The current status of surgical pilonidal sinus disease therapy in Germany

European Surgery - Treatment of pilonidal sinus disease (PSD) requires a tailored approach. A national guideline was published in 2014. The current status of surgical PSD therapy...     

Prosthesis-Patient Mismatch Increases Early and Late Mortality in Low Risk Aortic Valve Replacement

PPM was highly associated with long-term all-cause mortality. Small Aortic Valve Annulus MDT (SAVA-MDT) exploring options to prevent PPM, including the implantation of newer generation prosthetic valves, aortic root enlargement and TAVI, should be established.

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Atopic dermatitis disease registry in Japanese adult patients with moderate to severe atopic dermatitis (ADDRESS‐J): Baseline characteristics,treatment history and disease burden

Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.     

The Utility of Shear-Wave Elastography in the Evaluation of Myositis

Changes in muscle elasticity are expected in patients with untreated myositis. The purpose of this study was to define the accuracy of shear-wave elastography (SWE) in diagnosing myositis. This case control study included 21 patients (mean age, 49.4 y; 12 women) with myositis who underwent SWE, magnetic resonance imaging (MRI) and biopsy of the involved muscle group. SWE was performed accordingly in a control group (n = 24; mean age, 51.2 y; 8 women). Blood tests consisted of creatine kinase (CK) and aldolase. Two operators performed SWE in longitudinal and transverse planes of muscular fibers, quantifying the mean shear-wave velocity (SWV) and the pattern of stiffness. On MRI, short-TI inversion recovery (STIR) signal hyperintensity and T1 contrast enhancement of muscle was considered diagnostic for myositis. The patient group suffered from different types of myositis (nine patients with polymyositis, eight with dermatomyositis and four with other types of myositis). Blood tests showed significantly increased CK and aldolase values in patients with myositis (p < 0.001 and p < 0.0001). MRI showed a sensitivity of 0.95. In the patient group, the mean SWVs of longitudinal and transverse measurements were 2.8 ± 1.4 m/s and 3.1 ± 1.2 m/s, respectively. In the control group, SWVs were 2.3 ± 0.5 m/s and 2.4 ± 0.5 m/s, respectively. The difference between transverse measurements was significant (p = 0.02). Increased heterogeneity as a marker for myositis in transverse SWE showed a sensitivity of 0.8, specificity of 0.79, positive predictive value (PPV) of 0.76 and negative predictive value (NPV) of 0.82. Inter-observer difference was very low (κ = 0.92). Increased heterogeneity in both planes compared with histologic results showed a sensitivity of 0.56, specificity of 0.93, PPV of 0.91 and NPV of 0.62. Spearman correlation between CK <1000 U/L and SWE was 0.54. In conclusion, transverse orientation SWE may serve as an imaging biomarker for the diagnosis of myositis through the display of a heterogeneous pattern and increased absolute SWV values of inflamed muscles.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Intrinsic unfoldase/foldase activity of the chaperonin GroEL directly demonstrated using multinuclear relaxation-based NMR

