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Biomedical subjects

R Brunkhorst

Publications and source records attributed to R Brunkhorst.

At least 19 recordsLinked to original sources

Cardiovascular morbidity and mortality in patients with diabetes mellitus type I after kidney transplantation: a case-control study.

BACKGROUND: The proportion of diabetics among patients requiring renal replacement therapy continues to increase in most western countries. The acceptance rate for renal transplantation varies among transplant centers and is influenced by the current opinion on the outcome of transplantation in diabetics. Controlled data on patient and graft survival in type I diabetics, however, are scarce. METHODS: We performed a retrospective case-control analysis on patient and graft survival and the cardiovascular morbidity of patients with type I diabetes after renal transplantation versus carefully matched non-diabetic transplant recipients. Match criteria were duration of previous hemodialysis, age and date of renal transplantation. Moreover, risk factors for cardiovascular disease in uremic patients were evaluated at the time of registration for renal transplantation and at the end of the observation period. RESULTS: Seventy-seven matched pairs were enclosed. Patient survival was significantly worse in the diabetic patients, graft survival was comparable in both groups, when graft loss because of patient's death was censored. In the diabetic patients, risk of death (odds ratio: 4.38) as well as the prevalence of cardiovascular morbidity (odds ratio: 4.47) were significantly higher than in the matched nondiabetic controls. Cox regression analysis showed that diabetes mellitus was an independent risk factor for patient survival; no association was found with hypertension, hyperlipidemia, hyperparathyroidism, calcium x phosphate product, body mass index and HbA1c. Cardiovascular morbidity, however, was already significantly higher in the diabetic group at the time of registration. CONCLUSIONS: Diabetes mellitus type I has a dominant impact on morbidity and mortality after renal transplantation and is associated with an approximately 4-fold higher risk of death. Cardiovascular disease accounts for the significantly worse long-term outcome of diabetic patients after renal transplantation.

Adult↗

Long-term comparison of a calcium-free phosphate binder and calcium carbonate--phosphorus metabolism and cardiovascular calcification.

BACKGROUND: Calcium carbonate used as a phosphate binder may contribute to cardiovascular calcification. Long-term comparisons of sevelamer, a non-calcium polymeric phosphate binder, and calcium carbonate (CC) are lacking. METHODS: 114 adult hemodialysis patients were randomly assigned to open label sevelamer or CC for 52 weeks. Study efficacy endpoints included changes in serum phosphorus, calcium, calcium-phosphorus product, and lipids. In addition, initial and sequential electron beam computerized tomography scans were performed to assess cardiovascular calcification status and change during follow-up. Safety endpoints were serum biochemistry, blood cell counts and adverse events. RESULTS: Patients receiving sevelamer had a similar reduction in serum phosphorus as patients receiving CC (sevelamer -0.58 +/- 0.68 mmol/l, CC -0.52 +/- 0.50 mmol/l; p = 0.62). Reductions in calcium-phosphorus product were not significantly different (sevelamer -1.4 +/- 1.7 mmol2/l2, CC -0.9 +/- 1.2 mmol2/l2; p = 0.12). CC produced significantly more hypercalcemia (> 2.8 mmol/l in 0% sevelamer and 19% CC patients, p < 0.01) and suppressed intact parathyroid hormone below 150 pg/ml in the majority of patients. Sevelamer patients experienced significant (p < 0.01) reductions in total (-1.2 +/- 0.9 mmol/l, -24%) and LDL cholesterol (-1.2 +/- 0.9 mmol/l, -30%). CC patients had significant increases in coronary artery (median +34%, p < 0.01) and aortic calcification (median +32%, p < 0.01) that were not observed in sevelamer-treated patients. Patients on sevelamer required more grams of binder (sevelamer 5.9 g vs. CC 3.9 g) and experienced more dyspepsia than patients on calcium carbonate. CONCLUSIONS: Sevelamer is an effective phosphate binder that unlike calcium carbonate is not associated with progressive cardiovascular calcification in hemodialysis patients.

Adult↗

Endothelial tissue factor stimulation by proteinase 3 and elastase.

