospective randomized controlled trials, especially when dealing with chronic rare diseases. This analysis suggests that, during the first year of treatment, different recombinant glucocerebrosidases are bio-similar and non-inferior in safety and efficacy for surrogate biological response parameters. Enzyme replacement therapy given at 30 to 45 units/kg body weight every two to four weeks was generally as effective as the 60 unit/kg dose for the assessed clinical outcomes. The analysis emphasise the need to determine whether it is realistic to carry out multi-decade prospective clinical trials for rare diseases such as type 1 Gaucher disease. With large treatment effects on the classical manifestations of the disorder, therapeutic investigations in Gaucher disease mandate innovative trial designs and methodology to secure decisive data concerning long-term efficacy and safety - with the realization that knowledge about disease-modifying actions that are sustained are of crucial importance to people with this chronic condition.
Topics: 1-Deoxynojirimycin; Enzyme Inhibitors; Enzyme Replacement Therapy; Gaucher Disease; Glucosylceramidase; Hemoglobin A; Hepatomegaly; Humans; Platelet Count; Randomized Controlled Trials as Topic; Splenomegaly; Substrate Specificity
PubMed: 25812601
DOI: 10.1002/14651858.CD010324.pub2 -
Molecular Genetics & Genomic Medicine Mar 2024Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual... (Review)
Review
BACKGROUND
Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.
METHODS
We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.
RESULTS
We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.
CONCLUSION
We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.
Topics: Adult; Female; Humans; Asian People; Databases, Factual; Genotype; Intellectual Disability; Phenotype
PubMed: 38444259
DOI: 10.1002/mgg3.2398 -
Haematologica Aug 2019Although it is well known that myeloproliferative neoplasms occur in younger patients, few large cohorts of such patients have been reported. Thus, our knowledge about...
Although it is well known that myeloproliferative neoplasms occur in younger patients, few large cohorts of such patients have been reported. Thus, our knowledge about circumstances of diagnosis, outcome and treatment is limited, especially for children and young adults. We therefore performed a systematic review of cases, published since 2005, concerning patients aged below 20 years at the time of diagnosis of essential thrombocythemia or polycythemia vera. We identified 396 cases of essential thrombocythemia and 75 of polycythemia vera. The median age at diagnosis was 9.3 and 12 years, respectively, and females constituted 57.6% and 45% of the groups, respectively. Half of the patients were asymptomatic at diagnosis. The proportion of so-called triple negativity was high: 57% in essential thrombocythemia and 73% in polycythemia vera. The incidence of thrombosis during the follow-up was 9.3% in patients with polycythemia vera and less, 3.8%, in those with essential thrombocythemia. Venous events were predominant (84.2%), with hemorrhagic episodes being rarer (<5%). The risk of evolution also seemed low (2% to myelofibrosis and no reports of acute leukemia), but the median follow-up was only 50 months. Survival curves were not available. Half of the patients received an antithrombotic drug and 40.5% received a cytoreductive drug. All data should be analyzed with care because of the proportion of missing data (10.7% to 74.7%). This review highlights interesting points concerning this population of young patients with myeloproliferative neoplasms, including that such patients were identified as negative for all common driver mutations, but also shows the need for larger contemporary cohorts with longer follow-up to assess the true prognosis of these patients.
Topics: Adolescent; Asymptomatic Diseases; Child; Cytotoxins; Early Diagnosis; Fibrinolytic Agents; Gene Expression; Hemorrhage; Humans; Janus Kinase 1; Janus Kinase 2; Mutation; Polycythemia Vera; Prognosis; Splenomegaly; Thrombocythemia, Essential; Thrombosis; Young Adult
PubMed: 30679326
DOI: 10.3324/haematol.2018.200832 -
Zhonghua Gan Zang Bing Za Zhi =... Nov 2009To summarize the clinical features, diagnosis and treatment of patients with primary biliary cirrhosis (PBC) in China. (Review)
Review
OBJECTIVE
To summarize the clinical features, diagnosis and treatment of patients with primary biliary cirrhosis (PBC) in China.
