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BackgroundAlthough shoulder arthroplasty is less common than knee or hip arthroplasty, the number of procedures being performed is increasing rapidly. The treatment effect is a simple method to measure outcome of joint replacement. The method was applied to measure results of total hip/knee arthroplasty but not yet for shoulder arthroplasty.MethodsIncluded were patients with unilateral cuff arthropathy (Hamada grades > = 2) treated with reversed total shoulder arthroplasty (RSA) in this prospective multicenter study. The patients were assessed with the ASES questionnaire. The treatment effects (TE) was calculated for each patient. TE = score reduction/baseline score. A positive TE means amelioration, TE = 0 unchanged, and a negative TE means worse. The primary aim was to calculate the TE’s for RSA at 6, 12, 24, and 60 months postoperatively. The secondary aim was to analyze the influence of confounders (preoperative Hamada grade, age, gender, dominance, side of the affected shoulder, general co-morbidities measured using ASA grade).ResultsTwo hundred three patients were included for this analysis of whom 183 patients had a complete 2 year follow up. Two years postoperatively the mean ASES score augmented significant from 20.5 to 78.7 (p p-value 0.042). For age and dominant side there were weak associations where those aged 80+ and dominant side had better TE’s. The patients with higher ASA grade had lower TE’s (ASA grade 4+ vs. 1,p-value 0.013). The mean TE’s were 0.77 at 6-months, 0.81 at 1 year, 0.76 at 2 years and 0.73 at 5 years.ConclusionsThe outcome for reverse shoulder arthroplasty can be measured with the treatment effect method; the 2 years TE’s vary from 1 to 0.09. The mean treatment effects change little in the first five postoperative years (from 0.73 to 0.81). The confounders for better TE’s were: higher severity of cuff arthropathy (Hamada grade 3, 4 and 5), less co-morbidities (ASA Grade 1), higher age (80+) and dominant side. Gender did not influence the 2-year TE’s.Trial registrationComité intercantonal d’éthique (Jura, Fribourg, Neuchâtel), number 01/2008,24.09.2008.

Feature integration theory proposes that visual features, such as shape and color, can only be combined into a unified object when spatial attention is directed to their location in retinotopic maps. Eye movements cause dramatic changes on our retinae, and are associated with obligatory shifts in spatial attention. In two experiments, we measured the prevalence of conjunction errors (that is, reporting an object as having an attribute that belonged to another object), for brief stimulus presentation before, during, and after a saccade. Planning and executing a saccade did not itself disrupt feature integration. Motion did disrupt feature integration, leading to an increase in conjunction errors. However, retinal motion of an equal extent but caused by saccadic eye movements is spared this disruption, and showed similar rates of conjunction errors as a condition with static stimuli presented to a static eye. The results suggest that extra-retinal signals are able to compensate for the motion caused by saccadic eye movements, thereby preserving the integrity of objects across saccades and preventing their features from mixing or mis-binding. Electronic supplementary material The online version of this article (10.3758/s13414-019-01873-7) contains supplementary material, which is available to authorized users.

Background: The interest in outcome measurement in pediatric palliative care is rising. To date, the majority of studies investigating relevant outcomes of pediatric palliative care focus on children with cancer. Insight is lacking, however, about relevant outcome domains for children with severe neurological impairment and their families. Aim: The aim of this study was to identify meaningful outcome domains of pediatric palliative care for children with severe neurological impairment and their families. Design: A qualitative research design following a constructivist research paradigm was employed. Guided interviews were conducted with parents of children with life-limiting conditions and severe neurological impairment and professional caregivers. The data were analyzed using qualitative content analysis. Setting: Overall, 10 cooperating pediatric palliative care institutions across Germany (outpatient and inpatient settings) aided in the recruitment of eligible parents and professional caregivers. A total of 11 interviews with 14 parents and 17 interviews with 20 professional caregivers were conducted. Results: Six core outcome domains of pediatric palliative care for children with severe neurological impairment and their families were identified, namely (1) symptom control, (2) respite and support, (3) normalcy, (4) security, (5) empowerment, and (6) coping with the disease, each consisting of 1 to 13 individual aspects. Conclusion: As for other diagnostic groups, symptom control is a relevant outcome domain for children with severe neurological impairment. However, other outcome domains which focus on the whole family and take into account the long disease trajectory, such as respite and support, security, empowerment, and coping with the disease, are also crucial.

