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  • 1
    Language: English
    In: Journal of clinical oncology, 2012-06-10, Vol.30 (17), p.2112-2118
    Description: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity. Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS). From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B. IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.
    Subject(s): Biological and medical sciences ; Medical sciences ; Diseases of the osteoarticular system ; Tumors of striated muscle and skeleton ; Tumors ; Osteosarcoma - drug therapy ; Femur - pathology ; Humans ; Child, Preschool ; Male ; Tibia - pathology ; Cisplatin - administration & dosage ; Humerus - pathology ; Disease-Free Survival ; Ifosfamide - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Chemotherapy, Adjuvant - methods ; Adolescent ; Adult ; Female ; Methotrexate - administration & dosage ; Bone Neoplasms - drug therapy ; Child ; Doxorubicin - administration & dosage
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 2
    Language: English
    In: Fertility and sterility, 2009, Vol.91 (3), p.935.e15-935.e16
    Description: Objective To report on our experience with girls and young women who received treatment for Hodgkin lymphoma, underwent prior oophoropexy to preserve their ovarian function, and subsequently gave birth. Design Retrospective monoinstitutional evaluation. Setting National Cancer Institute. Patient(s) Eleven girls given treatment for Hodgkin lymphoma and undergoing bilateral ovarian transposition at a median age of 13 years. Intervention(s) The ovaries were positioned behind the uterus by the general surgeon. Main Outcome Measure(s) Fourteen pregnancies were recorded among these 11 women, with 12 live births (1 twin) and 3 miscarriages. Result(s) None of these women needed the ovaries to be relocated, and none of them resorted to artificial insemination. Their median age at the time of first pregnancy was 31 years, and the median time elapsing since ovarian transposition was 14 years. Conclusion(s) This series confirms that oophoropexy can preserve ovarian function and enable future pregnancy. We encourage pediatric oncologists, surgeons, and radiotherapists to bear this option in mind when considering female patients for pelvic irradiation.
    Subject(s): Internal Medicine ; Obstetrics and Gynecology ; Oophoropexy ; radiotherapy ; childhood cancer ; fertility ; Abortion, Spontaneous ; Humans ; Live Birth ; Gynecologic Surgical Procedures ; Laparoscopy ; Radiotherapy - adverse effects ; Pelvis ; Radiation Injuries - etiology ; Pregnancy ; Young Adult ; Hodgkin Disease - radiotherapy ; Ovary - surgery ; Radiation Injuries - prevention & control ; Adolescent ; Infertility, Female - etiology ; Adult ; Female ; Infertility, Female - prevention & control ; Retrospective Studies ; Child ; Pregnancy Rate ; Lymphomas ; Antitank weapons
    ISSN: 0015-0282
    E-ISSN: 1556-5653
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: Journal of inherited metabolic disease, 2017-11, Vol.40 (6), p.793-799
    Description: Long-term cognitive outcome and treatment of adult early treated (ET)PKU patients is a main issue in PKU research. We questioned whether the intellectual development of ETPKU patients is stable and to what extent its variation may be predicted by the quality of metabolic control. The aims of the present longitudinal retrospective study were to assess in young adult ETPKU patients: i) the relationship between IQ and metabolic control during the first two decades of life; and ii) the intra- and interindividual variability in the developmental trajectory which cannot be predicted by the disease’s biomarkers. We collected biochemical data from 65 ETPKU patients (diagnostic blood Phe 〉 360 μmol/l) who were assessed twice for IQ (Wechsler Intelligence Scale) during their lifetime (mean age: 10.2 and 19.6 years, respectively). Results show that in ETPKU patients IQ over the second decade of life remained stable in about half of the patients (51%); while the rest experienced a gain (7 to 15 points) or loss (7 to 28 points) in IQ scores (23 and 26% respectively) whatever the quality of metabolic control was. The main factor affecting the second IQ was the value of the first IQ (p 〈 0.000) whose effect overruled that of the markers of metabolic control. Looking at the developmental trajectory of our ETPKU patients, the present study disclosed a remarkable interindividual variability in their cognitive outcome and also an inconsistent linkage between cognitive performances and biochemical control, thus supporting the hypothesis of an individual resilience or vulnerability to Phe in young adult ETPKU.
    Subject(s): Human Genetics ; Biochemistry, general ; Pediatrics ; Internal Medicine ; Medicine & Public Health ; Metabolic Diseases ; Biomarkers - metabolism ; Humans ; Male ; Intelligence Tests ; Phenylketonurias - physiopathology ; Young Adult ; Intelligence - physiology ; Adolescent ; Cognition - physiology ; Adult ; Female ; Phenylketonurias - metabolism ; Retrospective Studies ; Child ; Longitudinal Studies ; Medicine, Experimental ; Medical research ; Index Medicus
    ISSN: 0141-8955
    E-ISSN: 1573-2665
    Source: Wiley Online Library All Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Journal of clinical oncology, 2009-02-01, Vol.27 (4), p.566-571
    Description: With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after intensive sequential chemotherapy. Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m(2)), etoposide (2.4 g/m(2)), cyclophosphamide (4 g/m(2)), and carboplatin (0.8 g/m(2)) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue. Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far. HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.
