Virtual Crossmatching in Kidney Transplantation: The Wait Is Over

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Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

High-Frequency Irreversible Electroporation Using 5,000-V Waveforms to Create Reproducible 2- and 4-cm Ablation Zones—A Laboratory Investigation Using Mechanically Perfused Liver

PurposeTo investigate if high-frequency irreversible electroporation (H-FIRE) treatments can be delivered at higher voltages and with greater energy delivery rates than currently implemented in clinical irreversible electroporation protocols.Materials and MethodsTreatments using 3,000 V and 5,000 V were administered to mechanically perfused ex vivo porcine liver via a single applicator and grounding pad (A+GP) as well as a 4-applicator array (4AA). Integrated energized times (IET) 0.01–0.08 seconds and energy delivery rates 25–300 μs/s were investigated. Organs were preserved at 4°C for 10–15 hours before sectioning and gross analysis using a metabolic stain to identify the size and shape of ablation zones.ResultsA+GP ablations measured between 1.6 cm and 2.2 cm, which did not increase when IET was increased from 0.02 seconds to 0.08 seconds (P > .055; range, 1.9–2.1 cm). Changes in tissue color and texture consistent with thermal damage were observed for treatments with energy delivery rates 50–300 μs/s, but not for treatments delivered at 25 μs/s. Use of the 4AA with a 3-cm applicator spacing resulted in ablations measuring 4.4–4.9 cm with energy delivery times of 7–80 minutes.ConclusionsH-FIRE treatments can rapidly and reproducibly create 2-cm ablations using an A+GP configuration. Treatments without thermal injury were produced at the expense of extended treatment times. More rapid treatments resulted in ablations with varying degrees of thermal injury within the H-FIRE ablation zone. Production of 4-cm ablations is possible using a 4AA.     

Corynebacterium species as one of the major causative pathogens of bacterial pneumonia

Recent advances using molecular methods, matrix-assisted laser desorption ionization time of flightmass spectrometry, and next-generation sequencers enable rapid and precise detection of bacterial species in the clinical samples, revealing bacterial diversities in the human body. Corynebacterium species are Gram-positive bacilli, which can cause pneumonia and have been reported as causative pathogens of lower respiratory tract infections since the 1970's. However, Corynebacterium spp. may be recognized and sorted as part of normal respiratory flora on Gram staining and culture, resulting in clinical under-recognition as pathogenic bacteria.The results of the clone library method using bacterial 16S ribosomal RNA gene sequence analysis in Japanese patients with hospital-acquired pneumonia revealed that bronchoalveolar lavage fluid obtained from the lung lesions contained 11.8% Corynebacterium spp., which was the second most predominant bacterial phylotype. Additionally, among patients in whom Corynebacterium spp. were detected, C. simulans was most commonly detected followed by C. striatum. In addition, almost half of the patients in whom C. simulans was detected was monophylotypic infection and/or co-detection of C. simulansand C. striatum. Further clinical information is expected on corynebacteria as pathogens of lower respiratory tract infection.     

Evidence for the origin of the binaural interaction component of the auditory brainstem response

The binaural interaction component (BIC) represents the mismatch between auditory brainstem responses (ABR) obtained with binaural stimulation and the sum of ABRs obtained with monaural left and right stimulation. It is generally assumed that the BIC reflects binaural integration. Its potential use as a diagnostic tool, however, is hampered by the lack of direct evidence about its origin. While an origin at the initial site of binaural integration seems likely, there is no general agreement on the contribution of the two primary candidate nuclei, the lateral and medial superior olives (LSO and MSO, respectively). Here, we recorded local field potentials (LFP) and responses of units in the LSO and MSO of Mongolian gerbils (Meriones unguiculatus), presenting clicks with an interaural time or level difference (ITD and ILD, respectively), while simultaneously recording ABR. We determined the BIC from the ABR and, importantly, from LFP and responses of units in the LSO and MSO. If stimulus‐induced changes in the ABR‐derived BIC have their source in the LSO and/or MSO, we expect coherent changes in the unit‐derived and the ABR‐derived BIC. We find that BIC obtained from LSO units exhibits the same ITD and ILD dependence as the ABR‐derived BIC. Neither BIC obtained from MSO units nor LFP‐derived BIC recorded in either LSO or MSO did. The data thus strongly suggest that it is the activity of LSO units in the gerbil that is decisive for the generation of the ABR‐derived BIC, determining its properties.     

