Clinical and event-based outcomes of patients with mucopolysaccharidosis VI receiving enzyme replacement therapy in Turkey: a case series

Abstract Background The objective of this study was to describe clinical manifestations and events of patients with mucopolysaccharidosis (MPS) VI in Turkey who are treated with galsulfase enzyme replacement therapy (ERT). Clinical data of 14 children with MPS VI who were followed up at the Department of Pediatrics of the Gazi University Faculty of Medicine in Ankara, Turkey were retrospectively collected from the patients’ medical records. Patients were selected based on availability of a pre-ERT baseline and follow-up clinical data for a similar period of time (1.9–3.2 years). Event data (occurrence of acute clinical events, onset of chronic events, surgeries) collected during hospital visits and telemedicine were available for up to 10 years after initiation of ERT (2.5–10 years). Results Age at initiation of ERT ranged from 2.8 to 15.8 years (mean age 7.5 years). All patients presented with reduced endurance and skeletal abnormalities (dysostosis multiplex) on radiography. Other common clinical manifestations were cardiac valve disease (N = 13), short stature (N = 11), cranial abnormalities on MRI (N = 10), spinal abnormalities on MRI (N = 7), and mild cognitive impairment (N = 6). School attendance was generally poor, and several patients had urinary incontinence. After 1.9 to 3.2 years of ERT, most patients showed improvements in endurance in the 6-min walk test and 3-min stair climb tests; the frequency of urinary incontinence decreased. ERT did not seem to prevent progression of cardiac valve disease, eye disorders, hearing loss, or bone disease. Long-term event-based data showed a high incidence of respiratory tract infections, adenotonsillectomy/adenoidectomy, reduced sleep quality, sleep apnea, and depression before initiation of ERT. The number of events tended to remain stable or decrease in all patients over 2.5–10 years follow-up. However, the nature of the events shifted over time, with a reduction in the frequency of respiratory tract infections and sleep problems and an increase in ophthalmologic events, ear tube insertions, and depression. Conclusions This case series shows the high disease burden of the MPS VI population in Turkey and provides a unique insight into their clinical journey based on real-life clinical and event-based data collected before and after initiation of ERT.

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Prognosis and treatment of 46 Chinese pediatric cystic fibrosis patients

BMC Pediatrics ◽

10.1186/s12887-021-02789-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qionghua Chen ◽

Yuelin Shen ◽

Hui Xu ◽

Xiaolei Tang ◽

Haiming Yang ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Respiratory Tract Infections ◽

Adverse Reactions ◽

Clinical Presentation ◽

Public Awareness ◽

Sputum Production ◽

Tract Infections ◽

Lost To Follow Up

Abstract Background Since public awareness of cystic fibrosis (CF) has increased, more children have been diagnosed with CF in China. This study aimed to investigate medical and other challenges faced by pediatric CF patients in China. Method Treatments and treatment outcomes were retrospectively analyzed for 46 pediatric CF patients diagnosed from August 2009 to June 2019. Pre- and post-treatment results were compared using independent samples t-test. Results Of 46 pediatric CF study patients, four died and five were lost to follow-up. Thirty-seven patients were monitored for 0.03 to 9.21 years; patients exhibited fewer attacks of respiratory tract infections after diagnosis (4.49 ± 2.13 episodes/year before diagnosis vs 1.97 ± 1.87 times/year after 1-year treatment, p < 0.05), significantly reduced sputum production and experienced 1.62 ± 1.71 exacerbations/year. Patient mean body mass index was 16.87 ± 3.53 and pancreatic malfunction persisted in 15 patients. For 17 children, no significant differences in lung function were found at follow-up as compared to lung function at diagnosis (FEV1: 82.45% ± 16.56% vs 75.26% ± 22.34%, FVC: 87.18% ± 13.64% vs 86.99% ± 19.95%, FEF75%: 46.51% ± 28.78% vs 36.63% ± 24.30%, P = 0.27, 0.97, 0.20, respectively). Pseudomonas aeruginosa (17/27) and bronchiectasis (22/22) were found during follow-up evaluation. Twenty-four patients (64.8%) maintained good adherence to therapies. Overall, azithromycin and tobramycin treatments were administered for 0.5–62 months and 0.5–48 months, respectively, and triggered no obvious adverse reactions. Conclusion No obvious declines in clinical presentation or lung function were found in Chinese pediatric CF patients after receiving standard therapeutic and active treatments, although malnutrition and low compliance were persistent challenges.

