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PubMedDate not supplied

Evaluation of the maximal excretion rate of indocyanin green as a prognostic indicator in patients undergoing biliary decompression for obstructive jaundice.

To assess the postoperative outcome of jaundiced patients and to select the optimal timing for surgical intervention, indocyanin green (ICG) concentrations in the bile were measured after biliary decompression in patients with obstructive jaundice. The maximal excretion rate of ICG in the bile was calculated as a function of time (ICG Bmax). Among 59 patients with positive ICG Bmax values, morbidity was 15.2% and postoperative hospital mortality was 3.3%. However, the morbidity and mortality in nine patients with values between -0.5 and 0 were 88.8 and 44.4%, respectively. The 13 patients with in ICG Bmax below -0.5 had a 76.9% morbidity and a 61.5% mortality. The patients with ICG Bmax values below 0 showed a significantly higher morbidity and mortality than positive ICG Bmax patients. In patients showing ICG Bmax values below -0.5, surgery is contraindicated despite intensive postoperative care. The ICG Bmax value improved according to the increasing effect of biliary decompression. The index is useful not only as a prognostic index in the early phase of biliary decompression but also as an index of bile secretory capacity at a given time. By means of time course measurement of this index, the suitable time for operation can be determined. The ICG Bmax is a useful and reliable indicator in the assessment of hepatobiliary functional reserve in jaundiced patients after biliary decompression and prior to further surgical intervention.

Adult↗
PubMed1999

Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients.

Nitric oxide (NO) is involved in tumor cell apoptosis and has additional effects on tumor blood flow, immune responses, and angiogenesis. We, therefore, studied endothelial cell NO synthase (ecNOS) protein expression in a retrospective series of 118 patients with primary invasive breast cancer. Immunocytochemically stained paraffin sections were used for determining the frequency of (a) tumor cells, (b) intratumoral microvessels, and (c) peritumoral microvessels that were positive for ecNOS. A high density of ecNOS positive microvessels in the normal tissue surrounding the tumor (measured by the variable PEMVD) was associated with significantly better recurrence-free and overall survival. The prognostic significance was observed in a representative series of premenopausal patients and was independent of other factors, including lymph node status. The counting procedure was highly reproducible and correlated to stereological measurements but was influenced by heterogeneity of the tissue samples. Analyzing two sections per patient improved the discriminative power by reducing the influence of tissue heterogeneity and produced highly significant results (recurrence-free survival, P < 0.001; overall survival, P < 0.0001). Immunoreactive ecNOS in microvessels is an independent prognostic factor in breast cancer and may reflect a mechanism of endothelial defense against invasion by tumor cells. Individual variations in ecNOS may be related to environmental, hormonal, and genetic factors and could represent a therapeutic target.

Adult↗
PubMed2000

Microsatellite analysis in multiple chromosomal regions as a prognostic indicator of primary bladder cancer.

This study investigated gene abnormalities in bladder cancer patients and the relationship between chromosomal alteration and the clinical outcome using microsatellite analysis. A total of 45 human bladder tumor patients were analyzed. The microsatellite markers for 18q21.1 (D18S46, D18S363, and D18S474), 9p21-22 (D9S171, D9S747, D9S1747, and IFNA), and 17p13.1 (TP53) were used for the loss of heterozygosity (LOH) detection. The clinical outcomes were estimated with univariate and multivariate analyses. The results show that patients with LOHs in 18q21.1 and 9p21-22 exhibited a significantly poor prognosis. LOHs of these chromosomal regions had the most predictable potential compared with the other known prognostic factors, such as tumor grade, TNM stage, and age. It is concluded that microsatellite analysis for 18q21.1 and 9p21-22 is capable of predicting the clinical outcome of bladder cancer patients.

Adult↗
PubMed2006

pT classification, grade, and vascular invasion as prognostic indicators in urothelial carcinoma of the upper urinary tract.

