Non-excisional techniques for the treatment of intergluteal pilonidal sinus disease:a systematic review

Non-excisional techniques for pilonidal sinus disease (PSD) have gained popularity over the last years. The aim of this study was to review short and long-term outcomes for non-excisional techniques with special focus on the additive effect of treatment of the inner lining of the sinus cavity and the difference between primary and recurrent PSD. A systematic search was conducted in Embase, Medline, Web of Science Core Collection, Cochrane and Google Scholar databases for studies on non-excisional techniques for PSD including pit picking techniques with or without additional laser or phenol treatment, unroofing, endoscopic techniques and thrombin gelatin matrix application. Outcomes were recurrence rates, healing rates, complication rates, wound healing times and time taken to return to daily activities. In total, 31 studies comprising 8100 patients were included. Non-excisional techniques had overall healing rates ranging from 67 to 100%. Recurrence rates for pit picking, unroofing and gelatin matrix application varied from 0 to 16% depending on the follow-up time. Recurrence rates after additional laser, phenol and endoscopic techniques varied from 0 to 29%. Complication rates ranged from 0 to 16%, and the wound healing time was between three and forty-seven days. The return to daily activities varied from one to nine days. Non-excisional techniques are associated with fast recovery and low morbidity but recurrence rates are high. Techniques that attempt to additionally treat the inner lining of the sinus have worse recurrence rates than pit picking alone. Recurrence rates do not differ between primary and recurrent disease.</p

Impact of sex on timing and clinical outcome of septal myectomy for obstructive hypertrophic cardiomyopathy

Background: Sex disparities are common in hypertrophic cardiomyopathy (HCM). Previous research has shown that at time of myectomy, women are older, have greater impairment of diastolic function and more advanced cardiac remodeling. The clinical impact of these differences is unknown. Method: This study included 162 HCM patients (61% m

BIO FOr CARE: biomarkers of hypertrophic cardiomyopathy development and progression in carriers of Dutch founder truncating MYBPC3 variants-design and status

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by truncating variants in the MYBPC3 gene. HCM is an important cause of sudden cardiac death; however, overall prognosis is good and penetrance in genotype-positive individuals is incomplete. The underlying mechanisms are poorly understood and risk stratification remains limited. AIM: To create a nationwide cohort of carriers of truncating MYBPC3 variants for identification of predictive biomarkers for HCM development and progression. METHODS: In the multicentre, observational BIO FOr CARe (Identification of BIOmarkers of hypertrophic cardiomyopathy development and progression in Dutch MYBPC3 FOunder variant CARriers) cohort, carriers of the c.2373dupG, c.2827C > T, c.2864_2865delCT and c.3776delA MYBPC3 variants are included and prospectively undergo longitudinal blood collection. Clinical data are collected from first presentation onwards. The primary outcome constitutes a composite endpoint of HCM progression (maximum wall thickness ≥ 20 mm, septal reduction therapy, heart failure occurrence, sustained ventricular arrhythmia and sudden cardiac death). RESULTS: So far, 250 subjects (median age 54.9 years (interquartile range 43.3, 66.6), 54.8% male) have been included. HCM was diagnosed in 169 subjects and dilated cardiomyopathy in 4. The primary outcome was met in 115 subjects. Blood samples were collected from 131 subjects. CONCLUSION: BIO FOr CARe is a genetically homogeneous, phenotypically heterogeneous cohort incorporating a clinical data registry and longitudinal blood collection. This provides a unique opportunity to study biomarkers for HCM development and prognosis. The established infrastructure can be extended to study other genetic variants. Other centres are invited to join our consortium

Frequency and Significance of Coronary Artery Disease and Myocardial Bridging in Patients With Hypertrophic Cardiomyopathy