The myogenic differentiation 1 gene (MYOD1) p.L122R somatic mutation was first discovered in a subset of clinically aggressive embryonal rhabdomyosarcomas and has since been described in both pediatric and adult spindle cell/sclerosing rhabdomyosarcomas. Relatively little is known about the clinical, molecular, and histopathological features of these tumors in children. In order to further characterize the genomic and clinical features of pediatric MYOD1-mutant sarcomas, we evaluated a cohort of soft-tissue sarcoma patients treated at Texas Children's Hospital. Tumor DNA was subjected to next-generation panel sequencing and/or Sanger sequencing of the MYOD1 hotspot mutation. The MYOD1 p.L122R mutation was identified in six tumors, with a variant allele fraction greater than 0.8 in three cases, suggestive of loss of heterozygosity. One sclerosing rhabdomyosarcoma lacking the MYOD1 hotspot mutation was observed to have a MYOD1 copy number gain, also with evidence of loss of heterozygosity. Cancer gene panel sequencing revealed potentially targetable alterations in six of seven (86%) patients with MYOD1 alterations, including four patients with an alteration in the PI3K-AKT pathway: two hotspot PIK3CA mutations and deletions in PTEN and TSC2. On histopathologic review, MYOD1-altered tumors exhibited spindle and/or round cells and varying degrees of hyaline sclerosis. At last follow-up, six patients had died of disease and the seventh progressed early and was subsequently lost to follow-up. Both pre- and post-therapy patient-derived xenograft models were generated from one patient's tumor. These models were confirmed to harbor the MYOD1 and PIK3CA mutations seen in the primary tumor and were shown to be sensitive to PI3K/mTOR inhibition in vitro and in vivo. In conclusion, this study adds to recent reports describing the clinicopathologic and genomic features of MYOD1-altered soft-tissue sarcomas in children, including dismal prognosis and potential molecular targets for therapy. The novel preclinical models developed will facilitate further biological and preclinical study of this rare and aggressive tumor. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A hallmark of the adaptive immune response is the ability of CD4 T cells to differentiate into a variety of pathogen appropriate and specialized effector subsets. A long-standing question in CD4 T cell biology is whether the strength of TCR signals can instruct one Th cell fate over another. The contribution of TCR signal strength to the development of Th1 and T follicular helper (Tfh) cells has been particularly difficult to resolve, with conflicting results reported in a variety of models. Although cumulative TCR signal strength can be modulated by the infection specific environment, whether or not TCR signal strength plays a dominant role in Th1 versus Tfh cell fate decisions across distinct infectious contexts is not known. Here we characterized the differentiation of CD4 TCR transgenic T cells responding to a panel of recombinant wild type or altered peptide ligand lymphocytic choriomeningitis viruses (LCMV) derived from acute and chronic parental strains. We found that while TCR signal strength positively regulates T cell expansion in both infection settings, it exerts opposite and hierarchical effects on the balance of Th1 and Tfh cells generated in response to acute versus persistent infection. The observation that weakly activated T cells, which comprise up to fifty percent of an endogenous CD4 T cell response, support the development of Th1 effectors highlights the possibility that they may resist functional inactivation during chronic infection. We anticipate that the panel of variant ligands and recombinant viruses described herein will be a valuable tool for immunologists investigating a wide range of CD4 T cell responses.Graphical abstractHighlightsIdentification of a wide panel of altered peptide ligands for the LCMV-derived GP61 peptideGeneration of LCMV variant strains to examine the impact of TCR signal strength on CD4 T cells responding during acute and chronic viral infectionThe relationship between TCR signal strength and Th1 differentiation shifts according to the infection context: TCR signal strength correlates positively with Th1 generation during acute infection but negatively during chronic infection.

