Suppressive mechanisms of regulatory B cells in mice and humans.

B cells include immune-suppressive fractions, called regulatory B cells (Bregs), which regulate inflammation primarily through an interleukin 10 (IL-10)-mediated inhibitory mechanism. Several B-cell fractions have been reported as IL-10-producing Bregs in murine disease models and human inflammatory responses including autoimmune diseases, infectious diseases, cancer and organ-transplant rejection. Although the suppressive functions of Bregs have been explored through the hallmark molecule IL-10, inhibitory cytokines and membrane-binding molecules other than IL-10 have also been demonstrated to contribute to Breg activities. Transcription factors and surface antigens that are characteristically expressed in Bregs are also being elucidated. Nevertheless, defining Bregs is still challenging because their active periods and differentiation stages vary among disease models. The identity of the diverse Breg fractions is also under debate. In the first place, since regulatory functions of Bregs are mostly evaluated by ex vivo stimulation, the actual in vivo phenotypes and functions may not be reflected by the ex vivo observations. In this article, we provide a historical overview of studies that established the characteristics of Bregs and review the various suppressive mechanisms that have been reported to be used by Bregs in murine and human disease conditions. We are only part-way through but the common phenotypes and functions of Bregs are still emerging.

The Absence of an Na+/Ca2+Exchanger (NCX) in Bullfrog Proximal Tubules and Cellular pH is More Influential Than Cellular Ca2+ on Proximal Na Transport.

BACKGROUND/AIMS: The functional significance of the Na+/Ca2+ exchanger (NCX) in basolateral membranes in the proximal tubule remains controversial. The key factor in crosstalk between the apical and basolateral sides is not known. METHODS: We investigated the basolateral membranes, using double-barreled Ca2+ or pH ion-selective microelectrodes. We used doubly perfused bullfrog kidneys in vivo, and switched the basolateral solution (renal portal vein) to experimental solutions. RESULTS: In the control, cellular pH (pHi) was 7.33 ± 0.032 (mean ± SE, n = 7) and in separate experiments, cellular Ca2+ activity (aCai) was 249.6 ± 35.54 nM (n = 28). Changing to respiratory acidosis, pHi was significantly acidified by 0.123 pH units on average and the change of aCai was +53.1 nM (n = 9 ns). In metabolic acidosis, pHi was reduced by 0.151 while aCai was reduced by 143.4. Using the 30 mM K+ solution, pHi was increased by 0.233 while aCai was reduced by 203.9, with depolarization. Both ionomycin and ouabain caused aCai to increase. In the 0.5 mM Na+ solution (replaced with BIDAC Cl), pHi was reduced by 0.177. No changes in aCai (+49.8 ns) were observed although we recorded depolarization of 15.2 mV. In the 0.5 mM Na+ solution, replaced with raffinose, no changes in aCai (-126.4 ns) were observed with depolarization (6.5 ns). CONCLUSION: Our results suggest that thermodynamic calculations of cellular Na+ concentration led to the conclusion that either a Na+/HCO3- exchanger (NBC) or NCX could be present in the same basolateral membrane. H+ ions are the most plausible key factor in the crosstalk.

The impact of left atrium size on selection of the pulmonary vein isolation method for atrial fibrillation: Cryoballoon or radiofrequency catheter ablation.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of ablation strategies for atrial fibrillation (AF), and noninferiority of cryoballoon (CB) over radiofrequency (RF) ablation has been previously reported. One of the risk factors of recurrence is left atrium (LA) enlargement. This study aimed to analyze the impact of LA enlargement on the selection of CB or RF ablation for AF patients. METHODS: A total of 2,224 AF patients (64.4 ±â€¯10.7 years, 65.5% male) who underwent PVI were analyzed retrospectively. Left atrial diameter (LAD) and volume (LAV) were measured using echocardiography before the procedures. LA enlargement was defined as LAD ≥40 mm and LAV index (LAVI) ≥35 mL/m2. Patients undergoing CB and RF ablation were propensity score matched, and 376 matched pairs were evaluated. RESULTS: Cox proportional hazard analysis revealed that LAD (95% CI, 1.01-1.05), LAV (95% CI, 1.01-1.02), and LAVI (95% CI, 1.01-1.03) were independent predictors of recurrence. CB showed equivalent clinical outcomes to those of RF with shorter procedure time required for patients without LA enlargement. CB was inferior to RF in patients with LA enlargement (LAD, 74.5% vs 84.6%, P = .028; LAVI, 74.7% vs 83.4%, P = .015), and large LAVI was associated with a higher prevalence of non-PV foci (35% vs 29%, P = .008). CONCLUSIONS: CB ablation may be recommended for patients without enlarged LA based on the short procedure time and efficacy, whereas RF would be more appropriate in large LAs. LAVI may be a valuable reference to predict PVI outcomes and in selecting the ablation method.

