Standard Medical Treatment Group Research Articles

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke

The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. EVT vs standard medical treatment (SMT). The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

Interventional embolisation for patients with cirrhosis and recurrent or persistent hepatic encephalopathy related to spontaneous portosystemic shunts: protocol for a prospective, non-randomised controlled study

IntroductionThe presence of spontaneous portosystemic shunts (SPSS) has been identified to be associated with hepatic encephalopathy (HE) in patients with cirrhosis. Nevertheless, the role of interventional embolisation in managing such...

Abstract 205: Efficacy and Safety of Mechanical Thrombectomy for Primary MeVO with Disabling Deficit

Introduction We aimed to evaluate the efficacy and safety of mechanical thrombectomy (MT) for medium vessel occlusion (MeVO) with the disabling deficit. Methods The study period was from January 2011 to December 2022. Inclusion criteria were 1) within 24 hours of stroke onset, 2) prestroke mRS score ≤1, 3) NIHSS score ≥4 or disabling deficit (complete hemianopia (≥2 on NIHSS), severe aphasia (≥2 on NIHSS), visual sensory extinction (≥1 on NIHSS), significant weakness with NIHSS subscore of paralysis ≥2), 4) MeVO (MCA distal M2, M3, ACA A1, A2, A3, PCA P1, P2, and P3). Outcomes were compared between the MT and standard medical treatment (SMT) groups. Outcome was defined as the favorable outcome (mRS score 0‐2 at 90 days), death within 90 days, and symptomatic intracranial hemorrhage (SICH). Results Of all, 192 patients (72 women, median age 78 years, median NIHSS score 11 points) were enrolled, and 76.6% (n=147) had distal M2 occlusion. Compared to the SMT group (n=153), the MT group (n=39) had a significantly larger median Tmax&gt;10 sec volume (median 25 mL vs. 5 mL, P&lt;0.01) and Tmax&gt; 6‐sec volume (61 mL vs. 44 mL, P&lt;0.01), while median NIHSS score (13 vs. 11, P=0.69) and intravenous thrombus (51.6％ vs. 55.3%, P=0.72) were significantly lower in the MT group. There were significantly more patients in the MT group with a favorable outcome (73.7% vs. 54.1%, adjusted odds ratio 2.59 95% confidence interval 1.07‐6.24), death within 90 days (7.9% vs. 3.1%), SICH (5.3% vs. 4.4%) were not significantly different. In subgroup analysis, MT was independently associated with age (&lt;80 years; 1.33, 1.21‐15.57, P=0.222) and neurological severity (NIHSS ≥10 points; 2.79, 1.07‐7.24, P=0.870) for a favorable outcome. Conclusion In MeVO with disabling deficits, MT was independently associated with more favorable outcomes than the SMT group.

Endovascular treatment versus standard medical treatment for basilar artery occlusion: a meta-analysis of randomized controlled trials.

Acute ischemic stroke caused by basilar artery occlusion (BAO) is devastating, but the optimal treatment for patients with BAO remains controversial. In this study, the authors aimed to investigate the safety and efficacy of endovascular treatment (ET) versus standard medical treatment (SMT) in patients with BAO. The PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs). The primary outcome was good functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary efficacy outcome was excellent functional outcome defined as an mRS score of 0-2 at 90 days. The safety outcomes included mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Subgroup analyses were carried out based on race (Asian or non-Asian). Four RCTs of 988 patients (556 in the ET group and 432 in the SMT group) were included in this meta-analysis. The proportion of good functional outcome in the ET group was significantly higher than that in the SMT group (45.1% vs 29.6%; number needed to treat 6.45; RR 1.54, 95% CI 1.16-2.06; p = 0.003, I2 = 60%). The subgroup analysis based on race showed a significant difference between Asian and non-Asian race in the primary outcome (p = 0.03, I2 = 78.5%). Patients in the ET group had a higher rate of excellent functional outcome at 90 days than those in the SMT group (34.9% vs 20.6%; RR 1.83, 95% CI 1.07-3.12; p = 0.03, I2 = 80%). Patients in the ET group had a lower mortality at 90 days (35.6% vs 45.4%; RR 0.77, 95% CI 0.66-0.89; p = 0.0007, I2 = 0%) but a higher rate of sICH (5.4% vs 0.5%; RR 8.29, 95% CI 2.49-27.66; p = 0.0006, I2 = 0%) than those in the SMT group. ET may improve the functional outcome and reduce mortality at 90 days but increase the risk of sICH compared with SMT in patients with BAO. This conclusion needs to be confirmed in non-Asian populations in future studies. Systematic review registration no.: CRD42022357718 (https://www.crd.york.ac.uk/prospero/).

