Biomedical subjects

Giacomo Aletti

Publications and source records attributed to Giacomo Aletti.

15 recordsLinked to original sources

PubMed2007

Low-dose interleukin-2 administered pre-operatively to patients with gastric cancer activates peripheral and peritumoral lymphocytes but does not affect prognosis.

BACKGROUND: There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case-control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery. METHODS: Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3(+) T, CD4(+) T, CD8(+) T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months. RESULTS: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3(+) T and CD4(+) T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients. CONCLUSIONS: According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis.

Adenocarcinoma↗

PubMed2006

Myocardial damage prevented by volatile anesthetics: a multicenter randomized controlled study.

OBJECTIVE: The purpose of this study was to evaluate the effects of volatile anesthesia versus total intravenous anesthesia on cardiac troponin release in off-pump coronary artery bypass grafting (OPCAB). DESIGN: The authors performed a multicenter randomized controlled study to compare cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for cardiac surgery on the beating heart, which is an excellent model of human myocardial ischemia. SETTING: Three university hospitals. PARTICIPANTS: The authors randomly assigned 57 patients to desflurane (volatile anesthetic) and 55 patients to propofol (intravenous anesthetic) in addition to an opiate-based anesthesia for OPCAB. INTERVENTIONS: The 2 groups of patients received either desflurane (volatile anesthetic) or propofol in addition to an opiate-based anesthesia for OPCAB. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. Prolonged hospitalization was considered as a secondary outcome. MEASUREMENTS AND MAIN RESULTS: Patient mean age was 69 years, and 82% were men. There was a significant (p < 0.001) reduction in postoperative median (25th-75th percentiles) peak of troponin I in patients receiving volatile anesthetics, 1.2 (0.9-1.9) ng/dL, compared with patients receiving total intravenous anesthesia, 2.7 (2.1-4.0) ng/dL. This myocardial protection resulted in a reduced (p = 0.04) number (percentage) of patients requiring postoperative inotropes, 20 (35%) versus 31 (56%), and a reduced number (percentage) of patients submitted to prolonged hospitalization (> or =7 days), 7 (12%) versus 20 (36%) in the 2 groups (p = 0.005). One patient receiving total intravenous anesthesia died within 30 days of surgery. CONCLUSIONS: Myocardial damage measured by cardiac troponin release could be reduced by volatile anesthetics during OPCAB. Because patients underwent cardiac surgery on the beating heart, these results could have implications for cardiac patients undergoing noncardiac surgery.

Aged↗

PubMed2005

Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial.

BACKGROUND: Acute renal failure is a serious complication of cardiac surgery causing high morbidity and mortality. The aim of this study was to evaluate the usefulness of fenoldopam, a specific agonist of the dopamine-1 receptor, in patients at high risk of perioperative renal dysfunction. METHODS AND RESULTS: A prospective single-center, randomized, double-blind trial was performed after local ethical committee approval and after written consent was obtained from 80 patients undergoing cardiac surgery. Patients received either fenoldopam at 0.05 microg/kg per minute or dopamine at 2.5 microg/kg per minute after the induction of anesthesia for a 24-hour period. All these patients were at high risk of perioperative renal dysfunction as indicated by Continuous Improvement in Cardiac Surgery Program score >10. Primary end point was defined as 25% creatinine increase from baseline levels after cardiac surgery. The 2 groups (fenoldopam versus dopamine) were homogeneous cohorts, and no difference in outcome was observed. Acute renal failure was similar: 17 of 40 (42.5%) in the fenoldopam group and 16 of 40 (40%) in the dopamine group (P=0.9). Peak postoperative serum creatinine level, intensive care unit and hospital stay, and mortality were also similar in the 2 groups. CONCLUSIONS: Despite an increasing number of reports of renal protective properties from fenoldopam, we observed no difference in the clinical outcome compared with dopamine in a high-risk population undergoing cardiac surgery.

Aged↗

PubMed2005

Perioperative magnesium supplementation to prevent atrial fibrillation after off-pump coronary artery surgery: a randomized controlled study.

