The role of different acetabular morphologies on patient-reported outcomes following periacetabular osteotomy in borderline hip dysplasia.

INTRODUCTION: The treatment option for borderline hip dysplasia (BHD) includes hip arthroscopy and periacetabular osteotomy (PAO). To the present day the controversial discussion remains, which intervention to prefer. Literature reports supporting an educated choice are scare, based on small patient cohorts and do not address the variability of acetabular morphology. Consequently, we intended to report PAO outcomes, from patients diagnosed with BHD, dependent on acetabular morphology, in a large patient cohort and aimed to define risk factors for poor clinical results and patient satisfaction. MATERIALS AND METHODS: A prospective monocentre study was conducted. Patients enrolled underwent PAO for symptomatic BHD (LCEA, 18°-25°). A total of 107 hips were included with 94 complete data sets were available for evaluation with a minimum follow-up of 1 year and a mean follow-up of 2.3 years. The mean age was 31 ± 8.2 years, and 81.3% were female. As the primary outcome measure, we utilized the modified Harris hip score (mHHS) with minimal clinically important change (MCID) of eight to define clinical failure. Results were compared after a comprehensive radiographic assessment distinguishing between lateral deficient vs. anterior/posterolateral deficient acetabular and stable vs. unstable hip joints. RESULTS: Overall, clinical success was achieved in 91.5% of patients and the mHHS improved significantly (52 vs. 84.7, p < 0.001). Eight hips failed to achieve the MCID and four had radiographic signs of overcorrection. Comparing variable joint morphologies, the rate of clinical success was higher in patients with an anterior/posterolateral deficient acetabular covarage compared to lateral deficient acetabular (95.2% vs. 90.4%). tThe highest rate of clinical failure was recorded in unstable hip joints (85.7% vs. 92.5% in stable hips). CONCLUSIONS: This study demonstrates that PAO is an effective means to treat symptomatic BHD with variable acetabular morphologies, achieving a clinical success in 91.5% of all patients. To maintain a high level of safety and patient satisfaction technical accuracy appears crucial.

Psychological Factors as Risk Contributors for Poor Hip Function after Periacetabular Osteotomy.

Psychologic comorbidities have been identified as risk factors for poor outcomes in orthopedic procedures, but their influence on the outcome of hip-preserving periacetabular osteotomy (PAO) remains uncertain. This retrospective cohort study aimed to assess the impact of patients' psychological health on the outcome of PAO in patients with hip dysplasia (HD) and acetabular retroversion (AR). The study included 110 patients undergoing PAO for HD or AR between 2019 and 2021. Standardized questionnaires were administered to assess psychological factors, postoperative hip function, and activity level (mean follow-up: 25 months). Linear regression analyses were used to examine the associations between psychological factors and postoperative hip function and activity level. Both HD and AR patients showed improved postoperative hip function and activity levels. Linear regression analyses revealed that depression significantly impaired postoperative outcomes in both groups, whereas somatization negatively influenced the outcome in AR patients. General health perceptions significantly contributed to an improved postoperative outcome. These findings highlight the importance of concomitantly addressing psychologically relevant factors in order to improve patient outcomes after PAO procedures. Future prospective studies should continue to investigate the impact of various psychological factors and explore possibilities of incorporating psychological support into routine postoperative care for these patient cohorts.

The roles of toll-like receptor 4, CD33, CD68, CD69, or CD147/EMMPRIN for monocyte activation by the DAMP S100A8/S100A9.

The S100A8/A9 heterocomplex is an abundant damage-associated molecular pattern and mainly expressed by monocytes, inflammatory activated keratinocytes and neutrophilic granulocytes. The heterocomplex as well as the heterotetramer are involved in a variety of diseases and tumorous processes. However, their detailed mode of action and especially which receptors are involved hereby remains to be fully revealed. Several cell surface receptors are reported to interact with S100A8 and/or S100A9, the best studied being the pattern recognition receptor TLR4. RAGE, CD33, CD68, CD69, and CD147, all of them are involved as receptors in various inflammatory processes, are also among these putative binding partners for S100A8 and S100A9. Interactions between S100 proteins and these receptors described so far come from a wide variety of cell culture systems but their biological relevance in vivo for the inflammatory response of myeloid immune cells is not yet clear. In this study, we compared the effect of CRISPR/Cas9 mediated targeted deletion of CD33, CD68, CD69, and CD147 in ER-Hoxb8 monocytes on S100A8 or S100A9 induced cytokine release with TLR4 knockout monocytes. Whereas deletion of TLR4 abolished the S100-induced inflammatory response in monocyte stimulation experiments with both S100A8 and S100A9, knockouts of CD33, CD68, CD69, or CD147 revealed no effect on the cytokine response in monocytes. Thus, TLR4 is the dominant receptor for S100-triggered inflammatory activation of monocytes.

