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PubMed1998

Long-term follow-up after subtotal parathyroidectomy in patients with renal failure.

OBJECTIVES/HYPOTHESIS: The most appropriate type of surgery for hyperparathyroidism secondary to renal failure remains controversial. We report a 5-year experience of patients with hyperparathyroidism secondary to end-stage renal disease who underwent subtotal parathyroidectomy. We believe that this is the procedure of choice, offering several advantages over total parathyroidectomy with and without reimplantation. STUDY DESIGN: Retrospective review. METHODS: Review of 14 consecutive renal failure patients who underwent subtotal parathyroidectomy by one surgeon (A.K.) was performed. Follow-up ranged from 4 to 54 months. All patients were receiving chronic maintenance dialysis. All patients came to surgery with clinical symptoms of parathyroid bone disease, elevated serum calcium levels (10.1-12.4 mg/dL), and intact parathyroid hormone levels (619-4160 pg/mL), despite maximal medical therapy. At exploration four glands were identified in all patients and three and a half were removed. RESULTS: All patients experienced symptomatic relief postoperatively with normalization or near-normalization of serum calcium concentration and intact parathyroid hormone concentrations. One patient developed recurrent disease 4 months after surgery, and on re-exploration a supernumerary substernal gland was identified. A second patient developed recurrent symptoms 4 years after surgery and at the time of this writing was awaiting re-exploration. CONCLUSIONS: All patients had either resolution of or marked improvement in their subjective complaints. There have been no cases of permanent hypoparathyroidism. We believe that subtotal parathyroidectomy is the best procedure for patients with refractory symptoms of secondary hyperparathyroidism.

Adult↗
PubMed2005

A controlled, prospective study of neuropsychological outcomes post parathyroidectomy in primary hyperparathyroid patients.

BACKGROUND: There is an increasing number of primary hyperparathyroidism (PHPT) patients with neuropsychological or psychiatric symptoms. Many of these patients do not have osseous or renal complications to satisfy the criteria for parathyroidectomy according to the NIH guidelines. OBJECTIVE: To assess whether there is any improvement in neuropsychological and mood symptoms following parathyroidectomy. PATIENTS AND DESIGN: Twenty PHPT patients undergoing parathyroidectomy and 20 orthopaedic controls matched for age, gender and estimated intelligence were subjects to pre and postoperative assessment of cognition and mood with a mean surgery-retest interval of 3 months. RESULTS: Using two tests of attentional flexibility [the Stroop test, the Digit symbol test of the Wechsler Adult Intelligence Scale-Revised (WAIS-R)], and two memory tests for prose and nonverbal material, no significant change was found between the groups when comparing scores before and after surgery. There was no improvement between pre and postoperative measures of verbal (dominant hemisphere) as opposed to visuo-spatial (nondominant hemisphere) function when compared to controls. There was no relationship between the reduction in serum calcium and the change in the neuropsychological measures postoperatively. CONCLUSION: This controlled, prospective study demonstrates no significant improvement in neuropsychological indices using objective, validated psychometric tools in an unselected cohort of PHPT patients. No relationship was found between serum calcium level and the degree of neuropsychological deficit. More studies are needed to assess whether the effect of parathyroidectomy is beneficial and sustainable in PHPT patients with neuropsychological symptoms alone.

Adult↗
PubMed2006

Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism.

OBJECTIVES: Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age-matched healthy controls, and the effects on BMD of parathyroidectomy. DESIGN, SUBJECTS AND INTERVENTION: A population-based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age-matched healthy controls. A 5-year follow-up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body. RESULTS: At study entry, BMD was 5-6% lower in the lumbar spine (L2-L4) and femoral neck in cases compared with matched controls. After the 5-year follow-up, BMD increased in L2-L4 by 2.9% (P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the cohort). CONCLUSION: In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2-L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population.

Absorptiometry, Photon↗
PubMed2000

Restoration of impaired T-cell proliferation after parathyroidectomy in hemodialysis patients.