OBJECTIVE: Atrial fibrillation is a common complication after cardiac surgery. Magnesium is an effective and safe antiarrhythmic agent for arrhythmias that develop after cardiac surgery. The authors performed a study to evaluate the role of perioperative magnesium for prophylaxis of atrial fibrillation after off-pump coronary artery surgery. DESIGN: Randomized controlled study. SETTING: University teaching hospital. PARTICIPANTS: One hundred sixty consecutive patients undergoing elective, isolated, off-pump coronary artery bypass grafting were prospectively randomized into 2 groups. INTERVENTIONS: Patients in the magnesium group (n = 80) received a 2.5-g (20 mEq) magnesium sulphate infusion intraoperatively over 30 minutes, and the placebo group (n = 80) received normal saline solution. MEASUREMENTS AND MAIN RESULTS: Postoperative atrial fibrillation occurred in 16 of 80 patients (20%) in the magnesium group and in 18 of 80 (22.5%) in the placebo group (p = 0.9). CONCLUSION: The use of 2.5 g of intraoperative magnesium showed no effect in preventing atrial fibrillation after off-pump coronary artery bypass.

Aged↗

PubMed2004

Clinical significance of a new Q wave after cardiac surgery.

OBJECTIVE: The appearance of new Q waves on the electrocardiogram (ECG) after cardiac surgery has been traditionally considered a sign of major myocardial tissue damage. The aim of this study was to investigate the clinical significance of new Q waves appearing following cardiac surgery and to correlate them with the release of myocardial cell damage biomarkers. METHODS: 206 consecutive patients undergoing cardiac surgery were prospectively evaluated. A 12 lead ECG was recorded and cardiac troponin I and creatinekinase subfraction MB assayed the day before surgery, on arrival at the intensive care Unit. 4 and 18 h postoperatively and every morning until the fifth postoperative day. RESULTS: The incidence of new Q waves was 7.3%. Patients with isolated ECG findings had an uneventful postoperative course; on the contrary, when ECG changes were coupled with the release of myocardial necrosis biomarkers, patients had a complicated postoperative course. CONCLUSIONS: The association of a new Q wave and high levels of myocardial necrosis biomarkers is strongly associated with postoperative cardiac events. On the contrary, the isolated appearance of a new Q wave has no impact on the postoperative cardiac outcome.

Aged↗

PubMed2004

Endometrial carcinoma: paraaortic dissemination.

OBJECTIVE: The objective of our study was to identify pathologic factors predictive of tumor dissemination to paraaortic lymph nodes (LNs) in endometrial carcinoma. The identification of the risk factors may potentially facilitate selection of patients for radical surgery or radiotherapy directed to the paraaortic area (PAA). METHODS: The study population was a cohort from 612 consecutive patients with endometrial cancer surgically managed at our institution over a 10-year period. Tumor dissemination to the PAA was identified by selecting those patients who had either paraaortic LNs positive for disease at the time of primary surgery or those who subsequently experienced paraaortic failure or both (n=41; the "PA mets" subgroup). Therefore, patients for whom no information was available about the status of paraaortic LNs but who had received adjuvant irradiation to the PAA and those for whom information was not available about sites of recurrent disease were excluded from the analysis, leaving 566 patients to compose the study population. RESULTS: On the basis of univariate analysis, numerous pathologic variables were significantly (P< or =0.01) associated with PA mets. However, logistic regression analysis identified only two independent factors predictive of PA mets: positive pelvic LNs (P<0.001, OR=5.00) and lymphovascular invasion (LVI) (P=0.01, OR=1.99). Notably, only 2% of patients with negative pelvic LNs had PA mets compared with 47% of those with positive pelvic LNs (P<0.001). When both pelvic LNs and LVI were negative, only 0.8% of the patients had PA mets compared with 31% of patients for whom at least one of the two variables was positive (P<0.001). CONCLUSION: Positive pelvic LNs and LVI identify a subgroup of high-risk patients (approximately one sixth of the overall population) who potentially may benefit from formal lymphadenectomy or adjuvant therapy or both directed to the PAA. Furthermore, with 47% of patients with positive pelvic LNs having PA mets, unstaged patients at risk for pelvic LN involvement should be considered candidates for both pelvic and paraaortic external beam radiotherapy or surgical restaging.

Adult↗

PubMed2004

Cardiac biomarker release after CABG with different surgical techniques.