Cryoballoon versus radiofrequency ablation for paroxysmal atrial fibrillation in hemodialysis patients.

INTRODUCTION: Little evidence exists regarding cryoballoon ablation (CBA) of paroxysmal atrial fibrillation (PAF) in hemodialysis (HD) patients. We compared CBA and radiofrequency ablation (RFA) of PAF in HD patients, referring to CBA of PAF in non-HD patients. METHODS AND RESULTS: This historical cohort study examined 88 patients who underwent catheter ablation of PAF, including 21 HD patients with a second-generation 28-mm cryoballoon (CB-HD group), 17 HD patients with a non-force-sensing radiofrequency catheter (RF-HD group), and 50 non-HD patients with a cryoballoon (CB-non-HD group). Pulmonary vein (PV) isolation alone aside from cavotricuspid isthmus ablation was performed in 14 (67%) in the CB-HD group, 12 (71%) in the RF-HD group, and 36 (72%) in the CB-non-HD group (P = 0.95), without isoproterenol-induced non-PV triggers. Non-PV trigger ablation was added to the other patients. The Kaplan-Meier estimated 1-year freedom from atrial tachyarrhythmia recurrence without antiarrhythmic drugs after a single procedure was 76%, 59%, and, 92% in the CB-HD, RF-HD, and CB-non-HD groups, respectively (P = 0.002). The mean procedure time was shorter in the CB-HD group than in the RF-HD group (127 vs. 199 min; P < 0.001). In the second procedure, the median number of reconnected pulmonary veins was 0.5 in the CB-HD group versus 2.0 in the RF-HD group (P = 0.17). CONCLUSION: For PAF in HD patients, CBA showed a comparable single-procedure efficacy to that of RFA with a short procedure time. CBA may be a reasonable initial procedure for HD patients suffering from symptomatic PAF.

Differences in the electrophysiological findings of repeat ablation between patients who first underwent cryoballoon ablation and radiofrequency catheter ablation for paroxysmal atrial fibrillation.

INTRODUCTION: Several studies have revealed that second-generation cryoballoon (CB)-based pulmonary vein (PV) isolation is noninferior to radiofrequency (RF)-based PV isolation for patients with drug-refractory paroxysmal atrial fibrillation (AF). However, electrophysiological differences in repeat ablation remain unclear. METHODS AND RESULTS: This study examined electrophysiological differences during the repeat ablation between patients who first underwent RF catheter ablation and CB ablation; PV durability and non-PV AF foci were assessed for these patients. We enrolled 919 and 491 patients who underwent CB ablation (CB group) and RF catheter ablation (RF group), respectively, for paroxysmal AF between January 2013 and June 2017 at our institution. PV isolation using RF ablation involved the left atrium (LA) antrum and part of the LA posterior wall. After 2 years of follow-up, 62 and 80 patients in the CB and RF groups, respectively, underwent repeat ablation. PV reconnections were more frequent in the RF group than in the CB group (left superior PV: 46.2% and 14.5%, P < .001; left inferior PV: 35.0% and 11.2%, P = .001; right superior PV: 40.0% and 22.6%, P = .031; right inferior PV: 36.2% and 19.4%, P = .039; PVs: 39.8% and 16.9%, P < .001). LA AF foci were more frequent in the CB group than in the RF group (27.4% and 7.5%; P = .002). Other non-PV foci were prevalent in both groups. CONCLUSION: Fewer LA-PV reconnections occurred with CB ablation. However, extensive PV isolation may eliminate many LA AF foci.

