Advanced interatrial block predicts ineffective cardioversion of atrial fibrillation: a FinCV2 cohort study

AimsRhythm control using electrical cardioversion (CV) is a common treatment strategy for patients with symptomatic atrial fibrillation (AF). To guide clinical decision making, we sought to assess if electrocardiographic interatrial blocks could predict CV failure or AF recurrence as the phenomenon is strongly associated with atrial arrhythmias.MethodsThis study included 715 patients who underwent a CV for persistent AF lasting >48 h. P-wave duration and morphology were analyzed in post-procedure or the most recent sinus rhythm electrocardiograms and compared with rates of CV failure and AF recurrence within 30 days after CV as well as their combination (ineffective CV).ResultsCV was unsuccessful in 63 out of 715 patients (8.8%) and AF recurred in 209 out of 652 (29.2%) patients within 30 days after CV. Overall, 272 (38.0%) CVs turned out ineffective. Advanced interatrial block (AIAB) defined as P-wave duration ≥120 ms and biphasic morphology in inferior leads (II, III and aVF) was diagnosed in 72 (10.1%) cases. AIAB was an independent predictor for CV failure (OR 4.51, 95%CI 1.76–11.56, p = .002), AF recurrence (OR 2.93, 95%CI 1.43–5.99, p = .003) and ineffective CV (OR 3.87, 95%CI 2.04–7.36, p < .001).ConclusionAIAB predicted CV failure, AF recurrence as well as their composite. This study presents an easy electrocardiographic tool for the identification of patients with persistent AF who might not benefit from an elective CV in the future.

KEY MESSAGES

• Interatrial blocks are very common in patients with atrial fibrillation.
• Advanced interatrial block predicts ineffective cardioversion.

     

Long-term results of arthroscopic Bankart repair: Minimum 10 years of follow-up

Purpose

This study investigated the long-term results of arthroscopic Bankart repair in terms of rates and timelines of recurrence of instability, with special interest in young adult patients aged ≤20 years.

Methods

Between 2000 and 2005, 186 shoulders [182 patients, 50 women, median age 26 (range 15–58) years] were operated on at a university hospital using arthroscopic Bankart repair because of instability after traumatic anteroinferior shoulder dislocation. Medical records were retrospectively reviewed and patients were assessed using postal questionnaires or telephone interview after a minimum of 10 years of follow-up [median 12.2 (range 10–16) years]. The primary outcome measure was recurrence of instability (assessed from 167 shoulders), other outcome measures included Oxford instability score (OIS), subjective shoulder value (SSV), and Western Ontario instability index (WOSI) (assessed from 157 shoulders).

Results

At the end of follow-up, 50/167 shoulders (30%) had recurrence of instability and 30/167 (18%) were subjected to reoperation due to instability symptoms. Twenty-six (52%) failures occurred within ≤2 years, 11 (22%) within 2–5 years, and 13 (26%) >5 years after surgery. Failure rate was 19/35 (54%) for patients aged ≤20 years and 31/132 (24%) for patients aged >20 years; reoperation rates were 11/35 (31%) and 19/132 (14%), respectively. Mean OIS was 20 (SD 9, range 12–50), SSV 83% (SD 21, range 10–100), and WOSI score 80 (SD 22, range 33–100).

Conclusions

Nearly one-third of patients had recurrence of instability after arthroscopic Bankart repair after a minimum of 10-year follow-up. Patients aged ≤20 years did poorly with more than half of the patients having recurrence; alternative stabilization techniques should probably be considered for these patients.

Level of evidence

IV.

     

A new quantitative measure of disc degeneration

Background Context

The ability to adequately measure a phenomenon is critical to studying and understanding it. Since 1957, a variety of subjective visual grading methods have been used to assess disc degeneration, but these have been limited by gross ordinal scales and imprecision, as well as suboptimal reliability. Conceptually sound, objective, precise measurements are needed to advance knowledge of disc degeneration and its causes, progression, and consequences.