Double Plasma Molecular Adsorption System with Sequential Low-dose Plasma Exchange in Patients with Hepatitis B Virus-related Acute-on-chronic Liver Failure: A Prospective Study.

To investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-dose plasma exchange (LPE) in treating early hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of patients with HBV-ACLF were prospectively collected, including patients in a DPMAS with sequential LPE (DPMAS+LPE) group and those in a standard medical treatment (SMT) group. The primary endpoint was death or liver transplantation (LT) at 12 weeks of follow-up. Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups. After 2 weeks, total bilirubin, alanine aminotransferase, blood urea nitrogen levels, and Chinese Group on the Study of Severe Hepatitis B score, were significantly lower in the DPMAS+LPE group than those in the SMT group (p<0.05). After 4 weeks, laboratory parameters of the two groups were similar. The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks (97.9% vs. 85.4%, p=0.027), but not at 12 weeks (85.4% vs. 83.3%, p=0.687). Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group (p<0.05). Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes, regulation of immune effect response, regulation of endotoxin response, and glial cell proliferation. DPMAS+LPE significantly improved the 4-week cumulative survival rate, and ameliorated the inflammatory response in patients. DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.

Effect of Pranayama as Adjuvant to Medical Treatment on Severity, Frequency, and Duration of Headache in Migraine Patients: An Open-Label Randomized Controlled Trial.

Migraine is the second leading cause of disability worldwide with high rates of dissatisfaction for allopathic treatment among patients. Pranayama is an easy, convenient, and cost-effective method that can supplement existing standard medical treatment of migraine. To study the effect of pranayama as an adjuvant to standard medical treatment of migraine on clinical outcome variables of migraine. This was a randomized controlled trial conducted on 80 consecutive migraine patients who were diagnosed as per International Classification of Headache Disorders-3 (ICHD-3) criteria and were randomly allocated into two groups, that is, standard medical treatment (SMT) group and standard medical treatment plus pranayama (SMT + P) group. The effect of pranayama on clinical outcome variables of migraine was evaluated by using standardized questionnaires. The data was statistically analyzed using SPSS Statistics 20 software. A P value of ≤0.05 was considered statistically significant. Intragroup analysis showed all clinical outcome variables of migraine reduced significantly in the SMT + P group whereas all clinical outcome variables of migraine except the duration of headache episodes reduced significantly in the SMT group. Although statistically non-significant, intergroup analysis demonstrates that reduction in headache severity, duration of headache episodes, and headache impact test-6 (HIT-6) score was more in the SMT + P group whereas reduction in headache frequency and migraine disability assessment (MIDAS) score was more in the SMT group. Pranayama supplements the standard medical treatment of migraine by reducing the duration of headache episodes in addition to the reduction in headache severity, headache frequency, HIT-6 scores, and MIDAS scores.

Outcome of endovascular treatment in acute basilar artery occlusion with National Institutes of Health Stroke Scale score 10-19.

Authors of this study aimed to investigate the efficacy and safety of endovascular treatment (EVT) versus standard medical treatment (SMT) alone in patients with acute basilar artery occlusion (BAO) and moderate deficit (National Institutes of Health Stroke Scale [NIHSS] score 10-19). Patients with moderate deficit caused by acute BAO in the period from January 2014 to May 2019 were included in the study. The patients were divided into groups based on treatment: EVT plus SMT group or SMT-alone group. The primary outcome was favorable functional outcome (modified Rankin Scale score 0-3) at 90 days, and safety outcomes were symptomatic intracerebral hemorrhage (sICH) and mortality at 90 days. A total of 173 patients had moderate deficits, 128 of whom had been treated with EVT and 45 with SMT alone. EVT was associated with a significant higher proportion of 90-day favorable outcomes compared with SMT (adjusted odds ratio [aOR] 4.09, 95% CI 1.39-12.04, p = 0.011). Younger age (aOR 0.96, 95% CI 0.92-0.99, p = 0.017), absence of diabetes mellitus (aOR 0.35, 95% CI 0.12-0.99, p = 0.048), higher baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS; aOR 1.48, 95% CI 1.07-2.05, p = 0.018), and modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b-3 (aOR 15.15, 95% CI 3.07-74.72, p = 0.001) were independent factors for a favorable outcome in the EVT group. Rates of mortality and sICH were comparable in the EVT and SMT groups. EVT leads to improved outcomes compared to those with SMT alone. Younger age, absence of diabetes mellitus, higher baseline pc-ASPECTSs, and mTICI score of 2b-3 were associated with better functional outcome in the EVT group.

Optimal timing of salvage intratympanic steroids in idiopathic sudden sensorineural hearing loss.

BackgroundSalvage intratympanic steroids (ITS) works in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) after failure of initial therapy, but optimal timing of administration is unknown.MethodsTwo hundred and seventy patients with ISSNHL were included. Among them, 180 were treated with ITS and standard medical treatment (SMT) and the other 90 received SMT along. The hearing threshold before and after salvage treatment were compared. The relationship between the salvage starting time and hearing recovery was analyzed.ResultsThe hearing of ITS group improved more than that of the SMT group in all frequency bands. The effect of both strategies decreases with the delay of the starting time. ITS can improve hearing even if being administrated 5 weeks after onset while SMT failed after 3 weeks.ConclusionPatients with profound ISSNHL can obtain extra hearing recovery from salvage ITS. The earlier salvage starts, the greater the patient benefits.

Endovascular treatment for distal basilar artery occlusion stroke.

BackgroundThis study aimed to investigate the clinical outcomes of endovascular treatment (EVT) for distal basilar artery occlusion (BAO) and compare them with the outcomes of standard medical treatment (SMT) in daily clinical practice.MethodsPatients with distal BAO enrolled in the BASILAR study from January 2014 to May 2019 were included. Differences in clinical outcomes were analyzed using Pearson's chi-square test and multivariable logistic regression. Clinical outcomes were evaluated using the modified Rankin Scale (mRS) score at 90 days, the mortality at 90 days, and the occurrence of symptomatic intracranial hemorrhage within 48 h.ResultsAmong the 267 patients with distal BAO (222 patients in the EVT group and 45 patients in the SMT group), compared with the SMT group, the EVT group was associated with a favorable outcome (mRS 0–3; 40.1 vs. 15.6%; aOR 5.44; 95% CI, 1.68–17.66; P = 0.005) and decreased mortality (44.6 vs. 71.1%, aOR 0.32, 95% CI, 0.13–0.77; P = 0.012). In the EVT group, multivariable analysis showed that the initial National Institutes of Health Stroke Scale (NIHSS) score and posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS) were associated with favorable functional outcomes and mortality.ConclusionOur study suggests that, compared with SMT, EVT is technically feasible and safe for patients with distal BAO.

Benefits of Endovascular Treatment in Late Window for Acute Ischemic Stroke Selected without CT Perfusion: A Real-World Study.

ObjectiveThis study examined the functional outcomes and safety of endovascular treatment (EVT) in acute ischemic stroke (AIS) patients owing to large vessel occlusion of the anterior circulation, presented during a late-time window (6–24 hours after last seen well (LSW)) in a real-world practice.MethodsThis was a retrospective analysis from a bi-center prospective cohort. According to the stroke treatment, patients with continuous Alberta Stroke Plan Early Aspect score (ASPECTS) ≥6 on non-contrast CT (NCCT) and moderate to good collateral state on CT angiography (CTA) were divided into EVT group and standard medical treatment (SMT) group. The primary outcome was the rate of functional independence (90-day mRS ≤2). Safety outcomes were the occurrence of symptomatic intracranial hemorrhage (sICH) and the 90-day mortality.ResultsAmong the 288 enrolled patients (53.5% male, median age 64 years), there were 167 patients in the EVT group and 121 in the SMT group. After multivariable adjustments for potential confounders, EVT was associated with functional independence (adjusted OR: 3.052; 95% confidence interval (CI): 1.553–5.997; p = 0.001). In the PSM cohort, 44.2% (42/95) of patients in the EVT group versus 18.9% (18/95) in the SMT group achieved functional independence (OR: 3.39, 95% CI: 1.763–6.517), and there was a significant difference favoring EVT over the SMT in the overall distribution of mRS (OR: 2.170, 95% CI: 1.302–3.618) at 90 days. The rate of sICH did not differ between the EVT and SMT groups (10.5% vs 8.4%, p = 0.804) nor did 90-day mortality (18.9% vs 22.1%, p = 0.719). No interaction was found in p-values with statistical significance in subgroup analysis.ConclusionThis real-world experience suggests that EVT for late-presenting stroke patients, based on small core on NCCT and moderate to good collaterals on CTA, is associated with better outcomes than SMT alone, with no increase in sICH and 90-day mortality rates.

Improving the Prognosis of Patients With Acute Ischemic Stroke Treated in the Late Time Window After the Introduction of Advanced Imaging Software: Benefits From Thrombectomy in the Extended Time Window.

Mechanical thrombectomy (MT) of ischemic stroke was recommended as a clinical guideline in 2015, and the indication for time was expanded in 2018 based on two clinical studies. We aimed to compare and analyze the prognosis of patients treated under the extended time indication before and after the introduction of advanced software. We obtained data from medical records between 2016 to 2020. From 2016 to 2017, patients who did not receive MT who visited the hospital within 24 hours from the last normal time (LNT) were classified as standard medical treatment (SMT) group. Among patients who underwent MT between 2019 and 2020, patients who visited the hospital between 6-24 hours from the LNT were classified into the extended MT (EMT) group. Good outcome was defined as 3-months modified rankin scale (mRS) ≤ 2, and a poor outcome as mRS ≥ 4. From 2016 to 2017, 1,058 patients were hospitalized for ischemic stroke, of which 60 (5.7%) received MT, and 27 patients were classified into the SMT group. Among 1,019 patients between 2019 and 2020, 85 (8.3%) received MT, and 24 patients were in the EMT group. Among the SMT group, only 3 had a good prognosis, and 24 (88.9%) had a poor prognosis. However, in the EMT group, 10 (41.7%) had a good prognosis, and 9 (37.5%) had a poor prognosis. The SMT group had a 49.1 times higher risk of poor prognosis compared to the EMT group (P = 0.008). The number of patients with ischemic stroke who receive MT has increased by using advanced imaging software. It was confirmed that patients treated based on the extended time indication also had a good prognosis.

Skills or Pills: Randomized Trial Comparing Hypnotherapy to Medical Treatment in Children With Functional Nausea

The potential effectiveness of gut-directed hypnotherapy (HT) is unknown for pediatric chronic nausea. This randomized controlled trial compared HT with standard medical treatment (SMT). One hundred children (ages, 8-18 y) with chronic nausea and fulfilling functional nausea (FN) or functional dyspepsia (FD) criteria were allocated randomly (1:1) to HT or SMT, with a 3-month intervention period. Outcomes were assessed at baseline, at the halfway point, after treatment, and at the 6- and 12-month follow-up evaluation. Children scored nausea symptoms in a 7-day diary. The primary outcome was treatment success, defined as a reduction in nausea of 50% or more, at the 12-month follow-up evaluation. Secondary outcomes included adequate relief of nausea. After treatment and at the 6-month follow-up evaluation, there was a trend toward higher treatment success in the HT group compared with the SMT group (45% vs 26%, P= .052; and 57% vs 40%, P= .099, respectively). At 12 months, treatment success was similar in both groups (60% in the HT group and 55% in the SMT group; P= .667). In the FN group, significantly higher success rates were found for HT, but no differences were found in patients with FD. Adequate relief was significantly higher in the HT group than in the SMT group at the 6-month follow-up evaluation (children: 81% vs 55%, P= .014; parents: 79% vs 53%; P= .016), but not at the 12-month follow-up evaluation. HT and SMT were effective in reducing nausea symptoms in children with FN and FD. In children with FN, HT was more effective than SMT during and after the first 6 months of treatment. Therefore, HT and SMT, applied separately or in combination, should be offered to children with FN as a treatment option (Clinical trials registration number: NTR5814).

Low Volume Plasma Exchange and Low Dose Steroid Improve Survival in Patients With Alcohol-Related Acute on Chronic Liver Failure and Severe Alcoholic Hepatitis – Preliminary Experience

Alcohol-related acute on chronic liver failure (A-ACLF) patients have high short-term mortality and are poor candidates for steroid therapy. Plasma exchange (PLEX) improves survival in ACLF patients. We analyzed our experience with low volume PLEX (50% of plasma volume exchanged per session) and low dose steroids to treat A-ACLF patients. We retrospectively compared the efficacy of low volume PLEX and low-dose steroids with standard medical treatment (SMT) in A-ACLF patients treated at our center between November 2017 to June 2019. The primary study outcome was one-year survival. Twenty-one A-ACLF patients in PLEX group [age 40 (29-56) years, median (range); MELD score 31 (29-46)] and 29 A-ACLF patients in SMT group [age 41.5 (28-63) years, MELD score 37 (21-48)] were studied. All 50 study patients had severe alcoholic hepatitis [mDF 84.7 (50-389)]. PLEX group patients had 3 (1-7) PLEX sessions with 1.5 (1.4-1.6) liters of plasma exchanged per session and oral Prednisolone 20mg daily, tapered over 1 month. Kaplan Meier analysis showed better survival over 1 year in the PLEX group compared to the SMT group (P=0.03). There was renal dysfunction in 10 patients in the PLEX group, which normalized in six patients after PLEX. In this preliminary report, compared to SMT, low volume PLEX and low dose steroid improved survival over one year in A-ACLF patients with severe alcoholic hepatitis. In patients with renal dysfunction, 60% showed improvement in renal function with PLEX. Studies with a larger number of patients are needed to validate these results.

Abstract P7: Prior Antithrombotic Medication May Affect Outcomes Following Alteplase at 0.6mg for Unknown Onset Stroke: THAWS Randomized Clinical Trial

Background and purpose: To assess the potential effect of prior antithrombotic medication for thrombolysis using alteplase at 0.6mg/kg in unknown onset stroke. Methods: This was a prespecified sub-analysis of a THAWS trial (an investigator-initiated, multicenter, randomized, open, blinded-endpoint trial). Stroke patients with a time last-known-well &gt;4.5 h who had a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6mg/kg or standard medical treatment (SMT). Patients were dichotomized by taking prior antithrombotic medication. The favorable outcome defined as a modified Rankin Scale score of 0-1 at 90 days and any intracranial hemorrhage within 22-36 h were compared in each group. Results: Of 126 patients (intention-to-treat population), 68 received alteplase and 58 had SMT. Seventeen in the alteplase group and 23 in the SMT group took antithrombotic medication (10 with antiplatelet alone, 5 with anticoagulant alone and 2 with both in the IVT group, and 14, 8 and 1, respectively, in the SMT group) before stroke onset. Antithrombotic therapy was more frequently initiated within 24 hours after randomization in the SMT group than in the alteplase group (86% vs. 12%, p&lt;0.0001). Both any intracranial hemorrhage (26% in the alteplase group vs. 14% in the SMT group) and favorable outcome (47% vs. 48%) were comparable between the two treatment groups. There was a significant treatment-by-cohort interaction for favorable outcome between patients with prior antithrombotic medication and those without (p=0.006). Favorable outcome was more common in the alteplase group than in the SMT group in patients with prior antithrombotic medication (59% vs. 26%; RR 2.25, 95% CI 1.02 to 4.99), but it tended to be less common in the alteplase group than in the SMT group in those without prior antithrombotic medication (43% vs. 63%; RR 0.69, 95% CI 0.46 to 1.03). The frequency of any intracranial hemorrhage did not differ significantly between the two treatment groups in any dichotomized patients. Conclusions: Alteplase at 0.6mg/kg appears more beneficial in patients with prior antithrombotic medication.

NONİNVAZİV MEKANİK VENTİLASYON DESTEĞİ OLAN VE OLMAYAN AKUT SOLUNUM YETMEZLİĞİNDE FONKSİYONEL BAĞIMSIZLIK VE KAS KUVVETİ

Purpose: Development of muscle weakness is common in the course of acute respiratory failure (ARF). This study aimed to compare muscle strength and physical function in subjects with ARF undergoing noninvasive mechanical ventilation (NIV) added to standard medical treatment (SMT) and SMT only in the intensive care unit. Methods: Thirty-two subjects with ARF (19 NIV and 13 SMT) were included. Subject characteristics were recorded. Peripheral muscle strength was measured using the Medical Research Council Scale (MRC) and handgrip strength. Functional independence was evaluated using the Barthel Index (BI). Results: In the NIV group, proximal muscle strength (shoulder abduction) was significantly lower than distal limb strength (wrist extension) (p=0.030). In both groups, proximal lower limb strength (hip flexion) was also significantly lower than distal limb strength (ankle dorsiflexion) (p=0.002). The BI total score was significantly lower in the NIV group than that of the SMT group (p=0.016). The BI score was significantly related to the MRC sum score (r=0.633) and handgrip strength (r=0.629, p&amp;lt;0.05). Conclusion: Functional independence and proximal muscle strength compared to distal adversely affected in patients undergoing NIV for ARF. Weakness or functional limitations may prevent patients from functioning adequately in rehabilitation practices in intensive care.

Artificial liver treatment improves survival in patients with hepatitis B virus-related acute-on-chronic liver failure: A case-control matched analysis.

The artificial liver support system (ALSS) is recognized as a bridge to liver transplantation in hepatitisB virus-related acute-on-chronic liver failure (HBV-ACLF) patients. However, patient survival remains unknown. We aim to assess the effects of ALSS on survival in HBV-ACLF patients. The clinical data of HBV-ACLF patients receiving standard medical treatment (SMT) plus ALSS (ALSS group, n = 507) or only SMT (SMT group, n = 417) were collected for survival assessment. The main end-points were cumulative survival rates at days21, 28, and 90. Four different rigorous analyses were carried out to reduce bias and confounding. In the entire cohort, the cumulative survival rates at days21, 28, and 90 were significantly higher in patients who underwent ALSS treatment (73.3% vs. 59.6%, 69.2% vs. 56.6%, 56.5% vs. 49.1%, respectively, P < 0.01) than in those who underwent SMT only. In the 276-pair case-control matched cohort, a significantly higher survival rate was also observed in the ALSS group than in the SMT group on days21, 28, and 90 (72.5% vs. 60.3%, 68.3% vs. 57.4%, 55.9% vs. 48.5%, respectively, P < 0.05), especially in patients with ACLF-1 and -2. By a multivariable-adjusted analysis, ALSS treatment was associated with a significantly lower risk of mortality, especially for ACLF-2 at days21, 28, and 90. These findings were also confirmed through propensity score matching and inverse probability treatment weighting analysis. ALSS treatment can improve short-term survival and is associated with a significantly lower risk of short-term mortality in patients with HBV-ACLF, especially ACLF-2.

Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma: Apreclinical F98 glioblastoma rat model study.

PurposeEven with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12–15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma. Cx43-mediated gap junctional communication has been observed between tumor cells, between astrocytes and between tumor cells and astrocytes. Therefore, gap junction directed therapy using a pharmacological suppressor or modulator, such as tonabersat, could be a promising target in the treatment of GB. In this preclinical study, we evaluated the possible therapeutic potential of tonabersat in the F98 model.ProceduresFemale Fischer rats were inoculated with ± 25.000 F98 tumor cells in the right frontal lobe. Eight days post-inoculation contrast-enhanced T1-weighted (CE-T1w) magnetic resonance (MR) images were acquired to confirm tumor growth in the brain. After tumor confirmation, rats were randomized into a Control Group, a Connexin Modulation Group (CM), a Standard Medical Treatment Group (ST), and a Standard Medical Treatment with adjuvant Connexin Modulation Group (STCM). To evaluate therapy response, T2-weighted (T2w) and CE-T1w sequences were acquired at several time points. Tumor volume analysis was performed on CE-T1w images and statistical analysis was performed using a linear mixed model.ResultsSignificant differences in estimated geometric mean tumor volumes were found between the ST Group and the Control Group and also between the STCM Group and the Control Group. In addition, significant differences in estimated geometric mean tumor volumes between the ST Group and the STCM Group were demonstrated. No significant differences in estimated geometric mean tumor volumes were found between the Control Group and the CM Group.ConclusionOur results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy.

Artificial Liver Treatment Improves Survival in Patients with Acute-on-Chronic Liver Failure

Background: The artificial liver support system (ALSS) is recognized as a bridge to liver transplantation (LT) in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients; however, its impact on patient survival remains unknown. This study aimed to assess the effects of ALSS on survival in patients with HBV-ACLF. Methods: The clinical data of HBV-ACLF patients receiving standard medical treatment (SMT) plus ALSS (ALSS group, n = 507) or only SMT (SMT group, n = 417) were collected for survival assessment. The main endpoints were cumulative survival rates at days 21, 28 and 90. A case-control matched analysis was used to reduce bias between the ALSS and SMT groups. A propensity score matching (PSM) and inverse probability treatment weighting (IPTW) analysis were performed to confirm the survival effect of ALSS. Findings: In the entire cohort, the cumulative survival rates at days 21, 28 and 90 were significantly higher in patients who underwent ALSS treatment (73.3% vs. 59.6%, 69.2% vs. 56.6%, 56.5% vs. 49.1%, respectively, P <0.01) than in those who underwent SMT only. In the 276-pair case-control matched cohort, a significantly higher survival rate was also observed in the ALSS group than in the SMT group on days 21, 28 and 90 (72.5% vs. 60.3%, 68.3% vs. 57.4%, 55.9% vs. 48.5%, respectively, P <0.05), especially in patients with ACLF-1 and -2. By a multivariable-adjusted analysis, ALSS treatment was associated with a significantly lower risk of mortality, especially for ACLF-2 at days 21, 28 and 90 (HR: 0.587, 0.596 and 0.640, respectively). These findings were also confirmed through PSM and IPTW analysis (HR: 0.482/0.538 and 0.538/0.552 at day 21/28, respectively, P <0.01). Interpretation: Compared with SMT, ALSS treatment improved the short-term survival and was associated with a significantly lower risk of short-term mortality in patients with HBV-ACLF, especially ACLF-2. Funding Statement: The authors declared: None. Declaration of Interests: The authors stated: No conflict. Ethics Approval Statement: The study protocol was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (No. 2011-13). All patients were well informed, and written consent was obtained from the study subjects or the legal surrogates of patients before enrolment.

Gut-directed hypnotherapy versus standard medical treatment for nausea in children with functional nausea or functional dyspepsia: protocol of a multicentre randomised trial

IntroductionThe treatment of chronic functional nausea or nausea due to functional dyspepsia in children is generally symptomatic. Moreover, these disorders pose a risk for worse psychosocial and health outcomes in...

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Italian Medicine Agency.