OBJECTIVE: To investigate the release of cardiac biomarkers (troponin I and CK-MB) in patients undergoing coronary artery bypass graft (CABG) with or without cardiopulmonary bypass (CPB). DESIGN: Prospective study. SETTING: University tertiary hospital. PARTICIPANTS: Sixty-five consecutive patients undergoing coronary artery bypass grafting (>or=2 vessel disease, ejection fraction >or=0.35%, elective procedure). INTERVENTIONS: Cardiac biomarkers were measured before surgery, at intensive care unit arrival, 4 and 18 hours after the end of the procedure. MEASUREMENTS AND MAIN RESULTS: Cardiac biomarker release was higher in on-pump than in off-pump patients at every time point. On multivariate analysis, CPB (p < 0.0001), number of distal grafts (p = 0.005), and hypertension treatment (p = 0.03) were the only independent predictors of peak cardiac troponin release. CONCLUSIONS: Cardiac troponin I release after multivessel CABG is associated with the technique. Different values for the normal range should be considered. OPCABG is minimally invasive for the heart as far as myocardial marker release is concerned.

Aged↗

PubMed2004

ECG changes after CABG: the role of the surgical technique.

OBJECTIVE: The purpose of this study was to determine whether coronary artery bypass grafting (CABG) surgery on the beating heart (BH) is associated with reduction of R-wave potentials on the precordial leads on the surface electrocardiogram (ECG) as previously shown for CABG with cardiopulmonary bypass. METHODS: Fifty-four patients undergoing CABG surgery at a single tertiary care university hospital were analyzed. Patients suffering a postoperative cardiac event (myocardial infarction) or nonspecific ECG changes were excluded. ECG results were recorded at arrival in the intensive care unit, after 4 and 18 hours postoperatively; simultaneously, myocardial cell damage biomarkers (CK-MB and cTnI) were assayed. A control group of 31 patients undergoing mitral valve repair was also evaluated. RESULTS: Patients operated with the BH (OPCABG) technique did not show any decrease of R-wave amplitude at 0, 4, and 18 hours postoperatively; whereas those operated with CPB, both for coronary artery surgery and for mitral repair, had a similar extent and pattern of R-wave reduction. The release of myocardial necrosis markers was significantly lower in coronary artery patients operated with BH than in those operated with CPB; however, no statistically significant correlation between the ECG changes and release of myocardial cell damage markers was observed in any of the groups. CONCLUSIONS: The findings indicate, for the first time, that CABG surgery on the BH is not followed by any reduction of R-wave amplitude on precordial leads and confirms that the BH technique is associated with a lower release of myocardial cell damage markers.

Aged↗

PubMed2004

The incidence and risk of acute renal failure after cardiac surgery.

OBJECTIVE: To evaluate outcome and risk factors of acute renal failure in a surgical population with or without preoperative renal dysfunction. DESIGN: Observational study. SETTING: Intensive care unit at a University Hospital. PARTICIPANTS: Five thousand sixty-eight consecutive adult patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Perioperative variables measured were age, sex, basic pathology, preoperative renal impairment defined as creatinine >1.4 mg/dL, ventricular dysfunction, preoperative neurologic event, chronic obstructive pulmonary disease, diabetes, type of surgery, use of intra-aortic balloon pump (IABP), cardiopulmonary bypass (CPB) duration, redo or emergency surgery, hemorrhage, blood transfusion, surgical revisions, and postoperative complications. MEASUREMENTS AND MAIN RESULTS: Acute renal failure (100% creatinine increase) developed in 171 (3.4%) patients, whereas 94 patients (1.9% of the population) had renal replacement therapy. Hospital mortality was 40.9% in patients with acute renal failure and increased to 63.8% when renal replacement therapy was requested. Sex, age, emergency surgery, low ejection fraction, IABP device, redo, diabetes, mitral valve surgery, CPB duration, and preoperative renal disease were independently associated with acute renal failure at a multivariate analysis. CONCLUSION: This study confirms that acute renal failure is one of the major complications of cardiac surgery, identifies the risk factors, and suggests that optimizing cardiac output and reducing CPB time could improve the outcome of patients at high risk of acute renal failure.

Acute Kidney Injury↗

PubMed2004

Predictors of atrial fibrillation after off-pump coronary artery bypass graft surgery.

