[Genetic diagnostics of mental health disorders in adulthood]. / Genetische Diagnostik bei psychischen Erkrankungen im Erwachsenenalter.

This review article provides insights into the role of genetic diagnostics in adult mental health disorders. The importance of genetic factors in the development of mental illnesses, from rare genetic syndromes to common complex genetic disorders, is described. Current clinical characteristics that may warrant a genetic diagnostic work-up are highlighted, including intellectual disability, autism spectrum disorders and severe psychiatric conditions with specific comorbidities, such as organ malformations or epilepsy. The review discusses when genetic diagnostics are recommended according to current guidelines as well as situations where they might be considered even in the absence of explicit guideline recommendations. This is followed by an overview of the procedures and the currently used diagnostic methods. Current limitations and possible developments in the field of genetic diagnostics in psychiatry are discussed, including the fact that, for many mental health conditions, genetic testing is not yet part of standard clinical practice; however, in summary genetic causes should be considered more frequently in certain clinical constellations, and genetic diagnostics and counselling should be offered where appropriate.

Ten year experience with the concomitant Maze IV procedure for atrial fibrillation.

OBJECTIVE: The Maze IV (M-IV) procedure is regarded as the golden standard in treatment for surgical ablation of atrial fibrillation (AF); however, long-term follow-up results are scarce. We present our institutional 10-year experience. METHODS: We collected data of 117 consecutive patients who have undergone a concomitant M-IV procedure between April 2006 and April 2016. Primary endpoints are freedom of atrial arrhythmias and freedom of atrial arrhythmias off antiarrhythmic drugs (AAD). RESULTS: Forty-seven patients (40.2%) had paroxysmal AF. Two-thirds of the procedures included mitral valve surgery. The average follow-up time per patient was 3.8 years (SD 2.8). Freedom of AF at 1 year was 79%, at 5 years freedom of AF was 69% and freedom of AF off AAD was 56%. Predictors of AF recurrence in multivariate analysis were age, preoperative pacemakers, redo cardiac surgery and in-hospital AF. Preoperative PVI ablation was found to be a protective factor. CONCLUSIONS: The long-term outcomes of the M-IV procedure are good and remain stable over the years. Results could be improved if follow-up were to be intensified and recurrences dealt with aggressively. Key question: How many patients are free from AF in a 10-year period after concomitant M-IV surgical ablation? Key findings: In the long term around 70% of patients are free of AF with an increasing need for anti-arrhythmic drugs. Take home message: Early to midterm freedom from AF after concomitant M-IV procedure is high and remains stable after 3 years.

Congenital left ventricular diverticulum: A rare cause of cardiac arrhythmia.

Congenital left ventricular diverticula are rare cardiac malformations that usually remain asymptomatic. However, life-threatening complications as ventricular arrhythmias, systemic embolism, spontaneous rupture and development of valvular regurgitation, are described. Diagnosis is based on excluding coronary artery disease, traumatic or inflammatory causes, and other underlying cardiomyopathies. Treatment is directed towards the potential complications, yielding mainly therapy of ventricular arrhythmia. Surgical resection is required for larger-sized congenital aneurysms with adverse hemodynamic effects. We present two cases of a left ventricular diverticulum causing cardiac arrhythmia which led to further surgical treatment.

Endovascular repair of an extracranial carotid artery aneurysm complicated by late stent thrombosis.

Extracranial carotid artery aneurysms (ECAA) are extremely rare, accounting for less than 1% of all peripheral artery aneurysms. The most common presentation is central neurologic dysfunction, typically due to embolization of thrombus from the aneurysm. Historically open surgical intervention is the treatment of choice for symptomatic ECAA. Recent data suggest that endovascular repair is a valuable alternative, with a high procedural success rate and relatively low complication rate. We present a case of an ECAA with symptoms of vision loss, successfully treated by endovascular covered stenting but complicated by late in stent thrombosis and cerebral infarction. The patient was subsequently treated with IV thrombolysis and life-long warfarin. The patient had discrete residual symptoms at follow-up 3 months later.

Ventricular septal rupture: successful delayed repair.

