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Biomedical subjects

R E Hobbs

Publications and source records attributed to R E Hobbs.

At least 19 recordsLinked to original sources
PubMed1999

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Adolescent↗
PubMed1999

Microsporidia infection in transplant patients.

BACKGROUND: Microsporidia are the most common cause of chronic diarrhea in patients infected with human immunodeficiency virus. Patients who have undergone organ transplantation may also be infected. The precise immune defect and the clinical picture in transplant patients have not been studied. METHODS: We report a case of microsporidia infection in a heart transplant patient and review three other cases reported in the literature. RESULTS: Infection in three solid organ transplant patients occurred when the patients were receiving immunosuppressive therapy for rejection 1.5-3 years after transplantation. Patients had chronic diarrhea, vomiting, dyspepsia, and weight loss for 1 month to 3 years. CONCLUSIONS: Microsporidia may be the cause of chronic unexplained diarrhea and gastrointestinal disturbances in transplant patients. Defects in cell-mediated immunity probably play a role in maintaining the chronicity of this infection. Specific screening requests should be made to the microbiology laboratory when microsporidia infection is suspected.

Animals↗
PubMed1998

Development of transplantation vasculopathy and progression of donor-transmitted atherosclerosis: comparison by serial intravascular ultrasound imaging.

BACKGROUND: Transplant coronary artery disease is a combination of atherosclerosis transmitted from the donor and new lesions of allograft vasculopathy. We sought to determine the morphological characteristics of allograft vasculopathy and differentiate it from donor-transmitted atherosclerosis with serial intravascular ultrasound. METHODS AND RESULTS: Intravascular ultrasound examination was performed in 93 patients at 27.2+/-15.0 and 369. 7+/-23.9 days after transplantation. The maximally and minimally diseased sites were selected in each segment as defined by Coronary Artery Surgery Study classification. For each matched site, maximal plaque thickness was measured. Lesions (maximum plaque thickness >/=0.5 mm) present at baseline examination were defined as donor lesions. On follow-up, lesions that developed at previously normal sites were defined as de novo lesions. The distribution and severity of donor and de novo lesions were similar in proximal, mid, and distal segments. The de novo lesions were less focal (43% vs 74%) and more circumferential (69% vs 45%) compared with the donor lesions, but there was significant morphological heterogeneity. Similar numbers of patients with and those without donor lesions developed de novo lesions. Moreover, progression of donor lesions was not associated with the presence or absence of de novo lesions. CONCLUSIONS: Differentiation between early allograft vasculopathy from conventional atherosclerosis by distribution and morphology of lesions alone is difficult. Serial intravascular ultrasound imaging with early baseline examination is necessary to make this distinction. This distinction is important because the progression of donor lesions and the development of de novo lesions are independent of each other.

Adolescent↗
PubMed1998

One hundred patients with the HeartMate left ventricular assist device: evolving concepts and technology.

BACKGROUND: Implantable left ventricular assist devices are common as a bridge to transplantation but are just reaching their goal as an alternative to transplantation. METHODS: From December 1991 until December 1996, 97 left ventricular assist devices were implanted as a bridge to transplantation, one as an alternative to transplantation, and two as a bridge to recovery. Included were 64 pneumatic devices and 36 electric devices. Most patients (69%) had ischemic cardiomyopathy and most (53%) had had previous cardiac surgery. Preoperative circulatory support (extracorporeal membrane oxygenation) was used in 25. RESULTS: Perioperative insertion of a right ventricular assist device was unusual (11%). The mean duration of support with a left ventricular assist device (bridge to transplantation) was 70 +/- 41 days (up to 206 days). Survival to transplantation was 76%. Cause of death included multiple organ failure (n = 13), perioperative stroke (n = 5), device failure (n = 5), and controller disconnect (n = 1). Significant risk factors for death included (1) preoperative need for ventilator or extracorporeal membrane oxygenation, (2) elevated blood urea nitrogen, creatinine, or bilirubin, and (3) low pulmonary artery pressures. Risks after insertion of the left ventricular assist device were reoperation for bleeding, support with a right ventricular assist device, dialysis, or device failure. Catastrophic failure of the device occurred 14 times in 12 patients and was treated by emergency pump exchange in six instances. Only two device-related thromboembolic episodes were detected. Positive blood cultures were found in 59% of patients, driveline infection in 28%, and pump infection in 11%. CONCLUSIONS: The HeartMate device provided excellent hemodynamic support with low device-related thromboembolic events. Infection and reliability of the device contributed to the high cost of therapy. These areas need to be improved for the left ventricular assist device to attain its goal as a viable alternative to transplantation.

