Early postoperative gain in activity levels of lower extremity sarcoma survivors positively affects long-term physical activity and performance.

PURPOSE: Little is known about the effect of sports activity levels on health-related quality of life (HRQOL) in long-term survivors of lower-extremity sarcoma. METHODS: Eighty-three long-term survivors of bone and soft tissue sarcoma of the lower extremities with a median follow-up of 14 (range: 5-35) years completed the University of California and Los Angeles (UCLA) activity scores before tumor resection, 1 year after surgery and at the latest follow-up, as well as a Short Form 36 (SF-36) health survey at the latest follow-up. Simple linear regression models as well as stepwise variable selection with Akaike information criterion (AIC) were undertaken. RESULTS: The preoperative UCLA activity level (median: 9, range: 2-10) dropped to a median of 4 (range: 1-10) 1 year after surgery before increasing to a score of 6 (range: 2-10) 5 years after surgery. The long-term SF-36 physical health component summary score (PCS) was 49 (SD: 9), and the mental health component summary score (MCS) was 54 (SD: 7). A linear model with stepwise variable selection identified a negative correlation of PCS with age at surgery (estimate: -0.2; p = 0.02), UCLA score at the last follow-up (estimate: 1.4; p = 0.02) and UCLA score 1 year after surgery (estimate: 1.0; p = 0.02). CONCLUSION: As not only the final activity levels but also the status immediately after surgery affect the PCS, higher early activity levels should be a goal of modern rehabilitation after sarcoma treatment. Further studies are needed to weigh the potential postoperative risks of higher sport activity levels against the benefits described in this study. LEVEL OF EVIDENCE: Level 4.

A six-year teaching life supportive first aid program to eventually generate peer trainer pupils: a prospective case control study.

BACKGROUND: Out of hospital cardiac arrest is a life-threatening condition. To improve the chances of survival, lay-person cardio-pulmonary-resuscitation (CPR) is a crucial factor. Many bystanders fail to react appropriately, even if life supporting first aid (LSFA) programs and campaigns including CPR tried to increase the handling of basic cardiac life support. To achieve an enhanced learning of CPR a pupil's grade after grade teaching program was established in a school with medical students. METHODS: The learning of CPR was investigated in a prospective, case-controlled study at an international school. Pupils (12 ± 3 years old) joining our LSFA courses (n = 538, female: 243, attendance for evaluation: 476) were compared to a control group (n = 129, female: 52, attendance for evaluation: 102). Surveys and quality of CPR (QCPR%) through a computer linked "Resusci Anne" dummy were compared with Chi-squared tests, t-tests pair wisely, and by one-way ANOVA. RESULTS: Knowledge and skills on the "Resusci Anne" were significantly better in trained grade 9 pupils compared to the control group (QCPR, 59 vs. 25%). The number of LSFA courses each grade 9 student had, correlated with improved practical performance (r2 = 0.21, p < 0.001). The willingness to deliver CPR to strangers increased with improved practical performance. Attitudes towards performing CPR were high in all participating grades. CONCLUSION: Repetitive teaching LSFA to grade 5-9 pupil's grade after grade by medical students has been successfully established. Pupils who finish the program will eventually be able to teach LSFA to younger students. This is furthermore a good way of sharing a "learning by teaching" role and it enables to have more pupils as trainers who can provide instruction to a larger number of pupils with the purpose of having a better-trained population in LSFA.

Impact of COVID-19 lockdown on routine oncology versus emergency care at a high volume cancer centre.

BACKGROUND: We investigated the influence of population-wide COVID-19 lockdown measures implemented on 16, March 2020 on routine and emergency care of cancer outpatients at a tertiary care cancer centre in Vienna, Austria. METHODS: We compared the number/visits of cancer outpatients receiving oncological therapies at the oncologic day clinic (DC) and admissions at the emergency department (ED) of our institution in time periods before (pre-lockdown period: 1 January - 15 March 2020) and after (post-lockdown period: 16 March- 31 May 2020) lockdown implementation with the respective reference periods of 2018 and 2019. Additionally, we analysed Emergency Severity Index (ESI) score of unplanned cancer patient presentations to the ED in the same post-lockdown time periods. Patient outcome was described as 3-month mortality rate (3-MM). RESULTS: In total, 16 703 visits at the DC and 2664 patient visits for the respective time periods were recorded at the ED. No decrease in patient visits was observed at the DC after lockdown implementation (P = .351), whereas a substantial decrease in patient visits at the ED was seen (P < .001). This translates into a 26%-31% reduction of cancer-related patient visits per half month after the lockdown at the ED (P < .001 vs. 2018 + 2019). There was no difference in the distribution of ESI scores at ED presentation (P = .805), admission rates or 3-MM in association with lockdown implementation (P = .086). CONCLUSION: We demonstrate the feasibility of maintaining antineoplastic therapy administration during the COVID-19 pandemic. However, our data underline the need for adapted management strategies for emergency presentations of cancer patients.

