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The rapid spread of the corona virus pandemic is an existential problem for many people in numerous countries. So far, there is no effective vaccine protection or proven therapy available against the SARS-CoV-2 virus. In this review, we describe the role of passive immunization in times of the corona virus. Passive immunization could be a bridging technology to improve the immune defense of critically ill patients until better approaches with effective medications are available.

Budd Chiari syndrome is a potentially treatable disease, and imaging is the key to its diagnosis. Clinical presentations may vary, ranging from asymptomatic to fulminant disease. Subacute BCS is the most common type encountered in clinical practice, characterized by ascites, hepatosplenomegaly, dilated abdominal wall veins, and varicosities in the lower limb and scrotum. While hepatic vein thrombosis is the leading cause in the West, membranous and short segmental occlusion are predominant in the Asian populations. These geographical variations have an impact on the treatment algorithm in managing BCS. Anticoagulation alone often fails to prevent disease progression, demanding further interventional therapy. Interventional therapy carries a lower morbidity and mortality than surgery. Anatomical recanalization and portosystemic shunting form the basis of endovascular management. Membranous or short-segment occlusion are best treated by angioplasty, which restores the physiological venous outflow and possibly disease reversal. Suboptimal results with angioplasty require stenting. Transjugular intrahepatic shunt (TIPS) or direct IVC to portal vein shunt (DIPS) decompresses the portal pressure and reduces the sinusoidal congestion, which in turn diminishes hepatocellular damage and hepatic fibrosis. Despite its ability to modify the disease course, TIPS carries several procedure and shunt-related complications, mainly hepatic encephalopathy. Thus, anatomical recanalization precedes TIPS in the traditional step-up approach in managing BCS. However, this concept is challenged by some authors, necessitating future reseach. TIPS is a valid bridge therapy in BCS with acute live failure awaiting liver transplantation. Despite all, interventional therapies fail in a subset of BCS patients, leaving them with only option of liver transplantation.

Background Radiotherapy (RT) with immunochemotherapy (ICT) followed by CAR T-cell therapy may have synergistic effects due to cytoreduction and enhancing antigen spread, thereby inducing anti-cancer immune responses. The aim of this study was to analyze retrospective comparative data on the use of RT prior to anti-CD19 directed CAR T-cell therapy with a special focus on cytoreduction and RT related side effects. Methods All patients aged ≥ 18 years with relapsed/ refractory Large B-Cell-lymphoma (r/r LBCL) treated with anti-CD19 CAR T-cell therapy in our institution from 05/ 2019–08/2023 were analyzed retrospectively, with the RT therapy group comprising all patients receiving RT with or without concomitant systemic therapy. The control (CO) group was manually matched on age, prior therapy lines and remission state at lymphodepletion. Post-RT tumor volumes (TV) were calculated for 6 out of 7 patients pre-CAR T and for 1 patient post-CAR T. Primary endpoints were reduction of TV and CAR T as well as RT related side effects. Secondary endpoints included overall survival (OS) and progression free survival (PFS). Results 8 patients receiving RT within 60 days prior to CAR T-cell infusion and 8 controls were included in the final analysis. 6 out of 8 patients received concomitant bridging therapy. RT alone or in combination with concomitant systemic therapy led to a significant reduction of TV (average reduction of 68%) within the radiated field from baseline to post RT ( p  = 0.028). The combination of RT and CAR T-cell therapy was not associated with an increased rate of CAR T related side effects or complications (cytokine release syndrome p  = 0.6, immune effector cell-associated neurotoxicity p  = 0.2, corticosteroid use p  > 0.9, Tocilizumab use p  > 0.9, transfer to intensive care unit p  = 0.6). OS and PFS did not differ between the RT- and CO-group (OS p  = 0.64, PFS p  = 0.35). Conclusions Our data indicate that RT is a feasible and effective way of cytoreduction before CAR T-cell therapy, also in combination with systemic chemotherapy. Clinical trial number Not applicable.

