Search

Kliniker berichten haufig von einer Veranderung des mimisch-affektiven Verhaltens im Laufe der Behandlung posttraumatischer Belastungsstorungen (PTBS). Dabei wird die Zunahme der Mimik in Zusammenhang mit dem Ruckgang der „Numbing“-Symptomatik gebracht. Die Zunahme des mimisch-affektiven Verhaltens (insbesondere des negativen Affekts) im Laufe einer Behandlung in Form des Eye Movement Desensitization and Reprocessing (EMDR) sollte dokumentiert werden. Des Weiteren erfolgte eine explorative Analyse der Zusammenhange der mimischen Veranderungen mit wichtigen Therapie-Outcomes. Das mimisch-affektive Verhalten wahrend der Therapiesitzungen wurde fur 16 Patientinnen, die vor ihrem 18. Lebensjahr traumatisiert wurden, mithilfe des „facial action coding system“ (FACS) im Vorfeld, wahrend und ein Jahr nach einer stationaren EMDR-Behandlung codiert. Zur Quantifizierung der Symptombelastung kamen die Impact of Event Scale Revised (IES-R), die Symptomcheckliste (SCL-90®), das Beck-Depressions-Inventar (BDI-V) sowie der Fragebogen zu Dissoziativen Symptomen (FDS) zum Einsatz. Es zeigt sich uber die 3 Erhebungszeitpunkte hinweg eine bedeutsame Mimikveranderung, die eine Zunahme der Gesamtmimik und den Ausdruck negativen Affekts betraf. Zusammenhange zu den Veranderungen der erhobenen Symptomschwere liesen sich jedoch nicht belegen. Anhand weiterer Untersuchungen wird geklart werden mussen, inwiefern die Zunahme des mimisch-affektiven Verhaltens relevant ist, um insbesondere im Hinblick auf soziale Interaktionen von Behandlungserfolg sprechen zu konnen.

Background: Although graft choice may be limited in the revision setting based on previously used grafts, most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome. Hypothesis: In the ACL revision setting, there would be no difference between autograft and allograft in rerupture rate and patient-reported outcomes (PROs) at 6-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Patients who had revision surgery were identified and prospectively enrolled in this cohort study by 83 surgeons over 52 sites. Data collected included baseline characteristics, surgical technique and pathology, and a series of validated PRO measures. Patients were followed up at 6 years and asked to complete the identical set of PRO instruments. Incidence of additional surgery and reoperation because of graft failure were also recorded. Multivariable regression models were used to determine the predictors (risk factors) of PROs, graft rerupture, and reoperation at 6 years after revision surgery. Results: A total of 1234 patients including 716 (58%) men were enrolled. A total of 325 (26%) underwent revision using a bone-patellar tendon-bone (BTB) autograft; 251 (20%), soft tissue autograft; 289 (23%), BTB allograft; 302 (25%), soft tissue allograft; and 67 (5%), other graft. Questionnaires and telephone follow-up for subsequent surgery information were obtained for 809 (66%) patients, while telephone follow-up was only obtained for an additional 128 patients for the total follow-up on 949 (77%) patients. Graft choice was a significant predictor of 6-year Marx Activity Rating Scale scores ( P = .024). Specifically, patients who received a BTB autograft for revision reconstruction had higher activity levels than did patients who received a BTB allograft (odds ratio [OR], 1.92; 95% CI, 1.25-2.94). Graft rerupture was reported in 5.8% (55/949) of patients by their 6-year follow-up: 3.5% (16/455) of patients with autografts and 8.4% (37/441) of patients with allografts. Use of a BTB autograft for revision resulted in patients being 4.2 times less likely to sustain a subsequent graft rupture than if a BTB allograft were utilized ( P = .011; 95% CI, 1.56-11.27). No significant differences were found in graft rerupture rates between BTB autograft and soft tissue autografts ( P = .87) or between BTB autografts and soft tissue allografts ( P = .36). Use of an autograft was found to be a significant predictor of having fewer reoperations within 6 years compared with using an allograft ( P = .010; OR, 0.56; 95% CI, 0.36-0.87). Conclusion: BTB and soft tissue autografts had a decreased risk in graft rerupture compared with BTB allografts. BTB autografts were associated with higher activity level than were BTB allografts at 6 years after revision reconstruction. Surgeons and patients should consider this information when choosing a graft for revision ACL reconstruction.

Visual Abstract, Highlights • Myocardial matrix hydrogel preserves LV volumes and apical wall thickening in a chronic MI model. • Myocardial matrix hydrogel trends toward reduced fibrosis. • In vivo differential gene expression analysis shows the matrix modulates cardiac muscle contraction, metabolism, fibrosis, and the inflammatory/immune response in a chronic MI model., Summary A first-in-man clinical study on a myocardial-derived decellularized extracellular matrix hydrogel suggested the potential for efficacy in chronic myocardial infarction (MI) patients. However, little is understood about the mechanism of action in chronic MI. In this study, the authors investigated the efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a rat chronic MI model. Assessment of cardiac function via magnetic resonance imaging demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent further negative LV remodeling in the chronic MI model through modulation of the immune response, down-regulation of pathways involved in heart failure progression and fibrosis, and up-regulation of genes important for cardiac muscle contraction.

Context Quadriceps weakness is associated with disability and aberrant gait biomechanics after anterior cruciate ligament reconstruction (ACLR). Strength-sufficiency cutoff scores, which normalize quadriceps strength to the mass of an individual, can predict who will report better function after ACLR. However, whether gait biomechanics differ between individuals who meet a strength-sufficiency cutoff (strong) and those who do not (weak) remains unknown. Objective To determine whether vertical ground reaction force, knee-flexion angle, and internal knee-extension moment differ throughout the stance phase of walking between individuals with strong and those with weak quadriceps after ACLR. Design Case-control study. Setting Laboratory. Patients or Other Participants Individuals who underwent unilateral ACLR >12 months before testing were dichotomized into strong (n = 31) and weak (n = 116) groups. Main Outcome Measures Maximal isometric quadriceps strength was measured at 90° of knee flexion using an isokinetic dynamometer and normalized to body mass. Individuals who demonstrated maximal isometric quadriceps strength ≥3.0 N·m·kg−1 were considered strong. Three-dimensional gait biomechanics were collected at a self-selected walking speed. Biomechanical data were time normalized to 100% of stance phase. Vertical ground reaction force was normalized to body weight (BW), and knee-extension moment was normalized to BW × height. Pairwise comparison functions were calculated for each outcome to identify between-groups differences for each percentile of stance. Results Vertical ground reaction force was greater in the weak group for the first 22% of stance (peak mean difference [MD] = 6.2% BW) and less in the weak group between 36% and 43% of stance (MD = 1.4% BW). Knee-flexion angle was greater (ie, more flexion) in the strong group between 6% and 52% of stance (MD = 2.3°) and smaller (ie, less flexion) between 68% and 79% of stance (MD = 1.0°). Knee-extension moment was greater in the strong group between 7% and 62% of stance (MD = 0.007 BW × height). Conclusions Individuals with ACLR who generated knee-extension torque ≥3.0 N·m·kg−1 exhibited different biomechanical gait profiles than those who could not. More strength may allow for better energy attenuation after ACLR.

Infection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient- and surgeon- dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting post-operative infections. Allografts had a higher risk of infection than autografts (odds ratio=6.8; 95% CI: 0.9-54.5; p=0.045). Diabetes (odds ratio=28.6; 95% CI: 5.5-149.9; p=0.004) was a risk factor for infection. Patient age, sex, BMI and smoking status were not associated with risk of infection after rACLR. STATEMENT OF CLINICAL SIGNIFICANCE: While there is a low rate of infection following rACLR, use of allograft and comorbidity with diabetes are associated with a higher risk of infection following this surgery.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health. This has been a successful intervention in patients with isolated tears and tears associated with anterior cruciate ligament (ACL) reconstruction. However, the results of meniscal repair in the setting of revision ACL reconstruction have not been documented. Purpose: To examine the prevalence and 2-year operative success rate of meniscal repairs in the revision ACL setting. Study Design: Case-control study; Level of evidence, 3. Methods: All cases of revision ACL reconstruction with concomitant meniscal repair from a multicenter group between 2006 and 2011 were selected. Two-year follow-up was obtained by phone and email to determine whether any subsequent surgery had occurred to either knee since the initial revision ACL reconstruction. If so, operative reports were obtained, whenever possible, to verify the pathologic condition and subsequent treatment. Results: In total, 218 patients (18%) from 1205 revision ACL reconstructions underwent concurrent meniscal repairs. There were 235 repairs performed: 153 medial, 48 lateral, and 17 medial and lateral. The majority of these repairs (n = 178; 76%) were performed with all-inside techniques. Two-year surgical follow-up was obtained on 90% (197/218) of the cohort. Overall, the meniscal repair failure rate was 8.6% (17/197) at 2 years. Of the 17 failures, 15 were medial (13 all-inside, 2 inside-out) and 2 were lateral (both all-inside). Four medial failures were treated in conjunction with a subsequent repeat revision ACL reconstruction. Conclusion: Meniscal repair in the revision ACL reconstruction setting does not have a high failure rate at 2-year follow-up. Failure rates for medial and lateral repairs were both

