Higher power short duration vs. lower power longer duration posterior wall ablation for atrial fibrillation and oesophageal injury outcomes: a prospective multi-centre randomized controlled study (Hi-Lo HEAT trial).

AIMS: Radiofrequency (RF) ablation for pulmonary vein isolation (PVI) in atrial fibrillation (AF) is associated with the risk of oesophageal thermal injury (ETI). Higher power short duration (HPSD) ablation results in preferential local resistive heating over distal conductive heating. Although HPSD has become increasingly common, no randomized study has compared ETI risk with conventional lower power longer duration (LPLD) ablation. This study aims to compare HPSD vs. LPLD ablation on ETI risk. METHODS AND RESULTS: Eighty-eight patients were randomized 1:1 to HPSD or LPLD posterior wall (PW) ablation. Posterior wall ablation was 40 W (HPSD group) or 25 W (LPLD group), with target AI (ablation index) 400/LSI (lesion size index) 4. Anterior wall ablation was 40-50 W, with a target AI 500-550/LSI 5-5.5. Endoscopy was performed on Day 1. The primary endpoint was ETI incidence. The mean age was 61 ± 9 years (31% females). The incidence of ETI (superficial ulcers n = 4) was 4.5%, with equal occurrence in HPSD and LPLD (P = 1.0). There was no difference in the median value of maximal oesophageal temperature (HPSD 38.6°C vs. LPLD 38.7°C, P = 0.43), or the median number of lesions per patient with temperature rise above 39°C (HPSD 1.5 vs. LPLD 2, P = 0.93). Radiofrequency ablation time (23.8 vs. 29.7 min, P < 0.01), PVI duration (46.5 vs. 59 min, P = 0.01), and procedure duration (133 vs. 150 min, P = 0.05) were reduced in HPSD. After a median follow-up of 12 months, AF recurrence was lower in HPSD (15.9% vs. LPLD 34.1%; hazard ratio 0.42, log-rank P = 0.04). CONCLUSION: Higher power short duration ablation was associated with similarly low rates of ETI and shorter total/PVI RF ablation times when compared with LPLD ablation. Higher power short duration ablation is a safe and efficacious approach to PVI.

High power short duration versus low power long duration ablation in patients with atrial fibrillation: A meta-analysis of randomized trials.

BACKGROUND: High-power-short-duration (HPSD) radiofrequency (RF) ablation is a viable alternative to low-power-long-duration (LPLD) RF for pulmonary vein isolation (PVI). Nevertheless, trials showed conflicting results regarding atrial fibrillation (AF) recurrences and few data concerning complications. Therefore, we conducted a meta-analysis of randomized trials comparing HPSD versus LPLD. METHODS: We systematically searched the electronic databases for studies published from inception to March 31, 2023 focusing on HPSD versus LPLD. The study endpoints were AF recurrence, procedural times and overall complications. RESULTS: Five studies enrolling 424 patients met the inclusion criteria (mean age 61.1 years; 54.3% paroxysmal AF; mean LVEF 58.2%). Compared to LPLD, HPSD showed a significantly lower AF recurrence rate [16.3% vs. 30,1%; RR: 0.54 (95% CI: 0.38-0.79); p = 0.001] at a mean 10.9 months follow-up. Moreover, HPSD led to a significant reduction in total procedural time [MD: -26.25 min (95%CI: -42.89 to -9.61); p = 0.002], PVI time [MD: -26.44 min (95%CI: -38.32 to -14.55); p < 0.0001], RF application time [MD: -8.69 min (95%CI: -11.37 to -6.01); p < 0.00001] and RF lesion number [MD: -7.60 (95%CI: -10.15 to -5.05); p < 0.00001]. No difference was found in either right [80.4% vs. 78.2%; RR: 1.04 (95% CI: 0.81-1.32); p = 0.77] or left [92.3% vs. 90.2%; RR: 1.02 (95% CI: 0.94-1.11); p = 0.58] first-pass isolation and overall complications [6% vs. 3.7%; RR: 1.45 (95%CI: 0.53-3.99); p = 0.47] between groups. CONCLUSION: In our metanalysis of randomized trials, HPSD ablation appeared to be associated to a significantly improved freedom from AF and shorter procedures, without increasing the risk of complications.

Lateral pelvic lymph node dissection can be omitted in lower rectal cancer in which the longest lateral pelvic and perirectal lymph node is less than 5 mm on MRI.

