scholarly journals Twenty-Five Years Diagnosing Gaucher’s Disease in Spain, What We Have Learned?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1110-1110
Author(s):  
Marcio M Andrade-Campos ◽  
Jose L Capablo ◽  
Jesus J Fraile ◽  
Mercedes Roca-Espiau ◽  
Pilar Irun ◽  
...  

Abstract Gaucher disease (GD), has a pan-ethnic distribution with incidence in non-Ashkenazi Jewish population about 1/70-140 thousand inhabitants. The deficiency in lysosomal acid beta-glucosidase enzyme secondary to variants in the GBA gene with autosomal recessive inheritance gives rise to a variable clinical picture. It appears at any age with symptoms that include anemia, thrombocytopenia, pain and vascular bone lesions, visceral enlargement, persistent fatigue. It was the first EDL to have enzymatic replacement and substrate reduction therapy that impact in the awareness of the disease. In 1993, the Spanish Registry of Gaucher Disease was created (REsEG), within the Spanish Foundation for the Study and Therapeutics of EG (FEETEG), with the aim of providing support to all those involved in the management of patients with EG and summarize experience at the national level. This work review the characteristics at diagnosis of type 1 adult GD (GD1) patients, diagnosed outside active early diagnosis programs, along of twenty five years of REsEG existence focus on leading diagnostic symptoms in order to answer the current challenges in patients suspicions. Aim: To analyze the evolving profile of GD1 patients diagnosed before and after 2000 based on the principal manifestations including visceral, hematological involvement, bone pain, bleeding in order to define the current suspicious characteristics in our population. Methods: Patients 18+ years old included in the REsEG were selected. Demographic, genetic, clinical (hematological, visceral, bone, neurological) data, severity index, biomarkers and other relevant information were included in a database created for this purpose. Platelets <140x109/L were considered as thrombocytopenia and hemoglobin below 12 g/dL in females and 13 g/dL in males were considered as anemia. Ethic board of SpRGD and FEETEG approved the development of the present work. To analyze the evolution in the diagnostic features of adult GD1 patients, a cut-off settled according the year of diagnosis, <2000 or 2000+, was used. The use of this cut-off was made considering the awareness for diagnostic increased progressively since ERT availability in mid 90's in Spain. The statistical analysis were made using comparative methods with a level of 95% interval of confidence. Results: Since 1993 a total of 223 GD1 with 18+ years old patients were diagnosed and included in the registry. 50.7% (113) were females, mean age at diagnosis 38.5 (18-87). The symptoms that led to the diagnostic of GD1 were: splenomegaly 71.1%, (3 of them detected during pregnancy work out), thrombocytopenia 83.3%, isolated anemia 39.0%, pancytopenia 8.5%, hepatomegaly 22.5%, bone pain: 57.9%(bone crisis 48.8% pathological fractures 3 cases), hemorrhagic diathesis (ecchymosis, epistaxis): 20.6%, peripartum bleeding: 3 cases, family study: 19.3%, early Parkinson's study 3 cases, other reasons for referral were MGUS 4 cases, hyperferritinemia 7 cases. Also we have recorded that bone marrow aspiration or biopsy was the first test in the diagnosis process in about 80% of cases. According the year of diagnosis 131 (58.7%) patients were diagnosed before 2000 (group A), mean age at diagnosis 36 (18-87) y.o and 92 (41.3%) after 2000 (group B). mean age at diagnosis 41.8 (18-79) y.o. General characteristics and genotype distribution are detailed in tables 1 and 2. Concerning profile's patient diagnosed before 2000 showing a more clinical aggressive behavior, even the presence of thrombocytopenia was similar in both groups, the severity of thrombocytopenia were higher in group A (69.8; 16-129 x109/L) vs group B (83.4; 14-131 x109/L) (p=0.006), also anemia, bone pain and visceral enlargement show higher incidences. During this time there 7 cases have developed Parkinson's disease, 2 patients with de novo mutations, 21 neoplasms and other interesting findings. Conclusion: In our population we have found that the classical main characteristics of GD1 adult patients at diagnosis has evolved to a less severe phenotype in the present century. Features like bone pain, anemia, thrombocytopenia, visceral involvement are decreasing in percentage and severity; in parallel mild genetic variants were more prevalent. These data suggest that we need to continue the efforts on training in young hematologist to increase the awareness and visibility of disease, also among primary care providers in order to improve the early diagnosis. Disclosures No relevant conflicts of interest to declare.