Combined anterior talofibular ligament (ATFL) lesion and anterolateral syndesmotic impingement after ankle sprain trauma in runners.

Anterior inferior tibiofibular ligament (AITFL) lesion have been shown to result in proliferation of cicatricial tissue ; concomitant insufficiency of the anterior talofibular ligament (ATFL) and AITFL Lesion may cause anterolateral syndesmotic impingement in the ankle joint of runners. Twenty-two runners with suspected syndesmotic impingement after ankle sprain were included in the study. An MRI of the ankle joint was performed followed by arthroscopy. Arthroscopy revealed an ATFL lesion in 20 patients (87%) and anterolateral syndesmotic impingement in 17 patients (77%). An ATFL lesion was detected in all patients with anterolateral syndesmotic impingement. The sensitivity of MRI was 24% (4 patients) on detecting anterolateral syndesmotic impingement, and 25% (5 patients) on ATFL lesion. A traumatic sprain of the ankle frequently results in a combined ATFL lesion and anterolateral syndesmotic impingement in runners. The abilities of MRI to detect this combined pathology are limited. Arthroscopy of the ankle joint should be performed. Study Design : Case series ; level of evidence 4.

Galectin-1 Couples Glycobiology to Inflammation in Osteoarthritis through the Activation of an NF-κB-Regulated Gene Network.

Osteoarthritis is a degenerative joint disease that ranks among the leading causes of adult disability. Mechanisms underlying osteoarthritis pathogenesis are not yet fully elucidated, putting limits to current disease management and treatment. Based on the phenomenological evidence for dysregulation within the glycome of chondrocytes and the network of a family of adhesion/growth-regulatory lectins, that is, galectins, we tested the hypothesis that Galectin-1 is relevant for causing degeneration. Immunohistochemical analysis substantiated that Galectin-1 upregulation is associated with osteoarthritic cartilage and subchondral bone histopathology and severity of degeneration (p < 0.0001, n = 29 patients). In vitro, the lectin was secreted and it bound to osteoarthritic chondrocytes inhibitable by cognate sugar. Glycan-dependent Galectin-1 binding induced a set of disease markers, including matrix metalloproteinases and activated NF-κB, hereby switching on an inflammatory gene signature (p < 10(-16)). Inhibition of distinct components of the NF-κB pathway using dedicated inhibitors led to dose-dependent impairment of Galectin-1-mediated transcriptional activation. Enhanced secretion of effectors of degeneration such as three matrix metalloproteinases underscores the data's pathophysiological relevance. This study thus identifies Galectin-1 as a master regulator of clinically relevant inflammatory-response genes, working via NF-κB. Because inflammation is critical to cartilage degeneration in osteoarthritis, this report reveals an intimate relation of glycobiology to osteoarthritic cartilage degeneration.

ROLE OF ADDITIONAL DEXAMETHASONE FOR THE MANAGEMENT OF PERSISTENT OR RECURRENT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION UNDER RANIBIZUMAB TREATMENT.

PURPOSE: To assess the efficacy of a combination therapy of intravitreal ranibizumab together with a dexamethasone implant in comparison with ranibizumab monotherapy in neovascular age-related macular degeneration. METHODS: Forty eyes of recurrent or persistent neovascular age-related macular degeneration were included in this prospective study. Patients were randomly assigned to two groups. Based on a pro re nata treatment regimen, the first group received intravitreal ranibizumab monotherapy (IVM). The second group received a combination of intravitreal dexamethasone implant and ranibizumab (intravitreal combination [IVC]) at baseline and was retreated with ranibizumab as needed. A second dexamethasone implant was allowed for retreatment after at least 6 months. Retreatment criteria included evidence of subretinal fluid, cystoid macular edema or new hemorrhage, and/or a visual acuity decrease of 5 Early Treatment Diabetic Retinopathy Study letters. RESULTS: During 12 months, a mean of 7.95/5.5 (IVM/IVC; P = 0.042) retreatments were given. The median time until first retreatment differed significantly between the groups (P = 0.004). Functional variables could be maintained in both groups with no differences between them. Visual acuity changed from 62 letters at baseline to 67 at Month 12 in the IVM and remained stable at 68 letters in the IVC group (P = 0.68); macular sensitivity changed from 6.95 dB to 7.01 dB in IVM and from 7.24 dB to 7.12 dB in IVC (P = 0.4). Central retinal thickness decreased, however, with no difference between the groups (P = 0.38). In the IVM/IVC group, 11/12 (55/60%) patients were phakic at the time of study entry. One (9%) patient from the IVM and 4 (33%) from the IVC group were referred to cataract surgery after study completion (P = 0.4). CONCLUSION: This pilot study indicates combined therapy to delay retreatment in patients with persistent/recurrent neovascular age-related macular degeneration and an overall reduction in required ranibizumab retreatments compared with ranibizumab monotherapy with consistent functional outcomes.