METHODS
Systematic analysis of clinical characteristics by searching the Chinese literatures.
RESULTS
From 1955 to 2007, 2740 PBC patients were reported in 103 papers (duplicated reports were deleted). The detailed information of 985 patients from 16 papers were collected. Female : male was 6.82:1. The age range was 42 to 56.2-year-old. The time from onset to diagnosis was 12 to 98.4 months. The most common symptoms were fatigue (72.40%), jaundice (67.41%), anorexia (68.58%) and pruritus (45.60%). 20% patients were asymptomatic at onset. The most frequent physical signs were splenomegaly (57.53%), hepatomegaly (43.56%) and ascites (18.45%). Serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) levels were markedly elevated in most of these patients. The immunological marks of AMA and M2 were positive in 88.98% and 82.65% patients, respectively. The most common comorbidity were Sjögren syndrome (9.14%), rheumatoid arthritis (3.95%) and diabetes type II (2.54%). Of the 507 patients treated with ursodeoxycholic acid (UDCA), 345 patients got complete or partial clinical biochemical response. The common complications were gastrointestinal bleeding (41.67%) and liver failure (41.67%). Liver transplantation was the only effective way for the treatment of the end-stage liver disease.
CONCLUSION
The clinical feature of primary biliary cirrhosis in China was similar to the overseas literatures. Further research should focus on epidemic investigation, early diagnosis, long term follow up of asymptomatic patients, immunological mechanism and the efficacy of liver transplantation.
Topics: Adult; Alanine Transaminase; Autoantibodies; Biomarkers; China; Female; Humans; Immunoglobulin M; Liver Cirrhosis, Biliary; Liver Function Tests; Liver Transplantation; Male; Middle Aged; Mitochondria, Liver; Retrospective Studies; Ursodeoxycholic Acid; gamma-Glutamyltransferase
PubMed: 19958649
DOI: No ID Found -
Frontiers in Oncology 2022Littoral cell angioma (LCA) is currently considered to be a rare splenic tumor with malignant potential. As the epidemiology, pathogenesis, clinical manifestation,...
OBJECTIVE
Littoral cell angioma (LCA) is currently considered to be a rare splenic tumor with malignant potential. As the epidemiology, pathogenesis, clinical manifestation, treatment, and prognosis remain unclear, the clinical diagnosis and treatment of LCA have not been standardized. Hence, we performed a comprehensive analysis of 189 observational studies comprising 435 patients to improve the current status of diagnosis and treatment.
METHODS
PubMed, Embase, WanFang and CNKI were searched from inception to May 2021 to identify LCA studies that were published in English and Chinese. The clinical information of LCA patients were extracted and analyzed.
RESULTS
The LCA has a male-to-female ratio of 0.90 and a solitary-to-multiple ratio of 0.31. In terms of clinical features, 69.7% of the patients showed splenomegaly, 49.7% were asymptomatic, and 39.2% experienced epigastric discomfort. As the imaging findings of patients with LCA were nonspecific, an image-guided biopsy (10/12) was a safe and effective method for diagnosing in this condition. Notably, results of the prognostic analysis indicated that LCA has a lower risk of recurrence and metastasis. The patient may develop a stable disease or the tumor will grow but will not metastasize. Besides, the novel immunohistochemical pattern of LCA was described as CD31/ERG/FVIII Antigen/CD68/CD163/lysozyme/CD8/WT1.
CONCLUSION
LCA should be reconsidered as a benign primary splenic vascular neoplasm, which is more like an intra-splenic manifestation of abnormal body function. Image-guided biopsy with follow-up might be a beneficial choice for LCA patients. For LCA patients with abdominal discomfort, pathological uncertainty or continuous tumor enlargement, splenectomy remains the preferred treatment.
PubMed: 35211400
DOI: 10.3389/fonc.2022.790332 -
The Cochrane Database of Systematic... Sep 2019Thalassaemia is a genetic disorder of the haemoglobin protein in red blood cells. It has been historically classified into thalassaemia minor, intermedia and major,...
