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Pediatric Allergy and Immunology :... Oct 2021Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and...
BACKGROUND
Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline mutations in the TNFRSF6 gene. In this study, we conducted a systematic review of patients with ALPS and ALPS-like syndrome.
METHODS
The literature search was performed in Web of Science, Scopus, and PubMed databases to find eligible studies. Additionally, the reference list of all included papers was hand-searched for additional studies. Demographic, clinical, immunological, and molecular data were extracted and compared between the ALPS and ALPS-like syndrome.
RESULTS
Totally, 720 patients with ALPS (532 genetically determined and 189 genetically undetermined ALPS) and 59 cases with ALPS-like phenotype due to mutations in genes other than ALPS genes were assessed. In both ALPS and ALPS-like patients, splenomegaly was the most common clinical presentation followed by autoimmune cytopenias and lymphadenopathy. Among other clinical manifestations, respiratory tract infections were significantly higher in ALPS-like patients than ALPS. The immunological analysis showed a lower serum level of IgA, IgG, and lymphocyte count in ALPS-like patients compared to ALPS. Most (85%) of the ALPS and ALPS-like cases with determined genetic defects carry mutations in the FAS gene. About one-third of patients received immunosuppressive therapy with conventional or targeted immunotherapy agents. A small fraction of patients (3.3%) received hematopoietic stem cell transplantation with successful engraftment, and all except two patients survived after transplantation.
CONCLUSION
Our results showed that the FAS gene with 85% frequency is the main etiological cause of genetically diagnosed patients with ALPS phenotype; therefore, the genetic defect of the majority of suspected ALPS patients could be confirmed by mutation analysis of FAS gene.
Topics: Autoimmune Diseases; Autoimmune Lymphoproliferative Syndrome; Heterozygote; Humans; Lymphoproliferative Disorders; Mutation; Phenotype; fas Receptor
PubMed: 33963613
DOI: 10.1111/pai.13535 -
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 -
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 -
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 -
World Journal of Surgery Feb 2021To review the evidence regarding the outcomes of laparoscopic techniques in cases of splenomegaly. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To review the evidence regarding the outcomes of laparoscopic techniques in cases of splenomegaly.
BACKGROUND
Endoscopic approaches such as laparoscopic, hand-assisted laparoscopic, and robotic surgery are commonly used for splenectomy, but the advantages in cases of splenomegaly are controversial.
REVIEW METHODS
We conducted a systematic review using PRISMA guidelines. PubMed/MEDLINE, ScienceDirect, Scopus, Cochrane Library, and Web of Science were searched up to February 2020.
RESULTS
Nineteen studies were included for meta-analysis. In relation to laparoscopic splenectomy (LS) versus open splenectomy (OS), 12 studies revealed a significant reduction in length of hospital stay (LOS) of 3.3 days (p = <0.01) in the LS subgroup. Operative time was higher by 44.4 min (p < 0.01) in the LS group. Blood loss was higher in OS 146.2 cc (p = <0.01). No differences were found regarding morbimortality. The global conversion rate was 19.56%. Five studies compared LS and hand-assisted laparosocpic splenectomy (HALS), but no differences were observed in LOS, blood loss, or complications. HALS had a significantly reduced conversion rate (p < 0.01). In two studies that compared HALS and OS (n = 66), HALS showed a decrease in LOS of 4.5 days (p < 0.01) and increase of 44 min in operative time (p < 0.01), while OS had a significantly higher blood loss of 448 cc (p = 0.01). No differences were found in the complication rate.
CONCLUSION
LS is a safe approach for splenomegaly, with clear clinical benefits. HALS has a lower conversion rate. Higher-quality confirmatory trials with standardized splenomegaly grading are needed before definitive recommendations can be provided. Prospero registration number: CRD42019125251.
Topics: Blood Loss, Surgical; Humans; Laparoscopy; Length of Stay; Operative Time; Postoperative Complications; Splenectomy; Splenomegaly; Treatment Outcome
PubMed: 33179126
DOI: 10.1007/s00268-020-05839-x -
British Journal of Haematology Apr 2021The majority of the global population of sickle cell disease (SCD) patients resides in Africa. Individuals with this condition are at great risk of serious infections...
