Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multicenter registry-"MYKKE".

BACKGROUND: Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. METHODS: Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. RESULTS: From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102). CONCLUSIONS: Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Twelve Years of Complete Atrioventricular Septal Defect Repair.

BACKGROUND: Surgical repair is the standard treatment for complete atrioventricular septal defect. At our institution, this repair is performed by single patch, modified single patch or two patch techniques, according to the surgeon preferences and the surgical anatomy of the defect. The goal of this study was to evaluate our results from the last twelve years. METHODS: From June 2006 to June 2018, 81 children with complete atrioventricular septal defect (without tetralogy of Fallot or unbalanced ventricles) were submitted to surgical repair at our institution. Data from all patients was retrospectively collected and evaluated. RESULTS: The average age was 6.9 ± 13.7 months and 84% had Down syndrome. Eighty percent were symptomatic and 6 patients were previously submitted to pulmonary artery banding. No more that mild left atrioventricular valve insufficiency was found in 84% and 89% of the patients, at discharge and follow-up, respectively. Small residual septal defects were present in 27% at discharge; during follow-up, 41% of these closed spontaneously. Pulmonary hypertension at discharge and follow-up appeared in 3.7% and 1.3%, respectively. Permanente pacemaker was implanted in 3 patients. Left ventricle outflow tract obstruction was found in 3 patients and 2 needed surgical correction. At follow-up (40 ± 38 months), 90% of the patients presented NYHA functional class I. No significant differences in the main repair outcomes were found between techniques, with the exception of small residual septal defects, although the groups were unmatched. CONCLUSIONS: Overall and regardless of the technique used for the repair of complete AVSD, good early and midterm outcomes were achieved.

Mitochondrial DNA mutation "m.3243A>G"-Heterogeneous clinical picture for cardiologists ("m.3243A>G": A phenotypic chameleon).

OBJECTIVE: In general, a mitochondrial disorder is diagnosed on the basis of symptom combinations and confirmed by genetic findings. However, patients carrying the m.3243A>G mutation in the mitochondrial tRNA leucine 1 (MT-TL1) do not always meet all the proposed criteria for the most frequently encountered mitochondrial syndrome "MELAS," an acronym for Mitochondrial Encephalomyopathy, Lactic Acidosis, and at least one Stroke-like episode. We here present various phenotypic characteristics of the mitochondrial mutation m.3243A>G with particular focus on cardiac manifestations. METHODS AND RESULTS: We followed nine patients (1 month to 68 years old; median 42 years; four female and five male) from nine different families with this m.3243A>G mutation in the MT-TL1. The classical "MELAS" criteria are met by only three of these patients. Electrocardiography (ECG) shows preexcitation pattern with short PR intervals and delta waves (Wolff-Parkinson-White) in three patients and sick sinus syndrome plus atrioventricular block I in one patient. Hypertrophic cardiomyopathy was found in eight patients with moderate to severe regurgitation of various valves. CONCLUSION: Cardiac manifestation can encompass hypertrophic or dilated cardiomyopathy, as well as preexcitation syndromes or conduction delay. In general, the clinical presentation to meet the "MELAS" criteria varies due to heteroplasmy. Thus, cardiologists should screen patients with unexplained cardiac features in the context of deafness, short stature and learning disabilities for mtDNA mutations, especially the m.3243A>G mutation. A clear diagnosis is essential as a basis for prognostic advice concerning the disease course and clinical impact on family testing.

Functional Recovery of a Human Neonatal Heart After Severe Myocardial Infarction.

RATIONALE: Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, cardiac regeneration has been demonstrated in fish and newborn mice after apex resection or cardiac infarctions. Two key issues remain to translate findings in model organisms to future therapies in humans: what is the mechanism and can cardiac regeneration indeed occur in newborn humans? OBJECTIVE: To assess whether human neonatal hearts can functionally recover after myocardial infarction. METHODS AND RESULTS: Here, we report the case of a newborn child having a severe myocardial infarction due to coronary artery occlusion. The child developed massive cardiac damage as defined by serum markers for cardiomyocyte cell death, electrocardiograms, echocardiography, and cardiac angiography. Remarkably, within weeks after the initial ischemic insult, we observed functional cardiac recovery, which translated into long-term normal heart function. CONCLUSIONS: These data indicate that, similar to neonatal rodents, newborn humans might have the intrinsic capacity to repair myocardial damage and completely recover cardiac function.