Ventricular septal rupture (VSR) occurs in approximately 1% of the patients who experience an acute myocardial infarction. The operative mortality of VSR repair decreases if surgery can be delayed until the infarct has healed and tissue strength improved. Because of heart failure or impending cardiogenic shock, surgical treatment can often not be delayed. We present a case in which a delayed repair of a VSR was possible. The patient was initially stabilized with an intra-aortic balloon pump. She was discharged and readmitted 5 weeks later for definitive repair. Repair was performed, according to the Daggett technique, using a bovine pericardial patch and a mitral annuloplasty was carried out to correct for the regurgitation. Recovery was uneventful. Cardiac ultrasound examination at discharge showed no residual defect.

Gastrocnemius fascia release under local anaesthesia as a treatment for neuropathic foot ulcers in diabetic patients: a short series.

BACKGROUND: Diabetic foot ulceration is the leading cause of major amputation in the developed world. Plantar neuropathic ulcers at the forefoot can be managed conservatively with off-loading, but treatment is not invariably successful. Achilles tendon lengthening procedures aim at increasing dorsiflexion and decreasing forefoot pressure but can be associated with complications and require prolonged postoperative immobilization to prevent tendon rupture. We assessed the feasibility and clinical outcome of a comparative minimal invasive procedure: the gastrocnemius fascia release. This technique targets the same goals but is performed under local anaesthesia and allows immediate postoperative weight bearing and ambulation. METHODS: Diabetic patients with plantar neuropathic ulcers Wagner grade 2 or 3 were recruited from our diabetic foot clinic. Patients with infected wounds or untreatable peripheral arterial disease were excluded from the study. Conservative treatment with off-loading and local wound care was attempted for six weeks and surgical procedure only contemplated upon failure. Primary end-points were improved range of dorsiflexion and time to healing. Secondary end-points were local ulcer recurrences, new plantar ulcers, and minor or major amputation. Post-operative follow-up was 12 months. RESULTS: Seven patients were included in the study. An improvement in dorsiflexion of 10.4° (mean) was recorded post-operatively (p < 0.01). After 30 days, complete healing was accomplished in six of the seven patients. Long-term results were excellent as no ulcer recurrence or amputation was noted. CONCLUSIONS: Gastrocnemius fascia release under local anaesthesia can be performed safely in diabetic patients with plantar neuropathic ulcers under the metatarsal heads. Clinical outcome is excellent and long-term results promising.

Aortic Root Remodeling in the Tricuspid Aortic Valve.

BACKGROUND: Aortic root remodeling is one of the principal forms of valve-preserving root replacement. Its value has been questioned by some, whereas others have achieved excellent valve durability. The purpose of this review is to summarize the existing information to determine which factors may have contributed both to failures and to successes. METHODS: Publications on root remodeling for aneurysm or dissection with tricuspid aortic valves with >15 patients were reviewed for specific details of preoperative and intraoperative management. RESULTS: The series were very heterogeneous. Most operations were performed for root aneurysm, and 10 publications included type A dissection. Connective tissue disease was present in 22% of patients. Mean patient age was 52 years, and 5-year survival varied between 58% and 100%. Most series did not include an annuloplasty. Importantly, no details on quantitative assessment of valve configuration were specified in most series, especially those with suboptimal valve function and durability. The introduction of the effective height concept to control valve configuration was associated with improved results and more frequent correction of cusp prolapse. Late freedom from aortic regurgitation and freedom from reoperation are good in the larger series. CONCLUSIONS: Root remodeling can lead to excellent valve durability if quantitative intraoperative measurement of valve configuration is performed. The addition of an annuloplasty seems to improve aortic valve competence further, even though its effect on durability is not unequivocally proven. The long-term results of root remodeling are good, also in the second postoperative decade, and it is a valid form of valve-preserving root replacement.

Right coronary sinus aneurysm repair.

In this case report, we describe the surgical treatment of a right coronary sinus aneurysm. A 69-year-old male patient was screened because of palpitations. He was finally diagnosed with an aneurysm of the sinus of Valsalva of the right coronary cusp. According to current aortic guidelines, surgical reconstruction was proposed. The patient underwent a cardiac operation through a median sternotomy under routine cardiopulmonary bypass. After aortic cross-clamping, the aorta was opened and the connection between the aorta and the aneurysm was clearly visualized, underneath the ostium of the right coronary artery. After excision of the right coronary button and the remaining right coronary sinus wall, this sinus was reconstructed with a Dacron graft, with subsequent coronary reimplantation. The postoperative course was uneventful. The patient was discharged on postoperative day 7. A complete sinus reconstruction was preferred over local patching of the defect because of the proximity of the aneurysm sac to the right coronary artery and the fragile, thin aortic tissue just underneath the coronary ostium.