Do Patients After Chondrosarcoma Treatment Have Age-appropriate Bone Mineral Density in the Long Term?

BACKGROUND: In long-term survivors of osteosarcoma and Ewing sarcoma treated with the addition of radio- and chemotherapy, low bone mineral density (BMD) and fractures have been observed, presumably resulting from these adjuvants. Because patients with chondrosarcoma usually are not treated with conventional adjuvant treatment, observation of low BMD in patients with chondrosarcoma presumably would be the result of other mechanisms. However, BMD in patients with a history of chondrosarcoma has not been well characterized. QUESTIONS/PURPOSES: The aim of our study was to address the following questions: (1) Do long-term survivors of chondrosarcoma have normal BMD and, if not, which factors contribute to low BMD? (2) Is there a greater risk of fracture and does the Fracture Risk Assessment Tool (FRAX(®)) score reflect fracture likelihood? METHODS: All known patients with a history of chondrosarcoma treated at our institution before 2006 were identified. Of 127 patients believed to be alive at the time of this study, 30 agreed to participate in this study (11 females, 19 males; mean age at surgery, 39 ± 12 years; mean followup, 12 ± 5 years). With the data available, the 30 participants were not different from the 97 nonparticipants in terms of age, sex, BMI, tumor grade, tumor location (axial versus appendicular, lower extremity versus elsewhere), and use of any treatment known to influence osteopenia (chemotherapy, lower extremity surgery). BMD was measured and history of fractures was assessed using a questionnaire. The patients´ BMD measurements in this study were sex- and age-matched with a normative sex- and age-categorized reference population reported by Kudlacek et al. Associations were tested by univariate regressions and ANOVAs of all measures of BMD and eligible oncologic and demographic factors. RESULTS: Eighteen of 30 (60%) patients had a pathologic BMD according to the WHO dual-energy x-ray absorptiometry definition, 15 (50%) had osteopenia, and three (10%) had osteoporosis. T-scores in the study cohort were lower than reference values for the femur neck (mean difference, 0.64; 95% CI, 0.27-1.01; p < 0.0015), but not for the spine (mean difference, 0.39; 95% CI, -0.06 to 0.84; p = 0.09). Thirteen patients (45%) reported a history of fractures not distinguishing between low and high impact. The incidence of fractures was 2.8 greater than expected from a comparison with a published microcensus survey of the Austrian population. No effect of the FRAX(®) score on fracture risk could be identified (p = 0.057). CONCLUSIONS: Long-term survivors of chondrosarcoma appear to be at greater risk for having low BMD develop than the healthy population. Although these results are preliminary and based on a very small sampling of patients, if they can be confirmed in larger studies, BMD assessment by dual-energy x-ray absorptiometry might be considered as these patients are followed posttreatment by sarcoma care units. The reasons for low BMD still must be elucidated. LEVEL OF EVIDENCE: Level IV, prognostic study.

Peroneal tendinosis as a predisposing factor for the acute lateral ankle sprain in runners.

PURPOSE: A painful episode in the region of the peroneal tendons, within the retromalleolar groove, is a common precipitating event of an acute lateral ankle sprain. A forefoot striking pattern is suspected to cause peroneal tendinosis. The aim of this study is to analyse the role of peroneal tendinosis as a predisposing factor for ankle sprain trauma in runners. METHODS: Fifty-eight runners who had experienced acute ankle sprain trauma, with pre-existing pain episodes for up to 4 weeks in the region of the peroneal tendons, were assessed clinically. Fractures were excluded by conventional radiography. An magnetic resonance imaging (MRI) scan had been performed within 14 days after the traumatic event and was subsequently evaluated by two experienced radiologists. RESULTS: MRI revealed peroneal tendinosis in 55 patients (95% of the total study population). Peroneus brevis (PB) tendinosis was found in 48 patients (87% of all patients with peroneal tendinosis), and peroneus longus (PL) tendinosis was observed in 42 cases (76%). Thirty-five patients (64%) had combined PB and PL tendinosis. A lesion of the anterior talofibular ligament was found to be the most common ligament injury associated with peroneal tendinosis (29 cases; 53%), followed by a lesion of the calcaneofibular ligament (16 cases; 29%) and a lesion of the posterior tibiofibular ligament (13 cases; 24%). CONCLUSION: The results of this study reflect the correlation between peroneal tendinosis and ankle sprain trauma. Injuries of one or more ligaments are associated with further complications. A period of rest or forbearance of sports as well as adequate treatment of the peroneal tendinosis is essential to prevent subsequent ankle injuries, especially in runners. Modification of the running technique would also be beneficial. LEVEL OF EVIDENCE: IV.

