Heart transplantation in Danon disease: Long term single centre experience and review of the literature

Danon disease is characterized by hypertrophic cardiomyopathy, skeletal myopathy, and intellectual disability due to deficiency of the lysosome-associated membrane protein-2 (LAMP-2). Although heart transplantation is considered an option for end stage Danon cardiomyopathy, scarce information is available about long term follow up. We report on long term follow up (14.7 years, IQ range 9–21 years) of 4 patients, transplanted for Danon disease cardiomyopathy, showing two LAMP-2 gene variants, the novel c.815T > C and the previously reported c.294G > A. We have also analysed previous published paper on this topic comparing available data from different follow up. Being a skeletal and cardiac muscle disease, with systemic effects, long term results about HTx are indispensable to justify any treatments in this subset of patients.     

Rising prevalence of food allergies in Taiwan: An epidemiological study

BackgroundFood allergies are becoming more prevalent globally. The purpose of this study was to investigate the epidemiology of food allergies in Taiwan.MethodsIn 2017, a food allergy questionnaire was administered to 6–7-year-old children, 13–14-year-old adolescents, and their parents in Taipei. The results were compared to those from a previous survey conducted in 2004.ResultsA total of 16,200 questionnaires were completed, revealing a rise in the prevalence of food allergies from 7.7% to 10.4% in the pediatric group and from 6.4% to 12.5% in the adult group. Peanut allergies also increased to 1.1%. Shrimp and crabs were the most common allergens, with urticaria being the most common symptom. Shortness of breath or wheezing occurred in 10% of individuals, while 2.1% experienced syncope or shock, and 0.1% were admitted to an intensive care unit. Personal history of allergic rhinitis and atopic dermatitis, as well as family histories of food allergies, were risk factors for food allergy in 6–7-year-old children. In the 13–14-year-old group, personal history of asthma, allergic rhinitis, or atopic dermatitis, recent use of acetaminophen, and living with dogs were risk factors. Females, personal histories of asthma, allergic rhinitis, atopic dermatitis, and moist and damp at home were risk factors in adults. Breastfeeding was a protective factor in 6–7-year-old children.ConclusionThe increasing prevalence of food allergies, including peanut allergies, in Taiwan warrants attention from physicians to provide appropriate care and education to patients with food allergies. The protective effect of breastfeeding against food allergies shall be emphasized.     

Gut microbiota as a promising therapeutic target for age-related sarcopenia

Sarcopenia is characterized by a progressive loss of skeletal muscle mass and function with aging. Recently, sarcopenia has been shown to be closely related with gut microbiota. Strategies such as probiotics and fecal microbiota transplantation have shown potential to ameliorate the muscle loss. This review will focus on the age-related sarcopenia, in particular on the relationship between gut microbiota and age-related sarcopenia, how gut microbiota is engaged in sarcopenia, and the potential role of gut microbiota in the treatment of age-related sarcopenia.     

Clostridioides difficile colonization among very young children in resource-limited settings

ObjectivesTo describe the epidemiology and risk factors for Clostridioides difficile (C. difficile) colonization among young children in eight low-resource settings.MethodsWe tested 41 354 monthly non-diarrhoeal and diarrhoeal stools for C. difficile toxin genes (TcdA and TcdB) using quantitative PCR (qPCR) in 1715 children from birth to age two years in a multisite birth cohort study. We estimated the prevalence, cumulative incidence, and seasonality of C. difficile colonization and investigated the associations of C. difficile detection with risk factors of infection, markers of enteropathy, and growth.ResultsThe prevalence of C. difficile detection was lower in diarrhoeal (2.2%; n = 151/6731) compared to non-diarrhoeal stools (6.1%; n = 2106/34 623). By 24 months of age, the cumulative incidence of C. difficile varied widely by site, with 17.9% (n = 44; Pakistan) to 76.3% (n = 148; Peru) of children having at least one positive stool. Only Bangladesh and Pakistan had seasonal differences in C. difficile detection. Female sex (adjusted risk ratio (aRR): 1.18; 95% CI: 1.02–1.35), cephalosporin use in the past 15 days (aRR: 1.73; 95% CI: 1.39–2.16), and treated water (aRR: 1.24; 95% CI: 1.02–1.50) were risk factors for C. difficile positivity. The presence of C. difficile was significantly associated with elevated faecal myeloperoxidase, neopterin, and α-1-antitrypsin, but no associations were found between C. difficile and child growth at 24 months of age.DiscussionC. difficile colonization among children ages 0–2 years was variable across low-resource settings. Significant elevation of intestinal inflammation and barrier disruption markers associated with C. difficile detection suggests a subclinical impact of colonization.     

