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The Journal of Infection Jan 2022Mycobacterium genavense is a fastidious slow growing mycobacterium (SGM) that causes disseminated infections in immunocompromised hosts. It has been described in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Mycobacterium genavense is a fastidious slow growing mycobacterium (SGM) that causes disseminated infections in immunocompromised hosts. It has been described in HIV-positive individuals and increasingly in patients without HIV. The infections are difficult to treat and the optimal antimycobacterial regimen is still unknown.
METHODS
An individual patient data meta-analysis was conducted aiming at including all hitherto published cases of infection with M. genavense. Clinical manifestations, microbiological data, dispositions and immunosuppression were recorded. Antimycobacterial therapies and mortality were analyzed by logistic regression and time-to-event analysis.
RESULTS
We included 223 patients with infection due to M. genavense published from 1992 to 2021. While the majority was HIV positive (n = 171, 76.7%), 52 patients were non-HIV-patients (23.3%), 36 of whom received immunosuppressive therapy (69%). We could confirm the bacterium's tropism for the gastrointestinal tract with abdominal pain, hepato-/splenomegaly and abdominal lymphadenopathy being major clinical manifestations. More than 90% of patients received antimycobacterial therapy. The regimens consisted mainly of macrolides, rifamycins and ethambutol. Overall mortality was high, but in logistic regression and time-to-event analysis a macrolide containing regimen was associated with better outcomes.
CONCLUSION
In this first individual patient data meta-analysis of infections with M. genavense we confirm its tropism for the gastrointestinal tract. The high overall mortality underlines the clinical relevance of infection with this bacterium for the individual patient. In addition, our data give a hint that a macrolide containing regimen is associated with better survival.
Topics: Anti-Bacterial Agents; Humans; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 34788633
DOI: 10.1016/j.jinf.2021.10.027 -
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 -
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 -
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 -
Expert Review of Molecular Diagnostics May 2021Visceral leishmaniasis (VL) is a systemic and neglected parasitic disease. Its main symptoms are fever, splenomegaly with or without hepatomegaly, and anemia, however,...
INTRODUCTION
Visceral leishmaniasis (VL) is a systemic and neglected parasitic disease. Its main symptoms are fever, splenomegaly with or without hepatomegaly, and anemia, however, most individuals remain asymptomatic. Due to the lack of a gold standard and the limitations of current diagnostic techniques, where parasitology is ethically unfeasible for individuals without symptoms and serological tests do not differentiate between past and present disease, molecular methodologies are the most suitable.
AREAS COVERED
We performed a systematic review analyzing the molecular techniques based on PCR used, so far, to detect asymptomatic cases of VL in humans. Structured searches were carried out on PubMed, LILACS, Scopus, and Web of Science databases without time and language restrictions. Two reviewers evaluated the studies, performed data extraction, and quality assessment by assigning scores.
EXPERT OPINION
qPCR using RNA targets can be used in the diagnosis of asymptomatic cases of human VL, due to its characteristics. We recommend further studies to analyze the methodology, mainly observing the use of different rRNA targets. Therefore, we hope that this technique contributed to the construction of public policies that address the diagnosis and handling of asymptomatic patients.
Topics: Humans; Leishmaniasis, Visceral; Nucleic Acid Amplification Techniques
PubMed: 33719847
DOI: 10.1080/14737159.2021.1900736 -
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 -
Pediatric Radiology Feb 2021We present a practical approach to imaging in suspected biliary atresia, an inflammatory cholangiopathy of infancy resulting in progressive fibrosis and obliteration of...
We present a practical approach to imaging in suspected biliary atresia, an inflammatory cholangiopathy of infancy resulting in progressive fibrosis and obliteration of extrahepatic and intrahepatic bile ducts. Left untreated or with failure of the Kasai procedure, biliary atresia progresses towards biliary cirrhosis, end-stage liver failure and death by age 3. Differentiation of biliary atresia from other nonsurgical causes of neonatal cholestasis is challenging because there is no single method for diagnosing biliary atresia, and clinical, laboratory and imaging features of this disease overlap with those of other causes of neonatal cholestasis. Concerning imaging, our systematic literature review shows that ultrasonography is the main tool for pre- and neonatal diagnosis. Key prenatal features, when present, are non-visualisation of the gallbladder, cyst in the liver hilum, heterotaxy syndrome and irregular gallbladder walls. Postnatal imaging features have a very high specificity when present, but a variable sensitivity. Triangular cord sign and abnormal gallbladder have the highest sensitivity and specificity. The presence of macro- or microcyst or polysplenia syndrome is highly specific but less sensitive. The diameter of the hepatic artery and hepatic subcapsular flow are less reliable. When present in the context of acholic stools, dilated intrahepatic bile ducts rule out biliary atresia. Importantly, a normal US exam does not rule out biliary atresia. Signs of chronic hepatopathy and portal hypertension (portosystemic derivations such as patent ductus venosus, recanalised umbilical vein, splenomegaly and ascites) should be actively identified for - but are not specific for - biliary atresia.
Topics: Biliary Atresia; Child, Preschool; Cholestasis; Female; Humans; Hypertension, Portal; Infant; Infant, Newborn; Magnetic Resonance Imaging; Pregnancy; Ultrasonography; Ultrasonography, Prenatal
PubMed: 33201318
DOI: 10.1007/s00247-020-04840-9