Background Pediatric papillary thyroid carcinoma (PTC) is clinically and biologically distinct from adult PTC. We sequenced a cohort of clinically annotated pediatric PTC cases enriched for high-risk tumors to identify genetic alterations of relevance for diagnosis and therapy. Methods Tumor DNA and RNA were extracted from FFPE tissue and subjected to next-generation sequencing (NGS) library preparation using a custom 124-gene hybridization capture panel and the 75-gene Archer Oncology Research Panel, respectively. NGS libraries were sequenced on an Illumina MiSeq. Results Thirty-six pediatric PTC cases were analyzed. Metastases were frequently observed to cervical lymph nodes (29/36, 81%), with pulmonary metastases less commonly found (10/36, 28%). Relapsed or refractory disease occurred in 18 patients (18/36, 50%). DNA sequencing revealed targetable mutations in 8 of 31 tumors tested (26%), most commonly BRAF p.V600E (n = 6). RNA sequencing identified targetable fusions in 13 of 25 tumors tested (52%): RET (n = 8), NTRK3 (n = 4), and BRAF. Mutually exclusive targetable alterations were discovered in 15 of the 20 tumors (75%) with both DNA and RNA analyzed. Fusion-positive PTC was associated with multifocal disease, higher tumor staging, and higher American Thyroid Association risk levels. Both BRAF V600E mutations and gene fusions were correlated with the presence of cervical metastases. Conclusions Targetable alterations were identified in 75% of pediatric PTC cases with both DNA and RNA evaluated. Inclusion of RNA sequencing for detection of fusion genes is critical for evaluation of these tumors. Patients with fusion-positive tumors were more likely to have features of high-risk disease.

ContextBaseball is played around the world, including in North America and Latin America. The repetitive and stressful act of throwing can lead to adaptations such as increased humeral retroversion (HR) in the throwing arm. This adaptation is often considered beneficial as it allows more glenohumeral external rotation during the cocking phase of pitching without soft tissue stretching. Therefore, it is speculated that throwing should be started at a young age to capitalize on this adaptation. Interestingly, athletes in different geographic regions of the world often begin organized baseball at different ages. However, range of motion (ROM), HR, and the starting age of baseball have never been examined based on geographic region.ObjectiveTo determine if ROM, HR, and the starting age of baseball players differed between professional baseball pitchers from North America and Latin America.DesignCross-sectional study.SettingClinical setting.Patients or Other ParticipantsThirty professional pitchers (North American = 19, Latin American = 11) with no current injury or surgery in the previous 6 months.Main Outcome Measure(s)Both ROM and HR were measured in the dominant and nondominant shoulder of each participant. The starting age for baseball was self-reported.ResultsThe Latin American group had more dominant-arm HR (8.7°; P = .034), more nondominant-arm external rotation (5.3°; P = .049), and a trend toward more nondominant-arm HR (6.5°; P = .058), yet they started playing baseball at a later age (by 3.7 years; P = .021) compared with the North American group.ConclusionsLatin American players had greater HR but started playing baseball at an older age. These findings contradict current thinking that HR would be more pronounced if baseball was started at a younger age. Additional research is required to better understand HR and the genetic, environmental, and nutritional factors that contribute to its development.

Background The negative effects of behavioural changes among dementia residents and the consequences for caregivers are a major problem in the care of people with dementia. Case conferences (CC) are recommended as a useful method to understand the underlying causes of the behaviour and to plan tailored interventions Objectives The aim of this article is to describe the effects of two dementia-specific CC models on the prevalence of behaviour that challenges and other secondary outcomes. Design Stepped-wedge cluster randomized trial. Setting Nursing homes: The inclusion criterion was the participation of at least two units with a minimum of 30 residents who were mainly cared for in the study units. Participants A total of 224 residents and 189 staff from six nursing homes in the IdA (Innovative dementia-orientated Assessment system) cohort and 241 residents and 284 staff from six nursing homes in the Neo (Narrative Approach) cohort were included in the study. The inclusion criteria were the following: medical diagnosis of dementia from nursing charts, FAST (Functional Assessment Staging) score > 1, living at least 15 days in the unit, and informed consent. Methods The nursing homes were randomized to the type of intervention and time point of intervention delivery. The two interventions in the form of the case conference models (Welcome-IdA and -Neo) differed in the type of behaviour analysis method. The intervention duration was seven months. The primary outcome was the change in the prevalence of behaviour that challenges. Secondary outcomes were residents’ quality of life, prescription of psychotropic medications, formal caregiver burnout, dementia-related stress, and vocational action competence. The outcomes were measured on seven data points every three months. Linear mixed-effects models were used to analyze intervention effects between the control, intervention and follow-up periods. Results No differences were found concerning the primary outcome between the control and intervention cohorts for both CC models. Further exploratory data analyses showed a reduction in behaviours such as apathy (18%) and eating disturbances (29%) for the IdA cohort and hallucination (27%) and delusion (28%) in the NEO cohort. Only staff in the IdA cohort demonstrated a reduction in work-related burnout from the control phase to the intervention phase. Conclusion Specific CC for behaviour that challenges do not decrease the overall prevalence of residents showing changes in behaviour. However, there are indications that the case conferences influence some types of behaviour and reduce the risk factors for work-related burnout