Actuarial Analysis↗
PubMed1997

Significance of positive cultures from donor left atrium and postpreservation fluid in heart transplantation.

BACKGROUND: The significance of positive perioperative cultures routinely obtained from the donor left atrium and postpreservation fluid during heart transplantation is unknown. METHODS: A retrospective chart review of 128 heart transplant recipients was done. RESULTS: A total of 106 of 128 patients had left atrial and/or postpreservation fluid cultures performed; 61 (57.5%) of them were positive. Forty-one positive left atrial or postpreservation cultures grew indolent organisms and 20 grew virulent organisms. Six donors had positive blood cultures, and five of the six did not have left atrial or postpreservation fluid cultures positive for the same organism. Seven recipients had positive blood cultures with organisms different from their corresponding left atrial or postpreservation fluid cultures. Three patients had sternal wound infections with organisms different from their donors' left atrial or postpreservation fluid cultures. Seven patients received additional antibiotics after heart transplantation specifically directed at a positive left atrial or postpreservation fluid culture for 5 to 7 days; none of them developed infection with these organisms. CONCLUSIONS: We found no evidence that positive donor left atrium or postpreservation fluid cultures increase the recipients' risk of infection. Nevertheless, we cannot refute that the small group of patients who received additional antibiotics might have developed an infection if they had not been treated. We recommend that the left atrial and postpreservation fluid cultures growing indolent organisms be discounted. However, if they grow more virulent organisms, consideration could be given to a brief course of specific therapy while awaiting recipient cultures.

Adult↗
PubMed1997

Permanent mechanical circulatory support with an implantable left ventricular assist device.

A 67-year-old man had end-stage ischemic cardiomyopathy. He had had two previous coronary bypass operations and a previous left ventricular aneurysmectomy. In December 1995 he underwent vented-electric HeartMate LVAD insertion as an alternative to transplantation. He was discharged from the hospital 13 days after the operation, and 5 months postoperatively he had returned to New York Heart Association functional class II.

Aged↗
PubMed1997

Does distance between home and transplantation center adversely affect patient outcomes after heart transplantation?

BACKGROUND: The emergence of heart transplantation referral centers, in an era of cost-conscious managed care programs, frequently leads to long-distance patient consultation and care. The purpose of this project was to review one center's experience regarding the effect of long distances from home to transplantation hospital on outcomes. METHODS: Three hundred twelve adult, noninternational, transplant recipients surviving at least 3 months were assessed for 10 events: rejection episodes, number of endomyocardial biopsies, emergency department visits, hospital admissions, return to full-time work or school, infections, coronary allograft vasculopathy, malignancies, retransplantation, and death. Presence of a locally involved physician was also determined. Distance from the transplantation center was analyzed in three discrete groups: 0 to 150 miles (n = 207), 151 to 300 miles (n = 69), and >300 miles (n = 36). RESULTS: There were no differences among the groups in mean length of follow-up (40.6, 36.9, 39.0 months, p = 0.27) or number of biopsies (20.5 +/- 0.16, 18.3 +/- 1.1, 18.0 +/- 1.1, p = 0.07). As the distance increased from the transplantation center, there was no greater incidence of adverse outcomes. Cellular rejection was the same among the groups (45%, 45%, 36%, p = 0.58). Likewise, emergency department visits and hospital admissions also did not vary: (9.7%, 5.8%, 8.3%, p = 0.61) and (22.2%, 13.0%, 16.7%, p = 0.23, respectively). There were no differences in the incidence of coronary vasculopathy (9.2%, 11.6%, 13.9%, p = 0.63). More importantly, the three groups did not differ in death/retransplantation rates (3-year survival, 84.5, 94.0 and 86.9, p = 0.14). Patients cared for by a local physician in addition to their transplant cardiologist had better survival rates than patients without a local physician (3-year survival rate, 90.7 vs 72.6, p = 0.0008). CONCLUSIONS: Long-distance management of heart transplant recipients is successful and is not associated with an increase in adverse outcomes. By itself, distance should not represent a contraindication to transplantation. Patients should be encouraged to maintain contact with a local physician, in addition to the regularly scheduled visits at the transplantation center.

Adolescent↗
PubMed1997

The incremental risk of female sex in heart transplantation: a multiinstitutional study of peripartum cardiomyopathy and pregnancy. Cardiac Transplant Research Database Group.