BACKGROUND AND OBJECTIVES: The goal of the study was to examine the use of magnetic resonance imaging (MRI) for identification of patients with lower rectal cancer who may benefit from lateral pelvic lymph node dissection (LPLD). METHODS: Diagnoses and oncological outcomes were examined in 160 cases. Patients in whom the long-axis diameter of the longest detected lymph node was < 5 mm or ≥ 5 mm were classified as LPLN(-) (n = 102) and LPLN(+) (n = 58), respectively. RESULTS: Diagnostic results gave a 21.6% positive predictive value (PPV) and a 95.0% negative predictive value (NPV) for the LPLN. These values were 59.6% and 91.5%, respectively, for the perirectal lymph node (PRLN). Multivariate analysis showed that a pathologic PRLN (pPRLN)(+) status was an independent prognostic factor for relapse-free survival (RFS) (P = 0.0424) in the LPLN(-) group. The 5-year RFS did not differ significantly between cases that did not and did undergo LPLD (90.0% vs. 83.8%) in the LPLN(-) and pPRLN(-) groups. CONCLUSIONS: The low PPV and high NPV indicate that it is difficult to identify patients who may benefit from LPLD. However, the results show that LPLD has no benefit in LPLN(-) and PRLN(-) cases and that these cases can be identified based on MRI findings.

Case Report: Next-Generation Sequencing Identified a Novel Pair of Compound-Heterozygous Mutations of LPL Gene Causing Lipoprotein Lipase Deficiency.

Lipoprotein lipase deficiency (LPLD) is a rare disease characterized by the accumulation of chylomicronemia with early-onset. Common symptoms are abdominal pain, hepatosplenomegaly, eruptive xanthomas and lipemia retinalis. Serious complications include acute pancreatitis. Gene LPL is one of causative factors of LPLD. Here, we report our experience on an asymptomatic 3.5-month-old Chinese girl with only milky blood. Whole-exome sequencing was performed and identified a pair of compound-heterozygous mutations in LPL gene, c.862G>A (p.A288T) and c.461A>G (p.H154R). Both variants are predicted "deleterious" and classified as "likely pathogenic". This study expanded the LPL mutation spectrum of disease LPLD, thereby offering exhaustive and valuable experience on early diagnosis and proper medication of LPLD.

Short-term outcomes of near-infrared imaging using indocyanine green in laparoscopic lateral pelvic lymph node dissection for middle-lower rectal cancer: A propensity score-matched cohort analysis.

Laparoscopic lateral pelvic lymph node dissection (LPND) is limited by complex neurovascular bundles in the narrow pelvic sidewall and various post-operative complications. Indocyanine green (ICG) has been applied to increase the number of harvested lymph nodes and reduce the injury of irrelevant vessels in patients with rectal cancer. However, few studies on the recurrence rate of ICG fluorescence imaging-guided laparoscopic LPND were reported. This retrospective study enrolled 50 middle- low rectal cancer patients who were treated by LPND. After propensity score matching, 20 patients were matched in each of the indocyanine green (ICG) guided imaging group (ICG group) and non-ICG guided imaging group (non-ICG group). The average follow-up time was 13.5 months (12-15 months). Our results showed that the total number of harvested lymph nodes in the ICG group was significantly higher than that in the non-ICG group (P < 0.05), and intraoperative blood loss and post-operative hospital stay times in the ICG group were less than those in the non-ICG group (P < 0.05). After 12 months of follow-up, no residual lymph node and local tumor recurrence were found for patients in the ICG group. Four patients in the non-ICG group detected residual lymph nodes at the 3-month visit. Our findings highlighted the importance of ICG fluorescence-guided imaging in LPND because it has unique advantages in improving the number of lymph node dissections, surgical accuracy, and decreasing the residual lymph nodes and local tumor recurrence. In addition, ICG fluorescence guidance technology can effectively shorten the operation time, and it is simple to operate, which is worth popularizing.

The burden of familial chylomicronemia syndrome from the patients' perspective.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare, inherited lipid disorder characterized by high levels of plasma triglycerides and chylomicrons, which may cause life-threatening acute pancreatitis. Currently no FDA-approved treatment exists. Management is low-fat diet (<20g fat/day), which is difficult to maintain. With the restricted diet, triglycerides may remain elevated. We conducted discussions with patients and caregivers to better understand the burden of FCS from their perspectives. METHODS: A panel of FCS patients and caregivers was assembled to discuss and assess the clinical and psychosocial burden of FCS. RESULTS: Ten adults with FCS (median age 48 yr) and their spouses/caregivers were asked specific questions about their experiences living with FCS. Patients with FCS stated their symptoms were abdominal pain, nausea, diarrhea, constipation, bloating, and fatigue. Patients reported a median of 34 episodes of acute pancreatitis over their lifetimes; half of these led to hospitalizations, each with an average stay of 6.5 days. The psychosocial burden of FCS was primarily associated with the restricted diet, anxiety and stress of FCS. CONCLUSIONS: Living with FCS imposes a significant clinical and psychosocial burden on patients and caregivers, who reported reduced quality of life, limited employment opportunities, socialization and increased burden on family.

The burden of familial chylomicronemia syndrome: interim results from the IN-FOCUS study.

