HARMONIZE Asia: A Phase III Randomized Study to Investigate the Efficacy and Safety of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China.

PURPOSE: Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. METHODS: This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. FINDINGS: In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS: Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.

Curative effect analysis of robot-assisted drainage surgery in treatment of spontaneous hypertensive brainstem hemorrhage.

Objective: Spontaneous hypertensive brainstem hemorrhage (HBSH) is characterized by sudden onset, rapid progression and poor prognosis. There has been a growing tendency of surgical treatment for HBSH. This study aimed to investigate outcomes and potential factors associated with the prognosis of robot-assisted drainage surgery for HBSH treatment. Methods: Patients with HBSH from July 2016 to March 2023 at a single neurosurgery center were included and divided into conservative group and surgical groups. Baseline and clinical data, radiographic characteristics, complications, and outcome evaluations were recorded and analyzed. Results: A total of 125 patients, with 74 in the conservative group and 51 in the surgical group, were enrolled in the study. Mortality at 6 months was 59/74 (79.7%) in the conservative group and 9/51 (17.6%) in the surgical group. Twenty-four patients (47.1%) achieved favorable outcomes in the surgical group, whereas this rate in the conservative group was only 5.4% (4/74). There was a significant difference in NIHSS, GCS, and mRS at 6 months between surviving patients in the conservative and surgical groups. In prognostic analysis in the surgical subgroup, initial GCS score [5 (IQR 4-7) vs. 3 (IQR 3-4), p < 0.001], NIHSS [36 (IQR 32-38) vs. 40 (IQR 38-40), p < 0.001], smoking history [45.8% (11/24) vs. 74.1% (20/27), p = 0.039], hematoma volume [6.9 (IQR 6.2-7.6) vs. 9.6 (IQR 7.3-11.4), p = 0.001], and hemorrhage location (p = 0.001) were potential risk factors for poor 6-month prognosis after robot-assisted surgery for HBSH. Conclusion: Based on the results of this study, robot-assisted minimally invasive drainage of brain stem hematoma may significantly reduce mortality and improve prognosis. Surgery should be conducted for selected patients.

Clinical effect of short-term spinal cord stimulation in the treatment of patients with primary brainstem hemorrhage-induced disorders of consciousness.

Objective: Recently, short-term spinal cord stimulation (st-SCS) has been used in neurorehabilitation and consciousness recovery. However, little is known about its effects on primary brainstem hemorrhage (PBSH)-induced disorders of consciousness (DOC). In this study, we examined the therapeutic effects of st-SCS in patients with PBSH-induced DOC. Methods: Fourteen patients received a 2-week st-SCS therapy. Each patient's state of consciousness was evaluated using the Coma Recovery Scale-Revised (CRS-R). CRS-R evaluation scores were recorded at the baseline (before SCS implantation) and 14 days later. Results: Over 70% (10/14) of the patients (CRS-R score increased to ≥2 points) responded to the SCS stimulation after 14 days of st-SCS treatment. All items included in the CRS-R exhibited a significant increase post-treatment compared with pretreatment. After 2 weeks of st-SCS treatment, seven patients showed diagnostic improvement, resulting in a 50% (7/14) overall effective rate. Approximately 75% (3/4) of patients with minimally conscious state plus (MCS+) improved to emergence from MCS (eMCS), and 50% (1/2) of patients with vegetative state or unresponsive wakefulness syndrome (VS/UWS) improved to MCS+. Conclusion: In PBSH-induced DOC, st-SCS is a safe and effective treatment. The clinical behavior of the patients improved significantly following the st-SCS intervention, and their CRS-R scores markedly increased. This was most effective for MCS+.

Primary intraosseous meningioma with subcutaneous and dural invasion: A case report and literature review.

