Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT.

OBJECTIVES: Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT). METHODS: This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis-related complications within 6 months. RESULTS: Thirty-five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new-onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new-onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms. CONCLUSION: Midodrine, when added to SMT, was effective in reducing the incidence of new-onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA.

Efectividad de la administración de urea para el tratamiento de la hiponatremia en la insuficiencia cardiaca / Effectiveness of urea administration for the treatment of hyponatremia in heart failure

Objetivos Valorar la eficacia y la seguridad de la urea en pacientes con hiponatremia e insuficiencia cardiaca (IC). Métodos y resultados Se trata de un estudio observacional retrospectivo analítico de pacientes con IC e hiponatremia (Na+ <135mmol/l). Se incluyeron 49 pacientes tratados con urea y 47 pacientes que no recibieron urea, todos ellos bajo tratamiento estándar (según práctica clínica habitual) de la IC, con seguimiento en el hospital Álvaro Cunqueiro de Vigo entre enero de 2013 y mayo de 2022. En el estudio se evaluó la normalización de los niveles de sodio (Na >135mmol/l). La natremia al inicio del tratamiento con urea oral era de 127±5,22mmol/l, a las 24horas el sodio era de 128±2,47 (p<0,009) y la media el día de la normalización fue de 135,19±4,23mmol/l (p<0,005). Los días de media para conseguir la normalización del sodio fueron 5,03±2,37. La uremia al inicio del tratamiento con urea era de 73±46,93mg/dl y la media el día de la normalización del Na+ fue de 116,05±63,64mg/dl (p<0,002). La dosis media de urea oral fue 22,5g/día. No se observaron efectos adversos relevantes, ni cambios en cuanto a las cifras de creatinina. Conclusiones El tratamiento con urea oral añadido al tratamiento estándar, durante cortos periodos de tiempo, es seguro y eficaz para corregir la natremia en pacientes con IC hipervolémica con hiponatremia.

Objectives To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). Methods and results This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. Conclusions Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia. (AU)

Efectividad de la administración de urea para el tratamiento de la hiponatremia en la insuficiencia cardiaca / Effectiveness of urea administration for the treatment of hyponatremia in heart failure

Objetivos Valorar la eficacia y la seguridad de la urea en pacientes con hiponatremia e insuficiencia cardiaca (IC). Métodos y resultados Se trata de un estudio observacional retrospectivo analítico de pacientes con IC e hiponatremia (Na+ <135mmol/l). Se incluyeron 49 pacientes tratados con urea y 47 pacientes que no recibieron urea, todos ellos bajo tratamiento estándar (según práctica clínica habitual) de la IC, con seguimiento en el hospital Álvaro Cunqueiro de Vigo entre enero de 2013 y mayo de 2022. En el estudio se evaluó la normalización de los niveles de sodio (Na >135mmol/l). La natremia al inicio del tratamiento con urea oral era de 127±5,22mmol/l, a las 24horas el sodio era de 128±2,47 (p<0,009) y la media el día de la normalización fue de 135,19±4,23mmol/l (p<0,005). Los días de media para conseguir la normalización del sodio fueron 5,03±2,37. La uremia al inicio del tratamiento con urea era de 73±46,93mg/dl y la media el día de la normalización del Na+ fue de 116,05±63,64mg/dl (p<0,002). La dosis media de urea oral fue 22,5g/día. No se observaron efectos adversos relevantes, ni cambios en cuanto a las cifras de creatinina. Conclusiones El tratamiento con urea oral añadido al tratamiento estándar, durante cortos periodos de tiempo, es seguro y eficaz para corregir la natremia en pacientes con IC hipervolémica con hiponatremia.

Objectives To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). Methods and results This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. Conclusions Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia. (AU)

Tolvaptan for Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in a Child with Corpus Callosum Agenesis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the common causes of euvolemic hyponatremia (serum Na+ < 135 mEq/L) in hospitalized children. It is characterized by increased serum ADH, leading to water retention via its action on V2 receptors in the distal renal tubules. Various conditions such as pain, the postoperative state, drugs, central nervous system infections, tumors, malformations, and pneumonia can predispose a person to SIADH. The conventional treatment of SIADH includes fluid restriction and salt supplementation. Occasionally, this may fail to control hyponatremia, mandating pharmacological therapy. V2-receptor antagonists are an FDA-approved therapy for adults with euvolemic and hypervolemic hyponatremia. However, there is limited experience with their use in the pediatric population. Here, the authors present a girl with corpus callosum agenesis with severe symptomatic hyponatremia due to SIADH who was successfully managed with the V2-receptor antagonist tolvaptan.

Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer.

PURPOSE: This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. METHODS: Preoperative DCF (docetaxel, 70 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; fluorouracil, 750 mg/m2/day, days 1-5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. RESULTS: According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3'-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). CONCLUSIONS: ABCC2-24C > T (rs717620), TYMS 3'-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

Use trends of chlorthalidone and hydrochlorothiazide among United States adults with hypertension: National Health and Nutrition Examination Survey 2009-2018.

OBJECTIVES: To estimate the national prevalence of chlorthalidone and hydrochlorothiazide use among adults diagnosed with hypertension by sociodemographic subgroup, healthcare access status, and clinical factors. METHODS: Data was extracted from the National Health and Nutrition Examination Survey for 2009-2010 through 2017-2018 survey waves. Patients at least 20 years old, diagnosed with hypertension, and on hydrochlorothiazide or chlorthalidone were included. Uni-variable logistic regression models estimated the odds of being on chlorthalidone compared with hydrochlorothiazide use by sociodemographic and clinical factors. Analyses were adjusted for multi-stage complex survey design and are nationally representative. RESULTS: Two thousand five hundred and eighty-five participants were included with 95.2% participants using hydrochlorothiazide and 4.8% using chlorthalidone. Participants over 65 years were more likely to be on chlorthalidone compared with younger counterparts [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.12-2.88]. Participants with hypokalemia (OR 2.62; 95% CI 1.56-4.42) or hyponatremia [OR 2.298; 95% CI 1.23-4.30) were more likely to be using chlorthalidone compared with patients with normal levels. CONCLUSION: Chlorthalidone, a potent and effective first-line antihypertensive agent and thoroughly studied thiazide diuretic with substantial cardiovascular benefits, continues to be underutilized in patients with hypertension. Findings demonstrated that individuals receiving chlorthalidone were more likely to be 65 years or older and to experience hyponatremia or hypokalemia. Sociodemographic factors, healthcare access and use, clinical factors, and medical conditions did not appear to sway the choice in thiazide diuretic use.

Desmopressin Dose Requirements in Adults with Congenital and Acquired Central Diabetes Insipidus.

Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analogue of vasopressin, desmopressin.The primary aim of this retrospective register study was to compare desmopressin dose requirements in patients with acquired and congenital DI, and secondly to assess the influence of BMI on dose requirement and risk of hyponatremia with different drug administrations. We included all patients with suspected DI attending the endocrine department at Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were included whereof 130/222 (58.6%) were females and median age was 53 years (IQR 35 to 63). The etiology included 7/222 (3.2%) congenital and 215/222 (96.8%) acquired. After converting nasal and sublingual doses to equivalent oral doses, the median daily dose requirement was 600 µg in patients with congenital etiology compared to 200 µg in patients with acquired etiology (p=0.005). We found no association between BMI and desmopressin dose requirements (p=0.6). During the past 12 months, 66/215 (30.7%) had sodium levels<136 mmol/l including 20/215 (9.3%) with sodium levels<131 mmol/l. No increased risk of hyponatremia was found, when nasal and oral were compared (p=0.9). Daily desmopressin dose requirements were higher in patients with congenital DI compared to patients with acquired DI. However, this result was associated with uncertainty due to the small congenital group. BMI did not influence daily dose requirements and nor did type of administration influence the risk of hyponatremia.

Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: a systematic literature review.

BACKGROUND: Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. OBJECTIVES: We aimed to review the safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. METHODS: Databases were searched for articles up to July 25, 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology for systematic reviews and meta-analyses was followed (PROSPERO CRD42022316490). RESULTS: Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 women during pregnancy and in 232 during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse events reported in 2 (1%, hyponatremia with neurologic symptoms). Overall, DDAVP was used as monotherapy in 234 pregnancies, with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, 2 children (3%) had a severe adverse event (preterm delivery n = 1; fetal growth restriction n = 1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery, and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n = 1; transient hyperbilirubinemia not associated with DDAVP n = 1). CONCLUSION: DDAVP use during pregnancy and delivery seems safe for the mother, with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted.