    Subject(s): Neurology ; Biological and medical sciences ; Medical sciences ; Tumors of the nervous system. Phacomatoses ; Tumors ; Cyclophosphamide - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Humans ; Child, Preschool ; Male ; Medulloblastoma - mortality ; Antimetabolites, Antineoplastic - administration & dosage ; Antineoplastic Agents, Phytogenic - administration & dosage ; Neoplasm Metastasis ; Medulloblastoma - radiotherapy ; Adult ; Dose Fractionation ; Female ; Child ; Radiotherapy Dosage ; Cerebellar Neoplasms - drug therapy ; Cerebellar Neoplasms - mortality ; Carboplatin - administration & dosage ; Etoposide - administration & dosage ; Survival Rate ; Treatment Outcome ; Combined Modality Therapy ; Adolescent ; Methotrexate - administration & dosage ; Medulloblastoma - drug therapy ; Cerebellar Neoplasms - radiotherapy
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 5
    Language: English
    In: American journal of medical genetics. Part A, 2016-06, Vol.170A (6), p.1538-1544
    Description: Tuberous Sclerosis Complex (TSC) is generally characterized by the presence of benign tumors, but some patients with malignancies have been reported in the literature. We examined a large Italian TSC population (240 individuals followed from 2001 to 2015, aged 3 months–74 years), assessing the frequency of malignancies to determine whether there is an increased risk for cancer in this disorder, and looking for possible features associated with the development of neoplasia. Fifteen patients had malignancies (6.25%); median age at diagnosis was 37.5 years (range of 1.6–58). Five of seven renal tumors were renal cell carcinomas. Eight patients had a non‐renal malignancy (3.3%), but we did not find a more prevalent type of cancer. No patient developed more than one malignancy. The prevalence of all malignant tumors was compatible with the prevalence in the general population (5.6%, 95%CI 2.99−9.31%, vs. 4.4% in Italy). Median age at cancer diagnosis was lower (37.5 years, 95%CI 28.6−44.7, vs. 66.0 years). Two patients (13.3%) died of their cancer, while outcome was favorable in the remaining individuals. Malignant tumors were more frequently diagnosed in patients with mutations in TSC1 when compared to TSC2 and patients with no mutation identified (P = 0.032). Our study demonstrated that TSC patients do not seem to have an increased risk for malignancies besides renal cell carcinoma. However, when cancer develops, age at diagnosis is lower than in the general population, and malignant tumors are more frequently diagnosed in patients with mutations in TSC1. Further studies are needed to confirm these data. ©2016 Wiley Periodicals, Inc.
    Subject(s): tuberous sclerosis complex ; malignancy ; TSC ; tumor ; TSC2 ; TSC1 ; cancer ; neoplasia ; Neoplasms - etiology ; Tuberous Sclerosis - complications ; Humans ; Middle Aged ; Child, Preschool ; Infant ; Male ; Risk ; Neoplasms - diagnosis ; Young Adult ; Germ-Line Mutation ; Adult ; Female ; Retrospective Studies ; Child ; SEER Program ; Tuberous Sclerosis - epidemiology ; Neoplasms - mortality ; Tuberous Sclerosis - genetics ; Tuberous Sclerosis - therapy ; Phenotype ; Adolescent ; Age of Onset ; Aged ; Population Surveillance ; Neoplasms - epidemiology ; Tuberous sclerosis ; Cancer ; Index Medicus
    ISSN: 1552-4825
    E-ISSN: 1552-4833
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Molecular genetics and metabolism reports, 2021-06, Vol.27, p.100759-100759
    Description: COVID19 pandemic urged the need to take severe measures for reducing the epidemic spread. Lockdowns were imposed throughout countries and even Inborn errors of metabolism (IEMs) affected patients had to face it and adapt, with management strategies changes coming along. Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism causing, when not treated, blood Phe increases and consequent central nervous system (CNS) damage. Dietary intervention is the main recognized treatment and must be maintained long-life, however adherence is often suboptimal in adulthood. Aim of this study was to evaluate whether and how the pandemic had impacted PKUs metabolic control and what factors may have played a role as potential modifiers. Patients ≥4 yo and in follow-up at our Metabolic Clinic were enrolled in this study, divided into subgroups according to age (GROUP A 〈 12 yo; GROUP B ≥ 12 yo). Videoconsults were conducted on a minimum monthly basis and collected DBS were studied and compared to previous year same time-period in order to evaluate possible changes. 39% of patients (n = 121) increased the number of performed DBS. “Non-compliant” patients were reduced (11–3%) with a − 14% of patients with mean Phe levels 〉600 umol/l and a − 8% of patients with 100% DBS above same level. GROUP A maintained substantially unchanged metabolic control among two analyzed time-periods. On the contrary, GROUP B demonstrated significant reductions in mean blood Phe concentrations (p 〈 0.0001) during the pandemic (mean 454 umol/l, SD ± 252, vs. 556.4 umol/l, SD ± 301). COVID19 pandemic strongly impacted people's life with lifestyle habits changing consistently. PKU patients had to adapt their dietary restrictions to the new environment they were exposed to and, if younger patients could have been less exposed (meals strictly according to diet plan independently from setting), adolescent and adults strongly reflected the obligation to stay home by showing better metabolic control. Multiple factors could have played a role in that and the availability of teleconsultancy may have contributed allowing easier connections, but our data demonstrate how the pandemic and the environment can strongly impact PKUs adherence to treatment and how removing distance barriers can ameliorate and optimize metabolic compliance.
