Enigmatic thymus: Variations in anatomical localisation of thymic tissue as an easily misdiagnosed congenital anomaly in surgical practice.

We point out the issue of differential diagnosis regarding the finding of ectopically localised thymic tissue (a thymic cyst) in the neck. Thymic tissue can be found anywhere along its developmental tract of descent, from the angle of the mandible to the upper mediastinum. Disruption of the thymic descent can result in ectopically/abnormally localised islets of accessory thymic tissue, which may undergo cystic changes, as described in a case report by Sun et al. This anatomical variation of the thymus may be clinically misinterpreted as a neoplasm or other congenital anomalies as a branchial cyst, lymphatic malformation or cystic hygroma. The present editorial focuses on the challenge of establishing a diagnosis of ectopically localised tissue of thymus often presented as a lateral cervical mass, especially in the case of cystic variation/degeneration of this thymic tissue. We summarise hypotheses on the origin of such congenital cervical thymic cysts from the point of view of evolutionary history and embryology. We also discuss lesser-known facts about the anatomy, histopathology and developmental biology of the thymus as one of the most enigmatic organs in the human body.

Noncomplex ventricular arrhythmia associated with greater freedom from recurrent ectopy at 1 year after mitral repair surgery.

Objective: The effect of mitral valve (MV) surgery on the natural history of ventricular arrhythmia (VA) in patients with arrhythmic MV prolapse remains unknown. We sought to evaluate the cumulative incidence of VA at 1 year after surgical mitral repair. Methods: A retrospective review of progressively captured data identified 204 consecutive patients who underwent elective MV repair for significant degenerative mitral regurgitation as a first-time cardiovascular intervention in a quaternary reference center between January 2018 and December 2020. A subset of 62 consecutive patients with diagnosed arrhythmic MV prolapse was further evaluated for recurrent VA after MV repair. Results: The median age was 62 years (range, 27-77 years) and 26 of 62 (41.9%) were female. The median time from initial mitral regurgitation/MV prolaspe diagnosis-to-referral was 13.8 years (interquartile range [IQR], 5.4-25) and from VA diagnosis-to-referral was 8 years (IQR, 3-10.6). Using the Lown-Wolf classification, complex VA (Lown grade ≥3) was identified in 36 of 62 patients (58%) at baseline, whereas 8 of 62 (13%) had a cardioverter/defibrillator implanted for primary (4/8) or secondary (4/8) prevention. Left ventricular myocardial scar was confirmed in 23 of 34 (68%) of patients scanned at baseline. The prevailing valve phenotype was bileaflet Barlow (59/62; 95.2%). All patients underwent surgical MV repair by the same team. Surgical repair was stabilized with an annuloplasty prosthesis (median size 36 mm [IQR, 34-38]). Concomitant procedures included tricuspid valve repair (51/62; 82.3%), cryo-maze ± left atrial appendage exclusion (14/62, 23%), and endocardial cryoablation of VA ectopy (4/62; 6.5%). The 30-day and 1-year freedom from recurrent VA were 98.4% and 75.9%, respectively. Absent VA after mitral repair was uniformly observed in patients with minor VA at baseline. Absent VA after mitral repair was uniformly observed in patients with minor VA preoperatively. Complex baseline VA was the strongest predictor of recurrent VA (hazard ratio, 10.8; 95% confidence interval, 1.4-84.2; P = .024), irrespective of myocardial fibrosis. Conclusions: In a series of 62 consecutive patients operated electively for arrhythmic mitral prolapse, VA remained undetected in 75.9% of patients at 1 year. Freedom from recurrent VA was greater among patients without complex VA preoperatively, whereas baseline Lown grade ≥3 was the strongest independent risk factor for recurrent VA at 1 year. These findings attest to the importance of early recognition and prompt referral of patients with mitral prolapse and progressive VA to specialty interdisciplinary care.

Prevalence and predictors of mitral annular disjunction and ventricular ectopy in mitral valve prolapse.

