Rapid Recuperation After Surgical Intervention and Rehabilitation in a Patient With Spinal Hemangioma: A Case Report.

This case report describes the remarkable recovery journey of a 42-year-old male who suffered from neurological symptoms over three months, including tingling in both lower extremities. It was determined that a spinal hemangioma, a normally non-cancerous medical ailment, was the cause of these symptoms, which were also accompanied by difficulty walking and problems with bowel and bladder incontinence. A laminectomy and spinal cord decompression surgery were the two most significant medical procedures the patient underwent as part of his treatment, followed by a carefully structured rehabilitation program, as part of a holistic approach. Astoundingly, the patient's physical condition showed considerable improvements in several areas just one week after surgery. The reduction of pain, increased range of motion (ROM), and increased muscular strength were the aspects where these changes were most noticeable. This quick recovery reflects the benefit of combining surgical and rehabilitation techniques in these patients. The patient was prescribed a home exercise program (HEP) at the time of his discharge from the hospital so that he could continue his recovery independently in the comfort of his own home. This HEP was created to ensure that the patient could keep up and continue to make progress. This case report sheds light on the benefits of adopting a comprehensive strategy while treating spinal hemangiomas. The combined efforts of the surgical and rehabilitation therapy teams greatly improved the patient's prognosis. This aspect of synergy helped develop a whole treatment strategy that included both surgical tumor removal and crucial postoperative rehab for optimum healing and function.

Unraveling Anastomosing Hemangioma: A Case Report.

Anastomosing hemangioma is a rare and benign subtype of capillary hemangioma, a soft tissue tumor. It tends to be asymptomatic, causes abdominal pain and hematuria, and is more common in the genitourinary tract. It can be confused with paragangliomas or ectopic pheochromocytomas. Pathology shares characteristics with angiosarcoma, particularly in well-differentiated areas. Diagnosis without a surgical specimen is difficult and is based on clinical characteristics, laboratories, and imaging behavior similar to hemangiomas in other locations. When in doubt, a diagnosis can be supported by a percutaneous biopsy. The prognosis is good, without relapses or metastases. Early identification with follow-up can avoid surgical interventions.

Subcutaneous fibroblastoma resembling hemangioma: A case of benign tumor of the chest wall.

Key Clinical Message: Desmoplastic fibroma presents similar to other soft tissue tumors to such an extent that even a gold standard investigation can miss. Abstract: This is to report a mass in a 47-year-old male arising from the chest wall, which was first thought to be a hemangioma but was later diagnosed as a case of desmoplastic fibroblastoma with the help of a biopsy.

Breast Hemangiomas: Imaging Features With Histopathology Correlation.

Breast hemangiomas are rare benign vascular lesions. In a previously performed review of approximately 10,000 breast surgical pathology results, roughly 0.15% (15/~10,000) were hemangiomas. Hemangiomas are more frequent in women and have a documented age distribution of 1.5 to 82 years. They are most often subcutaneous or subdermal and anterior to the anterior mammary fascia but may rarely be seen in the pectoralis muscles or chest wall. On imaging, breast hemangiomas typically present as oval or round masses, often measuring less than 2.5 cm, with circumscribed or mostly circumscribed, focally microlobulated margins, equal or high density on mammography, and variable echogenicity on US. Calcifications, including phleboliths, can be seen. Color Doppler US often shows hypovascularity or avascularity. MRI appearance can vary, although hemangiomas are generally T2 hyperintense and T1 hypointense with variable enhancement. Pathologic findings vary by subtype, which include perilobular, capillary, cavernous, and venous hemangiomas. If core biopsy pathology results are benign, without atypia, and concordant with imaging and clinical findings, surgical excision is not routinely indicated. Because of histopathologic overlap with well-differentiated or low-grade angiosarcomas, surgical excision may be necessary for definitive diagnosis. Findings that are more common with angiosarcomas include size greater than 2 cm, hypervascularity on Doppler US, irregular shape, and invasive growth pattern.

Efficacy of foam sclerotherapy with polidocanol for the management of oral venous malformations.

The present aimed to examine the effectiveness of polidocanol-based foam sclerotherapy for oral venous malformations (OVMs). The present study performed a retrospective analysis of patients with OVMs who underwent sclerotherapy using polidocanol. Patients achieving the complete resolution of OVM were categorized as having a complete response (CR), those with a reduction in size from the initial diagnosis were categorized as having a partial response (PR), those with no change in size as stable disease (SD), and those with an increase in size as progressive disease (PD). A total of 16 patients, comprising 4 males and 12 females, underwent treatment with polidocanol foam therapy, covering 22 affected areas. The treatment administered resulted in CR in 6 cases and PR in 10 cases, with no instances of SD or PD. Apart from localized injection site pain or swelling, there were no severe side-effects reported, such as circulatory dynamic changes or skin necrosis. On the whole, these findings underscore the effectiveness of foam sclerotherapy with polidocanol as a viable treatment for venous malformations in the oral and maxillofacial regions.