BACKGROUND: Controversy remains regarding the reason females seem to be at increased risk for rejection after heart transplantation. Therefore this study was performed to define the effect of a pretransplantation diagnosis of peripartum cardiomyopathy and the effect of previous pregnancy on the outcome (incidence of rejection and death) of females after heart transplantation. METHODS: In this multiinstitutional study of 3244 adult (greater than 13 years of age) heart transplant recipients, (a) the outcome of 40 females who underwent transplantation for peripartum cardiomyopathy was compared with that of 200 females of childbearing age (13 to 45 years) who underwent transplantation for other indications and (b) the posttransplantation outcome of 543 females with a history of pregnancy was compared with that of 101 nulliparous adult females and 2562 adult males. RESULTS: The posttransplantation outcome of females with a history of peripartum cardiomyopathy was similar to that of females of childbearing age who underwent transplantation for other indications. However, parous females had a significantly shorter time to first rejection (p < 0.0001) and greater cumulative rejection than nulliparous females or males. By multivariable analysis, the risk factors for cumulative rejection at 1 year were a history of pregnancy (p < 0.0001), younger recipient age (p < 0.0001), induction therapy (p < 0.0001), and the number of human leukocyte antigen-DR mismatches (p = 0.007). CONCLUSION: Our data suggest that it is previous pregnancy, and not sex per se, that is associated with an increased frequency of rejection in females after heart transplantation.

Actuarial Analysis↗
PubMed1996

Hemodynamic effects of a single intravenous injection of synthetic human brain natriuretic peptide in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Synthetic human brain natriuretic peptide (sBNP) is a polypeptide with the same amino acid sequence as the naturally occurring hormone. Preclinical studies have demonstrated that BNP has potent hemodynamic, diuretic, and natriuretic effects that might be beneficial in treating patients with heart failure. This study was a randomized, double-blind, placebo-controlled, ascending-dose trial of sBNP administered as a single intravenous bolus in 27 heart failure patients. Six groups of patients received sequentially increasing doses of sBNP (0.3, 1, 3, 10, 15, and 20 micrograms/kg, respectively) as a single intravenous injection, and hemodynamics were assessed by pulmonary artery monitoring catheter. The 10 and 15 micrograms/kg doses of sBNP resulted in significant reductions in pulmonary capillary wedge pressure (-73%, p < 0.001), mean pulmonary artery pressure (-41%, p < 0.001), mean arterial blood pressure (-28%, p = 0.001), and systemic vascular resistance (-53%, p = 0.004). Significant increases occurred in cardiac index (68%, p < 0.001) and stroke volume index (72%, p < 0.001). The magnitude and duration of hemodynamic changes were dose dependent. There were no adverse effects. sBNP injected as a single intravenous bolus in heart failure patients improves hemodynamics in a dose-related fashion. Further clinical investigations to determine the use of sBNP in decompensated heart failure are clearly warranted.

Cardiomyopathy, Dilated↗
PubMed1996

Dichotomous pattern of coronary atherosclerosis 1 to 9 years after transplantation: insights from systematic intravascular ultrasound imaging.

OBJECTIVE: The aim of this study was to evaluate the extent and distribution of coronary atherosclerosis after transplantation. BACKGROUND: Transplant coronary artery disease is an important cause of death after cardiac transplantation. Unlike coronary angiography, intravascular ultrasound is a sensitive tool for detection and quantitation of this disease. METHODS: We performed intravascular ultrasound imaging in 132 (106 men, 50 +/- 10 years) patients, 1 to 9 years after transplantation using a 30-MHz ultrasound catheter. RESULTS: All three coronary arteries were visualized in 49, two in 62 and one in 21 patients. Of the 1,188 coronary artery segments, 706 were imaged (74% proximal, 64% mid- and 40% distal). At least one site with atherosclerosis (intimal thickness > or = to 0.5 mm) was found in 83% of patients. Atherosclerosis was noted in 64% of proximal, 43% of mid- and 26% of distal segments. Disease was diffuse in 48% and focal in 52%, circumferential in 66% and noncircumferential in 34%. Focal atherosclerosis was more common in proximal (59%) than mid- (48%) and distal segments (27%) (p=0.001). Noncircumferential plaques were more common in the proximal (42%) than mid- (28%) and distal segments (12%) (p=0.001). This pattern of focal and noncircumferential disease proximally, diffuse and circumferential disease distally, was observed irrespective of the time from transplantation. CONCLUSION: Atherosclerosis was detected in more than 80% of patients, with proximal segments most frequently involved. Diffuse and circumferential atherosclerosis was more common in mid- and distal segments. However, focal and noncircumferential involvement was more frequent proximally, a similar pattern to native atherosclerosis. These findings suggest that transplant coronary artery disease has a dual etiology based on the dichotomous pattern of atherosclerosis seen by intravascular ultrasound.