In ANCA-associated vasculitis the activation of primed leucocytes by autoantibodies with subsequent release of proteases such as myeloperoxidase (MPO), proteinase 3 (PR3) and elastase is thought to play an important pathogenetic role. Whether these proteases contribute to the vascular lesions by stimulating the procoagulant activity of these cells is unknown. Tissue factor (TF) expression and activity were investigated in human umbilical vein endothelial cells after stimulation with MPO, PR3 and elastase. TF activity was measured using a one-stage clotting assay. Polyclonal antibodies to TF were used to prove specificity. TF mRNA was detected by reverse transcriptase-polymerase chain reaction. PR3 and elastase led to a significant increase in TF mRNA expression and increased activity. The stimulation was not mediated by IL-1. The stimulatory effect of PR3 did not depend on its proteolytic activity (no inhibition by alpha-1-antitrypsin), whereas the effect of elastase was blocked by alpha-1-antitrypsin. MPO had no effect on TF activity. These results show that PR3 and elastase stimulate TF expression in human endothelial cells. In ANCA-associated vasculitis the increased release of proteases may contribute to the development of microthrombi and consecutive necrosis.

Antibodies, Antineutrophil Cytoplasmic↗

C-reactive protein and chronic Chlamydia pneumoniae infection--long-term predictors for cardiovascular disease and survival in patients on peritoneal dialysis.

BACKGROUND: Accelerated arteriosclerosis with cardiovascular disease is the main cause of death in end-stage renal disease patients. Increased, levels of C-reactive protein (CRP) and evidence of chronic Chlamydia pneumoniae infection have been identified as risk factors for cardiovascular disease in the general population. We tested the hypothesis that elevation of CRP, indicating chronic inflammation, and positive serum antibody titres for C. pneumoniae are associated with an increased cardiovascular mortality in patients on chronic peritoneal dialysis. METHODS: We measured CRP and antibodies to C. pneumoniae in 34 patients on peritoneal dialysis. CRP was measured by a sensitive ELISA and C. pneumoniae antibodies by microimmunofluorescence. In addition, risk factors such as lipids, smoking status and hypertension were assessed. Coronary artery disease (CAD) was defined by cardiac stress testing and/or angiography. Patients showing clinical evidence of systemic or peritoneal dialysis-associated infection during the investigation period of 6 months (between 1990 and 1991) were excluded. RESULTS: The incidence of CAD was significantly increased in patients with CRP values >1.5 mg/l (odds ratio 7.0, P<0.022) during 72 months of follow-up. In addition, in patients seropositive for IgA C. pneumoniae antibodies, the incidence of CAD was significantly increased (odds ratio 7.2, P<0.014). These findings resulted in an increased risk of death in patients with mean CRP values >1.5 mg/l at the start of the study (odds ratio 20.0, P<0.001). Furthermore, in patients seropositive for IgA C. pneumoniae antibodies, the risk of death (odds ratio 10.2, P<0.005) was significantly increased. There was a highly significant correlation between CRP and seropositivity for IgA C. pneumoniae antibodies (r=0.445, P<0.01). CONCLUSIONS: Increased circulating CRP and seropositivity for C. pneumoniae in patients on chronic peritoneal dialysis are associated with reduced survival due to cardiovascular complications. CRP and C. pneumoniae antibodies may indicate a chronic inflammatory process as an underlying cause and/or result of arteriosclerosis.

Adult↗

Renal transplantation in older adults: is graft survival affected by age? A case control study.

BACKGROUND: The demand for kidney allografts in older patients is growing continually. Previously published data indicate that the higher rate of graft losses resulting from the age-related increased mortality in older transplant recipients is balanced by a significantly lower number of graft losses from immunological problems (acute and chronic rejection) in old patients. This single center study was performed to scrutinize these results with the methods of a case control analysis. METHODS: Ninety-one patients, 65 years and older (mean age 67), were included in the case group. Their data were compared with those obtained from two control groups, 40-55 and 18-35 years old, respectively (mean ages 48 and 29, respectively). Apart from age, the groups were matched with regard to HLA-mismatches and date of transplantation. RESULTS: The number of initially non-functioning grafts and donor age did not differ significantly between the case and the control groups. During the follow-up of 5 years, acute rejections were significantly more frequent in the older control group. In contrast to previous studies, however, graft losses caused by rejections were not significantly more frequent in younger patients than in transplant recipients over age 65 years. Thus, as a consequence of increased patient mortality, the total graft survival in the case group was significantly worse than in the control groups. CONCLUSIONS: In the presence of organ shortage, an indication for kidney transplantation in patients over 65 years has to be considered carefully because age did not prove to have a beneficial effect on graft survival. Nevertheless, patients of this age group should not be excluded from renal transplantation, because not only medical, but also ethical, issues are involved.