Serum apelin as a potential biomarker for infantile hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are common benign vascular tumors in infants. Apelin, an endogenous cytokine, is implicated in the angiogenesis of neoplastic diseases. We aimed to explore the association between apelin and IHs, providing a foundation for clinical applications. METHODS: We identified differential expression of apelin in proliferative IHs compared to healthy controls (HCs) through bioinformatics analysis of publicly available databases and verified by Immunofluorescence. Enzyme-linked immunosorbent assay was used to quantify the serum levels of apelin and vascular endothelial growth factor (VEGF) in a cohort of 116 cases of proliferative IHs, 65 cases of capillary malformations (CMs), and 70 HCs. RESULTS: Apelin and APJ (APLNR, apelin receptor) were identified as the significantly upregulated differentially expressed genes (DEGs) in proliferative IHs. Immunofluorescence staining indicated high expression of apelin in proliferative IHs, while minimal expression in non-IH lesions. Apelin in IHs was reduced following 6 months of propranolol treatment. Serum apelin levels were significantly higher in the IH group compared to both the CM and HC groups. Moreover, apelin exhibited excellent discriminatory ability in distinguishing IHs from HCs, with an area under the curve (AUC) exceeding 0.90. A positive correlation was observed between the levels of apelin and the size of superficial IHs. The expression profiles of VEGF and apelin in IHs were found to be consistent. CONCLUSIONS: Apelin shows promise as a potential biomarker for IHs. The association between apelin and IH size, as well as its responsiveness to propranolol treatment, indicates its possible utility as a valuable indicator for the therapeutic evaluation of IHs.

Could a low-dose definitive radiation therapy be the optimal treatment for choroidal hemangioma?

PURPOSE: To determine the efficacy of low-dose intensity-modulated radiation therapy (IMRT)/volumetric intensity-modulated arc therapy (VMAT) in the treatment of symptomatic choroidal hemangioma (CH). MATERIALS AND METHODS: Fifty-three consecutive patients with CH were retrospectively reviewed. All the patients underwent IMRT/VMAT as a unique treatment. Resolution of subretinal fluid (SRF), improvement of best-corrected visual acuity (BCVA), and reduction in tumor thickness were compared before and after radiotherapy. RESULTS: After definitive radiotherapy, 100 % of SRF and 76.7 % of exudative retinal detachment were resolved. 56.6 % of BCVA improvement in more than two lines was observed. The mean best-corrected visual acuity was 20/280 (range, 20/1200-20/40) at diagnosis and 20/100 (range, 20/1200-20/20) after treatment. The mean tumor thickness decreased significantly from 3.8 mm initially to 1.2 mm after treatment (p < 0.01). 66.0 % of patients were delivered with 21.6 Gy (range, 21.6-42 Gy), 84.9 % of fractional dose was 1.8 Gy (range, 1.8-2 Gy). No radiation-induced keratitis, retinopathy, or optic neuropathy were observed. Initial vision (p = 0.042), duration time of vision (p = 0.004), and tumor thickness (p = 0.049) were prognostic factors for vision recovery. CONCLUSION: Low-dose IMRT/VMAT could effectively induce involution of the CH, with reduction of subretinal fluid and relief of damage to the neurosensory retina, which is an effective treatment mode for CH.

Large, ulcerated infantile hemangioma of the chest wall complicated by life-threatening hemorrhage: Case report and literature review.

While ulceration is one of the most common infantile hemangioma (IH) complications, severe bleeding is a rare consequence, with a paucity of patients reported. We report a 5-month-old girl with a very large, mixed, partial segmental IH of the upper chest wall who, despite medical intervention, developed severe ulceration and multiple episodes of life-threatening bleeding that ultimately led to hemorrhagic shock. Experience in our patient and a review of six previous reports shows that severe bleeding is a risk when ulceration extends directly into an arterial feeding vessel that is often visible clinically. Other potential predictors for severe bleeding include large to very large IH size with extension of the tumor into underlying structures, segmental or partial segmental patterning, mixed and bulky morphology, and white discoloration as a sign of impending or worsening ulceration.

Clinical course of patients with conservatively managed cerebral cavernous malformations.