[Effectiveness of urea administration for the treatment of hyponatremia in heart failure]. / Efectividad de la administración de urea para el tratamiento de la hiponatremia en la insuficiencia cardiaca.

OBJECTIVES: To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). METHODS AND RESULTS: This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. CONCLUSIONS: Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia.

Tolvaptan and urea in paediatric hyponatraemia.

BACKGROUND: The syndrome of inappropriate antidiuretic hormone (SIADH) is usually treated with fluid restriction. This can be challenging in patients with obligate fluid intake for nutrition or medication. Pharmaceutical treatment with tolvaptan and urea is available but minimal paediatric data are available. We review the efficacy and safety of tolvaptan and urea in paediatric patients with SIADH. METHODS: Retrospective review of paediatric inpatients with clinical diagnosis of SIADH. Patients were identified from pharmacy records based on tolvaptan and urea prescriptions. Relevant information was extracted from patient electronic records. The main outcome measures included the number of days to sodium normalisation, the daily change in plasma sodium concentration, and the maximum increase of plasma sodium concentration in 24 h. Reported side effects were captured. RESULTS: Thirteen patients received tolvaptan and six urea. Five patients had both agents (tolvaptan converted to urea). Tolvaptan led to plasma sodium normalisation in 10/13 (77%) within 6 days (median 2.5 days, range [1, 6]), with a median change of sodium concentration of 7 mmol/L (- 1, 14) within the first 24 h of treatment. Three patients experienced a change in plasma sodium > 10 mmol/l/day but had no apparent side effects. Urea led to sodium normalisation in 5/6 (83%) patients. The median number of days to normalisation with urea was 2 (1, 10) with a median change of plasma sodium concentration of 2 mmol/L (- 1, 6) within the first 24 h. All patients tolerated tolvaptan and/or urea without unexpected side effects. CONCLUSIONS: Tolvaptan and urea appear to be safe and effective when fluid restriction is challenging in paediatric SIADH. A higher resolution version of the Graphical abstract is available as Supplementary information.

Palatability of two different formulations of urea for the treatment of hyponatremia: A double-blind, randomized, cross-over study.

BACKGROUND AND AIMS: Hyponatremia (HN) is the most common disorder of electrolytes encountered in clinical practice. Considering that HN is associated with high morbidity and mortality, it is important to identify treatments for these patients. The therapeutic approaches for HN depend on the severity and the character of the pathology (acute vs. chronic). Among intervention strategies, oral urea represents an effective, safe, and well-tolerated therapeutic approach in the management of chronic hyponatremia. Oral ureal is commonly prepared as a galenic formulation that is usually associated with distaste problems. A double-blind, randomized, cross-over clinical trial was conducted to evaluate and compare the palatability of two different urea formulations: a commercial urea formulation and a galenic one (trial registered on www.isrctn.com, number: ISRCTN18369035). MATERIALS AND METHODS: Thirty-six healthy subjects (18 female and 18 male, median age 55 years) were enrolled in the study and randomized to consume 7 g of formulation A (commercial formulation) or formulation B (galenic formulation) twice a day away from meals, solubilizing the products in 125 mL of water (T0). After three days of a wash-out, the formulations were crossed-over and consumed twice a day away from meals (T4). After the consumption of products, both in the morning and the evening, participants completed a specific questionnaire to evaluate the products' palatability. RESULTS: The commercial formulation was globally more appreciated than the galenic one, in terms of smell, taste, and aftertaste. The commercial formulation was better accepted as a potential treatment in 44 % of subjects compared to 14 % of subjects for galenic formulation. CONCLUSIONS: The clinical trial confirmed the better palatability of the commercial oral urea formulation, containing citrus flavor, which therefore represents a therapeutic strategy that could improve adherence to the therapy in chronic patients with hyponatremia.