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Morquio A syndrome and effect of enzyme replacement therapy in different age groups of Turkish patients: a case series

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01761-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Sebile Kılavuz ◽

Sibel Basaran ◽

Deniz Kor ◽

Fatma Derya Bulut ◽

Sevcan Erdem ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Clinical Data ◽

Treatment Initiation ◽

Case Series ◽

Enzyme Replacement ◽

Morquio A ◽

Over Time ◽

Morquio A Syndrome

Abstract Background This case series includes longitudinal clinical data of ten patients with Morquio A syndrome from south and southeastern parts of Turkey, which were retrospectively collected from medical records. All patients received enzyme replacement therapy (ERT). Clinical data collected included physical appearance, anthropometric data, neurological and psychological examinations, cardiovascular evaluation, pulmonary function tests, eye and ear-nose-throat examinations, endurance in the 6-min walk test and/or 3-min stair climb test, joint range of motion, and skeletal investigations (X-rays, bone mineral density). Results At the time of ERT initiation, two patients were infants (1.8 and 2.1 years), five were children (3.4–7.1 years), and three were adults (16.5–39.5 years). Patients had up to 4 years follow-up. Most patients had classical Morquio A, based on genotypic and phenotypic data. Endurance was considerably reduced in all patients, but remained relatively stable or increased over time in most cases after treatment initiation. Length/height fell below normal growth curves, except in the two infants who started ERT at ≤ 2.1 years of age. All patients had skeletal and/or joint abnormalities when ERT was started. Follow-up data did not suggest improvements in skeletal abnormalities, except in one of the younger infants. Nine patients had corneal clouding, which resolved after treatment initiation in the two infants, but not in the other patients. Hepatomegaly was reported in seven patients and resolved with treatment in five of them. Other frequent findings at treatment initiation were coarse facial features (N = 9), hearing loss (N = 6), and cardiac abnormalities (N = 6). Cardiac disease deteriorated over time in three patients, but did not progress in the others. Conclusions Overall, this case series with Morquio A patients confirms clinical trial data showing long-term stabilization of endurance after treatment initiation across ages and suggest that very early initiation of ERT optimizes growth outcomes.

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A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01645-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Atul Mehta ◽

Uma Ramaswami ◽

Joseph Muenzer ◽

Roberto Giugliani ◽

Kurt Ullrich ◽

...

Keyword(s):

Replacement Therapy ◽

Clinical Manifestations ◽

Lysosomal Storage Disorders ◽

Expert Committee ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Mps Ii ◽

Access Program ◽

Storage Disorders

Abstract Background Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifestations and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs. Methods The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of benefit, in selected countries, through donation of ERT to nonprofit organizations, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company. Results As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year. Conclusions The response rate for follow-up data at 1 year was high, with data collected for > 90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These findings suggest that the program can benefit selected patients previously unable to access disease-specific treatments. Further innovative solutions and efforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world.

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Effects of procalcitonin testing on antibiotic use and clinical outcomes in patients with upper respiratory tract infections. An individual patient data meta-analysis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0252 ◽

2017 ◽

Vol 56 (1) ◽

Cited By ~ 7

Author(s):

Jonas Odermatt ◽

Natalie Friedli ◽

Alexander Kutz ◽

Matthias Briel ◽

Heiner C. Bucher ◽

...