Elevated heart rate triggers action potential alternans and sudden death. translational study of a homozygous KCNH2 mutation.

BACKGROUND: Long QT syndrome (LQTS) leads to arrhythmic events and increased risk for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness. METHODS AND RESULTS: Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q) in the index patient (QTc ∼506 ms with notched T waves). Parents were I° cousins - both heterozygous for the mutation and clinically unremarkable (QTc ∼447 ms, father and ∼396 ms, mother). Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD) compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q. CONCLUSION: Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates.

Heart Transplantation in a 14-Year-Old Boy in the Presence of Severe Out-of-Proportion Pulmonary Hypertension due to Restrictive Left Heart Disease: A Case Report.

A 14-year-old boy after balloon valvuloplasty of severe aortic valve stenosis in the neonatal period was referred for heart-lung transplantation because of high grade pulmonary hypertension and left heart dysfunction due to endocardial fibroelastosis with severe mitral insufficiency. After heart catheterization, hemodynamic parameters were invasively monitored: a course of levosimendan and initiation of diuretics led to a decrease of pulmonary capillary wedge pressure (from maximum 35 to 24 mmHg). Instead of an expected decrease, mean pulmonary artery pressures (mPAP) increased up to 80 mmHg with increasing transpulmonary pressure gradient (TPG) up to 55 mmHg. Oral bosentan and intravenous epoprostenol then led to a ~50% decrease of mPAP (TPG between 16 and 22 mmHg). The boy was listed solely for heart transplantation which was successfully accomplished 1 month later.

How mechanical circulatory support helps not to need it--new strategies in pediatric heart failure.

During the past 3 years, seven potential candidates for mechanical circulatory support (MCS) were treated at our center. Ultimately, only one of them needed MCS (extracorporeal membrane oxygenation [ECMO] for 16 days), although 5 years earlier, all would have been considered for MCS at our center. Seven consecutive patients were seen in this period: four toddlers (three suffering from fulminant myocarditis and one with dilated cardiomyopathy associated with spongy myocardium) and three adolescents (two with postmyocarditis cardiomyopathy and one with hypertrophic cardiomyopathy and severe restrictive dysfunction after an ischemic event with cardiopulmonary resuscitation [stunned heart]). All patients presented in acute cardiocirculatory decompensation. All were admitted to the intensive care unit (ICU); all but one were sedated and intubated. A combination of levosimendan, milrinone, and nesiritide was administered to all patients. Use of catecholamines was kept short (<48 h in six individuals). MCS (ECMO, Berlin Heart Excor Pediatric, and Heartware) was always available. MCS initiation was indicated in only one patient, who was developing progressive multiorgan failure (MOF). The three toddlers with myocarditis recovered with complete normalization of myocardial function within 6 months. The fourth toddler is still at the ICU while waiting for transplantation. The three adolescents were listed with high urgency for heart transplantation, and all received a graft within 3 weeks. The adolescent with the stunned heart developed progressive MOF and was successfully supported with ECMO until transplantation. All six patients with completed course were discharged home in New York Heart Association Heart Failure Functional Classification System I condition without neurological deficits. Combined use of levosimendan, milrinone, and nesiritide, avoidance of catecholamines as much as possible, and MCS as backup are the new strategies at our center. This cardioprotective approach gives excellent outcome at lower risk and better cost-effectiveness in our pediatric patients with acute heart failure. Pediatric trials are recommended to evaluate combined use of newer cardioprotective drugs.

Thymectomy in early childhood: significant alterations of the CD4(+)CD45RA(+)CD62L(+) T cell compartment in later life.

