[Misdiagnosis of Gaucher disease in real life: Retrospective study of the French Gaucher's disease registry]. / Les erreurs diagnostiques de la maladie de Gaucher dans la vraie vie : étude rétrospective du Registre français de la Maladie de Gaucher.

INTRODUCTION: Gaucher disease is an autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase which leads to an accumulation of glucosylceramide in the macrophages. Splenomegaly, hepatomegaly, cytopenias (anemia, thrombocytopenia) and bone disorders are the main symptoms. The diagnosis is often delayed, leading to unnecessary investigations and treatments, and delaying the specific treatment. The primary objective of our study was to establish, in patients who had a diagnostic delay of more than one year, the reported misdiagnoses before the final diagnosis. The secondary objectives were to investigate the risk factors associated with error and delayed diagnosis. METHODS: Retrospective study including patients with Gaucher disease from the French Gaucher Disease Registry. Collection of data by a single investigator from a standardized form. RESULTS: Among 83 patients with a known diagnostic delay, 13 patients (15 %) had one or two misdiagnoses. These included osteo-articular diagnoses (osteomyelitis, osteoarthritis, arthritis, osteochondritis, rheumatic fever, n=8), haematological diagnoses (gestational thrombocytopenia, immunological thrombocytopenia, n=4), infectious diagnoses (visceral leishmaniasis, mononucleosis, n=2) and hemochromatosis. The osteo-articular and infectious diagnoses concerned the child and the adolescent while the haematological diagnoses and the hemochromatosis concerned the adult. No factors were found associated with misdiagnoses. Patients with a diagnostic delay greater than one year were less likely to have hepatosplenomegaly as the first symptom. CONCLUSION: There is a risk of diagnostic error related to phenotypic heterogeneity and lack of specificity of Gaucher disease symptoms. This study helps to better identify the misdiagnoses associated with Gaucher disease.

Early splenomegaly and septicaemia in homozygous sickle cell disease: A birth cohort study.

BACKGROUND: Patients with homozygous sickle cell disease (HbSS) and clinical splenomegaly by 6 months of age appeared at greater risk of invasive infections after 5 years of the Jamaican Cohort Study. We determined whether this risk remained significant over a longer study period, using a more rigorous definition of infection and examining the contribution of potential confounders. METHODS: Newborn screening of 100,000 consecutive deliveries during 1973-1981 detected 311 births with HbSS. Age at first clinical splenomegaly was used to categorize 285 of these patients in whom this could be determined: at or before 7 months (early), after 7 months (later), or 'never' palpated despite repeated examinations. Infective episodes were confined to 'first infections confirmed by positive culture'. Using a generalized linear model, the risk of septicaemia was assessed in each group, after adjusting for potential confounders. RESULTS: Of 93 'first infections', 42 occurred in 105 subjects in the 'early' group, 49 in 157 subjects in the 'later' group, and two in 23 subjects in the 'never' group; the observed to expected ratio of 1.42, 0.90 and 0.22 was highly significant (p = .003). Assessed as risk ratios, 'early' splenomegaly had a significantly higher risk ratio (RR) for septicaemia (RR = 7.4, confidence interval [CI]: 1.1-50.7, p < .05) when compared to the 'never' group adjusting for vaccine exposure and foetal haemoglobin concentration. The most common organisms were Streptococcus pneumoniae, Salmonella species, Haemophilus influenzae and Staphylococcus aureus. CONCLUSION: Early clinical splenomegaly in HbSS remains a predictor of septicaemia, defining a group that may require closer monitoring.

Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa.

Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) provides hydroxyurea at maximum tolerated dose (MTD) for children with sickle cell anemia (SCA) in sub-Saharan Africa. Beyond reducing SCA-related clinical events, documented treatment benefits include ∼50% reduction in malaria incidence. To identify associations and propose mechanisms by which hydroxyurea could be associated with lower malaria rates, infections were recorded across all clinical sites (Angola, Democratic Republic of Congo, Kenya, and Uganda). Hazard ratios (HR) with 95% confidence intervals (CIs) for baseline demographics, and time-varying laboratory and clinical parameters were estimated in a modified Cox gap-time model for repeated events. Over 3387 patient-years of hydroxyurea treatment, 717 clinical malaria episodes occurred in 336 of 606 study participants; over half were confirmed by blood smear and/or rapid diagnostic testing with 97.8% Plasmodium falciparum. In univariate analysis limited to 4 confirmed infections per child, malaria risk was significantly associated with absolute neutrophil count (ANC), splenomegaly, hemoglobin, and achieving MTD; age, malaria season, MTD dose, fetal hemoglobin, α-thalassemia, and glucose-6-phosphate dehydrogenase deficiency had no effect. In multivariable regression of confirmed infections, ANC was significant (HR, 1.37 per doubled value; 95% CI, 1.10-1.70; P = .0052), and ANC values <3.0 × 109/L were associated with lower malaria incidence. Compared with nonpalpable spleen, 1- to 4-cm splenomegaly also was associated with higher malaria risk (HR, 2.01; 95% CI, 1.41-2.85; P = .0001). Hydroxyurea at MTD is associated with lower malaria incidence in SCA through incompletely defined mechanisms, but treatment-associated mild myelosuppression with ANC <3.0 × 109/L is salutary. Splenomegaly is an unexplained risk factor for malaria infections among children with SCA in Africa.

Diagnostic and management strategies for Myeloproliferative Neoplasm-Unclassifiable (MPN-U): An international survey of contemporary practice.

Myeloproliferative Neoplasm-Unclassifiable (MPN-U) is defined as an MPN that fails to meet the diagnostic criteria for any of the other defined classical or 'non-classical' MPNs. The reported incidence is variable, dependent on appropriate recognition, and the clinical course can be highly variable ranging from an indolent disorder through to an aggressive disease course with a significant risk of thrombosis, bulky splenomegaly, and debilitating symptom burden. Clinicians frequently manage these conditions according to the clinical concerns e.g. splenomegaly akin to the phenotype, but no evidence base exists. Currently, there are no widely accepted guidelines to deal with both the diagnostic work up and subsequent clinical management of this entity. We hence surveyed major International MPN centres to gain an understanding of common challenges in MPN-U management in 2021 and aid identification of considerable practice variations where harmonisation would be desirable. Such information is vital to support future consensus guidelines in addition to informing further collaborative studies.

Noninvasive Assessment of Fibrosis Regression after Direct-acting Antiviral Treatment in Hepatitis C Virus Patients.

BACKGROUND: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited. OBJECTIVES: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest. METHODS: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two-dimensional SWE or FibroTest©; APRI and FIB-4 scores. RESULTS: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6-33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5-100), 13.4 kPa (range 5.5-51) at 6 months, and 11.4 kPa (range 6.1-35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment. CONCLUSIONS: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis.

Morbidity associated with Schistosoma mansoni infection in north-eastern Democratic Republic of the Congo.

BACKGROUND: Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. METHODS/PRINCIPAL FINDINGS: In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06-1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99-2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73-1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. CONCLUSIONS/SIGNIFICANCE: Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity.

Direct Relationship between Interleukin-10 Gene Polymorphism and Hepatocellular Carcinoma Complicated by Direct Acting Antiviral Treatment of Hepatitis C Virus.

OBJECTIVE: This study aimed to assess the correlation between the genotyping of interleukin-10 (IL-10 polymorphism rs 1800871) and the incidence hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV) treated with direct acting antivirals (DAAs). METHOD: For 200 patients with HCV infection who completed DAA treatment and followed up for 1 year, IL-10 polymorphism SNP(-819) rs 1800871 analysis was conducted via real time polymerase chain reaction. During the follow-up period, 100 patients who developed HCC were selected and compared with 100 patients who did not develop any complications. RESULTS: The studied patients were divided into two groups according to the incidence of complications after completion of DAA treatments. During the follow-up, 100 patients with HCV infection who developed HCC were selected and compared with 100 patients with HCV infection who did not develop any complications (positive control group). For the HCC group (n = 100), the mean age was 58.1 ± 6.4 years, with 92.7% being male and 7.3% being female; 91% had cirrhosis, 10% had lymphadenitis, 75% had splenomegaly, and 17% had ascites. In the positive control group (n = 100), mean age was 46.3 ± 9.4 years, with 68% being male and 32% being female; 20% had cirrhosis, 12% had splenomegaly, and 4.2% had ascites. The results demonstrated that sofosbuvir (SOF) + daclatasvir + ribavirin regimen was the most prevalent drug treatment for patients with HCC (72%), while SOF + Simeprevir was the most safe treatment for HCV infection among patients with HCC (2%). CT genotype was the most common genotype in the HCC group (56%), among different drug regimen (67.8%). T allele was the most prevalent in HCC group (61%), while the C allele was the least prevalent (39%). CONCLUSION: IL-10 genotyping may help in selecting the safest and most accurate drug regimen according to the safest genotype response relationship and follow-up of genotype resistance.

