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The Cochrane Database of Systematic... Mar 2020Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of salt and water movement across the membranes. In the liver this leads to focal biliary fibrosis resulting in progressive portal hypertension and end-stage liver disease in some individuals. This can be asymptomatic, but may lead to splenomegaly and hypersplenism, development of varices and variceal bleeding, and ascites; it has negative impact on overall nutritional status and respiratory function in this population. Prognosis is poor once significant portal hypertension is established. The role and outcome of various interventions for managing advanced liver disease (non-malignant end stage disease) in people with cystic fibrosis is currently unidentified. This is an updated version of a previously published review.
OBJECTIVES
To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 November 2019. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 01 January 2020.
SELECTION CRITERIA
Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both).
DATA COLLECTION AND ANALYSIS
Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review.
MAIN RESULTS
A comprehensive search of the literature did not identify any published eligible randomised controlled trials.
AUTHORS' CONCLUSIONS
In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.
Topics: Adult; Child; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Diseases; Randomized Controlled Trials as Topic
PubMed: 32227478
DOI: 10.1002/14651858.CD012056.pub3 -
Pediatric Pulmonology Feb 2020Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency disorder characterized by infectious and noninfectious complications.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency disorder characterized by infectious and noninfectious complications. Bronchiectasis continues to be a common respiratory problem and therapeutic challenge in CVID. The aim of this study is to estimate the overall prevalence of bronchiectasis and its associated phenotype in patients with CVID.
METHODS
A systematic literature search was performed in Web of Science, PubMed, and Scopus from the earliest available date to February 2019 with standard keywords. All pooled analyses of bronchiectasis prevalence and the corresponding 95% confidence intervals (CIs) were based on random-effects models.
RESULTS
Fifty-five studies comprising 8535 patients with CVID were included in the meta-analysis. Overall prevalence of bronchiectasis was 34% (95% CI: 30-38; I = 90.19%). CVID patients with bronchiectasis had significantly lower serum immunoglobulin A (IgA) and IgM levels at the time of diagnosis compared with those without bronchiectasis. Among the clinical features, the frequencies of splenomegaly, pneumonia, otitis media, and lymphocytic interstitial pneumonia were significantly higher in CVID patients with bronchiectasis compared with those without bronchiectasis, respectively.
CONCLUSION
A higher prevalence of bronchiectasis in patients with CVID should be managed by controlling recurrent and severe pneumonia episodes which are immune dysregulation since this complication is associated with poor prognosis in these patients.
Topics: Adult; Bronchiectasis; Common Variable Immunodeficiency; Female; Humans; Longitudinal Studies; Lung Diseases, Interstitial; Male; Otitis Media; Pneumonia; Prevalence
PubMed: 31833673
DOI: 10.1002/ppul.24599 -
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 -
Orphanet Journal of Rare Diseases Jun 2019Congenital tuberculosis is rare and carries a high mortality rate. Our objective was to summarize the current experience of the diagnosis and treatment of patients with... (Review)
Review
BACKGROUND
Congenital tuberculosis is rare and carries a high mortality rate. Our objective was to summarize the current experience of the diagnosis and treatment of patients with congenital tuberculosis.
METHODS
In total, 73 reported cases of congenital tuberculosis published in Chinese and 19 patients with congenital tuberculosis admitted to West China Second University Hospital, Sichuan University, were retrospectively reviewed.
RESULTS
Sixty-four male and 28 female patients were identified. The majority of the patients were less than 3 weeks old at the time of presentation (range, 0-67 days). With regard to the tuberculosis type, 89 patients had pulmonary tuberculosis, and 20 patients had hepatic tuberculosis. There was active tuberculosis in 71 mothers, no tuberculosis in 12 mothers, and an unknown history of tuberculosis in 9 mothers. Fever, cyanosis, jaundice, shortness of breath, cough, pulmonary moist rales, hepatomegaly, splenomegaly and abdominal distention were the main clinical symptoms at the time of presentation. The abnormal ratios of chest, abdomen and head radiographic images were 97.53, 75 and 81.25%, respectively. The positive rates of acid-fast staining of sputum smears and tuberculosis bacillus DNA were 62.50 and 66.67%, respectively. The misdiagnosis rate was 59.78%. The overall mortality due to congenital tuberculosis was 43.48%. Respiratory failure was the most common cause of death. Sixty-five patients received anti-tuberculosis therapy, and of those, only 16 (15.38%) died.