Background Baseball pitching places tremendous forces on the arm, which may lead to structural tissue adaptations that are represented by changes in rotational range of motion (ROM). These adaptations often include both bony and soft tissue; however, the contribution of each tissue to the change in motion is not always clinically attainable. The purposes of this study were to determine the adaptations of ROM, bone, and soft tissue bilaterally and to examine the correlation between clinical ROM and humeral retroversion (HR)–corrected ROM. We hypothesized that glenohumeral internal rotation (IR) and total motion would be decreased and glenohumeral external rotation (ER), posterior capsule thickness (PCT), and HR would be increased in the dominant arm; that HR-corrected ROM would be significantly different than clinical ROM; and that HR-corrected ROM would be correlated with total motion difference. Methods Thirty professional baseball pitchers participated in this study. HR, PCT, and glenohumeral IR and ER were evaluated in the dominant and nondominant shoulders of each subject. Results The dominant arm exhibited significantly more retroversion, ER, and PCT than the nondominant arm. The dominant arm also had significantly less IR and total motion than the nondominant arm. The total ROM difference was significantly correlated with both HR-corrected glenohumeral IR deficit and ER gain. Conclusion HR-corrected glenohumeral IR deficit and ER gain may more accurately reflect the contribution of soft-tissue changes to ROM. Unfortunately, measurement of HR is not always clinically attainable, making clinical management difficult.

Myeloid sarcoma (MS) is a neoplastic condition composed of immature myeloid cells involving an extramedullary site. We investigated underlying chromosomal and molecular alterations to assess potential molecular markers of prognosis and outcome in this rare pediatric disease. We conducted a retrospective review of clinicopathologic and cytogenetic data from 33 pediatric patients with MS (ages 1 month-18 years) at our institution over a 32 year period (1984-2016). Tissue-based cancer microarray and targeted next-generation sequencing analysis were performed on six cases. The median age at diagnosis was 2.8 years with a male-to-female ratio of 2.6:1. MS is commonly presented with concomitant marrow involvement (

A rotator cuff tear is a common injury in athletes and workers who repeatedly perform overhead movements, and it is not uncommon for this demographic to return to activity shortly after treatment. A biceps tenotomy is often performed in the presence of a rotator cuff tear to help reduce pain and improve joint function. However, the effect of this procedure on the surrounding tissues in the glenohumeral joint is unknown. Therefore, the purpose of this study was to investigate the effect of a biceps tenotomy in the presence of a supraspinatus rotator cuff tear followed by overuse activity on ambulatory function and mechanical and histologic properties of the remaining rotator cuff tendons and glenoid cartilage. 46 rats underwent 4weeks of overuse activity to create a tendinopathic condition, then were randomized into two groups: unilateral detachment of the supraspinatus tendon or detachment of the supraspinatus and long head of the biceps tendons. Ambulatory measurements were performed throughout the 8weeks prior to euthanasia, followed by analysis of the properties of the remaining intact tendons and glenoid cartilage. Results demonstrate that shoulder function was not effected in the biceps tenotomy group. However, the intact tendons and glenoid cartilage showed altered mechanical and histologic properties. This study provides evidence from an animal model that does not support the use of tenotomy in the presence of a supraspinatus tendon rotator cuff tear, and provides a framework for physicians to better prescribe long-term treatment strategies for patients.

Background The natural time course for recovery of glenohumeral internal rotation (IR) loss after a throwing episode is unknown. In addition, the effect of the sleeper stretch on the time course for recovery of motion after a throwing episode has never been investigated. Therefore, the objectives of this study were to (1) to determine the natural time course for spontaneous recovery of IR after a throwing episode and (2) to evaluate the effect of the sleeper stretch on the time course for recovery of IR after a throwing episode. Methods The study participants were 17 male high school baseball pitchers (aged 17.7 ± 0.9 years). A crossover designed was used over a 2-week period. For week 1, glenohumeral IR and external rotation (ER) were evaluated in the dominant shoulder 1 day before a throwing episode and at 2 hours, 1 day, 2 days, 3 days, 4 days, and 5 days after pitching. During week 2, participants completed a sleeper stretch protocol before measurements. Results The natural time course of spontaneous recovery for IR after a throwing episode was 4 days. Stretching reduced the time course of recovery for IR to 2 days. Conclusion A sleeper stretch program for high school baseball pitchers can accelerate the recovery of commonly observed IR loss and also may mitigate the cumulative effects observed over the course of a season.