Keyword(s):

Respiratory Tract ◽

Antibiotic Therapy ◽

Respiratory Tract Infections ◽

Meta Analysis ◽

Antibiotic Exposure ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Restricted Activity ◽

Tract Infections

AbstractBackground:Several trials found procalcitonin (PCT) helpful for guiding antibiotic treatment in patients with lower respiratory tract infections and sepsis. We aimed to perform an individual patient data meta-analysis on the effects of PCT guided antibiotic therapy in upper respiratory tract infections (URTI).Methods:A comprehensive search of the literature was conducted using PubMed (MEDLINE) and Cochrane Library to identify relevant studies published until September 2016. We reanalysed individual data of adult URTI patients with a clinical diagnosis of URTI. Data of two trials were used based on PRISMA-IPD guidelines. Safety outcomes were (1) treatment failure defined as death, hospitalization, ARI-specific complications, recurrent or worsening infection at 28 days follow-up; and (2) restricted activity within a 14-day follow-up. Secondary endpoints were initiation of antibiotic therapy, and total days of antibiotic exposure.Results:In total, 644 patients with a follow up of 28 days had a final diagnosis of URTI and were thus included in this analysis. There was no difference in treatment failure (33.1% vs. 34.0%, OR 1.0, 95% CI 0.7–1.4; p=0.896) and days with restricted activity between groups (8.0 vs. 8.0 days, regression coefficient 0.2 (95% CI –0.4 to 0.9), p=0.465). However, PCT guided antibiotic therapy resulted in lower antibiotic prescription (17.8% vs. 51.0%, OR 0.2, 95% CI 0.1–0.3; p<0.001) and in a 2.4 day (95% CI –2.9 to –1.9; p<0.001) shorter antibiotic exposure compared to control patients.Conclusions:PCT guided antibiotic therapy in the primary care setting was associated with reduced antibiotic exposure in URTI patients without compromising outcomes.

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MO061IS THE PM290I MUTATION RELATED TO ORGAN INVOLVEMENT OF FABRY DISEASE?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab080.0033 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Francisca Silva ◽

Nicole Pestana ◽

José Durães ◽

Nuno Guimarães Rosa ◽

Gil Silva

Keyword(s):

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Genetic Variant ◽

Clinical Manifestations ◽

Mutant Enzyme ◽

Enzyme Replacement ◽

Screening Study ◽

Gla Gene

Abstract Background and Aims Fabry disease (FD) is an X-linked hereditary disease. It results from mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A and progressive accumulation of undegraded glycosphingolipids in cell lysosomes. Enzyme replacement therapy improved the natural course of this disease, but an early diagnosis is crucial for a successful treatment. Method A screening study for GLA gene mutations was conducted for all patients under dialysis, from a single centre. All the probands with a detectable mutation were analysed individually. Data on the patient's family and personal pathological history were retrospectively collected, by consulting the clinical file. Results 35 years-old female diagnosed with chronic proteinuric kidney disease in the postpartum period. Despite optimal medical treatment the disease progressed, and she started renal replacement therapy with peritoneal dialysis. Five years later she was enrolled in a pilot screening study for FD and the heterozygous mutation c.870G>C (p.Met290Ile; M290I) in exon 6 of the GLA gene was found. The proband didn’t meet the criteria for a definitive FD diagnosis, but she remained under follow-up at our nephrology metabolic diseases consultation, as the mutation was described as pathogenic and associated with a classic FD phenotype. Later that same year, reassessment exams revealed a worsening left ventricle mass index, a new ischemic cerebral lesion and a substantial increase in serum globotriaosylsphingosine (LysoGb3) levels. These clinical changes led to the decision to initiate enzyme replacement therapy. Until now there are only a few descriptions of this genetic variant in the scientific literature. A Portuguese study analysed a total of 11 FD patients and described 2 patients with p.M290I mutation, without detectable Gb3 accumulation. Another study was designed to evaluate the genotype-phenotype relationship in 73 Chinese FD patients. Contrary to other reports, the p.M290I mutation was not associated to the classic FD phenotype. A Swiss investigation with a similar design analysed 69 FD patients during their routine annual examinations. M290I mutant enzyme was found in a 48-year-old heterozygous female with a classic FD phenotype but with a low serum LysoGb3. A Spanish newborn screening identified one male patient with FD and the p.M290I genetic variant but was unable to provide any information about the clinical expression of this mutation, since the diagnosis was made between the third and fifth days of life. The study describing the most patients carrying the M290I mutant enzyme is Brazilian and screened a total of 25,223 dialysis patients. Among 89 FD-positive patients, the p.M290I mutation was present in 22. However, the authors did not provide detailed information about the clinical manifestations or α-Gal A activity and LysoGb3 levels of these patients. Finally, a recent Portuguese screening of 150 hypertrophic cardiomyopathy patients found 25 patients with FD. Of these, one female carried the GLA gene variant p.M290I, with a non-detectable LysoGb3 plasma level. Conclusion We describe a case of FD due to a previously known but still poorly described GLA mutation, which offers strong evidence of its pathogenicity. To our knowledge, this is the first report of p.M290I mutation-associated disease activity evidenced by elevated levels of serum LysoGb3. Despite the absence of classic FD symptoms such as neuropathic pain, cornea verticillata and angiokeratoma, the presence of severe multiple organ evolvement, characterized by renal failure, cardiac disease and ischaemic stroke, strongly suggests a classic phenotype. Consequently, it is our opinion that the presence of a p.M290I GLA mutation should require a strict ongoing patient follow-up, as it may cause clinically significant disease.

