Lancet Infect Dis. 2021 May;21(5):597-598. doi: 10.1016/S1473-3099(21)00194-8.

NO ABSTRACT

PMID:33894839 | DOI:10.1016/S1473-3099(21)00194-8

Biochem Biophys Res Commun. 2021 Apr 21;557:254-260. doi: 10.1016/j.bbrc.2021.04.045. Online ahead of print.

ABSTRACT

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5). Our results showed that VAs, not an intravenous anesthetic, significantly attenuated the activation of TLR5 and the release of the neutrophil chemoattractant IL-8 from lung epithelial cells. Furthermore, flagellin-induced lung injury was significantly attenuated by VAs by inhibiting neutrophil migration to the bronchoalveolar space. The lungs of cystic fibrosis (CF) patients are highly colonized by Pseudomonas aeruginosa, which causes inflammation. The retrospective study of oxygenation in patients with CF who had received VA versus intravenous anesthesia suggested that VAs might have the protective effect for gas exchange. To understand the interaction between VAs and TLR5, a docking simulation was performed, which indicated that isoflurane and sevoflurane docked into the binding interphase between TLR5 and flagellin.

PMID:33894411 | DOI:10.1016/j.bbrc.2021.04.045

Cerebellum. 2021 Apr 24. doi: 10.1007/s12311-021-01257-4. Online ahead of print.

ABSTRACT

Ataxia telangiectasia (A-T) is a progressive and life-limiting disease associated with cerebellar ataxia due to progressive cerebellar degeneration. In addition to ataxia, which is described in detail, the presence of chorea, dystonia, oculomotor apraxia, athetosis, parkinsonism, and myoclonia are typical manifestations of the disease. The study aimed to evaluate the specificity and sensitivity of neurofilament light chain (NfL) as a biomarker of neurodegeneration in relation to SARA score. In this prospective trial, one visit of 42 A-T patients aged 1.3-25.6 years (mean 11.6 ± 7.3 years) was performed, in which NfL was determined from serum by ELISA. Additionally, a neurological examination of the patients was performed. Blood was collected from 19 healthy volunteers ≥ 12 years of age. We found significantly increased levels of NfL in patients with A-T compared to healthy controls (21.5 ± 3.6 pg/mL vs. 9.3 ± 0.49 pg/mL, p ≤ 0.01). There was a significant correlation of NfL with age, AFP, and SARA. NfL is a new potential progression biomarker in blood for neurodegeneration in A-T which increases with age.

PMID:33893614 | DOI:10.1007/s12311-021-01257-4

Br J Anaesth. 2021 Apr 20:S0007-0912(21)00172-0. doi: 10.1016/j.bja.2021.03.010. Online ahead of print.

ABSTRACT

BACKGROUND: Bilateral lung transplantation results in pulmonary vagal denervation, which potentially alters respiratory drive, volume-feedback, and ventilatory pattern. We hypothesised that Neurally Adjusted Ventilatory Assist (NAVA) ventilation, which is driven by diaphragm electrical activity (EAdi), would reveal whether vagally mediated pulmonary-volume feedback is preserved in the early phases after bilateral lung transplantation.

METHODS: We prospectively studied bilateral lung transplant recipients within 48 h of surgery. Subjects were ventilated with NAVA and randomised to receive 3 ventilatory modes (baseline NAVA, 50%, and 150% of baseline NAVA values) and 2 PEEP levels (6 and 12 cm H2O). We recorded airway pressure, flow, and EAdi.

RESULTS: We studied 30 subjects (37% female; age: 37 (27-56) yr), of whom 19 (63%) had stable EAdi. The baseline NAVA level was 0.6 (0.2-1.0) cm H2O μV-1. Tripling NAVA level increased the ventilatory peak pressure over PEEP by 6.3 (1.8), 7.6 (2.4), and 8.7 (3.2) cm H2O, at 50%, 100%, and 150% of baseline NAVA level, respectively (P<0.001). EAdi peak decreased by 10.1 (9.0), 9.5 (9.4) and 8.8 μV (8.7) (P<0.001), accompanied by small increases in tidal volume, 8.3 (3.0), 8.7 (3.6), and 8.9 (3.3) ml kg-1 donor's predicted body weight at 50%, 100%, and 150% of baseline NAVA levels, respectively (P<0.001). Doubling PEEP did not affect tidal volume.

