Leadless pacemaker implantation for pediatric patients through internal jugular vein approach: A case series of under 30 kg

BackgroundWe demonstrate a case series of 8 pediatric patients, all under 30 kg, who had leadless pacemaker implants via the internal jugular vein.MethodsA retrospective review of pediatric leadless pacing placement via the internal jugular vein at the University of Minnesota Masonic Children's Hospital and UC Davis Medical Center from 2018 through 2021 was performed. Rationales for pacing, demographics of patients, pacing thresholds, and longevity of devices were recorded.ResultsEight internal jugular pacemaker insertions were performed successfully in patients weighing between 10.9 kg and 29 kg. Five patients had Micra implantation via the right internal jugular vein, whereas 3 patients had insertion via the left internal jugular vein. No surgical cut-downs were performed. No venous complications occurred. Up to 3 years of follow-up were noted.ConclusionLeadless pacemaker implantation, via left or right internal jugular veins, is feasible without surgical cutdown in patients <30 kg     

Do all patients with implantable cardioverter defibrillator need a generator change? A health service evaluation of patients who underwent generator changes from a single tertiary center

BackgroundThe patient characteristics, therapy received and outcomes after one or more implantable cardioverter defibrillator (ICD) generator changes from contemporary practice is not well known.MethodsWe conducted a health service evaluation of patients who underwent ICD implantation and generator change. Patients who had generator changes from February 2016 to October 2019 were identified from our database and electronic records were reviewed for patient characteristics, number of generator changes, receipt of therapy and death.ResultsOur database included 88 patients with a generator change. A total of 22 patients (25.0%) received dual chamber ICD, 10 patients (11.4%) received single chamber ICD, 54 patients (61.3%) received cardiac resynchronization therapy defibrillator and 2 patients (2.3%) received subcutaneous ICD. A second generator change occurred in 18 patients and a third generator changes was performed in 6 patients. There were 29 deaths and a follow up period of 9.4 ± 2.9 years. From implant to initial generator change 39 patients had appropriate antitachycardia pacing (ATP), 6 patient had inappropriate ATP, 29 patients had appropriate shocks and 5 patients had an inappropriate shock. Between the 1st and 2nd generator change and the 2nd and 3rd there were no cases of inappropriate ATP or shock. Overall, 42 patients out of the 88 had appropriate therapy (47.7%) and 7 patients had inappropriate therapy (8.0%).ConclusionsMost patients with ICDs do not receive therapy and a minority have inappropriate therapy which typically occur before the first generator change as we observed no inappropriate therapy beyond the first generator change.     

Hemodynamic monitoring by intracardiac impedance measured by cardiac resynchronization defibrillators: Evaluation in a controlled clinical setting (BIO.Detect HF II study)

BackgroundIn patients with cardiac resynchronization therapy defibrillators (CRT-Ds), intracardiac impedance measured by dedicated CRT-D software may be used to monitor hemodynamic changes. We investigated the relationship of hemodynamic parameters assessed by intracardiac impedance and by echocardiography in a controlled clinical setting.MethodsThe study enrolled 68 patients (mean age, 66 ± 9 years; 74% males) at 12 investigational sites. The patients had an indication for CRT-D implantation, New York Heart Association class II/III symptoms, left ventricular ejection fraction 15%–35%, and a QRS duration ≥150 ms. Two months after a CRT-D implantation, hemodynamic changes were provoked by overdrive pacing. Intracardiac impedance was recorded at rest and at four pacing rates ranging from 10 to 40 beats/min above the resting rate. In parallel, echocardiography measurements were performed. We hypothesized that a mean intra-individual correlation coefficient (r_mean) between stroke impedance (difference between end-systolic and end-diastolic intracardiac impedance) measured by CRT-D and the aortic velocity time integral (i.e., stroke volume) determined by echocardiography would be significantly larger than 0.65.ResultsThe hypothesis was evaluated in 40 patients with complete data sets. The r_mean was 0.797, with a lower confidence interval bound of 0.709. The study hypothesis was met (p = 0.007). A stepwise reduction of stroke impedance and stroke volume was observed with increasing heart rate.ConclusionsIntracardiac impedance measured by implanted CRT-Ds correlated well with the aortic velocity time integral (stroke volume) determined by echocardiography. The impedance measurements bear potential and are readily available technically, not requiring implantation of additional material beyond standard CRT-D system.     