BACKGROUND: Mitral annular disjunction (MAD) is associated with ventricular arrhythmia in mitral valve prolapse (MVP). The proportional risk from MAD and other predictors of ventricular arrhythmia in MVP has not been well characterized. OBJECTIVE: This study aimed to identify predictors of complex or frequent ventricular ectopy (cfVE) in MVP and to quantify risk of cfVE and mortality in MVP with MAD. METHODS: We studied 632 adult patients with MVP on transthoracic echocardiography at the University of North Carolina Medical Center from 2016 to 2019 (median age, 64 [interquartile range, 52-74] years; 52.7% female; 16.3% African American). Resting and ambulatory electrocardiograms were used to identify cfVE. RESULTS: MAD was present in 94 (14.9%) patients. Independent associations of MAD were bileaflet prolapse (odds ratio [95% CI], 4.25 [2.47-7.33]; P < .0001), myxomatous valve (2.17 [1.27-3.71]; P = .005), absence of hypertension (2.00 [1.21-3.32]; P = .007), electrocardiogram inferior or lateral lead T-wave inversion (2.07 [1.23-3.48]; P = .006), and female sex (1.99 [1.21-3.25]; P = .006). cfVE was frequent with MAD (39 [41.5%] vs 93 [17.3%] without; P < .0001). Independent cfVE predictors were MAD (hazard ratio [95% CI], 2.23 [1.47-3.36]; P = .0001), bileaflet prolapse (1.86 [1.25-2.76]; P = .002), heart failure (1.79 [1.16-2.77]; P = .009), lower left ventricular ejection fraction (0.14 [0.03-0.61]; P = .009), coronary artery disease (1.60 [1.05-2.43]; P = .03), and inferior or lateral lead T-wave inversion (1.51 [1.03-2.22]; P = .03). After a median of 40 (33-48) months, there was increased mortality with MAD (P = .04). CONCLUSION: MAD in MVP is associated with bileaflet or myxomatous MVP, absence of hypertension, T-wave inversion, and female sex. There is increased cfVE and mortality with MAD, highlighting the need for closer follow-up of these patients.

Aerobic Exercise Improves Heart Rate Variability After an Implantable Cardioverter Defibrillator (ICD).

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00522340.

Narrow QRS ectopy with concealed connections from a para-Hisian origin to the proximal left fascicles.

INTRODUCTION: Catheter ablation of ectopy originating from the vicinity of the His bundle can be challenging. METHODS AND RESULTS: We report a case of a 33-year-old man with narrow QRS ectopy with preferential conduction from a para-Hisian origin to the proximal left fascicles, which was successfully eliminated by radiofrequency ablation in the right coronary cusp, guided by ultrahigh-resolution mapping of the His bundle, bundle branch, and fascicular electrograms. CONCLUSION: Some narrow QRS ectopy may originate from the vicinity of the conduction system, instead of the "true" conduction system, and have concealed connections from its origin to the conduction system.

Cardiac atrial pathology in Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Duchenne muscular dystrophy (DMD) is characterized by fibrofatty replacement of muscle. This has been documented in the ventricular myocardium of DMD patients, but there is limited description of atrial involvement. The purpose of this study is to examine the arrhythmia and ectopy burden in patients with DMD and non-DMD dilated cardiomyopathy (DCM) and to characterize the cardiac histopathologic changes in DMD patients across the disease spectrum. METHODS: This was a retrospective analysis of age-matched patients with DMD and non-DMD DCM who received a Holter monitor and cardiac imaging within 100 days of each other between 2010 and 2020. Twenty-four-hour Holter monitors were classified based on the most recent left ventricular ejection fraction at the time of monitoring. Cardiac histopathologic specimens from whole-heart examinations at the time of autopsy from three DMD patients and one DCM patient were reviewed. RESULTS: A total of 367 patients with 1299 Holter monitor recordings were included over the study period, with 94% representing DMD patients and 6% non-DMD DCM. Patients with DMD had more atrial ectopy across the cardiac function spectrum (p < 0.05). There was no difference in ventricular ectopy. Four DMD patients developed symptomatic atrial arrhythmias. Autopsy specimens from DMD patients demonstrated fibrofatty infiltration of both atrial and ventricular myocardium. DISCUSSION: The atrial myocardium in patients with DMD is unique. Autopsy specimens reveal fibofatty replacement of the atrial myocardium, which may be a nidus for both ectopy and arrhythmias in DMD patients.