BACKGROUND
Thalassaemia is a genetic disorder of the haemoglobin protein in red blood cells. It has been historically classified into thalassaemia minor, intermedia and major, depending on the genetic defect and severity of the disease. The clinical presentation of β-thalassaemia varies widely from a mild asymptomatic form in thalassaemia minor, to a severe disease in thalassaemia major where individuals are dependant on life-long blood transfusions. The hallmark of thalassaemia syndromes is the production of defective red blood cells that are removed by the spleen resulting in an enlarged hyperfunctioning spleen (splenomegaly). Removal of the spleen may thus prolong red blood cell survival by reducing the amount of red blood cells removed from circulation and may ultimately result in the reduced need for blood transfusions.
OBJECTIVES
To assess the efficacy and safety of splenectomy in people with β-thalassaemia major or intermedia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from searches of electronic databases and the handsearching of journals and conference abstract books. We also searched online trial registries and the reference lists of relevant articles and reviews (27 July 2018).Date of the most recent search of the Group's trials register: 02 August 2019.
SELECTION CRITERIA
We included randomised controlled and quasi-randomised controlled studies of people of any age with thalassaemia major or intermedia, evaluating splenectomy in comparison to conservative treatment (transfusion therapy and iron chelation) or other forms of splenectomy compared to each other (laparoscopic, open, radio-frequency).
DATA COLLECTION AND ANALYSIS
Two authors independently selected and extracted data from the single included study using a customised data extraction form and assessed the risk of bias. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
One study, including 28 participants was included in the review; the results were described, primarily, in a narrative manner. This study assessed the feasibility of splenectomy using a laparoscopic approach versus open surgery. Given the lack of detail regarding the study methods beyond randomisation, the overall risk of bias for this study was unclear. The study was carried out over a period of 3.5 years, with each participant followed up only until discharge (less than one week after the intervention); it did not assess the majority of the outcomes outlined in this review (including two of the three primary outcomes, frequency of transfusion and quality of life). A total of three serious post-operative adverse events (the review's third primary outcome) were reported in the laparoscopic splenectomy group (one case of atelectasis and two cases of bleeding), compared to two events of atelectasis in the open surgery group; however, there were no significant differences between the groups for either atelectasis, risk ratio (RR) 0.50 (95% confidence interval (CI) 0.05 to 4.90) or for bleeding, RR 5.00 (95% CI 0.26 to 95.61) (very low-quality evidence). In addition, the study also reported three serious cases of intra-operative bleeding in the laparoscopic group which mandated conversion to open surgery, although the difference between groups was not statistically significant, RR 7.00 (95% CI 0.39 to 124.14) (very low-quality evidence). These effect estimates are based on very small numbers and hence are unreliable and imprecise. From this small study, there appeared to be an advantage for the laparoscopic approach, in terms of post-operative hospital stay, although the group difference was not large (median difference of 1.5 days, P = 0.03).
AUTHORS' CONCLUSIONS
The review was unable to find good quality evidence, in the form of randomised controlled studies, regarding the efficacy of splenectomy for treating thalassaemia major or intermedia. The single included study provided little information about the efficacy of splenectomy, and compared open surgery and laparoscopic methods. Further studies need to evaluate the long-term effectiveness of splenectomy and the comparative advantages of surgical methods. Due to a lack of high quality evidence from randomised controlled studies, well-conducted observational studies may be used to answer this question.
Topics: Blood Transfusion; Humans; Laparoscopy; Quality of Life; Randomized Controlled Trials as Topic; Splenectomy; beta-Thalassemia
PubMed: 31529486
DOI: 10.1002/14651858.CD010517.pub3 -
Journal of Pediatric Hematology/oncology Aug 2017Macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis, is a rare and potentially fatal complication of Kawasaki disease (KD)....
Macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis, is a rare and potentially fatal complication of Kawasaki disease (KD). We report 2 cases, performed a literature search, and analyze the characteristics of MAS associated with KD. A total of 69 patients were evaluated, 34 reported the date of the diagnosis of MAS and KD, 6% had a diagnosis of MAS before KD, 21% had a simultaneous presentation, and 73% had the diagnosis of MAS after KD. Different treatment approaches were observed with corticosteroids administered in 87%, cyclosporine in 49%, etoposide (VP-16) in 39%, and monoclonal anti-TNF in 6% of cases. Coronary abnormalities were especially high in this group of patients (46%) and 9 patients died (13%). The persistence of fever with splenomegaly, hyperferritinemia, thrombocytopenia, and elevated aspartate aminotransferase (AST) should prompt the consideration of MAS complicating KD.
Topics: Adolescent; Adrenal Cortex Hormones; Antibodies, Monoclonal; Aspartate Aminotransferases; Child; Child, Preschool; Coronary Vessel Anomalies; Cyclosporine; Etoposide; Female; Fever; Humans; Infant; Macrophage Activation Syndrome; Male; Mucocutaneous Lymph Node Syndrome; Tumor Necrosis Factor-alpha
PubMed: 28562511
DOI: 10.1097/MPH.0000000000000872 -
Emergency Radiology Jun 2024Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic... (Review)
Review
Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for ectopic variceal management. A comprehensive search through PubMed, Scopus, Web of Science, and Embase was conducted until January 16, 2023, using relevant keywords. Case reports and case series with fewer than 10 patients on TIPS for ectopic variceal management were included. The quality assessment followed the Joanna Briggs Institute checklist for case reports. This systematic review evaluated 43 studies involving 50 patients with ectopic varices undergoing TIPS. Patients had a mean age of 54.3 years, half were female, and two were pregnant. Alcoholic liver disease (48%) and hepatitis C infection (26%) were common causes of portal hypertension. Ascites and splenomegaly were reported in 32% and 28% of the patients, respectively. Rectal, oral, and stomal variceal bleeding accounted for 62%, 16%, and 22% of the patients, respectively. Ectopic varices were mainly located in the duodenum (28%) and rectum (26%) regions. Complications affected 42% of the patients, re-bleeding in eleven and hepatic encephalopathy in seven. The follow-up lasted 12 months on average, and finally, 5 received a liver transplant. Mortality post-TIPS was 18%. Despite complications and a notable mortality rate, favorable outcomes were observed in almost half of the patients with ectopic variceal bleeding managed with TIPS. Further research is warranted to refine strategies and improve patient outcomes.
PubMed: 38935315
DOI: 10.1007/s10140-024-02258-6 -
Haematologica Apr 2019Advances in understanding the pathogenesis and molecular landscape of myelofibrosis have occurred over the last decade. Treating physicians now have access to an...
Advances in understanding the pathogenesis and molecular landscape of myelofibrosis have occurred over the last decade. Treating physicians now have access to an ever-evolving armamentarium of novel agents to treat patients, although allogeneic hematopoietic stem cell transplantation remains the only curative approach. Improvements in donor selection, conditioning regimens, disease monitoring and supportive care have led to augmented survival after transplantation. Nowadays, there are comprehensive guidelines concerning allogeneic hematopoietic stem cell transplantation for patients with myelofibrosis. However, it commonly remains difficult for both physicians and patients alike to weigh up the risk-benefit ratio of transplantation given the inherent heterogeneity regarding both clinical course and therapeutic response. In this timely review, we provide an up-to-date synopsis of current transplantation recommendations, discuss usage of JAK inhibitors before and after transplantation, examine donor selection and compare conditioning platforms. Moreover, we discuss emerging data concerning the impact of the myelofibrosis mutational landscape on transplantation outcome, peritransplant management of splenomegaly, poor graft function and prevention/management of relapse.
Topics: Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Primary Myelofibrosis; Recurrence; Survival Rate; Transplantation Conditioning; Transplantation, Homologous
PubMed: 30872371
DOI: 10.3324/haematol.2018.206151