Elbasvir/grazoprevir is effective and tolerable for the treatment of HCV GT1-infected patients: A real world multicenter observatory study in Taiwan

Background & aimsTreatment of hepatitis C virus (HCV) by elbasvir/grazoprevir (EBR/GZR) was found to be efficacious and well tolerated in clinical trials. This study aimed to evaluate the effectiveness and tolerability of EBR/GZR in the treatment of HCV genotype 1-infected Taiwanese patients.MethodsChronic hepatitis C patients infected with GT1b or 1a without resistance-associated substitution, and treated with 12-week EBR/GZR were enrolled from 10 hospitals in Taiwan between August 2017 and December 2018. All clinical and virologic data were collected at each participating center. Primary efficacy endpoint was sustained virologic response at week 12 (SVR12) after end of the EBR/GZR therapy, assessed in the per-protocol population, which excluded patients with important deviations from the protocol. Analysis was also performed based on the modified full analysis set, which included all allocated patients receiving at least 4-week medication. Virologic failure was recorded as breakthrough, nonresponse, or relapse. Safety was assessed through collection of adverse events, physical examination, vital signs, and standard laboratory evaluations.ResultsPer protocol SVR12 rates were 99.5% (1169/1175) for all HCV genotype 1 patients. Among patients with stage 4 or 5 chronic kidney diseases, 100% (107/107) achieved SVR12. In univariate analyses, variables associated with SVR12 were treatment termination (P < 0.0001) and treatment adherence (P < 0.0001) in the mFAS population. Overall, 22.3% of the patients experienced adverse events during treatment. Seven patients did not complete the treatment, five due to liver-unrelated deaths, one due to adverse event and one due to epilepsy.ConclusionsEBR/GZR treatment was highly effective and well tolerated.     

The triglyceride to HDL-cholesterol ratio and chronic graft failure in renal transplantation

BackgroundTransplant vasculopathy (TV) is a major contributing factor to chronic graft failure in renal transplant recipients (RTR). TV lesions resemble atherosclerosis in several ways, and it is plausible to believe that some risk factors influence both atherosclerotic plaque formation and formation of TV.ObjectiveThe objective of this prospective longitudinal study was to determine if dyslipidemia reflected by the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is prospectively associated with death censored chronic graft failure in RTR.Method454 prospectively included RTR with a functioning graft for at least one year, were followed for a median of 7 years. RTR were matched based on propensity scores to avoid potential confounding and subsequently the association of the TG/HDL-C ratio with the endpoint chronic graft failure, defined as return to dialysis or re-transplantation, was investigated.ResultsLinear regression analysis showed that concentration of insulin, male gender, BMI and number of antihypertensives predict the TG/HDL-C ratio. Cox regression showed that the TG/HDL-C ratio is associated with chronic graft failure (HR = 1.43, 95%CI = 1.12–1.84, p = 0.005) in competing risk analysis for mortality. Interaction testing indicated that the relationship of the TG/HDL-C ratio with graft failure is stronger in subjects with a higher insulin concentration.ConclusionOur results demonstrate that the TG/HDL-C ratio has the potential to act as a predictive clinical biomarker. Furthermore, there is a need for closer attention to lipid management in RTR in clinical practice with a focus on triglyceride metabolism.     

Effectiveness of hepatitis A vaccination among people living with HIV in Taiwan: Is one dose enough?