Anterior cruciate ligament reconstruction (ACLR) incurs a high risk of posttraumatic knee osteoarthritis (PTOA). Aberrant gait biomechanics contribute to PTOA and are attributable in part to quadriceps dysfunction. Vibration improves quadriceps function following ACLR, but its effects on gait biomechanics are unknown. The purpose of this study was to evaluate the effects of whole-body vibration (WBV) and local muscle vibration (LMV) on gait biomechanics in individuals with ACLR. Seventy-five volunteers (time since ACLR 27 ± 16 months) were randomized to WBV, LMV, or Control interventions. Walking biomechanics were assessed prior to and following a single exposure to the interventions. Outcomes included pre-post change scores in the ACLR limb for the peak vertical ground reaction force (vGRF) and its loading rate, peak internal knee extension (KEM) and abduction moments, and peak knee flexion and varus angles. LMV produced a significant decrease in the vGRF loading rate (-3.6 BW/s) that was greater than the changes in the WBV (-0.3 BW/s) and Control (0.5 BW/s) groups. Additionally, WBV produced an increase in the peak KEM (0.27% BW × Ht) that was greater than the change in the Control group (-0.17% BW × Ht) but not the LMV group (0.01% BW × Ht). Lower KEM and greater loading rates have been linked to declines in joint health following ACLR. WBV acutely increased the peak KEM and LMV decreased loading rates. These data suggest that vibration has the potential to mitigate aberrant gait biomechanics, and may represent an effective approach for reducing PTOA risk following ACLR.

Background: General practitioners (GPs) play a key role in the care of people with dementia (PwD). However, the role of the German Dementia Guideline in primary care remains unclear. The main objective of the present study was to examine the role of guideline-based dementia care in general practices.Methods: A cross-sectional analysis of data obtained from the DemTab study was conducted. Descriptive analyses of sociodemographic and clinical characteristics for GPs (N = 28) and PwD (N = 91) were conducted. Adherence to the German Dementia Guideline of GPs was measured at the level of PwD. Linear Mixed Models were used to analyze the associations between adherence to the German Dementia Guideline and GP factors at individual (age, years of experience as a GP, frequency of utilization of guideline, perceived usefulness of guideline) and structural (type of practice, total number of patients seen by a participating GP, and total number of PwD seen by a participating GP) levels as well as between adherence to the German Dementia Guideline and PwD’s quality of life. Results: Self-reported overall adherence of GPs was on average 71% (SD = 19.4, range: 25 – 100). Adherence to specific recommendations varied widely (from 19.2% to 95.3%) and the majority of GPs (79.1%) reported the guideline as only partially or somewhat helpful. Further, we found lower adherence to be significantly associated with higher numbers of patients (γ10 = -5.58, CI = -10.97, -0.19, p = .04). No association between adherence to the guideline and PwD’s quality of life was found (γ10 = -.86, CI = -4.18, 2.47, p = .61). Conclusion: The present study examined the role of adherence to the German Dementia Guideline recommendations in primary care. Overall, GPs reported high levels of adherence. However, major differences across guideline recommendations were found. Findings highlight the importance of guidelines for the provision of care. Dementia guidelines for GPs need to be better tailored and addressed. Further, structural changes such as more time for PwD may contribute to a sustainable change of dementia care in primary care.Trial registration: The DemTab trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413). Registered 01 April 2019, https://doi.org/10.1186/ISRCTN15854413

Cognitive impairments are strongly associated with schizophrenia (SZ) and bipolar disorder (BP) with executive functions (EF) impairments as a likely key feature. Studies of everyday behavior rated EF in young children at familial high risk of SZ (FHR-SZ) are scarce and, to our knowledge, non-existent in young children at familial high risk of BP (FHR-BP). We aimed to compare everyday behavior-rated EF of FHR-SZ, FHR-BP, and control children. A nationwide population-based cohort of 522 7-year-old children with parents diagnosed with either SZ (N = 202) or BP (N = 120) and matched controls (N = 200) were recruited using the Danish national registries. The children's EF were assessed with the Behavior Rating Inventory of Executive Functions questionnaire rated by primary caregivers and teachers. According to primary caregiver assessments, FHR-SZ children displayed widespread EF impairments and had an odds ratio of 3.7 (2.0-6.9) of having clinically significant global EF impairments compared to controls. FHR-BP children were most severely impaired regarding EF related to emotional control and had an odds ratio of 2.5 (1.2-5.1) of clinically significant global EF impairments compared to controls. Teacher assessments were overall comparable to primary caregiver assessments but teachers rated more difficulties in the FHR-SZ group than primary caregivers. Already at age 7, children with a parental history of SZ or BP displayed significant impairments of EF in everyday-life situations. FHR-SZ children displayed widespread significant impairments of EF, whereas FHR-BP children were most severely impaired on emotional control. Clinicians should be aware of potential EF impairments in FHR children.

Background: Choice of the fraction of inspiratory oxygen (FiO2) is controversial. The objective of this analysis was to evaluate whether intraoperative FiO2 was associated with recurrence-free survival after elective cancer surgery.Methods and Analysis: In this single-center, retrospective study, we analyzed 1,084 patients undergoing elective resection of pancreatic (n = 652), colorectal (n = 405), or hepatic cancer (n = 27) at Heidelberg University Hospital between 2009 and 2016. Intraoperative mean FiO2 values were calculated. For unstratified analyses, the study cohort was equally divided into a low- and a high-FiO2 group. For cancer-stratified analyses, this division was done within cancer-strata. The primary outcome measure was recurrence-free survival until the last known follow-up. Groups were compared using Kaplan–Meier analysis. A stratified log rank test was used to control for different FiO2 levels and survival times between the cancer strata. Cox-regression analyses were used to control for covariates. Sepsis, reoperations, surgical-site infections, and cardiovascular events during hospital stay and overall survival were secondary outcomes.Results: Median FiO2 was 40.9% (Q1–Q3, 38.3–42.9) in the low vs. 50.4% (Q1–Q3, 47.4–54.7) in the high-FiO2 group. Median follow-up was 3.28 (Q1–Q3, 1.68–4.97) years. Recurrence-free survival was considerable higher in the high-FiO2 group (p < 0.001). This effect was also confirmed when stratified for the different tumor entities (p = 0.007). In colorectal cancer surgery, increased FiO2 was independently associated with increased recurrence-free survival. The hazard for the primary outcome decreased by 3.5% with every 1% increase in FiO2. The effect was not seen in pancreatic cancer surgery and we did not find differences in any of the secondary endpoints.Conclusions: Until definite evidence from large-scale trials is available and in the absence of relevant clinical conditions warranting specific FiO2 values, perioperative care givers should aim for an intraoperative FiO2 of 50% in abdominal cancer surgery as this might benefit oncological outcomes.

Osteoarthritis is common following anterior cruciate ligament reconstruction (ALCR), and aberrant gait biomechanics are considered a primary contributor. Somatosensory dysfunction potentially alters gait biomechanics, but this association is unclear. Therefore, the purposes of this investigation were to compare somatosensory function between limbs and evaluate associations between somatosensory function and gait biomechanics linked to osteoarthritis development in individuals with ALCR. Seventy-three volunteers with ALCR participated. Gait biomechanics (peak vertical ground reaction force magnitude and loading rate, peak internal knee extension and valgus moments, peak knee flexion and varus angles, and quadriceps/hamstrings co-activation) were assessed as subjects walked at their preferred speed. The somatosensory function was assessed via joint position sense error (knee flexion) and vibratory perception threshold (femoral epicondyles, malleoli, and first metatarsal). Though somatosensory function did not differ between the ACLR and contralateral limbs, poorer joint position sense in the ACLR limb was associated with lower loading rates and internal knee extension moments, and greater co-activation. Poorer vibratory perception at the medial and lateral malleoli and first metatarsal head in the ACLR limb was associated with lower loading rates, greater internal knee valgus moments and varus angles, and greater co-activation. Poorer vibratory perception at the medial malleolus and first metatarsal head in the contralateral limb was associated with greater peak knee varus angles and internal knee valgus moments. These results suggest that future research evaluating rehabilitation approaches for improving somatosensory function is warranted as a potential approach for restoring normal gait biomechanics and reducing osteoarthritis risk. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:620-628, 2020.

