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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 -
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 -
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 -
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 -
Frontiers in Immunology 2021Diagnostic delay in common variable immunodeficiency disorders (CVID) is considerable. There is no generally accepted symptom-recognition framework for its early... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diagnostic delay in common variable immunodeficiency disorders (CVID) is considerable. There is no generally accepted symptom-recognition framework for its early detection.
OBJECTIVE
To systematically review all existing data on the clinical presentation of CVID.
METHODS
PubMed, EMBASE and Cochrane were searched for cohort studies, published January/1999-December/2019, detailing the clinical manifestations before, at and after the CVID-diagnosis.
RESULTS
In 51 studies (n=8521 patients) 134 presenting and 270 total clinical manifestations were identified. Recurrent upper and/or lower respiratory infections were present at diagnosis in 75%. Many patients had suffered severe bacterial infections (osteomyelitis 4%, meningitis 6%, septicemia 8%, mastoiditis 8%). Bronchiectasis (28%), lymphadenopathy (27%), splenomegaly (13%), inflammatory bowel disease (11%), autoimmune cytopenia (10%) and idiopathic thrombocytopenia (6%) were also frequently reported. A bimodal sex distribution was found, with male predominance in children (62%) and female predominance in adults (58%). 25% of CVID-patients developed other manifestations besides infections in childhood, this percentage was much higher in adults (62%). Immune-dysregulation features, such as granulomatous-lymphocytic interstitial lung disease and inflammatory bowel disease, were more prominent in adults.
CONCLUSIONS
The shift from male predominance in childhood to female predominance in adults suggests differences in genetic and environmental etiology in CVID and has consequences for pathophysiologic studies. We confirm the high frequency of respiratory infections at presentation, but also show a high incidence of severe bacterial infections such as sepsis and meningitis, and immune dysregulation features including lymphoproliferative, gastrointestinal and autoimmune manifestations. Early detection of CVID may be improved by screening for antibody deficiency in patients with these manifestations.
Topics: Adult; Age Factors; Autoimmunity; Bronchiectasis; Child; Common Variable Immunodeficiency; Humans; Incidence; Lymphadenopathy; Meningitis; Phenotype; Respiratory Tract Infections; Sex Factors
PubMed: 33833753
DOI: 10.3389/fimmu.2021.620709 -
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 -
Genetics in Medicine : Official Journal... Sep 2021Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of...
PURPOSE
Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature.
METHODS
Nineteen patients were phenotyped per local institutional procedures. A systematic review following PRISMA criteria identified 132 articles describing 161 patients. Main outcome analyses were performed for manifestation frequency, diagnostic delay, overall survival, symptom-free survival, and ulcer-free survival.
RESULTS
Our cohort presented a wide variability of severity. Autoimmune disorders were found in 6/19, including Crohn disease, systemic lupus erythematosus, and arthritis. Another immune finding was hemophagocytic lymphohistiocytosis (HLH). Half of published patients were symptomatic by age 4 and had a delayed diagnosis (mean delay 11.6 years). Ulcers were present initially in only 30% of cases, with a median age of onset at 12 years old.
CONCLUSION
Prolidase deficiency has a broad range of manifestations. Symptoms at onset may be nonspecific, likely contributing to the diagnostic delay. Testing for this disorder should be considered in any child with unexplained autoimmunity, lower extremity ulcers, splenomegaly, or HLH.
Topics: Child; Child, Preschool; Crohn Disease; Delayed Diagnosis; Humans; Leg Ulcer; Phenotype; Prolidase Deficiency
PubMed: 34040193
DOI: 10.1038/s41436-021-01200-2