Acute Disease↗

Native pyeloureterostomy after kidney transplantation: experience in 48 cases.

Necrosis and stenosis of the ureter are severe complications after kidney transplantation and occur with mean incidence of 2,9-13,4 %. Several surgical techniques like simple nephrostomy or complex urinary tract reconstruction have been applied for repair. In this study, our experience with native pyeloureterostomy (NPUS) using the native ureter is presented. Between March 1978 and June 1996, 2,592 kidney transplantations were performed in our institution. In 48 patients (1,9%), secondary urinary tract reconstruction by NPUS was necessary. These patients were evaluated retrospectively by review of the case notes. At the time of operation the mean age was 45 +/- 14 years. Indications for NPUS were distal ureteral stenosis (n = 29), necrosis (n = 17), bleeding (n = 1) or iatrogenic lesion of the ureter (n = 1). The mean time period between transplantation and urinary tract reconstruction was 20 +/- 23 days (range: 1-90 days) for necrosis and 404 +/- 637 days (range: 14-2,385 days) for stenosis. A pyeloureterostomy was technically feasible in all patients using the recipient's ipsilateral ureter. In 40 out of 48 patients the graft developed a normal function postoperatively (follow up: 39 +/- 48 months). A graft nephrectomy was necessary only in one patient, because of complete pyelonnecrosis 6 days after NPUS. Two grafts were lost due to acute rejection. Data of five patients were not available > 15 years after successful reconstruction. We can conclude that NPUS is a safe and simple rescue technique for the treatment of distal ureteral complications after kidney transplantation. Therefore, this technique should be the therapy of choice when secondary reconstruction by re-ureteroneocystostomy is not possible.

Female↗

Extended daily veno-venous high-flux haemodialysis in patients with acute renal failure and multiple organ dysfunction syndrome using a single path batch dialysis system.

BACKGROUND: In the treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT) are increasingly used because of excellent volume control in the presence of improved cardiovascular stability. Patients with MODS, however, are frequently catabolic and have a high urea generation rate requiring either cost-intensive high-volume CRRT or additional intermittent haemodialysis to provide adequate clearance of small-molecular waste products. We tested the closed-loop batch haemodialysis system (called Genius((R))) for the treatment of acute renal failure in patients with MODS in the intensive care unit. METHODS: Blood flow and countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate tank of the Genius((R)) system lasts for 18 h of extended single-path high-flux haemodialysis (18 h-HFD) using polysulphous F60 S((R)) dialysers. Blood pressure, body temperature, and venous blood temperature in the extracorporeal circuit (no heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea clearance, and total urea removal were monitored. In addition we tested the bacteriological quality of the spent dialysate at the end of 18-h treatments. RESULTS: Twenty patients with acute renal failure and MODS were investigated. Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8 l/day). Total removal of urea was 14.1+/-6.5 g/day keeping serum levels of urea below 13 mmol/l. Mean arterial pressure remained stable during the 18-h treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the venous blood tubing dropped by 5+/-0.5 degrees C during the 18-h treatment (0.28 degrees C/h) in the presence of unchanged core temperature in the patients. There was no bacterial growth in 2.5 l of spent dialysate (<0.0004 colony forming units/ml). CONCLUSIONS: Extended high-flux dialysis using the Genius((R)) system combines the benefits of CRRT (good cardiovascular stability, sterile dialysate) with the advantages of intermittent dialysis (high urea clearance, low treatment costs). High efficiency, simplicity and flexibility of the system offers the unique opportunity to use the same dialysis machine for extended time periods (18 h) as well as for shorter intermittent renal replacement therapy in critically ill patients.

Acute Kidney Injury↗

Detection of significant renal artery stenosis with color Doppler sonography: combining extrarenal and intrarenal approaches to minimize technical failure.