Diffuse large B-cell lymphoma (DLBCL) is a disease with heterogeneous outcome. Stromal signatures have been correlated to survival in DLBCL. Their use, however, is hampered by the lack of assays for formalin-fixed paraffin-embedded material (FFPE). We constructed a lymphoma-associated macrophage interaction signature (LAMIS) interrogating features of the microenvironment using a NanoString assay applicable to FFPE. The clinical impact of the signature could be validated in a cohort of 466 patients enrolled in prospective clinical trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Patients with high expression of the signature (LAMIShigh) had shorter EFS, PFS, and OS. Multivariate analyses revealed independence from IPI factors in EFS (HR 1.7, 95% CI 1.2–2.4, p-value = 0.001), PFS (HR 1.8, 95% CI 1.2–2.5, p-value = 0.001) and OS (HR 1.8, 95% CI 1.3–2.7, p-value = 0.001). Multivariate analyses adjusted for the IPI factors showed the signature to be independent from COO, MYC rearrangements and double expresser status (DE). LAMIShigh and simultaneous DE status characterized a patient subgroup with dismal prognosis and early relapse. Our data underline the importance of the microenvironment in prognosis. Combined analysis of stromal features, the IPI and DE may provide a new rationale for targeted therapy.

It is well established that children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) have a higher risk of developing mental disorders, however, little is known of to what degree the genetic and environmental vulnerabilities affect the quality of life and self-esteem of these children. We aimed to compare the quality of life and self-esteem between children with FHR-SZ or FHR-BP and controls. We used Danish nationwide registers to retrieve a cohort of 522 7-year-old children with FHR-SZ or FHR-BP and controls. Quality of life was assessed with the 'Health-related Quality of Life Screening Instrument', KIDSCREEN-27, and the scale 'Social Acceptance (Bullying)' from the KIDSCREEN-52. Self-esteem was assessed with the self-report scale 'I think I am'. Assessors were blind to familial risk status of the children. Children with FHR-SZ displayed lower levels of the general quality of life, as well as lower scores on the 'Psychological Well-being' scale and the 'School Environment' scale of the KIDSCREEN-27 compared with controls. Both children with FHR-SZ and FHR-BP reported more bullying victimization compared with controls. Children with FHR-SZ reported lower self-esteem on the total scale of 'I think I am', as well as on the 'Skills and talents', the 'Psychological well-being', and the 'Relationships with others' subscales compared with controls. The findings of lower quality of life and self-esteem in children with FHR-SZ together with more bullying victimization in both familial high-risk groups call for studies on low risk, early intervention strategies towards this group of vulnerable children.

After a stroke involving the left occipitotemporal cortex our patient shows a word-length effect and has problems to identify letters or numbers in strings of symbols. But he is normal in identifying isolated letters and in non-verbally categorizing even complex images such as faces or natural scenes. His cortical lesion is stretching from the visual word form area (VWFA) anteriorly causing additional problems to name visual stimuli and to match acoustic stimuli with images. We conclude that our patient suffers from pure alexia without deficits to identify even complex visual stimuli. Our results directly contradict several explanations for letter-by-letter reading.

Background: Anterior cruciate ligament (ACL) revision cohorts continually report lower outcome scores on validated knee questionnaires than primary ACL cohorts at similar time points after surgery. It is unclear how these outcomes are associated with physical activity after physician clearance for return to recreational or competitive sports after ACL revision surgery. Hypotheses: Participants who return to either multiple sports or a singular sport after revision ACL surgery will report decreased knee symptoms, increased activity level, and improved knee function as measured by validated patient-reported outcome measures (PROMs) and compared with no sports participation. Multisport participation as compared with singular sport participation will result in similar increased PROMs and activity level. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 1205 patients who underwent revision ACL reconstruction were enrolled by 83 surgeons at 52 clinical sites. At the time of revision, baseline data collected included the following: demographics, surgical characteristics, previous knee treatment and PROMs, the International Knee Documentation Committee (IKDC) questionnaire, Marx activity score, Knee injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A series of multivariate regression models were used to evaluate the association of IKDC, KOOS, WOMAC, and Marx Activity Rating Scale scores at 2 years after revision surgery by sports participation category, controlling for known significant covariates. Results: Two-year follow-up was obtained on 82% (986 of 1205) of the original cohort. Patients who reported not participating in sports after revision surgery had lower median PROMs both at baseline and at 2 years as compared with patients who participated in either a single sport or multiple sports. Significant differences were found in the change of scores among groups on the IKDC ( P < .0001), KOOS-Symptoms ( P = .01), KOOS–Sports and Recreation ( P = .04), and KOOS–Quality of Life ( P < .0001). Patients with no sports participation were 2.0 to 5.7 times more likely than multiple-sport participants to report significantly lower PROMs, depending on the specific outcome measure assessed, and 1.8 to 3.8 times more likely than single-sport participants (except for WOMAC-Stiffness, P = .18), after controlling for known covariates. Conclusion: Participation in either a single sport or multiple sports in the 2 years after ACL revision surgery was found to be significantly associated with higher PROMs across multiple validated self-reported assessment tools. During follow-up appointments, surgeons should continue to expect that patients who report returning to physical activity after surgery will self-report better functional outcomes, regardless of baseline activity levels.

Context: Orthotic devices such as medial unloader knee braces and lateral heel wedges may limit cartilage loading following trauma or surgical repair. However, little is known regarding their effects on gait biomechanics in young, healthy individuals who are at risk of cartilage injury during physical activity due to greater athletic exposure compared with older adults. Objective: Determine the effect of medial unloader braces and lateral heel wedges on lower-extremity kinematics and kinetics in healthy, young adults. Design: Cross-sectional crossover design. Setting: Laboratory setting. Patients: Healthy, young adults who were recreationally active (30 min/d for 3 d/wk) between 18 and 35 years of age, who were free from orthopedic injury for at least 6 months, and with no history of lower-extremity orthopedic surgery. Interventions: All subjects completed normal over ground walking with a medial unloader brace at 2 different tension settings and a lateral heel wedge for a total of 4 separate walking conditions. Main Outcome Measures: Frontal plane knee angle at heel strike, peak varus angle, peak internal knee valgus moment, and frontal plane angular impulse were compared across conditions. Results: The medial unloader brace at 50% (−2.04° [3.53°]) and 100% (−1.80° [3.63°]) maximum load placed the knee in a significantly more valgus orientation at heel strike compared with the lateral heel wedge condition (−0.05° [2.85°]). However, this difference has minimal clinical relevance. Neither of the orthotic devices altered knee kinematics or kinetics relative to the control condition. Conclusions: Although effective in older adults and individuals with varus knee alignment, medial unloader braces and lateral heel wedges do not influence gait biomechanics in young, healthy individuals.

Revision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes than primary ACL reconstruction. The reasons remain varied and not completely understood. METHODS: Patients undergoing revision ACL reconstruction were prospectively enrolled. Data collected included baseline demographics, surgical technique and pathological condition, prescribed rehabilitation instructions, and a series of validated patient-reported outcome instruments. Patients were followed for 2 years and asked to complete a set of outcome instruments identical to those completed at baseline. Subsequent surgical procedures on the ipsilateral knee were recorded. Regression analysis was used to control for age, sex, activity level, baseline outcome scores, and the above-mentioned rehabilitation-related variables in order to assess the factors affecting clinical outcomes 2 years after revision ACL reconstruction. RESULTS: A total of 843 patients met the inclusion criteria and were successfully enrolled, and 82% (695) were followed for 2 years. Two rehabilitation-related factors were found to influence outcome. First, patients who were prescribed an ACL brace for their return to sports had a significantly better Knee injury and Osteoarthritis Outcome Score (KOOS) for sports and recreational activities at 2 years (odds ratio [OR] =1.50, 95% confidence interval [CI] = 1.07 to 2.11; p = 0.019). Second, patients prescribed an ACL brace for the postoperative rehabilitation period were 2.3 times more likely to have subsequent surgery by 2 years (OR = 2.26, 95% CI = 1.11 to 4.60; p = 0.024). The odds of a graft rerupture were not affected by any type of brace wear. CONCLUSIONS: Rehabilitation-related factors that the physician can control at the time of an ACL reconstruction have the ability to influence clinical outcomes at 2 years. Weight-bearing and motion can be initiated immediately postoperatively. Bracing during the early postoperative period is not helpful. Use of a functional brace early in the postoperative period was associated with an increased risk of a reoperation. Use of a functional brace for a return to sports improved the KOOS on the sports/recreation subscale. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Classical Hodgkin lymphoma is dominated by the non-neoplastic microenvironment, while the neoplastic Hodgkin-Reed-Sternberg cells compose only a minority of cells in the lymphoma tissue. Both the Hodgkin-Reed-Sternberg cells due to their expression of CD30 and PD-L1 and the microenvironment with abundant T cells and expression of PD1 are specifically targeted by new treatment concepts. We aimed to understand the dynamics of therapeutic targets in patients treated with conventional chemotherapy. We analyzed sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype, and microenvironmental components. The morphological subtype changed between primary and relapse biopsy in 20% of cases. The immunophenotype was stable with respect to CD30, CD3, and LMP1 but variable with respect to CD15 and CD20 expression. Gene expression revealed 8 upregulated and 20 downregulated genes at relapse (p