Time to initiation of pre-emptive therapy for cytomegalovirus impacts overall survival in pediatric hematopoietic stem cell transplant recipients

Background aimsCytomegalovirus (CMV) reactivation is a significant complication following allogeneic hematopoietic stem cell transplant (HSCT) and affects upwards of 40% of pediatric HSCT patients. Pre-emptive therapy remains the only effective treatment strategy available for pediatric patients following CMV reactivation. Little is known about how the timing of induction treatment following CMV reactivation impacts outcomes in pediatric patients, especially following ex vivo T-cell-depleted (TCD) HSCT.MethodsThe authors evaluated how the timing of induction treatment after CMV reactivation impacts overall survival (OS) and CMV disease in pediatric patients undergoing TCD HSCT at a single institution. The authors retrospectively analyzed patients treated on the pediatric service who received an initial ex vivo TCD HSCT at Memorial Sloan Kettering Cancer Center (MSKCC) from January 2010 to June 2018. CMV reactivation was defined as ≥1 CMV polymerase chain reaction >500 copies/mL in whole blood or >137 IU/mL in plasma within the first 180 days after allogeneic HSCT. To analyze the impact of the timing of induction treatment, the authors’ primary study outcome was OS and secondary outcome was CMV disease.ResultsA total of 169 patients who underwent an initial allogeneic TCD HSCT on the pediatric service at MSKCC from January 2010 to June 2018 were included in the analysis. Thirty-seven (22%) patients reactivated CMV during the first 180 days following HSCT. Of those patients who reactivated CMV, CMV donor/recipient (D/R) serostatus was as follows: D+/R+ n = 28 (76%) and D–/R+ n = 9 (24%). There was no CMV reactivation observed among recipients who were CMV-seronegative irrespective of donor serostatus. In those patients who reactivated CMV, the median time from HSCT to CMV reactivation was 24 days (interquartile range, 20–31). Eleven patients ultimately developed CMV disease in addition to CMV viremia, whereas the remaining patients had only CMV viremia. The cumulative incidence of CMV reactivation at 60 days was 45.2% (95% confidence interval [CI], 32.8–57.5) in the D+/R+ subgroup and 31% (95% CI, 14.2–47.9) in the D–/R+ subgroup. For those patients who reactivated CMV, 30 (81%) received induction treatment with ganciclovir or foscarnet. To analyze the impact of the timing of induction treatment on clinical outcomes, the authors restricted the analysis to those patients who reactivated CMV and received induction treatment (n = 30). The timing of induction treatment was significantly associated with OS, with optimal timing of initiation within a week of CMV reactivation (P = 0.02). There was no significant impact on the timing of induction treatment and risk of CMV disease (P = 0.30).ConclusionsIn ex vivo TCD HSCT in pediatric patients, early initiation of induction treatment after CMV reactivation is associated with improved OS.     

Type 1 Diabetes Mellitus and Lipohypertrophy - Impact of the Intervention on Glycemic Control via Patient’s Examination and Retraining on Change of Infusion Set

ObjectiveLipohypertrophy (LH) is a common complication of insulin therapy in type 1 diabetes mellitus (T1DM). We examined whether an intervention consisting of LH assessment and retraining on insulin infusion set use improves glycemic control on subcutaneous insulin infusion (CSII) in patients with T1DM.MethodsThe intervention was conducted in 79 consecutive patients with T1DM. Data on glucose levels, glycated hemoglobin (HbA1c), and insulin doses were collected at baseline and after a median of 22 weeks (20-31.75 weeks).ResultsA total of 46 patients with T1DM (23 [50%] women) participating in the follow-up were characterized by a median age of 29 years (25-33.8 years), body mass index of 24.6 ± 3.3 kg/m², T1DM duration of 16.5 years (8.3-20 years), and subcutaneous insulin infusion duration of 7 years (4-10.8 years). Patients’ median HbA1c fell from 7.4% (6.7%-8.2%) to 7.05% (6.4%-7.6%) (P < .001), daily insulin dose/kg decreased (0.7 ± 0.20 vs 0.68 ± 0.15 IU/kg; P = .017) together with the total daily insulin dose (50.3 [40.5-62.7] vs 47.6 [39.8-62.1] IU; P = .019]. Furthermore, the percentage of basal insulin dose increased (43.0% [36-50] vs 44.0% [39.0-50.0]; P = .010], whereas the percentage of bolus dose decreased (57% [50-64] vs 56% [50-61], P = .010).ConclusionsThe structured LH-related intervention in patients with T1DM on insulin pumps resulted in better glycemic control and a decrease in total daily insulin dose.     

