Cooled-Tip Ablation Results in Increased Radiofrequency Power Delivery and Lesion Size in the Canine Heart: Importance of Catheter-Tip Temperature Monitoring for Prevention of Popping and Impedance Rise

Since myocardial lesion size during radio-frequency (RF) ablation is limited at high power by impedance rise when electrode tip temperature exceed 100 °C, controlling tip temperature by continuous intraelectrode saline infusion could permit generation of larger lesion. (1) Two dogs randomly received either standard or cooled tip RF ablation at 4 to 6 separate LV sites. Power output of 30 W was delivered via modified 7 Fr deflectable catheter with 4 mm tip for up to 120 sec or until impedance rise occurred. (2) Six dogs randomly received cooled tip RF ablation at power output of 20, 30, 40 W for 120 sec. (3) Three dogs randomly received cooled tip RF ablation using room temperature saline (21–25 °C) or chilled saline (1–4 °C) infusion. Results: Overall, peak tip temperature was lower for cooled vs standard RF deliveries (97±17 °C vs. 42±8 °C). Lesion depth and volume were significantly larger for cooled burns. Lesion depth and volume and the incidence of abrupt impedance rise/popping did not differ between room temperature saline and chilled saline infusion. The catheter-tip temperature at the onset of popping and abrupt impedance rise was 54±5 °C(48–60 °C) and 59±10 °C(50–75 °C). Conclusion: Cooled tip RF current delivery at high power is associated with increased myocardial lesion size which may facilitate successful ablation of ventricular tachycardia associated with acquired structural heart disease. Catheter-tip temperature should be maintained below 45 °C to prevent popping and abrupt impedance rise during RF energy delivery.     

Bile acids induce monocyte differentiation toward interleukin-12 hypo-producing dendritic cells via a TGR5-dependent pathway

Dendritic cells (DCs) are known as antigen-presenting cells and play a central role in both innate and acquired immunity. Peripheral blood monocytes give rise to resident and recruited DCs in lymph nodes and non-lymphoid tissues. The ligands of nuclear hormone receptors can modulate DC differentiation and so influence various biological functions of DCs. The role of bile acids (BAs) as signalling molecules has recently become apparent, but the functional role of BAs in DC differentiation has not yet been elucidated. We show that DCs derived from human peripheral blood monocytes cultured with a BA produce lower levels of interleukin-12 (IL-12) and tumour necrosis factor-α in response to stimulation with commensal bacterial antigens. Stimulation through the nuclear receptor farnesoid X (FXR) did not affect the differentiation of DCs. However, DCs differentiated with the specific agonist for TGR5, a transmembrane BA receptor, showed an IL-12 hypo-producing phenotype. Expression of TGR5 could only be identified in monocytes and was rapidly down-regulated during monocyte differentiation to DCs. Stimulation with 8-bromoadenosine-cyclic AMP (8-Br-cAMP), which acts downstream of TGR5 signalling, also promoted differentiation into IL-12 hypo-producing DCs. These results indicate that BAs induce the differentiation of IL-12 hypo-producing DCs from monocytes via the TGR5-cAMP pathway.     

Harnessing the potential of reverse-phase protein array technology: Advancing precision oncology strategies

The last few decades have seen remarkable strides in the field of cancer therapy. Precision oncology coupled with comprehensive genomic profiling has become routine clinical practice for solid tumors, the advent of immune checkpoint inhibitors has transformed the landscape of oncology treatment, and the number of cancer drug approvals has continued to increase. Nevertheless, the application of genomics-driven precision oncology has thus far benefited only 10%–20% of cancer patients, leaving the majority without matched treatment options. This limitation underscores the need to explore alternative avenues with regard to selecting patients for targeted therapies. In contrast with genomics-based approaches, proteomics-based strategies offer a more precise understanding of the intricate biological processes driving cancer pathogenesis. This perspective underscores the importance of integrating complementary proteomic analyses into the next phase of precision oncology to establish robust biomarker-drug associations and surmount challenges related to drug resistance. One promising technology in this regard is the reverse-phase protein array (RPPA), which excels in quantitatively detecting protein modifications, even with limited amounts of sample. Its cost–effectiveness and rapid turnaround time further bolster its appeal for application in clinical settings. Here, we review the current status of genomics-driven precision oncology, as well as its limitations, with an emphasis on drug resistance. Subsequently, we explore the application of RPPA technology as a catalyst for advancing precision oncology. Through illustrative examples drawn from clinical trials, we demonstrate its utility for unraveling the molecular mechanisms underlying drug responses and resistance.     