INTRODUCTION: There is uncertainty whether patients with a cerebral cavernous malformation (CCM) should undergo conservative or surgical treatment, resulting in practice variation among hospitals. Our objective was to report clinical outcomes of patients with primarily conservatively managed CCMs. PATIENTS AND METHODS: This single-center cohort study included consecutive adult CCM patients, diagnosed in 2000-2023, who underwent conservative management as primary treatment strategy. Data were extracted from medical records, and we systematically conducted telephone and questionnaire follow-up. Functional status was assessed on the modified Rankin Scale (mRS). RESULTS: Of 345 patients, we included 265 patients with a CCM (median age 46 years; 45% male). At baseline, 131 (49%) patients presented with symptomatic hemorrhage (SH), and 134 (51%) with other symptoms or asymptomatically. During 58 months (IQR 35-94) median follow-up, 51 (19%) patients experienced a SH, 33 (12%) a seizure, and 13 (5%) focal neurological deficits. Fourteen (5%) patients underwent intervention (surgery n = 11, radiosurgery n = 4). Presentation with SH was associated with higher annual bleeding rates (6.0% vs 1.5%, p < 0.001), and higher cumulative 5-/10-year bleeding risks (31%/41% vs 7%, p < 0.001). Brainstem CCM was associated with higher cumulative 5-/10-year bleeding risks (27%/38% vs 17%/21%, p = 0.038). Nineteen (7%) patients died; two (0.8%) directly attributable to CCM. Of 246 surviving patients, 205 (83%) completed the questionnaire. At follow-up, 172/224 (77%) patients were functionally independent (mRS score ⩽2). DISCUSSION AND CONCLUSION: The majority of conservatively managed CCM patients remained free of a SH during follow-up. Few patients required intervention, and death attributable to the CCM was rare. These data may help patient counseling and treatment decisions.

A case report of lobular intradural extramedullary capillary hemangioma in a 14-year-old patient: resection and reconstruction.

Background: Intradural, extramedullary capillary hemangiomas of the cauda equina are exceedingly rare malformations arising from the endothelial cells of the nervous system vasculature. Roughly 20 cases have been reported in the literature, with the youngest and only pediatric case being in a 17-year-old patient. We report the youngest case of intradural extramedullary capillary hemangioma of the cauda equina in a 14-year-old patient. Case Description: A 14-year-old female presented with two-month history of low back pain with bilateral leg pain and numbness. Magnetic resonance imaging (MRI) revealed an L2 well-defined homogenous contrast-enhancing intradural, extramedullary mass causing severe spinal canal stenosis. Patient underwent laminoplasty for resection of an intradural tumor. Intraoperative hemostasis was readily achieved via early identification and coagulation of the predominate feeding vessel. Postoperatively, the patient awoke with no deficits and resolved leg pain. A 3-month postoperative MRI revealed no tumor recurrence and fully healed lamina. Conclusions: Given the benign nature, the operative goal is complete excision of the tumor without damage to surrounding neural structures. Postoperatively the goal is relief of pain and improvement in neurologic function. To our knowledge we report the first case in which laminoplasty is utilized for the treatment of this pathology in a pediatric patient. Evidence for laminoplasty in this patient population is sparse and future studies are still needed. In any case, reconstruction of the surgical site in a manner that returns the patient's normal anatomy should be strongly considered especially in younger patients.

PHACE syndrome: a case report and a comprehensive review.

Introduction and importance: PHACE syndrome is a rare neurocutaneous disorder characterized by large segmental hemangiomas on the face and is associated with multiple developmental defects. PHACE stands for posterior fossa malformations, hemangiomas, arterial abnormalities, cardiac defects, and eye anomalies, with the most common manifestation being hemangioma in the cervico-facial region in early childhood. Case presentation: The authors report a case of a 15-year-female with complaints of facial hemangioma which on multisystemic imaging showed features of central nervous system (CNS) anomalies that led to the diagnosis of PHACE syndrome. The patient was started on propanolol which decreased the size of hemangioma in follow-up visits. Clinical discussion: The hemangioma in the frontotemporal and frontonasal area of the face are associated more with CNS and cardiovascular anomalies needing a detailed multisystem approach. CNS anomalies include posterior cerebral fossa enlargement, cystic dilation of the fourth ventricle, arachnoid cyst, and cerebellar hypoplasia which were present in our case. Propanolol is considered the first-line drug for facial hemangioma with reported evidence of remarkable improvement and good tolerance. However, regular follow-up of the patient is needed to rule out any recurrence. Conclusion: PHACE syndrome, although being a rare occurrence, must be kept as a differential diagnosis in infants and children with facial hemangioma. Imaging modalities like MRI/magnetic resonance arteriography must be used to rule out possible associations related to PHACE syndrome and focus on early treatment to prevent possible complications.