Clinicopathologic features predictive of patient outcome in upper urinary tract urothelial carcinoma are not well defined. The aim of this study was to assess the role of pT classification, tumor grade, and vascular invasion in predicting metastasis-free survival. A total of 190 consecutive invasive upper urinary tract urothelial cancers operated between 01/1984 and 12/2004 were re-evaluated with respect to pT classification, tumor grade (according to the three-tiered WHO 1973 and the recent two-tiered grading system following the WHO/ISUP consensus classification), as well as presence of lymph and/or blood vessel invasion. Prognostic impact was analyzed using the Kaplan-Meier method and the Log-Rank test. For multivariate testing, a Cox's proportional hazards regression model was used. pT1 was present in 81 (43%), pT2 in 29 (15%), pT3 in 73 (38%), and pT4 in seven (4%) cases. There were 12 (6%) G1, 96 (51%) G2, and 82 (43%) G3 tumors or 84 (44%) low-grade and 106 (56%) high-grade tumors according to the two-tiered system. The presence of vascular invasion in 72/190 (38%) tumors was associated with high pT classification (P<0.001) and high tumor grade (P<0.001). Disease progression occurred in 39% of patients, with 5- and 10-year metastasis-free survival rates of 56 and 45%, respectively. On univariate analysis, all investigated parameters showed prognostic significance. The negative influence of vascular invasion on patient outcome was strikingly strong in high pT classification and high-grade cancers. On multivariate analysis, pT classification (P<0.001) and vascular invasion (P<0.001) proved to be independent prognostic factors, whereas tumor grade according to the two-tiered system missed statistical significance (P=0.06). In conclusion, pT classification and vascular invasion are independent prognostic factors with respect to metastasis-free survival and should be used to guide adjuvant therapy strategies in affected patients. Presence (or absence) of vascular invasion should be commented upon separately in the pathology report.

Adult↗
PubMedDate not supplied

Prognostic indicators of local recurrence in patients operated for rectal cancer.

BACKGROUND/AIMS: To identify subgroups of patients at high risk of local relapse after curative surgery for rectal cancer. METHODOLOGY: Thirty-five variables of 216 patients observed from January 1987 to December 1995 were retrospectively analyzed according to univariate and multivariate methods. Median follow-up was 38 months. RESULTS: High and moderate grade (P = 0.0001), Size > or = 5 cm (P = 0.013), lymph nodes involvement (P = 0.002) and patients with locally advanced rectal cancer underwent extensive surgery and postoperative radiation significantly increased local relapse; whereas surgical procedure and experience of surgeons had no influence. CONCLUSIONS: The above-mentioned prognostic factors of rectal cancer that show a risk of local relapse 2- to 3.5-times higher than comparative conditions could be useful in identifying subgroups of patients at high risk for local recurrence. These patients should undergo a careful selection according to risk factors of relapse in order to increase local control of disease performing "optimal" primary surgery, effective postoperative radiation and tailored follow-up.

Adenocarcinoma↗
PubMed1988

Bladder cancer prognostic indices: analysis of 286 patients treated with radical radiation therapy.

From 1974 through 1982, 286 patients with histologically proven bladder cancer (Tis 8, T1 62, T2 109, T3 86, T4 21 NXMO) were treated with external irradiation after transurethral resection. Irradiation was given with 260 degrees arc technique photon beam from a Cobalt Unit; the tumor doses ranged from 52.5 to 65 Gy in 21-50 days, with a TDF between 75 and 110. The analysis was conducted with the log rank test on the cumulative percent survival (CPS) at 5 years. The study pointed out the importance of risk factors other than clinical stage on cumulative survival in bladder cancer. Prognostic factors associated with a relatively successful outcome (p less than 0.001) were the Karnofsky performance status (100 vs others) (CPS 75% vs 30%), the absence of ureteral obstruction on the initial intravenous pyelogram (CPS 50% vs 35%), a negative urine culture (CPS 60% vs 30%), normal bladder capacity (CPS 50% vs 35%), low-grade histology (CPS 65% vs 35%), and grossly complete resection (55% vs 40%). The data from this analysis should be taken into consideration when radical radiotherapy is considered in new clinical trials.

Cobalt Radioisotopes↗
PubMed1997

High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices.

One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.

Adolescent↗
PubMed1990

Survival of patients with ovarian cancer. Apart from stage and grade, tumor progesterone receptor content is a prognostic indicator.