European Respiratory Society statement for defining respiratory exacerbations in children and adolescents with bronchiectasis for clinical trials.

Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6-7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.

Conversational Agents as Mediating Social Actors in Chronic Disease Management Involving Health Care Professionals, Patients, and Family Members: Multisite Single-Arm Feasibility Study.

BACKGROUND: Successful management of chronic diseases requires a trustful collaboration between health care professionals, patients, and family members. Scalable conversational agents, designed to assist health care professionals, may play a significant role in supporting this collaboration in a scalable way by reaching out to the everyday lives of patients and their family members. However, to date, it remains unclear whether conversational agents, in such a role, would be accepted and whether they can support this multistakeholder collaboration. OBJECTIVE: With asthma in children representing a relevant target of chronic disease management, this study had the following objectives: (1) to describe the design of MAX, a conversational agent-delivered asthma intervention that supports health care professionals targeting child-parent teams in their everyday lives; and (2) to assess the (a) reach of MAX, (b) conversational agent-patient working alliance, (c) acceptance of MAX, (d) intervention completion rate, (e) cognitive and behavioral outcomes, and (f) human effort and responsiveness of health care professionals in primary and secondary care settings. METHODS: MAX was designed to increase cognitive skills (ie, knowledge about asthma) and behavioral skills (ie, inhalation technique) in 10-15-year-olds with asthma, and enables support by a health professional and a family member. To this end, three design goals guided the development: (1) to build a conversational agent-patient working alliance; (2) to offer hybrid (human- and conversational agent-supported) ubiquitous coaching; and (3) to provide an intervention with high experiential value. An interdisciplinary team of computer scientists, asthma experts, and young patients with their parents developed the intervention collaboratively. The conversational agent communicates with health care professionals via email, with patients via a mobile chat app, and with a family member via SMS text messaging. A single-arm feasibility study in primary and secondary care settings was performed to assess MAX. RESULTS: Results indicated an overall positive evaluation of MAX with respect to its reach (49.5%, 49/99 of recruited and eligible patient-family member teams participated), a strong patient-conversational agent working alliance, and high acceptance by all relevant stakeholders. Moreover, MAX led to improved cognitive and behavioral skills and an intervention completion rate of 75.5%. Family members supported the patients in 269 out of 275 (97.8%) coaching sessions. Most of the conversational turns (99.5%) were conducted between patients and the conversational agent as opposed to between patients and health care professionals, thus indicating the scalability of MAX. In addition, it took health care professionals less than 4 minutes to assess the inhalation technique and 3 days to deliver related feedback to the patients. Several suggestions for improvement were made. CONCLUSIONS: This study provides the first evidence that conversational agents, designed as mediating social actors involving health care professionals, patients, and family members, are not only accepted in such a "team player" role but also show potential to improve health-relevant outcomes in chronic disease management.

Obstructive Sleep Apnoea in Children and Adolescents with Ehlers-Danlos Syndrome.

BACKGROUND: In Ehlers-Danlos syndrome (EDS), a group of monogenic disorders affecting connective tissues, obstructive sleep apnoea (OSA) is highly prevalent in adults. The prevalence of OSA in children with EDS is unknown. OBJECTIVES: This prospective cross-sectional study aimed at determining the prevalence of OSA in paediatric EDS patients. METHODS: Children with EDS (n = 24) were recruited from the Children's Hospital Zurich and matched to healthy controls. Participants completed home respiratory polygraphy and questionnaires (Sleep-Related Breathing Disorder Scale [SRBD], Epworth Sleepiness Scale [ESS], and Child Health Questionnaire [CHQ]). The American Academy of Sleep Medicine criteria were applied for OSA diagnosis (obstructive apnoea-hypopnoea index [oAHI] ≥1/h). Conditional logistic regression was used to compare the prevalence of OSA and to adjust for possible confounding. RESULTS: OSA was found in 42% of paediatric EDS patients and in 13% of matched controls (OR = 4.5, 95% CI = 0.97-20.83, p = 0.054). The median oAHI was higher in EDS patients than in controls (0.77/h, IQR = 0.19-1.76, vs. 0.24/h, IQR = 0.0-0.60, p < 0.001 adjusted for age, sex, and BMI z-score). EDS patients had lower scores in most CHQ scales and higher SRBD and ESS scores than controls (0.26, IQR = 0.1-0.35, vs. 0.07, IQR = 0-0.19, p = 0.004); 7 ± 4 vs. 5 ± 4, p = 0.033, respectively). CONCLUSION: OSA is a previously underestimated EDS-related complication increasing disease burden.