Ultrasound-guided axillary vein puncture for cardiac devices implantation in patients under antithrombotic therapy

BackgroundUltrasound-guided axillary venous puncture (UGAVP) for cardiac devices implantation has been developed because of its rapidity, safety and potential long-term lead protection. Early work excluded defibrillators (ICD), cardiac resynchronization therapy (CRT) and upgrade procedures. Compared to the cephalic approach, in previous studies, there was a greater use of pressure dressings with this technique, suggesting a higher risk of bleeding.AimsTo assess UGAVP in patients under antithrombotic therapy (ATT) undergoing cardiac devices implantation including CRT/ICD.MethodsProspectively, consecutive patients eligible for a pacemaker or ICD implantation were included. All procedures were performed by a single operator, experienced with UGAVP for femoral access, and fluoroscopy-guided axillary vein access. Guidewires insertion time (from lidocaïne administration), and complications were systematically studied.ResultsFrom 457 cardiac device implantations, 200 patients (77.8 ± 10 y, male 58%) 360 leads were implanted by UGAVP including 36 ICD, 54 CRT and 14 upgrade procedures. A majority (90%) was under ATT: Vitamin K Antagonist or Heparin (n = 58, 29%), direct oral anticoagulant (n = 46, 23%), dual antithrombotic therapy (n = 18, 9%) and single antiplatelet drug (n = 82, 41%). UGAVP was successful in 95.78%. Mean insertion time for 1.8 guidewires per patient was 4.68 ± 3.6 min. No complication (no hematoma) was observed during the follow-up (mean of 45 ± 10 months). Guidewires insertion time reached its plateau after 15 patients.ConclusionUGAVP is fast, feasible and safe for patients under ATT undergoing device implantation including CRT/ICD and upgrade procedures, with a short learning curve.     

Wearable cardioverter-defibrillator (life-vest): A feasible bridging treatment in adult congenital heart disease

BackgroundWearable cardioverter-defibrillators (WCDs) are currently used in patients at temporarily heightened risk for sudden cardiac death (SCD) who are temporarily unable to receive an implantable cardioverter-defibrillator (ICD). WCD can safely record and terminate life-threatening arrhythmias through a non-invasive electrode-based system. The current clinical indications for WCD use are varied and keep evolving as experience with this technology increases.MethodsWe reviewed and explored the data behind indications for WCD use and discuss its usefulness in congenital heart disease (CHD) patients.ResultsWe considered 8 consecutive patients (mean age 35.25 years, range 18–51 years, average duration of WCD use 4 months, range 3–6 months) with complex CHD, in which a WCD was used between June 2018 and January 2022. No sustained ventricular arrhythmias requiring shocks were recorded in the observation period. No inappropriate shocks were recorded. All the patients showed a good compliance and a very high mean wear time per day (21.2 ± 1 h a day). Four patients implanted a permanent device (3 CRT-D, 1 ICD), three underwent cardiac surgery at the end of the WCD period and one is still on the waiting list for the operation.ConclusionsLarger trial could confirm the possible conceivable benefit from an extended use of the WCD in certain populations with complex CHD as in our case series, especially in patients with life-treating ventricular arrhythmias waiting for surgery for residual cardiac defects or in the early phases following the surgical/hemodynamic interventions, patients with tachycardiomyopathy expected to improve after the arrhythmias are removed and patients awaiting implantation of an ICD at high risk due to active infection.     

Weight gain during treatment course of allogenic hematopoietic stem cell transplantation in patients with hematological malignancies affects treatment outcome

Background aimsAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for patients with hematological malignancies; however, allo-HSCT does not come without the cost of treatment-related morbidity and mortality. Early detection of risk factors could be helpful in identifying patients who could benefit from early interventions. Many patients gain weight during the allo-HSCT treatment, although little is known about the impact of weight gain.MethodsWeight gain in 146 consecutively enrolled adult patients undergoing allo-HSCT was explored.ResultsIn total, 141 patients (97%) gained weight along the course of allo-HSCT. Median weight increase was 4.8 kg (range 0.0–16.1 kg), with median increase in body weight 6.5% (range 0.0%–30.8%). Maximum weight increase was observed at day +7 (range day –8, +44). Weight gain was associated with increased incidence of acute graft-versus-host disease. Patients with weight gain >10% had a significantly greater 5-year mortality compared with those with lower weight gain (P = 0.031, rank sum test).ConclusionsWeight gain is a simple variable with the ability to provide prognostic information for patients undergoing allo-HSCT.     

