THE ROLE OF DIGOXIN IN THE SUCCESSFUL TERMINATION OF A RESISTANT MATERNAL ATYPICAL AV NODAL REENTRY TACHYCARDIA

Here, we describe the case of a patient during her gestational period with resistant tachycardia that failed front line treatment options and was treated using an older agent.

Thyroid-related ophthalmopathy development in concurrence with growth hormone administration

Background Thyroid stimulating hormone (TSH) receptor and local infiltrate lymphocytes have been considered as major pathological factors for developing thyroid-related ophthalmopathy. Overexpression of insulin-like growth factor-I (IGF-I) receptor has emerged as a promising therapeutic target for refractory patients. However, the relationship between activation of growth hormone (GH)/IGF-I receptor signaling and development or exacerbation of thyroid ophthalmopathy has not been elucidated. Herein we describe a case that provides further clarification into the association between thyroid-related ophthalmopathy and GH/IGF-I receptor signaling. Case presentation A 62-year-old Japanese female diagnosed with thyroid-related ophthalmopathy was admitted to Kurume University Hospital. She had received daily administration of GH subcutaneously for severe GH deficiency; however, serum IGF-I levels were greater than + 2 standard deviation based on her age and sex. She exhibited mild thyrotoxicosis and elevation in levels of TSH-stimulating antibody. Discontinuation of GH administration attenuated the clinical activity scores of her thyroid-related ophthalmopathy. Additionally, concomitant use of glucocorticoid and radiation therapies resulted in further improvement of thyroid-related ophthalmopathy. The glucocorticoid administration was reduced sequentially, followed by successful termination. Thereafter, the patient did not undergo recurrence of thyroid-related ophthalmopathy and maintained serum IGF-I levels within normal physiological levels. Conclusions We describe here a case in which development of thyroid-related ophthalmopathy occurred upon initiation of GH administration. GH/IGF-I signaling was highlighted as a risk factor of developing thyroid-related ophthalmopathy. Additionally, aberrant TSH receptor expression was suggested to be a primary pathophysiological mechanism within the development of thyroid-related ophthalmopathy. Physicians should be aware of the risks incurred via GH administration, especially for patients of advanced age, for induction of thyroid-related ophthalmopathy.

Connexin43 in Germ Cells Seems to Be Dispensable for Murine Spermatogenesis

Testicular Connexin43 (Cx43) connects adjacent Sertoli cells (SC) and SC to germ cells (GC) in the seminiferous epithelium and plays a crucial role in spermatogenesis. However, the distinction whether this results from impaired inter-SC communication or between GC and SC is not possible, so far. Thus, the question arises, whether a GC-specific Cx43 KO has similar effects on spermatogenesis as it is general or SC-specific KO. Using the Cre/loxP recombinase system, two conditional KO mouse lines lacking Cx43 in premeiotic (pGCCx43KO) or meiotic GC (mGCCx43KO) were generated. It was demonstrated by qRT-PCR that Cx43 mRNA was significantly decreased in adult pGCCx43KO mice, while it was also reduced in mGCCx43KO mice, yet not statistically significant. Body and testis weights, testicular histology, tubular diameter, numbers of intratubular cells and Cx43 protein synthesis and localization did not show any significant differences in semi-quantitative Western blot analysis and immunohistochemistry comparing adult male KO and WT mice of both mouse lines. Male KO mice were fertile. These results indicate that Cx43 in spermatogonia/spermatids does not seem to be essential for successful termination of spermatogenesis and fertility as it is known for Cx43 in somatic SC, but SC-GC communication might rather occur via heterotypic GJ channels.

Medical Abortion of a First-Trimester Pregnancy with Large Multiple Uterine Leiomyomata

Introduction. Termination of pregnancy in a patient with huge uterine leiomyomata poses significant challenges to clinicians. In this study, we report the successful termination of pregnancy in a patient with large multiple uterine leiomyomata using a combined regimen of drugs for medical abortion. Case. A 42-year-old woman, 6 weeks pregnant, presented to the Family Planning Clinic with an unintended pregnancy. She had a large, irregular abdominal midline mass, equivalent in size to 30-32 weeks of pregnancy. Abdominal and transvaginal ultrasound examinations revealed a small intrauterine gestational sac with a yolk sac and multiple large uterine leiomyomata. Treatment with mifepristone (200 mg) was initiated at the clinic. In addition, she was instructed to sublingually take 800 μg of misoprostol after 24–48 h. Two weeks later, at the follow-up visit, the patient complained of continued light bleeding. A pelvic examination showed that her cervix was dilated by 1 cm. In addition, abdominal and transvaginal ultrasound revealed a thick, inhomogeneous endometrium. Owing to light bleeding and no anemia or infection, the patient received two additional doses of 800 μg misoprostol vaginally. Her bleeding subsided for 61 days, and she resumed her normal menstrual cycle. Conclusion. A first-trimester pregnancy with large multiple uterine leiomyomata can be safely terminated using a combination regimen of drugs for medical abortion. However, an additional dose of misoprostol is required for the successful termination of pregnancy.