Effects of the wood extractives dehydroabietic acid and betulinol on reproductive physiology of zebrafish (Danio rerio)-a two-generation study

Two wood extractives, dehydroabietic acid (DHAA) and betulinol (BET), present in wood industry effluents were evaluated for their potential effects on the reproductive physiology of zebrafish. Adult zebrafish (F0) were exposed in a continuous flow-through system to 50 microg/l DHAA, 5 microg/l BET and 0.27 microg/l (1 nM) 17beta-estradiol (E2) for 3 months. Eggs were collected from F0 fish and the following F1 generation was exposed for 6 months. Biomarkers analyzed in both F0 and F1 fish were plasma vitellogenin (Vtg), testosterone (T), E2 (only females) and gonadal histology. DHAA and BET affected growth in terms of increased condition factor, and spawning was stimulated in BET-exposed fish of the F0 generation. F0 males exposed to DHAA and F0 females exposed to BET showed lower plasma Vtg concentration, but F1 males exposed to BET showed an increase in Vtg. In fish exposed to E2, the positive control for estrogenic effects, a pronounced increase in Vtg concentration was observed. Plasma sex steroids were not significantly affected by the wood extractives. However, although not statistically significant, the T concentration tended to be lower in fish of all BET treatments. The histological study revealed alterations in spermatogenic stages of F0 males exposed to DHAA and BET, which were different from those caused by E2. In F1 females, the percentage of vitellogenic oocytes was decreased in DHAA, BET and E2 exposures. This study shows that DHAA and BET may contribute to growth alterations and reproductive disturbances reported in fish exposed to pulp and paper mill effluents. Further, these wood extractives may have different effects in F0 and F1 generation fish, which highlights the value of two-generation studies in investigations regarding endocrine disrupting compounds.     

A methylester of the glucuronide prodrug DOX-GA3 for improvement of tumor-selective chemotherapy

The glucuronide prodrug of doxorubicin, DOX-GA3, can be selectively activated in tumors by extracellular human beta-glucuronidase, resulting in a better therapeutic index than doxorubicin. DOX-GA3, however, is rapidly excreted by the kidney. We hypothesized that slow release of DOX-GA3 from its methylester, DOX-mGA3, by esterase activity in blood would result in improved circulation half-life (t(1/2)) of DOX-GA3. DOX-mGA3 was synthesized more efficiently with an overall yield of 60% as compared to 37% in the case of DOX-GA3. We showed that DOX-mGA3 was enzymatically converted to DOX-GA3 with a t(1/2) of approximately 0.5 min in mouse plasma to 2.5 h in human plasma, which was in agreement with differences in esterase activity between species. DOX-mGA3, similar to DOX-GA3, was at least 37-fold less potent than the parent drug doxorubicin in growth inhibition of four different human malignant cell lines in vitro. Incubation of OVCAR-3 cells with DOX-mGA3 in combination with an excess of human beta-glucuronidase (0.05 U mL(-1)) resulted in a similar growth inhibition to that of doxorubicin. Intravenous administration of DOX-mGA3 in FMa-bearing mice resulted in an area under the concentration versus time curve (AUC) of DOX-GA3 in tumor and most normal tissues that was 2.5- to 3-fold higher than after the same dose of DOX-GA3 itself. In tumor tissue, this was accompanied by a 2.7-fold increase in the AUC of doxorubicin from DOX-mGA3 than from DOX-GA3. In conclusion, an advantage of DOX-mGA3 over DOX-GA3 is that this prodrug can be produced with a higher yield. Another important advantage is the improved pharmacokinetics of the lipophilic DOX-mGA3 as compared to that of the hydrophilic DOX-GA3. This effect may even be more pronounced in man, because of the lower plasma esterase activity than measured in mice.     

Human pHyde is not a classical tumor suppressor gene in prostate cancer

A novel putative tumor suppressor gene, pHyde, was recently cloned from rat prostate. The rat gene has been shown to inhibit prostate cancer cell proliferation both in vitro and in vivo. However, the role of human pHyde in prostate cancer has not been studied before. Here, we analyzed human prostate cancer cell lines (LNCaP, DU145, PC-3, 22Rv1), xenografts (LuCaP 23.1, 35, 41, 49, 58, 69, 70 and 73) and clinical prostate carcinomas for genetic alterations and expression of pHyde. The expression of pHyde in normal human tissues as well as in prostate cancer was studied by Northern analysis and real-time quantitative RT-PCR. It was ubiquitously expressed in all normal tissues analyzed. Although, the expression was significantly (p=0.007) lower in poorly differentiated than in well and moderately differentiated carcinomas, there were no differences in the expression levels between benign prostate hyperplasia, untreated primary and recurrent hormone-refractory prostate carcinomas (p=0.607). Altogether, missense mutations were detected in 2 out of 68 samples studied ( approximately 3%) by denaturing high-performance liquid chromatography (DHPLC) and sequencing. One of the samples with the mutation also exhibited a loss of a gene copy by fluorescence in situ hybridization (FISH). This was the only sample that exhibited a genetic alteration in both alleles, suggesting that the human pHyde is not a classical prostate tumor suppressor gene. The reduced expression of the gene found in some tumors warrant further studies.