Identification of chronic kidney disease patients at risk of progressing to end-stage renal disease (ESRD) is essential for treatment decision-making and clinical trial design. Here, we explored whether proton nuclear magnetic resonance (NMR) spectroscopy of blood plasma improves the currently best performing kidney failure risk equation, the so-called Tangri score. Our study cohort comprised 4640 participants from the German Chronic Kidney Disease (GCKD) study, of whom 185 (3.99%) progressed over a mean observation time of 3.70 ± 0.88 years to ESRD requiring either dialysis or transplantation. The original four-variable Tangri risk equation yielded a C statistic of 0.863 (95% CI, 0.831-0.900). Upon inclusion of NMR features by state-of-the-art machine learning methods, the C statistic improved to 0.875 (95% CI, 0.850-0.911), thereby outperforming the Tangri score in 94 out of 100 subsampling rounds. Of the 24 NMR features included in the model, creatinine, high-density lipoprotein, valine, acetyl groups of glycoproteins, and Ca2+-EDTA carried the highest weights. In conclusion, proton NMR-based plasma fingerprinting improved markedly the detection of patients at risk of developing ESRD, thus enabling enhanced patient treatment.

(1) Background: Reconditioning of the paraspinal lumbar extensor muscles by isolated lumbar extension resistance exercises (ILEX) has shown good clinical results for patients with chronic unspecific low back pain. However, the clinical value and safety for patients with specific spine pathologies is unclear. In this study, clinical outcome and influencing factors were retrospectively analyzed for patients with lumbar disk herniation (LDH) and radiculopathy. (2) Methods: 189 consecutive patients (123 men and 66 women, mean age, 36 years) with clinically diagnosed LDH and relative indications for surgery started a 9-week rehabilitation program (2x/week) including ILEX in limited range of motion (ROM) adjusted to patients’ symptoms. Patients diagnosed with advanced levels of spine degeneration were excluded. Pain/radiculopathy (PR), influence on mental health (IOMH), satisfaction rates were measured via Numeric Rating Scales (NRS, 0–10), and overall clinical outcome was stated in % (100% = full recovery). Isometric extension strength was tested before and after the program. (3) Results: 168 patients (88.9%) completed the program. For 162 out of 168 patients (96.4%) there was a significant reduction of clinical symptoms, whereas 6 patients reported no changes in symptoms. Scores (mean) for symptom intensity decreased from 4.2 (±1.5) to 1.9 (±1.5) (p &lt, 0.001), the impact on mental health decreased from 5.9 (±2.3) to 2.4 (±2.0) (p &lt, 0.001). There was a (weak) correlation between lower scores for PR and IOMH before the study and better clinical outcomes, PR also weakly correlated with satisfaction. Other factors such as age, strength increase, level/location and number of LDH did not have a significant impact on the clinical results. (4) Conclusion: The results indicate that ILEX in limited ROM can be an effective treatment for the majority of patients with LDH. For patients with high pain levels, the results are less consistent, and surgery may be considered.

Context Hypertrophy of the infrapatellar fat pad (IFP) in idiopathic knee osteoarthritis has been linked to deleterious synovial changes and joint pain related to mechanical tissue impingement. Yet little is known regarding the IFP's volumetric changes after anterior cruciate ligament reconstruction (ACLR). Objectives To examine changes in IFP volume between 6 and 12 months after ACLR and determine associations between patient-reported outcomes and IFP volume at each time point as well as the volume change over time. In a subset of individuals, we examined interlimb IFP volume differences 12 months post-ACLR. Study Design Prospective cohort study. Setting Laboratory. Patients or Other Participants We studied 26 participants (13 women, 13 men, age = 21.88 ± 3.58 years, body mass index = 23.82 ± 2.21 kg/m2) for our primary aims and 13 of those participants (8 women, 5 men, age = 21.15 ± 3.85 years, body mass index = 23.01 ± 2.01 kg/m2) for our exploratory aim. Main Outcome Measure(s) Using magnetic resonance imaging, we evaluated the IFP volume change between 6 and 12 months post-ACLR in the ACLR limb and between-limbs differences at 12 months in a subset of participants. International Knee Documentation Committee subjective knee evaluation (IKDC) scores were collected at 6-month and 12-month follow-ups, and associations between IFP volume and patient-reported outcomes were determined. Results The IFP volume in the ACLR limb increased from 6 months (19.67 ± 6.30 cm3) to 12 months (21.26 ± 6.91 cm3) post-ACLR. Greater increases of IFP volume between 6 and 12 months were significantly associated with better 6-month IKDC scores (r = .44, P = .03). The IFP volume was greater in the uninjured limb (22.71 ± 7.87 cm3) than in the ACLR limb (20.75 ± 9.03 cm3) 12 months post-ACLR. Conclusions The IFP volume increased between 6 and 12 months post-ACLR; however, the IFP volume of the ACLR limb remained smaller than that of the uninjured limb at 12 months. In addition, those with better knee function 6 months post-ACLR demonstrated greater increases in IFP volume between 6 and 12 months post-ACLR. This suggests that greater IFP volumes may play a role in long-term joint health after ACLR.

Classical Hodgkin Lymphoma (cHL) is a B cell-derived lymphoid malignancy, affecting 2.5–3/100,000 people per year. To date, in patients diagnosed with advanced cHL no reliable tool is able to—a priori—distinguish the subset of patients at high risk for relapse or refractory disease. Clinical risk indices for cHL, such as the International Prognostic Score (IPS), have not been successfully applied as a treatment decision tool in advanced stage cHL [1]. In this study we show, that a previously published gene expression-based predictor in advanced stage cHL patients treated with ABVD [2] does not prove prognostic in 401 BEACOPP-treated advanced stage cHL patients. Using transcriptome profiling, we identified however that three individual genes, PDGFRA, TNFRSF8 (encoding CD30) and CCL17 (encoding TARC), were significantly associated with progression-free survival (PFS) after multiple test correction in the BEACOPP-treated cohort, highlighting the potential of a modified gene expression profiling approach for pre-treatment risk assessment., Letter

Background Plantaris tendinopathy and plantaris-associated Achilles tendinopathy can be responsible for chronic pain in the Achilles tendon midportion, often accompanied by medial tenderness. As conservative treatments are less successful for this patient group, proper diagnosis is important for decision making. This report presents a case with plantaris tendinopathy in a rare (superficial) location. Case presentation This article describes a pain history and treatment timeline of a professional Swedish female soccer player (32 years old, Northern European ethnicity, white) who suffered from sharp pain in the Achilles tendon midportion and tenderness on the medial and superficial side for about 2 years. Conservative treatments, including eccentric exercises, were not successful and, to some extent, even caused additional irritation in that region. Ultrasound showed a wide and thick plantaris tendon located on the superficial side of the Achilles tendon midportion. The patient was surgically treated with local removal of the plantaris tendon. After surgery there was a relatively quick (4–6 weeks) rehabilitation, with immediate weight bearing, gradual increased loading, and return to running activities after 4 weeks. At follow-up at 8 weeks, the patient was running and had not experienced any further episodes of sharp pain during change of direction or sprinting. Conclusions The plantaris tendon should be considered as a possible source of Achilles tendon pain. This case study demonstrates that the plantaris tendon can be found in unexpected (superficial) positions and needs to be carefully visualized during clinical and imaging examinations.

In order to differentiate prognostic subgroups of patients with aggressive B-cell lymphoma, we analyzed the expression of 800 miRNAs with the NanoString nCounter human miRNA assay on a cohort of 228 FFPE samples of patients enrolled in the RICOVER-60 and MegaCHOEP trials. We identified significant miRNA signatures for overall survival (OS) and progression-free survival (PFS) by LASSO-penalized linear Cox-regression. High expression levels of miR-130a-3p and miR-423-5p indicate a better prognosis, whereas high levels of miR-374b-5p, miR-590-5p, miR-186-5p, and miR-106b-5p increase patients' risk levels for OS. Regarding PFS high expression of miR-365a-5p in addition to the other two miRNAs improves the prognosis and high levels of miR374a-5p, miR-106b-5p, and miR-590-5p, connects with increased risk and poor prognosis. We identified miRNA signatures to subdivide patients into two different risk groups. These prognostic models may be used in risk stratification in future clinical trials and help making personalized therapy decisions.