Could tranexamic acid be a suitable alternative to cryotherapy for symptomatic cervical ectopy? Results from a randomized clinical trial.

OBJECTIVE: Cervical ectropion occurs due to the eversion of the endocervix that exposes glandular cells to the vaginal milieu. The aim of the present study was to evaluate and compare the clinical efficacy of effervescent vaginal tablets of tranexamic acid and cryotherapy in women with symptomatic cervical ectopy. METHODS: The current randomized clinical trial was conducted on 92 samples of women with cervical erosive ectropion from March 20, 2022 to August 27, 2022. Participants were divided into two groups; the intervention group (n = 46) was treated with a 400 mg effervescent vaginal tablet of tranexamic acid and the control group (n = 46) underwent cryotherapy. All the patients were requested to visit weekly in the first month and then monthly for the next 3 months, and the outcomes encompass improvement of symptoms (leukorrhea, dyspareunia, pelvic pain, post-coital bleeding, and suprapubic pain) and cervical erosive ectropion view were monitored based on repeated examinations. RESULTS: In this study, no statistically significant difference was observed in cure rate of symptoms between study groups (P value > 0.05). Women in both the tranexamic acid and cryotherapy groups reported significant improvements in dyspareunia (34 [75%] vs 31 [67%]), pelvic pain (34 [75%] vs 34 [74%]), post-coital bleeding (37 [81%] vs 31 [67%]), leukorrhea (36 [78%] vs 36 [78%]), suprapubic pain (32 [71%] vs 33 [73%]) disappearance of cervical ectropion tranexamic acid (40 [86%], vs 39 [84%]). CONCLUSION: Our findings highlighted the equal effect of tranexamic acid and cryotherapy for treating cervical ectropion. Due to the ease of use, availability, and fewer side effects of tranexamic acid, it can be a suitable alternative to cryotherapy. TRIAL REGISTRATION: IRCT20220115053719N1. The name of the registry: Iranian Registry of Clinical Trials. URL of registration: https://en.irct.ir/trial/61483.

Identification of Germline FOXE1 and Somatic MAPK Pathway Gene Alterations in Patients with Malignant Struma Ovarii, Cleft Palate and Thyroid Cancer.

Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue, papillary TC (PTC) and CP. Two rare germline heterozygous variants in the FOXE1 promoter were identified: F1) c.-522G>C, in the proband (MSO) and her mother (asymptomatic); F2) c.9C>T, in the proband (PTC), her sister and her mother (CP). Functional studies using rat normal thyroid (PCCL3) and human PTC (TPC-1) cells revealed that c.9C>T decreased FOXE1 promoter transcriptional activity in both cell models, while c.-522G>C led to opposing activities in the two models, when compared to the wild type. Immunohistochemistry and RT-qPCR analyses of patients' thyroid tumours revealed lower FOXE1 expression compared to adjacent normal and hyperplastic thyroid tissues. The patient with MSO also harboured a novel germline AXIN1 variant, presenting a loss of heterozygosity in its benign and malignant teratoma tissues and observable ß-catenin cytoplasmic accumulation. The sequencing of the F1 (MSO) and F2 (PTC) probands' tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours' malignant transformation.

Results of uretero-ureteral anastomosis in pathological duplex kidney.