Diagnosis and Management of Asthma - The Swiss Guidelines.

The Global Initiative for Asthma (GINA) is a network of individuals, organizations, and public health officials that was established to disseminate information about the care of patients with asthma and to improve asthma care. The GINA ("Global Strategy for Asthma Management and Prevention") report has been updated annually since 2002. Due to new knowledge and therapeutic development in the field, the Swiss Respiratory Society felt the need to provide a new document that is based on both the available literature and the recommendations of the 2016 GINA report. Key new features of the 2016 GINA report include a "new" definition of asthma, underscoring its heterogeneous nature, and the core elements of variable symptoms and variable expiratory airflow limitation; the importance of confirming the diagnosis of asthma in order to minimize both under- and overtreatment; practical tools for the assessment of symptom control and risk factors for adverse outcomes; a comprehensive approach to asthma management that acknowledges the foundational role of inhaled corticosteroid therapy, but also provides a framework for individualizing patient care; an emphasis on maximizing the benefit of available medications by addressing common problems such as incorrect inhaler technique and poor adherence; a continuum of care for worsening asthma, starting with early self-management and progressing to primary care or acute care management; and diagnosis of the asthma/chronic obstructive pulmonary disease overlap syndrome. This document is meant to advice the key stakeholders on the diagnosis and management of asthma and highlights the need to individualize the care of each and every asthmatic patient.

Impaired type I and type III interferon induction and rhinovirus control in human cystic fibrosis airway epithelial cells.

BACKGROUND: Rhinoviruses are important triggers of pulmonary exacerbations and possible contributors to long-term respiratory morbidity in cystic fibrosis (CF), but mechanisms leading to rhinovirus-induced CF exacerbations are poorly understood. It is hypothesised that there is a deficient innate immune response of the airway epithelium towards rhinovirus infection in CF. METHODS: Early innate immune responses towards rhinoviruses (RV-16, major-type and RV-1B, minor-type) in CF and non-CF bronchial epithelial cell lines and primary nasal and bronchial epithelial cells from patients with CF (n=13) and healthy controls (n=24) were studied. RESULTS: Rhinovirus RNA expression and virus release into supernatants was increased more than tenfold in CF cells compared with controls. CF cells expressed up to 1000 times less interferon (IFN) type I (ß) and type III (λ) mRNA and produced less than half of IFN-ß and IFN-λ protein compared with controls. In contrast, interleukin 8 production was not impaired, indicating a selective deficiency in the innate antiviral defence system. Deficient IFN production was paralleled by lower expression of IFN-stimulated genes including myxovirus resistance A, 2',5'-oligoadenylate synthetase, viperin and nitric oxide synthase 2. Addition of exogenous type I and III IFNs, particularly IFN-ß, restored antiviral pathways and virus control in CF cells, underscoring the crucial role of these molecules. CONCLUSIONS: This study describes a novel mechanism to explain the increased susceptibility of patients with CF to rhinovirus infections. A profound impairment of the antiviral early innate response in CF airway epithelial cells was identified, suggesting a potential use of IFNs in the treatment of rhinovirus-induced CF exacerbations.

Correlation of spirometry and symptom scores in childhood asthma and the usefulness of curvature assessment in expiratory flow-volume curves.