Since the outbreak of the COVID-19 pandemic, the use of face masks is recommended to prevent droplets from traveling from one person to another. A commandment to wear masks applies in most public places to contain the widespread of the virus. Some public debates concern myths regarding risks caused by wearing a mask, like, e.g., decreased blood oxygen levels and impaired cognitive capabilities. The present, pre-registered study aims to contribute clarity by delivering a direct comparison of wearing an FFP2 (N95) respirator and wearing no mask. We focused on a demanding situation to show that cognitive efficacy and the person's state is equivalent in both conditions of a randomized-controlled cross-over study design. We measured physiological (blood oxygen saturation and heart rate variability), behavioral (parameters of performance in the task), and subjective (perceived mental load) data to substantiate our assumption as broad as possible. We analyzed data from 44 participants regarding both statistical equivalence and differences. All of the investigated dimensions showed statistical equivalence given our pre-registered equivalence boundaries. None of the dimensions showed a significant difference between wearing a mask and not wearing a mask.

Identifying the structures of the lateral knee is critical during knee posterolateral corner reconstruction. Several methods exist that can help estimate the femoral insertions of these structures on lateral radiographs. However, it is important to recognize the limitations of these methods and that anatomic visualization is often more practical and more accurate. Until percutaneous or more minimally invasive techniques become standardized, intraoperative fluoroscopy is seldom needed or used for posterolateral corner reconstruction, whereas radiographic analysis of lateral knee structures could be of benefit in cases of failed reconstruction to assess tunnel placement.

Objectives: Individuals with an anterior cruciate ligament (ACL) injury are at high risk of developing posttraumatic osteoarthritis (PTOA). A comprehensive study is needed to determine the time course of joint tissue metabolic changes occurring following ACL injury and reconstruction (ACLR). The purpose of this longitudinal nested comparison-control study was to simultaneously evaluate serum biomarkers of inflammation and cartilage matrix damage in ACL injured patients prior to ACLR and 6 and 12 months post-ACLR, as well as in matched uninjured controls. Methods: Serum was collected from 34 ACL injured individuals (53% female, 20.7±2.4 years old, 24.2±4.1 body mass index [BMI]) within 14 days of primary ACL injury (baseline), as well as at 6 and 12 months following bone-patellar-tendon-bone autograft ACLR. Serum was also collected from 34 uninjured matched controls (53% Female, 20.5±2.4 years old, 24.1±3.5 BMI) at a single timepoint. Blood was collected from the antecubital fossa, centrifuged and stored at -80°C prior to batch analysis. Commercial enzyme-linked immunosorbent assays were used to evaluate concentrations of: 1) a pro-inflammatory cytokine [Monocyte Chemoattractant Protein; MCP-1]; 2) a matrix degrading enzyme [matrix metalloproteinase-3; MMP-3]; 3) a cartilage breakdown biomarker [cartilage oligomeric matrix protein; COMP]; and type-II collagen turnover [type-II collagen cleavage: synthesis; C2C:CPII]. Separate Bonferroni-corrected independent t-tests were used to determine differences between the ACL injured group at each timepoint and uninjured controls for each biomarker (P ≤ 0.015). Similarly, separate Bonferroni-corrected dependent t-tests were used to determine differences in biomarker concentrations over time for the ACLR group. Results: Serum concentrations of MCP-1 and COMP were greater in the ACL injured individuals at all timepoints compared to the controls (P ≤ 0.015, Table 1), yet no differences were found over time in the ACL injured group. MMP-3 concentrations increased between baseline and 6 months post-ACLR (P ≤ 0.015, see Table), yet no differences were found between 6 and 12 months post-ACLR, between baseline and 12 months, or between ACLR and controls at any of the time points. C2C:CPII was not different between ACL injured individuals and controls at baseline or 6 months post-ACLR. C2C:CPII was significantly increased between 6 and 12 months-post ACLR, and was found to be greater than baseline and greater than controls at 12 months post-ACLR (P ≤ 0.015, see Table). Conclusion: Our study is critical in demonstrating the time course of multiple joint tissue metabolic changes following ACL injury and ACLR. Elevated serum MCP-1 and COMP concentrations, linked to early deleterious metabolic processes associated with PTOA development, are evident soon after ACL injury and persist at 12 months post-ACLR. Serum MMP-3 concentrations were elevated 6 months post-ACLR compared to the baseline measurements, suggesting factors occurring after ACLR initiate upregulation of matrix degrading enzymes. Furthermore, elevated C2C:CPII occurs within the first 12 months post ACLR but not until after the 6-month post-ACLR timepoint. Further studies are needed to determine how long these joint tissue metabolic changes persist after ACL injury and ACLR, as well as how joint tissue metabolism is affected by the type and timing of different surgical and nonsurgical treatments.

Autoimmune pathology of acute disseminated encephalomyelitis (ADEM) is generally restricted to the brain. Our objective is to expand the phenotype of ADEM. A four-year-old girl was admitted to the pediatric emergency room of a university medical center five days after a common upper respiratory tract infection. Acute symptoms were fever, leg pain, and headaches. She developed meningeal signs, and her level of consciousness dropped rapidly. Epileptic seizure activity started, and she became comatose, requiring intubation and mechanical ventilation. Serial brain magnetic resonance imaging (MRI) illustrated the fulminant development of ADEM. Treatment escalation with high-dose corticosteroids, immunoglobulins, and plasma exchange did not lead to clinical improvement. On day ten, the patient developed treatment-refractory cardiogenic shock and passed away. The postmortem assessment confirmed ADEM and revealed acute lymphocytic myocarditis, likely explaining the acute cardiac failure. Human metapneumovirus and picornavirus were detected in the tracheal secrete by PCR. Data sources–medical chart of the patient. This case is consistent with evidence from experimental findings of an association of ADEM with myocarditis as a postinfectious systemic autoimmune response, with life-threatening involvement of the brain and heart.

Plantaris tendon is implicated in some cases of load-resistant Achilles tendinopathy. The tendon courses close to the medial Achilles tendon mid-portion prior to insertion onto the medial calcaneus, although there is variation in course and insertion. Clinical suspicion of plantaris involvement includes persistent medial Achilles pain unresponsive to a rehabilitation programme and imaging revealing a thickened plantaris tendon and/or focal medial Achilles tendinosis. Potential mechanisms include compression or shearing forces between the plantaris and Achilles tendons. Initial treatment should consist of a modified loading programme avoiding end-range loading. Resistant cases may be amenable to surgical excision of the plantaris demonstrating good clinical outcomes in the short and long term, although the evidence is limited to case series. Percutaneous methods show promise but require further evaluation.

Biomaterials, such as extracellular matrix (ECM) hydrogels, have been widely used in preclinical studies as injectable tissue engineering therapies; however, injectable therapies are limited as they can cause localized trauma or organ perforation. We have developed a new ECM therapy, the low molecular weight fraction derived from decellularized, digested ECM, for intravascular infusion. This new form of ECM can be infused after injury, specifically localize to injured tissues by coating the leaky microvasculature, and promote cell survival and tissue repair. In this study, we show the feasibility and targeting of intravascular ECM infusions using models of acute myocardial infarction (MI), traumatic brain injury, and pulmonary arterial hypertension. Furthermore, safety and efficacy were demonstrated in small and large animal models of acute MI following intracoronary infusion, which included using a clinically-relevant catheter in the large animal model. Functional improvements, specifically reduced left ventricular volumes and improved wall motion scores were observed after ECM infusions post-MI. Genes related to tissue repair and inflammation were differential expressed in response to ECM infusions. This study shows proof-of-concept for a new paradigm of delivering pro-healing ECM biomaterials via intravascular infusion to heal tissue from the inside out.