Effect of extracorporeal shockwave therapy (ESWT) on pulpal blood flow after orthodontic treatment: a randomized clinical trial.

OBJECTIVES: The effect of non-invasive extracorporeal shockwaves on pulpal blood flow in orthodontic patients who have undergone active treatment was investigated. MATERIALS AND METHODS: Seventy-two adult patients were enrolled in the clinical trial and allocated by block randomization to a treatment or a placebo group at a 1:1 ratio. The patients were required to be otherwise healthy. Blinding was performed for the subjects and the outcome assessor. The region of interest was the mandibular incisors and canines, which were vital, unrestored, and had experienced no trauma. The active treatment group received a single shockwave treatment with 1000 impulses at 0.19-0.23 mJ/mm(2) while the placebo group was treated with a deactivated shockwave applicator but acoustic sham. Pulpal blood flow was evaluated four times over a period of 6 months starting from the day of bracket removal, using a laser Doppler device. RESULTS: Thirty patients were evaluated in each group. Orthodontic patients who have undergone active treatment tend to have high levels of pulpal blood flow which decrease over a period of 6 months. Pulpal blood flow did not differ significantly over 6 months between the placebo and treatment group. Shockwave treatment was associated with no significant effect in respect of tooth type, age, sex, or mean blood pressure, and had no unintended pernicious effects. CONCLUSIONS: Extracorporeal shockwaves had no statistically significant effect on pulpal blood flow. Multiple applications of ESWT in a pathological setup may be needed in future studies to demonstrate significant differences. CLINICAL RELEVANCE: The absence of any adverse effects justifies further principal investigations of the use of shockwave treatment in the oral cavity.

Do long term survivors of ewing family of tumors experience low bone mineral density and increased fracture risk?

BACKGROUND: Multimodal treatment regimens for Ewing's sarcoma have led to survival rates approaching 70% of patients with no metastases at diagnosis. However, these treatments have long-term side effects. Low bone mineral density (BMD) and risk of fractures can occur owing in part to chemotherapy and limited mobility from local control of the primary tumor. QUESTIONS/PURPOSES: We performed this study to answer the following questions: (1) Do long-term survivors of the Ewing family of tumors sustain low BMD? (2) Which factors are associated with BMD in these patients? (3) Do they experience fractures? (4) Are BMD and fractures associated with each other? METHODS: We queried our institutional registry to identify all known survivors of Ewing tumors who were treated before 2005. Of 100 such patients, 67 (67%) responded to a postal survey to participate in this study, and an additional 11 (11%) patients were excluded according to prespecified criteria. In the remaining 56 long-term survivors (27 females, 29 males; mean±SD age at followup, 32±10 years; mean followup, 15±7 years), BMD was measured by dual-energy x-ray absorptiometry and history of fractures was assessed using a questionnaire. Associations were tested using univariate and multivariate models by stepwise variable selection procedure, including Bonferroni correction. RESULTS: Thirty-one of 56 (56%) patients had a pathologic BMD. Seven (13%) had osteoporosis and 24 (43%) had osteopenia. Factors related to low BMD after Bonferroni correction were the length of time between surgery and followup and the BMI at followup. Twenty-one patients reported 29 fractures. With the numbers available, BMD levels were not associated with fractures. CONCLUSIONS: We could not confirm some potentially important predictors for fractures to be associated with clinical events of interest. However, the data are valuable as hypothesis-generating pilot data for future, multicenter prospective studies. If BMD changes cannot explain the propensity of fractures, there may be other bone characteristics like microarchitectural changes of bone to more accurately explain the effect. LEVEL OF EVIDENCE: Level IV, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Impact of extracorporeal shock wave therapy (ESWT) on orthodontic tooth movement-a randomized clinical trial.