BACKGROUND: Renal artery disease can cause both hypertension and renal failure, and color Doppler sonography (CDS) may be a good screening method to detect it. Presently reported techniques of Doppler sonography have either a high rate of technical failure (4-42%), or low sensitivity and specificity, or detect only stenoses greater than 70%, or exclude patients with renal failure from analysis. In previous studies Doppler detection of renal artery stenosis (RAS) was based either on increased intrastenotic velocity or on the detection of post-stenotic Doppler phenomena. In the present prospective study these two approaches were combined to detect RAS (> or = 50% diameter reduction) in 226 consecutive patients (144 with normal and 82 with impaired renal function). METHODS: Stenosis of 50% or more was diagnosed if the maximal systolic velocity in the main renal artery was more than 180 cm/sec and velocity in the distal renal artery less than one quarter of the maximum velocity. When these velocities could not be determined a diagnosis of RAS was made when the acceleration time in intrarenal segmental arteries exceeded 70 msec. All patients subsequently underwent arteriography as the gold standard for the detection of RAS. RESULTS: With this combined approach, the technical failure rate of CDS was 0% in both patients with normal and those with impaired renal function. The mean time required for the Doppler investigation was 17 minutes. The sensitivity and specificity for detection of a significant stenosis in a given vessel (including accessory arteries), as compared to angiography, were 96.7% and 98.0%. CONCLUSION: Color Doppler sonography, evaluating both main renal and intrarenal arteries is an ideal screening method for detection of RAS of 50% or more because it allows accurate and rapid detection of stenosis in all patients, irrespective of renal function.

Blood Flow Velocity↗

Attitudes of patients before and after transplantation towards various allografts.

BACKGROUND: The presence of an allogeneic graft inside the body may have psychological impact on transplant patients. It was the aim of this study to evaluate the attitude of patients before and after different types of organ transplantation towards organ allografts. METHODS: A total of 1,049 patients (722 patients after and 327 patients on the waiting list for either kidney, liver, heart, or lung transplantation) under care of a single transplant center were studied using a questionnaire with blinded analysis of the data. Mental condition of the patients, their attitude towards the allograft and its donor, emotional stress caused by a graft, and correlation of the attitudes with clinical and demographic parameters were analyzed. RESULTS: The self-reported mental condition of the patients was markedly and consistently better after organ transplantation; 27% of patients before and 60% after transplantation were in good mental condition. Sixty-two percent of transplant patients considered the graft as their own organ, 37% regarded it as a foreign organ now belonging to their body, and 1% considered it as a foreign body; among waiting list patients, 40%, 55%, and 5% assumed they would perceive their graft accordingly. The graft caused considerable emotional stress for 2% of transplant patients, whereas for 70% it did not cause any stress; the latter was assumed by 47% of patients before transplantation. Eleven percent of transplant patients frequently think about the origin of their graft, and 30% would like to have information about their donor. Knowledge about different religion, opposite sex, homosexuality, suicidal death, and age above 65 years of their donor would be of moderate or major concern for 0%, 3%, 21%, 24%, and 38% of the patients, respectively. CONCLUSIONS: The comprehensive survey shows that transplant patients incorporate their graft well into their body image. Emotional stress caused by the graft is very low and is generally less than assumed before transplantation. Knowledge about certain characteristics of the donor may cause increased concerns in some patients.

Adult↗

Five cases of Kaposi's sarcoma in kidney graft recipients: possible influence of the immunosuppressive therapy.

BACKGROUND: Kaposi's sarcoma (KS) is an human herpesvirus 8-associated tumor, occurring in immunocompromised patients. We report here an increased incidence of KS among kidney graft recipients (KGRs) during the last 2 years, concomitant to the introduction of the immunosuppressant mycophenolate mofetil (MMF). METHODS: A total of 1835 KGRs, receiving organs between 1987 and 1997, were surveyed for the development of KS. A total of 371 patients received therapy including MMF (group A), whereas 1464 patients were treated with an MMF-free protocol (group B). RESULTS: 3/371 patients (0.8%) of group A versus 2/1464 patients (0.1%) of group B developed KS. In group A, KS became evident 7+/-2 months after initiation of MMF therapy. CONCLUSIONS: At our center, during the last 2 years, the incidence of KS has increased in KGRs, and it is not clear whether the introduction of MMF contributes to the phenomenon.