Reconstructing spleno-mesenterico-portal cofluence by bifurcated allogeneic vein in local advanced pancreatic cancer-a feasible method to avoid left-sided portal hypertension.

BACKGROUND: Left-sided portal hypertension is usually found in patients undergoing pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) confluence resection. This study is to explore the outcomes of S-M-P confluence reconstruction after resection by using bifurcated allogeneic vein. METHODS: Clinicopathologic data of patients who underwent extensive PD with S-M-P confluence resection for carcinoma of pancreatic head/uncinate process in our hospital between December 2011 and August 2018 were retrospectively reviewed and clinical outcomes of vein reconstruction after resection were analyzed. RESULTS: Of the 37 patients enrolled, S-M-P reconstruction by bifurcated allogeneic vein was performed in 24 cases (group 1) and simply splenic vein ligation in 13 cases (group 2). Items including pathological results, blood loss, and complications were comparable between the two groups, operation time was longer in group 1 (573.8 vs. 479.2 min, p = 0.018). Significantly decreased platelet count (205.9 vs. 133.1 × 109 /L, p = 0.001) and increased splenic volume (270.9 vs. 452.2 ml, p < 0.001) were observed in group 2 at 6 months after operation. The mean splenic hypertrophy ratio was 1.06 in group 1 and 1.63 in group 2, respectively (p < 0.001). There were four patients with varices were found in group 2, none in group 1. CONCLUSIONS: Without increased complications, reconstructing S-M-P confluence by bifurcated allogeneic vein after resection may help to avoid left-sided portal hypertension.

Serological evidence of avian HEV antibodies in apparently healthy chickens in southwest Nigeria.

Avian hepatitis E virus (aHEV) is associated with hepatitis-splenomegaly syndrome, big liver and spleen disease and hepatic rupture haemorrhage syndrome. However, the knowledge about aHEV in commercial layer chickens in Nigeria is scarce. In this study, 460 serum samples obtained from 36 apparently healthy commercial layer chicken flocks in three states (Ogun, Osun and Oyo States) of southwestern Nigeria were analysed by enzyme linked immunosorbent assay for the presence of anti-aHEV immunoglobulin Y (IgY) antibodies. In total, the overall seroprevalence of anti-aHEV antibodies was 14.6%. The serological analysis revealed that 75% of the flocks examined were positive for anti-aHEV IgY antibodies from chickens of various ages in all three states. The percentage of the seropositive chickens in the three states varied from flock to flock ranging from 60% to 88.8% and seropositive chickens were detected at any age (24-52 weeks of age) without significant differences between the age groups. This is the first report assessing the presence of aHEV antibodies in chickens from Nigeria. The detection of anti-aHEV antibodies in commercial layer chickens in this study emphasizes the importance of serosurveillance in disease monitoring due to the economic threat posed by aHEV as a result of decreased egg production and increased mortality in affected commercial layer chicken farms. However, further studies are essential to reveal the clinical implications and to assess the real burden of aHEV in Nigeria.

Prevalence of Malaria Parasite Infections among U.S.-Bound Congolese Refugees with and without Splenomegaly.

All U.S.-bound refugees from sub-Saharan Africa receive presumptive antimalarial treatment before departing for the United States. Among U.S.-bound Congolese refugees, breakthrough malaria cases and persistent splenomegaly have been reported. In response, an enhanced malaria diagnostic program was instituted. Here, we report the prevalence of plasmodial infection among 803 U.S.-bound Congolese refugees who received enhanced diagnostics. Infections by either rapid diagnostic test (RDT) or PCR were detected in 187 (23%) refugees, with 78 (10%) by RDT only, 35 (4%) by PCR only, and 74 (9%) by both. Infections identified by PCR included 103 monoinfections (87 Plasmodium falciparum, eight Plasmodium ovale, seven Plasmodium vivax, and one Plasmodium malariae) and six mixed infections. Splenomegaly was associated with malaria detectable by RDT (odds ratio: 1.8, 95% CI: 1.0-3.0), but not by PCR. Splenomegaly was not strongly associated with parasitemia, indicating that active malaria parasitemia is not necessary for splenomegaly.