OBJECTIVES: This randomized clinical trial investigated the effect of extracorporeal shock waves on the amount of orthodontic tooth movement and periodontal parameters. MATERIAL AND METHODS: Twenty-six adult orthodontic patients participated in this clinical trial; all of them receiving lower second molar mesially directed movement. The fixed orthodontic device included superelastic coil springs (200 cN) and miniscrews as temporary anchorage device. The active treatment group received a single shock wave treatment with 1,000 impulses in the region of tooth movement. The placebo group was treated with deactivated shock wave applicator with an acoustic sham. The study period lasted 4 months with a monthly data exploration. RESULTS: No statistically significant difference in posterior-anterior tooth movement between the treatment and placebo group was seen during observation period. Gender had no significant influence on tooth movement in either group. No significant difference occurred in mesio-distal tipping and rotation, but a significant difference (p = 0.035) in bucco-lingual tipping of the molars was found. Periodontal status of the patients (sulcus probing depth, gingival index) did not significantly differ in both groups. The plaque index showed a significant difference (p = 0.003). CONCLUSIONS: Single application of extracorporeal shock wave treatment was associated neither with a statistically significant acceleration of tooth movement nor with an altered periodontal status in vivo. CLINICAL RELEVANCE: Shock waves showed no harmful effects in the investigated area. Their clinical use for lithotripsy during orthodontic therapy might be permitted.

The impact of education on the perception of facial profile aesthetics and treatment need.

BACKGROUND: The purpose of this study was to evaluate the influence of education on the perception of various male and female Caucasian profiles with respect to attractiveness and treatment need. METHODS: Four hundred questionnaires were distributed among six groups of raters (nonacademic laymen, academic laymen, preclinical students, clinical students, orthodontists, and maxillofacial surgeons). Male and female profile images were altered digitally in the sagittal and vertical dimensions resulting in nine different male and female profiles. The raters had to assess the images according to attractiveness and treatment needs. RESULTS: Three hundred four questionnaires were completed in this study. Age and gender of the rater had no significant influence on the perception of profile attractiveness. The different groups of raters perceived the Class I normodivergent profiles as most attractive. Significant differences in the perception of attractiveness were seen between laymen, orthodontists, and maxillofacial surgeons. The orthodontists and maxillofacial surgeons reported treatment needs the most. The orthodontists were most sensitive in discerning profiles. CONCLUSION: Attractive male and female profiles are recognizable by any rater. Education seemed to have a significant influence on facial profile perception and recommendation for treatment need of unattractive profiles. Professionals should be aware of their judgment discrepancy to laymen. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Influence of different conditioning methods on immediate and delayed dentin sealing.

STATEMENT OF PROBLEM: Data are needed to evaluate the effect of various conditioning methods on immediate and delayed dentin sealing. PURPOSE: The purpose of this study was to test bond strength and surface configuration of immediate and delayed dentin sealing surfaces after applying different surface conditioning methods. MATERIAL AND METHODS: A total of 96 premolars were allocated to the immediate and delayed groups. The groups differed in the timing of dentin sealing. The immediate-group specimens were sealed with a self-etching adhesive immediately after preparation. The delayed-group specimens were sealed before the final ceramic restoration bonding. Provisional restorations were cemented on immediate-group and delayed-group specimens for 1 week. Four conditioning methods were used: polishing with fluoride-free pumice paste, airborne-particle abrasion with silicoated aluminum oxide, glycin, or calcium carbonate. After 24-hour storage, the shear bond strength was tested. The fractured specimens were optically inspected with a stereomicroscope. An optical 3-dimensional surface analysis was performed for quantitative and qualitative evaluation. A 2-way ANOVA with post hoc Tukey honestly significant difference tests for significant effects was performed to investigate effects of the 2 factors, sealing and conditioning, and their interaction (α=.05). RESULTS: Two-way ANOVA found significant differences between the sealing and conditioning groups. The immediate group had significantly lower bond strengths than the delayed group. In all groups, surface polishing produced the highest bond strengths, and airborne-particle abrasion with calcium carbonate produced the lowest. Fracture analysis found more failures in the adhesive layers in the immediate groups and a prevalence of mixed failures in the delayed groups. The surface analysis found significant abrasion and roughness when airborne-particle abrasion with silicoated aluminum oxide was used for immediate and delayed dentin sealing surfaces. CONCLUSIONS: Polishing and airborne-particle abrasion with silicoated aluminum oxide or glycin are efficient methods in conditioning immediate and delayed dentin sealing surfaces. Airborne-particle abrasion with silicoated aluminum oxide leaves significant surface alterations on both types of surfaces.

Impact of extracorporeal shock-wave therapy on the stability of temporary anchorage devices in adults: a single-center, randomized, placebo-controlled clinical trial.