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 898 ◽  
Author(s):  
Virginia E. Kimonis ◽  
Roy Tamura ◽  
June-Anne Gold ◽  
Nidhi Patel ◽  
Abhilasha Surampalli ◽  
...  

Prader–Willi syndrome (PWS) is an imprinting genetic disorder characterized by lack of expression of genes on the paternal chromosome 15q11–q13 region. Growth hormone (GH) replacement positively influences stature and body composition in PWS. Our hypothesis was that early diagnosis delays onset of obesity in PWS. We studied 352 subjects with PWS, recruited from the NIH Rare Disease Clinical Research Network, to determine if age at diagnosis, ethnicity, gender, and PWS molecular class influenced the age they first become heavy, as determined by their primary care providers, and the age they first developed an increased appetite and began seeking food. The median ages that children with PWS became heavy were 10 years, 6 years and 4 years for age at diagnosis < 1 year, between 1 and 3 years, and greater than 3 years of age, respectively. The age of diagnosis and ethnicity were significant factors influencing when PWS children first became heavy (p < 0.01), however gender and the PWS molecular class had no influence. Early diagnosis delayed the onset of becoming heavy in individuals with PWS, permitting early GH and other treatment, thus reducing the risk of obesity-associated co-morbidities. Non-white individuals had an earlier onset of becoming heavy.


Obesity Facts ◽  
2021 ◽  
pp. 1-9
Author(s):  
Serdar Sahin ◽  
Havva Sezer ◽  
Ebru Cicek ◽  
Yeliz Yagız Ozogul ◽  
Murat Yildirim ◽  
...  

<b><i>Introduction:</i></b> The aim of this was to describe the predictors of mortality related to COVID-19 infection and to evaluate the association between overweight, obesity, and clinical outcomes of COVID-19. <b><i>Methods:</i></b> We included the patients &#x3e;18 years of age, with at least one positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients were grouped according to body mass index values as normal weight &#x3c;25 kg/m<sup>2</sup> (Group A), overweight from 25 to &#x3c;30 kg/m<sup>2</sup> (Group B), Class I obesity 30 to &#x3c;35 kg/m<sup>2</sup> (Group C), and ≥35 kg/m<sup>2</sup> (Group D). Mortality, clinical outcomes, laboratory parameters, and comorbidities were compared among 4 groups. <b><i>Results:</i></b> There was no significant difference among study groups in terms of mortality. Noninvasive mechanical ventilation requirement was higher in group B and D than group A, while it was higher in Group D than Group C (Group B vs. Group A [<i>p</i> = 0.017], Group D vs. Group A [<i>p</i> = 0.001], and Group D vs. Group C [<i>p</i> = 0.016]). Lung involvement was less common in Group A, and presence of hypoxia was more common in Group D (Group B vs. Group A [<i>p</i> = 0.025], Group D vs. Group A [<i>p</i> &#x3c; 0.001], Group D vs. Group B [<i>p</i> = 0.006], and Group D vs. Group C [<i>p</i> = 0.014]). The hospitalization rate was lower in Group A than in the other groups; in addition, patients in Group D have the highest rate of hospitalization (Group B vs. Group A [<i>p</i> &#x3c; 0.001], Group C vs. Group A [<i>p</i> &#x3c; 0.001], Group D vs. Group A [<i>p</i> &#x3c; 0.001], Group D vs. Group B [<i>p</i> &#x3c; 0.001], and Group D vs. Group C [<i>p</i> = 0.010]). <b><i>Conclusion:</i></b> COVID-19 patients with overweight and obesity presented with more severe clinical findings. Health-care providers should take into account that people living with overweight and obesity are at higher risk for COVID-19 and its complications.


