Examining the significance of arginine vasopressin release to elucidate the often multifactorial etiology of hypotonic hyponatremia: A novel criterion.

Clinical hyponatremia guidelines, protocols and flowcharts are a convenient means for clinicians to quickly establish an etiological diagnosis for hyponatremia, and facilitate its often complex analysis. Unfortunately, they often erroneously attribute multifactorial hyponatremia to a single cause, which is potentially dangerous. In this manuscript, a novel criterion is proposed to quickly determine the physiological relevance of non-osmotic arginine vasopressin (AVP) release, and to add nuance to hyponatremia analysis. While analyzing hypotonic hyponatremia, it is imperative to not only verify whether or not a certain degree of inappropriate AVP release is present, but also to ascertain whether it-in itself-could sufficiently explain the observed hyponatremia, as these two are not always synonymous. Using well-known concepts from renal physiology to combine the electrolyte-free water balance and solute-free water balance, a novel physiological criterion is derived mathematically to easily distinguish three common hyponatremia scenarios, and to further elucidate the underlying etiology. The derived criterion can hopefully facilitate the clinician's and physiologist's interpretation of plasma and urine parameters in a patient presenting with hyponatremia, and warn against the important clinical pitfall of attributing hyponatremia too readily to a single cause.

Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 µg in Japanese men with nocturia due to nocturnal polyuria. METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. RESULTS: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 µg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. CONCLUSIONS: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

Long-Term Sodium Deficiency Reduces Sodium Excretion but Impairs Renal Function and Increases Stone Formation in Hyperoxaluric Calcium Oxalate Rats.

Excessive sodium intake is associated with nephrolithiasis, but the impact of sodium-deficient (SD) diets is unknown. Hence, we investigated the effects of short- and long-term SD diets on the expression of renal aquaporins and sodium transporters, and thus calcium oxalate (CaOx) crystal formation in hyperoxaluria rats. In a short-term sodium balance study, six male rats received drinking water and six received 0.75% ethylene glycol (EG) to induce hyperoxaluria. After a 30-day period of feeding on normal chow, both groups were treated with a normal-sodium diet for 5 days, followed by a sodium-free diet for the next 5 days. In a long-term SD study (42 days), four groups, induced with EG or not, were treated with normal-sodium water and sodium-free drinking water, alternately. Short-term sodium restriction in EG rats reversed the daily positive sodium balance, but progressively caused a negative cumulative water balance. In the long-term study, the abundant levels of of Na/H exchanger, thiazide-sensitive Na-Cl cotransporter, Na-K-ATPase, and aquaporins-1 from SD + EG rats were markedly reduced, corresponding to a decrease in Uosm, as compared to SD rats. Increased urine calcium, AP(CaOx)index, and renal CaOx deposition were also noted in SD + EG rats. Although the SD treatment reduced sodium excretion, it also increased urinary calcium and impaired renal function, ultimately causing the formation of more CaOx crystals.

[Afferent baroreflex failure with hyponatremia: A case report].

Afferent baroreflex failure (ABF) is a rare disease. It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medulla. The recognized causes include trauma, surgery in related areas (radical neck tumor surgery, carotid endarterectomy), neck radiotherapy, brain stem stroke, tumor growth paraganglioma and hereditary diseases, among which the most common cause is extensive neck surgery or radiotherapy for neck cancer. The main manifestations are fluctuating hypertension, orthostatic hypotension, paroxysmal tachycardia and bradycardia. This case is a young man, whose main feature is blood pressure fluctuation, accom-panied by neurogenic orthostatic hypotension (nOH). After examination, the common causes of hypertension and nOH were ruled out. Combined with the previous neck radiotherapy and neck lymph node dissection, it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection, which was called ABF. At the same time, the patient was complicated with chronic hyponatremia. Combined with clinical and laboratory examination, the final consideration was caused by syndrome of in- appropriate antidiuretic hormone (SIADH). Baroreceptors controlled the secretion of heart rate, blood pressure and antidiuretic hormone through the mandatory "inhibition" signal. We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery, which leads to abnormal blood pressure regulation and nOH, while the function of inhibiting ADH secretion was weakened, resulting in higher ADH than normal level and mild hyponatremia. The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate, and to alleviate the onset of symptomatic hypotension. At present, drug treatment is still controversial, and non-drug treatment may alleviate some patients' symptoms, but long-term effective treatment still needs further study. The incidence of ABF is not high, but it may lead to serious cardiovascular and cerebrovascular events, and the mechanism involved is extremely complicated, and there are few related studies. The reports of relevant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complications.