Endoscopic ultrasound-guided lauromacrogol injection for treatment of colorectal cavernous hemangioma: Two case reports.

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

Epithelioid Hemangioma of the Popliteal Artery: A Case Report.

An epithelioid hemangioma (EH) is a rare benign vascular lesion that is usually seen in superficial small vessels within the dermis and subcutaneous tissue. Intravascular epithelioid hemangiomas of large and medium-sized vessels are rare, and only a handful of cases have been reported in the literature. Intravascular epithelioid hemangiomas are biologically benign and best treated by complete surgical excision. On occasion, lesions have been associated with aneurysmal changes in the affected vessel. Local recurrence may occur, and close clinical follow-up is advised. Herein, we report the second case in the literature of an EH originating from the popliteal artery. A 57-year-old male patient presented with a one-month history of knee pain without claudication. Imaging highlighted a right popliteal aneurysm, 5x5 cm, with partial distal thrombosis and inadequate outflow. The patient subsequently underwent popliteal artery ligation above and below the aneurysm, reconstructed with a superficial femoral artery (SFA) to distal anterior tibial artery (ATA) reverse saphenous vein bypass graft. Patient recovery was complicated by the development of a 5x5 cm right-sided mid-thigh hematoma, requiring evacuation under anesthesia. A post-one-year arterial duplex of the affected limb demonstrated a recurrent enlarging popliteal aneurysm measuring 5.7x4.8x9.1 cm. The aneurysm was reported to be mostly thrombosed with noted vascularity, but patency of the original bypass was noted. The patient underwent excision of the recurrent aneurysm with subsequent ligation of the feeding arteries. Pathology and histology confirmed the final diagnosis of EH of the popliteal artery. An 18-month follow-up after the excision procedure demonstrated no recurrence of vascular lesion and patency of the original bypass graft.

Case report: A cystic capillary hemangioma located at the conus medullaris mimicking hemangioblastoma.

Capillary hemangiomas, usually found in skin and mucosal tissues, are rarely encountered within the spinal cord, presenting a significant diagnostic challenge. We report a rare case of intradural extramedullary capillary hemangioma at the conus medullaris in a 66-year-old female patient. Our initial diagnosis leaned towards a cystic hemangioblastoma based on MRI findings due to the presence of cystic formation with an enhanced mural nodule. However, surgical exploration and subsequent pathological examination revealed the lesion as a capillary hemangioma. To the authors' knowledge, this case may represent the first documented instance of a spinal capillary hemangioma that mimics a cystic hemangioblastoma.

Successful interventional treatment of huge hepatic haemangioma in a neonate following failed medical approach.

An outborn male term neonate presented with a complaint of respiratory distress since birth on day 9 of life. On examination, baby was having tachypnoea, tachycardia and hepatomegaly. The baby was delivered at term gestation and cried immediately after birth. The chest X-ray showed cardiomegaly. The abdomen ultrasound showed a complex cystic vascular lesion suggestive of hepatic haemangioma. The echocardiography showed an atrial septal defect. The baby was initially treated conservatively along with specific treatment (steroids and propranolol) for haemangioma for 6 weeks. However, the symptoms persisted and there was non-resolution, therefore, particle embolisation of the right hepatic artery was performed. Subsequently, it resulted in complete resolution of the lesion.

CCL2 regulated by the CTBP1-AS2/miR-335-5p axis promotes hemangioma progression and angiogenesis.

Context: Hemangioma (HA) is a benign vascular neoplasm that can lead to permanent scarring. C-C motif chemokine ligand 2 (CCL2) plays a crucial role in facilitating growth and angiogenesis during HA progression. However, the mechanism regulating CCL2 in HA remains poorly elucidated.Objective: To elucidate the mechanism regulating CCL2 in HA.Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was employed to determine the expression levels of CCL2, long noncoding RNA (lncRNA) CTBP1 divergent transcript (CTBP1-AS2), and microRNAs (miRNAs). Proliferation, migration, invasion, and angiogenic abilities of human HA endothelial cells (HemECs) were assessed using cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell, and tube formation assays. Bioinformatics analysis, RNA pull-down, and luciferase reporter assays were conducted to investigate whether CCL2 targets miR-335-5p. Additionally, rescue experiments were performed in this study.Results: CCL2 expression was markedly upregulated in HemECs. CCL2 promoted HA cell proliferation, migration, invasion, and angiogenesis while inhibiting apoptosis. CCL2 was directly targeted by miR-335-5p. Additionally, we found that CTBP1-AS2 could function as a competing endogenous RNA (ceRNA) to sponge miR-335-5p, thereby upregulating CCL2.Conclusion: Our findings suggest that targeting the CTBP1-AS2/miR-335-5p/CCL2 axis may hold promise as a therapeutic strategy for HA.