INTRODUCTION: Duplex renal collecting system or duplex kidney (DK) commonly is associated with uropathy, with upper pole obstruction or lower pole vesicoureteral reflux (VUR). Its management is variable, ranging from therapeutic abstention to total nephrectomy. In case of damage to a single renal pole, uretero-ureteral anastomosis (UUA) is one of the surgical techniques for preserving the pathological pole. It can be performed by laparotomy, laparoscopy, or both. The aims of this study are to report the results of UUA in pathological DK, and compare outcomes depending on the surgical approach. METHODS: This is a retrospective analysis study over 20 years, from April 2002 to July 2022, including all children from 0 to 15 years old who underwent UUA for a DK. Outcome measure included per- and post-operative complications, the occurrence of urinary tract infections and ultrasound measurements during follow-up. RESULTS: Thirty-three children underwent an UUA over 20 years. The median age at diagnosis was 25 days (range: 1 day-12 years). The median age at surgery was 13 months (range: 2 months - 13 years). The sex ratio was 0.22. Prenatal diagnosis was made in 87.9 % of cases (n = 29). The left kidney was affected in 72.7 % of cases. Twenty-seven children (81.8 %) had an ectopic ureteral opening of the upper pole ureter; four children (12.1 %) had ureterocele of the upper pole and 2 children (6.1 %) had vesicoureteral reflux of the inferior pole. UUA was performed by inguinal approach (laparotomy) in 17 children (51.5 %), by laparoscopy in 9 cases (27.3 %), and by laparoscopy combined with laparotomy in 7 cases (21.2 %). The complication rate was 12.1 % (n = 4), including recurrent pyelonephritis with superior polar hydronephrosis (n = 2); iatrogenic injury of the lower pole ureter (n = 1) and a urinoma (n = 1), that all required surgical management with a polar nephrectomy. Between each surgical approach, there were no significant differences in operative time, hospital stay, complications. CONCLUSION: UUA is an effective therapeutic option in duplex kidneys as it allows the preservation of the pathological pole with low complication rates, regardless of the surgical approach.

Predictors and possible mechanisms of premature ventricular contraction induced cardiomyopathy.

Premature ventricular complexes (PVCs) are encountered frequently in clinical practice. While PVCs may have various causes, a small number of individuals with PVCs develop cardiomyopathy in the absence of other potential etiologies. When correctly identified, patients with PVC-incuded cardiomyopathy can have dramatic improvement of their cardiomyopathy with treatment of their PVCs. In this focused review, we discuss potential predictors of PVC-induced cardiomyopathy, including PVC frequency, PVC characteristics, and modifiable patient risk factors. We also review some proposed mechanisms of PVC-induced cardiomyopathy and conclude with future directions for research and clinical practice.

Dental Anomaly in Hapalodectes dux (Hapalodectidae, Mesonychia) from the Late Paleocene of Mongolia.

The holotype of Hapalodectes dux Lopatin, 2001 from the Upper Paleocene of Mongolia (Tsagan-Khushu locality, Naran Bulak Formation, Zhigden Member) is a lower jaw with complete dentition, showing healed alveoli in place of the right P3. Examination of the holotype using X-ray microtomography revealed a rare dental anomaly previously unknown in fossil mammals, namely the presence of the inverted (positioned upside down and rotated lingual side labially) impacted premolar inside the dentary. The cause of this anomaly may be an aberration of a tooth bud location or an injury.

Cervical and Vaginal Deciduosis: Insights on Management and a Systematic Review of Observational Studies on Pregnancy Complications and Management Outcomes (Including Vaginal Birth).

INTRODUCTION: Deciduosis is an ectopic transformation of connective tissue into decidual-like cells. This is the first systematic review describing the clinical course, associated pregnancy complications, and management outcomes of cervical and vaginal deciduosis. METHODS: Our search covered worldwide observational studies published in English in five databases (PubMed, PubMed Central (PMC), Europe PMC, ScienceDirect, and Google Scholar) from inception to February 24, 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and critically appraised studies using CAse REport (CARE) and Joanna Briggs Institute (JBI) tools. Then, we extracted patient characteristics, clinical features, management-related information, and outcomes. RESULTS: The selection process identified 15 studies describing 30 pregnancies. Macroscopic cervical and vaginal deciduosis presented as recurrent vaginal bleeding in over 16 of 24 women (57%). Differential diagnoses included miscarriages, cervical pregnancy, placenta previa, and malignancy. Significant antenatal hemorrhages, preterm rupture of membranes, and preterm birth were the most frequent pregnancy complications. Only one of 27 electively performed procedures resulted in biopsy-induced uncontrolled vaginal bleeding (0.04%), suggesting the relative safety of the interventions. Lesion resection led to the cessation of recurrent symptoms in eight of eight patients (100%) compared to eight of 15 women (53%) under observation management. All women with polypoid deciduosis over 1.5 cm entered labor and delivered without complications. CONCLUSIONS: We described the clinical course, pregnancy complications, diagnostic-related challenges, management, and associated outcomes in women with macroscopic cervical and vaginal deciduosis. We supported the analysis with the current state of the problem and discovered gaps for prospective studies.