OBJECTIVE: Atrial fibrillation is the most common complication after coronary artery bypass graft surgery. This arrhythmia may lead to hemodynamic compromise, prolonged hospitalization, and increased risk for cerebral thromboembolism. Older age is the only variable consistently associated with the development of postoperative atrial fibrillation; however, no strong predictive model exists. The purpose of this study was to identify perioperative characteristics associated with new-onset atrial fibrillation in patients undergoing off-pump coronary artery bypass grafting. DESIGN: Prospective, observational. SETTING: University tertiary care hospital. PARTICIPANTS: One hundred sixty consecutive patients undergoing off-pump coronary artery bypass grafting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Incidence of postoperative atrial fibrillation was the major outcome. Atrial fibrillation occurred in 33 patients (20.6%). Multivariate analysis identified reintervention (odds ratio 26.8), revascularization of the ramus medianus (odds ratio 3.9), and age (odds ratio 1.069 per year) as the only independent predictors of postoperative atrial fibrillation. All patients were in sinus rhythm at hospital discharge. One hospital death was noted. CONCLUSIONS: Despite the less invasive approach, the incidence of postoperative atrial fibrillation is high after off-pump coronary artery bypass grafting. Older age, grafting of the ramus medianus, and a redo operation were predictors of new-onset postoperative atrial fibrillation. It is possible that left atrial stretching with heart dislocation during revascularization of the lateral wall could lead to postoperative atrial fibrillation.

Aged↗

PubMed2003

Endometrial cancer: predictors of peritoneal failure.

OBJECTIVE: To assess determinants of peritoneal failure in endometrial cancer patients after definitive primary treatment. METHODS: Of 599 patients with endometrial cancer who had primary surgery at our institution during the decade before 1994, 131 had relapse. We defined "peritoneal failure" as relapse when it occurred in the upper abdomen or involved the pelvic peritoneum (or both). Mean follow-up was 72.8 months. RESULTS: Peritoneal failure was detected in 37 of 599 (6%) patients and represented 28% of identified failures. Stage IV disease, cervical stromal invasion, adnexal involvement, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, lymph node metastasis, histologic grade 3, nonendometrioid histologic subtype, absence of associated hyperplasia, and lymphovascular invasion correlated significantly (P < 0.01) with peritoneal failure. However, on regression analysis, only stage IV disease (P < 0.001, relative risk [RR] = 7.53), nonendometrioid histologic subtype (P = 0.02, RR = 3.01), and cervical stromal invasion (P = 0.04, RR = 2.83) were independent predictors of peritoneal failure. Because 22 of 37 (59%) peritoneal failures were in patients with stage IV disease, we considered separately the 545 patients with stage I-III disease. On regression analysis, nonendometrioid histologic subtype (P < 0.001, RR = 11.58), positive peritoneal cytology (P = 0.009, RR = 6.72), lymph node metastasis (P = 0.02, RR = 5.10), and cervical stromal invasion (P = 0.04, RR = 3.10) were independent predictors of peritoneal failure. Of the 38 patients in whom at least two of these four predictors were positive, 26% had peritoneal failure at 5 years, compared with 1% of the 507 patients who had none or only 1 predictor (P < 0.001). CONCLUSION: Patients with stage IV disease and those with stage I-III disease and at least two of the four independent predictors (nonendometrioid histology, positive peritoneal cytology, cervical stromal invasion, and lymph node metastasis) would be candidates for new therapeutic trials incorporating surgical and adjuvant treatment targeting the entire abdominal cavity.

Adult↗

PubMed2003

Fractal dimension rectified meter for quantification of liver fibrosis and other irregular microscopic objects.

OBJECTIVE: To introduce a new mathematical method based on the principles of fractal geometry analysis that permits more realistic quantification of some of the physical (morphologic) aspects of irregular bodies appearing under microscopy. STUDY DESIGN: The principles of the method were tested on microscopic images of irregular collagen deposition in liver tissue. The method uses an ad hoc rectified meter implemented in a computer-assisted planar image analysis system that has been adapted to give metric measures of irregular outlines and surfaces that can be used to produce an index capable of quantifying the typical wrinkledness of biologic objects. Prototypical example measures of liver fibrosis were made on biopsy specimens showing chronic hepatitis C virus-related disease. Measurements were also made of the microscopic images of the abnormal deposition of lipid droplets in hepatocytes, a case of amyloid deposition in an osteoarthromuscular structure and a cytologic specimen of human dendritic cells. RESULTS: The proposed computer-aided method permits rapid measurements of the image of a whole biopsy section digitized at high magnification. The snapshot measurement of liver fibrosis deposition offered by a biopsy pattern is a valid means of more rigorously identifying the staging of the process. CONCLUSION: This method can measure liver fibrosis during chronic liver disease as well as any other irregular biologic structure that cannot be correctly quantified using traditional Euclidean-based metric methodologies.

Biopsy, Needle↗

PubMed2002

Predictors of lymphatic failure in endometrial cancer.

