Pneumococcal immunity and PCV13 vaccine response in SOT-candidates and recipients

BackgroundSolid organ transplantation (SOT) candidates and recipients are highly vulnerable to invasive pneumococcal diseases (IPD). Data on which to base optimal immunization recommendations for this population is scant. The national distribution of IPD serotypes led the Swiss Health Authorities to recommend in 2014 one dose of pneumococcal-13-valent-conjugate-vaccine (PCV13), without any subsequent dose of the 23-valent-polysaccharide-pneumococcal-vaccine (PPV23).MethodsThis is a retrospective analysis of pneumococcal immunity using a multiplex binding assay, to assess seroprotection rates against a selection of seven PCV13- and seven PPV23-serotypes in SOT-candidates and recipients evaluated and/or transplanted in 2014/2015 in the University Hospitals of Geneva. Seroprotection was defined as serotype-specific antibody concentration greater than 0.5 mg/l and overall seroprotection when this was achieved for ≥ 6/7 serotypes.ResultsPre-vaccination and at time of transplant sera were available for 35/43 (81%), and 43/43 (100%) SOT-candidates respectively. At listing, 17/35 (49%) SOT-candidates were seroprotected against PCV13 and 21/35 (60%) against PPV23 serotypes. Following one systematic dose of PCV13 at listing, 35/43 (81%) SOT-recipients were seroprotected at day of transplant against PCV13-serotypes and 34/43 (79%) against PPV23 serotypes, compared to 21/41 (51%) and 28/41 (68%) respectively in the controls transplanted in 2013, before the systematic PCV13-vaccination.ConclusionsThe systematic vaccination with PCV13 of all SOT candidates without additional PPV23 is a good strategy as it confers seroprotection against a wide range of pneumococcal serotypes. Indeed, one of five PCV13-vaccinated SOT-candidates was nevertheless not seroprotected at time of transplant, reflecting their partial immune competence, and indicating the need for additional dose of pneumococcal vaccines before transplant.     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

Numerical Integrators for Dispersion-Managed KdV Equation

In this paper, we consider the numerics of the dispersion-managed Korteweg-de Vries (DM-KdV) equation for describing wave propagations in inhomogeneous media. The DM-KdV equation contains a variable dispersion map with discontinuity, which makes the solution non-smooth in time. We formally analyze the convergence order reduction problems of some popular numerical methods including finite difference and time-splitting for solving the DM-KdV equation, where a necessary constraint on the time step has been identified. Then, two exponential-type dispersion-map integrators up to second order accuracy are derived, which are efficiently incorporated with the Fourier pseudospectral discretization in space, and they can converge regardless of the discontinuity and the step size. Numerical comparisons show the advantage of the proposed methods with the application to solitary wave dynamics and extension to the fast & strong dispersion-management regime.     

载As2O3 pH敏感钙砷复合物脂质体的制备及体外评价

目的 制备pH敏感释药的As₂O₃脂质体，并进行体外评价。方法 采用薄膜分散法制备含钙离子脂质体，然后用离子沉淀法孵育制备钙砷复合物脂质体（CaAs-LP）。测定CaAs-LP的粒径、Zeta电位及多分散系数（PDI）；透射电子显微镜观察脂质体的形态；电感耦合等离子体发射光谱仪测定纳米药物的载药量与包封率；透析袋法考察其体外释药特性。噻唑蓝（MTT）法考察未载药脂质体及CaAs-LP对人源性乳腺癌MCF-7细胞、人源性脑胶质瘤U87细胞和人源性肝癌HepG2细胞的毒性；共聚焦显微镜考察U87细胞对CaAs-LP的摄取效率。结果 制备的CaAs-LP呈规整类球型，粒径约为（117.16±1.94）nm，包封率和载药量分别为（74.31±2.11）%、（8.31±0.13）%。体外释放研究表明，CaAs-LP具有明显的缓释以及pH响应释药特征。未载药的脂质体在MCF-7、U87、HepG2和L02细胞中的生物相容性良好；CaAs-LP抑制肿瘤细胞生长的作用较原药有所上升，半数抑制浓度（IC₅₀）值分别为11.91、4.90、19.41、27.59 μmol/L。细胞摄取研究表明肝癌细胞对脂质体具有良好的摄取。结论 CaAs-LP具备显著的缓释以及pH响应释药的特性，在肿瘤治疗方面具有较好的应用前景。     

Comparative Analysis of Safety and Efficacy of Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma in Patients with and without Pre-Existing Transjugular Intrahepatic Portosystemic Shunts

PurposeTo compare the safety and efficacy of transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients with and without transjugular intrahepatic portosystemic shunts (TIPS).Materials and MethodsThis single-institution study included a retrospective review of 50 patients who underwent transarterial chemoembolization for HCC between January 2010 and April 2017. Twenty-five patients had preexisting TIPS, and 25 patients were selected to control for age, sex, and target tumor size. Baseline median Model for End-Stage Liver Disease (MELD; 13 TIPS, 9 control; P < .001) and albumin-bilirubin (ALBI; 3 TIPS, 2 control; P < .001) differed between groups. Safety was assessed on the basis of Common Terminology Criteria for Adverse Events (CTCAE) and change in MELD and ALBI grade assessed between 3 and 6 months. Efficacy was assessed by tumor response and time to progression (TTP).ResultsThere was 1 severe adverse event (CTCAE grade >2) in the TIPS group. There was no difference in the change in MELD or ALBI grade. Although there was no difference in tumor response (P = .19), more patients achieved a complete response in the control group (19/25, 76%) than in the TIPS group (13/25, 52%). There was no difference in TTP (P = .82). At 1 year, 2 patients in the control group and 3 patients in the TIPS group received a liver transplant. Seven patients died in the TIPS group.ConclusionsTransarterial chemoembolization is as safe and effective in patients with TIPS as in patients without TIPS, despite worse baseline liver function. Severe adverse events are rare and may be transient.     

Complications of total joint arthroplasty in solid organ transplant patients versus a large control group

BackgroundSolid organ transplant patients are theoretically at increased risk for complications after total joint replacement due to immunosuppressive medication regimens and multiple medical co-morbidities. There are a number of studies that report on outcomes of total joint arthroplasty (TJA) following solid organ transplant, however, the results are heterogeneous. This study evaluated the outcomes of TJA in solid organ transplant patients as compared to non-organ transplant controls at one academic medical center.MethodsThis study was a single institution retrospective review of a consecutive series of patients who underwent joint replacement following solid organ transplant as compared to a control cohort over a 10-year period. Univariable and multivariable generalized linear mixed effects models were used to compare the odds of readmission, infection, mortality, and being discharged home between transplanted (cases) and non-transplanted (control) patients.ResultsTransplant and non-transplant cohorts had similar BMI, although transplant patients were younger (61 versus 65 years) and had a higher incidence of Diabetes (55% vs. 16%). On multivariable analysis, there was no difference in the odds of re-admission or rate of infection, but there was an increased risk of death and admission to a rehab facility in the transplant cohort.ConclusionOverall, this study demonstrates that solid organ transplant alone does not increase the risk of peri-operative complications in patients who underwent hip and knee replacement. However, it should be expected that these patients have a higher mortality rate and that many of them will need to be discharged to a post-acute care facility.     

Advanced diffusion magnetic resonance imaging in patients with Alzheimer’s and Parkinson’s diseases

The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques. Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues. Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings;however, it has several limitations. To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases. This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer's and Parkinson's diseases, the first and second most common neurodegenerative diseases, respectively.