Hand ◽  
2021 ◽  
pp. 155894472110085
Author(s):  
Landis R. Walsh ◽  
Laura C. Nuzzi ◽  
Amir H. Taghinia ◽  
Brian I. Labow

Background Although pediatric hand fractures are common and generally have good outcomes, they remain a considerable source of anxiety for non–hand surgeons, who are less familiar with these injuries. We hypothesized that this anxiety may manifest as inefficiency in referral patterns. Methods The records of pediatric patients with isolated, closed hand fractures without concurrent trauma seen at our institution by a hand surgeon between January 2017 and December 2018 were retrospectively reviewed. Results There were 454 patients included; 62.1% were men, and the mean age was 9.6 years at initial encounter. Most patients (89.6%) were treated nonoperatively and incurred few complications (0.5%). Roughly half of all cases (n = 262) initially presented to an outside provider. Of these, 24.0% (n = 64 of 262) were evaluated by 2+ providers before a hand surgeon. Most commonly, these patients were referred from an outside emergency department (ED) to our ED before hand surgeon evaluation (n = 45 of 64). Forty-seven patients required surgery; however, none were performed urgently. Although a greater proportion of 7- to 11-year-old patients saw 2+ providers prior to a hand surgeon ( P = .007), fewer required surgery ( P < .001). Conclusions Pediatric closed hand fractures are mainly treated nonoperatively and nonemergently with generally excellent outcomes. Our data suggest that many patients continue to be referred through the ED or multiple EDs/providers for treatment. These inefficient referral patterns demonstrate the need for better education for ED and primary care providers, as well as better communication between these providers and local pediatric hand surgeons. Advancements in these areas are likely to improve efficiency of care and decrease costs.


Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1323
Author(s):  
Hessa A. Al-Sharif ◽  
Sherif A. El-Kafrawy ◽  
Jehad M. Yousef ◽  
Taha A. Kumosani ◽  
Mohammad A. Kamal ◽  
...  

Human respiratory syncytial virus (HRSV) is a main cause of hospital admission for lower respiratory tract infection. In previous studies from Saudi Arabia, higher prevalence of the NA1 genotype in group A was observed from Riyadh and Taif. This study recruited respiratory cases from Jeddah during January to December, 2017. RSV represented 13.4% in the recruited cases with 64% of them belonging to group A and 36% to group B. All group A cases in this study were ON1 type characterized by duplication of 72 nucleotides, 24 amino acids in the C-terminal in the second hypervariable region of the G gene. In addition, for group B all of the cases were clustered under BA9, which had uniquely characterized as duplication of 60 nucleotides in the G protein. Our sequences showed similarity with earlier sequences from Saudi Arabia, Kuwait, Thailand, South Africa, Spain, the USA and Cyprus. Some amino acid substitutions in the investigated sequences would cause a change in potential O-glycosylation and N-glycosylation profiles from prototype ON1. The predominance of the ON1 and BA9 genotype of RSV-A in Jeddah compared to previous Saudi studies showing predominance of the NA1 genotype for group A. This difference in genotype prevalence could be due to fast spread of the ON1 genotype worldwide or due to the flux of travelers through Jeddah during hajj/umrah compared to Riyadh and Taif. This shift in genotype distribution requires continuous surveillance for genetic characterization of circulating respiratory infections including RSV. These findings may contribute to the understanding of RSV evolution and to the potential development of a vaccine against RSV.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Alfredo Escartín ◽  
Marta González ◽  
Elena Cuello ◽  
Ana Pinillos ◽  
Pablo Muriel ◽  
...  

Background. The aim of this study was to evaluate the characteristics, management, and outcomes of acute cholecystitis in patients ≥80 years. Methods. This was a retrospective analysis of data from a prospective single-center patient registry. Results. The study population was composed of 348 patients, which were divided into two groups: those younger (Group A) and those older (Group B) than the median age (85.4 years). Although demographic and clinical characteristics of the two groups were similar, the disease management was clearly different, with older patients undergoing cholecystectomy less frequently (n=80 46.0% in Group A vs n=39 22.4% in Group B; p<0.001). The outcomes in both groups of age were similar, with 30-day mortality of 3.7%, morbidity of 17.2%, and readmissions of 4.2% and two-year AC recurrence in nonoperated patients of 22.5%. No differences were seen between operated and no operated patients. Severe (Grade III) AC was the only independent factor significantly associated with mortality (OR 86.05 (95% CI: 11–679); p<0.001). Conclusions. In elderly patients with AC, the choice of therapeutic options was not limited by the age per se, but rather by the disease severity (grade III AC) and/or poor physical status (ASA III-IV). In case of grade I-II AC, laparoscopic cholecystectomy can be safely performed and yield good results even in very old patients. Patients with grade III AC present high risk of morbidity and mortality, and the treatment should be individualized. ASA IV patients should avoid cholecystectomy, being antibiotic treatment and cholecystectomy the best option.


