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HPB : the Official Journal of the... Dec 2011Pancreatitis-induced splenic vein thrombosis (PISVT) is an acquired anatomic abnormality that impacts decision making in pancreatic surgery. Despite this influence, its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatitis-induced splenic vein thrombosis (PISVT) is an acquired anatomic abnormality that impacts decision making in pancreatic surgery. Despite this influence, its incidence and the rate of associated gastrointestinal (GI) bleeding are imprecisely known.
METHODS
The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to June 2010 for abstracts documenting PISVT in acute (AP) or chronic pancreatitis (CP). Two reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% confidence intervals.
RESULTS
After review of 241 abstracts, 47 studies and 52 case reports were graded as relevant. These represent a cohort of 805 patients with PISVT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidences of PISVT of 14.1% in all patients, 22.6% in patients with AP and 12.4% in patients with CP. The incidence of associated splenomegaly was only 51.9% in these patients. Varices were identified in 53.0% of patients and were gastric in 77.3% of cases. The overall rate of GI bleeding was 12.3%.
CONCLUSIONS
Although reported incidences of PISVT vary widely across studies, an overall incidence of 14.1% is reported. Splenomegaly is an unreliable sign of PISVT. Although the true natural history of PISVT remains unknown, the collective reported rate of associated GI bleeding is 12.3%.
Topics: Disease Progression; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Incidence; Pancreatitis; Splenic Vein; Splenomegaly; Venous Thrombosis
PubMed: 22081918
DOI: 10.1111/j.1477-2574.2011.00375.x -
Autopsy & Case Reports 2023Endocarditis is a rare, often fatal complication of rat bite fever caused by . Only 39 cases have been reported (including this case) as of 2022. We describe a case and...
INTRODUCTION
Endocarditis is a rare, often fatal complication of rat bite fever caused by . Only 39 cases have been reported (including this case) as of 2022. We describe a case and aim to perform this entit's first systematic literature review.
METHODS
We performed a systematic review in CENTRAL, EMBASE, MEDLINE, SciELO, and LILACS. The terms used were terms used were (but not limited to) rat bite fever, , and endocarditis. We included all abstracts and articles with patients with echocardiographic or histologic-proven endocarditis. In case of discordance, a third reviewer was involved. Our protocol was submitted to PROSPERO (CRD42022334092). We also performed searches for studies on the reference list of included articles.
RESULTS
We retrieved 108 and included 36 abstracts and articles. A total of 39 patients (including our report) were identified. The mean age was 41.27, and 61.5% were males. The most common findings were fever, murmur, arthralgias, fatigue, splenomegaly, and rash. Underlying heart disease was present in 33%. Exposure to rats was noted in 71.8% of patients, with 56.4% recalling a rat bite. Anemia was seen in 57%, leukocytosis in 52%, and elevated inflammatory markers in 58% that had lab work performed. The mitral valve was most affected, followed by the aortic, tricuspid, and pulmonary valves. Surgical intervention was required in 14 (36%) cases. Of those, 10 required valve replacement. Death was reported in 36% of cases. Unfortunately, the literature available is limited to case series and reports.
CONCLUSION
Our review allows clinicians to suspect better, diagnose, and manage Streptobacillary endocarditis.
PubMed: 37101553
DOI: 10.4322/acr.2023.423 -
Frontiers in Cellular and Infection... 2022() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of...
() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of can be life-threatening without timely and effective antifungal therapy. Rapid and accurate pathogenic microbiological diagnosis is particularly critical for these patients. A total of 505 patients with IEI were admitted to our hospital between January 2019 and June 2022, among whom was detected in 6 patients by metagenomic next-generation sequencing (mNGS), and their clinical and immunological characteristics were summarized. We performed a systematic literature review on infections with published immunodeficiency-related gene mutations. All patients in our cohort were confirmed to have genetic mutations in , , , , and . was detected in both the blood and lymph nodes of P1 with mutations, and the clinical manifestations were serious and included recurrent fever, weight loss, severe anemia, splenomegaly and lymphadenopathy, all requiring long-term antifungal therapy. These six patients received antifungal treatment, which relieved symptoms and improved imaging findings. Five patients survived, while one patient died of sepsis after hematopoietic stem cell transplantation. The application of mNGS methods for pathogen detection in IEI patients and comparison with traditional diagnosis methods were investigated. Traditional diagnostic methods and mNGS tests were performed simultaneously in 232 patients with IEI. Compared to the traditional methods, the sensitivity and specificity of mNGS in diagnosing infection were 100% and 98.7%, respectively. The reporting time for detection was approximately 26 hours by mNGS, 3-14 days by culture, and 6-11 days by histopathology. infection was first reported in IEI patients with gene mutation, which expanded the IEI lineage susceptible to . For IEI patients with infection, we highlight the application of mNGS in pathogenic detection. mNGS is recommended as a front-line diagnostic test for rapidly identifying pathogens in complex and severe infections.