CONCLUSIONS: NAVA ventilation was feasible in the majority of patients during the early postoperative period after bilateral lung transplantation. Despite surgical vagotomy distal to the bronchial anastomoses, bilateral lung transplant recipients maintained an unmodified respiratory pattern in response to variations in ventilatory assistance and PEEP.

CLINICAL TRIAL REGISTRATION: NCT03367221.

PMID:33892948 | DOI:10.1016/j.bja.2021.03.010

J Allergy Clin Immunol Pract. 2021 Apr 20:S2213-2198(21)00451-7. doi: 10.1016/j.jaip.2021.04.011. Online ahead of print.

NO ABSTRACT

PMID:33892172 | DOI:10.1016/j.jaip.2021.04.011

J Paediatr Child Health. 2021 Apr 23. doi: 10.1111/jpc.15517. Online ahead of print.

NO ABSTRACT

PMID:33890359 | DOI:10.1111/jpc.15517

Clin Chem Lab Med. 2021 Apr 22. doi: 10.1515/cclm-2020-1849. Online ahead of print.

ABSTRACT

OJECTIVES: Since health care budgets are limited and must be allocated efficiently, there is an economic pressure to reduce the costs of health care interventions. This study aims to investigate the cost of testing within a Clinical Chemistry laboratory.

METHODS: This study was conducted in the Clinical Chemistry laboratory of the University Hospital UZ Brussel, Belgium, in which 156 tests were included and an average cost per test was calculated for the year 2018. Activity-based costing (ABC) was applied, using a top-down perspective. Costs were first allocated to different activity centers and subsequently to different tests. Number of tests, parameters, analyzers and time estimates were used as activity cost drivers.

RESULTS: The blood glucose test on the point-of-care testing (POCT) analyzer Accu Chek Inform II had the lowest unit cost (€0.92). The determination of methanol, ethanol and isopropanol on the GC-FID (7820A) is the test with the highest unit cost (€129.42). In terms of average cost per test per activity center, core laboratory (€3.37) scored lowest, followed consecutively by POCT (€3.49), diabetes (€22.09), toxicology (€31.52), metabolic disorder (€41.53) and cystic fibrosis (€86.02). The cost per test was mainly determined by staff (57%), costs of support services (23%) and reagents (14%).

CONCLUSIONS: High-volume and automated tests have lower unit costs, as is the case with the core laboratory. ABC provides the ability to identify high average cost tests that can benefit from optimizations, such as focusing on automation or outsourcing low-volume tests that can benefit from economies of scale.

PMID:33887812 | DOI:10.1515/cclm-2020-1849

J Pediatr. 2021 Apr 19:S0022-3476(21)00344-9. doi: 10.1016/j.jpeds.2021.04.018. Online ahead of print.

NO ABSTRACT

PMID:33887330 | DOI:10.1016/j.jpeds.2021.04.018

PLoS One. 2021 Apr 22;16(4):e0249580. doi: 10.1371/journal.pone.0249580. eCollection 2021.

ABSTRACT

Measuring airways in chest computed tomography (CT) scans is important for characterizing diseases such as cystic fibrosis, yet very time-consuming to perform manually. Machine learning algorithms offer an alternative, but need large sets of annotated scans for good performance. We investigate whether crowdsourcing can be used to gather airway annotations. We generate image slices at known locations of airways in 24 subjects and request the crowd workers to outline the airway lumen and airway wall. After combining multiple crowd workers, we compare the measurements to those made by the experts in the original scans. Similar to our preliminary study, a large portion of the annotations were excluded, possibly due to workers misunderstanding the instructions. After excluding such annotations, moderate to strong correlations with the expert can be observed, although these correlations are slightly lower than inter-expert correlations. Furthermore, the results across subjects in this study are quite variable. Although the crowd has potential in annotating airways, further development is needed for it to be robust enough for gathering annotations in practice. For reproducibility, data and code are available online: http://github.com/adriapr/crowdairway.git.