The spectrum of splenic complications in patients with sickle cell disease in Africa: a systematic review.

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.

Left-sided portal hypertension after pancreatoduodenectomy with resection of the portal/superior mesenteric vein confluence. Results of a systematic review.

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.

Clinical relevance of endpoints in clinical trials for acid sphingomyelinase deficiency enzyme replacement therapy.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) also known as Niemann-Pick disease, is a rare lysosomal storage disorder with a diverse disease spectrum that includes slowly progressive, chronic visceral (type B) and neurovisceral forms (intermediate type A/B), in addition to infantile, rapidly progressive fatal neurovisceral disease (type A). PURPOSE AND METHODS: We review the published evidence on the relevance of splenomegaly and reduced lung diffusion capacity to the clinical burden of chronic forms of ASMD. Targeted literature searches were conducted to identify relevant ASMD and non-ASMD studies for associations between diffusing capacity of the lungs for carbon monoxide (DLCO) and splenomegaly, with clinical parameters and outcome measures. RESULTS: Respiratory disease and organomegaly are primary and independent contributors to mortality, disease burden, and morbidity for patients with chronic ASMD. The degree of splenomegaly correlates with short stature, atherogenic lipid profile, and degree of abnormality of hematologic parameters, and thus may be considered a surrogate marker for bleeding risk, abnormal lipid profiles and possibly, liver fibrosis. Progressive lung disease is a prevalent clinical feature of chronic ASMD, contributing to a decreased quality of life (QoL) and an increased disease burden. In addition, respiratory-related complications are a major cause of mortality in ASMD. CONCLUSIONS: The reviewed evidence from ASMD natural history and observational studies supports the use of lung function and spleen volume as clinically meaningful endpoints in ASMD trials that translate into important measures of disease burden for patients.

Clinical Sequelae Associated with Unresolved Tropical Splenomegaly in a Cohort of Recently Resettled Congolese Refugees in the United States-Multiple States, 2015-2018.

Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0-27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04-1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15-2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73-17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03-2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.

Cystic fibrosis-associated liver disease in children.

As improvements in nutritional and pulmonary care increase the life expectancy of cystic fibrosis (CF) patients, CF-associated liver disease (CFLD) is emerging as a cause of mortality. CFLD is the third leading cause of death in CF patients. We performed a search on PubMed and Google Scholar for published articles on CFLD. We reviewed the articles found in the literature search and gave priority to recent publications and studies with larger sample sizes. The prevalence of CFLD in the CF population is around 23% with a range of 2-62% and that prevalence increases linearly with age from 3.7% at age 5 to 32.2% at age 30. CFLD can present clinically in various ways such as hepatomegaly, variceal hemorrhage, persistent elevation of liver enzymes, and micro-gallbladder. Due to the focal nature of fibrosis in majority cases of CFLD, liver biopsies are sparsely performed for diagnosis or the marker of liver fibrosis. Although the mechanism of CFLD development is still unknown, many potential factors are reported. Some mutations of CFTR such as having a homozygous F508del mutation has been reported to increase the risk of developing CFLD and its severity. Having the SERPINA1 Z allele, a history of pancreatic insufficiency, a history meconium ileus, CF-related diabetes, or being male increases the risk of developing CFLD. Environmental factors do not appear to have significant effect on modulating CFLD development. Ursodeoxycholic acid is commonly used to treat or prevent CFLD, but the efficacy of this treatment is questionable.

Clinical, ocular motor, and imaging profile of Niemann-Pick type C heterozygosity.