Transcutaneous electrical nerve stimulation (TENS) facilitates quadriceps voluntary activation in experimental settings. Augmenting therapeutic exercise (TE) with TENS may enhance the benefits of TE in individuals with knee osteoarthritis (KOA) and quadriceps voluntary activation failure (QVAF). PURPOSE This study aimed to determine the effect of TENS + TE on patient-reported function, quadriceps strength, and voluntary activation, as well as physical performance compared with sham TENS + TE (Sham) and TE alone in individuals with symptomatic KOA and QVAF. METHODS Ninety individuals participated in a double-blinded randomized controlled trial. Everyone received 10 standardized TE sessions of physical therapy. TENS + TE and Sham groups applied the respective devices during all TE sessions and throughout activities of daily living over 4 wk. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC), quadriceps strength, and voluntary activation, as well as a 20-m walk test, chair-stand test, and stair-climb test were performed at baseline, after the 4-wk intervention (post 1) and at 8 wk after the start of the intervention (post 2). Mixed-effects models were used to determine between-group differences between baseline and post 1, as well as baseline and post 2. RESULTS Improvements in WOMAC subscales, quadriceps strength, and voluntary activation, 20-m walk times, chair-stand repetitions, and stair-climb time were found at post 1 and post 2 compared with baseline for all groups (P < 0.05). WOMAC Pain and Stiffness improved in the TENS + TE group compared with TE alone at post 1 (P < 0.05); yet, no other between-group differences were found. CONCLUSIONS TE effectively improved patient-reported function, quadriceps strength, and voluntary activation, as well as physical performance in individuals with symptomatic KOA and QVAF, but augmenting TE with TENS did not improve the benefits of TE.

Background: Few population-based descriptive studies on the incidence of anterior cruciate ligament (ACL) reconstruction and concomitant pathology exist. Hypothesis: Incidence of ACL reconstruction has increased from 2002 to 2014. Study Design: Descriptive clinical epidemiology study. Level of Evidence: Level 3. Methods: The Truven Health Analytics MarketScan Commercial Claims and Encounters database, which contains insurance enrollment and health care utilization data for approximately 158 million privately insured individuals younger than 65 years, was used to obtain records of ACL reconstructions performed between 2002 and 2014 and any concomitant pathology using Current Procedures Terminology (CPT) and International Classification of Diseases, Ninth Revision (ICD-9) codes. The denominator population was defined as the total number of person-years (PYs) for all individuals in the database. Annual rates were computed overall and stratified by age, sex, and concomitant procedure. Results: There were 283,810 ACL reconstructions and 385,384,623 PYs from 2002 to 2014. The overall rate of ACL reconstruction increased 22%, from 61.4 per 100,000 PYs in 2002 to 74.6 per 100,000 PYs in 2014. Rates of isolated ACL reconstruction were relatively stable over the study period. However, among children and adolescents, rates of both isolated ACL reconstruction and ACL reconstruction with concomitant meniscal surgery increased substantially. Adolescents aged 13 to 17 years had the highest absolute rates of ACL reconstruction, and their rates increased dramatically over the 13-year study period (isolated, +37%; ACL + meniscal repair, +107%; ACL + meniscectomy, +63%). Rates of isolated ACL reconstruction were similar for males and females (26.1 vs 25.6 per 100,000 PYs, respectively, in 2014), but males had higher rates of ACL reconstruction with concomitant meniscal surgery than females. Conclusion: Incidence rates of isolated ACL reconstruction and rates of concomitant meniscal surgery have increased, particularly among children and adolescents. Clinical Relevance: A renewed focus on adoption of injury prevention programs is needed to mitigate these trends. In addition, more research is needed on long-term patient outcomes and postoperative health care utilization after ACL reconstruction, with a focus on understanding the sex-based disparity in concomitant meniscal surgery.

The study sought to determine the association between gait biomechanics (vertical ground reaction force [vGRF], vGRF loading rate [vGRF-LR]) collected 6 months following anterior cruciate ligament reconstruction (ACLR) with patient-reported outcomes at 12 months following ACLR. Walking gait biomechanics and all subsections of the Knee Injury and Osteoarthritis Outcomes Score (KOOS) were collected at 6 and 12 months following ACLR, respectively, in 25 individuals with a unilateral ACLR. Peak vGRF and peak instantaneous vGRF-LR were extracted from the first 50% of the stance phase. Limb symmetry indices (LSI) were used to normalize outcomes in the ACLR limb to that of the uninjured limb (ACLR/uninjured). Linear regression analyses were used to determine associations between biomechanical outcomes and KOOS while accounting for walking speed. Receiver operator characteristic curves were used to determine the accuracy of 6-month biomechanical outcomes for identifying individuals with acceptable patient-reported outcomes, using previously defined KOOS cut-off scores, 12 months post-ACLR. Individuals with lower peak vGRF LSI 6 months post-ACLR demonstrated worse patient-reported outcomes (KOOS Pain, Activities of Daily life, Sport and Recreation, Quality of Life) at the 12-month exam. A peak vGRF LSI ≥0.99 6 months following ACLR associated with 13.33× higher odds of reporting acceptable patient-reported outcomes 12 months post-ACLR. Lesser peak vGRF LSI during walking at 6-months post-ACLR may be a critical indicator of worse future patient-reported outcomes. Clinical significance achieving early symmetrical lower extremity loading and minimizing under-loading of the ACLR limb during walking may be a potential therapeutic target for improving patient-reported outcomes post-ACLR. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2932-2940, 2018.

This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR-SZ) or bipolar disorder (FHR-BP) with population-based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven-year-old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM-IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD-Rating Scale, the Test Observation Form, and the State-Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR-SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2-5.7, p

Diffuse large B-cell lymphoma (DLBCL) is subdivided by gene expression analysis (GEP) into two molecular subtypes named germinal center B-cell-like (GCB) and activated B-cell-like (ABC) after their putative cell-of-origin (COO). Determination of the COO is considered mandatory in any new-diagnosed DLBCL, not otherwise specified according to the updated WHO classification. Despite the fact that pathologists are free to choose the method for COO classification, immunohistochemical (IHC) assays are most widely used. However, to the best of our knowledge, no round-robin test to evaluate the interlaboratory variability has been published so far. Eight hematopathology laboratories participated in an interlaboratory test for COO classification of 10 DLBCL tumors using the IHC classifier comprising the expression of CD10, BCL6, and MUM1 (so-called Hans classifier). The results were compared with GEP for COO signature and, in a subset, with results obtained by image analysis. In 7/10 cases (70%), at least seven laboratories assigned a given case to the same COO subtype (one center assessed one sample as not analyzable), which was in agreement with the COO subtype determined by GEP. The results in 3/10 cases (30%) revealed discrepancies between centers and/or between IHC and GEP subtype. Whereas the CD10 staining results were highly reproducible, staining for MUM1 was inconsistent in 50% and for BCL6 in 40% of cases. Image analysis of 16 slides stained for BCL6 (N = 8) and MUM1 (N = 8) of the two cases with the highest disagreement in COO classification were in line with the score of the pathologists in 14/16 stainings analyzed (87.5%). This study describes the first round-robin test for COO subtyping in DLBCL using IHC and demonstrates that COO classification using the Hans classifier yields consistent results among experienced hematopathologists, even when variable staining protocols are used. Data from this small feasibility study need to be validated in larger cohorts.

Background:Articular cartilage health is an important issue following anterior cruciate ligament (ACL) injury and primary ACL reconstruction. Factors present at the time of primary ACL reconstruction may influence the subsequent progression of articular cartilage damage.Hypothesis:Larger meniscus resection at primary ACL reconstruction, increased patient age, and increased body mass index (BMI) are associated with increased odds of worsened articular cartilage damage at the time of revision ACL reconstruction.Study Design:Case-control study; Level of evidence, 3.Methods:Subjects who had primary and revision data in the databases of the Multicenter Orthopaedics Outcomes Network (MOON) and Multicenter ACL Revision Study (MARS) were included. Reviewed data included chondral surface status at the time of primary and revision surgery, meniscus status at the time of primary reconstruction, primary reconstruction graft type, time from primary to revision ACL surgery, as well as demographics and Marx activity score at the time of revision. Significant progression of articular cartilage damage was defined in each compartment according to progression on the modified Outerbridge scale (increase ≥1 grade) or >25% enlargement in any area of damage. Logistic regression identified predictors of significant chondral surface change in each compartment from primary to revision surgery.Results:A total of 134 patients were included, with a median age of 19.5 years at revision surgery. Progression of articular cartilage damage was noted in 34 patients (25.4%) in the lateral compartment, 32 (23.9%) in the medial compartment, and 31 (23.1%) in the patellofemoral compartment. For the lateral compartment, patients who had >33% of the lateral meniscus excised at primary reconstruction had 16.9-times greater odds of progression of articular cartilage injury than those with an intact lateral meniscus ( P < .001). For the medial compartment, patients who had Conclusion:Excision of the medial and lateral meniscus at primary ACL reconstruction increases the odds of articular cartilage damage in the corresponding compartment at the time of revision ACL reconstruction. Increased age is a risk factor for deterioration of articular cartilage in both tibiofemoral compartments, while increased BMI and the use of allograft for primary ACL reconstruction are associated with an increased risk of progression in the patellofemoral compartment.