Ineffectiveness of radiotherapy for the treatment of keratoacanthoma centrifugum marginatum: A case report.

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacantoma (KA). Although KCM shares histological and clinical features with KA, KCM has no tendency of spontaneous regression, and presents with progressive peripheral expansion with a bank-shaped outer wall and concurrent central healing. As such, early diagnosis and proper treatment of the patient are required. However, because of its rarity, previous reports are insufficient to evaluate which treatment should be selected. Here, we report a case of KCM that responded to radiotherapy, but relapsed 6 months later.

Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions.

Transforming growth factor-ß (TGF-ß) is involved in vascular formation through activin receptor-like kinase (ALK)1 and ALK5. ALK5, which is expressed ubiquitously, phosphorylates Smad2 and Smad3, whereas endothelial cell (EC)-specific ALK1 activates Smad1 and Smad5. Because ALK5 kinase activity is required for ALK1 to transduce TGF-ß signaling via Smad1/5 in ECs, ALK5 knockout (KO) mice were not able to give us the precise mechanisms by which TGF-ß/ALK5/Smad2/3 signaling is implicated in angiogenesis. To delineate the role of Smad2/3 signaling in endothelium, the Smad2 gene in Smad3 KO mice was selectively deleted in ECs using Tie2-Cre transgenic mice, termed EC-specific Smad2/3 double KO (EC-Smad2/3KO) mice. EC-Smad2/3KO embryos revealed hemorrhage leading to embryonic lethality around E12.5. EC-Smad2/3KO embryos exhibited no abnormality of vasculogenesis and angiogenesis in both the yolk sac and the whole embryo, whereas vascular maturation was incomplete because of inadequate assembly of mural cells in the vasculature. Wide gaps between ECs and mural cells could be observed in the vasculature of EC-Smad2/3KO mice because of reduced expression of N-cadherin and sphingosine-1-phosphate receptor-1 (S1PR1) in ECs from those mice. These results indicated that Smad2/3 signaling in ECs is indispensable for maintenance of vascular integrity via the fine-tuning of N-cadherin, VE-cadherin, and S1PR1 expressions in the vasculature.

CD69 Is Indispensable for Development of Functional Local Immune Memory in Murine Contact Hypersensitivity.

Local immune memory develops at the site of antigen exposure and facilitates a rapid and strong local adaptive defense upon re-exposure. Resident memory T (TRM) cells play a role in local immune memory, and their cell-surface molecules CD69 and CD103 promote their tissue residency. However, the contribution of these molecules to skin immune memory remains unclear. In this study, by inducing contact hypersensitivity (CHS) in CD69KO (CD69-deficient) and CD103-deficient mice, where different degrees of TRM cell contribution are observed by repeated challenges on the right ear and a single challenge on the left ear, we found that the deficiency of CD69 but not CD103 leads to impaired CHS upon repeated antigen challenges, even although TRM cells-like CD8 T cells developed at the challenged site of CD69KO. CHS responses in both ears were diminished in CD69KO by FTY720 or CD8 neutralization, suggesting that CHS in CD69KO is ascribed to circulating CD8 T cells and that the developed TRM cell-like CD8 T cells do not behave as TRM cells. The infiltration of macrophages was reduced in the rechallenged site of CD69KO, along with the downregulation of Cxcl1 and Cxcl2. Thus, CD69 is considered essential for an effective recall response, involving the development of functional TRM cells and the recruitment of macrophages.

Eribulin mesylate exerts antitumor effects via CD103.