PMID:33886587 | DOI:10.1371/journal.pone.0249580

J Palliat Med. 2021 Apr 20. doi: 10.1089/jpm.2020.0725. Online ahead of print.

ABSTRACT

Background: Individuals with cystic fibrosis (CF) experience symptoms affecting quality of life and may benefit from palliative care (PC). Objectives: To present results of content analysis from open-ended survey questions assessing knowledge and experiences with PC among CF stakeholders. Design, Setting, Subjects: Online surveys were sent to CF stakeholders through CF-specific listservs predominantly in the United States. Measurements: Responses to five open-ended questions about CF PC-delivery, health care provider training, and lung transplant-underwent content analysis. Responses were coded using NVivo12 Software™. Results: Forty-eight CF adults, 59 caregivers, and 229 providers responded to the open-ended survey questions. Analysis showed 5 primary categories related to CF PC: (1) stakeholder perceptions of PC for CF, (2) delivering PC to people with CF, (3) conversations about PC for CF, (4) perceptions that PC services are underutilized for people with CF, and (5) beliefs that PC services are critical for people with CF considering or pursuing lung transplant. Analysis showed variation among and within groups in defining PC for CF, when, and how to deliver it. Many respondents felt PC was underutilized in CF. Most saw PC as particularly important when considering lung transplant, managing anxiety around transplant, and for goals of care discussions. Some believed PC and lung transplant were mutually exclusive. Conclusion: Respondents felt PC is underutilized for CF, and that people with CF may miss out on the benefits of PC. Among stakeholders, respondents felt people with CF would benefit from access to primary and secondary PC services.

PMID:33885355 | DOI:10.1089/jpm.2020.0725

J Cyst Fibros. 2021 Apr 18:S1569-1993(21)00097-7. doi: 10.1016/j.jcf.2021.03.015. Online ahead of print.

ABSTRACT

OBJECTIVE: We evaluated the prevalence, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene profile, clinical data, management and outcome for infants with a CFTR-related metabolic syndrome/CF Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) designation from six Italian centres.

METHODS: All newborn bloodspot screening (NBS) positive infants born from January 2011 to August 2018 with a CF diagnosis or a CRMS/CFSPID designation were enrolled. Data on sweat testing, genetics, clinical course and management were collected.

RESULTS: We enrolled 257 CF patientsand 336 infants with a CRMS/CFSPID designation (CF: CRMS/CFSPID ratio of 1:1.30).Blood immuno-reactive trypsinogen (IRT) was significantly lower in CRMS/CFSPID infants and the F508del variant accounted for only 20% of alleles. Children with CRMS/CFSPID showed a milder clinical course, pancreatic sufficiency compared to CF infants. Varied practice across centres was identified regarding sweat testing, chest radiograph (8-100%) and salt supplementation (11-90%). Eighteen (5.3%) CRMS/CFSPID infants converted or were reclassified to diagnosis of CF. Four infants (1.3%) developed a clinical feature consistent with a CFTR-related disorder (1.2%). Twenty-seven were re-classified as healthy carriers (8.0%) and 16 as healthy infants (4.8%).

CONCLUSIONS: We have identified considerable variability in the evaluation and management of infants with an inconclusive diagnosis following NBS across six Italian centres. CRMS/CFSPID is more regularly seen in this population compared to countries with higher prevalence of F508del.Conversion to a CF diagnosis was recorded in 18 (5.3%) of CRMS/CFSPID infants and in 16 was as a result of increasing sweat chloride concentration.

PMID:33883100 | DOI:10.1016/j.jcf.2021.03.015

J Cyst Fibros. 2021 Apr 18:S1569-1993(21)00105-3. doi: 10.1016/j.jcf.2021.03.023. Online ahead of print.

NO ABSTRACT

PMID:33883099 | DOI:10.1016/j.jcf.2021.03.023

J Cyst Fibros. 2021 Apr 8:S1569-1993(21)00106-5. doi: 10.1016/j.jcf.2021.03.024. Online ahead of print.