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Perioperative Respiratory Adverse Events in General Anesthesia Among Pediatric Surgical Patients in Comprehensive Specialized Hospitals in Northwest Ethiopia, 2020; A Cross-Sectional Follow-Up

10.21203/rs.3.rs-138101/v1 ◽

2021 ◽

Author(s):

Yophtahe Woldegerima ◽

Desalegn Muche ◽

Wubie Birlie ◽

Habtu Adane ◽

Misganaw Mengie

Keyword(s):

Adverse Events ◽

Respiratory Tract Infections ◽

Northwest Ethiopia ◽

Surgical Patients ◽

Upper Respiratory Tract Infections ◽

Upper Respiratory Tract ◽

Cross Sectional ◽

Upper Respiratory ◽

Tract Infections

Abstract Introduction: Perioperative respiratory adverse events (PRAEs) are the most frequent complications in pediatrics which frequently result in morbidity and mortality. They are accountable for 75% of perioperative critical incidents and 33% of cardiac arrests. The occurrence and severity of PRAEs depends on the natures of surgery, anesthesia & patient’s status.Objective: To assess the incidence and factors associated with PRAEs in general anesthesia among pediatric surgical patients at the University of Gondar and Tibebe-Ghion Comprehensive Hospital and Specialized Hospitals, Northwest Ethiopia, 2020.Methods: After obtaining the ethical approval, a hospital-based prospective cross-sectional follow-up study was conducted among pediatric surgical patients who underwent variety of surgical operations. A total of 225 patients were included. The associations between independent variables and the outcome variables were determined at 95% CI with the Chi-squared test, Fisher–exact test, bivariate, and multivariate logistic regression. Hosmer-Lemeshow test was used to assess the goodness of fit. Variables with a p-value < 0.05 were considered significant.Results: The incidence of PRAEs among 210 (93.3% response rate) pediatrics surgical patients was 26.2% (95% CI: 20.5, 30.9). A total of 129 episodes of PRAEs were observed. Most of the adverse events (89 (69.0%)) were occurred postoperatively. Desaturation was found to be the predominant adverse event which was occurred 61 (47.3%) times. Age < 1 year (AOR: 3.6, 95% CI: 1.3, 10.0), ASA ≥ 3 (AOR: 5.2, 95% CI: 1.9, 22.9), upper respiratory tract infections (AOR: 7.6, 95% CI: 1.9, 30.2), presence of secretions in the upper airway (AOR: 4.8, 95% CI: 1.4, 15.9) and airway related procedures (AOR: 6.0, 95% CI: 1.5, 24.1) were significantly associated PRAEs.Conclusions: The incidence of PRAEs among pediatric surgical patients was relatively high (26.2%). Especially, the postoperative phase is the most critical time for the occurrence of PRAEs and desaturation was the predominant adverse event. Age less than a year, presence of upper respiratory tract infections, presence of secretions in the upper airways, ASA ≥ 3 and airway related procedures were associated with PRAEs. Clinicians should carry out effective risk assessment, optimization and adequate preparation for the management of perioperative respiratory adverse events.