    Subject(s): COVID-19 ; Adherence ; Lockdown ; PKU ; Diet ; Metabolic control
    ISSN: 2214-4269
    E-ISSN: 2214-4269
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Medical oncology (Northwood, London, England), 2017-12, Vol.34 (12), p.1-8
    Description: To improve the poor prognosis for children with metastatic osteosarcoma (OS), interleukin-2 (IL-2) was added to the standard treatment due to its capacity to activate lymphocytes and differentiate lymphocyte subsets into lymphokine-activated killer (LAK) cells that are capable of recognizing and killing various tumor cells. This study concerns a cohort of unselected patients aged 〈 18 years with metastatic OS, who were treated with IL-2, high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, LAK reinfusion, and surgery, between 1995 and 2010. Thirty-five patients aged 4–17 years were involved. Thirty-two of the 35 patients underwent surgery on their primary tumor, and 25 had surgery on lung metastases too. Twenty-seven patients received IL-2 plus LAK reinfusion. The median follow-up was 130 months (77–228), and the 3-year event-free and overall survival rates were 34.3 and 45.0%, respectively. Eleven patients remained alive, all of whom achieved a complete surgical removal of the primary tumor and lung metastases (1 patient did not receive lung resections due to complete lung metastases remission). Patients who had a complete surgical remission of the primary and metastatic sites and who responded well to chemotherapy had a better event-free survival. These results confirm the importance of complete surgical remission and point to a noteworthy (though still be ameliorate) survival rate in our series of patients, underling a potential role for immunotherapy with IL-2 and LAK/NK cell activation.
    Subject(s): Lung metastases ; Pathology ; Chemotherapy ; Medicine & Public Health ; Hematology ; Osteosarcoma ; Surgery ; Oncology ; Internal Medicine ; IL-2 ; Children ; Anthracyclines ; Metastasis ; Interleukins ; Methotrexate ; Immunotherapy ; Bone cancer ; Cytokines ; Medical prognosis ; Index Medicus
    ISSN: 1357-0560
    E-ISSN: 1559-131X
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Cancers, 2020-09-01, Vol.12 (9), p.1
    Description: INTRODUCTIONDue to the rarity of nongerminomatous germ cell tumors (NGGCT) with non-standard treatment as yet, we report retrospectively our 30 year experience with chemotherapy followed by craniospinal irradiation (CSI), plus a boost of whole ventricular irradiation (WVI)/tumor bed (TB), tailored to pre-radiation chemotherapy response. METHODSBetween 1988 and 2016, 28 patients received four cycles of PEB (cisplatin/etoposide/bleomycin), then CSI, and two further PEB cycles. Between 1988 and1994, CSI was 25.5 Gy for patients in complete remission (CR), 30 Gy if in partial remission (PR) or metastatic, with a boost to TB up to 45-54 Gy. In the period of 1995-2010, the boost included WVI and any extra-ventricular tumor sites up to 45 Gy. After 2010, CSI was reduced to 25.5 Gy for all non-metastatic patients, and a boost was given only to TB up to 40.5/45.5 Gy, depending on patients' CR/PR status. After 2003, patients with alfafetoprotein (αFP) 〉 1000 ng/mL received intensified treatment, also including autologous stem cell transplantation. RESULTSAmong 28 patients (23 males; median age 12 years, 6 metastatic), 25 responded to PEB, and three progressed (PD) after one to four cycles; 26 received radiotherapy obtaining 13 CR, 7 PR and 5 stable disease (SD), 1 PD; 6 (21%) died (5 for disease, 1 for pneumonia while in CR). Five-year overall survival (OS) and progression-free survival (PFS) were both 81%; 10 year OS and PFS 81% and 76%, respectively (median follow-up 11 years). CONCLUSIONSSurvival for children with NGGCT, independently from disease extent, was encouraging. Further studies should elucidate which patients could benefit from reduced volume and dose irradiation.