Uso de ibuprofeno en el tratamiento de pacientes pediátricos con poliuria y disnatremia. Reporte de una serie de casos / Ibuprofen use for the treatment of pediatric patients with polyuria and dysnatremia. A case series report

Los niños con lesiones selares y/o supraselares pueden presentar diabetes insípida central con posterior secreción inadecuada de hormona antidiurética. Nosotros observamos, en algunos casos, aumento de la incidencia de poliuria, natriuresis e hiponatremia, tríada diagnóstica del síndrome cerebral perdedor de sal. Aquí comunicamos la evolución de 7 pacientes con antecedentes de daño agudo del sistema nervioso central y diabetes insípida central seguida por síndrome cerebral perdedor de sal. Como tratamiento aportamos secuencialmente fluidos salinos parenterales, cloruro de sodio oral, desmopresina, mineralocorticoides e incluso tiazidas. Ante la persistencia de poliuria con hiponatremia, agregamos ibuprofeno. Como resultado de este esquema terapéutico secuencial, este grupo redujo significativamente los valores de diuresis diaria de 10 ml/kg/h a 2 ml/kg/h en un tiempo promedio de 5 días, normalizando también las natremias (de 161 mEq/L a 143 mEq/L) en un tiempo promedio de 9 días. En ningún caso observamos efectos adversos asociados al tratamiento.

Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/ kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.

A retrospective study on tolvaptan prescription in clinical practice in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) using the Japanese claims database.

We aimed to survey the status of tolvaptan administration in routine clinical practice since the approval of a novel indication for treating syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in Japan. Data from a population of 3,152 patients aged ≥18 years and diagnosed with SIADH between July 1, 2020 and June 30, 2021 were extracted from a Japanese database. Tolvaptan was administered to 586 patients while 2,566 patients were followed up without tolvaptan. In the tolvaptan-treated group, the standard initial doses were 3.75 mg and 7.5 mg in 290 (49.5%) and 250 (42.7%) patients, respectively. The dose was increased in 112 (38.6%) and 71 (28.4%) and decreased in 8 (2.8%) and 46 (18.4%) of patients with 3.75 and 7.5 mg initial doses, respectively. Of the total 586 SIADH patients treated with tolvaptan, serum sodium concentrations were analyzed in 60 patients. In both treatment groups of 3.75 and 7.5 mg initial doses, the serum sodium concentration was elevated from the second day of treatment and reached 135 mEq/L on the fourth day, which was maintained for 2 weeks. Rapid correction of hyponatremia (>10 mEq/L increase in serum sodium concentration over 1 day or >18 mEq/L increase over 2 days) occurred in 26.7% patients with a 7.5 mg initial dose (4 of 15 patients) but not in the patients with a 3.75 mg initial dose (n = 16), suggesting that an initial dose of 3.75 mg of tolvaptan may be a better choice for the safe and proper correction of hyponatremia.

[Reset osmostat syndrome - when hyponatremia become «a normal¼: diagnostics, case report].

Reset osmostat syndrome (ROS) is characterized by a change of normal plasma osmolality threshold (decrease or increase), which leads to chronic dysnatremia (hypo- or hypernatremia). We have described a clinical case of ROS and chronic hyponatremia in a patient with chordoid glioma of the III ventricle. It is known that the patient had previously been diagnosed with hyponatremia (131-134 mmol/l). She has not hypothyroidism and hypocorticism. There is normal filtration function of the kidneys was (CKD-EPI 91.7 ml/mi/1,73m2). Urine osmolality and sodium level were studied to exclude of concentration kidney function disorder. During first three days after removal of the tumor of the third ventricle (chordoid glioma, WHO Grade II), the sodium level decreased to 119 mmol/l. Repeated infusions of 200-300 ml hypertonic 3% sodium chloride solution, gluco- and mineralocorticoid therapy was ineffective, increasing plasma sodium levels by 2-3 mmol/l with the return to the initial level during 6-8 hours. Hypopituitary disorders did not develop after surgery. With further observation, the sodium level remained within 126-129 mmol/l for 6 months after surgery. The water load test make exclude the classic syndrome of inappropriate secretion of antidiuretic hormone, and confirmed the diagnosis of RSO. Because of absence of clinical symptoms associated with hyponatremia, no medical correction was required, patient was recommended to clinical follow-up.