OBJECTIVE: To characterize subclinical abnormalities in asymptomatic heterozygote NPC1 mutation carriers as markers of neurodegeneration. METHODS: Motor function, cognition, mood, sleep, and smell function were assessed in 20 first-degree heterozygous relatives of patients with Niemann-Pick disease type C (NPC) (13 male, age 52.7 ± 9.9 years). Video-oculography and abdominal ultrasound with volumetry were performed to assess oculomotor function and size of liver and spleen. NPC biomarkers in blood were analyzed. 18F-fluorodesoxyglucose PET was performed (n = 16) to detect patterns of brain hypometabolism. RESULTS: NPC heterozygotes recapitulated characteristic features of symptomatic NPC disease and demonstrated the oculomotor abnormalities typical of NPC. Hepatosplenomegaly (71%) and increased cholestantriol (33%) and plasma chitotriosidase (17%) levels were present. The patients also showed signs seen in other neurodegenerative diseases, including hyposmia (20%) or pathologic screening for REM sleep behavior disorder (24%). Cognitive function was frequently impaired, especially affecting visuoconstructive function, verbal fluency, and executive function. PET imaging revealed significantly decreased glucose metabolic rates in 50% of participants, affecting cerebellar, anterior cingulate, parieto-occipital, and temporal regions, including 1 with bilateral abnormalities. CONCLUSION: NPC heterozygosity, which has a carrier frequency of 1:200 in the general population, is associated with abnormal brain metabolism and functional consequences. Clinically silent heterozygous gene variations in NPC1 may be a risk factor for late-onset neurodegeneration, similar to the concept of heterozygous GBA mutations underlying Parkinson disease.

An ultrasound-based referential of body height-adjusted normal liver organometry in school children from Bokito in rural Cameroon.

The grading system for ultrasonographic assessment of Schistosoma mansoni morbidity is crucial for evaluation of control programs. This requires prior definition of normal liver organometric ranges in the population from the endemic area. A cross-sectional study was conducted in a S. mansoni endemic area in rural Cameroon. 1002 Participants were screened and 234 of them, free from all common liver-affecting diseases in the area (schistosomiasis, malaria, hepatitis B and C) and with no ultrasonographic signs of liver disease were selected and their liver parameters measured by ultrasonography. All statistics were considered significant for p-values < 0.05. Normal dimensions of livers lobe sizes, portal vein wall thickness and portal vein diameters are reported. The liver organometric data are presented for the entire study population as a whole and separately for males and females as prediction plots, with observed values and fitted regression line with 95% confidence. Reference ranges for liver parameters (size, portal vein thickness and diameter) adjusted for body height established in the current study are novel for Cameroon. The prediction plots generated should improve the accuracy of the assessment of liver morbidity by ultrasonography in the region.

Evaluation and characterisation of Chronic myeloid leukemia and various treatments in Saudi Arabia: A retrospective study.

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal BCR-ABL1-positive myelo-proliferative disorder resulting from an acquired genetic mutation, characterized by the presence of the Philadelphia (Ph) chromosome. CML is associated with significantly high granulocyte numbers in the bone marrow and peripheral blood. MATERIALS AND METHODS: This retrospective study conducted at the Hematology Unit of King Saud University Medical City aimed to evaluate the incidence and characteristics of CML and the various treatments in Saudi Arabia. We have evaluated the demographic, clinical, and hematological data of 56 consecutive patients who visited the hospital from Jan 2012 to Jan 2018. RESULTS: The diagnosis and stage of CML were determined based on the World Health Organization criteria, following polymerase chain reaction analysis of bone marrow aspirates. Our study group had equal numbers of genders with a age mean of 43.3+18.1 years. The predominance of younger patients and equal incidence in males and females could be due to the racial and socioeconomic disparities among our patients compared to those in previous studies. While the most predominant symptom was fatigue and bone pain, the most common clinical sign was hepato-splenomegaly, followed by remarkable weight loss, and epistaxis. CONCLUSION: A patient with an increased WBC count, abdominal pain, left side distension, and hepato-splenomegaly should clearly be evaluated for CML.

Portal hypertension caused by pancreatic cancer: Multidetector computed tomography diagnosis and multivariate analysis of variceal hemorrhage.

CONTEXT: Pancreatic cancer portal hypertension (PCPH) is a rare cause of gastrointestinal bleeding. This study retrospectively assessed gastrointestinal bleeding risk factors in 57 PCPH patients diagnosed via multidetector computed tomography (MDCT). MATERIALS AND METHODS: The data of patients with pancreatic cancer from January 2008 to January 2018 at Qingdao Municipal Hospital were reviewed. PCPH patients were screened with MDCT and followed up. MDCT findings (e.g., the location of the venous obstruction, type of variceal veins pathway, and splenomegaly) were recorded. Variceal hemorrhage was recorded. The MDCT findings and clinical data of the PCPH patients were used in this analysis to explore the risk factors of variceal hemorrhage using binary logistic regression and multivariate logistic regression model. RESULTS: Fifty-seven of the 182 patients were diagnosed with PCPH. A total of 7 draining routes and 11 types of varices were found. Of these patients, eight experienced variceal hemorrhage. Univariate analysis showed that splenomegaly (odds ratio [OR] = 10.364, P = 0.003) was significantly associated with an increased risk of variceal hemorrhage. Multivariate analysis showed that splenomegaly (OR = 66.491, 95% confidence interval: 2.790-1584.643, P = 0.009) was an independent influencing factor for variceal hemorrhage in PCPH patients. CONCLUSIONS: Patients with pancreatic cancer have high morbidity of PCPH. The splenomegaly is more prone to hemorrhage. Splenomegaly was an independent risk factor of variceal hemorrhage. MDCT can provide insight into the stenosis and occlusion of the portal vein system and the drainage routes of variceal veins and is one of the best ways to diagnose PCPH.