The study was aimed to assess indicators of immunosenescence, such as the total counts of peripheral blood CD4(+)CD45RA(+)CD62L(+) (naive) T cells, the numbers of T cell receptor excision circles (TRECs), and Ki67-expression as marker of peripheral replication in thymectomized patients (TP) (n=101) compared to age-matched healthy donors (HD) (n=81). In TP, there was an inverse correlation between naive T cells and chronological age (p<0.001) or time post thymectomy (p<0.001). TP demonstrated lower TREC numbers in naive T cells compared to HD (p<0.001). TREC numbers negatively correlated with time post thymectomy (p<0.001). Percentages of Ki67-expresssing naive T cells were higher in TP compared to HD (p<0.05). The findings of the presented long-term follow up cohort of thymectomized patients indicate that changes of the peripheral naive T cell subset in TP may resemble the findings of an aging immune system in elderly persons after thymic involution. Our data provide evidence that peripheral T cell homeostasis in TP is maintained at minimal levels mainly by extrathymic expansion of existing naive T cells in the periphery to compensate the diminished thymic output.

Prolonged but successful weaning from left ventricular assist device after cardiac decompensation due to late-recognized coarctation of the aorta in a toddler.

A 2-year-old boy was presented with late-recognized coarctation of the aorta and pulmonary hypertension due to left ventricular failure. The coarctation was corrected at the day of admission with a good postoperative result. However, weaning from the respirator failed despite multiple drug support due to left ventricular failure. Consequently, a left ventricular assist device (LVAD) was implanted 22 days later. The further course was complicated by systemic hypertension and ongoing pulmonary hypertension requiring extensive antihypertensive therapy. The first attempt to wean from LVAD failed and the left ventricle was left completely unloaded for additional 4 weeks. The second weaning attempt, using a very smooth weaning protocol, led to a recovered left ventricle and facilitated the removal of the assist device after a total of 120 days. The patient was discharged with normal cardiac function, but he still requires antihypertensive therapy. We believe that the slow reduction of the LVAD support was the key measure that leads to the successful weaning of the patient, thereby avoiding heart transplantation.

Acute lung failure during mechanical circulatory support.

The use of venoarterial extracorporal membrane oxygenation and ventricular assist-devices in children with end stage heart failure is well established. The use of a bridge-to-bridge strategy leads to excellent survival rates in pediatric patients. We present an adolescent, who acquired acute respiratory failure, due to possible transfusion related lung injury, and who was successfully treated with venovenous extracorporal membrane oxygenation while on ventricular assist-device support.

The pediatric mechanical circulatory support program in Innsbruck, Austria, and the impact of such programs on lack of donor hearts in Europe.

Strategy and results of the Innsbruck Mechanical Circulatory Support Program are presented, and the impact of such programs on pediatric heart transplantation (HTX) in Europe is discussed. Venoarterial extracorporeal membrane oxygenation (vaECMO) and ventricular assist devices (VADs) were used in 21 pediatric patients (median age 3.3 years, 2 days to 17 years) for acute heart failure (AHF) following a bridge or bridge-to-bridge strategy. Twelve patients were treated with vaECMO: eight were weaned after 2-10 days, two died, and two were switched to a VAD. Of the last, one was weaned 47 days later and the other underwent HTX 168 days later. In nine patients, VAD was implanted without preceding vaECMO. One such patient died (cerebral hemorrhage) after 236 days; of the remaining eight patients three were weaned and five underwent HTX. Waiting time for HTX (high-urgency status) varied from 4 to 372 days. Fifteen patients were discharged (follow up: 2-74 months); 14 are doing very well (New York Heart Association (NYHA) Functional Classification Class I, neurologically normal), whereas one suffers from severe neurologic damage, presumably from resuscitation before vaECMO. Data from Eurotransplant on pediatric HTX in 2004, 2005, and 2006 (33, 49, and 34 transplanted hearts, respectively; recipients <16 years of age) are discussed. Mechanical circulatory support (MCS) substantially improves survival with AHF in pediatric patients. Medium-term support (up to 400 days in our patients) is possible and outcome of survivors is excellent. Wide spread use of MCS might slightly aggravate the lack of donor organs, which could result in longer support times.

NT-proBNP concentrations indicate cardiac disease in pediatric patients.