Study of Serum Electrolytes (Sodium and Potassium) Abnormalities in Acute Stroke.

Stroke is the common cause of death and disability worldwide, as well as in Bangladesh. Serum electrolytes abnormalities or dyselectrolytaemia is one of the major acute complications of stroke. Dyselectrolytaemia or serum electrolytes (sodium and potassium) abnormalities are more common in patients with acute stroke that can be easily measured. The study was planned to find out the serum electrolytes (sodium and potassium) abnormalities in acute stroke patients. This cross-sectional study was conducted in the Department of Neurology and Medicine, Mymensingh Medical College and Hospital from January 2019 to June 2020. Total 84 purposively selected patients with acute strokes were evaluated following informed written consent. Diagnosis was confirmed by neuroimaging of brain. Moreover, serum electrolytes level was measured for each patient. Data were collected by interviews, clinical examinations & laboratory investigations of the patients using a case record form and analysis was carried out by the help of SPSS 25.0. Mean age of the patients with acute strokes were 57.65±15.79 years. About two thirds (60.7%) of the patients were male and the remaining (39.3%) were female. Sodium imbalances were observed in 32.2% and potassium imbalances in 25.0% cases. About 66.7% haemorrhagic strokes patients and 42.2% ischaemic strokes patients had dyselectrolytaemia (p<0.05). More than twenty eight percent (28.6%) of all stroke patients had hyponatraemia, which was more common (35.9%) among haemorrhagic strokes patients (p<0.05). Of all stroke patients 21.4% had hypokalaemia, which was more common (28.2%) in haemorrhagic strokes patients (p<0.05). This study reveals that, serum electrolytes (sodium and potassium) abnormalities are more common in haemorrhagic than ischaemic strokes, which is mainly hyponatraemia and hypokalaemia.

Frequency of Hyponatremia in Adults with Acute Bacterial Meningitis.

Bacterial meningitis is a life-threatening disease. Bacterial meningitis patients are prone to develop acute hyponatremia. In the central nervous system infection hyponatremia could be due to the Syndrome of Inappropriate Anti Diuretic Hormone secretion. The frequency of hyponatremia in adults with acute bacterial meningitis patients was seen in this study. This cross-sectional study was conducted in the Internal Medicine Department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from February 2016 to July 2016. A total of 50 patients were enrolled in this study by purposive sampling. Among 50 acute bacterial meningitis patients, 33 (66%) were diagnosed as hyponatremic state. The mean serum sodium level of 33 hyponatremic bacterial meningitis cases was 130.66±2.95 mmol/L. Most of the cases (78.79%) were mild hyponatremic state (130 mmol/L-135 mmol/L) whereas 18.18% were revealed as moderate hyponatremia (125 mmol/L-129 mmol/L). Only 3.03% of cases were presented as severe cases (≤124 mmol/L). The result revealed that a large number of patients with acute bacterial meningitis were suffering from hyponatremia and in the majority of cases were mildly hyponatremic.

Medicina de precisión: «Point of Care Ultrasound» (PoCUS) en el abordaje diagnóstico del paciente con hiponatremia / Precision medicine: “Point of Care Ultrasound” (PoCUS) in the diagnostic approach to the patient with hyponatremia

La hiponatremia es un trastorno multifactorial definido como una disminución en la concentración plasmática de sodio. Su diagnóstico diferencial requiere una evaluación adecuada del volumen extracelular. Sin embargo, la determinación del volumen extracelular, simplemente basada en la historia clínica, las constantes vitales, el examen físico y los hallazgos de laboratorio, conducen en ocasiones a un diagnóstico erróneo por lo que el enfoque terapéutico puede ser equivocado. El empleo de ecografía a pie de cama (Point-of-Care Ultrasound [PoCUS]), mediante la combinación de ecografía pulmonar (Lung Ultrasound [LUS]), Venous Excess UltraSound (VExUS) y la ecocardioscopia (Focused Cardiac Ultrasound [FoCUS]) permiten, en combinación con el resto de los parámetros, una valoración holística mucho más precisa del estado del volumen extracelular del paciente.(AU)

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume. However, extracellular volume determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (PoCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's extracellular volume status in combination with the other parameters.(AU)

Worldwide productivity and research trend of publications concerning SIAD: a bibliometric study.