The etiology of chest pain in hypertrophic cardiomyopathy (HC) is diverse and includes coronary artery disease (CAD) as well as HC-specific causes. Myocardial bridging (MB) has been associated with HC, chest pain, and accelerated atherosclerosis. We compared HC patients with age-, gender- and CAD pre-test probability-matched outpatients presenting with chest pain to investigate differences in the presence of MB and CAD using coronary computed tomography angiography (CCTA). We studied 84 HC patients who underwent CCTA and compared these with 168 matched controls (age 54 ± 11 years, 70% men, pre-test probability 12% [5% to 32%]). MB, calcium score, plaque morphology and presence and extent of CAD were assessed for each patient. Linear mixed models were used to assess differences between cases and controls. MB was more often seen in HC patients (50% vs 25%, p <0.001). Calcium score and the presence of obstructive CAD were similar in both groups (9 [0 to 225] vs 4 [0 to 82] and 18% vs 19%; p = 0.22 and p = 0.82). In the HC group, MB was associated with pathogenic DNA variants (p = 0.04), but not with the presence of chest pain (74% vs 76%, p = 0.8), nor with worse outcome (log-rank p = 0.30). In conclusion, the prevalence and extent of CAD was equal among patients with and without HC, demonstrating that pre-test risk prediction using the CAD Consortium clinical risk score performs well in HC patients. MB was twice as prevalent in the HC group compared with matched controls, but was not associated with chest pain or decreased event-free survival in these patients

Deep neuromuscular block does not improve surgical conditions in patients receiving sevoflurane anaesthesia for laparoscopic renal surgery

Background: Deep neuromuscular block is associated with improved working conditions during laparoscopic surgery when propofol is used as a general anaesthetic. However, whether deep neuromuscular block yields similar beneficial effects when anaesthesia is maintained using volatile inhalation anaesthesia has not been systematically investigated. Volatile anaesthetics, as opposed to intravenous agents, potentiate muscle relaxation, which potentially reduces the need for deep neuromuscular block to obtain optimal surgical conditions. We examined whether deep neuromuscular block improves surgical conditions over moderate neuromuscular block during sevoflurane anaesthesia.Methods: In this single-centre, prospective, randomised, double-blind study, 98 patients scheduled for elective renal surgery were randomised to receive deep (post-tetanic count 1-2 twitches) or a moderate neuromuscular block (train-of-four 1-2 twitches). Anaesthesia was maintained with sevoflurane and titrated to bispectral index values between 40 and 50. Pneumoperitoneum pressure was maintained at 12 mm Hg. The primary outcome was the difference in surgical conditions, scored at 15 min intervals by one of eight blinded surgeons using a 5-point Leiden-Surgical Rating Scale (L-SRS) that scores the quality of the surgical field from extremely poor(1) to optimal(5).Results: Deep neuromuscular block did not improve surgical conditions compared with moderate neuromuscular block: mean (standard deviation) L-SRS 4.8 (0.3) vs 4.8 (0.4), respectively (P=0.94). Secondary outcomes, including unplanned postoperative readmissions and prolonged hospital admission, were not significantly different.Conclusions: During sevoflurane anaesthesia, deep neuromuscular block did not improve surgical conditions over moderate neuromuscular block in normal-pressure laparoscopic renal surgery.Transplant surger

Simultaneous Detection of Circulating Autoreactive CD8+ T-Cells Specific for Different Islet Cell–Associated Epitopes Using Combinatorial MHC Multimers

textabstractOBJECTIVE - Type 1 diabetes results from selective T-cell-mediated destruction of the insulin-producing β-cells in the pancreas. In this process, islet epitope-specific CD8+T-cells play a pivotal role. Thus, monitoring of multiple islet-specific CD8+T-cells may prove to be valuable for measuring disease activity, progression, and intervention. Yet, conventional detection techniques (ELISPOT and HLA tetramers) require many cells and are relatively insensitive. RESEARCH DESIGN AND METHODS - Here, we used a combinatorial quantum dot major histocompatibility complex multimer technique to simultaneously monitor the presence of HLA-A2 restricted insulin B10-18, prepro-insulin (PPI)15-24, islet antigen (IA)-2797-805, GAD65114-123, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)265-273, and pre-pro islet amyloid polypeptide (ppIAPP)5-13-specific CD8+T-cells in recent-onset diabetic patients, their siblings, healthy control subjects, and islet cell transplantation recipients. RESULTS - Using this kit, islet autoreactive CD8+T-cells recognizing insulin B10-18, IA-2797-805, and IGRP265-273were shown to be frequently detectable in recent-onset diabetic patients but rarely in healthy control subjects; PPI15-24proved to be the most sensitive epitope. Applying the "Diab-Q-kit" to samples of islet cell transplantation recipients allowed detection of changes of autoreactive T-cell frequencies against multiple islet cell-derived epitopes that were associated with disease activity and correlated with clinical outcome. CONCLUSIONS - A kit was developed that allows simultaneous detection of CD8+T-cells reactive to multiple HLA-A2-restricted β-cell epitopes requiring limited amounts of blood, without a need for in vitro culture, that is applicable on stored blood samples