Failure of Tricuspid Annuloplasty for Functional Tricuspid Regurgitation: Impact of Patient's Body Size.

Tricuspid repair is recommended for significant functional tricuspid regurgitation (FTR) or tricuspid annulus (TA) dilation, based on TA >40 mm or >21 mm/m². The concordance between both TA dimensions related to the patient's body size has not been investigated. Patients who underwent rigid ring tricuspid annuloplasty for FTR between 2009 and 2017 were included. Assuming equality between both TA diameter criteria, patients were divided per body surface area (BSA): group 1 = BSA ≤1.9 m² and group 2 = BSA >1.9 m². The primary outcome was TR recurrence at 5 years. Tricuspid annuloplasty was performed in 186 patients (group 1: 130 patients [69.9%]; group 2: 56 patients [30.1%]). Group 1 comprised more female (70.8% to 23.2%, p <0.001) and older patients (77.1 ± 9.3 years; 74.2 ± 8.2 years, p = 0.048). Group 1 had a smaller absolute TA diameter (group 1: 45.3 ± 5.2 mm; group 2: 48.2 ± 5.6 mm, p <0.001), whereas the indexed TA size was inversely higher (group 1: 26.3 ± 3.4 mm/m²; group 2: 24.2 ± 2.7 mm/m², p <0.001). The tenting height was comparable (group 1: 7.8 ± 3.0 mm; group 2: 8.0 ± 2.7 mm, p = 0.714). The median ring size was 30 (interquartile range 28 to 32) and 32 (interquartile range 30 to 34) for groups 1 and 2, respectively (p <0.001). TR recurrence at 5 years was noticed in 20.2% and 6.5% of group 1 and 2 (p = 0.035). Indexed TA diameter (hazard ratio 1.43, 95% confidence interval 1.10 to 1.87, p = 0.008) and tenting height (hazard ratio 5.52, 95% confidence interval 1.87 to 14.57, p = 0.002) were independent predictors of TR recurrence. In conclusion, when the absolute TA diameter is used as the primary criterion, smaller patients are at a higher risk for TR recurrence by having a proportionally larger TA at the time of repair. An individualized approach guided by patient's body size might be more appropriate to indicate FTR correction to adjust for the annuloplasty sizing method.

Aberrant inflammasome activation as a driving force of human autoimmune skin disease.

Autoimmune skin diseases are understood as conditions in which the adaptive immune system with autoantigen-specific T cells and autoantibody-producing B cells reacting against self-tissues plays a crucial pathogenic role. However, there is increasing evidence that inflammasomes, which are large multiprotein complexes that were first described 20 years ago, contribute to autoimmune disease progression. The inflammasome and its contribution to the bioactivation of interleukins IL-1ß and IL-18 play an essential role in combating foreign pathogens or tissue damage, but may also act as a pathogenic driver of myriad chronic inflammatory diseases when dysfunctionally regulated. Inflammasomes containing the NOD-like receptor family members NLRP1 and NLRP3 as well as the AIM2-like receptor family member AIM2 have been increasingly investigated in inflammatory skin conditions. In addition to autoinflammatory diseases, which are often associated with skin involvement, the aberrant activation of the inflammasome has also been implied in autoimmune diseases that can either affect the skin besides other organs such as systemic lupus erythematosus and systemic sclerosis or are isolated to the skin in humans. The latter include, among others, the T-cell mediated disorders vitiligo, alopecia areata, lichen planus and cutaneous lupus erythematosus as well as the autoantibody-driven blistering skin disease bullous pemphigoid. Some diseases are characterized by both autoinflammatory and autoimmune responses such as the chronic inflammatory skin disease psoriasis. Further insights into inflammasome dysregulation and associated pathways as well as their role in forming adaptive immune responses in human autoimmune skin pathology could potentially offer a new field of therapeutic options in the future.

Midterm Comparison Between Different Annuloplasty Techniques for Functional Tricuspid Regurgitation.