The majority of the global population of sickle cell disease (SCD) patients resides in Africa. Individuals with this condition are at great risk of serious infections and early mortality secondary to splenic dysfunction without preventative measures. This review investigated the spectrum of splenic complications encountered in SCD among populations in Africa. We systematically searched several databases for all articles published through March 3, 2020. We included 55 studies from 14 African countries. This review reveals the difference in frequency of splenic complications in SCD in Africa when compared with their counterparts in the United State and Europe. While several studies (n = 45) described splenomegaly with a prevalence of 12% to 73% among children, and 4% to 50% among adults with HbSS, the reported prevalence for acute splenic sequestration crisis (n = 6 studies) and hypersplenism (n = 4 studies) was <10% and <5% respectively. A total of 30 surgical splenectomy was reported across eight studies. Only two (3.7%) studies provided data on spleen function. A conflicting pattern was observed amongst studies that evaluated the relationship between splenomegaly and the presence of bacterial and malaria infections. This review reveals the paucity of studies describing the role of SCD-induced splenic dysfunction in morbidity and infection related mortality in Africa.
Topics: Adolescent; Adult; Africa; Anemia, Sickle Cell; Bacterial Infections; Case-Control Studies; Child; Child, Preschool; Female; Hemoglobin, Sickle; Humans; Hypersplenism; Malaria; Male; Middle Aged; Prevalence; Retrospective Studies; Splenectomy; Splenic Diseases; Splenic Rupture; Splenomegaly
PubMed: 33161568
DOI: 10.1111/bjh.17179 -
Journal of Travel Medicine Dec 2020Numerous publications focus on fever in returning travellers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous publications focus on fever in returning travellers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever. Such a review is necessary in order to develop appropriate practice guidelines.
OBJECTIVES
Primary objectives of this review were (i) to determine the aetiology of fever in travellers/migrants returning from (sub) tropical countries as well as the proportion of patients with specific diagnoses, and (ii) to assess the predictors for specific tropical diseases.
METHOD
Embase, MEDLINE and Cochrane Library were searched with terms combining fever and travel/migrants. All studies focusing on causes of fever in returning travellers and/or clinical and laboratory predictors of tropical diseases were included. Meta-analyses were performed on frequencies of etiological diagnoses.
RESULTS
10 064 studies were identified; 541 underwent full-text review; 30 met criteria for data extraction. Tropical infections accounted for 33% of fever diagnoses, with malaria causing 22%, dengue 5% and enteric fever 2%. Non-tropical infections accounted for 36% of febrile cases, with acute gastroenteritis causing 14% and respiratory tract infections 13%. Positive likelihood ratios demonstrated that splenomegaly, thrombocytopenia and hyperbilirubinemia were respectively 5-14, 3-11 and 5-7 times more likely in malaria than non-malaria patients. High variability of results between studies reflects heterogeneity in study design, regions visited, participants' characteristics, setting, laboratory investigations performed and diseases included.
CONCLUSION
Malaria accounted for one-fifth of febrile cases, highlighting the importance of rapid malaria testing in febrile returning travellers, followed by other rapid tests for common tropical diseases. High variability between studies highlights the need to harmonize study designs and to promote multi-centre studies investigating predictors of diseases, including of lower incidence, which may help to develop evidence-based guidelines. The use of clinical decision support algorithms by health workers which incorporate clinical predictors, could help standardize studies as well as improve quality of recommendations.
Topics: COVID-19; Communicable Disease Control; Diagnosis, Differential; Fever; Humans; Practice Guidelines as Topic; Transients and Migrants; Travel Medicine; Tropical Medicine
PubMed: 33146395
DOI: 10.1093/jtm/taaa207 -
Tropical Doctor Jan 2021Visceral leishmaniasis is a tropical parasitic disease caused by the species of the genus The clinical picture includes fever, splenomegaly, leucopenia, anaemia and...