Discontinuation of colchicine therapy in children with Familial Mediterranean Fever

Objective Colchicine has been considered a life-long therapy for Familial Mediterranean fever (FMF). Recent studies describe patients who discontinued colchicine, but data pertaining to predictors of success were not provided. The aims of our study are to describe a cohort of pediatric patients with FMF who discontinued colchicine therapy, and to identify factors predicting successful termination of colchicine. Methods This study describes a cohort of pediatric patients with FMF who discontinued colchicine therapy following a relatively prolonged attack-free period (≥6 month), and identifies factors predicting successful termination. Data collected included demographic, clinical, and laboratory characteristics of children diagnosed with FMF < 16 years who underwent a trial of colchicine discontinuation. Data from patients who successfully ceased colchicine therapy were compared to that of patients who relapsed. Results Of 571 patients with FMF, 59 (10.3%) discontinued colchicine therapy. The average attack-free period before enrollment was 1.4±0.97 years. Follow-up after ceasing colchicine was 5.0±3.05 years during which time 11 (20%) patients had an attack. The most common symptoms were fever (92%) and abdominal pain (84.6%). For those failing discontinuation, colchicine was restarted within 1.3 years (range: 0.3-5.0; median 0.7 years). A longer attack-free period prior to colchicine discontinuation predicted success. Myalgia and arthritis prior to colchicine cessation were more common among children who required renewal of colchicine. Conclusion Cessation of colchicine therapy should be considered following prolonged remission in a select group of patients. Patients with arthritis or myalgia are more likely to have an attack after ceasing colchicine therapy.

Extent of atrium with 1:1 electrogram activation predicts response to ablation of atrial fibrillation

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): US National Institutes of Health Background Mechanisms associated with successful termination of persistent atrial fibrillation (AF) are still under debate. We sought to study the association between spatial extent of atrium with organized conduction and AF ablation success. We hypothesized that patients with large areas of atrium having 1:1 electrogram activation akin to ‘atrial tachycardia’ may have a higher likelihood of AF termination by ablation. Methods In n = 40 AF patients, n = 20 had termination by ablation ("Term"), and the remaining did not have AF termination by ablation ("Non-term"). Basket catheters (64 poles) were used to record unipolar electrograms (EGMs) in one or both atrium. Ablation targeted localized rotational/focal regions, after which pulmonary vein isolation was performed. Unipolar EGMs of 4sec duration at each 2x2 electrode neighborhood within 8x8 catheter grid were processed using a statistical correlation technique to identify the duration of 1:1 activations. Any EGM activation cycle that had a correlation above 80% was considered to be 1:1. Duration of contiguous 1:1 cycles was determined as percentage of total duration (4 sec). Results Spatial area of atrium (percentage of mapping field) and the corresponding 1:1 durations were assessed for patients in Term and Non-term groups. Fig A shows spatial 1:1 maps of a Term and a Non-term patient. Fig B shows examples of 1:1 and non-1:1 EGMs. Patients in Term group had higher average 1:1 atrial area than non-term group for any 1:1 duration (Fig C, 15 ± 22% vs 2 ± 4% with ≥70% 1:1 duration, p = 0.03). Positive and negative predictive values of duration≥70% for AF termination were 64.7%, and 75%, with specificity 60% and sensitivity 78.6%, exceeding clinical risk scores. Conclusion Persistent AF atrium shows areas of organized 1:1 conduction. Larger 1:1 atrial areas were identified in patients in whom AF terminated by ablation. Future studies should investigate mechanistic bases of organized conduction in AF. Abstract Figure.