BACKGROUND: Several tricuspid annuloplasty (TA) techniques are used for concomitant repair of functional tricuspid regurgitation (TR). This study compared the midterm clinical and valvular outcome among 3 annuloplasty techniques. METHODS: TA was performed in 307 patients (aged 75.9 ± 10.4 years) with a rigid ring (RA) in 184, a flexible band (FA) in 80, or a suture annuloplasty (SA) in 43. Study end points were survival and recurrence of TR >grade 2 at 5 years. RESULTS: TA was performed concomitantly to mitral valve surgery in 136 patients (44.3%), aortic valve surgery in 18 (5.9%), coronary artery bypass grafting in 13 (4.2%), or a combined procedure in 140 (45.6%). Most had TR >grade 2 (78.5%), without significant differences between the TA groups (P = .878). Within a median follow-up of 3.4 years (interquartile range, 2.2-5.0 years), the 5-year survival was 80.1% ± 3.4% for RA, 83.5% ± 4.7% for FA, and 85.1% ± 6.5% for SA (P = .471). Independent risk factors for late mortality were renal impairment (hazard ratio [HR], 2.83; 95% CI, 1.16-6.89; P = .022), diabetes (HR, 2.10; 95% CI, 1.07-4.11; P = .030), and severe right ventricular dysfunction by tricuspid annulus plane systolic excursion <10 mm (HR, 11.52; 95% CI, 4.98-26.66; P < .001). Pulmonary hypertension was nearly significant (HR, 1.92; 95% CI, 0.98-3.74; P = .057). The cumulative incidence of TR recurrence at 5 years was 15.9%, 19.4%, and 21.1% for RA, FA, and SA, respectively (P = .342). Severe pulmonary hypertension (HR, 2.64; 95% CI, 1.38-5.07; P = .003), preoperative TR grade (HR, 1.82; 95% CI, 1.01-3.27; P = .046), and residual TR >grade 2 at discharge (HR, 3.38; 95% CI, 1.64-6.96; P = .001) were predictive for later TR recurrence, regardless of the annuloplasty technique. CONCLUSIONS: This study demonstrates that advanced pathophysiological right circulatory impairment, such as severe pulmonary hypertension and right ventricular dysfunction, affects the midterm survival and TR recurrence rate more than the annuloplasty technique used for concomitant repair of functional TR.

Impact of mean perfusion pressure and vasoactive drugs on occurrence and reversal of cardiac surgery-associate acute kidney injury: A cohort study.

PURPOSE: Low cardiac output and kidney congestion are associated with acute kidney injury after cardiac surgery (CSA-AKI). This study investigates hemodynamics on CSA-AKI development and reversal. MATERIALS AND METHODS: Adult patients undergoing cardiac surgery were retrospectively included. Hemodynamic support was quantified using a new time-weighted vaso-inotropic score (VISAUC), and hemodynamic variables expressed by mean perfusion pressure and its components. The primary outcome was AKI stage ≥2 (CSA-AKI ≥2) and secondary outcome full AKI reversal before ICU discharge. RESULTS: 3415 patients were included. CSA-AKI ≥2 occurred in 37.4%. Mean perfusion pressure (MPP) (OR 0.95,95%CI 0.94-0.96, p < 0.001); and central venous pressure (CVP) (OR 1.17, 95%CI 1.13-1.22, p < 0.001) are associated with CSA-AKI ≥2 development, while VISAUC/h was not (p = 0.104). Out of 1085 CSA-AKI ≥2 patients not requiring kidney replacement therapy, 76.3% fully recovered of AKI. Full CSA-AKI reversal was associated with MPP (OR 1.02 per mmHg (95%CI 1.01-1.03, p = 0.003), and MAP (OR = 1.01 per mmHg (95%CI 1.00-1.02), p = 0.047), but not with VISAUC/h (p = 0.461). CONCLUSION: Development and full recovery of CSA-AKI ≥2 are affected by mean perfusion pressure, independent of vaso-inotropic use. CVP had a significant effect on AKI development, while MAP on full AKI reversal.

Subclavian artery stenosis caused by a prominent first rib.

Thoracic outlet syndrome is a mechanical space problem in which the brachial plexus and/or subclavian vessels are compressed. Arterial compression is least common and almost always associated with a bony anomaly. We present a case of a 49-year-old woman with a prominent first rib which caused a subclavian artery stenosis. There are many options for subclavian artery repair through open surgery. In high-risk patients, minimal invasive techniques are favorable. To date, few case reports exist on an endovascular artery repair combined with open first rib resection. While long-term follow-up will be necessary, our preliminary results seem promising.