Primary intraosseous meningiomas (PIOMs) are a rare subset of meningiomas, comprising fewer than 1% of all such tumors. Furthermore, PIOMs presenting as osteogenic lesions that invade both the dura and subcutaneous tissue are extremely rare. Unlike intracranial meningiomas, diagnosing and treating PIOMs are challenges due to their insidious clinical behavior and a lack of clear radiological diagnostic criteria. We report the case of a 60-year-old female with headache and a slightly outward protrusion of the parietal region of the skull. CT showed an osteogenic lesion in the right parietal bone. MR imaging indicated mild to moderate homogeneous enhancement with an intense dural reaction. The suggested clinical diagnosis was lymphoma, so we performed a skull biopsy, which revealed an intraosseous benign meningioma. A precise resection strategy was planned with a neuronavigation system accompanied by a one-step customized titanium mesh cranioplasty. The lesion was completely removed, and pathological analysis confirmed a meningothelial meningioma (WHO Grade I) of intraosseous layer origin invading the dura mater and subcutaneous tissue. This case highlights the need for an initial biopsy when the lesion is difficult to diagnose on imaging. Complete resection should be attempted to minimize the risk of recurrence.

Development and validation of a prediction nomogram for a 6-month unfavorable prognosis in traumatic brain-injured patients undergoing primary decompressive craniectomy: An observational study.

Objective: This study was designed to develop and validate a risk-prediction nomogram to predict a 6-month unfavorable prognosis in patients with traumatic brain-injured (TBI) undergoing primary decompressive craniectomy (DC). Methods: The clinical data of 391 TBI patients with primary DC who were admitted from 2012 to 2020 were reviewed, from which 274 patients were enrolled in the training group, while 117 were enrolled in the internal validation group, randomly. The external data sets containing 80 patients were obtained from another hospital. Independent predictors of the 6-month unfavorable prognosis were analyzed using multivariate logistic regression. Furthermore, a nomogram prediction model was constructed using R software. After evaluation of the model, internal and external validations were performed to verify the efficiency of the model using the area under the receiver operating characteristic curves and the calibration plots. Results: In multivariate analysis, age(p = 0.001), Glasgow Score Scale (GCS) (p < 0.001), operative blood loss of >750 ml (p = 0.045), completely effaced basal cisterns (p < 0.001), intraoperative hypotension(p = 0.001), and activated partial thromboplastin time (APTT) of >36 (p = 0.012) were the early independent predictors for 6-month unfavorable prognosis in patients with TBI after primary DC. The AUC for the training, internal, and external validation cohorts was 0.93 (95%CI, 0.89-0.96, p < 0.0001), 0.89 (95%CI, 0.82-0.94, p < 0.0001), and 0.90 (95%CI, 0.84-0.97, p < 0.0001), respectively, which indicated that the prediction model had an excellent capability of discrimination. Calibration of the model was exhibited by the calibration plots, which showed an optimal concordance between the predicted 6-month unfavorable prognosis probability and actual probability in both training and validation cohorts. Conclusion: This prediction model for a 6-month unfavorable prognosis in patients with TBI undergoing primary DC can evaluate the prognosis accurately and enhance the early identification of high-risk patients.

Outcomes of Traumatic Brain-Injured Patients With Glasgow Coma Scale < 5 and Bilateral Dilated Pupils Undergoing Decompressive Craniectomy.

Objective: Decompressive craniectomy (DC) plays an important role in the treatment of patients with severe traumatic brain injury (sTBI) with mass lesions and intractably elevated intracranial hypertension (ICP). However, whether DC should be performed in patients with bilateral dilated pupils and a low Glasgow Coma Scale (GCS) score is still controversial. This retrospective study explored the clinical outcomes and risk factors for an unfavorable prognosis in sTBI patients undergoing emergency DC with bilateral dilated pupils and a GCS score <5. Methods: The authors reviewed the data from patients who underwent emergency DC from January 2012 to March 2019 in a medical center in China. All data, such as patient demographics, radiological findings, clinical parameters, and preoperative laboratory variables, were extracted. Multivariate logistic regression analysis was performed to determine the factors associated with 30-day mortality and 6-month negative neurological outcome {defined as death or vegetative state [Glasgow Outcome Scale (GOS) score 1-2]}. Results: A total of 94 sTBI patients with bilateral dilated pupils and a GCS score lower than five who underwent emergency DC were enrolled. In total, 74 patients (78.7%) died within 30 days, and 84 (89.4%) had a poor 6-month outcome (GOS 1-2). In multivariate analysis, advanced age (OR: 7.741, CI: 2.288-26.189), prolonged preoperative activated partial thromboplastin time (aPTT) (OR: 7.263, CI: 1.323-39.890), and low GCS (OR: 6.162, CI: 1.478-25.684) were associated with a higher risk of 30-day mortality, while advanced age (OR: 8.812, CI: 1.817-42.729) was the only independent predictor of a poor 6-month prognosis in patients undergoing DC with preoperative bilateral dilated pupils and a GCS score <5. Conclusions: The mortality and disability rates are extremely high in severe TBI patients undergoing emergency DC with bilateral fixed pupils and a GCS score <5. DC is more valuable for younger patients.

Predictors of 30-Day Mortality in Traumatic Brain-Injured Patients after Primary Decompressive Craniectomy.

OBJECTIVE: Primary decompressive craniectomy (DC) is an important therapeutic technique for severe head-injured patients with space-occupying lesions in emergency situations, but these patients are still at high risk for unfavorable outcomes. This study aimed to investigate the predictors of 30-day mortality in adult patients undergoing primary DC after traumatic brain injury (TBI). METHODS: All adult patients (≥18 years of age) who underwent primary DC from January 2012 to March 2019 were included. Demographic, clinical, surgical, and laboratory variables were collected for analysis. Early mortality was defined as 30-day mortality after DC. First, a univariate analysis (P < 0.05) was used to compare survivors and nonsurvivors. Multivariate logistic regression analysis was used to identify the predictors of 30-day mortality for patients who underwent primary DC. RESULTS: A total of 387 patients were enrolled in the study. The 30-day mortality was 31.52% (122/387). The median age at presentation was 49 years (interquartile range, 38-60), and 316 (81.65%) patients were male. In the multivariate logistic regression analysis, the factors associated with 30-day mortality included age (odds ratio [OR], 1.068; 95% confidence interval [CI], 1.040-1.096; P < 0.001), bilateral unreactive pupils (OR, 12.734; 95% CI, 4.129-39.270; P < 0.001), subdural hemorrhage (OR, 3.468; 95% CI, 1.305-9.218; P < 0.013), completely effaced basal cistern (OR, 3.52; 95% CI, 1.568-7.901; P = 0.002), intraoperative hypotension (OR, 11.532; 95% CI, 4.222-31.499; P < 0.001), preoperative activated partial thromboplastin time (OR, 6.905; 95% CI, 2.055-23.202; P = 0.002), and Injury Severity Score (OR, 1.081; 95% CI, 1.031-1.133; P = 0.002). CONCLUSIONS: In patients undergoing primary DC after traumatic brain injury, the predictors of 30-day mortality include age, bilateral unreactive pupils, subdural hemorrhage, completely effaced basal cistern, intraoperative hypotension, preoperative activated partial thromboplastin time, and Injury Severity Score.

Fourteen-Day Mortality in Pediatric Patients with Traumatic Brain Injury After Early Decompressive Craniectomy: A Single-Center Retrospective Study.

OBJECTIVE: The purpose of this study was to analyze the risk factors for 14-day mortality in pediatric patients undergoing early decompressive craniectomy (DC) after traumatic brain injury (TBI). METHODS: This retrospective analysis included all pediatric patients (≤16 years of age) undergoing DC within 12 hours of TBI between August 2011 and July 2017 at the authors' institute. Demographic information, clinical characteristics, surgical information, and laboratory parameters were retrieved from medical records. Risk factors for 14-day mortality were analyzed using multivariate logistic regression models. First, potentially relevant variables were compared between those who died within 14 days versus those who did not. Variables with P < 0.10 were entered into the final multivariate regression analysis. RESULTS: A total of 36 patients (23 boys and 13 girls; median age, 7 years) were included in the analysis. Fall (n = 19, 52.8%) was the leading cause of injury. The 14-day mortality was 38.9% (14/36). At the time of admission, the median Glasgow Score Scale (GCS) was 6 (IQR 4-8), and the mean Injury Severity Score (ISS) (± standard deviation) was 29.03 ± 8.54. Preoperative hypoxia, defined as oxyhemoglobin arterial saturation <90% or apnea >20 seconds, was observed in 6 patients (16.7%). Coagulopathy was present in 14 patients (38.9%). Multivariate logistic regression analysis suggested an association between 14-day mortality and younger age (odds ratio [OR] = 0.708, 95% confidence interval [CI]: 0.513-0.978; P = 0.036) and higher ISS (OR = 1.399; 95% CI: 1.023-1.914; P = 0.035). CONCLUSIONS: In children undergoing early DC after TBI, risk factors for 14-day mortality include younger age and higher ISS.