    Subject(s): Medical research ; Prognosis ; Central nervous system ; Radiation ; Transplantation ; Metastasis ; Radiotherapy ; Chemotherapy ; Tuberculosis ; Germ cell tumors ; Stem cells ; Medicine, Experimental ; Cancer ; craniospinal irradiation ; radiotherapy ; NGGCT ; CNS germ cell tumors ; chemotherapy ; late effects
    ISSN: 2072-6694
    E-ISSN: 2072-6694
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Journal of clinical oncology, 2010-03-10, Vol.28 (8), p.1322-1328
    Description: In this study on a series of 205 patients with rhabdomyosarcoma, we investigated whether the prognostic effect of tumor size, at diagnosis or in terms of tumor response after induction chemotherapy, differed when tumor diameter or tumor volume were considered. Tumor size was assessed radiologically at diagnosis and, for the 108 patients with measurable disease, after three courses of chemotherapy. The analysis was based on multivariable models (linear for association between size and patient/tumor characteristics, Cox for association with survival). The predictive performance of the Cox model (estimated by V measure) was compared for the tumor's diameter and volume. Initial tumor size was significantly larger in male or older patients and in T2 or alveolar tumors, but was not associated with the achievement of complete surgical resection. Initial tumor size significantly influenced overall survival. The risk of death was comparable for tumors 10 cm in maximum diameter and 194.0 cm(3) in volume. The predictive performance of the Cox model was much the same when the tumor's diameter or volume was considered. Tumor response was a significant predictor of survival, again irrespective of the type of tumor measurement considered. In our analysis, initial tumor size and tumor response were significant prognostic factors in rhabdomyosarcoma, regardless of whether tumor diameter or volume was considered. Three-dimensional tumor assessment was of no greater prognostic value than one-dimensional assessment, neither initially nor after induction treatment.
    Subject(s): Biological and medical sciences ; Medical sciences ; Diseases of the osteoarticular system ; Tumors of striated muscle and skeleton ; Tumors ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Humans ; Decision Support Techniques ; Proportional Hazards Models ; Child, Preschool ; Magnetic Resonance Imaging - methods ; Rhabdomyosarcoma - pathology ; Tomography, X-Ray Computed - methods ; Male ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Adolescent ; Survival Analysis ; Female ; Italy ; Rhabdomyosarcoma - drug therapy ; Imaging, Three-Dimensional ; Child ; Index Medicus
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Frontiers in medicine, 2021, Vol.8, p.652358-652358
    Description: Inherited Metabolic Diseases (IMDs) are rare diseases caused by genetic defects in biochemical pathways. Earlier diagnosis and advances in treatment have improved the life expectancy of IMD patients over the last decades, with the majority of patients now surviving beyond the age of 20. This has created a new challenge: as they grow up, the care of IMD patients' needs to be transferred from metabolic pediatricians to metabolic physicians specialized in treating adults, through a process called "transition." The purpose of this study was to assess how this transition is managed in Europe: a survey was sent to all 77 centers of the European Reference Network for Hereditary Metabolic Disorders (MetabERN) to collect information and to identify unmet needs regarding the transition process. Data was collected from 63/77 (81%) healthcare providers (HCPs) from 20 EU countries. Responders were mostly metabolic pediatricians; of these, only ~40% have received appropriate training in health issues of adolescent metabolic patients. In most centers (~67%) there is no designated transition coordinator. About 50% of centers provide a written individualized transition protocol, which is standardized in just ~20% of cases. In 77% of centers, pediatricians share a medical summary, transition letter and emergency plan with the adult team and the patient. According to our responders, 11% of patients remain under pediatric care throughout their life. The main challenges identified by HCPs in managing transition are lack of time and shortage of adult metabolic physician positions, while the implementations that are most required for a successful transition include: medical staff dedicated to transition, a transition coordinator, and specific metabolic training for adult physicians. Our study shows that the transition process of IMD patients in Europe is far from standardized and in most cases is inadequate or non-existent. A transition coordinator to facilitate collaboration between the pediatric and adult healthcare teams should be central to any transition program. Standardized operating procedures, together with adequate financial resources and specific training for adult physicians focused on IMDs are the key aspects that must be improved in the rare metabolic field to establish successful transition processes in Europe.
    Subject(s): challenge ; rare disease ; inherited metabolic disease(s) ; adulthood (18 years and older) ; continuity of care ; transition process
    ISSN: 2296-858X
    E-ISSN: 2296-858X
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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