Bullous pemphigoid associated with dipeptidyl peptidase‐4 inhibitors: A report of five cases

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder. Recently, BP induced by dipeptidyl peptidase‐4 (DPP‐4) inhibitors has been a concern. Although DPP‐4 inhibitors are commonly used in the Asian population because of their safety and efficacy, BP associated with DPP‐4 inhibitors is sometimes seen in clinical settings. Here, we report five Japanese cases of BP associated with the agents. In the present cases, BP occurred in older adults using four different DPP‐4 inhibitors, which showed various clinical manifestations in terms of latency period for BP, sex, glycemic control and diabetes duration. Withdrawal of DPP‐4 inhibitors was effective in improving BP, and achieved remission even in cases requiring oral steroid administration and intravenous immunoglobulin therapy. Clinicians should note the importance of early diagnosis of this clinical condition and initiate prompt withdrawal of DPP‐4 inhibitors.     

Frequency-Dependent Electrophysiological Effect of Ibutilide on Human Atrium and Ventricle

Most of the class III antiarrhythmic agents developed in recent years blocks the rapid component of delayed rectifier potassium current (IKr). IKr blocker shows reverse use-dependency and also may cause torsades de pointes at slower heart rate. Ibutilide fumarate, a novel class III antiarrhythmic agent, increases window Na(+) current at the action potential plateau phase. We studied the rate-dependent effect of ibutilide on the electrophysiological parameters of human atrium and ventricle. Franz catheter and a pacing catheter were placed closely in the high right atrium and right ventricular apex to record monophasic action potentials (MAP) during pacing at cycle length (PCL) of 600 ms and 350 ms in eight patients who underwent electrophysiological study. MAP duration of right atrium (RA-MAPD) and right ventricle (RV-MAPD), effective refractory period of RA and RV (RA-ERP and RV-ERP), intra-atrial conduction time (IACT) and intra-ventricular conduction time (IVCT) were measured before and after intravenous administration of ibutilide (0.01 mg/kg up to 1mg). A conduction time from RA pacing spike to distal coronary sinus potential was used to measure IACT, while QRS duration of surface ECG during RV pacing was used to measure IVCT. Ibutilide prolonged RA-MAPD by 60 ms at PCL 600 ms and by 53 ms at PCL 350 ms; RV-MAPD by 48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and RV-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human atrium and ventricle without reverse use-dependency.     

Short Report

Background : Most aphasia therapists appear to assume that people with aphasia undergo psychological distress that is associated with communication problems. However, the relationship between aphasia and psychological status has not been sufficiently investigated. Aim : The aim of this study was to explore the relationship between verbal communication and psychological status in people with aphasia. Methods & Procedure : A total of 25 people with aphasia were assessed by the Observational Profile of Communication (OPC), the Questionnaire of Verbal Communication (QVC), and the Standard Language Test of Aphasia (SLTA). Two items of the OPC—Interpersonal Attitude and Emotional State—were used as measures of psychological status. Two domains of the QVC—Receptive Ability and Expressive Ability—were used as measures of verbal communication activity. The overall scoring system of the SLTA was used to rate the severity of aphasia. Correlations were calculated between the OPC and other variables, namely, Receptive Ability, Expressive Ability, the SLTA, age, and time since onset. The group effects of gender and aphasia type were examined. Outcome & Results : Interpersonal Attitude had a moderate and significant correlation with Receptive Ability, but not with Expressive Ability, the SLTA, age, and time since onset. Emotional State had moderate and significant correlations with the SLTA and time since onset, but not with Receptive Ability, Expressive Ability, and age. Gender and aphasia type did not have a significant relationship with the measures of psychological status. Conclusions : The relationship between verbal communication and psychological status was not straightforward in this small exploratory study. The severity of the communication problem in aphasic people does not necessarily appear to relate to psychological status.