OBJECTIVE To evaluate the clinical outcomes of reverse shoulder arthroplasty (RSA) in elderly patients with proximal humeral fractures and assess the role of tuberosity healing on the outcome. DESIGN Case series. SETTING Multicenter clinical study of Level-2 trauma centers. PATIENTS/PARTICIPANTS We included 81 patients with a mean age of 78.5 ± 6.5 years (range, 58.5-90.9 years) and a nonreconstructable proximal humeral fracture. INTERVENTION Modular reverse fracture shoulder arthroplasty. MAIN OUTCOME MEASUREMENTS We determined range of motion, constant score, and the American Shoulder and Elbow Surgeons Shoulder Score as clinical outcomes and evaluated tuberosity healing at 6 weeks, 6 months, 1 year, and 2 years. RESULTS Tuberosities healed in most patients; 37 patients had completely healed tuberosities, and 33 patients had partially healed tuberosities, whereas 11 patients had unhealed tuberosities. However, no significant differences were found in the functional outcomes among the 3 groups (P > 0.05). CONCLUSIONS Our results with a modular reverse prosthesis confirmed similar constant scores, American Shoulder and Elbow Surgeons Shoulder Scores, and tuberosity healing rates as reported in the current clinical evidence for RSA. We could not confirm that tuberosity healing improved functional outcomes; however, it should be noted that tuberosity healing was assessed using standard radiographs. Nevertheless, our study strengthens the consensus that RSA can be recommended for well-selected elderly patients with complex displaced proximal humeral fractures. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The New York State Department of Health conducted the Healthy Fishing Communities Program in collaboration with the Agency for Toxic Substances and Disease Registry to assess human exposure to contaminants common to Lake Ontario, Lake Erie and surrounding rivers and waterways among populations in western New York State who eat locally caught fish. The program enrolled licensed anglers and Burmese refugees and immigrants, living near four designated Great Lakes Areas of Concern: Buffalo River, Niagara River, Eighteenmile Creek, and the Rochester Embayment. These target populations were sampled and enrolled independently into the program between February and October of 2013. A core set of contaminants were measured in blood and urine of 409 licensed anglers and 206 Burmese refugees and immigrants which included lead, cadmium, mercury, PCBs, PBDEs, organochlorine pesticides (hexachlorobenzene, mirex, DDT, DDE, and chlordane and its metabolites oxychlordane and trans-Nonachlor), and PFOS and PFOA. Biomonitoring results showed that both groups had higher geometric means for blood lead, total blood mercury, and serum PFOS compared to the 2013–2014 NHANES reference levels. The Burmese refugee group also showed higher geometric means for creatinine-adjusted urine mercury and lipid-adjusted serum DDE compared to national levels. Licensed angler participants reported eating a median of 16 locally caught fish meals in the past year. Burmese participants consumed local fish throughout the year, and most frequently in the summer (median 39 fish meals or 3 times a week). The study results provide valuable information on populations at high risk of exposure to contaminants in the Great Lakes Basin of western New York. The results provide the foundation for developing and implementing public health actions to reduce potential exposures to Great Lakes pollutants.

Nodular fasciitis is a self-limited myofibroblastic lesion that can be misdiagnosed as a sarcoma as a result of its rapid growth, cellularity, and sometimes prominent mitotic activity. A recurrent translocation t(17;22) has been identified in nodular fasciitis, fusing the coding region of USP6 to the promoter region of MYH9, and resulting in increased USP6 expression. A subset of cases show USP6 rearrangement without the typical fusion variants by RT-PCR, or any MYH9 rearrangement by FISH. We sought to further characterize such tumors using molecular diagnostic assays. A novel RT-PCR assay was designed to detect the two known MYH9-USP6 fusion types in formalin-fixed paraffin-embedded and frozen tissue, and a break-apart FISH assay was designed to detect USP6 rearrangement. Twenty-six cases of nodular fasciitis diagnosed between 2002 and 2013 were retrieved from the pathology files of our institutions and were confirmed to be positive by FISH and/or RT-PCR. Seven samples showed USP6 rearrangement by FISH but were negative for MYH9-USP6 fusion by RT-PCR; these cases were subjected to a next-generation sequencing assay utilizing anchored multiplex PCR technology. This assay targets a single partner gene associated with fusions in bone and soft tissue tumors for agnostic detection of gene fusion partners. Novel fusion partners were identified in all seven cases and confirmed by RT-PCR. Structurally, all fusions consisted of the juxtaposition of the entire coding region of USP6 with the promoter of the partner gene, driving increased USP6 expression. This study confirms the neoplastic nature of nodular fasciitis, defines additional pathogenic fusion partners, and adds to the growing body of literature on USP6-associated neoplasia. Given the diagnostic challenges of these tumors, molecular assays can be useful ancillary tools; however, the prevalence of promoter swapping must be recognized when interpreting results.