BACKGROUND/AIMS: Severe secondary hyperparathyroidism is not infrequent in hemodialysis patients and recent studies suggest that parathyroid hormone (PTH) may play a role in the genesis of cell immunity abnormalities in uremia. The aim of the present study is to describe the effect of parathyroidectomy on T- and B-cell functions in hemodialysis patients. METHODS: The study was performed on 6 patients with severe secondary hyperparathyroidism. iPTH, B, CD4(+), CD8(+), total number of lymphocytes, lymphoproliferative response to PHA, PWM and Candidin, and IgG, IgM, IL-2 production in vitro were determined 1 day before and 4 months after parathyroidectomy. RESULTS: The lymphoproliferative response to PHA increased significantly after parathyroidectomy. We also observed a trend to an increase in production of IgG and IgM after PWM stimulation before therapy. CONCLUSION: The present study suggests that patients with extremely high levels of PTH show a complete restoration of impaired T-cell proliferation after parathyroidectomy.

Adult↗
PubMed1999

[Intraoperative blood sampling for parathyroid hormone measurement during total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism].

Normalisation of intact parathyroid hormone serum level confirms sufficient resection of parathyroid tissue after total parathyroidectomy in patients with secondary hyperparathyroidism. The short half-life of the intact parathyroid hormone is such that complete resection may even be confirmed by intraoperative monitoring of the hormone, and operative exploration thus reduced. We tested intact parathyroid hormone serum levels in 9 patients during total parathyroidectomy, preoperatively, after the removal of each gland, after autotransplantation and 1 month postoperatively. The serum levels of the intact parathyroid hormone were significantly reduced after removal of each gland. The total percentage decrement after parathyroidectomy with autotransplantation was 77%. However intact parathyroid hormone levels had normalised in all patients one month after the operation. The absence of perioperative normalisation of intact parathyroid hormone serum levels in our patients cannot be defined as a predictor of incomplete resection in total parathyroidectomy. The definition of an intraoperative cut-off-level concerning the decrement of intact parathyroid hormone levels remains to be proven in further studies.

Adult↗
PubMed2000

The effect of clinical pathway implementation on total hospital costs for thyroidectomy and parathyroidectomy patients.

Clinical pathways have long been used to guide the delivery of patient care in varied practice settings. There is little information in the literature to document the effectiveness of pathway implementation in general surgical populations. This study reports the effect of clinical pathway implementation in two general surgical patient groups, thyroidectomy and parathyroidectomy. Clinical pathways were implemented to serve patients undergoing thyroidectomy and parathyroidectomy surgery. The effects of both clinical pathways on total hospital costs, length of hospitalization, variances, and outcomes were collected and evaluated from July 1998 through July 1999. These data were compared to data from the previous year. The average length of stay for parathyroidectomy patients decreased from 2.4 to 1.5 days (P = 0.26) for pathway patients as compared to prepathway patients. The average cost per case decreased from $5071 to $4291 (P = 0.50) for parathyroidectomy pathway versus prepathway patients. The average length of stay decrease for thyroidectomy patients was 1.4 to 1.2 (P = 0.16) for the pathway to prepathway comparison. The average cost per case decrease was minor at $4117 to $4111. Pharmacy costs and laboratory utilization were effectively reduced. Perioperative costs rose dramatically during this period, operating room/central sterile supply cost per case rose 12 per cent, anesthesia supply cost per case rose 15 per cent, and surgical pathology costs increased 110 per cent overall for both patient groups. Clinical pathway implementation has allowed us to reduce or maintain total hospital costs in the face of rising perioperative costs. We conclude that implementation of these clinical pathways has allowed us to improve consistency with which we deliver care while maintaining the quality of patient outcomes and reducing the costs of care and length of hospital stay.

Adolescent↗
PubMedDate not supplied

Maxillary brown tumor in secondary hyperparathyroidism requiring urgent parathyroidectomy.