Estrogen (ER), progesterone (PR), and androgen receptors (AR) were determined by saturation analysis in 100 cases of primary ovarian cancer and correlated with patient survival. The mean follow-up period was 5.4 years (range, 4 to 6.5 years). Positivity for PR was associated with a significantly better survival rate (P less than 0.05). A similar observation was made for AR (P less than 0.05). Tumor ER content did not correlate with survival. Ten patients with tumors that had negative results for both PR and AR all died of the disease. In 91 cases of serous, endometrioid, and mucinous carcinomas, grade, stage, and tumor PR content, but not AR content, were identified as independent prognostic factors with the use of the Cox proportional hazards model. The relative risk of patients with PR-negative tumors was 2.3 times higher than that of patients with tumors containing high (greater than or equal to 30 fmol/mg) PR levels.

Adolescent↗
PubMedDate not supplied

Tie-1 tyrosine kinase is an independent prognostic indicator for invasive breast cancer.

Receptor tyrosine kinases are known to be involved in the growth, progression and metastasis of solid tumors. We investigated the relationship between tie-1 expression and progression of invasive ductal breast carcinoma with immunohistochemical analysis. Tie-1 protein was detected in the microvessel endothelial cells and cytoplasm of tumor cells. The tumor size and stage were significantly associated with the expression of tie-1, which portends a worse 5-year disease-free status (39.3% v 59.2%, p = 0.07) and overall survival rate (67.3% v 93%, p = 0.02) than those without tie-1 expression. Multivariate analysis demonstrated that larger tumor size, presence of lymph node metastasis and tie-1 expression were independent prognostic parameters, both in 5-year disease-free survival and overall survival. Patients with lymph node metastases and tie-1 expression had the worst 5-year disease-free survival (0%) and overall survival (42.4%) compared to those without tie-1 expression (50.2%, 85%). In lymph node negative patients, those without tie-1 expression had better 5-year disease-free survival and overall survival (72.9%, 100%) compared to those with tie-1 expression (65.5%, 87.7%). We conclude that tie-1 expression is an independent prognostic factor for invasive ductal breast carcinoma, adversely affecting survival of breast cancer patients with positive nodes to a significant extent.

Biomarkers, Tumor↗
PubMed2006

Amplification of D22S283 as a favorable prognostic indicator in liver fluke related cholangiocarcinoma.

AIM: To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma (CCA) and define its correlation with clinical parameters. METHODS: Quantitative real time PCR (qPCR) was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the chi2 test. Cox regression analysis was used for determining patient's survival. RESULTS: Amplifications of the TP (22q13.33), TOB2 (22q13.2-13.31), D22S283 (22q12.3), TIMP3 (22q12.3) and NF2 (22q12.2) were found in 35 (53.8%), 28 (43.1%), 27 (41.5%), 24 (36.9%), and 24 (36.9%), respectively. Losses at the D22S423 (22q13.1-13.2) and BIK (22q13.31) were detected in 26 (40%) and 23 (35.4%), respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK (P = 0.025) and D22S283 (P = 0.041). Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis (P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779) and blood vessel invasion as an independent poor prognostic factor (P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571) in CCA patients. CONCLUSION: This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA. This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA.

Adult↗
PubMed2001

Base excess and lactate as prognostic indicators for patients admitted to intensive care.

OBJECTIVE: To examine whether values of arterial base excess or lactate taken on admission to a general intensive care unit indicate prognosis, and whether this can be used as a screening tool for future intensive care admissions. DESIGN: Observational study. SETTING: University teaching hospital general adult intensive care unit. PATIENTS: 148 consecutive patients admitted to the intensive care unit. INTERVENTIONS: Arterial blood samples were obtained on admission to the intensive care unit and 24 h following admission. MEASUREMENTS AND RESULTS: Arterial base excess and lactate concentrations were measured from the blood samples. Both base excess and arterial lactate samples on admission have good prognostic abilities (area under the curve on receiver operator characteristic analysis of 0.73, 0.78, respectively). The value of base excess on admission with the best predictive ability was a base excess more negative than -4 mmol/l, and the corresponding value for lactate was greater than 1.5 mmol/l. The combination of these two markers on admission to the intensive care unit led to a sensitivity of 80.3 % and a specificity of 58.7 % for mortality. The achievement of this combination was associated with an increased mortality (50.6 % vs. 15 %, p < 0.0001), older age (70 vs. 61.5 years, p < 0.05), a greater requirement for inotropic support (30.9 % vs. 4.5%, p < 0.0001) and higher organ failure scores both on admission and for the subsequent 24 h. CONCLUSIONS: Both base excess and lactate, or the combination of the two, can be used to predict outcome in patients admitted to the intensive care unit. These variables could be utilized to identify patients who have a high risk for mortality and thus who should be admitted to the intensive care unit.