Eribulin mesylate (ERB) is a synthetic analog of halichondrin B, inhibiting tumor cell growth by disrupting microtubule function. Recently, anticancer drugs have been shown to not only act directly on tumor cells but also to exert antitumor effects by modifying the tumor environment. Although ERB has also been speculated to modify the tumor microenvironment including the immune response to tumors, the precise mechanism remains unclear. In our study, ERB suppressed the tumor growth of MC38 colon cancer in wildtype mice, whereas ERB failed to inhibit the tumor growth in Rag1-deficient mice which lack both B and T cells. Moreover, depletion of either CD4+ or CD8+ T cells abrogated the antitumor effect of ERB, indicating that both CD4+ and CD8+ T cells play an important role in ERB-induced antitumor effects. Furthermore, ERB treatment increased the number of tumor infiltrating lymphocytes (TILs) as well as the expression of activation markers (CD38 and CD69), immune checkpoint molecules (LAG3, TIGIT and Tim3) and cytotoxic molecules (granzyme B and perforin) in TILs. ERB upregulated E-cadherin expression in MC38. CD103 is a ligand of E-cadherin and induces T-cell activation. ERB increased the proportion of CD103+ cells in both CD4+ and CD8+ TILs. The ERB-induced antitumor effect with the increased TIL number and the increased expression of activation markers, inhibitory checkpoint molecules and cytotoxic molecules in TILs was abrogated in CD103-deficient mice. Collectively, these results suggest that ERB exerts antitumor effects by upregulation of E-cadherin expression in tumor cells and subsequent activation of CD103+ TILs.

Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and ROCK-II.

Rho-associated coiled-coil-forming protein serine/threonine kinase (ROCK) consisting of two isoforms, ROCK-I and ROCK-II, functions downstream of the small GTPase Rho for assembly of actomyosin bundles. To examine the role of ROCK isoforms in vivo, we previously generated and examined mice deficient in each of the two isoforms individually. Here, we further examined the in vivo role of ROCK isoforms by generating mice deficient in both isoforms. Cross-mating of ROCK-I(+/-) ROCK-II(+/-) double heterozygous mice showed that all of the ROCK-I(-/-) ROCK-II(-/-) homozygous mice die in utero before 9.5 days post-coitum (dpc) and ROCK-I(-/-) ROCK-II(+/-) homo-heterozygous or ROCK-I(+/-) ROCK-II(-/-) hetero-homozygous mice die during a period from 9.5 to 12.5 dpc, whereas mice of other genotypes survive until 12.5 dpc with the expected Mendelian ratio. All of the ROCK-I(+/-) ROCK-II(-/-) or ROCK-I(-/-) ROCK-II(+/-) mice showed impaired body turning and defective vascular remodeling in the yolk sac. Impairment of vascular remodeling was also observed in wild-type embryos treated ex vivo with a ROCK inhibitor, Y-27632. These results suggest that ROCK isoforms function redundantly during embryogenesis and play a critical role in vascular development.

The impact of lesion complexity on predicting mortality of coronary artery disease patients after out-of-hospital cardiac arrest.

INTRODUCTION: Coronary artery disease (CAD) is the most frequent cause of out-of-hospital cardiac arrest (OHCA). Nevertheless, there have been limited studies focusing on the impact of lesion complexity on resuscitated CAD patients. The purpose of the present study was to investigate the association between coronary lesion complexity and the mortality of CAD patients after OHCA. METHODS: From pooled database of two centers, which comprised 706 successfully resuscitated OHCA patients, 172 patients undergoing coronary angiography were retrospectively investigated. A total of 148 patients exhibited coronary stenosis on angiogram and were included in the final analysis. Baseline characteristics, pre-and post-hospital care, general status after resuscitation and angiographical findings were compared between the patients who deceased within 30 days and those who survived and the predictors of 30-day mortality were determined. RESULTS: Ninety-four patients (63.5%) survived at 30 days. Bystander cardiopulmonary resuscitation (CPR) (Odds ratio (OR) 0.36; 95% confidence interval (CI) 0.14-0.96; P = 0.041), revascularization of coronary stenosis (OR 0.15; 95% CI 0.19-0.86; P < 0.001), GRACE risk score (OR 1.04; 95% CI 1.02-1.05; P < 0.001) and SYNTAX score (OR 1.07; 95% CI 1.01-1.13; P = 0.025) were independent predictors of 30-day mortality. As multiple predictors such as bystander CPR, GRACE score and SYNTAX score were combined, the 30-day mortality gradually deteriorated. CONCLUSIONS: In addition to bystander CPR, GRACE score and revascularization, SYNTAX score independently predicted 30-day mortality of CAD patients after OHCA.

Effect of isolation feasibility of non-pulmonary vein foci on efficacy of ablation for atrial fibrillation: comparison of the isolation and focal ablation methods.