Incidence and outcome of prosthetic valve endocarditis after transcatheter aortic valve replacement in the Netherlands

Background

Transcatheter aortic valve replacement (TAVR) is increasingly being used as an alternative to conventional surgical valve replacement. Prosthetic valve endocarditis (PVE) is a rare but feared complication after TAVR, with reported first-year incidences varying from 0.57 to 3.1%. This study was performed to gain insight into the incidence and outcome of PVE after TAVR in the Netherlands.

Methods

A multicentre retrospective registry study was performed. All patients who underwent TAVR in the period 2010–2017 were screened for the diagnosis of infective endocarditis in the insurance database and checked for the presence of PVE before analysis of general characteristics, PVE parameters and outcome.

Results

A total of 3968 patients who underwent TAVR were screened for PVE. During a median follow-up of 33.5 months (interquartile range (IQR) 22.8–45.8), 16 patients suffered from PVE (0.4%), with a median time to onset of 177 days (IQR 67.8–721.3). First-year incidence was 0.24%, and the overall incidence rate was 0.14 events per 1000 person-years. Overall mortality during follow-up in our study was 31%, of which 25% occurred in hospital. All patients were treated conservatively with intravenous antibiotics alone, and none underwent a re-intervention. Other complications of PVE occurred in 5 patients (31%) and included aortic abscess (2), decompensated heart failure (2) and cerebral embolisation (1).

Conclusion

PVE in patients receiving TAVR is a relatively rare complication and has a high mortality rate.

     

Single-center experience with wearable cardioverter-defibrillator as a bridge before definitive ICD implantation

BackgroundThe wearable cardioverter-defibrillator (WCD) has been approved for patients with poor left ventricular ejection fraction (LVEF) who are at risk of sudden arrhythmic death for a limited period but are not candidates for a definitive implantable cardioverter-defibrillator (ICD). The present study sought to retrospectively analyse our single-centre experience.Methods and resultsAll consecutive WCDs applied between April 2017 and September 2018 in our centre were enrolled. An exercise test was performed in all patients in order to evaluate the absence of false detection of ventricular arrhythmias by the device. A total of 16 patients (57.7 ± 14.8 years old; 75% males) were taken into consideration for the analysis. Mean LVEF was 32 ± 11% at diagnosis and 42 ± 10% at last follow-up (mean, 3.1 ± 1.7 months; median, 3 months). At the end of the “wearing period” 11/16 patients (69%) did not have ICD implant indications and only 5 (31%) underwent ICD implantation. Neither appropriate nor appropriate shocks occurred during the follow up.ConclusionsThe WCD represents a useful tool to bridge a temporarily increased risk for sudden cardiac death. The proportion of patients with an improvement of LVEF> 35% beyond the WCD-application period was considerable.     

Hematopoietic stem cell transplantation with umbilical cord multipotent stromal cell infusion for the treatment of aplastic anemia—a single-center experience

Background aimsThe purpose of this study was to observe the outcome of co-transfusion of umbilical cord multipotent stromal cells (UC-MSC) and allogeneic hematopoietic stem cells in the treatment of heavily-transfused patients with severe aplastic anemia.MethodsOf the 22 patients, eight cases received haploidentical hematopoietic stem cells from granulocyte colony-stimulating factor–primed bone marrow and peripheral blood grafts; the other patients received granulocyte colony-stimulating factor–mobilized peripheral blood grafts from human leukocyte antigen–matched related (six cases) and unrelated donors (eight cases). MSCs were intravenously infused at a mean dose of 1.2 × 10⁶/ kg (range, 0.27–2.5 × 10⁶/kg). Fludarabine-based conditioning was conducted, and graft-versus-host disease prophylaxis containing cyclosporine A, methotrexate and mycophenolate mofetil with or without addition of anti-CD25 monoclonal antibody was performed. Hematopoietic engraftment, the occurrence of graft-versus-host disease (GVHD) and infections and overall survival were documented.ResultsAll patients had rapid engraftment; mean time for neutrophil and platelet recovery was 13.95 d and 20.27 d, respectively. No acute toxicity associated with UC-MSC transfusion was observed. Acute GVHD developed in seven cases (grade I–II), and none had development of chronic GVHD. Cytomegalovirus reactivation was observed in 11 cases. One patient died of pulmonary complication 6 months after transplantation. Twenty-one patients are currently alive, at a median follow-up of 15 months; they are transfusion-independent and reached full donor chimerism at the time of reporting.ConclusionsUC-MSC infusion might be an alternative option to promote hematopoietic engraftment and reduce the occurrence of GHVD in hematopoietic stem cell transplantation in the treatment of heavily transfused patients with severe aplastic anemia.     