INTRODUCTION: In this randomized, placebo-controlled clinical trial, we investigated the effect of noninvasive extracorporeal shock waves on the stability of temporary anchorage devices (TADs) under orthodontic loading. METHODS: Thirty adult orthodontic patients of the Bernhard Gottlieb University Clinic in Vienna, Austria, were enrolled in this clinical trial and allocated by block randomization (size, 4) in a 1:1 ratio to either the treatment or the placebo group. Randomization was performed with software, and the allocations were concealed in sealed envelopes. Eligibility criteria included healthy adult patients with mesially directed orthodontic movement of the mandibular second molar into the extraction site of the mandibular first molar. The fixed orthodontic devices included active superelastic coil springs (200 cN) and TADs in the mandibular alveolar bone. Blinding was performed for the subjects and the outcome assessor. The treatment group received 1 shock-wave application with 1000 impulses at 0.19 to 0.23 mJ per square millimeter in the region of the TADs. The placebo group was treated with a deactivated shock-wave applicator and acoustic sham. The TADs positions were evaluated at placement and after 4 months. The reliability and precision of the impression process of the TADs were evaluated in an in-vitro model. RESULTS: Thirteen participants finished the investigation successfully in the treatment group but only 12 finished in the placebo group because 1 TAD loosened. The difference of the total TAD displacement for the 4-month time period between the placebo and treatment groups was 0.17 ± 0.95 mm (95% CI: -0.96, 0.62). No statistically significant difference between the 2 groups was found when sex was evaluated. Primary stability of the TADs as measured by placement torque, amount of tooth movement, and age of the patients did not influence displacement of the TADs. The reliability and precision of TAD impressions were confirmed. No unintended pernicious effects occurred after shock-wave treatment during the study period. CONCLUSIONS: A single application of extracorporeal shock-wave treatment did not improve the stability of the TADs during orthodontic loading. Sufficient interradicular space should be provided to minimize the risk of periodontal and dental root defects. REGISTRATION: This trial was registered at https://clinicaltrials.gov. PROTOCOL: The protocol was published before trial commencement, NCT01695928. FUNDING: No funding or conflict of interest to be declared.

The one-minute sit-to-stand-test performance is associated with health-related quality of life in patients with pulmonary hypertension.

INTRODUCTION: Patients with pulmonary hypertension (PH) have an impaired functional capacity and poor health-related quality of life (HRQoL). The one-minute sit-to-stand test (1-min STST) can be used for the assessment of functional capacity. AIMS: Our aim was to evaluate the 1-min STST performance and its association with patient-reported HRQoL in patients with PH. METHODS: We prospectively assessed functional capacity in 98 PH patients (mean age 66 ± 15 years, 55% female) using the 1-min STST. Patients had to stand up and sit down from a chair as many times as possible within one minute. Patients' HRQoL was evaluated with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire, which consists of the three subcategories symptoms, activities and quality of life (QoL). RESULTS: We observed a significant correlation of the 1-min STST performance with all HRQoL subcategories assessed with the CAMPHOR questionnaire: A lower number of 1-min STST repetitions correlated with more symptoms (rs = -.398, p < .001), worse functioning (rs = -.551, p < .001) and a decreased QoL (rs = -.407, p < .001). Furthermore, in the multivariable linear regression analysis, adjusted for age, sex, body mass index (BMI) and mean pulmonary artery pressure (mPAP), lower 1-min STST performance was an independent predictor for worse symptoms (est. ß = -0.112, p = .003), activities (est. ß = -0.198, p < .001) and QoL (est. ß = -0.130, p < .001) assessed with the CAMPHOR questionnaire. CONCLUSION: Our results indicate that regardless of age, sex, BMI and mPAP the 1-min STST performance is associated with all CAMPHOR HRQoL subcategories in patients with PH. Therefore, the 1-min STST performance might be a new option to assess functional capacity correlated to HRQoL in patients with PH.

Efficacy and safety of mTOR inhibition in cutaneous sarcoidosis: a single-centre trial.