PURPOSE: Atrial fibrillation (AF) mainly originates from the pulmonary vein (PV). However, some AF triggers originate from other sites, namely non-PV foci, which are related to recurrence after AF ablation. This study aimed to evaluate the effects of isolation feasibility (isolability) of non-PV foci on the efficacy of AF ablation. METHODS: Overall, 1855 patients with AF (age, 64.6 ± 10.9 years; 82% paroxysmal) underwent PV isolation, followed by induction and ablation of non-PV foci. Among them, 545 (29%) patients had non-PV foci; these patients were categorized into those with isolable non-PV foci (n = 196, 36%) and those with non-isolable non-PV foci (n = 349, 64%). RESULTS: During a mean follow-up of 31.2 ± 15.6 months, recurrence was higher in the non-isolable group than in the isolable group (34% vs. 19%, P < 0.01). Kaplan-Meier analyses revealed a significantly better 1-year clinical outcome in the isolable group than in the non-isolable group (88.0% vs. 78.4%, P < 0.001; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.39-0.81). This outcome was not inferior to that of patients without non-PV foci (88.3% vs. 90.8%, P = 0.81). The non-isolable group showed poorer clinical outcomes than patients without non-PV foci (78.4% vs. 90.8%, P < 0.001; HR, 1.37; 95% CI, 1.22-1.53). Cox regression analysis revealed that isolability (HR, 0.56; 95% CI, 0.36-0.89) and unmappability (HR, 2.89; 95% CI, 1.55-5.37) of non-PV foci were significant predictors of arrhythmia recurrence. CONCLUSION: The isolability of non-PV foci was a significant factor affecting the achievement of better clinical outcomes following AF ablation in patients with non-PV foci.

Ganglioside GD3 May Suppress the Functional Activities of Benign Skin T Cells in Cutaneous T-Cell Lymphoma.

In cutaneous T-cell lymphoma (CTCL), which arises from skin-tropic memory T cells, malignant T cells and benign T cells are confined in the same skin lesions. It is thus difficult to evaluate the phenotypic characteristics and functional activities of benign T cells in CTCL. Disialoganglioside with three glycosyl groups (GD3) is increasingly expressed on the surface of solid malignant tumor cells and takes part in tumor progression and suppression of tumor immunity. However, the role of GD3 in CTCL is not well-understood. In this study, the malignant and benign T cells in CTCL skin lesions were distinguished by flow cytometry and their phenotypic characteristics were compared with those of T cells from control skin specimens. In CTCL skin lesions, the benign T cells included limited resident memory T cells (TRM), which are sessile in skin and known to exert strong antitumor function. The benign T cells showed diminished Th17 property, and the expression of GD3 was high in the malignant T cells. The expression of GD3 in the malignant T cells inversely correlated with IL-17A production from the benign CD4 T cells. GD3 from the malignant T cells was implied to be involved in suppressing the Th17 activity of the benign T cells independent of the regulation of TRM differentiation in CTCL. Revealing the role of GD3 in inhibiting the production of IL-17A in CTCL would aid the understanding of the suppressive mechanism of the antitumor activity by malignant tumor cells.

Skin T cells maintain their diversity and functionality in the elderly.

Recent studies have highlighted that human resident memory T cells (TRM) are functionally distinct from circulating T cells. Thus, it can be postulated that skin T cells age differently from blood-circulating T cells. We assessed T-cell density, diversity, and function in individuals of various ages to study the immunologic effects of aging on human skin from two different countries. No decline in the density of T cells was noted with advancing age, and the frequency of epidermal CD49a+ CD8 TRM was increased in elderly individuals regardless of ethnicity. T-cell diversity and antipathogen responses were maintained in the skin of elderly individuals but declined in the blood. Our findings demonstrate that in elderly individuals, skin T cells maintain their density, diversity, and protective cytokine production despite the reduced T-cell diversity and function in blood. Skin resident T cells may represent a long-lived, highly protective reservoir of immunity in elderly people.

Presence of non-pulmonary vein foci in patients with atrial fibrillation undergoing standard ablation of pulmonary vein isolation: Clinical characteristics and long-term ablation outcome.