A prospective phase II randomized study of docetaxel combined with lobaplatin versus TPF regimen induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.

PURPOSE: To compare the toxicity and clinical efficacy of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma. METHODS AND PATIENTS: In total, 128 patients with locally advanced head and neck cancer were prospectively enrolled between August 2016 and April 2021. They were randomly divided into trial group and control group, all using chronological dosage mode. The trial group used TL regimen induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy; the control group used TPF regimen induction chemotherapy and cisplatin concurrent chemotherapy. The endpoints were adverse events and survival rates at 1, 3 and 5 years. RESULTS: Median follow-up was 42 months (20-71 months). (1) Adverse events: During induction chemotherapy, compared with TPF group, grade 3-4 leukocytes and neutrophils, diarrhea, 1-2 hyperbilirubinemia, nausea / vomiting, oral mucositis, fatigue, anorexia, hyponatremia were significantly lower in TL group (p<0. 05): 6% vs. 35%, 14% vs. 53%, 0% vs. 6%, 15% vs. 40%, 9% vs. 56%, 0% vs. 10%, 3% vs. 13%, 2% vs. 23%, 15% vs. 74%. During chemoradiotherapy, the incidence of hyponatremia, hypokalaemia and grade 1-2 nausea was significantly lower in the TL group (p<0. 05), with 24% vs. 69%, 20% vs. 65% and 24% vs. 44%, respectively. However, more grade 3-4 thrombocytopenia were observed in the TL group (15% vs. 3%, p<0. 05). (2) There was no significant difference in the recent objective response rate (ORR) between patients with TL group and TPF group (p=0.961). (3) There was no statistical difference in 1, 3 and 5 years OS between TL group and TPF group, respectively, (71.0% vs. 67.5%, p=0.573), (56.6% vs. 56.9%, p=0.814), (52.5% vs. 52.9%, p=0.841); 1, 3 and 5 years PFS are: (63.4% vs. 64.0%, p=0.883), (51.1% vs. 54.0%, p=0.705) and (47.3% vs. 45.9%, p=0.887), None of them were significantly different. Multivariate analysis of COX regression showed that T stage (p=0.01) and surgery (p=0.046) were independent factors affecting PFS and OS, respectively. OS subgroup analysis shows that people receiving the TL regimen in postoperative and nodal stage N1 and N2 patients tended to survive longer than those receiving the TPF regimen. CONCLUSION: Patients with postoperative, N1 or N2 stage locally advanced head and neck squamous cell carcinoma (HNSCC) may have more significant clinical benefits when treated with TL regimen. TL regimen has advantages in reducing toxic side effects and can be used as one of the first-line treatment options. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT03117257).

Efficacy and safety of tolvaptan in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Tolvaptan has been approved for the management of cirrhosis-related complications according to the Japanese and Chinese practice guidelines, but not the European or American practice guidelines in view of FDA warning about its hepatotoxicity. This study aimed to systematically evaluate its efficacy and safety in cirrhosis. METHODS: The PubMed, EMBASE, and Cochrane library databases were searched to identify randomized controlled trials (RCTs) evaluating the efficacy and/or safety of tolvaptan in cirrhosis. Risk ratios (RRs) and weight mean differences (WMDs) were calculated. The incidence of common adverse events (AEs) was pooled. RESULTS: Eight RCTs were included. Tolvaptan was significantly associated with higher rates of improvement of ascites (RR = 1.49, P < 0.001) and hyponatremia (RR = 1.80, P = 0.005) and incidence of any AEs (RR = 1.18, P = 0.003), but not serious AEs (RR = 0.86, P = 0.410). Tolvaptan was significantly associated with reductions in body weight (WMD = -1.30 kg, P < 0.001) and abdominal circumference (WMD = -1.71 cm, P < 0.001), and increases in daily urine volume (WMD = 1299.84 mL, P < 0.001) and serum sodium concentration (WMD = 2.57 mmol/L, P < 0.001). The pooled incidences of dry mouth, thirst, constipation, and pollakiuria were 16%, 24%, 6%, and 17%, respectively. CONCLUSION: Short-term use of tolvaptan may be considered in cirrhotic patients with ascites who have inadequate response to conventional diuretics and those with hyponatremia.

[Figure: see text].