Visceral leishmaniasis is a tropical parasitic disease caused by the species of the genus The clinical picture includes fever, splenomegaly, leucopenia, anaemia and hypergammaglobulinaemia. There may also be a drop in plasma fibrinogen levels or an increase in plasma fibrinolytic activity. Furthermore, visceral leishmaniasis may be the trigger for secondary haemophagocytic lymphohistiocytosis. On the other hand, disseminated intravascular coagulation may also result. The International Society of Thrombosis and Hemostasis has recommended the use of a scoring system for disseminated intravascular coagulation. An association between visceral leishmaniasis and consumption coagulopathy is not frequent. Our systematic literature review from 1967 to 2019 pointed to the report of only 16 cases. Our case demonstrates that it is necessary to be aware of the existence of this association.
Topics: Adult; Disseminated Intravascular Coagulation; Humans; Leishmania infantum; Leishmaniasis, Visceral; Male
PubMed: 33108965
DOI: 10.1177/0049475520967239 -
Surgery Sep 2020Pancreatoduodenectomy with synchronous resection of the portal vein/superior mesenteric vein confluence may result in the development of left-sided portal hypertension....
BACKGROUND
Pancreatoduodenectomy with synchronous resection of the portal vein/superior mesenteric vein confluence may result in the development of left-sided portal hypertension. Left-sided portal hypertension presents with splenomegaly and varices and may cause severe gastrointestinal bleeding. The aim of the study is to review the incidence, treatment, and preventive strategies of left-sided portal hypertension.
METHODS
A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to identify all studies published up to September 30, 2019 reporting data on patients with left-sided portal hypertension after pancreatoduodenectomy with venous resection.
RESULTS
Eight articles including 829 patients were retrieved. Left-sided portal hypertension occurred in 7.7% of patients who had splenic vein preservation and 29.4% of those having splenic vein ligation. Fourteen cases of gastrointestinal bleeding owing to left-sided portal hypertension were reported at a mean interval of 28 months from pancreatoduodenectomy. Related mortality at 1 month was 7.1%. Treatment of left-sided portal hypertension consisted of splenectomy in 3 cases (21%) and colectomy in 1 (7%) case, whereas radiologic, endoscopic procedures or conservative treatments were effective in the other cases (71%).
CONCLUSION
Left-sided portal hypertension represents a potentially severe complication of pancreatoduodenectomy with venous resection occurring at greater incidence when the splenic vein is ligated and not reimplanted. Left-sided portal hypertension-related gastrointestinal bleeding although rare can be managed depending on the situation by endoscopic, radiologic procedures or operative intervention with low related mortality.
Topics: Carcinoma, Pancreatic Ductal; Colectomy; Conservative Treatment; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Incidence; Ligation; Mesenteric Veins; Pancreatic Neoplasms; Pancreaticoduodenectomy; Portal Vein; Postoperative Complications; Splenectomy; Splenomegaly; Treatment Outcome
PubMed: 32600882
DOI: 10.1016/j.surg.2020.04.030 -
The Canadian Journal of Infectious... 2020Splenic complications of acute infection include splenomegaly, splenic infarct, and splenic rupture. These complications are relatively rarely reported, and the aim of... (Review)
Review
Splenic complications of acute infection include splenomegaly, splenic infarct, and splenic rupture. These complications are relatively rarely reported, and the aim of this research was to synthetize data on this topic according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the PubMed database. In this review, we find that unlike other severe complications of babesiosis, splenic infarct and rupture occur in younger and immunocompetent patients, and they do not correlate with parasitemia level. Furthermore, admission hemoglobin of 10 mg/dl or less, platelet count of 50 × 10⁹/L or less, presence of hemodynamic instability, and splenic rupture were associated independently with an increased risk of requiring splenectomy. As babesiosis is an emerging tick-borne zoonosis, we hope that this review will help to raise awareness among clinicians regarding this rare but potentially life-threatening complication.
PubMed: 32566058
DOI: 10.1155/2020/6934149