1993 ◽  
Vol 11 (12) ◽  
pp. 2330-2341 ◽  
Author(s):  
R Ladenstein ◽  
C Lasset ◽  
O Hartmann ◽  
D Frappaz ◽  
A Garaventa ◽  
...  

PURPOSE Relapse from stage 4 neuroblastoma usually carries a poor prognosis. A retrospective study using the European Bone Marrow Transplant (EBMT) Solid Tumor Registry was undertaken to define the role of megatherapy (MGT) in relapsed patients. PATIENTS AND METHODS After relapse, 33 boys and 15 girls with previous stage 4 neuroblastoma received intensification by MGT followed by either autologous (n = 42) or allogeneic (n = 6) bone marrow rescue in 11 European institutions. The median age at diagnosis was 47 months (range, 14 to 134) and the median interval from diagnosis to relapse was 16 months (range, 4 to 94). Thirty patients had received only conventional-dose primary treatments (group A), whereas 18 patients had previously received intensification with MGT (group B). The median follow-up time of the total group is 95 months (range, 25 to 185). RESULTS The actuarial overall survival rate at 2 years after MGT for relapse is 27% for group A and 0% for group B (P = .02). Three adverse, independent prognostic factors were confirmed by multivariate analysis using the Cox proportional hazards regression model: an interval of less than 12 months between diagnosis and relapse (P < .0001), nonresponding or untreated relapse (P = .0002), and previous MGT during primary treatments (P = .055). None of the other variables analyzed, such as sex, age, bone or bone marrow involvement at diagnosis or at relapse, and type of MGT at relapse, influenced outcome in this patient cohort. CONCLUSION Responding patients who relapse more than 12 months from diagnosis who had not received previous MGT appear to benefit from consolidation MGT. Relapse patients who do not fulfill these criteria gain no advantage from this cost-intensive procedure and should be treated differently.


2021 ◽  
Vol 11 (3) ◽  
pp. 667-671
Author(s):  
Jiang Jie ◽  
Qin Zhanxiong ◽  
Wu Li ◽  
Xie Xiaojie ◽  
Zhao Xunran ◽  
...  

Objective: To investigate the value on early diagnosis of experimental rat according to computed tomography (CT) combined with the serum level of Serum Soluble Mesothelin-related Proteins (SMRP). Methods: Thirty-two SD rat were divided into three groups, including group A (experimental group) of 20 rats with pleural cavity injection of crocidolite suspension, group B (negative control group) of 6 rats with pleural cavity injection of saline, group C (blank control group) of 6 rats without any processing. Chest and abdominal CT scan and enhancement were performed in the three months and six months after induction and the pleural thickening was analyzed. The serum level of SMRP was measured at the different time period including pre-injection, the postinjection first month, the second month, the third month and the sixth month. The correlation between pleural thickening and serum level of SMRP was analyzed. Results: In group A: 20 cases were performed on CT scan in post-injection third month and we found 13 cases without pleural lesions and 7 cases with pleural lesions including of 4 cases with mild pleural thickening, 1 moderate thickening and 2 severe thickening (2 cases died). Moreover, 18 cases were done by CT in post-injection third month and we found 3 cases without pleural lesions and 15 cases with pleural lesions including of 6 cases with mild pleural thickening, 5 moderate thickening and 4 severe thickening (3 cases died). No pleural lesions were found in group B and group C. SMRP expression level differences in the three groups was statistically significant. However, there was no difference in pre-injection in the three groups and there were no difference in group B and C at the different time period. In group A, there was no difference between post-injection first month and second month, whereas, there had statistically difference in post-injection third and sixth month. In group A, SMRP level gradually increased over time. The high correlation between pleural thickening and serum level of SMRP was seen at the post-injection third and sixth month, which the expression of SMRP gradually increased as the pleural thickening. Conclusion: Serum SMRP expression level has a certain value for early diagnosis and staging of MPM, which can be used as an important biomarker for early screening of high-risk groups exposed to asbestos.


2021 ◽  
Author(s):  
Mengdi Chen ◽  
Deyue Liu ◽  
Weilin Chen ◽  
Weiguo Chen ◽  
Kunwei Shen ◽  
...  