Topics: Antifungal Agents; China; High-Throughput Nucleotide Sequencing; Humans; Mycoses; Talaromyces; Technology
PubMed: 36159645
DOI: 10.3389/fcimb.2022.987692 -
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 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
PLoS Neglected Tropical Diseases Feb 2017Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity.
METHODOLOGY/PRINCIPAL FINDINGS
This review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome.
CONCLUSION/SIGNIFICANCE
While there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully curative, reductions in egg output are significantly correlated with decreased morbidity and can be used to project diminution in disease burden when contemplating more aggressive strategies to minimize infection intensity.
Topics: Animals; Anthelmintics; Humans; Praziquantel; Schistosoma; Schistosomiasis
PubMed: 28212414
DOI: 10.1371/journal.pntd.0005372 -
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 -
Frontiers in Genetics 2022Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease,...
Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease, pancreatitis and/or multiple organ failures before diagnosis. Better guidelines for the recognition and early diagnosis of rare dyslipidaemias are urgently required. Genomic DNA was isolated from blood samples of a Pakistani paediatric patient with hypertriglyceridemia, and from his parents and siblings. Next-generation sequencing (NGS) was performed, and an expanded dyslipidaemia panel was employed for genetic analysis. The NGS revealed the presence of a homozygous missense pathogenic variant c.230G>A (NM_178172.6) in exon 3 of the (glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1) gene resulting in amino acid change p.Cys77Tyr (NP_835466.2). The patient was 5.5 years old at the time of genetic diagnosis. The maximal total cholesterol and triglyceride levels were measured at the age of 10 months (850.7 mg/dl, 22.0 mmol/L and 5,137 mg/dl, 58.0 mmol/L, respectively). The patient had cholesterol deposits at the hard palate, eruptive xanthomas, lethargy, poor appetite, and mild splenomegaly. Both parents and sister were heterozygous for the familial variant in the gene. Moreover, in the systematic review, we present 62 patients with pathogenic variants in the gene and clinical findings, associated with hyperlipoproteinemia. In a child with severe hypertriglyceridemia, we identified a pathogenic variant in the gene causing hyperlipoproteinemia (type 1D). In cases of severe elevations of plasma cholesterol and/or triglycerides genetic testing for rare dyslipidaemias should be performed as soon as possible for optimal therapy and patient management.
PubMed: 36051701
DOI: 10.3389/fgene.2022.983283 -
Journal of the American Board of Family... 2021The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be confirmed. Improving the diagnosis of IM based on the clinical findings could prompt physicians to identify better which patients need a diagnostic test for IM. This study performed a systematic review to determine the accuracy of symptoms, signs, and hematologic parameters in patients with suspected IM that used heterophile antibody test or viral capsid antigen tests as the reference standard.
METHODS
The PubMed database was searched for all relevant articles. Two reviewers reviewed all studies in parallel and assessed the quality of the selected studies using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) criteria. The pooled measures of diagnostic performance were calculated by bivariate meta-analysis for each clinical finding, which included sensitivity, specificity, likelihood ratios, the diagnostic odds ratios, and the area under the receiver operating characteristic curve.
RESULTS
Seventeen studies were included in our final analysis. The prevalence of IM ranged from 2.1% to 80% among prospective cohort studies. The presence of splenomegaly (positive likelihood ratio [LR+], 2.39; 95% confidence interval [CI], 1.11-5.51), palatal petechiae (LR+, 1.32-11.40), posterior cervical lymphadenopathy (LR+, 3.16; 95% CI, 1.45-5.20), and axillary or inguinal cervical lymphadenopathy (LR+, 3.05; 95 CI, 1.85-4.70) were moderately useful for ruling in IM. The most helpful hematologic parameters for ruling in IM include lymphocytes greater than 4 × 10/L and greater than 40% to 50%, or atypical lymphocytes greater than 40%. A combination of lymphocytes greater than 50% and atypical lymphocytes greater than 10% (LR+, 50.40; 95% CI, 8.43-162) was also found to be helpful to rule in disease. Most of the clinical findings have limited diagnostic value in ruling out the disease when absent.
CONCLUSIONS
Although most symptoms and signs were unhelpful, the likelihood of IM is appreciably increased by several examination findings. Hematologic parameters were more accurate than symptoms and signs. Since most clinical findings have limited diagnostic value in ruling out the disease, physicians should not rely on the absence of any individual symptom or clinical sign for ruling out IM.
Topics: Diagnostic Tests, Routine; Humans; Infectious Mononucleosis; Neck; Prospective Studies; ROC Curve; Sensitivity and Specificity
PubMed: 34772769
DOI: 10.3122/jabfm.2021.06.210217