CONCLUSIONS
The clinical manifestations and radiographic findings of congenital tuberculosis are nonspecific. It is important to thoroughly evaluate the mothers of infants with suspected congenital tuberculosis. Good outcomes can be achieved in infants with the early identification of congenital tuberculosis and early administration of anti-tuberculosis treatment.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Respiratory Insufficiency; Retrospective Studies; Tuberculosis; Tuberculosis, Hepatic; Tuberculosis, Pulmonary; Young Adult
PubMed: 31182120
DOI: 10.1186/s13023-019-1101-x -
The Journal of Allergy and Clinical... 2019LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency and immune dysregulation syndrome caused by biallelic mutations in the LRBA...
BACKGROUND
LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency and immune dysregulation syndrome caused by biallelic mutations in the LRBA gene. These mutations usually abrogate the protein expression of LRBA, leading to a broad spectrum of clinical phenotypes including autoimmunity, chronic diarrhea, hypogammaglobulinemia, and recurrent infections.
OBJECTIVE
Our aim was to systematically collect all studies reporting on the clinical manifestations, molecular and laboratory findings, and management of patients with LRBA deficiency.
METHODS
We searched in PubMed, Web of Science, and Scopus without any restrictions on study design and publication time. A total of 109 LRBA-deficient cases were identified from 45 eligible articles. For all patients, demographic information, clinical records, and immunologic and molecular data were collected.
RESULTS
Of the patients with LRBA deficiency, 93 had homozygous and 16 had compound heterozygous mutations in LRBA. The most common clinical manifestations were autoimmunity (82%), enteropathy (63%), splenomegaly (57%), and pneumonia (49%). Reduction in numbers of CD4 T cells and regulatory T cells as well as IgG levels was recorded for 21.6%, 65.6%, and 54.2% of evaluated patients, respectively. B-cell subpopulation analysis revealed low numbers of switched-memory and increased numbers of CD21 B cells in 73.5% and 77.8% of patients, respectively. Eighteen (16%) patients underwent hematopoietic stem cell transplantation due to the severity of complications and the outcomes improved in 13 of them.
CONCLUSIONS
Autoimmune disorders are the main clinical manifestations of LRBA deficiency. Therefore, LRBA deficiency should be included in the list of monogenic autoimmune diseases, and screening for LRBA mutations should be routinely performed for patients with these conditions.
Topics: Adaptor Proteins, Signal Transducing; Humans; Immunologic Deficiency Syndromes
PubMed: 30995531
DOI: 10.1016/j.jaip.2019.04.011 -
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 -
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 -
Current Pediatric Reviews 2019Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease...
IMPORTANCE
Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease in children. Although clinical practice guidelines exist for the management of AAT deficiency, especially with regards to pulmonary involvement, there are no published recommendations that specifically relate to the management of the liver disease and monitoring for lung disease associated with this condition, particularly in children.
OBJECTIVE
To review the literature on the management of AAT deficiency-associated liver disease in adults and children.
EVIDENCE REVIEW
A systematic search for articles indexed in PubMed and published was undertaken. Some earlier selected landmark references were included in the review. Search terms included: "alpha1-antitrypsin deficiency"; "liver disease"; "end-stage liver disease"; "liver transplantation" and "preventative management". Recommendations for the management of children with suspected or confirmed AAT deficiency were made according to the Strength of Recommendation Taxonomy scale.