Background Rotator cuff tears are common conditions that often require surgical repair to improve function and to relieve pain. Unfortunately, repair failure remains a common problem after rotator cuff repair surgery. Several factors may contribute to repair failure, including age, tear size, and time from injury. However, the mechanical mechanisms resulting in repair failure are not well understood, making clinical management difficult. Specifically, altered scapular motion (termed scapular dyskinesis) may be one important and modifiable factor contributing to the risk of repair failure. Therefore, the objective of this study was to determine the effect of scapular dyskinesis on supraspinatus tendon healing after repair. Methods A rat model of scapular dyskinesis was used. Seventy adult male Sprague-Dawley rats (400-450 g) were randomized into 2 groups: nerve transection of the accessory and long thoracic nerves (SD) or sham nerve transection (Sham control). After this procedure, all rats underwent unilateral detachment and repair of the supraspinatus tendon. All rats were sacrificed at 2, 4, and 8 weeks after surgery. Shoulder function, passive joint mechanics, and tendon properties (mechanical, histologic, organizational, and compositional) were evaluated. Results Scapular dyskinesis alters joint function and may lead to compromised supraspinatus tendon properties. Specifically, diminished mechanical properties, altered histology, and decreased tendon organization were observed for some parameters. Conclusion This study identifies scapular dyskinesis as one underlying mechanism leading to compromise of supraspinatus healing after repair. Identifying modifiable factors that lead to compromised tendon healing will help improve clinical outcomes after repair.

Introduction This study documents 2-year clinical and radiographic results following reversed total shoulder arthroplasty using a novel prosthesis with inverted bearing materials (polyethylene glenoid; metal humeral component). This design was intended to avoid massive PE abrasion on the humeral side. Therefore, we predicted a lack of subsequent osteolysis-induced exacerbation of scapular notching, and because of other design features and modified operating technique a reduced notching rate. Materials and methods An ongoing, prospective, international, multicenter study of patients implanted with a novel prosthesis at six European centers. The current analysis presents 2-year follow-up data (patients operated between December 2007 and July 2009). Clinical evaluation tools comprised the Constant–Murley score (CS), the American Shoulder and Elbow Surgeon score, range of motion, and a visual analog scale to assess pain and satisfaction. Radiographs were evaluated for notching and radiolucent lines. Any complications were recorded. Results In total, 113 prostheses (113 patients) with a mean follow-up of 27.6 (±3.6) months were analyzed. CS increased from 22.5 (±13.7) to 65.3 (±14.9) points (p = 0.06). Inferior scapular notching (only grade 1 and 2) was identified in 20.5 % of patients, with no signs of PE-induced osteolysis. 4.4 % of patients experienced an implant-related complication. Conclusions Inversion of the materials led to another type of notching with no signs of PE-induced osteolysis and no increase in the risk of short-term complications. Clinical results were comparable with other prostheses. Mid- to long-term results are required before any firm conclusions on clinical outcome and survival can be drawn.

Shoulder tendon injuries are common clinical conditions and are a significant source of pain and dysfunction. These conditions are more common in individuals who perform repetitive overhead activities and in individuals who have abnormal scapular kinematics, termed scapular dyskinesis (SD). However, the long term consequences associated with overuse activity in the presence of SD are unknown. Therefore, the objective of this study was to determine the effect of overuse in combination with SD on joint mechanics and properties of the rotator cuff and biceps tendons. A rat model of scapular dyskinesis was used. 90 adult male Sprague-Dawley rats (400–450 grams) were randomized into three groups: nerve transection (SD), sham nerve transection + overuse (OV), or nerve transection + overuse (SD + OV). Rats were sacrificed at 2, 4, and 8 weeks after surgery. Shoulder function and passive joint mechanics were evaluated over time and tendon properties (mechanical, histological, organizational, and compositional) were measured. Results demonstrated that overuse activity and SD are each independently detrimental to tendon properties (e.g., diminished mechanical properties, disorganized collagen). However, tendon damage caused by the addition of overuse may be worse, with more parameters altered, than damage caused by the addition of SD. This study helps define the mechanical mechanisms leading to tendon damage and provides a framework for distinguishing treatment strategies for active patients and those with abnormal scapular mechanics.