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Influence of Renin-Angiotensin System Inhibitors on Lower Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II

10.2337/figshare.12398024 ◽

2020 ◽

Author(s):

Timothy M E Davis ◽

Wendy A Davis

Keyword(s):

Type 2 Diabetes ◽

Respiratory Tract ◽

Phase Ii ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Study Phase ◽

Lower Respiratory Tract Infections ◽

Tract Infections

Objective: To determine whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) protect against lower respiratory tract infections complicating type 2 diabetes. Research design and methods: Of 1,732 participants with diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II (FDS2) between 2008 and 2011, 1,482 had confirmed type 2 diabetes (mean age of 65.8 years, 51.6% were males, median diabetes duration 9.0 years). All were followed for hospitalizations for/with, or deaths from, pneumonia/influenza ascertained from validated administrative data linkage from study entry to end-2016. Cox and competing risk regression were used to identify independent predictors of this outcome. Results: Two-thirds of participants (n=982) were taking an ACEi and/or ARB at study entry (498 (33.6%) ACEi, 408 (27.5%) ARB, 76 (5.1%) both). During 9,511 person-years of follow-up (mean 6.4±2.0 years), 174 participants had incident pneumonia/influenza (156 hospitalizations, 18 deaths without hospitalization). In Cox regression analysis, baseline ACEi/ARB use was independently associated with a reduced risk of incident pneumonia/influenza (cause-specific hazard ratio (HR) (95% confidence interval) 0.64 (0.45, 0.89), P=0.008). Allowing for the competing risk of death did not change this finding (subdistribution HR 0.67 (0.48, 0.95), P=0.024), and similar reductions were seen for ACEi, ARB alone, and ACEi/ARB combination therapy. There was no significant change in use of ACEi/ARB during follow-up (interaction with ln(time), P=0.70). Other significant predictors of incident pneumonia/influenza were previously reported, clinically plausible variables. Conclusions: ACEi/ARB reduce the risk of pneumonia/influenza in community-based people with type 2 diabetes.

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Influence of Renin-Angiotensin System Inhibitors on Lower Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II

10.2337/figshare.12398024.v1 ◽

2020 ◽

Author(s):

Timothy M E Davis ◽

Wendy A Davis

Keyword(s):

Type 2 Diabetes ◽

Respiratory Tract ◽

Phase Ii ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Study Phase ◽

Lower Respiratory Tract Infections ◽

Tract Infections

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Therapeutic evaluation of sclerotherapy for limb venous malformations: A case series

Phlebology The Journal of Venous Disease ◽

10.1177/0268355520926789 ◽

2020 ◽

Vol 35 (9) ◽

pp. 663-671

Author(s):

Tenghui Zhan ◽

Fanggang Cai ◽

Pingfan Guo ◽

Yujie Lian ◽

Hui Zhuang ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Doppler Ultrasound ◽

Clinical Examination ◽

Clinical Manifestations ◽

Case Series ◽

Venous Malformations ◽

Resonance Imaging ◽

Percutaneous Sclerotherapy

Objectives To examine three different methods for evaluating the effect of percutaneous sclerotherapy on limb venous malformations in a series of patients with a relatively long follow-up. Method The study was a retrospective study. Results Thirty-eight patients treated with percutaneous sclerotherapy underwent sclerotherapy, with a median number of sessions of 4 (range, 1–10). They were followed up for 1–60 months (average 12.5 months). The kappa between clinical manifestations and Doppler ultrasound was 0.684 ( P < 0.001). The kappa between clinical manifestations and magnetic resonance imaging was 0.217 ( P = 0.006). The kappa between Doppler ultrasound and magnetic resonance imaging was 0.323 ( P < 0.001). The rate of grade IV patients evaluated by clinical manifestations was significantly higher than that by Doppler ultrasound and magnetic resonance imaging. Conclusions Magnetic resonance imaging is the gold standard for VM imaging. Its consistency with clinical examination and Doppler ultrasound is poor, and Doppler ultrasound and clinical examination could be more appropriate for follow-up imaging after sclerotherapy.

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