Independent prognostic value of high-risk ventricular premature complexes during exercise or recovery in asymptomatic patients: A meta-analysis of observational studies.

INTRODUCTION: Ventricular premature contractions (VPCs) are a common finding during cardiac stress tests. The independent prognostic value of these findings in patients in asymptomatic patients is unclear. METHODS: We conducted a systematic review and meta-analysis of observational studies exploring the independent prognostic value of VPCs to predict all-cause mortality. The secondary outcome was cardiovascular (CV) mortality. We excluded studies that did not report outcomes after adjusting for ≥1 confounder. Random effect meta-analyses were used to predict cumulative hazard ratios. We stratified results based on VPC during exercise or recovery. RESULTS: We found 7 studies with 24,518 patients that met our inclusion criteria. Two studies reported all-cause mortality only, 1 study reported CV mortality only, rest 4 reported both. There was significant heterogeneity in the baseline population, definition of high-risk VPCs, and variables used in adjusted models. Using multivariable summary estimates from individual studies, only VPCs during exercise were associated with a higher risk of all-cause mortality (HR 1.27, 95 % CI 1.07, 1.48). Both VPCs during exercise and recovery were associated with a higher risk CV mortality (HR 1.69, 95 % CI 1.19, 2.20, I2 = 17.6 % and 1.62, 95 % CI 1.25, 2.00, p < 0.001 for both). CONCLUSION: High-risk VPCs during exercise is associated with increased risk of all-cause and CV mortality, while those during recovery are associated with an increased risk of CV mortality only.

Catheter Ablation vs Antiarrhythmic Drug Therapy for Treatment of Premature Ventricular Complexes: A Systematic Review.

There is variability in treatment modalities for premature ventricular complexes (PVCs), including use of antiarrhythmic drug (AAD) therapy or catheter ablation (CA). This study reviewed evidence comparing CA vs AADs for the treatment of PVCs. A systematic review was performed from the Medline, Embase, and Cochrane Library databases, as well as the Australian and New Zealand Clinical Trials Registry, U.S. National Library of Medicine ClinicalTrials database, and the European Union Clinical Trials Register. Five studies (1 randomized controlled trial) enrolling 1,113 patients (57.9% female) were analyzed. Four of five studies recruited mainly patients with outflow tract PVCs. There was significant heterogeneity in AAD choice. Electroanatomic mapping was used in 3 of 5 studies. No studies documented intracardiac echocardiography or contact force-sensing catheter use. Acute procedural endpoints varied (2 of 5 targeted elimination of all PVCs). All studies had significant potential for bias. CA seemed superior to AADs for PVC recurrence, frequency, and burden. One study reported long-term symptoms (CA superior). Quality of life or cost-effectiveness was not reported. Complication and adverse event rates were 0% to 5.6% for CA and 9.5% to 21% for AADs. Future randomized controlled trials will assess CA vs AADs for patients with PVCs without structural heart disease (ECTOPIA [Elimination of Ventricular Premature Beats with Catheter Ablation versus Optimal Antiarrhythmic Drug Treatment]), with impaired LVEF (PAPS [Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy] Pilot), and with structural heart disease (CAT-PVC [Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease]). In conclusion, CA seems to reduce recurrence, burden, and frequency of PVCs compared with AADs. There is a lack of data on patient- and health care-specific outcomes such as symptoms, quality of life, and cost-effectiveness. Several upcoming trials will offer important insights for management of PVCs.

Dual Atrioventricular Nodal Non-Re-Entrant Tachycardia.

A patient presented with symptoms of palpitations. Her standard 12-lead electrocardiogram captured 3 potential causes of her symptoms (premature atrial contractions, junctional rhythm, and narrow complex tachycardia). Further workup uncovered dual atrioventricular node physiology with 1:2 sinus conduction and resultant alternating QRS from a slow and fast conduction pathway. (Level of Difficulty: Intermediate.).