Allogeneic hematopoetic stem cell transplantation (allo SCT) is a treatment option with a unique chance of cure for patients with high-risk AML or MDS. However, the optimal path for an individual patient on its way to allo SCT is far from clear and subject of ongoing debates. Upfront transplantation “as soon as possible” competes with strategies to achieve deep remission or at least stabilization of the disease. In this context, we performed a survey among German transplant centers to assess their preferred strategies for patients before SCT in five typical scenarios of AML and MDS. We obtained replies from 22 centers, revealing a heterogenous use of possible strategies. Upfront transplantation was a preferred option (68%) in intermediate risk MDS, chemotherapy was preferred (64%) as bridging for AML in remission, whereas hypomethylating agents (HMA) and induction chemotherapy for relapsed AML were highly controversial. Further prospective evaluation of different options is desirable.

Background and purpose Acute myeloid leukemia (AML) is an aggressive disease with suboptimal overall survival, especially in relapsed/refractory patients. The primary goal of salvage therapy in this patient is to achieve optimal disease control, thereby allowing the transition to hematopoietic stem cell transplantation (HSCT), which remains the only curative option for a subset of these patients. Allogeneic KIR ligand-mismatched CD56 + NK/NKT-like cells have demonstrated antileukemic activity and represent a promising platform for the development of novel cellular therapies. Study design Relapsed/refractory non-M3 AML patients who were not HSCT candidates were included in this phase I clinical trial. Patients received the FLAG conditioning regimen followed by three escalating doses (1 × 10⁶, 3 × 10⁶, 5 × 10⁶ cells/kg) of CD56 + NK/NKT-like cells at 5-day intervals. Results A total of 11 patients with a median age of 41.5 years were enrolled in the study. On average, they received three lines of prior chemotherapy and showed 18% blasts in their bone marrow. The infusion of CD56⁺ NK/NKT-like cells was safe, with no serious toxicity or graft-versus-host disease (GVHD) observed in any patient. Following this treatment protocol, five patients (45.4%) achieved complete remission (CR), with or without hematologic count recovery. Four of these patients (36.3%) underwent successful HSCT and remained event-free to the end of the follow-up period. Conclusion Overall, these trials indicated that the FLAG regimen chemotherapy combined with allogeneic KIR ligand-mismatched CD56 + NK/NKT-like cell infusion is safe and may serve as an effective bridge to HSCT in 36.3% of patients with refractory/relapsed non-M3 AML. Graphic Abstract

CD19-directed chimeric antigen receptor T-cell (CAR T-cell) therapy has markedly improved the prognosis of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). However, disease progression during the manufacturing period remains a major barrier to successful treatment. Bridging therapy (BT), defined as anti-lymphoma treatment administered between leukapheresis and lymphodepleting chemotherapy, serves two primary purposes: to prevent disease progression ensuring eligibility for CAR T-cell infusion, and to modulate the immune microenvironment to potentially enhance CAR T-cell efficacy or mitigate its toxicity. This review provides a comprehensive overview of current strategies and clinical evidence regarding BT in the context of CAR T-cell therapy. We systematically examine the efficacy and safety profiles of various BT strategies, including chemotherapy, targeted or immunotherapy agents, and radiotherapy. Furthermore, we summarize and compare findings from pivotal clinical trials and real-world studies, offering insights into the practical application and outcomes of BT in diverse clinical settings. Unresolved questions remain, including the optimal implementation of bispecific antibodies as BT regimens, the timing and duration of Bruton’s tyrosine kinase inhibitors administration, the safety and efficacy of reusing polatuzumab vedotin in previously exposed patients, and the standardization of radiotherapy protocols. In conclusion, the rational selection and application of BT strategies hold promise for improving the clinical outcomes of R/R LBCL patients undergoing CAR T-cell therapy.