Comparison of processing speed,balance, mobility and fear of falling between hypertensive and normotensive individuals

BackgroundHypertension (HT) contributes substantially to poor physical function, cognitive dysfunction, cardiovascular problems and to all-cause mortality. Performance in activities requiring attention, speed and coordination might also be affected in individuals with HT.ObjectiveThis study compared the processing speed, static and dynamic balance, functional mobility and fear of falling between individuals with hypertension (HT group) and normotensive individuals (NT group).MethodsOne-hundred and twenty-eight individuals were included: NT group (n = 64) and HT group (n = 64). The Choice Stepping Reaction Time Test was used for the evaluation of processing speed, Single Leg Stance test for static balance evaluation, “Y” Balance Test for dynamic balance evaluation, Timed Up and Go test with single and dual tasking for the evaluation of functional mobility and Falls Efficacy Scale for assessing fear of falling.ResultsThe processing speed of the HT group was slower than that of the NT group; the total response time (RsT) in Stepping Reaction Test (SRT) (mean difference [MD] = −0.2, 95% CI = −0.3, 0), and Stroop Test (ST) [ST-A (MD = −0.4, 95% CI = −0.5, −0.2), ST-B (MD = −0.5, 95% CI = −0.7, −0.2) and ST-C (MD = −0.6, 95% CI = −0.8, −0.3). Additionally, the static [single leg stance, eyes open, right side (MD = 12.7, 95% CI = 6.3, 19.0) and left side (MD = 13.6, 95% CI = 7.2, 19.9)] and dynamic balance [Y balance test, composite score, right lower extremity (MD = 8.5, 95% CI = 4.4, 12.5) and left lower extremity (MD = 5.2, 95% CI = 1.5, 8.8) scores of the HT group were lower than those of the NT group. The HT group required a longer time to complete the functional mobility test measured with Timed Up And Go Test during both single task (MD = −0.8, 95% CI = −1.1, −0.4), cognitive dual task (MD = −1.5, 95% CI = −2.4, −0.5) and manual dual task (MD = −0.9, 95% CI = −1.3, −0.4) in comparison to the NT group. Also, the HT group had higher levels of fear of falling (MD = −7.6, 95% CI = −10.9, −4.2).ConclusionHypertensive individuals present slower processing speed, reduced static and dynamic balance, decreased functional mobility and higher fear of falling in comparison to normotensive individuals.     

Influence of sample centrifugation on plasma platelet count and activated partial thromboplastin time using patient samples

BackgroundDiagnostic coagulation testing is vulnerable to factors of the pre-analytical phase such as sample centrifugation. Despite this, centrifugation conditions differ widely among European laboratories. Here we use samples from patients referred for Activated partial thromboplastin time (APTT) testing to investigate if different centrifugation conditions result in platelet-poor plasma (PPP) (plasma platelet count < 10 × 10⁹/L) and how the variation in centrifugation conditions affect APTT measurements.MethodsCentrifugation of 2000g (10 min) were compared with 3000g (10 min) using samples from patients referred for APTT testing (n = 70). Plasma platelet count and APTT were measured to investigate the influence of the centrifugation conditions. Differences were evaluated using Bland Altman Plots and Student’s t-test.ResultsCentrifugation at 3000g for 10 min produced PPP for more of the samples (64%) than centrifugation at 2000g (6%) (p < 0.001). No statistically significant difference for APTT (p = 0.265) was found for samples with APTT < 37 s while samples with prolonged APTT (>37 s) showed a statistically significant difference (p = 0.025). The Bland Altman plot did not reveal a clinically significant difference (mean difference 0.30 s/0.68%) when compared to a maximum acceptable bias of 10%.ConclusionNone of the centrifugation conditions used in this study adequately secured PPP for all samples. Despite a statistically significant difference between samples with prolonged APTT, no clinically significant difference was observed when comparing all APTT measurements.