Drug Therapy, Combination↗

Attitude of patients toward transplantation of xenogeneic organs.

BACKGROUND: The prospect of xenotransplantation has stimulated considerable hopes as well as major concerns. The question of whether or not patients accept xenografts is influenced not only by scientific facts but also by psychological factors. It was the aim of this study to analyze the attitudes of patients toward transplantation of xenogeneic organs and evaluate factors influencing these attitudes. METHODS: To this end, attitudes toward xenogeneic compared with allogeneic organ grafts were evaluated by means of detailed questionnaires in 1049 patients in Germany, who either had received transplants (n=722) or were on the waiting list for various organ grafts (n=327). Answers were correlated to demographic data as well as to the physical and mental conditions of the patients. RESULTS: The survey indicates that 77% of patients would accept xenografts while 7% would refuse them if results of xenotransplantation were comparable with those of allotransplantation. If xenotransplantation were associated with increased risks due to more intensive medication 58% would still basically accept xenografts. Acceptance of xenografts was significantly higher in patients who had received transplants and among males. Age, religion, waiting time, and type of organ were not found to influence acceptance rates. Xenografts were thought to be associated with considerable or severe emotional stress by 23% of patients, versus 3% for allografts. The pig was the preferred donor animal, and gene therapeutic manipulation for improvement of results would be accepted by 84%. Inadequate graft function/increased risk of rejection and risk of disease transmission were the major concerns for 60% and 52% of patients, respectively; emotional concerns were the major concerns for 24% and animal-rights concerns for 15%. CONCLUSIONS: These findings show that the potential acceptance rate of xenografts would be quite high, with a more positive attitude in transplanted patients than in waiting-list patients; there was no major difference in acceptance rate for various types of organs. Major concerns about xenotransplantation currently are functional inferiority and transmission of diseases.

Adult↗

Exhaled nitric oxide in patients with Wegener's granulomatosis.

In Wegener's granulomatosis (WG), a pathogenic role of infections, in particular of a chronic colonization of the nasal mucosa with Staphylococcus aureus, has been postulated. Nitric oxide (NO), which is thought to play a role in primary host defence and inflammation, is produced endogenously within the respiratory tract, mainly from the paranasal sinuses. In order to further characterize its role in WG, nasal and pulmonary NO excretion in WG patients in comparison to healthy volunteers was measured. Seventeen patients with WG were included in the study. Five patients had active disease (bloody rhinitis with ulceration and crusting) and immunosuppressive therapy (IST), and 12 were in remission (six with, and six without, IST). S. aureus was found in the swabs of all patients with active WG and in three patients in remission. NO was measured in exhaled gas using a chemiluminescence analyser. The NO excretion rate in nasally sampled gas was significantly reduced (p<0.05) in patients with active WG ((mean+/-SD)102+/-100 nL x min(-1)) compared to healthy controls (299+/-13 nL x min(-1)), and patients in remission (281+/-86 nL x min(-1) with IST, 280+/-133 nL x min(-1) without IST). Pulmonary NO excretion in active or nonactive WG patients did not significantly differ from that of healthy volunteers (48+/-21 nL x min(-1)). These results demonstrate a reduced nasal NO excretion in active Wegener's granulomatosis. This may be caused by destruction and/or functional impairment of sinus epithelium. The reduced NO concentration may well compromise host defence in the upper airways, thus contributing to colonization with Staphylococcus aureus and further promoting Wegener's granulomatosis.

Adult↗

Discrimination of infectious and noninfectious causes of early acute respiratory distress syndrome by procalcitonin.