BACKGROUND: The clinical characteristics of atrial fibrillation (AF) resulting from non-pulmonary vein (PV) triggers remain unknown. This study aimed to evaluate the clinical characteristics of patients with AF caused by non-PV triggers, localization of non-PV foci, clinical differences, and clinical outcomes after catheter ablation in each AF focus. METHODS: A total of 2967 patients who underwent initial catheter ablation for paroxysmal or persistent AF were examined. After PV isolation, all patients underwent high-dose isoproterenol infusion to assess the existence of non-PV foci. RESULTS: Non-PV foci were identified in 564 patients (19.2%). The localization of successfully ablated non-PV foci in 514 patients were the superior vena cava (SVC: 213 cases), interatrial septum (IAS: 125 cases), coronary sinus (CS: 98 cases), right atrium (RA: 125 cases), left atrium (LA: 114 cases), and unmappable (50 cases). Multivariate analysis revealed that female gender, low body mass index (BMI), non-paroxysmal AF (PAF), and sick sinus syndrome were independent and significant indicators of non-PV foci. In the multivariate analysis of each AF focus, female gender, low BMI, and non-PAF were significant predictors of IAS and CS foci, RA and IAS foci, and CS foci, respectively. In addition, dilatation of the LA was significantly associated with LA foci, whereas RA, LA, IAS, and CS foci were associated with AF recurrence. CONCLUSION: These findings could help to identify patients at a higher risk of AF caused by non-PV triggers and clarify the clinical difference according to the localization of non-PV foci.

Serum lactate dehydrogenase level as a possible predictor of treatment preference in psoriasis.

BACKGROUND: The efficacy of small molecule inhibitors for intracellular signal mediators varies among the individuals, and their mechanism of action is broad. A phosphodiesterase 4 inhibitor apremilast shows a dramatic effect on a certain proportion of psoriatic patients by modulating the cellular metabolism and regulating the production of pro-inflammatory molecules. However, it is unclear to which disease subtype this drug benefits. While psoriasis is a Th17-mediated disease, how immune cells are affected by the modulation of cellular metabolism is not fully evaluated, either. OBJECTIVE: This study aims to identify the indices which predict the efficacy of apremilast in psoriasis, and to investigate the impact of metabolic activity in immune cells on the psoriatic pathogenesis. METHODS: The association of treatment efficacy with clinical and laboratory data of the 58 psoriatic patients was evaluated. The reflector of the associated index was also sought among the indices of cellular metabolic pathways by use of an extracellular flux analyzer. RESULTS: There was a correlation between clinical improvement and the serum lactate dehydrogenase (LDH) level in the patients treated with apremilast but not in those with biologics. Serum LDH level did not correlate with the cutaneous disease severity but correlated with the oxygen consumption rate of blood T cells. CONCLUSION: Psoriatic patients with high serum LDH level can be benefitted by apremilast. The serum LDH level reflects the augmented respiratory activity of T cells in psoriasis. Our results would highlight the importance of regarding metabolic skew in immune cells as a treatment target in psoriasis.

Catheter ablation for atrial fibrillation in patients with congestive heart failure.

BACKGROUND: We evaluated the 1-year success rate of maintaining sinus rhythm after catheter ablation (CA) for atrial fibrillation (AF) in patients with or without congestive heart failure (CHF). METHODS: In this single-centre retrospective matched-pair cohort study of 3,018 AF patients who underwent initial CA between January 2012 and June 2018, 227 pairs with (CHF group) or without CHF (control group) were matched using propensity scores. In the CHF group, 108 patients were assigned to the arrhythmia-induced cardiomyopathy (AIC) group whose left ventricular systolic dysfunction was explained only by lasting AF or atrial tachycardia; the remaining 119 had organic heart diseases (non-AIC group). We evaluated the 1-year AF-free survival and changes in clinical findings before and after CA. RESULTS: The CHF and control groups showed similar AF-free survival; however, AIC patients had significantly better survival than non-AIC patients. AF recurrence was significantly related to CHF re-hospitalisation, which was significantly more frequent in the non-AIC group than in the AIC group. The clinical outcomes of left atrial dilation, brain natriuretic peptide level, and left ventricular ejection function improved significantly before and after CA in both groups. The degree of improvement was significantly better in the AIC group than in the non-AIC group. CONCLUSIONS: The 1-year success rate was not significantly different between the CHF and control groups. The 1-year success rate in the AIC group was similar to that in the AIC-control group and was better than that in the non-AIC group. CHF clinical outcomes were improved significantly.