BackgroundSingle dose hepatitis A virus (HAV) vaccine had been proven its efficacy in immunocompetent but not immunocompromised hosts. We aim to investigate the effectiveness of one dose versus 2 doses HAV vaccine among people living with HIV (PLHIV).MethodWe conducted a 1:1 single center retrospective case–control study for PLHIV in Northern Taiwan. Case patients were those who received single dose HAV vaccine and controls were those who completed standard 2 doses HAV vaccine. Nationwide campaign of single dose HAV vaccine had been practiced for high risk population including PLHIV and those who had newly diagnosed sexually transmitted diseases.ResultsDuring February 2016 and December 2017, 90 cases received single dose HAV vaccine provided while the other 90 age-matched controls received 2 doses vaccine were enrolled. We found more injection drug users (22.22% vs. 1.11%, p < 0.0001), more co-infection with viral hepatitis C (28.89% vs. 5.56%, p < 0.0001), and history of syphilis infection (56.67% VS 30%, p = 0.0003) in single dose group than 2 doses group. Seroconversion rate at one year was significantly higher in 2 doses group (97.78% vs 56.67%, p < 0.0001). Among single dose group, people with hepatitis B or C virus co-infection (HBV: p = 0.02, aOR: 0.03, 95% CI: 0.002–0.55; HCV: p = 0.002, aOR: 0.22, 95% CI: 0.08–0.58) were less likely to achieve seropositivity, while those who had higher CD4 count at baseline and one year, had better response to vaccine.ConclusionTwo doses HAV vaccine is necessary among PLHIV to achieve sustained seroresponse rather than single dose.     

Gut microbiota development during infancy: Impact of introducing allergenic foods

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Virtual crossmatch for deceased donor kidney transplantation in the United States: A survey of histocompatibility lab directors and transplant surgeons

Virtual crossmatch (VXM) is used as an alternative to or in conjunction with a cell-based physical crossmatch (PXM) for assessing HLA (human leukocyte antigen) compatibility prior to deceased donor kidney transplantation (DDKT). Data on practice patterns and perceptions regarding VXM use in the US are limited. We performed a survey of US HLA directors and transplant surgeons regarding HLA testing and crossmatch strategies. 53 (56 %) HLA directors and 68 surgeons (representing ～ 23 % of US transplant centers) completed the survey. Both groups agreed that VXM could reduce cold ischemia time (CIT), costs and improve allocation efficiency. VXM use increased following the 2021 kidney allocation change. Reducing CIT was the primary reason for favoring VXM over PXM. Preference for VXM reduced as candidates’ panel reactive antibodies increased. Regulations, program policies and limitations of HLA technology were cited as important reasons for preferring PXM over VXM. Surgeons reported similar perceptions, but findings are limited by the low response rate. Finally, half the labs reported lacking specific protocols for VXM use. In conclusion, improved HLA technology and protocols along with changes to institutional procedures and policy regulations are needed for safer expansion of VXM in DDKT.     

Current donor selection strategies for allogeneic hematopoietic cell transplantation

Since the first allogeneic hematopoietic stem cell transplantation (HCT) was performed by Dr. E. Donnall Thomas in 1957, the field has advanced with new stem cell sources, immune suppressive regimens, and transplant protocols. Stem cells may be collected from bone marrow, peripheral or cord blood from an identical twin, a sibling, or a related or unrelated donor, which can be human leukocyte antigen (HLA) matched, mismatched, or haploidentical. Although HLA matching is one of the most important criteria for successful allogeneic HCT (allo-HCT) to minimize graft vs host disease (GVHD), prevent relapse, and improve overall survival, the novel immunosuppressive protocols for GVHD prophylaxis offered improved outcomes in haploidentical HCT (haplo-HCT), expanding donor availability for the majority of HCT candidates. These immunosuppressive protocols are currently being tested with the HLA-matched and mismatched donors to improve HCT outcomes further. In addition, fine-tuning the DPB1 mismatching and discovering the B leader genotype and mismatching may offer further optimization of donor selection and transplant outcomes. While the decision about a donor type largely depends on the patient’s characteristics, disease status, and the transplant protocols utilized by an individual transplant center, there are general approaches to donor selection dictated by donor-recipient histocompatibility and the urgency for HCT. This review highlights recent advances in understanding critical factors in donor selection strategies for allo-HCT. It uses clinical vignettes to demonstrate the importance of making timely decisions for HCT candidates.     