Chi-Square Distribution↗
PubMed1996

Implantable LVAD infections: implications for permanent use of the device.

BACKGROUND: Infection in implantable left ventricular assist device (LVAD) patients is common and has serious implications regarding permanent use of the LVAD. METHODS: Thirty-three patients had HeartMate LVAD insertion as a bridge to heart transplantation. The mean length of hospital stay was 8 days before LVAD insertion. Before insertion 6 patients (18%) had positive pulmonary cultures and 5 patients (15%) had bacteremia. RESULTS: During LVAD support 18 patients (55%) had bloodstream infection. Of 24 patients (73%) successfully bridged to transplantation, 12 (50%) had positive blood cultures including Staphylococcus species (n = 9), Candida (n = 3), Pseudomonas (n = 2), and Enterococcus (n = 2). Infectious complications encountered in this series included driveline infection requiring surgical revision, septic embolus, "cleared" device infection, "suppressed" device infection, and LVAD infection treated by device removal in 1 patient and device exchange in another. CONCLUSIONS: Infection in implantable LVAD patients is common, especially in patients in whom multiple organ failure develops, requiring prolonged stay in the intensive care unit. Strategies are needed to prevent these infections in recipients of the permanent LVADs because treatment of an established infection is difficult and expensive.

Adult↗
PubMed1996

Bench repair of donor mitral valve before heart transplantation.

Bench repair of the donor mitral valve was performed before orthotopic heart transplantation in a 57-year-old status I recepient. Mitral regurgitation in the structurally normal mitral valve was due to annular dilatation at the attachment of the posterior leaflet and was corrected with posterior annuloplasty. The patient is clinically well 18 months after transplantation.

Heart Transplantation↗
PubMed1996

Risk factors for early, cumulative, and fatal infections after heart transplantation: a multiinstitutional study.

BACKGROUND AND METHODS: By multivariable analysis, risk factors were identified for initial infection of any type, cumulative infections during the first 6 months and fatal infection among 2210 heart transplant recipients at 30 institutions. RESULTS AND CONCLUSIONS: Of the 1218 infections in 695 patients, bacterial infections were most frequent (47%), followed by viral (42%), fungal (8%), and protozoal (4%). Risk factors for earlier infection included older recipient age (p < 0.0001), ventilator support at time of transplant (p < 0.0001), ventricular assist device at time of transplant (p = 0.02), OKT3 induction therapy (p < 0.0001), donor black race (p = 0.0007), and positive donor cytomegalovirus serology (for cytomegalovirus infection) (p = 0.0007). Cumulative infections during the first 6 months were increased by older recipient age (p < 0.0001), ventilator support at transplant (p = 0.0004), ventricular assist at transplant (p = 0.009), Black donor (p = 0.03), female donor (p = 0.03), and OKT3 induction therapy (p = 0.005). The actuarial freedom from fatal infection was 96% at 1 year and 95% at 3 years. Risk factors for death from infection included very old (p = 0.002) and very young recipients (p = 0.004), ventilator support at time of transplant (p = 0.004), older donor (p < 0.0001), and longer donor ischemic time (p = 0.02). The risk of death from infection within the first 3 months exceeded 20% among older recipients (> 55 years) on ventilator support at time of transplantation who received an older (> 50 years) donor heart.

Actuarial Analysis↗
PubMed1995

Effect of the implantable left ventricular assist device on neuroendocrine activation in heart failure.

BACKGROUND: The HeartMate left ventricular assist device has been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement in their heart failure after HeartMate implantation, we studied the physiological effect of this device on the neurohormonal axis. METHODS AND RESULTS: In 13 patients awaiting transplant (mean cardiac index, 1.7 +/- 0.3 L.min-1.m-2) who underwent HeartMate implantation, venous atrial natriuretic peptide, epinephrine, norepinephrine, plasma renin activity, angiotensin, and arginine vasopressin were measured immediately before insertion and at explant/transplantation. Mean time to explant was 86 +/- 40 days. All patients were taken off inotropic medications within 1 month. Mean cardiac index on support before explant was 3.1 +/- 0.9 L.min-1.m-2. Plasma renin activity decreased from 57 +/- 56 ng.mL-1.h-1 at baseline (before insertion) to 3 +/- 3 ng.mL-1.h-1 at explant (mean percent change, 92%; P < .001). Angiotensin II level decreased from 237 +/- 398 U/L at baseline to 14 +/- 14 U/L at explant (mean percent change, 73%; P < .001). Plasma epinephrine level fell from 6800 +/- 1323 pg/mL at baseline to 46 +/- 46 pg/mL at explant (mean percent change, 86%; P < .001). Norepinephrine level decreased from 2953 +/- 1457 pg/mL at baseline to 518 +/- 290 pg/mL at explant (mean percent change, 79%; P < .001). Atrial natriuretic peptide fell from baseline values of 227 +/- 196 to 168 +/- 40 pg/mL at explant (mean percent change, -49%; P = 519); and arginine vasopressin level decreased from 6 +/- 6 pg/mL at baseline to 0.8 +/- 0.5 pg/mL (mean percent change, 69%; P = .002). CONCLUSIONS: We provide data supporting that the neurohormonal axis markedly improves after HeartMate implantation, providing biochemical confirmation of the improvement in hemodynamic status.