BACKGROUND: Sarcoidosis is an inflammatory condition that can affect various organs and tissues, causing the formation of granulomas and subsequent functional impairment. The origin of sarcoidosis remains unknown and there are few treatment options. Mechanistic target of rapamycin (mTOR) activation is commonly seen in granulomas of patients across different tissues and has been shown to induce sarcoidosis-like granulomas in a mouse model. This study aimed to examine the efficacy and safety of the mTOR inhibitor sirolimus as a treatment for cutaneous sarcoidosis. METHODS: We did a single-centre, randomised study treating patients with persistent and glucocorticoid-refractory cutaneous sarcoidosis with sirolimus at the Vienna General Hospital, Medical University of Vienna (Vienna, Austria). We recruited participants who had persistent, active, and histologically proven cutaneous sarcoidosis. We used an n-of-1 crossover design in a placebo-controlled, double-blind topical treatment period and a subsequent single-arm systemic treatment phase for 4 months in the same participants. Participants initially received either 0·1% topical sirolimus in Vaseline or placebo (Vaseline alone), twice daily. After a washout period, all participants were subsequently administered a 6 mg loading dose followed by 2 mg sirolimus solution orally once daily, aiming to achieve serum concentrations of 6 ng/mL. The primary endpoint was change in the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) after topical or systemic treatment. All participants were included in the safety analyses, and patients having completed the respective treatment period (topical treatment or systemic treatment) were included in the primary analyses. Adverse events were assessed at each study visit by clinicians and were categorised according to their correlation with the study drug, severity, seriousness, and expectedness. This study is registered with EudraCT (2017-004930-27) and is now closed. FINDINGS: 16 participants with persistent cutaneous sarcoidosis were enrolled in the study between Sept 3, 2019, and June 15, 2021. Six (37%) of 16 participants were men, ten (63%) were women, and 15 (94%) were White. The median age of participants was 54 years (IQR 48-58). 14 participants were randomly assigned in the topical phase and 2 entered the systemic treatment phase directly. Daily topical treatment did not improve cutaneous lesions (effect estimate -1·213 [95% CI -2·505 to 0·079], p=0·066). Systemic treatment targeting trough serum concentrations of 6 ng/mL resulted in clinical and histological improvement of skin lesions in seven (70%) of ten participants (median -7·0 [95% CI -16·5 to -3·0], p=0·018). Various morphologies of cutaneous sarcoidosis, including papular, nodular, plaque, scar, and tattoo-associated sarcoidosis, responded to systemic sirolimus therapy with a long-lasting effect for more than 1 year after treatment had been stopped. There were no serious adverse events and no deaths. INTERPRETATION: Short-term treatment with systemic sirolimus might be an effective and safe treatment option for patients with persistent glucocorticoid-refractory sarcoidosis with a long-lasting disease-modulating effect. The effect of sirolimus in granulomatous inflammation should be investigated further in large, multi-centre, randomised clinical trials. FUNDING: Vienna Science and Technology Fund, Austrian Science Fund.

A diagnostic score for the prediction of spontaneous resolution of acute hepatitis C virus infection.

BACKGROUND & AIMS: IL28B polymorphisms, jaundice, decline in HCV-RNA, IP-10, and gender have been proposed to be indicative of spontaneous clearance of acute hepatitis C virus infection. The aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development of viral persistence and need for early antiviral treatment. METHODS: 136 patients (74 male; 35 ± 15 years) were analyzed. From variables predictive of spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cut-offs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cut-offs were: (I) presence of IL28B C/C (p=0.027), (II) age (p=0.031; cut-off: 35 years), (III) peak-bilirubin (p=0.018; cut-off: 6 mg/dl), (IV) HCV-RNA decline within 4 weeks (p<0.001;cut-off: >2.5 log), (V) serum IP-10 (p=0.003; cut-off: 546 pg/ml), (VI) presence of CD4(+) Th1 cells (p=0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA decline of ≥ 1 log 10 but <2.5 log 10 to 1 point, a decline of ≥ 2.5 log 10 to 2 points. Three scores were evaluated (Score 1: I-IV; Score 2: I-V; Score 3: I-VI). RESULTS: A cut-off of ≥ 3 points out of 5 in Score 1 (AUROC: 0.82; DeLong 95% CI: 0.76-0.93) predicted spontaneous clearance with a sensitivity of 71% (95% CI: 0.53-0.86) and specificity of 87% (95% CI: 0.73-0.95). PPV and NPV were 79% and 82%. Corresponding findings for Score 2 including IP-10 (AUROC: 0.93; DeLong 95% CI: 0.86-0.93) at a cut-off of ≥ 4 were: sensitivity 81%, specificity 95% (PPV: 100%; NPV: 77%). A cut-off of ≥ 5 in Score 3 (AUROC: 0.98; DeLong 95% CI: 0.95-1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV: 100%; NPV: 88%). CONCLUSIONS: The scores enable a reliable discrimination between AHC-patients with high potential for spontaneous clearance from candidates for early therapeutic intervention due to marginal chance of spontaneous resolution.

Risk factors for "PTH spikes" during surgery for primary hyperparathyroidism.