ABSTRACT

The effects of the concomitant infection by COVID-19 and Burkholderia cepacia (Bc) in CF are not known. We describe the case of a 34 years woman with CF, colonized by Bc and found SARS-CoV2 positive. In the first hospital week she suffered acute respiratory failure and chest imaging showed interstitial involvement and multiple thickenings. She was treated with antibiotics, dexamethasone, remdesivir and heparin, with gradual improvement and discharge at day 20th. The reciprocal role of SARS-CoV-2 and Bc, their potential interactions and the contribution of the individual therapies to the favourable outcome are unclear. It is debatable whether it was SARS-CoV2 that triggered a Bc pulmonary exacerbation or if the chronic Bc infection facilitated the development of a COVID-19 more aggressive than usually seen in CF. If the latter hypothesis were confirmed by similar cases, Bc colonization should be regarded as a risk factor for severe COVID-19 expression in CF.

PMID:33883098 | DOI:10.1016/j.jcf.2021.03.024

Ital J Pediatr. 2021 Apr 21;47(1):98. doi: 10.1186/s13052-021-01047-y.

ABSTRACT

BACKGROUND: Despite ibuprofen widely recognized safety profile, an increase of suspected adverse events has been reported in the last decade in parallel with its growing over-the-counter use. The aims of this study were to assess the therapeutic approach to the feverish child and to evaluate the main indications and the most frequent adverse events related to ibuprofen administration in children.

METHODS: A specific questionnaire-form regarding the management of ibuprofen therapy in children was distributed among a sample of pediatricians all over the Italian territory between September and October 2020. An electronic data collection through a specifically designed web-based platform was performed among the participating pediatricians.

RESULTS: One-hundred-eighty-one pediatricians completed the survey. In case of fever, 177 (98%) participants prescribe paracetamol, while only 4 (2%) preferred ibuprofen as first choice. One-hundred-twenty-eight pediatricians (71%) administer paracetamol alone, while 53 (29.2%) use the combined/alternating treatment with ibuprofen. Ibuprofen is mostly administered for musculoskeletal pain (30%), upper respiratory tract infection (20%), headache (15%) and post-surgical pain (9%). Sixty-three (35%) out of 181 participating pediatricians reported 191 adverse events during ibuprofen administration. The most common were gastrointestinal (GI), with GI bleeding being reported in 30/191 cases (15.7%), epigastric pain in 29/191 (15.1%), non-specified abdominal pain in 22/191 (11.1%) and nausea/vomiting in 21/191 (11%). Severe adverse events including kidney damage (3.1%), complicated infections (0.5%), pneumonia associated empyema (0.5%), soft tissue infection (0.5%) and disseminated intravascular coagulation (0.5%) were also reported. The adverse events led to a hospitalization in 12% of children. In 53/191 cases (28%) the adverse events were related to a wrong dosage or prolonged therapy or errors in frequency of administration.

CONCLUSIONS: This survey demonstrate a sufficient awareness of Italian pediatricians regarding ibuprofen-prescribing patterns with the only possible concern related to the relatively high percentage of pediatricians performing a combining/alternating use of paracetamol and ibuprofen. The reported adverse events were mild in most of the cases and often related to errors in dosage, frequency and treatment duration, emphasizing the need for a major caution of both practitioners and patients in their use.

PMID:33883005 | DOI:10.1186/s13052-021-01047-y

BMC Pulm Med. 2021 Apr 21;21(1):131. doi: 10.1186/s12890-021-01500-y.

ABSTRACT

BACKGROUND: The extend of lung disease remains the most important prognostic factor for survival in patients with cystic fibrosis (CF), and lack of adherence is the main reason for treatment failure. Early detection of deterioration in lung function and optimising adherence are therefore crucial in CF care. We implement a randomized controlled trial to evaluate efficacy of telemonitoring of adherence, lung function, and health condition in combination with behavior change interventions using innovative digital technologies.