Background: Syndrome of inappropriate antidiuretic(SIAD) occurs secondary to various diseases, which is characterised by hypotonic hyponatremia and impaired urinary diluting capacity. Research on SIAD in both domestic and international contexts has a long history. This study objectively and comprehensively analyses the research trends, hotspots and development of SIAD research of the past 20 years using the method of bibliometric analysis. Methods: The 2003-2022 data in the Web of Science Core Collection database were searched. The Bibliometrix software package, VOSviewer and CiteSpace were used to mine, extract and visualise the retrieved literature, and the generated maps were used in analysing the main topics and trends in the field of SIAD research. Results: A total of 1215 articles published in 623 journals were included in the analysis, with a total of 18,886 citations. Results showed that the research output on SIAD has continuously increased in the past 20 years, and the United States had the highest number of publications and citations. Keywords with the highest burst strength in recent years were the most mentioned keywords, in addition to the search terms 'hyponatremia', 'covid-19', and 'mortality'. Thus, the relationship among SIAD, covid-19 and mortality may become research frontiers and trends. Fifteen milestone articles were identified through co-citation analysis, which mainly focused on the pathophysiology and treatment of SIAD. Conclusion: Based on bibliometric analysis and knowledge mapping, this study summarises development trends in the field of SIAD research, providing references for current and future research into SIAD.

Safety and efficacy of proactive versus reactive administration of desmopressin in severe symptomatic hyponatremia: a randomized controlled trial.

This randomized controlled trial aimed to evaluate the safety and efficacy of proactive versus reactive desmopressin (DDAVP) strategies in treating severe symptomatic hyponatremia. Conducted from June 20, 2022, to February 20, 2023, it involved 49 patients with serum sodium levels below 125 mmol/L. Patients were assigned to either the proactive group, receiving DDAVP immediately upon diagnosis, or the reactive group, receiving DDAVP only if the serum sodium level tended to be overcorrected. The primary outcome was the incidence of overcorrection. The study revealed no significant difference in the overcorrection incidence between the proactive (16.7%) and reactive (28%) groups (p = 0.54). The change in serum sodium levels at 1, 6, 12, and 24 h were not different, however, at 48 h, the proactive group exhibited a higher but still safe change in serum sodium levels compared to the reactive group (10.3 ± 3.6 mmol/L vs. 7.7 ± 3.6 mmol/L, p = 0.013). Other parameters including time to symptom improvement, total intravenous fluid administered, DDAVP dose, urine volume, hospital stay duration, osmotic demyelination syndrome incidence, and 28-day mortality did not significantly differ between the groups. In conclusion, our findings suggest that there was no significant disparity in overcorrection rates between proactive and reactive DDAVP strategies for treating severe symptomatic hyponatremia. However, further large-scale studies are warranted to validate these results.

Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia-The Neonatal Type of Alexander Disease.

INTRODUCTION: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD. METHOD: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband's DNA extracted from blood. CASE DESCRIPTION: In the first weeks of life, the child presented with signs of increased intracranial pressure, which led to ventriculoperitoneal shunt implementation. Recurrent focal-onset motor seizures with secondary generalization occurred despite phenobarbital treatment. Therapy was modified with multiple anti-seizure medications. In MRI contrast-enhanced lesions in basal ganglia, midbrain and cortico-spinal tracts were observed. During the diagnostic process, GLUT-1 deficiency, lysosomal storage disorders, organic acidurias, and fatty acid oxidation defects were excluded. The NGS panel of EIEE revealed no abnormalities. In WES analysis, GFAP missense heterozygous variant NM_002055.5: c.1187C>T, p.(Thr396Ile) was detected, confirming the diagnosis of AxD. CONCLUSION: AxD should be considered in the differential diagnosis in all neonates with progressive, intractable seizures accompanied by macrocephaly.