PURPOSE: Increased intraoperative parathyroid hormone excretion ("PTH spikes") due to unintended manipulation of parathyroid adenoma can be observed frequently during surgery for primary hyperparathyroidism. This may lead to difficulties in interpreting intraoperative PTH curves. The aim of this study was to elucidate possible risk factors for PTH spikes and to evaluate the impact on different interpretation criteria of intraoperative PTH curves. METHODS: Eight hundred forty-seven patients with primary hyperparathyroidism were included. The probability of PTH spikes was analyzed regarding preoperative PTH- and creatinine levels, and size of adenoma and their impact on the Vienna, Miami, and Halle criteria was evaluated. RESULTS: PTH spikes occurred in 102 patients (12 %) and revealed to be independent of PTH- and creatinine levels (p = 0.13) preoperatively. There was a significant negative correlation between "manipulation PTH" and "baseline PTH" values and the gland volume, respectively. Patients presenting with smaller adenomas and those with low-baseline PTH values show significantly higher manipulation values. No risk factor for manipulation was exposed and no significantly higher risk of misclassification as "false positive" in case of PTH spikes was detected for any interpretation criterion. For the "Vienna Criterion," however, a significant increase in the risk of "false negative" misclassification was observed with increasing manipulation values. CONCLUSIONS: In patients with PTH spikes, none of the analyzed criteria show a significant increase in missed adenomas. Nevertheless, the Vienna criterion shows a higher rate of potentially unnecessary explorations with increasing manipulation values. Thus, caution is warranted in detecting PTH spikes and in individual interpretations of specific PTH curves is recommended. The Miami criterion seems to be favorable in this group of patients.

Long-term adherence to pessary use in women with pelvic organ prolapse: A retrospective cohort study.

PURPOSE OF THE RESEARCH: Vaginal pessary use is an established, non-surgical treatment option for pelvic organ prolapse. While satisfaction rates are initially high, they seem to decline over time. We aimed to determine the median duration of pessary use among our patients and to evaluate reasons for discontinuation. METHODS: All patients who were treated with a vaginal pessary for pelvic organ prolapse between 2007 and 2022 at our institution (a maximum observation period of 15 years) were included in this retrospective cohort study. Data were collected from the in-house electronic databases and the date of pelvic floor surgery was defined as the primary endpoint. In case of no documented surgery, the date of the last follow-up visit (for patients lost to follow-up or who discontinued pessary use without subsequent surgery) or the date of final data collection (for those with presumed continued pessary use) was used as the primary endpoint. Duration of pessary use is represented by Kaplan-Meier curves. Effects of possible confounders were investigated by Cox regression models. A Cox regression model was evaluated for patients with the three most common types of pessary: ring, cube and shell. A chi-square test was performed to compare therapy adherence according to pessary type. PRINCIPAL RESULTS: Data of 779 patients could be included in the statistical analysis. The estimated median duration of pessary use was 173 weeks (95 % CI 104-473) - approximately 3.3 years. Overall, 30 % of patients opted for surgical therapy and the majority of them did so within 4 months of initiation of pessary use (median time: 19 weeks, 95 % CI 16-26). In 5 % of cases a discontinuation of pessary use without subsequent surgery was documented and 18 % were lost to follow-up before a planned visit, thus leaving 47 % of our patients with presumed continued pessary use. Possible confounding factors for discontinuation of pessary use were tested but were found to be non-significant (body mass index, Pelvic Organ Prolapse - Quantification score, pelvic floor training, age, parity, menopausal status, nicotine consumption, incontinence or size of pessary). Reasons for discontinuation of pessary use were documented in 51 % of patients: unspecified patient wish (23 %), pessary use tiredness (10 %), general dissatisfaction with pessary therapy (7 %), unspecified reasons (5 %), pessary self-change not possible (1 %), erosion, bleeding, pain (2 %); none of the pessary types fitted (2 %). CONCLUSIONS: According to our data, almost half of our patients with pelvic organ prolapse and pessary therapy continued pessary use until a maximum follow-up time of 15 years, whereas about one-third of patients finally opted for surgical repair (a majority of these within 4 months after pessary therapy initiation). The remaining patients were either lost to follow-up or discontinued pessary use without subsequent surgery. The stated reasons for discontinuation of pessary use were mostly non-specific, but only 1 % reported that pessary self-change was not possible. Erosion bleeding or pain was documented in only 2 % of cases as reason for discontinuation. This information helps clinicians to inform their patients with pelvic organ prolapse about expected pessary therapy success and strengthens individual counselling. Furthermore, our data indicates vaginal pessary use for pelvic organ prolapse is feasible and safe for all women and that therapy adherence can extend beyond 5 years.