METHODS: This is a multi-centre, randomized, controlled, non-blinded trial aiming to include 402 patients ≥ 12 years-of-age with CF. A standard-of-care arm is compared to an arm receiving objective, continuous monitoring of adherence to inhalation therapies, weekly home spirometry using electronic devices with data transmission to patients and caring physicians combined with video-conferencing, a self-management app and professional telephone coaching. The duration of the intervention phase is 18 months. The primary endpoint is time to the first protocol-defined pulmonary exacerbation. Secondary outcome measures include number of and time between pulmonary exacerbations, adherence to inhalation therapy, changes in forced expiratory volume in 1 s from baseline, number of hospital admissions, and changes in health-related quality of life. CF-associated medical treatment and care, and health care related costs will be assessed by explorative analysis in both arms.

DISCUSSION: This study offers the opportunity to evaluate the effect of adherence interventions using telemedicine capable devices on adherence and lung health, possibly paving the way for implementation of telemedicine in routine care for patients with CF.

TRIAL REGISTRATION: This study has been registered with the German Clinical Trials Register (Identifier: DRKS00024642, date of registration 01 Mar 2021, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024642 ).

PMID:33882893 | DOI:10.1186/s12890-021-01500-y

PLoS One. 2021 Apr 21;16(4):e0250036. doi: 10.1371/journal.pone.0250036. eCollection 2021.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) leads to pancreatic endocrine dysfunction with progressive glycemic disturbance. Approximately 30%-50% of people with CF eventually develop CF-related diabetes (CFRD). Pre-CFRD states progress from indeterminant glycemia (INDET) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Screening guidelines recommend inconvenient annual 2-hour oral glucose tolerance tests (OGTTs), beginning at age 10 years. More efficient methods, such as hemoglobin A1C (HbA1c), have been evaluated, but only limited, relatively small studies have evaluated the association between HbA1c and pre-CFRD dysglycemic states.

OBJECTIVE: To determine whether HbA1c is an appropriate screening tool for identifying patients with pre-CFRD dysglycemia to minimize the burden of annual OGTTs.

METHODS: This retrospective review evaluated medical records data of all University of Massachusetts Memorial Health System CF patients with an HbA1c result within 90 days of an OGTT between 1997 and 2019. Exclusion criteria were uncertain CF diagnosis, other forms of diabetes, or incomplete OGTT. In total, 56 patients were included and categorized according to OGTT results (American Diabetes Association criteria): normal glucose tolerance, INDET, IFG, or IGT. Associations were evaluated between HbA1c and OGTT results and between HbA1c and pre-CFRD dysglycemic states.

RESULTS: Mean HbA1c was not significantly different between patients with normal glucose tolerance and those in the INDET (p = 0.987), IFG (p = 0.690), and IGT (p = 0.874) groups. Analysis of variance confirmed the lack of association between HbA1c and glycemia, as mean HbA1c was not significantly different amongst the four categories (p = 0.250).

CONCLUSION: There is increasing awareness of the impact of pre-CFRD states, including reduced pulmonary function and nutritional status. Unfortunately, our results do not support using HbA1c as a screening tool for pre-CFRD dysglycemia, specifically INDET, IFG, and IGT. Further studies are warranted to evaluate more efficient screening methods to reduce the burden of annual OGTTs.

PMID:33882078 | DOI:10.1371/journal.pone.0250036

Acc Chem Res. 2021 Apr 21. doi: 10.1021/acs.accounts.1c00040. Online ahead of print.