Brown tumors are unusual but serious complications of renal osteodystrophy, and can be successfully treated by parathyroidectomy or by pharmacological treatment of hyperparathyroidism. Brown tumors in patients with severe hyperparathyroidism (HPT) secondary to renal failure have been increasingly reported. We describe an unusual case of brown tumors at the maxillary bone and the seventh right rib, in a 57-year old man with a long history of hemodialysis. The maxillary lesion caused serious local discomfort due to its rapid growth. In this setting, surgical total parathyroidectomy was chosen as the most adequate therapeutic approach, given the previous unsatisfactory response to calcitriol. After successful parathyroidectomy, rapid healing was achieved with sclerosis of both brown tumors, as documented by serial computerized tomograms. In conclusion, although vitamin D therapy has been beneficial in several cases of secondary hyperparathyroidism complicated by brown tumors, we propose that whenever regression of the tumor bulk is urgently needed, as in our case, parathyroidectomy should be the first treatment choice.

Bone Neoplasms↗
PubMedDate not supplied

Improved health-related quality of life and left ventricular hypertrophy among dialysis patients treated with parathyroidectomy.

BACKGROUND: We prospectively studied changes in the perception of health-related quality of life, pruritus, and degree of left ventricular hypertrophy in end-stage renal disease patients with tertiary hyperparathyroid disorder, before and 6 months after total parathyroidectomy treatment. METHODS: A series of 12 consecutive patients were enrolled. Throughout the follow-up period, all subjects completed the Kidney Disease Quality of Life Short Form-36 (KDQOL SF-36) questionnaire at inclusion and after 6 months. Serial clinical and physiological parameters including uremic pruritus, blood pressure control and left ventricular hypertrophy measured by echocardiography were recorded. RESULTS: Mean scores of the KDQOL SF-36 questionnaires were substantially higher 6 months after parathyroidectomy, with reference to physical functioning, bodily pain, role-physical, role-emotional, symptom list and burden of kidney disease. Parathyroidectomy resulted in a 22% reduction in left ventricular mass index, with significant improvement from the baseline value of 246 +/- 131 to 192 +/- 131 g/m2 (p = 0.03). CONCLUSION: Our findings highlight the potential importance of parathyroidectomy in improving health-related quality of life and left ventricular hypertrophy among dialysis patients with tertiary hyperparathyroidism.

Female↗
PubMedDate not supplied

[Video-assisted minimally invasive parathyroidectomy with lateral approach in patients with primary hyperparathyroidism].

INTRODUCTION: Different minimally invasive techniques of parathyroidectomy have been described. We performed a retrospective study to evaluate the indications and results of video-assisted parathyroidectomy (VAP) in the management of patients with primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: Between 1998 and 2002, 528 patients were operated on because PHPT. VAP was proposed for patients with sporadic PHPT, without associated goiter and previous neck surgery, in whom a single adenoma was localized. VAP was performed by lateral approach with insufflation for patients with adenoma located deeply in the neck and by gasless midline approach for anteriorly located adenomas. A quick parathyroid (qPTH) assay was used during the surgical procedure. Calcemia, phosphoremia and PTH were systematically evaluated after surgery. RESULT: Of 528 patients with PHPT, 228 (43%) were not eligible for VAP because associated nodular goiter (99 cases), previous neck surgery (42 cases), suspicion of multiglandular disease (25 cases), lack of preoperative localization (48 cases), and miscellaneous causes (14 cases). VAP was performed in 300 patients with sporadic PHPT: 282 lateral access, 17 midline access and one thoracoscopy. Mean operative time was 50'. Conversion to conventional parathyroidectomy was required in 14% of cases. One patient presented a definitive recurrent nerve palsy. One persistent and one recurrent PHPT were observed. CONCLUSION: VAP can be proposed for patients with PHPT. Immediate results of VAP are similar to those obtained with conventional parathyroidectomy; no conclusions can be drawn in terms of influence of VAP on the outcome of the patients operated for PHPT.

Humans↗
PubMed2004

Post-parathyroidectomy hypocalcemia: incidence, risk factors, and management.