Acid-Base Equilibrium↗
PubMed1992

Prognostic indicators in node-negative early stage breast cancer.

With the increasing availability of screening mammography, more women are diagnosed as having breast cancers at an early, node-negative stage. The majority of these patients would be cured with total mastectomy or breast conservation treatment. However, about 30% of the patients would have recurrence of disease in distant sites. In recent randomized clinical trials, adjuvant systemic therapy has been shown to reduce the rate of recurrence in these patients. Proper selection of patients for adjuvant therapy is necessary to avoid exposing many patients with low risk of recurrence to treatments for whom the benefit is not justified by the toxicity and the cost. In this article, we review the clinical and pathologic prognostic factors in early stage, node-negative breast cancer patients, including tumor size, nuclear and histologic grades, estrogen and progesterone receptors, menopausal status, proliferative rate, HER-2/neu oncogene amplification, and cathepsin D level. Favorable prognostic factors include tumor size less than or equal to 2 cm, low nuclear and histologic grades, low S-phase fraction, diploid state, low cathepsin-D level, and positive estrogen and progesterone receptor status. The value of HER-2/neu oncogene overexpression is controversial, and further studies are needed to define its role as a prognostic factor in patients with node-negative breast cancer. Based on these prognostic factors, it is possible to identify subsets of patients who have a low risk of recurrence and would not benefit significantly from adjuvant systemic therapy.

Breast Neoplasms↗
PubMed1982

Trial of labor after previous cesarean section: prognostic indicators of outcome.

A cross-sectional analytic survey of 92 patients permitted to attempt vaginal delivery after previous lower segment cesarean section ("trial of scar") is reported. Variables which may predict mode of delivery were assessed. Fifty patients (54.3%) were delivered vaginally; 42 patients (45.7%) had repeat cesarean sections in labor. There were three cases of scar dehiscence (3.2%). There were no maternal or fetal mortality. When the cervix was less than 3 cm dilated at initial examination in labor, 10 of 37 patients (27%) were delivered vaginally, compared to 38 of 55 patients (69%) who were delivered vaginally when the cervix was greater than 3 cm dilated. Assessment of cervical dilatation on admission in labor proved to be the most significant prognostic factor at the onset of labor, with regard to successful vaginal delivery in a patient with a lower segment cesarean section scar.

Cervix Uteri↗
PubMed2004

Evaluation of pregnancy-associated plasma protein A as a prognostic indicator in acute coronary syndrome patients.

BACKGROUND: Higher circulating concentrations of pregnancy-associated plasma protein A (PAPP-A), a potential proatherosclerotic metalloproteinase, have been associated with increased risk for acute coronary syndrome (ACS). Our goal was to determine the ability of circulating concentrations of PAPP-A to predict adverse events in patients presenting to the Emergency Department (ED) with symptoms of ACS. METHODS: A total of 346 patients with symptoms of ACS were included in the study. Serum samples obtained immediately after enrollment were analyzed for PAPP-A and cardiac troponin T (cTnT). The occurrence of adverse events during a 30-day follow-up period was recorded, and receiver-operating characteristic (ROC) curve analysis was performed to evaluate the prognostic characteristics of PAPP-A and cTnT. RESULTS: A total of 33 (9.5 %) patients developed adverse events during the follow up period. At a cut-off concentration of 0.22 mIU/l, PAPP-A was a predictor of adverse events with a sensitivity and specificity (95% C.I.) of 66.7% (48.2-82.0) and 51.1% (45.4-56.8), respectively. The sensitivity and specificity of cTnT were 51.5% (33.6-69.2) and 82.1% (77.4-86.2), respectively, using a 0.01-ng/ml cut-off value, which was obtained using ROC analysis. CONCLUSIONS: PAPP-A appears to be a modest predictor of adverse events in patients presenting to the ED with ACS symptoms, being inferior to cTnT in predicting adverse events in an ED setting. PAPP-A appears to be as sensitive as cTnT, but it is less specific.