Severe hyponatremia and diabetes insipidus caused by low-dose cyclophosphamide in breast cancer patients: A case report and literature review.

RATIONALE: Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is uncommon, it can lead to serious complications and even death. PATIENT CONCERNS: A 44-year-old woman with left-sided breast cancer suddenly experienced headaches, disorientation and weakness after receiving low-dose neoadjuvant chemotherapy combined with CTX and doxorubicin. DIAGNOSES: The patient pathology showed invasive breast carcinoma. She developed severe hyponatremia and a generalized seizure after completing the first cycle of neoadjuvant chemotherapy with CTX and doxorubicin. Laboratory tests showed a serum sodium of 118 mmol/L (normal range 135-145 mmol/L) and potassium sodium 3.16 mmol/L (normal range 3.5-5.5 mmol/L). Subsequently, the patient developed secondary diabetes insipidus 4 hours after sodium supplementation, her 24-hour urine volume was 4730 mL (normal range 1000-2000 mL/24 hours), and the urine specific gravity decreased to 1.005. INTERVENTIONS: The patient was given intravenous sodium chloride (500 mL of 3%NaCl, 100 mL/hour) and potassium chloride (500 mL of 0.3%KCl, 250 mL/hour). Meanwhile, she was advised to reduce her water intake, and pituitrin was administered to prevent dehydration caused by diabetes insipidus. OUTCOMES: The patient completely recovered after correcting of the serum sodium concentration (137 mmol/L) without any neurological deficits. After discontinuing pituitrin, her 24-hour urine volume was 2060 mL and the urine specific gravity was 1.015. LESSONS: This is a typical case of severe hyponatremia induced by low-dose CTX. Clinicians and healthcare providers should be aware of this potential toxicity, and appropriate monitoring should be implemented.

Syndrome of inappropriate antidiuretic hormone release secondary to central nervous system coccidioidomycosis with vasculitis.

A man in his 60s presented to the clinic due to night sweats and weight loss following pneumonia. He was found to have hyponatraemia due to a syndrome of inappropriate antidiuretic hormone (SIADH). CT of the thorax was concerning for pulmonary nodules. He was ultimately diagnosed with pulmonary coccidioidomycosis (CM) and started on fluconazole 400 mg daily with improvement in symptoms. Due to the report of headaches, head MRI was conducted which suggested central nervous system (CNS) involvement. Cerebrospinal fluid analysis was consistent with CNS CM and head magnetic resonance angiography confirmed the presence of CNS vasculitis. Fluconazole dose was increased to 800 mg daily which the patient continued to tolerate and showed improvement. This report depicts a case of SIADH associated with CNS CM with vasculitis and demonstrates the importance of high clinical suspicion for SIADH secondary to CNS CM in the setting of hyponatraemia and headache.

A case report of drug interaction between co-packaged nirmatrelvir-ritonavir and tacrolimus causing hyponatremia in a lung transplant recipient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection in lung transplant recipients can be lethal owing to the use of immunosuppressants. Antiviral agents may be administered to these patients. Co-packaged nirmatrelvir-ritonavir is a new agent currently being used in combination. CASE PRESENTATION: In this report, we present a case of a 64-year-old woman, a lung transplant recipient, who experienced hyponatremia and showed a high serum tacrolimus concentration following the administration of the co-packaged nirmatrelvir-ritonavir combination. CONCLUSION: Although the nirmatrelvir-ritonavir and tacrolimus combination is not contraindicated, other treatment strategies should be considered first, if available, and the dose of tacrolimus should be reduced when using the nirmatrelvir-ritonavir combination. In cases where combination therapy is necessary, serum tacrolimus levels should be closely monitored in lung transplant recipients. Documentation of more such reports is important to identify drug interactions between nirmatrelvir-ritonavir and other agents, with the aim of preventing severe adverse effects.

A retrospective study: exploring preoperative hyponatremia in elderly patients with hip fractures.