OBJECTIVE: The aim of this study was to identify determinants of lymphatic failure in patients with endometrial cancer after definitive primary treatment. METHODS: We observed 142 relapses in endometrial cancer patients who had primary surgery at our institution during the decade before 1994. We defined lymphatic failure as a relapse occurring on the pelvic sidewall (PSW), para-aortic area (PAA), or other node-bearing area (i.e., groin, axilla, supraclavicular, mediastinal). Mean follow-up was 72.8 months. RESULTS: We observed 44 instances of lymphatic failure--6 on the PSW only, 16 in the PAA only, 12 concomitantly in the PAA and on the PSW, and 10 confined in other node-bearing areas. By univariate analysis, body mass index > or = 30 kg/m(2), para-aortic lymph node biopsy, cervical stromal invasion (CSI), positive adnexa, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, positive lymph nodes (pelvic and/or para-aortic), radiotherapy, grade 3 tumor, nonendometrioid histology, and lymph--vascular invasion (LVI) significantly (P < or = 0.05) correlated with lymphatic failure. However, on Cox regression analysis, only LVI (P < 0.01, relative risk [RR] = 4.27), nodal involvement (P = 0.02, RR = 3.43), and CSI (P = 0.049, RR = 2.26) were independent predictors of lymphatic failure. Moreover, lymph node metastases (P = 0.01, RR = 19.82) and CSI (P = 0.050, RR = 3.57) independently predicted failure on the PSW, and only lymph node involvement (P < 0.01, RR = 10.15) predicted relapse in the PAA. CONCLUSION: LVI, positive lymph nodes, and CSI were the strongest predictors of lymphatic failure in endometrial cancer (31% of patients with at least one of the above three variables had a failure at 5 years). Patients with none of the above three factors had an extremely low (<1%) risk of lymphatic failure.

Adult↗

PubMed2002

Assessment of prognostic factors in stage IIIA endometrial cancer.

OBJECTIVE: The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. METHODS: Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involvement (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P = 0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendometrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of (32)P, 2 had pelvic external radiotherapy (PRT)]. By contrast, of the 15 patients with either nonendometrioid histologic subtype or LVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or (32)P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83% and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). CONCLUSION: Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cytologic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prognosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy.

Adult↗

PubMed2002

Stage IIIC endometrioid corpus cancer includes distinct subgroups.

OBJECTIVE: Because stage IIIC corpus cancer is a heterogeneous substage, the outcomes of patients with stage IIIC disease were assessed according to the extent of extrauterine disease. METHODS: From 1984 through 1993, 51 patients with surgical stage IIIC corpus cancer were treated at our institution; 5 patients had tumors with nonendometrioid histologic features and were excluded from the analyses. Of the 46 patients with endometrioid carcinoma, 22 had lymph nodes as the only site of extrauterine disease (stage IIIC(0)) and 24 also had peritoneal cytologic, uterine serosal, adnexal, or vaginal involvement or a combination of these (stage IIIC(ab)). The mean number of lymph nodes removed was 18 pelvic and 8 aortic nodes. Median follow-up for surviving patients was 84 months. RESULTS: Patients with stage IIIC(0) cancer had a 5-year cause-specific survival (CSS) of 72% and a 5-year recurrence-free survival (RFS) of 68%, and those with stage IIIC(ab) had a CSS of 33% and an RFS of 25% (P < 0.01). Of the 22 patients with stage IIIC(0) endometrioid cancer, 21 had adjuvant radiotherapy (1 also received chemotherapy) and 1 was not treated. Relapse occurred in 7 (32%) patients, with only 1 having an initial failure component outside the node-bearing areas (lung). Of the 24 patients with stage IIIC(ab) cancer, 16 received adjuvant radiotherapy (1 had concomitant chemotherapy), 2 had chemotherapy, 4 had hormonal therapy, and 2 were not treated. We observed 16 recurrences (67%). Of the 14 patients with known initial sites of failure, 9 had an extranodal failure component. CONCLUSION: Assessment of CSS, RFS, and sites of relapse suggests that FIGO surgical stage IIIC endometrioid corpus cancer includes two distinct and readily separable subgroups: (1) stage IIIC(0), nodal involvement only, and (2) stage IIIC(ab), nodal plus cytologic, uterine serosal, adnexal, or vaginal involvement, or a combination of these. Our results also suggest that different treatment strategies are needed for these subgroups.

Adult↗