ABSTRACT

ConspectusAntibiotic resistance (AMR) is an increasing public health crisis worldwide. This threatens our ability to adequately care for patients with infections due to multi-drug-resistant (MDR) pathogens. As such, there is an urgent need to develop new classes of antimicrobials that are not based on currently utilized antibiotic scaffolds. One promising avenue of antimicrobial research that deserves renewed examination involves the use of peptides. Although antimicrobial peptides (AMPs) have been studied for a number of years, innovations in peptide design and their applications are increasingly making this approach a viable alternative to traditional small-molecule antibiotics. This review will provide updates on two ways in which peptides are being explored as antibiotics. The first topic will focus on novel types of peptides and conjugation methods that are being exploited to act as antibiotics themselves. These direct-acting modified peptides could serve as potentially useful drugs while mitigating many of the known liabilities of AMPs. The second topic relates to the use of peptides as delivery vehicles for other active compounds with antimicrobial activity. Cell-penetrating peptides (CPPs) are peptides designed to carry compounds across cell membranes and are a promising method for delivering a variety of antimicrobial compounds. When conjugated to other compounds, CPPs have been shown to be effective at increasing the uptake of both small- and large-molecular-weight compounds. This includes conjugation to antisense molecules and traditional antibiotics, resulting in increased effectiveness of these antimicrobials. One particular approach utilizes CPPs conjugated to phosphorodiamidate morpholino oligomers (PMOs). PMOs are designed to target particular pathogens in a gene-specific way. They target mRNA and block protein translation. Peptide-conjugated PMOs (PPMOs) allow for efficient delivery into the Gram-negative cytoplasm, and recent updates to their in vitro and in vivo activity are reviewed. This includes recent data to suggest that PPMOs maintain activity in the setting of multi-drug-resistant (MDR) strains, an important finding as it relates to the further development of this therapeutic approach. Other topics include the ability to have activity in the biofilm setting, a finding that likely relates to the peptide portion of the conjugate. Finally, what is known and anticipated related to the development of resistance to these peptides will be discussed.

PMID:33881843 | DOI:10.1021/acs.accounts.1c00040

Biomater Sci. 2021 Apr 21. doi: 10.1039/d1bm00483b. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa (P. aeruginosa) is a popular hospital pathogen and the major cause of morbidity and mortality in patients with cystic fibrosis (CF) and impaired immune system. Herein, we designed and synthesized a series of organic molecules MTEBT-n (n = 1, 2, 3) to specifically and effectively kill P. aeruginosa. Hydrophobic triphenylamine was selected as the skeleton, and hydrophilic primary ammonium salts that can easily penetrate the cell walls of Gram-negative bacteria and accumulate in the bacteria were used to adjust the hydrophilic-hydrophobic ratio of the molecules, resulting in different antibacterial activity. As the hydrophilic-hydrophobic ratio increased in the structures from MTEBT-1 to MTEBT-3, the antibacterial activity of the three molecules were gradually enhanced with killing effects of 25%, 75% and 95% against P. aeruginosa, respectively. The antibacterial mechanisms of MTEBT-n were demonstrated to destroy the bacterial membrane, which could effectively prevent the development of drug resistance. In addition, MTEBT-3 with the highest antibacterial activity could inhibit P. aeruginosa biofilm very well, and heal the P. aeruginosa infected scald wounds. This work provides a potential organic antimicrobial material for clinical antimicrobial therapy of P. aeruginosa infection, and offers a molecular engineering strategy for designing new antimicrobials.

PMID:33881420 | DOI:10.1039/d1bm00483b

Stat Med. 2021 Apr 20. doi: 10.1002/sim.9002. Online ahead of print.

ABSTRACT

Insights regarding the merits of recurrent event and time-to-first-event analyses are needed to provide guidance on strategies for analyzing intervention effects in randomized trials involving recurrent event responses. Using established asymptotic results we introduce a framework for studying the large sample properties of estimators arising from semiparametric proportional rate function models and Cox regression under model misspecification. The asymptotic biases and power implications are investigated for different data generating models, and we study the impact of dependent censoring on these findings. Illustrative applications are given involving data from a cystic fibrosis trial and a carcinogenicity experiment, following which we summarize findings and discuss implications for clinical trial design.

PMID:33880781 | DOI:10.1002/sim.9002

Cochrane Database Syst Rev. 2021 Apr 21;4:CD008708. doi: 10.1002/14651858.CD008708.pub5.

ABSTRACT

BACKGROUND: Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In β-thalassaemia there is an underproduction of β-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for β-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review.

OBJECTIVES: To evaluate the effectiveness and safety of different types of hematopoietic stem cell transplantation, in people with transfusion-dependent β-thalassaemia.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of the most recent search: 07 April 2021.

SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).

DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials and had planned to extract data and assess risk of bias using standard Cochrane methodologies and assess the quality using GRADE approach, but no trials were identified for inclusion in the current review.

MAIN RESULTS: No relevant trials were retrieved after a comprehensive search of the literature.

AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent β-thalassaemia. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

PMID:33880750 | DOI:10.1002/14651858.CD008708.pub5