BACKGROUND: Familial Chylomicronemia Syndrome (FCS) is a rare genetic disorder that is caused by a decrease or an absence of lipoprotein lipase activity. FCS is characterized by marked accumulation of chylomicrons and extreme hypertriglyceridemia, which have major effects on both physical and mental health. To date, there have been no systematic efforts to characterize the impact of chylomicronemia on FCS patients' lives. In particular, the impact of FCS on the burden of illness (BoI) and quality of life (QoL) has not been fully described in the literature. METHODS: IN-FOCUS was a comprehensive web-based research survey of patients with FCS focused on capturing the BoI and impact on QoL associated with FCS. Sixty patients from the US diagnosed with FCS participated. Patients described multiple symptoms spanning across physical, emotional and cognitive domains. RESULTS: Patients on average cycled through 5 physicians of varying specialty before being diagnosed with FCS, reflecting a lengthy journey to diagnosis Nearly all respondents indicated that FCS had a major impact on BoI and QoL and significantly influenced their career choice and employment status, and caused significant work loss due to their disease. CONCLUSION: FCS imparts a considerable burden across multiple domains with reported impairment on activities of daily living and QoL.

The role of registries in rare genetic lipid disorders: Review and introduction of the first global registry in lipoprotein lipase deficiency.

A good understanding of the natural history of rare genetic lipid disorders is a pre-requisite for successful patient management. Disease registries have been helpful in this regard. Lipoprotein Lipase Deficiency (LPLD) is a rare, autosomal-recessive lipid disorder characterized by severe hypertriglyceridemia and a very high risk for recurrent acute pancreatitis, however, only limited data are available on its natural course. Alipogene tiparvovec (Glybera®) is the first gene therapy to receive Marketing Authorization in the European Union; GENIALL (GENetherapy In the MAnagement of Lipoprotein Lipase Deficiency), a 15-year registry focusing on LPLD was launched in 2014 as part of its Risk Management Plan. The aim of this publication is to introduce the GENIALL Registry within a structured literature review of registries in rare genetic lipid disorders. A total of 11 relevant initiatives/registries were identified (homozygous Familial Hypercholesterolemia (hoFH) [n = 5]; LPLD [n = 1]; Lysosomal Acid Lipase Deficiency [LALD, n = 1], detection of mutations in genetic lipid disorders [n = 4]). Besides one product registry in hoFH and the LALD registry, all other initiatives are local or country-specific. GENIALL is the first global prospective registry in LPLD that will collect physician and patient generated data on the natural course of LPLD, as well as long-term outcomes of gene therapy. CONCLUSION: There is a limited number of international initiatives focusing on the natural course of specific rare genetic lipid disorders. The GENIALL LPLD Registry could be the first step towards a future broader global initiative that collects data related to familial chylomicronemia syndrome and their underlying genetic causes.

Association of CTRC and SPINK1 gene variants with recurrent hospitalizations for pancreatitis or acute abdominal pain in lipoprotein lipase deficiency.

BACKGROUND: There are important inter-individual variations in the incidence and severity of acute pancreatitis in patients with severe hypertriglyceridemia. Several genes involved in triglyceride-rich lipoprotein metabolism or serine proteases pathways are known to influence the risk of pancreatitis. AIM: To evaluate the association between genes regulating serine proteases, chymotrypsin C (CTRC) and serine peptidase inhibitor kazal type1 (SPINK1), and recurrence of hospitalizations for acute pancreatitis or severe abdominal pain in patients with Lipoprotein Lipase Deficiency (LPLD), a rare and extreme monogenic model of severe hypertriglyceridemia and pancreatitis. METHOD: The CTRC and SPINK1 genes promoter and coding regions sequencing has been performed in a sample of 38 LPLD adults (22 men and 16 women) and 100 controls (53 men and 47 women). Estimation of the association of CTRC and SPINK1 gene variants or combinations of variants with history of hospitalizations for pancreatitis or acute abdominal pain in LPLD was investigated using non-parametric analyses with correction for multiple testing and logistic regression models controlling for age, gender, family history, and life habits. RESULTS: Gene sequencing followed by genotype-stratified analyses of the CTRC and SPINK1 genes in LPLD and controls revealed a positive association between recurrence of hospitalizations and the rs545634 (CTRC)-rs11319 (SPINK1) combination [OR = 41.4 (CI: 2.0-848.0); p = 0.016]. In all models, a positive family history of pancreatitis was a significant predictor of recurrent hospitalizations independently of the contribution of SPINK1 or CTRC (p < 0.001). CONCLUSION: These results suggest that a positive family history of pancreatitis and genetic markers in the serine protease pathways could be associated with a risk of recurrent hospitalization for acute pancreatitis in severe hypertriglyceridemia due to LPLD.

Expression of the calcium binding proteins Necab-1,-2 and -3 in the adult mouse hippocampus and dentate gyrus.

The family of EF-hand calcium binding proteins is composed of more than 250 members. In search for other neuronal markers, we studied the expression pattern of Necab-1, -2 and -3 in the Ammons horn of adult mice at the gene- and protein levels using in-situ hybridization and immunohistochemistry. The genes for the three Necab's were expressed in specific, non-overlapping areas of the hippocampus. A minority of the Necab-positive interneurons were GABA-ergic, and they virtually never coexpressed one of the classical calcium binding proteins (calretinin, calbindin D-28k and parvalbumin). Necab's are promising new neuronal markers in the brain.