[Digestives diseases associated to sickle cell anemia in Lubumbashi: epidemiological and clinical aspects]. / Pathologies digestives associées à la drépanocytose à Lubumbashi: aspects épidémiologiques et cliniques.

INTRODUCTION: sickle cell disease is a genetic disease with autosomal inheritance associated with haemoglobin structure abnormality which causes the formation of hemoglobin S. The purpose of our study was to collect data on digestive diseases in patients with sickle cell disease in Lubumbashi and to highlight their epidemiological and clinical features. METHODS: We conducted a retrospective, descriptive, cross-sectional study at the Research Center for Sickle Cell Disease in Lubumbashi. All the records of patients on follow-up for sickle cell disease with digestive disease during our 3-year period (January 2015 to December 2017) were analyzed. Data were collected using a survey taking into account different study parameters including: age, sex, the reason for consultation, diagnosis, the type of vaso-occlusive crisis, the paraclinical examinations made, hydroxyurea treatment. RESULTS: out of a total of 403 medical records examined we found 206 cases (n=206) of sickle cell disease associated with digestive disease, accounting for a rate of 51,11% of patients with sickle cell disease who suffered from digestive diseases. Both sexes were represented with a slight female predominance (51.94%) and a sex ratio M/F of 0.92. The most represented age ranges 1-6 years (32.52%), the average age was 11.8 years; the standard deviation was 21.9; the extreme ages were 13 months and 38 years. The reason for consultation was dominated by fever (60,67%), abdominal pain (44.66%) and digestive disorders (30,09%). Vaso-occlusive abdominal crises were found in 65 patients (31.55%) among whom 36 had only 1 crisis, 24 had 2 crises and 5 had 3 crises. Intestinal diseases were found in 121 patients (69,41%) dominated by intestinal parasites (found in 58 patients whose collection of stool samples showed 4 parasites: Yersinia enterocolitis, Entamoeba histolytica, Giardia intestinalis and Clostridium difficile). Gastric diseases were found in 105 patients ( 50,97%) divided into peptic ulcer (45 patients) and gastritis (60 patients); biliary vesicular disease was found in 40 patients (19.41%) including vesicular lithiasis without cholecystitis (32 patients), lithiasic cholecystitis (5 patients) and lithiasis in the main biliary tract (3 cases); there was 1 single case diagnosed with acute pancreatitis. The most common associated diseases in our study were respiratory diseases (169 cases;82,03%), oto-rhino-laryngological diseases (157 cases;76.21%), bony, vaso-occlusive crises (146 cases; 70,87%), urogenital diseases (64 cases; 31.06%) and malaria (51 patients; 24.75%). Hepatic diseases and diseases of the spleen were found in 18 cases (8.73%) and 47 cases (22,81%) respectively. Ultrasound was requested in 79 patients but only 31 of them underwent it because of the lack of financial means (it costs 20 U.S. dollars). In the case of clinically obvious splenomegaly, the search for Howell-Jolly bodies was requested in 23 patients but it was only performed in 2 patients because it costs 10 U.S. dollars). Routine blood count, hemoglobin, hematocrit, inflammatory assessment and thick drop examination were performed in all our patients but liver assessment, tests done on stool samples, urine test were recommended based on patient's complaint. Out of 206 patients, only 60 were under hydroxyurea treatment (29,16%). CONCLUSION: digestive diseases are common in patients with sickle cell disease and account for almost half of patients with diagnosed sickle cell disease. Unfortunately, best management is limited by poverty leading to less very useful paraclinical examinations in patients with digestive diseases resulting from sickle cell disease.