OBJECTIVE: To test the performance of N-terminal pro B-type natriuretic peptide to distinguish from cardiac and non-cardiac disease in the pediatric patient population. METHOD: NT-proBNP concentrations were retrospectively analysed in 102 pediatric patients (median age: 5.96 years; 0-18 years) with cardiac diseases comprising left-to-right-shunt lesions (n=42), left heart lesions (n=47) and right heart lesions (n=13) and in 65 pediatric patients (median age: 3.37 years; 0.03-18 years) with acute infection, minor trauma or neurological disorder. RESULTS: NT-proBNP levels between patients without heart disease and patients with heart disease differed significantly with a median NT-proBNP value of 224.9 ng/l, 108.7 ng/l-945.6 ng/l (25th-75th percentile) versus 76.7 ng/l, 35.0 ng/l-122.4 ng/l, p<0.0001. The diagnostic performance of NT-proBNP to differentiate between patients with and without cardiac diseases was high with an area under curve of 0.81 (95% confidence intervals 0.75-0.87). At a cut-off value of 134 ng/l the specificity was 83% (95% CI: 74-92%). The presence of heart failure (p<0.0001) had a significant impact on NT-proBNP concentrations. CONCLUSIONS: NT-proBNP measurement is a helpful addition to identify pediatric patients with heart disease.

Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia.

OBJECTIVE: To investigate electrophysiological and functional signs of myocardial damage in patients with propionic acidemia (PA), an inborn error of metabolism caused by deficiency of propionyl CoA carboxylase (PCC). STUDY DESIGN: In an observational longitudinal study 10 patients with PA (6 boys and 4 girls) ranging between 2.5 and 20.2 (median 9.0) years of age at last follow-up were investigated over a period of up to 20 (mean 7.4) years using 12-lead electrocardiograms (ECGs), 24-hour continuous ECG recordings, bicycle exercise testings, and echocardiography with special focus on repolarization abnormalities such as corrected QT interval (QTc) prolongation, ventricular dysrhythmias, and left ventricular systolic function. RESULTS: QTc interval was prolonged (>440 ms) in 70% of patients beyond infanthood. Continuous ECG recordings revealed rhythm disturbances in 20% of patients. M-mode echocardiographic left ventricular function was reduced (fractional shortening [FS] <30%) in 40%. One patient showed signs of dilated cardiomyopathy. CONCLUSIONS: The majority of patients with PA (even in clinically stable situations) have disturbances in cardiac electrophysiology that can contribute to cardiac complications. Possible mechanisms include effects of toxic metabolites or deprivation of essential substrates. To avoid life-threatening complications, we recommend regular cardiological evaluations in this group of patients.

Interventional and medical treatment of acute heart failure due to inflammation: four cases.

Four patients (aged 15-41 years, mean age 26.7 years) with fulminant myocarditis undergoing mechanical circulatory support are reported. All patients suffered from acute low-output syndrome refractory to inotropic support. Diagnosis was confirmed by histology and immunohistochemistry. RT-PCR (reverse transcription-polymerase chain reaction) from endomyocardial biopsy specimens revealed parvovirus B19 in two patients and a coinfection with Chlamydia pneumoniae and parvovirus B19 in one patient. Midterm support with the biventricular Thoratec system was preceded by implantation of an extracorporeal membrane oxygenation (ECMO) device in two patients. Two patients regained full cardiac function and were successfully weaned from the ventricular assist device (VAD) after 12 and 40 days. Heart transplantation was performed in another patient without evidence of myocardial recovery after 53 days. One patient died of cerebral hemorrhage on day 12 after VAD implantation. In summary, patients with life-threatening fulminant myocarditis can be successfully bridged to recovery or transplantation with mechanical circulatory support.

Different patterns of aortic wall elasticity in patients with Marfan syndrome: a noninvasive follow-up study.