Abstract Background: Young patients were under-evaluated in the construction and validation of the 21-gene Assay Recurrence Score (RS). Previous evidence suggested that RS performed differently according the ages of patients. Our study aimed to explore the molecular driving patterns in patients of different ages.Methods: A total of 1,078 estrogen receptor (ER)-positive breast cancer patients between Jan 2009 and Mar 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were divided into three subgroups: Group A, ≤40y and premenopausal (n=97); Group B, >40y and premenopausal (n=284); Group C, postmenopausal (n=697). The correlation of RS and its modules and the variance of RS modules was explored.Results: Estrogen module had a stronger correlation with RS in patients >40y (ρ = -0.76 in Group B and -0.79 in Group C) compared with patients ≤40y (ρ = -0.64). Contrarily, the correlation between RS and invasion group was weaker in patients >40y (ρ = 0.29 in Group B and 0.25 in Group C) than in patients ≤40y (ρ = 0.44). The proliferation module contributed most to the variance in young patients (37.3%) while ER module contributed most in old patients (54.1% in Group B and 53.4% in Group C). For RS >25, proliferation module was the leading driver in all three subgroups (ρ = 0.38, 0.53 and 0.52 in Group A, B and C) while estrogen module had a weaker association with RS. The negative impact of ER related features on RS was stronger in clinical low-risk patients while the positive effect of proliferation module was stronger in clinical high-risk patients.Conclusions: RS was primarily driven by estrogen module in patients regardless of age, but the proliferation module had a stronger impact on RS in patients ≤40y than in those >40y. The impact of modules varied in patients with different genetic and clinical risk.


2013 ◽  
Vol 79 (9) ◽  
pp. 922-927 ◽  
Author(s):  
Ammar Al-Hassani ◽  
Mazin Tuma ◽  
Ismail Mahmood ◽  
Ibrahim Afifi ◽  
Ammar Almadani ◽  
...  

Blunt bowel and mesenteric injury (BBMI) is frequently a difficult diagnosis at initial presentation. We aimed to study the predictors for early diagnosis and outcomes in patients with BBMI. Data were collected retrospectively from the database registry between January 2008 and December 2011 in the only Level I trauma unit in Qatar. Patients with BBMI were divided into Group A (surgically treated within 8 hours) and Group B (treated after 8 hours). Data were analyzed and χ2, Student's t test, and multivariate regression analysis were performed appropriately. Among 984 patients admitted with blunt abdominal trauma (BAT), 11 per cent had BBMI with mean age of 35 ± 9.5 years. Polytrauma and isolated bowel injury were identified in 53 and 42 per cent, respectively. Mean Injury Severity Score (ISS) was higher in Group A in comparison to Group B (18 ± 11 vs 13 ± 8; P = 0.02). Presence of pain and seatbelt sign ( P = 0.02) were evident in Group B. Hypotension ( P = 0.004) and hypothermia ( P = 0.01) were prominent in Group A. The rate of positive Focused Assessment Sonography for Trauma was greater in Group A ( P = 0.001). Among operative findings, bowel perforation was more frequent in Group B ( P = 0.04), whereas mesenteric full-thickness hematoma was significantly higher in Group A. Pelvic fracture was more frequent finding in Group A ( P = 0.005). The overall mortality rate was 15.6 per cent. In patients with BAT, the presence of abdominal pain, hypotension, ISS greater than 16, hypothermia, pelvic fracture, and mesenteric hematoma might help in early diagnosis of BBMI. Moreover, base deficit and mean ISS were independent predictors of mortality. Delayed operative interventions greater than 8 hours increased morbidity rate but had no significant impact on mortality.


2021 ◽  
Vol 85 (1) ◽  
pp. 59-82
Author(s):  
Dagmar Steinmair ◽  
Richard Horn ◽  
Felix Richter ◽  
Guoruey Wong ◽  
Henriette Löffler-Stastka

The psychological strain of many psychiatric disorders arises from difficulties encountered in social interactions. Social withdrawal is often the first symptom of neuropsychiatric disorders. The authors explore the various options for training social cognition skills. Social cognition was assessed using the Movie for the Assessment of Social Cognition (MASC). After completion of mentalization-based therapy (MBT) training, MASC scores improved significantly in health care providers (p = .006, r = .57). Mentalizing (operationalized with reflective functioning [RF]) was assessed in the MBT group (Group A) and compared with RF in a control group (Group B). RF was significantly higher in Group A (RF = 4.35, SD = 1.19) than in Group B (RF = 3.43, SD = 1.70) (p = .0385; Cohen's d = 0.65). MBT might be a promising intervention in social cognition training. Mentalizing skills might be associated with attitude.


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