The incidence of diffuse large B-cell lymphoma (DLBCL) increases with age being patient age at diagnosis an adverse prognostic factor. However, elderly patients are often underrepresented in common studies. To investigate the effect between age and biological characteristics in DLBCL, we analyzed data of 1534 patients encompassing all adult age groups, enriched for the age ≥75 years. Follicular lymphoma (FL) grade 3B with histopathological characteristics of DLBCLs were included. Gender, centroblastic cytology, FL grade 3B morphology, CD10 expression, and ABC/non-GCB-subtype were significantly associated with age after correction for multiple testing and after adjusting for cohorts. Analysis of a subgroup points towards an association of MYC expression with age. Our data indicate that biological features of DLBCL and FL grade 3B are associated with increasing age among adult patients. The prevalence of the ABC/non-GCB-subtype in elderly patients suggests that therapies targeting this molecular subtype should be specifically explored in this subgroup.

Chronic tendinopathies represent a major problem in the clinical practice of sports orthopaedic surgeons, sports doctors and other health professionals involved in the treatment of athletes and patients that perform repetitive actions. The lack of consensus relative to the diagnostic tools and treatment modalities represents a management dilemma for these professionals. With this review, the purpose of the ESSKA Basic Science Committee is to establish guidelines for understanding, diagnosing and treating this complex pathology.

Background Assortative mating is common in patients with mental disorders, both for specific disorders and across the spectrum of mental disorders. Assortative mating may play a key role in mental disorders because the person with the close relation to an individual with a mental disorder is also likely to have mental disorders, poorer cognitive abilities or lower social functioning, which may further intensify problems for both partners and their offspring. When one parent is ill, the care for the child will often depend on the other parent. Thus, assortative mating will most likely contribute to outcomes in the offspring. Therefore, the objective of this study was to investigate possible diagnoses of a mental illness, cognitive ability and social functioning in individuals who have biological children by partners with schizophrenia or bipolar disorder. Further, we also aimed to explore differences in polygenic risk scores derived from genome-wide association studies for schizophrenia, bipolar disorder, and depression. Methods This study was based on data from The Danish High Risk and Resilience Study - VIA7, a population-based cohort study conducted in Denmark between 2013 and 2016. Subjects were identified through the Danish Civil registration System and the Danish Psychiatric Central Research register. The VIA7 cohort consists of 522 children aged 7 years with parents diagnosed with schizophrenia or bipolar disorder in the Danish registries (index parents) and their partners (non-index parents). This study focuses on the non-index parents (N = 492) without schizophrenia or bipolar disorder in the Danish registries. All participants were interviewed with a diagnostic interview (SCAN 2.0). Main outcomes were intelligence, processing speed, verbal working memory, and social functioning. A linear mixed effect model was applied for each of the outcomes, including parent status (index parent or non-index parent), group (schizophrenia, bipolar disorder, and control), and interaction between parent status and group. Results Non-index parents having children by a partner with schizophrenia or bipolar disorder more often fulfilled the criteria for a mental disorder compared to non-index parents in the control group. Non-index parents having children by a partner with schizophrenia or bipolar disorder had lower levels of social functioning compared to non-index parents in the control group and performed poorer on intelligence and processing speed. Discussion Individuals who have children by partners with schizophrenia or bipolar disorder are more likely to have a mental disorder and to have lower levels of cognitive and social functioning compared to individuals who have children by partners without schizophrenia or bipolar disorder. Assortative mating may have important implications for our understanding of the familial transmission of these disorders. The findings presented in this study should be considered in future genetic research in psychiatry, specifically in the investigation of potential risk factors for children with a parent with schizophrenia or bipolar disorder.

We aimed to examine the prevalence of psychotic experiences (PEs) in children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and, in exploratory analyses, to examine the possible associations between PEs and mental disorders as well as level of functioning. A cohort of seven-year-old children with FHR-SZ (N = 199), FHR-BP (N = 118) and controls (N = 196) was recruited through Danish nationwide registers. Lifetime PEs were assessed through interviews using the psychosis section of the ‘Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version’ (K-SADS-PL). Lifetime DSM-IV diagnoses were ascertained through K-SADS-PL and the level of functioning of the children through ‘Children's Global Assessment Scale’. Both children with FHR-SZ (OR = 2.9, 95% CI = 1.4–6.2, p = 0.005) and FHR-BP (OR = 2.9, 95% CI = 1.3–6.7, p = 0.011) had an increased risk of having experienced “severe” PEs compared with controls. In the overall cohort PEs were associated with any lifetime mental disorder, Attention-Deficit/Hyperactivity Disorder, anxiety disorders and a lower level of functioning. The findings of a higher proportion of high risk children reporting PEs could represent an early manifestation of later more severe psychopathology or simply an unspecific transitory symptom. Future follow-up studies of this cohort will explore the predictive value of the occurrence of PEs at age seven.

BackgroundInsertional Achilles tendinopathy is well known to be difficult to treat, especially when there is intra-tendinous bone pathology. This study is a case series on patients with chronic insertional Achilles tendon pain and major intra-tendinous bony pathology together with bursa and tendon pathology, treated with excision of the subcutaneous bursa alone.MethodsEleven patients (eight men and three women) with a mean age of 44 years (range 24–62) and a chronic (>6 months) painful condition from altogether 15 Achilles tendon insertions were included. In all patients, ultrasound examination showed intra-tendinous bone pathology together with pathology in the tendon and subcutaneous bursa, and all were surgically treated with an open excision of the whole subcutaneous bursa alone. This was followed by full weight-bearing walking in a shoe with open heel for 6 weeks.ResultsAt follow-up 21 (median, range 12–108) months after surgery, 9/11 patients (12/15 tendons) were satisfied with the result of the operation and 10/11 (13/15 tendons) were back in their previous sport and recreational activities. The median VISA-A score had improved from 41 (range 0–52) to 91 (range 33–100) (pConclusionIn patients with chronic painful insertional Achilles tendinopathy with intra-tendinous bone pathology, tendon and bursa pathology, open removal of the subcutaneous bursa alone can relieve the pain and allow for Achilles tendon loading activities. The results in this case series highlight the need for more studies on the pain mechanisms in insertional Achilles tendinopathy and the need for randomised studies to strengthen the conclusions.Level of evidenceIV Case series.

BACKGROUND: Attention deficits are found in children at familial high risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP) using assessment methods relying on motor-based response latency. This study compares visual attention functions in children at FHR-SZ or FHR-BP with controls using an unspeeded task unconfounded by motor components.METHODS: Visual attention was assessed in 133 7-year-old children at FHR-SZ (N = 56) or FHR-BP (N = 32), and controls (N = 45) using the unspeeded paradigm, TVA-based whole report. We compared four parameters of visual attention: visual processing speed, visual short-term memory, threshold for visual perception, and error rate. Further, we investigated their potential relationships with severity of psychopathology, adequacy of the home environment, and neurocognitive measures.RESULTS: Children at FHR-SZ displayed significant deficits in perceptual processing speed of visual attention compared with controls (p LIMITATIONS: Larger group sizes would have permitted inclusion of more predictors in the search for neurocognitive and other factors associated with the parameters of TVA-based whole report.CONCLUSIONS: Young children at FHR-SZ and FHR-BP display significant deficits in processing speed of visual attention, which may reflect the effect of shared vulnerability risk genes. Early identification of children at FHR-SZ and FHR-BP with perceptual processing speed impairments may represent a low-cost basis for low-risk interventions.

OBJECTIVE: The home environment provided by the caregivers of a child is an influential single factor for development and wellbeing. We aimed to compare the quality of the home environment of children at familial high-risk of schizophrenia or bipolar disorder with population-based controls.METHODS: Danish nationwide registers were used to retrieve a cohort of 522 7-year-old children of parents diagnosed with schizophrenia (N= 202), bipolar disorder (N = 120) or none of these diagnoses (N = 200). The home environment was assessed using the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory).RESULTS: The proportion of children living in home environments that were evaluated not to meet the needs of a 7-year old child was significantly larger in the two familial high risk groups. This was true for 21% of the children with familial predisposition for schizophrenia and 7% of children with familial disposition for bipolar disorder.CONCLUSION: Children born to parents diagnosed with schizophrenia and to a lesser extent bipolar disorder are at an increased risk of growing up in a home environment with an insufficient level of stimulation and support. Identifying families with inadequate home environments is a necessary step towards specialized help and support to at-risk families. This article is protected by copyright. All rights reserved.