Background Treatment-resistant schizophrenia (TRS) is defined as nonresponse to at least two adequate antipsychotic trials at therapeutic doses for six or more weeks. Currently, clozapine is the only antipsychotic approved for TRS by the FDA and a plethora of evidence indicates that it is the most efficacious antipsychotic for treatment of chronic and refractory cases of schizophrenia. However, its utilization is often limited by metabolic, hematologic, and anticholinergic side effects. Notably, clozapine-induced obsessive-compulsive symptoms (OCS) or obsessive-compulsive disorder (OCD) have been increasingly recognized, attributed to its potent serotonergic antagonism. In 2024, the FDA approved xanomeline-trospium, a dual agent combining a central muscarinic M1/M4 agonist with a peripheral antimuscarinic, which offers a novel approach to treating psychosis. Early evidence suggests comparable efficacy to other antipsychotics, with fewer metabolic and extrapyramidal side effects. We present a case of a woman with longstanding schizophrenia and clozapine-induced OCD successfully transitioned to xanomeline-trospium, resulting in remission of both psychotic and obsessive-compulsive symptoms. Case presentation A 57-year-old woman with a chronic history of schizophrenia, requiring multiple hospitalizations and maintenance electroconvulsive therapy (ECT), stabilized on clozapine 300 mg nightly after failing several antipsychotics. Despite adherence, she exhibited persistent hallucinations, negative symptoms, and later developed clozapine-induced OCD characterized by intrusive counting and numerical obsessions refractory to high-dose sertraline. Due to distressing OCD and passive suicidal ideation, she was admitted for a discontinuation of clozapine and initiation of xanomeline-trospium. Clozapine was tapered and discontinued before initiating xanomeline-trospium, titrated to 100 mg/20 mg twice daily. Within one week after starting xanomeline-trospium, her counting obsessions resolved, psychosis improved, and suicidality resolved. At discharge, three weeks post-admission, she remained stable on xanomeline-trospium, ziprasidone, and sertraline, with complete remission of hallucinations and obsessions. Conclusion This case highlights a successful switch from clozapine to xanomeline-trospium for management of chronic schizophrenia and clozapine induced OCD. The patient’s improvement raises important considerations regarding clozapine-induced OCD, cautious discontinuation, and the benefit of muscarinic receptor agonists. Xanomeline-trospium may represent a viable alternative for patients intolerant of clozapine. Clinical trial number Not applicable.

Background and purposeMechanical thrombectomy (MT) is an effective treatment for patients with acute ischaemic stroke secondary to internal carotid artery (ICA) occlusion. Intravenous thrombolysis (IVT) prior to MT is also commonly administered in suitable patients. This study aimed to compare the outcomes of patients with acute ICA stroke who were treated with direct MT versus combined IVT plus MT. Additionally, analysis was performed in different subgroups of patients such as those with large artery stenosis (LAA) to evaluate which subgroup of patients would benefit most from bridging IVT.MethodsThis multicenter retrospective cohort study included patients who were treated for acute ICA stroke from three comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale (mRS) 0–2 measured at 90 days after discharge. Secondary outcome measures included mRS on discharge, inpatient mortality and complications such as symptomatic intracranial hemorrhage (sICH), subarachnoid haemorrhage (SAH) and embolism of thrombus to new territories.ResultsAmong 352 patients, 178 (50.6%) patients underwent bridging IVT followed by MT and 174 (49.4%) underwent direct MT. The mean ± standard deviation age was 69.8 ± 14.6 years, 50.9% were male and median National Institutes of Health Stroke Scale was 16. At 90-days after discharge, patients who underwent bridging IVT had similar functional outcomes as those who underwent direct MT (OR = 1.53; 95% CI 0.68–3.42; p = 0.303). Bridging IVT was also not associated with improvement in discharge mRS score, decreased inpatient mortality, or difference in rate of complications compared to direct MT. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (33.9% vs. 14.0%, p = 0.022).ConclusionsBridging IVT is not associated with better functional outcomes compared to direct MT in ICA stroke. However, in the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT appears to potentially confer beneficial outcomes. This should be validated in larger studies.

