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.     

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.     

Same-Day Yttrium-90 Radioembolization: Feasibility with Resin Microspheres

Purpose

To evaluate the feasibility of a same-day yttrium-90 (⁹⁰Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Reproducibility of LI-RADS treatment response algorithm for hepatocellular carcinoma after locoregional therapy

PurposeTo determine inter-reader agreement in categorizing hepatocellular carcinoma (HCC) treated with locoregional therapy using the Liver Imaging Reporting and Data System (LI-RADS) treatment response (LR-TR) algorithm.Materials and methodsA total of 93 patients with a total of 112 HCC nodules that were treated using thermal ablation or transarterial chemoembolization were prospectively included. There were 79 men and 14 women with a mean age of 55 ± 2.6 (SD) years (range: 48–63 years). All patients underwent magnetic resonance imaging (MRI) examination of the liver and MR images were analyzed by two independent observers. Treated HCC nodules were categorized into four groups according to LR-TR scoring system including: (i) LR-TR non-evaluable (treated, response not evaluable); (ii) LR-TR nonviable (treated, probably or definitively not viable); (iii) LR-TR equivocal (treated, equivocally viable) and (iv) LR-TR viable (treated, probably or definitively viable). The inter-observer agreement in LR-TR categorization was assessed using the kappa statistics.ResultsThere was excellent inter-observer agreement between the two reviewers for overall treated HCC according to LR-TR algorithm (kappa = 0.938; 95% CI: 0.89–1.00; P = 0.001) with 97.31% agreement. The LR-TR categories by both reviewers were non-viable (77/112; 69.6% and 76/112; 67.9%), viable (30/112; 26.8% and 32/112; 27.7%) and equivocal (5/112; 4.4% and 4/112; 3.6%). There was excellent inter-observer agreement for LR-TR nonviable (kappa = 0.938; 95% CI: 0.87–1.0; P = 0.001) with 97.3% agreement, LR-TR viable (kappa = 0.955; 95% CI: 0.89–1.00; P = 0.001) with 98.2% agreement and good inter-observer agreement for LR-TR equivocal (kappa = 0.700; 95% CI: 0.28–1.0; P = 0.001) with 97.3% agreement.ConclusionLR-TR algorithm conveys high degrees of inter-observer agreement for the evaluation of treatment response of HCC after thermal ablation and transarterial chemoembolization.