A case of pregnancy complicated with Evance syndrome and heparin-induced thrombocytopenia

The simultaneous development of autoimmune hemolytic anemia and immune thrombocytopenia is known as Evans syndrome. This pathology is extremely rare during pregnancy, requires careful differential diagnosis and is associated with a high risk of hemorrhagic and thromboembolic complications. Treatment approaches for autoimmune hemolytic anemia and immune thrombocytopenia are similar, but in the case of autoimmune hemolytic anemia, thromboprophylaxis is mandatory. Heparin-induced thrombocytopenia is a serious adverse event of anticoagulation. One presents with a decrease in platelets but a paradoxical increase in thrombotic risk and mandates switching of the anticoagulant agent to a non-heparin one. Clinical case. We describe the case of pregnancy complicated with Evans syndrome and development of heparin-induced thrombocytopenia at 28 weeks. Treatment of the underlying disease was effective on the use of first-line therapy. Fondaparinux and vitamin K antagonist (warfarin) have been used to treat heparin-induced thrombocytopenia. Monitoring of the fetal condition is carried out with careful control of Doppler ultrasound of the middle cerebral artery. Successful change of anticoagulant, close surveillance and carefully selected therapy allowed to achieve a successful termination of pregnancy. A healthy female newborn with body weight 2450 g, 8–8 Apgar scores was vaginally delivered uneventful at the 38th week. There were neither neonatal thrombocytopenia nor anemia. During the year after birth, the woman's condition is not worse, the child develops according to age. An analysis of similar cases of pregnancy from the literature is described. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the author. Key words: thrombocytopenia, hemolytic anemia, pregnancy, Evans syndrome, heparin-induced thrombocytopenia.

Efficacy and Safety of Ibutilide for the Cardioversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Background: Ibutilide has been approved for cardioversion of Atrial Fibrillation (AF), but its side-effects include a high risk of torsade de pointes, besides, one recent meta-analysis showed ibutilide was inferior to vernakalant for conversion (AF<7 days). Hence, the aim of this study is to evaluate the efficacy and safety of ibutilide for the cardioversion of AF within 90 days. Methods: The Embase, PubMed, Web of Science, Cochrane Central databases and clinical trials.gov were comprehensively searched for relevant studies from January 1991 to May 2020 using the keywords “ibutilide” and “atrial fibrillation”. Only Randomized Controlled Trials (RCTs) comparing ibutilide with placebo or other Anti-Arrhythmic Drugs (AADs) for the termination of AF (duration of AF ≤90 days) were included. The primary outcome was successful cardioversion in response to ibutilide versus placebo or other AADs within 4h. Related adverse events were defined as secondary outcomes. Results: A total of 1712 patients in 13 RCTs met the eligibility criteria. Four trials compared ibutilide to placebo; nine trials compared ibutilide to other active drugs. The results revealed that ibutilide had a higher success rate for the termination of recent-onset atrial fibrillation compared to placebo within 4h [Risk Ratio (RR), 4.64; 95% Confidence Interval (CI), 1.30-16.56, P=0.006]; and ibutilide also showed superiority to DL-sotalol, Propafenone, Procainamide for successful termination of recent-onset AF within 4h. As compared to other active drugs, Ibutilide was associated with a lower risk of hypotension (RR 0.23, 95% CI 0.09-0.57, P=0.002); but significantly increased the incidence of Polymorphic ventricular tachycardia (RR 3.78, 95% CI 1.08-13.23, P=0.04). Conclusion: Intravenous ibutilide could be an accessible choice for the cardioversion of recent-onset AF patients without contraindications, but under strict monitored condition is needed for at least 6 hours.

Input–Output Slope Curve Estimation in Neural Stimulation Based on Optimal Sampling Principles

This paper discusses some of the practical limitations and issues, which exist for the input – output (IO) slope curve estimation (SCE) in neural, brain and spinal, stimulation techniques. The drawbacks of the SCE techniques by using existing uniform sampling and Fisher-information-based optimal IO curve estimation (FO-IOCE) methods are elaborated. A novel IO SCE technique is proposed with a modified sampling strategy and stopping rule which improve the SCE performance compared to these methods. The effectiveness of the proposed IO SCE is tested on 1000 simulation runs in transcranial magnetic stimulation (TMS), with a realistic model of motor evoked potentials (MEPs). The results show that the proposed IO SCE method successfully satisfies the stopping rule, before reaching the maximum number of TMS pulses in 79.5% of runs, while the estimation based on the uniform sampling technique never converges and satisfies the stopping rule. At the time of successful termination, the proposed IO SCE method decreases the 95th percentile (mean value in the parentheses) of the absolute relative estimation errors (AREs) of the slope curve parameters up to 7.45% (2.2%), with only 18 additional pulses in average compared to that of the FO-IOCE technique. It also decreases the 95th percentile (mean value in the parentheses) of the AREs of the IO slope curve parameters up to 59.33% (16.71%), compared to that of the uniform sampling method. The proposed IO SCE also identifies the peak slope with higher accuracy, with the 95th percentile (mean value in the parentheses) of AREs reduced up to 9.96% (2.01%) compared to that of the FO-IOCE method, and up to 46.29% (13.13%) compared to that of the uniform sampling method.