A tryptophan metabolite of the skin microbiota attenuates inflammation in patients with atopic dermatitis through the aryl hydrocarbon receptor

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Respiratory pathogens – Some altered antibiotic susceptibility after implementation of pneumococcus vaccine and antibiotic control strategies

Background/purposeAntimicrobial resistance in Taiwan has been on the rise for two decades. The implementation of pneumococcal conjugate vaccination (PCV13) and enhanced antimicrobial control (2013–2015) by the government may have changed the antibiotic resistance.MethodsFour respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Moraxella catarrhalis) isolated in a single medical center during 2008–2017 were studied. We defined three temporal stages: (a) the first era (2008–2012), prior to implementation of the national immunization program (PCV13 vaccination), (b) the second era (2013–2015), during which an enhanced antibiotic control strategy was implemented, and (c) the third era (2016–2017), after implementation. Antimicrobial drug sensitivities were collected from two other hospitals: one from east Taiwan, one from west-central Taiwan.ResultsS. pneumoniae was frequently isolated during the first era. It declined progressively during the second era of PCV13 vaccination. S. pyogenes and M. catarrhalis were not frequently isolated. The drug susceptibility of S. pneumoniae to ceftriaxone and vancomycin remained high. The antimicrobial susceptibility of H. influenzae to amoxillin/clavulante declined over the three temporal stages, from 91.9%-79.5%–58.5% (all p < 0.05).ConclusionAntimicrobial resistance of H. influenzae increased during the latter part of the study period. The PCV13 vaccination program reduced the invasive pneumococcal disease and reduced the stress on the emergent drug resistance. This enhanced antibiotic control strategy was effective in terms of nosocomial drug resistance but not for community-associated pathogens.     

Association between SARS-CoV-2 infection and de novo HLA donor specific antibody production in lung transplant recipients: Single-center study

The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients. Respiratory viral infections may be associated with de-novo HLA donor-specific antibody production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in lung transplant recipients include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo HLA donor specific antibody production in lung transplant recipients. We performed a retrospective chart review of 24 consecutive lung transplant recipients diagnosed with COVID-19 to investigate this concern. We observed no significant differences in the CPRA or MFI levels of HLA class I and II antibodies pre- COVID-19 compared to 1 and 6 months post-COVID-19 diagnosis in 11/24 (45.8 %) LTR (p = 0.98 and p = 0.63 respectively). HLA class I and II DSA were detected in 5/24 LTR pre-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.89). De-novo HLA class I and II DSA were detected in 1/24 (4.2 %) LTR at one month post-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.54). Our results suggest that there was no significant association between SARS-CoV-2 infection and immunomodulation on pre-existing or de novo HLA donor specific antibodies.     

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

BackgroundIn allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients, the inter-relationship between post-transplant cytomegalovirus (CMV) and subsequent invasive fungal infections (IFIs) is conflicting and the association of CMV serostatus with IFIs has not been evaluated.ObjectivesTo determine the relationship between CMV infection/serostatus and IFIs in allo-HSCT populations.Data sourcesA systematic literature search was conducted from existence until 11 July 2021 using Medline, Embase and ISI Web of Science databases.Study eligibility criteriaCross-sectional, prospective cohort, retrospective cohort and case–control studies that reported allo-HSCT recipients with CMV and without CMV who developed or did not develop IFIs after CMV infection.ParticipantsAllo-HSCT recipients.InterventionsNot applicable.MethodsA systematic search, screening, data extracting and assessing study quality were independently conducted by two reviewers. The Newcastle–Ottawa scale was used to assess risk of bias. data were analysed using the pooled effect estimates of a random-effects model.ResultsA total of 18 and 12 studies were included for systematic review and meta-analysis, respectively. Post-transplant CMV infection significantly increased the risk of IFIs with a pooled hazard ratio (pHR) of 2.58 (1.78, 3.74), I² = 75%. Further subgroup analyses by timing of IFIs, CMV definitions, study continents, study design and adjustment of effect estimates showed that post-transplant CMV infection consistently increased the risk of subsequent IFIs. High-risk CMV serostatus (D–/R+) increased the risk of IFIs with a pooled odds ratio (OR) of 1.33 (1.04, 1.71), I² = 0%, but low-risk CMV serostatus (D–/R–) decreased the risk of IFIs with a pOR of 0.69 (0.55, 0.87), I² = 0%.ConclusionsPost-transplant CMV infection and high-risk CMV serostatus increased the risk of IFIs, but low-risk CMV serostatus decreased risk of IFIs among allo-HSCT recipients. Further studies are needed to identify at-risk allo-HSCT recipients as well as to focus on fungal diagnostics and prophylaxis to prevent this fungal-after-viral phenomenon.