BACKGROUND: Spirometry, and in particular forced expiratory volume in the first second (FEV(1)), are standard tools for objective evaluation of asthma. However, FEV(1) does not correlate with symptom scores, and hence its value in the assessment of childhood asthma may be limited. Therefore, some clinicians subjectively assess the presence of curvature in the maximum expiratory flow-volume (MEFV) curves obtained from spirometry, where concave patterns are observable despite normal FEV(1) values. OBJECTIVE: To evaluate the usefulness of subjective and objective measures of the curvature in the descending phase of the MEFV curve for the assessment of asthma. METHODS: We obtained symptom scores and performed spirometry in 48 patients with asthma (21 females, mean +/- SD age 10.8 +/- 2.4 y). We measured FEV(1), the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC), maximum expiratory flow at one quarter of the way, and at halfway, through the forced expiratory maneuver (MEF(25) and MEF(50), respectively), and maximum expiratory flow in the middle half of the forced expiratory maneuver (MEF(25-75)). Expiratory obstruction was ranked independently by 3 pediatric pulmonologists, by subjective assessment of the MEFV curve. In addition, the curvature of the descending limb of the MEFV curve was quantitatively estimated by introducing an "average curvature index." RESULTS: No significant correlations were found between FEV(1), MEF(50), MEF(25), and MEF(25-75,) respectively, and symptom score (r = -0.22, p = 0.14; r = -0.23, p = 0.11; r = -0.28, p = 0.057; r = -0.27, p = 0.06). A weak correlation was found for FEV(1)/FVC and symptom score (r = -0.33, p = 0.021). However, quantitatively determined average curvature index (ACI) correlated significantly better with measured symptom scores (r = 0.53, p < 0.001) and were in good agreement with the assessment of expiratory obstruction from subjective curvature assessment. CONCLUSIONS: Our general findings show that individual lung function variables do not correlate well with symptoms, whereas subjective curvature assessment is thought to be helpful. With the average curvature index we have illustrated a potential clinical usefulness of quantifying the curvatures of MEFV curves.

Deposition of aerosols in infants and children.

There is still a lack of knowledge in the field of aerosol therapy in children, particularly in young children. The amount of drug delivered from a commercially available inhalation device that reaches the lungs of children is generally low. The choice of an optimal combination of delivery device and drug formulation based on individual patient related factors is crucial. Aerosols with a small MMAD and a narrow GSD are required for a sufficient inhalation therapy in early childhood. The development of combinations of delivery devices and drug formulations fulfilling the requirements for an efficient inhalation therapy in young children is likely to increase the therapeutical options in this age group.

Frequency and clinical features of visceral malignancy in a consecutive case series of patients with periocular sebaceous gland carcinoma.

PURPOSE: To report the frequency and clinical features of internal visceral malignancy in an unselected series of patients with sebaceous gland carcinoma (SGC). METHODS: A non-comparative retrospective case series of consecutive patients with a histologically proven diagnosis of periocular sebaceous cell carcinoma treated at the University Eye Hospital, University of Erlangen-Nürnberg between 1981 and 2000. RESULTS: Twenty-three patients were identified, each with one tumor. Men and women were almost equally affected with a mean age at diagnosis of 62 years (range 37-83 years). The majority of tumors were located in the upper lid, but five tumors were situated in the lower lid or caruncle. In 22 of the 23 patients the diagnosis at referral was either incorrect or not suspected. In all cases, the SGC was treated by surgical excision. In the systems review, 11 of the 23 patients (48%) had evidence of previous systemic malignancy, the most common being colorectal cancer followed by liver and bronchial carcinoma. Forty-five percent of patients with SGC and internal visceral malignancy eventually died as a result of their tumors. CONCLUSION: Periocular SGC remains an underdiagnosed entity for which a high level of clinical suspicion is critical for early recognition. Almost half the patients additionally had an internal visceral malignancy. Internal visceral malignancy in unselected patients with SGC may be more common and have a more guarded prognosis than has been appreciated.

Loss of fragile histidine triad (FHIT) expression and microsatellite instability in periocular sebaceous gland carcinoma in patients with Muir-Torre syndrome.

PURPOSE: To report fragile histidine triad expression and microsatellite instability in periocular sebaceous gland carcinoma. DESIGN: Interventional case series. METHODS: Biopsy specimens of periocular sebaceous gland carcinoma obtained from six patients (mean age, 60 +/- 17 years; range, 38 to 83 years, 5 male, 1 female) with Muir-Torre syndrome and histopathologically proven sebaceous gland carcinoma were studied immunohistochemically for the presence of fragile histidine triad protein. Polymerase chain reaction-based analysis of the markers BAT25, BAT26, D2S123, D5S346, and D17S250 was performed for microsatellite instability in tumorous and matching normal tissues. RESULTS: Fragile histidine triad protein was detectable in the sebaceous gland carcinoma from one patient with microsatellite instability. It was not detectable in sebaceous gland carcinoma specimens from five patients without any evidence of microsatellite instability. CONCLUSION: Inactivation of fragile histidine triad tumor suppressor gene or inactivation of the mismatch-repair system resulting in microsatellite instability may contribute to the development of periocular sebaceous gland carcinoma in Muir-Torre syndrome.