OBJECTIVE: Aortic complications determine the life expectancy of most patients with Marfan syndrome. To find out whether there is heterogenous aortic involvement among patients and, if there is, to characterize aortic patterns and response to long-term beta-blocker therapy, we investigated aortic elastic properties before and during beta-blocker treatment. METHODS: In 46 patients with Marfan syndrome (age, 17.4 +/- 11.1 years) and 46 healthy control subjects, ascending and descending aortic elastic parameters were determined noninvasively before and after 39 +/- 16 months of beta-blocker treatment with atenolol. RESULTS: Aortic diameters and distensibility distinguished Marfan patients and controls with a sensitivity of 85% and a specificity of 87%. Cluster analysis revealed 4 patterns of aortic phenotypic expression: (1) reduced ascending aortic elasticity (46% of patients), (2) diminished ascending and descending aortic elasticity (17%), (3) minimal alterations of ascending and descending aortic elasticity (20%), and (4) reduced descending aortic elasticity (17%). During follow-up, aortic elastic properties improved in 21 (70%) of 30 patients and deteriorated in 9 (30%) irrespective of beta-blocker dosage. Improvement was observed in 100% of patients (n = 7; age, 5.3 +/- 4.2 years) with end-diastolic aortic root diameters between 20 and 30 mm and in 61% of patients (14/23; age, 20.5 +/- 10.0 years) with root diameters between 30 and 52 mm. CONCLUSIONS: Aortic elastic parameters distinguish between patients with Marfan syndrome and healthy controls and show the pattern of regional aortic involvement. Improvement or deterioration during follow-up can influence therapeutic decisions to prevent aortic dissection and rupture. Young age, small root diameter, and high distensibility are favorable prognostic factors.

Diagnostic power of aortic elastic properties in young patients with Marfan syndrome.

BACKGROUND: In patients with Marfan syndrome, progressive aortic dilation implicates a still-unpredictable risk of life-threatening aortic dissection and rupture. We sought to quantify aortic wall dysfunction noninvasively, determine the diagnostic power of various aortic parameters, and establish a diagnostic model for the early detection of aortic abnormalities associated with Marfan syndrome. METHODS: In 19 patients with Marfan syndrome (age, 17.7 +/- 9.5 years) and 19 age- and sex-matched healthy control subjects, computerized ascending and abdominal aortic wall contour analysis with continuous determination of aortic diameters was performed out of transthoracic M-mode echocardiographic tracings. After simultaneous oscillometric blood pressure measurement, aortic elastic properties were determined automatically. RESULTS: The following ascending aortic elastic parameters showed statistically significant differences between the Marfan group and the control group: (1) decreased aortic distensibility ( P < .001), (2) increased wall stiffness index ( P < .01), (3) decreased systolic diameter increase ( P < .01), and (4) decreased maximum systolic area increase ( P < .001). The diagnostic power of all investigated parameters was tested by single logistic regression models. A multiple logistic regression model including solely aortic parameters yielded a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: In young patients with Marfan syndrome, a computerized image-analyzing technique revealed decreased aortic elastic properties expressed by parameters showing high diagnostic power. A multiple logistic regression model including merely aortic parameters can serve as useful predictor for Marfan syndrome.

High prevalence and morbidity of Schistosoma mansoni along the Albert Nile in Uganda.

An epidemiological cross sectional study of Schistosoma mansoni was conducted in two hyper endemic fishing villages of Rhino Camp and Obongi both in West Nile district in northern Uganda in 1991 and 1992. People with various water contacts were registered. A small group of civil servants and clergies with less water contact in the river Nile were studied for control of infection and morbidity. An overall prevalence of 81.5% of the 1367 people studied in both fishing villages of Rhino Camp and Obongi were excreting from 100 to > or = 500 Schistosoma mansoni eggs per gram (epg). 253 18.5% did not have Schistosoma mansoni eggs in their faeces. The influence of socioeconomic factors on infections in the study population was high among poorer illiterates who have frequent water contacts activities with River Nile. The sonomorphological abnormalities of periportal thickening (PT) due to Schistosoma mansoni were performed using ultrasound. 664 patients were found to have various stages of (PT stages 0, I, II and III). A total of 703 (51.4%) patients did not have any periportal thickening (PT 0) in their livers despite the fact that 450 (32.9%) of them had Schistosoma. mansoni eggs in their faeces. The gravities of schistosomiasis in the two villages were similar showing greater morbidity in the younger adults.