Hydrocephalus shunt malfunction can—also in children—occur insidiously without clear symptoms of raised intracranial pressure (ICP) or changes in ventricular size, imposing a diagnostic challenge. Computerized shunt infusion studies enable quantitative shunt function assessment. We report on feasibility and results of this technique in children in a two center cross-sectional study. Shunt infusion study (SIS) is performed with two needles inserted into a pre-chamber for ICP recording and CSF infusion. After baseline ICP recording, constant rate infusion is started until a new ICP plateau (ICPpl) is reached. Dedicated software containing the shunt’s resistance characteristics calculates ICP and its amplitude outflow resistance and critical shunt pressure (CSP). Overall, 203 SIS were performed in 166 children. Shunts were defined as functional if ICPpl was 5 mmHg above CSP and borderline in between. Forty-one shunts (20.2%) were found obstructed, 26 (12.8%) had borderline characteristics, and 136 (67%) were functional. Baseline ICP in obstructed shunts was significantly above shunt operating pressure. CSF outflow resistance (Rout) and ∆ICP plateau were significantly elevated in obstructed shunts, with cut-off thresholds of 8.07 mmHg min/ml and 11.74 mmHg respectively. Subgroup analysis showed smaller ventricles in 69% of revised cases. SIS is a feasible, reliable, and radiation-free technique for quantitative shunt assessment to rule out or prove shunt malfunction. Dedicated software containing shunt hydrodynamic characteristics is necessary and small children may need short-term sedation. Due to the clinical and inherent economic advantages, SIS should be more frequently used in pediatric neurosurgery.

Clinical response to electroconvulsive therapy (ECT) depends on eliciting a generalized seizure. Though there are multiple ictal and other parameters to assess seizure quality, factors that influence these parameters have only been identified to a limited extend in antecedent studies (e.g., stimulus dosage, age). In the context of ECT, electrolyte concentrations have hardly been investigated so far—although hyponatremia is one well-known clinical factor to increase the risk of spontaneous seizures. In 31 patients with unipolar or bipolar depressive disorder, blood concentrations of sodium (Na), potassium (K), and calcium (Ca) were measured immediately prior to repeated sessions of maintenance ECT. Generalized linear mixed models were used to analyze the influence of Na, K, and Ca on seven seizure quality parameters: postictal suppression index (PSI), maximum sustained coherence (MSC), midictal amplitude, average seizure energy index, seizure duration (EEG/motor), and peak heart rate. Results show a statistically significant relationship between the serum sodium level and MSC: in the model, a reduction of 1 mmol/l led to an increase in interhemispheric coherence of 0.678%. The further markers remained unaffected by changes in electrolyte concentrations. This finding provides first evidence that a lower blood concentration of sodium could enhance the quality of ECT-induced seizures in terms of higher interhemispheric coherence.

BACKGROUND: Prior studies have established that partners are similar to each other in many aspects. They correlate positively and strongly on age, social attitudes, and religiosity; correlate moderately on general intelligence, education, and physical attractiveness; and correlate weakly on height, weight, and personality traits. It remains unknown if and how this affects partners of individuals with schizophrenia or bipolar disorder. This aspect is clinically relevant when we want to characterize the risk factors for children growing up in families where one parent is living with schizophrenia or bipolar disorder. Therefore, the objective of this study is to investigate the diagnoses of a mental illness, cognitive ability, social functioning and polygenic risk in individuals who have children together with individuals with schizophrenia or bipolar disorder compared to controls. METHODS: The Danish High Risk and Resilience Study - VIA7 is a nationwide cohort study conducted in Denmark between January 1, 2013 and January 31, 2016. The VIA7 cohort consists of 522 children aged 7 years with 0, 1 or 2 parents diagnosed with schizophrenia or bipolar disorder and both of their biological parents. Subjects were identified through the Danish Civil registration System and the Danish Psychiatric Central Research register. This study will focus on the biological co-parents (N = 443) without schizophrenia or bipolar disorder in the Danish registries. All participants were interviewed with SCAN and social functioning was measured using PSP. Further, we assessed intelligence (RIST), verbal working memory (Letter-Number Sequencing - WAIS-IV), and processing speed (Coding - WAIS-IV). RESULTS: Data analysis is on-going and data will be presented at the conference. DISCUSSION: Data analysis is on-going and data will be presented at the conference.

BACKGROUND: Psychotic like experiences (PLEs) are frequently found among children from the general population. PLEs are often transitory phenomena, but are for some predictive of later psychopathology, e.g. psychotic disorders and non-psychotic disorders. For both schizophrenia and bipolar disorder, the single largest risk factor for developing the disorder is a positive family history of the disorder. Therefore, early antecedents of schizophrenia and bipolar disorder can be identified by studying children of parents with these disorders. However, little is known of the occurrence of PLEs in children with familial high risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP). We aimed to explore PLEs and their associations to mental disorders and level of functioning in young children with FHR-SZ and FHR-BP compared with controls. METHODS: The Danish High Risk and Resilience Study – VIA7 is a population-based cohort study. We retrieved a representative cohort of seven-year-old children with FHR-SZ (N=202), FHR-BP (N=120), and population-based controls(N=200) using Danish nationwide registers. PLEs were assessed through interview with the psychosis appendix of the ‘Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version’ (K-SADS-PL). Both children and primary caregivers were interviewed. Lifetime DSM-IV diagnoses were identified by interview with the K-SADS-PL. The general level of functioning was assessed with the Children’s Global Assessment Scale. RESULTS: The three groups displayed clear differences in the prevalence of PLEs. Additionally, the associations between PLEs and psychopathology as well as level of functioning are explored. These findings will be presented at the session. CONCLUSIONS: Our findings suggest that further studies of the long-term implications of PLEs in young children with familial high risk of severe mental disorders are needed. In particular with regard to the effect of PLEs on general level of functioning and mental health of these children.

Background Mobile app–based therapies are increasingly being employed by speech-language pathologists in the rehabilitation of people with aphasia as adjuncts or substitutes for traditional in-person therapy approaches. These apps can increase the intensity of treatment and have resulted in meaningful outcomes across several domains. Objective VoiceAdapt is a mobile therapy app designed with user and stakeholder feedback within a user-centered design framework. VoiceAdapt uses two evidence-based lexical retrieval treatments to help people with aphasia in improving their naming abilities through interactions with the app. The purpose of the randomized controlled trial (RCT) proposed here is to examine the feasibility and clinical efficacy of training with VoiceAdapt on the language and communication outcomes of people with aphasia. Methods A multicenter RCT is being conducted at two locations within Canada. A total of 80 people with aphasia will be recruited to participate in a two-arm, waitlist-controlled, crossover group RCT. After baseline assessment, participants will be randomized into an intervention group or a waitlist control group. The intervention group participants will engage in 5 weeks of training with the app, followed by posttreatment and follow-up assessments after an additional 5 weeks. Those in the waitlist control group will have no training for 5 weeks; this is followed by pretreatment assessment, training for 5 weeks, and posttreatment assessment. All trial procedures are being conducted remotely given the COVID-19 pandemic. Results Recruitment of participants started in September 2020, and the study is expected to be completed by March 2022. Publication of results is expected within 6 months of study completion. Conclusions The results of the RCT will provide information on evidence-based practice using technology-based solutions to treat aphasia. If positive results are obtained from this RCT, the VoiceAdapt app can be recommended as an efficacious means of improving lexical retrieval and communicative functioning in people with aphasia in an easily accessible and a cost-effective manner. Moreover, the implementation of this RCT through remote assessment and delivery can provide information to therapists on telerehabilitation practices and monitoring of app-based home therapy programs. Trial Registration ClinicalTrials.gov NCT04108364; https://clinicaltrials.gov/ct2/show/NCT04108364 International Registered Report Identifier (IRRID) DERR1-10.2196/30621

ObjectivesChronic painful insertional Achilles tendinopathy is known to be difficult to manage. The diagnosis is not always easy because multiple different tissues can be involved. The plantaris tendon has recently been described to frequently be involved in chronic painful mid-portion Achilles tendinopathy. This study aimed to evaluate possible plantaris tendon involvement in patients with chronic painful insertional Achilles tendinopathy.MethodsNinety-nine consecutive patients (74 males, 25 females) with a mean age of 40 years (range 24–64) who were surgically treated for insertional Achilles tendinopathy, were included. Clinical examination, ultrasound (US)+Doppler examination, and surgical findings were used to evaluate plantaris tendon involvement.ResultsIn 48/99 patients, there were clinical symptoms of plantaris tendon involvement with pain and tenderness located medially at the Achilles tendon insertion. In all these cases, surgical findings showed a thick and wide plantaris tendon together with a richly vascularised fatty infiltration between the plantaris and Achilles tendon. US examination suspected plantaris involvement in 32/48 patients.ConclusionPlantaris tendon involvement can potentially be part of the pathology in chronic painful insertional Achilles tendinopathy and should be considered for diagnosis and treatment when there is distinct and focal medial pain and tenderness.Level of evidenceIV case series.