OBJECTIVE: To test the sepsis marker procalcitonin (PCT) for its applicability to discriminate between septic and nonseptic causes of acute respiratory distress syndrome (ARDS). DESIGN: Prospective study, assessing the course of PCT serum levels in early (within 72 hrs after onset) ARDS. The three other inflammation markers neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP) were tested in parallel. SETTING: Twenty-four-bed medical intensive care unit of a 1,990-bed primary hospital, providing health care for an estimated 39,000 patients. PATIENTS: Twenty-seven patients, 18 male and nine female, aged 16-85 yrs, with early ARDS of known cause (17 with septic and ten with nonseptic ARDS) were enrolled in a prospective study between May 1994 and May 1995. INTERVENTIONS: Serum samples were drawn every 4-6 hrs for measurement of PCT, neopterin, IL-6, and CRP concentrations. Blood cultures, tracheal aspirates, and urine samples were obtained every 12-24 hrs. In 24 of 27 patients, bronchoscopic cultures were also obtained. Clinical sepsis criteria as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were checked daily. MEASUREMENTS AND MAIN RESULTS: Assessment of inflammation marker serum levels in septic vs. nonseptic ARDS. PCT serum levels were significantly higher (p < .0005) in the patients with septic ARDS than in patients with nonseptic ARDS within 72 hrs after onset of ARDS. There was no overlap between the two groups. Also, neopterin allowed a differentiation (p < .005), although a substantial overlap between serum levels of septic and nonseptic patients was observed. No discrimination could be achieved by determination of CRP and IL-6 levels. CONCLUSION: PCT determination in early ARDS could help to discriminate between septic and nonseptic underlying disease.

APACHE↗

Short- and long-term effects of fish oil on proteinuria, morphology and renal hemodynamics in the Milan normotensive rat model of spontaneous glomerulosclerosis.

BACKGROUND/AIMS: A diet rich in polyunsaturated Omega3 fatty acids has been shown to modulate the course of several experimental models of renal disease. The short- and long-term effects of an 8% fish oil (FO) chow on proteinuria, renal blood flow and glomerular morphology were evaluated in Milan normotensive rats that spontaneously develop progressive glomerulosclerosis. METHODS: Eight rats each were pairfed FO- versus cholesterol-enriched or control diets for either 2 or 32 weeks. 4/48 animals died (2-week trial: 1 rat on the FO and 1 rat on the control diet; 32-week trial: 1 rat on the cholesterol and 1 rat on the control diet) and were excluded from all statistic analyses. RESULTS: After 2 weeks the renal blood flows were higher in the FO animals versus controls (8.75+/-2.19 vs. 6.87+/-1.91 ml/min/g, p<0.05), and the prostaglandin E2/thromboxane B2 ratio shifted towards the vasodilatative prostaglandin E2 (1. 76+/-0.18 vs. 0.91+/-0.19, p<0.05). During the long-term trial proteinuria in the FO animals progressed faster and to a higher level (176.5+/-32.2 vs. 82.7+/-36.7 mg/24 h at week 32, p<0.01). After 32 weeks the renal blood flow was significantly lower in th FO group 2.8+/-1.1 vs. 4.6+/-1.9 ml/min/g, (p<0.05), and the rats had an accelerated development of nephrosclerosis, with sclerotic lesions in 60.3+/-6.6% of the glomeruli as compared with 46.5+/-9.8% in the cholesterol and 39.8+/-5.9 in the control group (p<0.05). CONCLUSION: The short-time effects of FO on renal hemodynamics did not alleviate the progress of renal damage in Milan normotensive rats, but the morphologic and functional signs of injury were rather pronounced with FO feeding.

Animals↗

CMV in kidney transplantation: a single center experience over 22 years.

Analysis of a historic renal transplant population for risks of developing CMV disease demonstrated a low mortality (0.2%) and morbidity. In our population of 1,959 patients, 411 (21%) developed subclinical CMV infection and 220 (11%) had CMV disease which was severe in 41 (2%). Important factors for infection were baseline immunosuppression, indicating that triple therapy with the proliferation inhibitors, azathioprine and MMF, had significantly higher infection numbers in comparison to dual, CsA-based immunosuppression. The cumulative dose of steroids correlated strongly with an increased number of CMV infections and disease, as did the addition of ALG/ATG or OKT3 for either steroid-resistant rejections or induction therapy. While CMV serology had an impact on infection in cases of seropositive donors to seronegative recipients, seropositive patients, in general, demonstrated increased infection rates most likely due to reactivation of the virus. Prophylaxis had no impact on the incidence of infection but reduced the severity.

Adult↗