Conquering the cytokine storm in COVID-19-induced ARDS using placenta-derived decidua stromal cells

Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14–68) years with COVID-19-induced ARDS. DSCs were administered 1–2 times at a dose of 1 × 10⁶/kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69–88) to 95% (range 78–99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0–253.4) to 11 (range 4.0–38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5–169) to 6 (range 2–31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3–12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19.     

Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial

Background aimsCerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion.MethodsIn this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow–derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733).ResultsA median of 13.12 × 10⁸ TNCs (range, 4.83–53.87) including 10.02 × 10⁶ CD34+ cells (range, 1.02–29.9) in a volume of 7 mL (range, 4–10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10⁸ TNCs (range, 1.36–17.85), with 3.39 × 10⁶ cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found.ConclusionsSubarachnoid placement of autologous bone marrow–derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function.     

Mauriac syndrome still exists

Background/objectiveMauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS.Materials and methodsA retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed.ResultsFrom a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13–17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia.ConclusionsAlthough MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control.     

New allergies after cord blood transplantation

Background aimsUmbilical cord blood transplantation (CBT) is an effective treatment for benign and malignant diseases. Late effects of CBT are not well described in the literature. In the present study, we present our experience of new-onset allergies in long-term survivors after CBT.MethodsAfter an initial patient had a severe peanut allergic reaction after CBT, all CBT patients were prospectively followed for new allergy development. Fifty patients received CBT between March 2006 and June 2011.ResultsThe median follow-up after CBT was 447 days (range, 12–2022). At the time of analysis, 30 patients were alive, with 3-year survival of 55.5%; median follow-up of surviving patients was 910 days (range, 68–2022). The allergic syndrome developed in five patients, with the cumulative incidence of new allergies at 2 years of 18.4% (95% confidence interval, 10.8–26). The median time to onset of new allergy after transplantation was 298 days (range, 250–809).ConclusionsAllergy development has been linked to a delayed maturation of the immune system in several studies. We present the first case series of patients who had new allergies after CBT. Further study of this novel complication as well as counseling of patients after CBT would be important.     

The HAV pattern in pediatric patients with atrioventricular node reentrant tachycardia

ObjectivesThe purpose of this study is to assess the prevalence of a His-Atrial-Ventricular (HAV) pattern, i.e. the atrial electrogram following the His bundle -HB- electrogram and preceding the ventricular one, on the catheter placed in the His position in pediatric patients during typical atrioventricular node reentry (AVNRT).Materials and methodsThe pediatric electrophysiology databases of two separate institutions were queried for patients with a diagnosis of AVNRT. Demographic, clinical data and the electrophysiology study (EPS) information were assessed.ResultsThirty-nine consecutive patients were included. Twenty-five were female. The average age at the time of the EPS was 12 ± 3.7 years. Induction was achieved with atrial pacing in 23, with a single atrial extra stimulus in 8 and with dual atrial extra stimuli in 8. Isoproterenol was needed to induce tachycardia in 21. Tachycardia cycle length averaged 320 ± 50 ms. An HAV pattern was present in 35 (74%) of the patients, and in 100% of the patients younger than 8.ConclusionsAn HAV pattern on the catheter placed in the His position, is common in pediatric patients with AVNRT, occurring in up to 74% of the patients in this population, being more common in younger patients.     

A retrospective analysis of health care utilization for patients with mitochondrial disease in the United States: 2008–2015

Background

Oral cholic acid (CA) replacement has been shown to be an effective therapy in children with primary bile acid synthesis defects, which are rare and severe genetic liver diseases. To date there has been no report of the effects of this therapy in children reaching adulthood. The aim of the study was to evaluate the long-term effectiveness and safety of CA therapy.

Methods

Fifteen patients with either 3β-hydroxy-Δ⁵-C₂₇-steroid oxidoreductase (3β-HSD) (n = 13) or Δ⁴–3-oxosteroid 5β-reductase (Δ⁴–3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed prospectively.