IntroductionEndovascular treatment (EVT) is an effective treatment for patients with acute ischemic stroke (AIS); however, it remains to be determined if treatment with intravenous thrombolysis (IVT) prior to EVT confers any benefit in octogenarians and older. This study aimed to address if bridging tPA has improved functional outcomes or complications in patients 80 years and older.MethodsThis multicentre retrospective cohort study included patients 80 years old and above who underwent endovascular therapy for large vessel occlusion acute ischaemic stroke in 10 compressive stroke centres across China and Singapore between 2018 and 2024. Clinical and procedural factors of patients in Singapore and China were compared using multivariate binary logistic regression. The primary outcome measured was 3-month functional independence defined as modified rankin scale (mRS) 0–2. Secondary outcomes included 3-month independent ambulation as defined as mRS 0–3, 3-month mortality rates and achieving successful recanalization. Data on intracranial haemorrhage was also collected.ResultsBridging IVT was not associated with improvement in 3-month functional independence (24.47% vs. 20.97%; p = 0.505), improvement in 3-month independent ambulation (32.80% vs. 41.49%; p = 0.512), 3-month mortality rates (36.17% vs. 33.33%; p = 0.637) or increased rates of successful recanalisation (89.36% vs. 87.63%; p = 0.672),. Instead, patients who underwent bridging IVT had higher rates of haemorrhage compared to patients who did not undergo bridging IVT even after adjusting for confounding factors (OR = 1.921; 95% CI 1.026–3.596; p = 0.041).ConclusionThe findings of this study suggest that bridging IVT prior to EVT may not improve functional outcomes or mortality rates. However, it appears to be associated with an increase in risk of intracranial haemorrhage.

Relapsed or refractory (R/R) non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) shows poor clinical outcomes. Bruton tyrosine kinase (BTK) inhibitors have established therapeutic activity by targeting B-cell receptor signaling, with promising results in treating DLBCL. The monotherapy of zanubrutinib, a selective BTK inhibitor, or second-line salvage chemotherapy has shown limited efficacy in patients with R/R DLBCL. Thus, the present study evaluated the efficacy and safety of zanubrutinib-combined therapy in heavily treated patients with non-GCB DLBCL. This retrospective study consists of 27 heavily treated patients with non-GCB DLBCL who received zanubrutinib-combined therapy between January 2021 and February 2024 in Shanghai Tongji Hospital and Zhejiang Second Affiliated Hospital. Efficacy outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), whereas safety outcomes included incidence of adverse events. Of all the 27 enrolled patients' baseline,24 patients (88.9%) showed a high IPI score (≥3), 23 patients (85.2%) had a high proliferation score (Ki 67≥80%) and 20 patients (74.1%) were heavily treated with ≥3 lines of previous treatments. The ORR in all patients was 74.1% (95%CI, 53.7%-88.9%), the partial response (PR) was 66.7% (95%CI, 46.0%-83.5%). With a median follow-up of 36.6 months, the median PFS was 10.6 months (95%CI 7.3-14) and median OS was 19.6 months (95%CI 12.3-not reached). The grade ≥3 hematologic toxicities included neutropenia (85.1%, 23/27) and thrombocytopenia (37%, 10/27). The grade ≥3 nonhematologic AEs were hypokalemia (11.1%, 3/27) and pulmonary infection (11.1%, 3/27). No treatment-related deaths occurred. Subgroups stratified by gender, age, and presence/absence of extranodal lesions all maintained an ORR of over 70%. The efficacy of the combined therapy seemed to be not affected by most baseline characteristics and was associated with high response even in high-risk subgroups. Of all the evaluated 27 patients, 2 patients got complete response (CR) received autologous stem cell transplantation and lenalidomide maintenance therapy respectively. 19 patients got no CR were bridged to CD19 chimeric antigen receptor (CAR)-T cell therapy, while the other 6 patients received additional salvage chemotherapy. In the CAR-T cohort, the ORR was 89.5% (95%CI: 67.0%~98.2%) and CR was 57.9% (95%CI: 34.5%~78.9%), the median PFS was 14 months (95% CI: 5.2-37.9) and median OS was 27.7 months (95% CI: 10.1- not reached). The CAR-T group was associated with improved overall survival relative to the non-CAR-T group (HR = 0.21, 95% CI: 0.05-0.79, P = 0.02). In the landmark analysis, the survival probability of CART group was 80% at 12 months post-landmark, the non-CAR-T group exhibited an earlier initial drop with survival decreasing to 57.1% at 12 months. Zanubrutinib-combined therapy was effective and safe for the treatment of heavily treated patients with non-GCB DLBCL. It offers a promising treatment option and serving as an effective bridge to CAR-T therapy, with manageable toxicity. Future prospective studies with larger cohorts are needed to validate these findings.