Acute Disease↗
PubMed2004

Prognostic indicators and scoring systems for predicting outcome in patients with myelodysplastic syndromes.

A number of clinical, laboratory, morphological and genetic factors are useful to predict the natural course of Myelodysplastic syndromes (MDS). The identification of these factors resulted in the development of scoring systems that aid to differentiate high risk patients from those with a better prognosis. At the initial approach towards a patient with MDS the clinician will take into account the individual's age and performance score, and the morphological characteristics of the peripheral blood and bone marrow, including number of dysplastic lineages and blast count, as proposed by the new World Health Organization classification. Some laboratory features like the neutrophil and platelet count and the lactate dehydrogenase levels are of additional independent prognostic importance. Finally, the karyotype of the malignant hematopoietic cells is a very strong prognostic variable and therefore mandatory in the assessment of patients with MDS. By using part of the above-mentioned factors, the International Prognostic Scoring System has proven reliable in grouping MDS patients into one of four risk categories and can be used in the stratification of patients in therapeutic trials. With the avenue of more sophisticated molecular techniques like gene expression profiling, it might become possible not only to predict the natural course of the disease more precisely, but also to identify patient populations that are prone to respond to specific drugs especially designed for specific genetic lesions.

Anemia, Refractory, with Excess of Blasts↗
PubMed1985

Immunocytochemical staining of breast carcinoma with the monoclonal antibody NCRC 11: a new prognostic indicator.

The staining of breast cancer with a new monoclonal antibody, NCRC 11, was studied in a series of 126 women with primary breast carcinoma. Tumour samples embedded in paraffin were tested, and the minimum duration of follow up was five years or to death. Altogether 119 tumours stained positively. There was a strong relation between the intensity of staining, divided on a four point scale, and patient survival. Patients whose tumours exhibited intense staining had an improved survival compared with those with less intensely staining tumours (p less than 0.0001). Staining related weakly to histological grade but not significantly to oestrogen receptor state or the pathological stage of lymph node disease. Mathematical analysis showed the relation to survival to be independent of the other known prognostic factors. Inclusion of intensity of staining with other factors in a prognostic index might permit a more accurate estimation of prognosis in patients with breast cancer.

Antibodies, Monoclonal↗
PubMed1997

Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.

Adult↗
PubMed2000

MIB-1 labeling index as a prognostic indicator for survival in patients with FIGO stage IB squamous cell carcinoma of the cervix.

OBJECTIVE: The goal of this study was to assess whether the MIB-1 labeling index (LI) and conventional parameters could distinguish between a good and a poor prognosis in patients with squamous cell cervical carcinoma of the same FIGO stage. METHODS: The study included 97 cases of stage IB squamous cell cervical carcinoma which were treated with radical hysterectomy between 1989 and 1991. The relation of the MIB-1 LI, conventional clinicopathologic parameters, and survival was evaluated. RESULTS: The MIB-1 LI of the entire group of tumors was 57.1 +/- 15.9 (mean +/- SD). The MIB-1 LI was significantly different only in living and dead patients, while it was not related to conventional clinicopathologic prognostic parameters. The 5- and 10-year survival rates of patients with an MIB-1 LI </=55 were 90.0 and 88.6%, respectively, which were significantly better than the survival rates of patients with LI >55, which were 73.1 and 66%, respectively. Multivariate analyses showed that MIB-1 LI >55, lymph node metastasis, and tumor size >/=40 mm were powerful predictors of shorter survival. CONCLUSIONS: Lymph node metastasis, tumor size, and MIB-1 LI were significant prognostic markers in patients with stage IB squamous cell cervical carcinoma.

Adult↗