FINDINGS
Liver complications arising from AAT deficiency result from the accumulation of mutated AAT protein within hepatocytes. Liver disease occurs in 10% of children, manifested by cholestasis, pruritus, poor feeding, hepatomegaly, and splenomegaly, but the presentation is highly variable. A diagnostic test for AAT deficiency is recommended for these children. Baseline liver function tests should be obtained to assess for liver involvement; however, the only curative treatment for AAT deficiency-associated liver disease is organ transplantation. Conclusion and Relevance: There should be a greater vigilance for AAT deficiency testing among pediatricians. Diagnosis should prompt assessment of liver involvement. Children with AATdeficiency- associated liver disease should be referred to a liver specialist and monitored throughout their lifetimes for the symptoms of AAT-deficiency-related pulmonary involvement.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Liver; Liver Diseases; Liver Transplantation; Male; Transition to Adult Care; alpha 1-Antitrypsin Deficiency
PubMed: 30421678
DOI: 10.2174/1573396314666181113094517 -
Clinics and Research in Hepatology and... Feb 2019Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is...
BACKGROUND AND AIMS
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is the first systematic review of the epidemiology, natural history and burden of PFIC.
METHODS
MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life (HRQoL) of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
Of 1269 records screened, 20 were eligible (epidemiology, 17; humanistic burden, 5; both, 2). Incidence of intrahepatic cholestasis, including but not limited to PFIC, was 1/18 000 live births in one study that did not use genetic testing. In two studies of infants and children (2-18 years) with cholestasis, 12-13% had genetically diagnosed PFIC. Of the three main PFIC subtypes, PFIC2 was the most common (21-91% of patients). Common symptoms (e.g. pruritus, jaundice, hepatomegaly, splenomegaly) generally appeared at about 3 months of age and tended to emerge earliest in patients with PFIC2. Patients reported that pruritus was often severe and led to dermal damage and reduced HRQoL. Disease progression led to complications including liver failure and hepatocellular carcinoma, with 20-83% of patients requiring liver transplantation. Mortality was 0-87% across 10 studies (treatment varied among studies), with a median age at death of ~4 years in one study.
CONCLUSIONS
Patients with PFIC face debilitating symptoms and poor prognosis. Further research is needed to inform patient management and clinical trial design. Published data on the epidemiology and socioeconomic burden of PFIC is limited.
Topics: Cholestasis, Intrahepatic; Humans
PubMed: 30236549
DOI: 10.1016/j.clinre.2018.07.010 -
Reviews in Medical Virology Nov 2018We systematically searched and meta-analyzed the epidemiological characteristics, frequency of clinical signs, and outcomes of dengue-associated hemophagocytic... (Meta-Analysis)
Meta-Analysis
We systematically searched and meta-analyzed the epidemiological characteristics, frequency of clinical signs, and outcomes of dengue-associated hemophagocytic lymphohistiocytosis. Ten electronic databases were searched systematically plus manual search of reference lists to identify relevant articles published until May 2017. The highest number of reported cases were from South-East Asia region (62 cases), followed by Western Pacific region (20 cases), and America (31 cases). The term "dengue hemorrhagic fever" predominated in studies that used the World Health Organization 1997 definition (59.7%), whereas "severe dengue" predominated in studies using the World Health Organization 2009 definition (76.8%). Among 122 cases, fever, splenomegaly, hepatomegaly, anemia, thrombocytopenia, and serum ferritin ≥500 μg/L were likely to report by articles representing by large sample size. The pooled proportion of these findings were as follows: fever 97.2%, hepatomegaly 70.2%, splenomegaly 78.4%, thrombocytopenia 90.1%, anemia 76.0%, and serum ferritin ≥500 μg/L 97.1%. This study highlighted a high case fatality rate (14.6%) and co-infection among dengue hemophagocytic lymphohistiocytosis patients. We suggest that long fever duration, persistent thrombocytopenia, elevated serum ferritin, and lactate dehydrogenase levels could be good diagnostic indicators for dengue-associated hemophagocytic syndrome. Bone marrow aspiration could be used as one criterion for diagnosis but is not obligatory. Further research is needed to examine the possible risk difference for development of hemophagocytic syndrome and to explore potential relationships between specific dengue classifications and dengue-associated hemophagocytic syndrome.
Topics: Americas; Asia, Southeastern; Dengue; Humans; Lymphohistiocytosis, Hemophagocytic; Pacific Islands; Risk Factors; Survival Analysis; Treatment Outcome
PubMed: 30109914
DOI: 10.1002/rmv.2005