BACKGROUND: This research aims to examine the frequency, age-related distribution, and intensity of preoperative hyponatremia among elderly individuals with hip fractures. This study aims to provide valuable insights into the diagnosis of preoperative hyponatremia in this patient population. METHODS: This research involved the analysis of clinical data obtained from 419 elderly individuals with hip fractures (referred to as the fracture group) and 166 elderly individuals undergoing routine health examinations (designated as the control group). A comprehensive comparison was conducted, examining baseline characteristics such as age, gender, and comorbidities between these two groups. We further investigated variations in the incidence rate of hyponatremia, age distribution, and the severity of hyponatremia. Additionally, a subgroup analysis compared patients with femoral neck fractures to those with intertrochanteric femur fractures, specifically examining the incidence rate and severity of hyponatremia in these distinct fracture types. RESULTS: The incidence of cerebrovascular disease was found to be higher in the fracture group as compared to the control group in our research. Nevertheless, no significant differences in general health and other comorbidities were observed between the two groups. Notably, the fracture group exhibited a greater preoperative prevalence of hyponatremia, with its severity increasing with age. Furthermore, among elderly patients with intertrochanteric femur fractures, the incidence of preoperative hyponatremia was not only higher but also more severe when compared to those with femoral neck fractures. CONCLUSION: Elderly individuals experiencing hip fractures exhibit a notable prevalence of preoperative hyponatremia, predominantly mild to moderate, with an escalating occurrence linked to advancing age. This phenomenon is especially conspicuous among patients with intertrochanteric fractures, warranting dedicated clinical scrutiny. The administration of sodium supplementation is advisable for the geriatric demographic as deemed necessary. Addressing hyponatremia becomes crucial, as it may play a role in the etiology of hip fractures in the elderly, and rectifying this electrolyte imbalance could potentially serve as a preventive measure against such fractures.

Hand knob sign in osmotic demyelinating syndrome.

BACKGROUND: Osmotic demyelinating syndrome, commonly recognized as a consequence of the rapid correction of hyponatremia, has been known to cause motor, neuropsychiatric, or extrapyramidal symptoms. We reported a patient with an unusual presentation involving bilateral hand weakness, and pseudobulbar affect. The imaging was compatible with osmotic demyelinating syndrome with bilateral hand knob lesions, despite no history of overcorrection of hyponatremia. CASE PRESENTATION: A 44-year-old female presented with three weeks of emotional lability, spastic dysarthria, and bilateral hand weakness following ankle surgery and a mild head injury. Physical examination revealed weakness in the intrinsic hand muscles, leading to a claw-like deformity of the hands, although sensation remained unimpaired. Magnetic resonance imaging (MRI) of the brain revealed several hyperintensities on fluid-attenuated inversion recovery imaging involving various areas, including the hand knob area of the bilateral precentral gyri, caudate, lentiform nuclei, and pons, suggestive of osmotic demyelinating syndrome. Clinical improvement was observed following a trial of intravenous pulse methylprednisolone and plasmapheresis. CONCLUSIONS: Bilateral hand weakness is an unusual manifestation of osmotic demyelinating syndrome. The precentral gyrus, specifically in the hand knob area, is the vulnerable region that can result from osmotic demyelinating syndrome.

Serum sodium level fluctuations following the resection of childhood-onset craniopharyngioma.

BACKGROUND: Craniopharyngiomas are low-grade malignancies (WHO I) in the sellar region. Most cases of childhood-onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. OBJECTIVE: To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. METHODS: This retrospective study measured the serum sodium levels of 202 patients aged 0-18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. RESULTS: The mean age of the cohort was 8.35 ± 4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+  > 150 mmol/L and serum Na+  < 130 mmol/L) within 14 days after surgery was 66.3%, 72.8%, 37.1%, and 40.6%, respectively. The mean postoperative serum sodium level showed a triphasic pattern, characterized by two peaks separated by a nadir. Sodium levels peaked on days 2 (143.6 ± 7.6 mmol/L) and 14 (143.2 ± 6.7 mmol/L) and reached their lowest on day 6 (135.5 ± 7.5 mmol/L). A total of 31 (15.3%) patients met the diagnostic threshold for hyponatremia and hypernatremia of the triphase response, whereas 116 (57.4%) patients presented this pattern, regardless of met the diagnostic criteria or not. The prevalence of severe hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. CONCLUSIONS: Serum sodium levels after craniopharyngioma resection in children showed a triphasic pattern in most cases. The risk of postoperative hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach.