[Successful bridging therapy with alectinib prior to allogeneic stem cell transplantation for refractory ALK-positive anaplastic large cell lymphoma].

Although alectinib is effective for relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL) and has a favorable safety profile, its role as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the role of allo-HSCT itself in this setting are unknown. A 35-year-old man with ALK-positive ALCL experienced relapse after first-line therapy with CHOP. Brentuximab vedotin led to partial response and high-dose chemotherapy combined with autologous HSCT was performed. However, disease progressed 15 months after transplantation, and alectinib was initiated. Complete response (CR) was achieved after three months of treatment, and alectinib was continued for 5 months. After cessation of alectinib, allogeneic bone marrow transplantation from an HLA 1-locus mismatched unrelated donor was performed after conditioning with fludarabine, busulfan, and total body irradiation. GVHD prophylaxis consisted of tacrolimus and short-term methotrexate. The post-transplant course was unremarkable except for grade I acute GVHD. The lymphoma has not recurred for 2 years after allo-HSCT without resuming alectinib. The clinical course of our case suggests that alectinib bridging therapy and allo-HSCT are effective in relapsed/refractory ALK-positive ALCL.

Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Comparison of the Efficacy and Safety Between Intravenous Thrombolysis, Direct Endovascular Therapy, and Bridging Therapy for Acute Basilar Artery Occlusion in Cerebral Infarction Patients.

OBJECTIVE: To compare the efficacy and safety of intravenous thrombolysis, direct endovascular therapy (EVT), and bridging therapy (BT = intravenous thrombolysis + EVT) for acute basilar artery occlusion cerebral infarction. METHODS: One hundred and fourteen patients with acute basilar artery occlusion cerebral infarctions admitted between January 2020 and August 2023 were selected. Differences in the reperfusion rate, prognosis, incidence of stroke-associated pneumonia, and mortality rate were compared among the 3 groups. RESULTS: There was no statistically significant difference in the percentage of patients who achieved successful reperfusion (86.8% vs. 84.2%) or complete reperfusion (72.1% vs. 68.4%) between the direct EVT and BT groups (both P > 0.05). There were no statistically significant differences in the rates of symptomatic intracranial hemorrhage (3.7% vs. 10.3% vs. 10.5%, P = 0.763). There were statistically significant differences in the rates of good prognosis (modified ranking scale score 0-2) (59.3% vs. 30.9% vs. 26.3%, P = 0.021), stroke-related pneumonia (29.6% vs. 66.2% vs. 36.8%, P = 0.002), and mortality (14.8% vs. 48.5% vs. 42.1%, P = 0.010) among the 3 treatment groups. According to the binary logistic regression analysis, a good prognosis was independently associated with a baseline National Institutes of Health Stroke Scale score ≤ 10 (odds ratio, 3.714; 95% confidence interval, 1.207-11.430; P = 0.022) and the incidence of stroke-associated pneumonia (odds ratio, 0.640; 95% confidence interval, 0.484-0.845; P = 0.002). CONCLUSIONS: Although there were differences in prognosis, mortality, and incidence of complications among the 3 treatment groups, after adjusting for confounding factors, prognosis was independently correlated only with the baseline NIHSS score and stroke-associated pneumonia but not with treatment methods.

Risk Factors and Prognosis of Early Neurological Deterioration after Bridging Therapy.

BACKGROUND: Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes. OBJECTIVE: We aimed to study the incidence, risk factors and prognosis of END after BT. METHODS: From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors. RESULTS: The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001). CONCLUSION: It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.

Meta-analysis of direct endovascular thrombectomy vs bridging therapy in the management of acute ischemic stroke with large vessel occlusion.

BACKGROUND: Debates persist when using intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). This systematic review and meta-analysis synthesized evidence on outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), comparing bridging therapy (BT) with MT alone. METHOD: We conducted searches of PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to July 2023 to identify pertinent clinical trials and observational studies. RESULT: 76 studies, involving 37,658 patients, revealed no significant difference in 90-day functional independence between DEVT and BT. However, a trend favoring BT for achieving functional independence with a modified Rankin Scale (mRS) of 0-1 was observed, having Odds ratio (OR) of 0.75 (95% CI 0.66-0.86; p < 0.001). DEVT was associated with higher postprocedural mortality (OR 1.44;95% CI 1.25-1.65; p < 0.001), but a lower risk of symptomatic intracranial hemorrhage compared to BT (OR 0.855; 95% CI 0.621-1.177; p = 0.327). Successful recanalization rates favored BT, emphasizing the importance of individualized treatment decisions (OR 0.759; 95% CI 0.594-0.969; p = 0.027). Sensitivity analyses were conducted to identify key contributors to heterogeneity. CONCLUSION: Our meta-analysis underscores the intricate equilibrium between functional efficacy and safety in the evaluation of DEVT and BT for ACS-LVO. Fundamentally, while BT appears more efficacious, concerns about safety arise due to the superior safety profile demonstrated by DEVT. Individualized treatment decisions are imperative, and further trials are warranted to enhance precision in clinical guidance.

Outcomes of transplant-eligible patients with myelodysplastic syndrome with excess blasts registered in an observational study: The JALSG-CS11-MDS-SCT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the sole curative therapy for myelodysplastic syndrome (MDS). However, whether bridging therapy (BRT) including azacitidine (AZA) and combination chemotherapy (CCT) prior to allo-SCT should be performed is unclear. We analyzed BRT and the outcomes of patients with myelodysplastic syndrome with excess blasts (MDS-EB) who were ≤ 70 years old at the time of registration for a prospective observational study to clarify the optimal allo-SCT strategy for high-risk MDS. A total of 371 patients were included in this study. Among 188 patients (50.7%) who were considered for allo-SCT, 141 underwent allo-SCT. Among the patients who underwent allo-SCT, 64 received AZA, 29 received CCT, and 26 underwent allo-SCT without BRT as the initial treatment. Multivariate analysis identified BRT as an independent factor influencing overall survival (AZA vs. without BRT, hazard ratio [HR] 3.33, P = 0.005; CCT vs. without BRT, HR 3.82, P = 0.003). In multivariate analysis, BRT was independently associated with progression-free survival (AZA vs. without BRT: HR, 2.23; P = 0.041; CCT vs. without BRT: HR, 2.94; P = 0.010). Transplant-eligible patients with MDS-EB should undergo allo-SCT when clinically acceptable, and upfront allo-SCT without BRT may be superior to AZA or CCT.

Bridging therapy improves functional outcomes and reduces 90-day mortality compared with direct endovascular thrombectomy in patients with acute posterior ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: It remains unclear whether bridging therapy can achieve better neurologic outcomes than direct endovascular thrombectomy (EVT) in patients with posterior ischemic stroke. METHODS: We systematically searched PubMed, EMBASE, and Cochrane databases with posterior artery occlusion treated with bridging therapy vs. EVT. Efficacy was assessed based on functional independence at 90 days and successful recanalization, whereas safety was assessed by mortality, rate of symptomatic intracranial hemorrhage (sICH), and occurrence of any hemorrhage. All data were analyzed with Review Manager software v5.3 and the risk of bias was determined using the Methodological Index for Non-randomized Studies. RESULTS: We included 17 studies with a total of 3278 patients (1211 in the bridging therapy group and 2067 in the EVT group). Patients in the bridging group had a better functional outcome at 90 days, as evidenced by a higher proportion with a Modified Rankin Scale (mRS) score of 0-2 compared with the EVT group (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.54-2.19, P < 0.01), while no difference in mRS score of 0-3 (OR = 1.18, 95% CI: 0.96-1.45, P = 0.11). Patients in the bridging therapy group also had lower 90-day mortality rate (OR = 0.75, 95% CI: 0.59-0.95, P = 0.02). There were no significant differences between groups in rates of successful recanalization (OR = 0.96, 95% CI: 0.74-1.25, P = 0.77), sICH (OR = 1.27, 95% CI: 0.86-1.89, P = 0.24), and hemorrhage (OR = 1.22, 95% CI: 0.60-2.50, P = 0.58). CONCLUSIONS: Among patients with posterior ischemic stroke, bridging therapy may be superior to EVT in achieving a good functional outcome and lowering the mortality without increasing the risks of hemorrhage.

Bridging techniques compared with direct endovascular therapy for stroke due to tandem occlusion: A systematic review and meta-analysis.

The superiority of the bridging strategy of intravenous thrombolysis (IVT) plus endovascular therapy (EVT) to EVT alone for the anterior circulation with tandem vascular occlusion (TO) has not been specifically addressed by a single randomized trial. Analysis of 15 studies (n = 1857 patients) revealed that 90 Day good functional outcomes (MRS≤2) were better for bridging therapy (IVT + EVT) than for dEVT (OR:1.39, 95%CI: 1.09-1.79, p = 0.008); 90-day mortality was lower for IVT + EVT than for dEVT (OR: 0.57; 95%CI: 0.40-0.81, p = 0.002) and rates of successful recanalization were higher for IVT + EVT than for dEVT (OR: 1.79, 95%CI: 1.36-2.36, p<0.0001). However, there was no significant difference in the incidence of symptomatic. intracranial hemorrhage (sICH) between groups (OR 0.91, 95%CI 0.64-1.31, p = 0.62).In conclusion, Patients receiving IVT + EVT have a better functional outcome, lower death rate and a higher rate of successful recanalization than those receiving dEVT but there was no difference in sICH risk between the two treatments.

Reperfusion strategies in stroke with medium-to-distal vessel occlusion: a prospective observational study.

INTRODUCTION: Medium vessel occlusion (MeVO) accounts for 30% of acute ischemic stroke cases. The risk/benefit profile of endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or the combination of the two (bridging therapy (BT)) is still unclear in MeVO. Here, we compare reperfusion strategies in MeVO for clinical and radiological outcomes. METHODS: This prospective single center study enrolled consecutive patients with AIS due to primary MeVO undergoing IVT, EVT, or BT at a comprehensive stroke center. Primary outcome was good functional status, defined as modified Rankin Scale (mRS) 0-2 at 3-month follow-up. Additional outcomes included mortality, successful recanalization, defined as mTICI ≥ 2b, stroke severity at discharge, and symptomatic intracerebral hemorrhage (sICH) according to SITS-MOST criteria. Logistic regression was modeled to define independent predictors of the primary outcome. RESULTS: Overall, 180 consecutive people were enrolled (IVT = 59, EVT = 38, BT = 83), mean age 75. BT emerged as independent predictor of primary outcome (OR = 2.76, 95% CI = 1.08-7.07) together with age (OR = 0.94, 95% CI = 0.9-0.97) and baseline NIHSS (OR = 0.88, 95% CI = 0.81-0.95). BT associated with a 20% relative increase in successful recanalization compared to EVT (74.4 vs 56.4%, p = 0.049). Rates of sICH (1.1%) and procedural complications (vasospasm 4.1%, SAH in 1.7%) were very low, with no difference across groups. DISCUSSION: BT may carry a higher chance of good functional outcome compared to EVT/IVT only in people with AIS due to MeVO, with marginally higher rates of successful recanalization. Randomized trials are needed to define optimal treatment tailoring for MeVO.

Integrating CAR-T cell therapy into the management of DLBCL: what we are learning.

INTRODUCTION: Chimeric Antigen Receptor ;(CAR) T cells therapies have become part of the standard of care for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The weakness of CAR-T therapies is that there are no comparative clinical trials, although many publications based on real-life data have confirmed the results obtained in pivotal studies. After several years of the commercialization of CAR-T, some points still need to be fully clarified. Healthcare professionals have questions about identifying patients who may benefit from therapy. There are aspects inherent in the accessibility of care related to improved relationships between CAR-T-delivering and referral centers. AREAS COVERED: Open questions are inherent in the salvage and bridge therapy, predictive criteria for response and persistence of CAR-T after infusion. Managing toxicities remain a top priority and one of the points on which further knowledge is needed. EXPERT OPINION: This review aims to describe the current landscape of CAR-T cells in DLBCL, outline their outcomes and toxicities, and explain the outstanding questions that remain to be addressed.

Stroke risk related to intentional discontinuation of antithrombotic therapy for invasive procedures.

OBJECTIVE: Antithrombotic medications pose a challenge for conducting surgical or invasive procedures, because their discontinuation is required to avoid postprocedural hemorrhagic complications but potentially increases the ischemic risk for the patient. This study aimed to estimate the increased risk of developing cerebral ischemic events during hospitalization requiring discontinuation of antithrombotic therapy. METHODS: This investigation was a single-center retrospective observational study. Clinical data in patients scheduled for admission between January 1, 2021, and December 31, 2022, were collected. Patients requiring discontinuation of antithrombotic therapy were identified by referring to the admission database. Patients who developed cerebral ischemia were identified by referring to the institution's stroke center database. RESULTS: Seven hundred ninety-six patients scheduled for nonneurosurgical procedures and 39 scheduled for neurosurgical procedures underwent discontinuation of antithrombotic therapy. Anticoagulation therapy was prescribed in 40.0%, and antiplatelet therapy was prescribed in 69.1% of the patients. A total of 9.2% of the entire cohort of patients were receiving both anticoagulation and antiplatelet therapy. Bridging therapy was administered in 20.9% of nonneurosurgical patients. No ischemic event was observed in the patients undergoing neurosurgical procedures. Among the entire cohort, 3 patients encountered some kind of thrombotic event-2 of which were cerebral ischemia-accounting for an incidence of 0.24%, which was significantly higher than incidental in-hospital stroke unrelated to discontinuation of antithrombotic therapy (p = 0.04). Patients undergoing both anticoagulation and antiplatelet therapy harbored a significantly higher risk for cerebral ischemia related to discontinuation of antithrombotic therapy (p < 0.0001). CONCLUSIONS: Discontinuing antithrombotic therapy during hospitalization for elective invasive procedures-including neurosurgical procedures-entailed a relatively small risk of developing cerebral ischemic events, but the risk was significantly higher compared to hospitalized patients without discontinuation of antithrombotic therapy.

Efficacy and safety of bridging therapy versus direct thrombectomy for tandem lesions in acute stroke: A systematic review and meta-analysis.

BACKGROUND: Current studies have concluded that MT (Mechanical Thrombectomy) is safe and effective for tandem lesions (TL). However, The benefit of bridging therapy for TL is controversial. OBJECTIVE: To compare efficacy and safety between bridging therapy and direct thrombectomy of tandem lesions. METHOD: We conducted a systematic review and meta-analysis of studies comparing bridging therapy versus direct thrombectomy among TL patients with regards to symptomatic intracerebral hemorrhage(sICH), Parenchymal hemorrhage (PH), 3-month mortality, modified Rankin Scale (mRS) score within 3 months, successful reperfusion, and excellent reperfusion. The meta-analysis of proportions was conducted with a common effects model. RESULT: Five studies (n = 1198 patients) were identified for the systematic review. For safety outcomes, the bridging group had no significant difference in the rate of symptomatic intracranial hemorrhage (OR = 0.78, 95% CI = 0.49-1.25, P = 0.31) and the rate of PH (OR = 0.67, 95% CI = 0.39-1.13, P = 0.13) but significantly lower rate of 3-month mortality (OR = 0.53, 95% CI = 0.37-0.75, P = 0.0004) compared to the direct thrombectomy group. In terms of efficacy outcomes, the bridging therapy group had a significantly higher rate of 3- month good functional outcome (mRS 0-2) (OR = 1.76, 95% CI = 1.38-2.24, P < 0.00001) and successful recanalization (OR = 1.69, 95% CI = 1.27-2.25, P = 0.0003) but no significant difference in the rate of excellent recanalization(OR = 1.21, 95% CI = 0.91-1.59, P = 0.19) in patients with TL compared to direct thrombectomy group. CONCLUSION: Bridging therapy is effective in improving the 3-month functional prognosis and increasing the rate of arterial recanalization without increasing the risk of intracranial hemorrhage in patients with TL compared to direct thrombectomy. A large multicentre clinical RCT is expected, as are advanced intravenous thrombolysis and endovascular thrombectomy techniques.

Real-world clinical outcomes in patients with relapsed and refractory multiple myeloma receiving VTD-PACE treatment in the era of monoclonal antibodies.

Bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) are commonly used as salvage treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE. The median follow-up period was 11.1 months, during which they received a median of two cycles of VTD-PACE. The overall response rate (ORR) was 66.7%; ORRs of 53.1 and 82.1% were noted in patients with ≥ 4 and ≤ 3 prior lines (P = 0.027), respectively. The median overall survival (OS) was 17 months, with a median progression-free survival (PFS) of 9.8 months. Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and OS of patients who received or did not receive HSCT or CART after VTD-PACE treatment. Patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell therapy (CART) following VTD-PACE showed a trend of longer PFS and OS than those who did not undergo subsequent HSCT or CART. The median OS in patients with and without renal dysfunction was 10.7 months and 21.5 months, respectively (P = 0.0091). Therefore, VTD-PACE is useful as a bridging therapy for HSCT or CART, as a response can be expected regardless of organ damage, disease risk, or history of anti-CD38 antibody use.

ECMO as a bridge to cardiac surgery: stabilizing unstable patients for a definitive procedure.

Introduction: Extracorporeal membrane oxygenation (ECMO) in adults has been used in post-cardiotomy patients who decline hemodynamically. Cardiogenic shock in patients with potential surgically correctable cardiac conditions are at significantly higher risk for post-operative morbidity and mortality. We present experience with a pre-emptive approach of ECMO institution pre-operatively to stabilize patients with cardiogenic shock. Materials and methods: This study expands on a pilot study with a group of twenty patients who were supported with ECMO pre-operatively in different institutions over a period between 2011 and 2021. The patients presented with cardiogenic shock. Peripheral veno-arterial (VA) ECMO support was used in all the patients. Cardiac surgery was performed via median sternotomy utilizing the in situ ECMO cannulae to institute cardiopulmonary bypass (CPB). Results: Seventeen patients were weaned off ECMO support following a mean duration of support of 156 h. Fifteen patients survived to discharge. The 30-day mortality and in-hospital mortality were 25% (expected 67% by European System for Cardiac Operative Risk Evaluation (EuroSCORE) II). The causes of mortality included persistent bleeding in 2 patients due to liver dysfunction, and one with low platelet counts. The other two had multi-organ failure. Conclusions: Variable period of pre-operative ECMO support provides hemodynamic stability and may prevent or reverse the multi-organ dysfunction if instituted on time in patients presenting with cardiogenic shock. This strategy allows cardiac surgery to be performed with acceptable risk.

BRAF/MEK Inhibition as a Bridge to Immunotherapy for Symptomatic BRAF V600 Melanoma Brain Metastases: A Case Series.

Targeted and immune therapies have changed the paradigm of treatment for patients with metastatic melanoma. Treatment of patients with symptomatic melanoma brain metastases, however, is complicated by the frequent use of immune suppression for the management of vasogenic edema and the urgency in addressing disease burden. Use of BRAF/MEK inhibitors in patients with a corresponding BRAF V600 mutation often results in rapid response but is hindered by high rates of disease relapse and progression. Immunotherapy has higher durability of response, but the rate of response is slower and responses can be significantly diminished for patients on concurrent steroid therapy. Considering this gap in evidence-based guidance for optimal adjuvant therapy sequence in immunosuppressed patients with BRAF V600-mutant melanoma brain metastases, we report on 4 cases utilizing BRAF/MEK inhibitors as a bridging therapy for brain metastases management before initiation of immune checkpoint inhibitor therapy. Future prospective studies will be required to determine the optimal treatment sequencing for patients in this population with high unmet medical need.

Symptomatic Intracranial Hemorrhage after Ischemic Stroke Treated with Bridging Revascularization Therapy.

(1) Background: bridging revascularization therapy is now the standard of care in patients with ischemic stroke due to large vessel occlusion. This study aimed to determine the frequency of symptomatic intracranial hemorrhage (sICH) related to this treatment, and to assess contributing factors and patients' outcomes. (2) Methods: consecutive ischemic stroke patients treated with bridging therapy were prospectively enrolled. sICH (intracranial hemorrhage with an increase in NIHSS score of ≥4 points) was assessed on imaging at 24 h. The functional status of patients was measured at 6 months using the mRS score; (3) Results: 176 patients were included (mean age 68.7 ± 1.2 years, 52.3% women), among whom 15 (8.5%) had sICH. Patients with sICH had more frequent alcohol abuse (30.1% versus 9.7%, p = 0.023), prestroke use of dual antiplatelet therapy (14.3% versus 1.3%, p = 0.002), higher NIHSS scores at admission (median score 20.5 versus 15, p = 0.01), greater systolic blood pressure upon admission, more frequent vascular intracranial calcifications (p = 0.004), leukoaraiosis (p = 0.001), and intracranial atheroma (p = 0.02), and higher neutrophil-to-lymphocyte ratios (p = 0.02) and neutrophil-to-platelet ratios (p = 0.04). At 6-month follow-up, 9 (60%) patients with sICH died, versus 18% of patients without sICH (p < 0.001). Only 1 (7%) patient with sICH had a good functional outcome, defined as an mRS score of 0 to 2, versus 51% of patients without sICH. (4) Conclusions: one in twelve ischemic stroke patients treated with bridging therapy suffered sICH. Given the observed poor outcomes after sICH, further studies are required to better identify patients at risk to help clinicians in guiding therapeutic strategies.

Healthcare utilization and outcomes of living donor liver transplantation for patients with APASL-defined acute-on-chronic liver failure.

BACKGROUND: Liver transplantation (LT) is associated with excellent survival in patients with acute-on-chronic liver failure (ACLF). There is a lack of data assessing the healthcare utilization and outcomes of patients with APASL-defined ACLF undergoing living donor liver transplantation (LDLT). Our aim was to assess pre-LT healthcare utilization and post-LT outcomes in such patients. METHODS: Patients with ACLF who underwent LDLT at our center between 1st April 2019 and 1st October 2021 were included. RESULTS: Seventy-three ACLF patients willing to undergo LDLT were listed; eighteen patients died within 30 days. Fifty-five patients underwent LDLT (age:38.05 ± 14.76 years; alcohol:52.7%; males:81.8%). Most were in grade II ACLF (87.3%) at the time of LDLT (APASL ACLF Research Consortium [AARC] score: 9.05 ± 1; MELD NA: 28.15 ± 4.13). Survival rate was 72.73%; mean follow-up period of 925.21 days; 58.2% (32/55) developed complications during the first year post-LT; 45% (25/55) and 12.7% (7/55) developed infections within and after 3 months. Pre-LT, each patient required a median of 2 (1-4) admissions for 17 (4-45) days. Fifty-six percent (31/55) of patients underwent plasma exchange pre-LDLT. A median amount of Rs. 8,25,090 (INR 26,000-43,58,154) was spent to stabilize the patient (who were sicker and waited longer to undergo LDLT); though post-LT survival benefit was not observed. CONCLUSIONS: LDLT was associated with 73% survival and, thus, is a viable option in those with APASL-defined ACLF. There was a pre-LT high healthcare resource utilization of plasma exchange, with the intention of optimization, while survival benefit has not been demonstrated.

Associating liver partition and portal vein ligation for staged hepatectomy as bridging therapy for liver transplantation in an infant with an advanced hepatic rhabdoid tumor.

BACKGROUND: Malignant rhabdoid tumors (MRTs) are rare, aggressive tumors that mainly affect children and currently lack effective chemotherapeutic regimens. Liver MRTs are particularly challenging to manage due to the difficulty of performing one-stage liver resection, and preemptive liver transplantation is associated with high recurrence rates. However, the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique offers a promising surgical approach for advanced-stage liver tumors where conventional liver resection is not feasible. CASE REPORT: A patient with a large liver rhabdoid tumor that had invaded the three main hepatic veins underwent four courses of cisplatin-pirarubicin chemotherapy. ALPPS was performed due to insufficient residual liver capacity, with hepatic parenchymal dissection between the anterior and posterior liver zones in the first stage of surgery. After confirming adequate remaining liver volume, the liver was resected except for S1 and S6 on postoperative day 14. LDLT was performed 7 months after ALPPS due to the gradual deterioration of liver function caused by chemotherapy. The patient was recurrence-free 22 and 15 months after ALPPS and LDLT, respectively. CONCLUSIONS: The ALPPS technique is a curative option for advanced-stage liver tumors that cannot be managed with conventional liver resection. In this case, ALPPS was used successfully to manage a large liver rhabdoid tumor. Then, liver transplantation was performed after chemotherapy. The ALPPS technique should be considered a potential treatment strategy for patients with advanced-stage liver tumors, particularly those who can undergo liver transplantation.

Glatiramer acetate or IFN-ß bridging therapy in women with relapsing multiple sclerosis planning a pregnancy.

Aim: To assess bridging glatiramer acetate (GA) or IFN-ß for relapse prevention in women with relapsing multiple sclerosis planning pregnancy. Materials & methods: Participants discontinued disease-modifying therapies (DMTs) and received GA/IFN (early- or delayed-start) or no DMT (control) until pregnancy. Results: Annualized relapse rate was lower in delayed-start GA/IFN cohort versus control during washout/bridging. During washout/bridging, bridging with GA/IFN in this cohort reduced clinical activity, while disease activity increased in controls versus baseline. Conclusion: More data on GA/IFN bridging are needed. Women with low relapsing multiple sclerosis activity in the year prior to DMT discontinuation due to pregnancy planning benefited from GA/IFN bridging with lower annualized relapse rate versus no treatment and reduced clinical activity versus baseline during washout/bridging and pregnancy.

When women with relapsing multiple sclerosis (RMS) plan a pregnancy, doctors must think about the possible effects of medicines. Patients can take medicines with a well-defined safety profile to reduce the risk of attacks after stopping strong treatments. In this study, women stopped taking their RMS medicines and either: took well-defined RMS medicines, glatiramer acetate (GA) or IFN-ß; or stopped all RMS medicines. The rate of attacks (in a year) was lower in patients who started taking GA/IFN a while after stopping their previous RMS medicines compared with patients who took no more medication. Women with low RMS activity in the year before stopping RMS treatment because of pregnancy planning may benefit from GA/IFN treatment prior to conception.