The Sequential Organ Failure Assessment (SOFA) score predicts mortality and neurological outcome in patients with post-cardiac arrest syndrome.

BACKGROUND: Patients experiencing out-of-hospital cardiac arrest (OHCA) and subsequent post-cardiac arrest syndrome are often compromised by multi-organ failure. The Sequential Organ Failure Assessment (SOFA) score has been used to predict clinical outcome of patients requiring intensive care for multi-organ failure. Thus, the assessment of SOFA score is recommended as a criterion for sepsis. Although post-cardiac arrest patients frequently develop sepsis-like status in ICU, there are limited reports evaluating the SOFA score in post-cardiac arrest patients. We investigated the predictive value of the SOFA score in survival and neurological outcomes in patients with post-cardiac arrest syndrome. METHODS: A total of 231 cardiovascular arrest patients achieving return of spontaneous circulation (ROSC) were finally extracted from the institutional consecutive database comprised of 1218 OHCA patients transferred to the institution between January 2015 and July 2018. The SOFA score was calculated on admission and after 48h. Predictors of survival and neurological outcome defined as having cerebral-performance-category (CPC) 1 or 2 at 30 days were determined. RESULTS: SOFA score was lower in survived patients (5.0 vs 10.0, p<0.001) and those with favorable neurological outcome (5.0 vs 8.0, p<0.001) as compared with the counterparts. The SOFA score on admission was an independent predictor of survival (OR 0.68, 95% confidence interval [CI] 0.59-0.78; p<0.001) and favorable neurological performance (OR 0.79; 95% CI 0.69-0.90; p<0.001) at 30 days. Furthermore, a change in SOFA score (48-0h) was predictive of favorable 30-day neurological outcome (OR 0.71, 95% CI 0.60-0.85; p<0.001). CONCLUSIONS: Evaluation of the SOFA score in the ICU is useful to predict survival and neurological outcome in post-cardiac arrest patients.

Pulmonary vein isolation plus left atrial posterior wall isolation and additional nonpulmonary vein trigger ablation using high-dose isoproterenol for long-standing persistent atrial fibrillation.

BACKGROUND: Little evidence exists regarding the endpoint and optimum approach to catheter ablation for long-standing persistent atrial fibrillation (LSPAF). We examined the efficacy of pulmonary vein isolation (PVI) plus left atrium posterior wall isolation (PWI) and additional non-PV trigger ablation using high-dose isoproterenol for LSPAF. METHODS: One-hundred and fifty-five patients (median AF duration, 36 months) underwent catheter ablation for LSPAF; After PVI plus PWI, they underwent provocation of non-PV triggers by high-dose isoproterenol and were divided into 3 groups based on the results: group A, PVI plus PWI alone, without induced non-PV triggers (single procedure: 105 patients, multiple procedures: 90 patients); group B, mappable non-PV triggers demonstrated and ablated (single procedure: 41 patients, multiple procedures: 45 patients); group C, if non-PV triggers were unmappable or could not be induced in repeated procedures, adjunctive complex fractionated atrial electrogram ablation was performed (single procedure: 9 patients, multiple procedures: 20 patients). RESULTS: The Kaplan-Meier estimate of the 1-year freedom from atrial tachyarrhythmias without antiarrhythmic drugs was 65% in all patients, (73%, 56%, and 11% in groups A, B, and C, respectively) after a single procedure, which improved to 86% in all patients (93%, 86%, and 53% in groups A, B, and C, respectively) after multiple procedures. CONCLUSION: Even for LSPAF, in approximately 60% of patients, non-PV triggers were not elicited, and PVI plus PWI alone achieved good outcomes. Although the inducibility of non-PV triggers was associated with recurrence of atrial tachyarrhythmias, additional non-PV trigger ablation may improve the outcome after multiple procedures.