The purpose of this study was to evaluate the incidence and severity of hypocalcemia after parathyroidectomy and delineate its risk factors. Data was retrieved from a prospective database. Patients with postoperative hypocalcemia were identified and risk factors were investigated including primary versus renal hyperparathyroidism (HPT), preoperative calcium, parathyroid hormone (PTH) and alkaline phosphatase levels, gland weight, pathology, extent of surgery, and reoperative surgery. Of the 162 patients who underwent parathyroidectomy, 84 (52%) were hypocalcemic postoperatively: 55 (42%) of 132 patients with primary and 29 (97%) of 30 patients with renal HPT (P = 0.0001). Patients with renal HPT had more profound hypocalcemia with a mean +/- SD calcium of 7.34 mg/dL +/- 1.07 versus 7.76 mg/dL +/- 0.59 for patients with primary HPT (P < 0.05). Symptoms were present in 28 (51%) of 55 patients with primary and 13 (45%) of 29 patients with renal HPT. Only three (2%) patients with primary compared to 29 (97%) with renal HPT were treated with intravenous calcium. The average length of stay for hypocalcemic patients was 0.7 days for primary HPT versus 4.7 days for renal HPT (P < 0.0005). Patients with primary HPT who underwent subtotal parathyroidectomy had significantly lower postoperative calcium levels (7.95 mg/dL +/- 0.64) than patients who had a single or double adenoma removed (8.49 mg/dL +/- 0.79) (P = 0.036). No other factor was predictive of postoperative hypocalcemia. Patients with renal HPT develop profound postoperative hypocalcemia requiring intravenous calcium and vitamin D therapy. Hypocalcemia in patients with primary HPT develop less severe hypocalcemia that is amenable to outpatient oral calcium therapy and should be routinely initiated following subtotal parathyroidectomy.

Calcium↗
PubMed2004

A transitory polycytaemia after parathyroidectomy for secondary hyperparathyroidism--a literature survey and a case study.

The present study is a literature review of a nephrological problem--secondary hyperparathyroidism, its surgical treatment and the effect of the intervention on the anemic syndrome in patients with chronic renal failure (CRF) on hemodialysis treatment. We present a case of a 29-year-old female hemodialysis patient with a transitory polycytaemia (duration of 5 months) after parathyroidectomy for secondary hyperparathyroidism. Prior to surgery she was constantly anemic in spite of epoetin treatment lasting 10 years. Ten days after the parathyroidectomy there was a crucial decline of parathormone (from 900.4 pg/ ml to 21.4 pg/ml) and ionized calcium (iCa) (from 1.23 mmol/l to 0.79 mmol/l) and the hemoglobin level reached 170 g/l with a hematocrit of 0.53. After discontinuation of epoetin treatment (58.8 U/kg/week) in the following 5 months hemoglobin level declined reaching 144 g/l. Two years after parathyroidectomy the patient is still with normal hemoglobin level (125-135 g/l) without epoetin treatment. We discuss the likely mechanisms for the early onset of polycytaemia after parathyroidectomy as well as the importance of adequate control of secondary hyperparathyroidism in the management of anemia in chronic renal insufficiency.

Adult↗
PubMed2004

Efficacy of whole PTH assay and 1-84/non-(1-84) PTH ratio in patients on hemodialysis or undergoing parathyroidectomy.

For measurement of parathyroid hormone (PTH), the intact PTH (I-PTH) assay is generally used. However, I-PTH assay apparently detects PTH 7-84 fragments, in addition to PTH 1-84. The whole PTH (W-PTH) assay exhibits no cross-reactivity with PTH 7-84. Ratio of PTH 1-84 to non-(1-84) PTH has been proposed as a non-invasive indicator of bone turnover in patients with end-stage renal disease (ESRD). We evaluated the efficacy of W-PTH assay and 1-84/non-(1-84) PTH ratio in hemodialysis patients and patients who had undergone parathyroidectomy. PTH levels were measured using W-PTH and I-PTH assays in 138 hemodialysis patients, 27 healthy controls and 10 patients who were scheduled to undergo parathyroidectomy for secondary hyperparathyroidism. Alkaline phosphatase, bone alkaline phosphatase and intact osteocalcin were also measured for comparison with 1-84/non-(1-84) PTH ratio. W-PTH was strongly correlated with I-PTH in both groups, and with all three bone metabolic markers in hemodialysis patients. In hemodialysis patients, both PTH and bone metabolic markers were significantly lower in the subgroup with a PTH ratio < 1.0 than in the subgroup with a PTH ratio > or = 1.0. However, PTH ratio exhibited no significant correlation with bone metabolism markers. PTH ratio was higher after parathyroidectomy than before. W-PTH and I-PTH assays offer identical indicators of bone metabolism in ESRD patients. However, 1-84/non-(1-84) PTH ratio may be of limited diagnostic use regarding bone turnover if a cut-off value of 1.0 is used. PTH 1-84 may be secreted relatively more than non-(1-84) PTH after parathyroidectomy, due to decreases in serum calcium. As the W-PTH assay allows easy calculation of non-(1-84) PTH by subtracting the I-PTH value, this assay contributes to identification of the function of non-(1-84) PTH fragments in various conditions.