T-cells play an important role in the remission-maintenance in AML-patients (pts) after SCT, however the role of LAA- (WT1, PR1, PRAME) or minor-histocompatibility (mHag, HA1) antigen-specific CD4(+) and CD8(+)T-cells is not defined. A LAA/HA1-peptide/protein stimulation, cloning and monitoring strategy for specific CD8(+)/CD4(+)T-cells in AML-pts after SCT is given. Our results show that (1) LAA-peptide-specific CD8+T-cells are detectable in every AML-pt after SCT. CD8(+)T-cells, recognizing two different antigens detectable in 5 of 7 cases correlate with long-lasting remissions. Clonal TCR-Vβ-restriction exemplarily proven by spectratyping in PRAME-specific CD8(+)T-cells; high PRAME-peptide-reactivity was CD4(+)-associated, as shown by IFN-γ-release. (2) Two types of antigen-presenting cells (APCs) were tested for presentation of LAA/HA1-proteins to CD4(+)T-cells: miniEBV-transduced lymphoblastoid cells (B-cell-source) and CD4-depleted MNC (source for B-cell/monocyte/DC). We provide a refined cloning-system for proliferating, CD40L(+)CD4(+)T-cells after LAA/HA1-stimulation. CD4(+)T-cells produced cytokines (GM-CSF, IFN-γ) upon exposure to LAA/HA1-stimulation until after at least 7 restimulations and demonstrated cytotoxic activity against naive blasts, but not fibroblasts. Antileukemic activity of unstimulated, stimulated or cloned CD4(+)T-cells correlated with defined T-cell-subtypes and the clinical course of the disease. In conclusion we provide immunological tools to enrich and monitor LAA/HA1-CD4(+)- and CD8(+)T-cells in AML-pts after SCT and generate data with relevant prognostic value. We were able to demonstrate the presence of LAA-peptide-specific CD8(+)T-cell clones in AML-pts after SCT. In addition, we were also able to enrich specific antileukemic reactive CD4(+)T-cells without GvH-reactivity upon repeated LAA/HA1-protein stimulation and limiting dilution cloning.

Behavioral avoidance tasks (BATs) have been used for decades in the assessment of specific phobias, but they also involve a number of prohibitive difficulties. This study investigated a new imaginal/self-report instrument, the Behavioral Avoidance Task Using Imaginal Exposure (BATIE), and evaluated whether it was an efficient paper-and-pencil alternative. Forty-nine adults diagnosed with specific phobias were matched to 49 participants without those particular phobias who served as control participants. The participants were 89.8% female and 79.6% Caucasian and had a mean age of 20.81 years (SD = 3.62). Diagnosis was determined using the Anxiety Disorders Interview Schedule (Brown, DiNardo, & Barlow, 1994). Participants completed a BAT following a BATIE. Results indicated BATIE ratings significantly correlated with BAT performance and ratings. Significant differences were also found between the phobic and control groups on all BATIE ratings (all differences indicated poorer performance or more fear in those with specific phobias). Also, the BATIE scores demonstrated good evidence of convergent and discriminant validity compared to other self-reports, significantly predicted BAT performance even when controlling for those measures of fear and anxiety, and significantly predicted diagnostic severity ratings. Overall, results indicated that the BATIE may be a reasonable alternative to in vivo BATs in certain situations (e.g., clinical practice, unavailability of BAT stimuli).