Laparoscopic liver resection or enucleation for giant hepatic hemangioma: how to choose?

BACKGROUND: Laparoscopic treatment has been increasingly adopted for giant hepatic hemangioma (HH), but the role of liver resection or enucleation remains uncertain. The aim of this study is to compare the laparoscopic resection (LR) with laparoscopic enucleation (LE) for HH, and to provide evidence on how to choose the most suitable approach for HH. METHODS: A retrospective analysis of HH patients underwent laparoscopic treatment between March 2015 and August 2022 was performed. Perioperative outcomes were compared based on the surgical approaches, and risk factors for increased blood loss was calculated by logistic regression analysis. RESULTS: A total of 127 patients in LR group and 287 patients in LE group were enrolled in this study. The median blood loss (300 vs. 200 mL, P < 0.001) was higher in LE group than that in LR group. Independent risk factors for blood loss higher than 400 mL were tumor size ≥ 10 cm, tumor adjacent to major vessels, tumor occupying right liver or caudate lobe, and the portal phase enhancement ratio (PER) ≥ 38.9%, respectively. Subgroup analysis showed that LR was associated with less blood loss (155 vs. 400 mL, P < 0.001) than LE procedure in patients with high PER value. Both LR and LE approaches exhibited similar perioperative outcomes in patients with low PER value. CONCLUSIONS: Laparoscopic treatment for HH could be feasibly and safely performed by both LE and LR. For patients with PER higher than 38.9%, the LR approach is recommended.

Electrochemotherapy in Aggressive Hemangioma of the Spine: A Case Series and Narrative Literature Review.

(1) Background: this case series and literature review aims to evaluate the efficacy and safety of electrochemotherapy in the management of aggressive spinal hemangiomas, presenting two distinct cases. (2) Methods: we present two cases of spinal aggressive hemangioma which were refractory to conventional treatments and underwent electrochemotherapy. Case 1 involves a 50-year-old female who presented with an aggressive spinal hemangioma of L1, who previously underwent various treatments including surgery, radio-chemotherapy, and arterial embolization. Case 2 describes a 16-year-old female with a T12 vertebral hemangioma, previously treated with surgery and stabilization, who faced limitations in treatment options due to her young age and the location of the hemangioma. (3) Results: in Case 1, electrochemotherapy with bleomycin was administered following the failure of previous treatments and resulted in the reduction of the lesion size and improvement in clinical symptoms. In Case 2, electrochemotherapy was chosen due to the risks associated with other treatments and was completed without any adverse events. Both cases demonstrated the potential of electrochemotherapy as a viable treatment option for spinal hemangiomas, especially in complex or recurrent cases. (4) Conclusions: electrochemotherapy with bleomycin is a promising treatment for aggressive spinal hemangiomas when conventional therapies are not feasible or have failed. Further research is needed to establish definitive protocols and long-term outcomes of electrochemotherapy in spinal hemangioma management.

Giant hepatic hemangioma in a patient with cirrhosis: challenging to manage.

Giant hepatic hemangiomas are occasional in patients with cirrhosis. It remains a challenge to decide on the need for treatment and choose the most appropriate intervention. A 62-year-old woman was recently diagnosed with cirrhosis and complained of upper abdominal fullness, reduction in oral food intake, and weight loss of 6 kg over the last three years. Upper digestive endoscopy evidenced thin-caliber esophageal varices and significant extrinsic compression of the lesser gastric curvature. Abdominal computed tomography revealed an exophytic tumor in the left hepatic lobe, measuring 11.5 cm, which had progressive centripetal contrast enhancement from the arterial phase, compatible with hepatic hemangioma. Serum tumor markers were negative, and her liver function was unimpaired. The patient underwent surgical resection (non-anatomical hepatectomy of segments II and III) which had no immediate complications, and the histopathological evaluation confirmed cavernous hepatic hemangioma. Two weeks later, she was admitted to the emergency room with jaundice, signs of hepatic encephalopathy, and moderate ascites, and was further diagnosed with secondary bacterial peritonitis. As no perforations, abscesses, or fistulas were observed on subsequent imaging tests, clinical management was successfully carried out. This case highlights that giant hepatic hemangiomas may be symptomatic and warrant treatment. In the setting of cirrhosis and portal hypertension, physicians should be aware of the risk of hepatic decompensation following surgical resection, even in patients with Child-Pugh class A.

Regimen for accelerated propranolol initial dosing (RAPID).

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. RESULTS: Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). CONCLUSION: Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.