Biomarkers↗
PubMed1992

[Clinical study of parathyroidectomy of secondary hyperparathyroidism in patients with chronic renal failure].

We performed parathyroidectomy for renal osteodystrophy due to secondary hyperparathyroidism on 16 patients with chronic renal failure who were refractory to medical management; subtotal parathyroidectomy on one patient and total parathyroidectomy with autotransplantation on 15 patients. Postoperative clinical improvement, i.e., bone and/or joint pain, pruritus and radiographic signs of renal osteodystrophy, was marked. After the operation, serum calcium decreased rapidly and adequate calcium replacement therapy was necessary. The levels of intact parathyroid hormone decreased rapidly and serum concentration of alkaline phosphatase gradually decreased for a few months postoperatively. Recurrence was diagnosed in one patient, who underwent excision of the transplanted parathyroid tissue. Osteomalasia due to hypoparathyroidism was not seen clinically in this series. In preoperative image diagnosis, ultrasonotomogram (US) showed the highest detective rate of the enlarged parathyroid glands. However, combination of US, computerized tomography and 99mTcO4(-)-201T1C1 scintigram can be recommended as a localizing diagnostic method for compensating the disadvantages of each method. Clinical results after parathyroidectomy for secondary hyperparathyroidism are considered to be good. However, long-term followup is mandatory for early detection of persistent hyperparathyroidism or hypoparathyroidism.

Adult↗
PubMed1993

[Changes in plasma renin and aldosterone after parathyroidectomy in patients with hyperparathyroidism].

The plasma renin activity and its changes after parathyroidectomy indicate a preserved internal secretory renal function in dialyzed patients. The PRA values before parathyroidectomy are not unequivocally related to the blood pressure reading. After parathyroidectomy during the initial months the renin and aldosterone plasma levels decline in patients with secondary and primary HPT (p < 0.001), the urinary Na/K quotient rises in primary HPT (p < 0.05) and the systemic blood pressure declines in dialyzed patients with secondary HPT (p < 0.001). The findings suggest relations between the two hormonal systems during hyperparathyroidism and in the early stage after parathyroidectomy. Parathormone probably stimulates renin secretion. After a prolonged time interval following operation the parathormone levels in the blood steam reach normal levels and the same probably applies to intracellular calcium in cells of the iuxtaglomerular apparatus along with PRA.

Adult↗
PubMed1997

Large, rapid skeletal changes after parathyroidectomy.

We report dramatic increases in spine and hip bone mineral density six weeks following parathyroidectomy in renal patients. We have previously reported a cross-sectional association between parathyroidectomy and higher axial bone mineral density in dialysis patients. Large axial increases in bone mineral density after surgery for primary hyperparathyroidism have been recorded by others at one year postoperatively. Bone mineral density was recorded before and six weeks after parathyroidectomy. Scans were performed at the lumbar spine, hip and non-dominant radius. Values were expressed as Z-scores (standard deviations from the mean of an age- and gender-matched reference population). Large increases in lumbar were spine and femoral neck bone mineral density seen at six weeks post parathyroidectomy. Median increases were 0.57 (p = 0.006) and 0.26 (p = 0.039) Z-score units for these sites, respectively. Individual six-week increases were as large as 1.3 Z-score units at the spine and 1.0 Z-score units at the femoral neck. No significant cohort change was detected at the forearm but individual forearm changes were highly variable. Several mechanisms to explain these large rapid increases can be postulated. These include: mineralization of osteoid and/or contraction of the remodeling space. The changes illustrate the extent to which the skeleton is capable of rapid and profound change in mineral content. Our findings emphasize that the skeleton is a heterogeneous organ and that bone density should be measured at multiple skeletal sites.