Results

The median age at last follow-up and the median time of follow-up with treatment were 24.3 years (range: 15.3–37.2) and 21.4 years (range: 14.6–24.1), respectively. At last evaluation, physical examination findings and blood laboratory test results were normal in all patients. Liver sonograms were normal in most patients. Mean daily CA dose was 6.9 mg/kg of body weight. Mass spectrometry analysis of urine showed that excretion of the atypical metabolites remained low or traces in amount with CA therapy. Liver fibrosis scored in liver biopsies or assessed by elastography in 14 patients, after 10 to 24 years with CA therapy, showed a marked improvement with disappearance of cirrhosis (median score < F1; range: F0-F2). CA was well tolerated in all patients, including five women having 10 uneventful pregnancies during treatment.

Conclusions

Oral CA therapy is a safe and effective long-term treatment of 3β-HSD and Δ⁴–3-oxo-R deficiencies and allows affected children to reach adulthood in good health condition without the need for a liver transplantation.

     

Depletion of T-cell receptor alpha/beta and CD19 positive cells from apheresis products with the CliniMACS device

Background aimsThe CliniMACS device (Miltenyi Biotec, Bergisch Gladbach, Germany) was used for depletion of T-cell receptor alpha/beta positive (TCRαβ⁺) and CD19 positive (CD19⁺) cells from apheresis products.MethodsInvestigators performed 102 separations. Apheresis products with a median 5.8 (minimum to maximum, 1.2–10.4) × 10¹⁰ mononuclear cells were used with a median 358 (92–1432) × 10⁶ CD34⁺ cells. There were 24.8% (6.1–45.7%) median TCRαβ⁺ cells and 4.4% (1.2–11.7%) median B cells in the apheresis product.ResultsAfter depletion, a median 0.00097% (0.00025–0.0048%) of TCRαβ⁺ cells could be detected, and B cells, as determined as CD20⁺ cells, were reduced to 0.0072% (0.0008–0.072%). TCRαβ⁺ cells were depleted by log 4.7 (3.8–5.5), and B cells were depleted by log 4.1 (3.0–4.7). Recovery of mononuclear cells was 55% (33–77%), and recovery of CD34⁺ cells was 73% (43–98%). Recovery of CD56⁺/3^? natural killer cells was 80% (35–142%), recovery of TCR gamma/delta positive (TCRγδ⁺) T cells was 83% (39–173%) and recovery of CD14⁺ cells was 79% (22–141%). Viability of cells was 98% (93–99%) after separation (all values median).ConclusionsProfound depletion of TCRαβ⁺ T cells can be achieved with the CliniMACS system. Recovery of CD34⁺ stem cells is in the same range than after CD34⁺ enrichment and CD3/CD19 depletion. Transplantation with >4 × 10⁶ CD34⁺ cells/kg can be performed for every patient with 1–5 × 10⁴ TCRαβ⁺ cells/kg and about 5–10 × 10⁶ TCRγδ⁺ cells/kg with two rounds of apheresis.     

Infusion of haploidentical hematopoietic stem cells combined with mesenchymal stem cells for treatment of severe aplastic anemia in adult patients yields curative effects

Background aimsDespite the great advances in immunosuppressive therapy for severe aplastic anemia (SAA), most patients are not completely cured. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been recommended as an alternative treatment in adult SAA patients. However, haplo-HSCT presents a higher incidence of graft failure and graft-versus-host disease (GVHD). The authors designed a combination of haplo-HSCT and umbilical cord-derived mesenchymal stem cells (UC-MSCs) for treatment of SAA in adult patients and evaluated its effects.MethodsAdult patients (≥18 years) with SAA (N = 25) were given HLA-haploidentical hematopoietic stem cells (HSCs) combined with UC-MSCs after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin and intensive GVHD prophylaxis, including cyclosporine, basiliximab, mycophenolate mofetil and short-term methotrexate. Additionally, the effects of the protocol in adult SSA patients were compared with those observed in juvenile SAA patients (N = 75).ResultsAll patients achieved myeloid engraftment after haplo-HSCT at a median of 16.12 days (range, 11–26). The median time of platelet engraftment was 28.30 days (range, 13–143). The cumulative incidence of grade II acute GVHD (aGVHD) at day +100 was 32.00 ± 0.91%. No one had grade III–IV aGVHD at day +100. The cumulative incidence of total chronic GVHD was 28.00 ± 0.85%. The overall survival was 71.78 ± 9.05% at a median follow-up of 42.08 months (range, 2.67–104). Promisingly, the protocol yielded a similar curative effect in both young and adult SAA patients.ConclusionsThe authors’ data suggest that co-transplantation of HLA-haploidentical HSCs and UC-MSCs may provide an effective and safe treatment for adult SAA.