The prototypical chaperonin GroEL assists protein folding through an ATP-dependent encapsulation mechanism. The details of how GroEL folds proteins remain elusive, particularly because encapsulation is not an absolute requirement for successful re/folding. Here we make use of a metastable model protein substrate, comprising a triple mutant of Fyn SH3, to directly demonstrate, by simultaneous analysis of three complementary NMR-based relaxation experiments (lifetime line broadening, dark state exchange saturation transfer, and Carr–Purcell–Meinboom–Gill relaxation dispersion), that apo GroEL accelerates the overall interconversion rate between the native state and a well-defined folding intermediate by about 20-fold, under conditions where the “invisible” GroEL-bound states have occupancies below 1%. This is largely achieved through a 500-fold acceleration in the folded-to-intermediate transition of the protein substrate. Catalysis is modulated by a kinetic deuterium isotope effect that reduces the overall interconversion rate between the GroEL-bound species by about 3-fold, indicative of a significant hydrophobic contribution. The location of the GroEL binding site on the folding intermediate, mapped from ¹⁵N, ¹H_N, and ¹³C_methyl relaxation dispersion experiments, is composed of a prominent, surface-exposed hydrophobic patch.Chaperone networks have evolved to correctly fold native proteins and protect against the damaging effects of misfolding and aggregation on protein homeostasis (1, 2). The chaperonins, a ubiquitous subclass of chaperones, are barrel-shaped, multisubunit assemblies composed of two ring cavities, transiently capped by either an extrinsic cochaperone or a built-in lid domain, which assist protein folding in an ATP-dependent manner (3–6). Although the encapsulation mechanism and accompanying allosteric transitions driven by ATP have been extensively studied, the details of how chaperonins fold proteins remain elusive (3, 6, 7). Further, encapsulation does not appear to be an absolute requirement for successful re/folding (8). Moreover, hydrogen/deuterium exchange experiments on several protein substrates (9–12) and fluorescence-based refolding experiments (13) suggest that the prototypical chaperonin GroEL may possess intrinsic unfoldase activity. Here we take advantage of a monomeric, nonaggregating, well-defined system—a triple mutant of the Fyn SH3 domain that exists in dynamic equilibrium between the major native state and a sparsely populated folding intermediate (14, 15)—to directly demonstrate, using NMR relaxation-based methods (16), the ability of apo GroEL to accelerate the interconversion between these two states by almost three orders of magnitude. Simultaneous analysis of lifetime line-broadening (17), dark state exchange saturation transfer (DEST) (18), and Carr–Purcell–Meinboom–Gill (CPMG) relaxation dispersion (19) data permitted us to determine the catalytic rate constants and ascertain the location of the GroEL binding site on the folding intermediate under conditions where the population of GroEL-bound native and intermediate states is less than 1%. Further, GroEL unfoldase/foldase activity is modulated by SH3 deuteration, indicating that catalysis of the exchange reaction between folded and intermediate states involves direct interaction of the substrate with the walls of the GroEL chambers. These results provide a basis for how chaperonins, in the absence of cofactors and encapsulation, may be able to passively protect the cell from the deleterious effects of misfolded protein accumulation.     

Brief relaxation versus music distraction in the treatment of dental anxiety: a randomized controlled clinical trial

BACKGROUND: Dental anxiety is a significant cause of poor dental health. Because patients often prefer nonpharmacological interventions, the clinical effectiveness of clearly structured approaches is of particular interest. METHODS: This prospective randomized controlled study compares a brief relaxation method (BR) with music distraction (MD) and with a control group (C). The authors randomly assigned 90 patients with dental anxiety to BR, MD or C groups. They assessed the outcomes by means of the state anxiety subscale of the State-Trait Anxiety Inventory. RESULTS: Both BR and MD reduced dental anxiety significantly. In contrast, patients in the C group did not exhibit a significant change in their anxiety level. BR was significantly superior to MD. Stratification according to the patient's general level of dental anxiety revealed that BR also was particularly effective in highly anxious subjects, whereas MD did not have a clinically relevant effect on these subjects. CONCLUSIONS: BR appears to be a safe, economically sound and effective nonpharmacological approach to the short-term reduction of dental anxiety. Additional investigations are needed to validate these findings in a larger clinical trial and to determine the long-term effects of this intervention. CLINICAL IMPLICATIONS: Relaxation techniques are a pragmatic, effective and cost-saving method of facilitating dental treatment in anxious patients.     

Pediatric transplantation in Europe during the COVID-19 pandemic: Early impact on activity and healthcare

The current pandemic SARS-CoV-2 has required an unusual allocation of resources that can negatively impact chronically ill patients and high-complexity procedures. Across the European Reference Network on Pediatric Transplantation (ERN TransplantChild), we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified and restricted to selected ones, and the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients, and their families.