Absorptiometry, Photon↗
PubMed1987

Adrenal responses to subtotal parathyroidectomy for primary hyperparathyroidism.

Although it is well known that hypertension is often associated with primary hyperparathyroidism and that parathyroidectomy reverses or reduces this abnormality, the etiology of elevated blood pressure in hyperparathyroidism is still conjectural. We have analyzed serum calcium, blood pressure, and metabolites of adrenal cortical hormones before and after surgical therapy for hyperparathyroidism in 10 normotensive and six hypertensive patients with primary hyperparathyroidism. Successful parathyroidectomy lowered serum calcium (P less than 0.01) and diastolic blood pressure (P less than 0.05) in all subjects. Mean urinary aldosterone and Porter-Silber chromagens were within normal limits preoperatively in normotensive as well as hypertensive subjects. After parathyroidectomy, aldosterone levels as well as Porter-Silber chromagens decreased significantly in all patients (P less than 0.01). However, when normotensive and hypertensive subjects were analyzed separately, the decrease in aldosterone levels was significant only in the normotensive group (P less than 0.05) whereas the decrease in Porter-Silber chromagens reached significancy only in the hypertensive group (P less than 0.01). The results indicate that surgical therapy for hyperparathyroidism lowers serum calcium and blood pressure and is associated with a decrease in the excretion of adrenal steroid metabolites. It is suggested that the temporal relationship which exists between ionized calcium and steroidogenesis in hyperparathyroid patients contributes at least in part to the generalized decrease in blood pressure observed after successful parathyroidectomy.

17-Hydroxycorticosteroids↗
PubMed1981

Changes in bone and serum minerals after parathyroidectomy and their prevention by portacaval shunt.

The effect of portacaval shunt and parathyroidectomy on the concentration of calcium, magnesium, phosphate and hydroxyproline in the bone and the concentration of the three minerals in the serum has been studied in the growing rat. Parathyroidectomy produced a decreased net bone reabsorption as evidenced by higher concentrations of calcium, magnesium and phosphate; and a reduced net matrix formation, as evidenced by lower concentrations of hydroxyproline. Portacaval shunt, when performed with parathyroidectomy, prevented the development of these changes and produced "normal" concentrations of most of those elements, comparable to their concentrations in the control animals. The changes in serum calcium and magnesium produced by parathyroidectomy were prevented when portacaval shunt was performed in conjunction with the former procedure. Portacaval shunt alone produced no significant changes except for hypophosphatemia. This hypophosphatemia is speculated to have stimulated the production of 1,25-(OH)2D3 in the kidney, which in turn produced those observed effects of portacaval shunt in the parathyroidectomized rat.

Animals↗
PubMed1984

Subtotal versus total parathyroidectomy with forearm autograft for secondary hyperparathyroidism in chronic renal failure.

Forty-three patients with chronic renal failure and secondary hyperparathyroidism underwent parathyroidectomy; 20 of the 43 underwent subtotal parathyroidectomy (Group A) and 23 patients underwent total parathyroidectomy and parathyroid autotransplant in the forearm (Group B). Postoperative clinical improvement was similar in both groups. In the immediate postoperative period eight patients in Group A who had severe bone changes and 21 patients in Group B needed supplemental calcium administration. The grafted tissues in all cases functioned well; reimplantation of the cryopreserved parathyroid tissues was unnecessary. One case in each group showed a recurrence. One patient in Group A was submitted to reexploration of the neck with a lateral approach. The other patient in Group B underwent excisions of the transplanted parathyroid tissues on three separate occasions under local anesthesia. The second operation was definitely easier and safer to manage after a total parathyroidectomy with autotransplantation to the forearm.

Adult↗