Mutation location of HCM-causing troponin T mutations defines the degree of myofilament dysfunction in human cardiomyocytes

Background: The clinical outcome of hypertrophic cardiomyopathy patients is not only determined by the disease-causing mutation but influenced by a variety of disease modifiers. Here, we defined the role of the mutation location and the mutant protein dose of the troponin T mutations I79N, R94C and R278C. Methods and results: We determined my

Incremental Value of an Insertable Cardiac Monitor in Patients with Hypertrophic Cardiomyopathy with Low or Intermediate Risk for Sudden Cardiac Death

Aims: The aim of the present study was to compare the rate of actionable arrhythmic events between patients with hypertrophic cardiomyopathy (HCM) who are monitored with an insertable cardiac monitor (ICM) or Holter monitoring. Methods: We studied 50 patients (mean age 52 years, 72% men) with HCM at low or intermediate risk for sudden cardiac death (SCD), of whom 25 patients received an ICM between November 2014 and February 2019. We retrospectively identified a control group of 25 patients who were matched on age, sex, and HCM Risk-SCD score category. The mean HCM Risk-SCD score was 3.41 ± 1.31 and 3.31 ± 1.43 for the ICM and Holter groups, respectively. The primary endpoint was an actionable event which was defined as an arrhythmic event resulting in a change in patient management. The secondary endpoint was the occurrence of ventricular tachycardia (VT). Results: The cumulative actionable event rate at 30 months was higher in the ICM group (51 vs. 27%, log-rank p value <0.01). De novo atrial fibrillation requiring oral anticoagulation occurred onlyin the ICM group (n = 3). Overall, 4 implantable cardioverter-defibrillators were implanted for primary prevention (n = 2 in each group). The cumulative rate of VT episodes at 30 months was similar between groups (23% [ICM group] vs. 42% [Holter group], log-rank p value = 0.71). Furthermore, the characteristics of VT were similar between groups with regard to the number of beats and rate. Conclusions: In adults with HCM, an ICM will detect more arrhythmic events requiring an intervention than a conventional Holter strategy. In contrast, the diagnostic yield of detecting VT seems similar for both groups

Effect of body surface area and gender on wall thickness thresholds in hypertrophic cardiomyopathy

Background: Family screening for hypertrophic cardiomyopathy (HCM) is based on genetic testing and clinical evaluation (maximal left ventricular wall thickness (MWT) ≥15 mm, or ≥13 mm in first-degree relatives of HCM patients). The aim of this study was to assess the effect of gender and body size on diagnosis of HCM and prediction of clinical outcome. Methods: This study includes 199 genotype-positive subjects (age 44 ± 15 years, 50% men) referred for cardiac screening. Gender-specific reference values for MWT indexed by body surface area (BSA), height and weight were derived from 147 healthy controls. Predictive accuracy of each method for HCM-related events was assessed by comparing areas under the receiver operating characteristic curves (AUC). Results: Men had a higher absolute, but similar BSA- and weight-indexed MWT compared with women (14.0 ± 3.9 mm vs 11.5 ± 3.8 mm, p  0.05). Applying BSA- and weight-indexed cut-off values decreased HCM diagnoses in the study group (48% vs 42%; 48% vs 39%, both p < 0.05), reclassified subjects in the largest, lightest and heaviest tertiles (≥2.03 m2: 58% vs 45%; ≤70 kg: 37% vs 46%; ≥85 kg: 53% vs 25%, all p < 0.05) and improved predictive accuracy (AUC 0.76 [95% CI 0.69–0.82] vs 0.78 [0.72–0.85]; and vs 0.80 [0.74–0.87]; both p < 0.05). Conclusions: In genotype-positive subjects referred for family screening, differences in MWT across gender are mitigated after indexation by BSA or weight. Indexation decreases the prevalence of HCM, particularly in larger men, and improves the predictive accuracy for HCM-related events