Adult↗
PubMed1995

The prevalence of coronary artery disease in liver transplant candidates over age 50.

The prevalence of angiographically proven coronary artery disease (CAD) in adults with end-stage liver disease who undergo evaluation for liver transplantation is unknown; also it is unclear if cholestatic liver disease represents an independent risk factor. Patients with end-stage liver disease over age 50 having liver transplantation were studied using coronary angiography. Arterial stenosis was graded as normal, mild (< 30%), moderate (30 to 70%), or severe (> 70%). Risk factors for CAD were also assessed (male sex, smoking, hypertension, diabetes, family history of premature heart disease). Complications related to the angiography and decision making based on the findings were recorded. Thirty seven patients (23 females) with a median age of 61 years (range 50 to 71) underwent angiography. Thirteen patients (35.1%) had cholestatic liver disease. Thirty patients had no history of heart disease. The overall prevalence of severe coronary artery disease was 16.2% (95% confidence interval [CI] = 6.2% to 32.0%). No association was detected between CAD and cholestatic liver disease (P = 0.72). After eliminating seven patients with a prior history of angina (n = 1), myocardial infarction (n = 1), or coronary revascularization (n = 5), the frequency of moderate or severe CAD was 13.3% (95% CI = 3.8% to 30.7%). No association was detected between unsuspected CAD and cholestatic liver disease (P = 0.61). Diabetes was the most important risk factor for moderate or severe disease (P = 0.01). Patients without risk factors had significantly less CAD than the group as a whole regardless of the liver disease type (P = 0.02). Two patients experienced transient renal insufficiency after the angiography. Three patients with severe CAD were denied transplantation. We conclude that CAD represents a significant problem in patients over age 50 undergoing liver transplant evaluation. Cholestatic liver disease was not associated with a significantly higher prevalence of moderate or severe CAD in our population. Diabetes was the most predictive risk factor, and those without risk factors do not require extensive preoperative cardiac evaluation.

Age Factors↗
PubMed1995

Occult and frequent transmission of atherosclerotic coronary disease with cardiac transplantation. Insights from intravascular ultrasound.

BACKGROUND: Transplant coronary artery disease is a major cause of morbidity and mortality after cardiac transplantation. However, limited data exist regarding the potential contribution of coronary atherosclerosis in the donor heart to cardiac-allograft vasculopathy. METHODS AND RESULTS: We performed quantitative coronary angiography and intravascular ultrasound imaging in 50 of 62 consecutive heart-transplant recipients (40 men, 10 women, mean age, 53 +/- 9 years) 4.6 +/- 2.6 weeks after transplantation. The donor population consisted of 30 men and 20 women (mean age, 32 +/- 12 years). Ultrasound imaging visualized all three coronary arteries in 22 patients, two coronary arteries in 23, and one coronary artery in 5. Ultrasound imaging detected coronary atherosclerosis (intimal thickness > or = 0.5 mm) in 28 patients (56%). However, the angiography was abnormal in only 13 patients (26%). The sensitivity and specificity of coronary angiography were 43% and 95%, respectively. With ultrasound, the average atherosclerotic plaque thickness was 1.3 +/- 0.6 mm and the cross-sectional area narrowing was 34 +/- 16%. Atherosclerotic involvement frequently was focal (85%), eccentric (mean eccentricity index, 87 +/- 8), and near arterial bifurcations. Donors of the transplant recipients with coronary atherosclerosis were older than those without atherosclerosis (37 +/- 12 versus 25 +/- 10 years, P = .001). Maximal intimal thickness correlated with donor age (r = .54, P = .0001). Multivariate analysis demonstrated that donor age (P = .0001), male sex of donor (P = .0006), and recipient age (P = .03) were independent predictors of atherosclerosis. CONCLUSIONS: Coronary atherosclerosis is frequently but inadvertently transmitted by means of cardiac transplantation from the donor to the recipient. Long-term outcomes of donor-transmitted coronary artery disease will require further evaluation.

Adult↗