Objective To compare the effectiveness, safety and cost of Tristel Fuse (chlorine dioxide) with Cidex OPA (ortho-phthaldehyde; 1,2–benzenedicarboxaldehyde) in an automated endoscopic reprocessor (AER) for high-level disinfection of flexible cystoscopes. Patients and Methods A randomised single-blind study comparing the high-level disinfectants Tristel Fuse as a simple office-based soak and Cidex OPA using an AER was performed. Participants were ‘blinded’ to the agent used for disinfection of the flexible cystoscopes. All patients had negative mid-stream urine at baseline, (MSU) no symptoms suggestive of urinary tract infection (UTI) on the day of investigation, no recent antibiotic use or current indwelling urinary catheter. Patients who underwent cystoscopic biopsy during the procedure were excluded. A urine analysis was done before and 3–5 days after cystoscopy and multiple equipment cultures were performed. The Urogenital Distress Inventory (UDI-6 + two questions from the ‘long-form’), symptom and quality-of-life scores were assessed before and after cystoscopy as were ease-of-use assessments and a full cost analysis. Results In all, 180 of 465 screened participants were randomised 1:1 and the mean age was 72.1 years, 17% were females and 57% of procedures were performed for bladder tumour surveillance. The urine analysis was positive in 5.4% of patients in each group and 29% (Tristel) vs 20% (Cidex) of patients had urinary leukocyturia (p = ns) after cystoscopy. The turnover (minutes per cycle) was 7.5 (Tristel) vs 26.7 (Cidex). The per-procedure costs were $11.67 (American dollars) for Tristel Fuse and $21.82 for Cidex OPA with fixed costs of $4788 for Tristel Fuse and $60 514 for Cidex OPA. Conclusions Tristel Fuse appears to be as effective and more cost-effective than Cidex OPA for high-level disinfection of flexible cystoscopes. This has significant cost implications for the office urologist.

This study ( n = 304) examined the relationship between somatic symptoms and social anxiety. Significant differences in the experience of somatic symptoms were found among four groups (i.e. performance anxious, interaction anxious, generalized socially anxious, and controls). Post hoc analyses revealed that those who exceeded the clinical cutoff for generalized social anxiety exhibited more somatic symptoms than those who exceeded the clinical cutoff in the other two social anxiety domains or controls. Individuals in each group exhibited more somatic symptoms than controls, but subtypes did not differ in the amount of somatic symptoms experienced. Additionally, regression analyses revealed that type of somatic symptoms experienced varied depending on subtype.

Introduction Mucormycosis of the head and neck is a rare disease increasingly occurring in immunocompromised patients. We report on two cases with different outcomes. Case reports A 63-year-old female presented with a recently developed deformation of her right cheek and nose combined with a loosening of the teeth. Further examination revealed mucormycosis of the maxilla. Hemimaxillectomy and secondary bony reconstruction with oral rehabilitation were performed. The second patient was a 54-year-old male who suffered from multiple myeloma. After receiving an allogeneic haematopoietic stem cell transplant, he developed a necrotizing infection of the right midface. Histopathological investigation confirmed the diagnosis of mucormycosis. The patient died one day after radical surgical resection. Discussion These two cases demonstrate the variability of mucormycosis. Although slow progression of the disease is possible, a high level of attentiveness and expedient treatment are necessary due to the high risk of a devastating course.

Objectives:To compare the microbiological efficacy, turnaround time, cost, convenience, and patient and user tolerance of Tristel Trio Wipes, PeraSafe solution and Cidex OPA solution for the high-level disinfection of flexible nasendoscopes.Methods:Flexible nasendoscopes were used in routine clinical encounters. They were then disinfected with one of the three disinfectant methods. Surveillance cultures were taken before and after each disinfection process. Data relating to each of the study parameters were recorded.Results:Positive bacterial cultures were discovered on nasendoscopes disinfected with PeraSafe and Cidex OPA. Tristel Trio Wipes have no capital outlay cost, the lowest running cost, the greatest convenience and the fastest turnaround time. PeraSafe had a faster turnaround time than Cidex OPA, and lower running costs.Conclusion:Tristel Trio Wipes are equal to PeraSafe and Cidex OPA in terms of microbiological efficacy. Turnaround time and cost are dramatically reduced when using Tristel Trio Wipes compared to the other disinfectant methods.

Background There are various definitions and diagnostic criteria for dementia, leading to discrepancies in case ascertainment in both clinical practice and research. We reviewed the different definitions, approaches and measurements used to operationalize dementia in health care studies in German nursing homes with the aim of discussing the implications of different approaches. Methods We conducted a systematic search of the MEDLINE and CINAHL databases to identify pre-2016 studies conducted in German nursing homes that focused on residents with dementia or cognitive impairment. In- or exclusion of studies were consented by all authors; data extraction was independently carried out by 2 authors (RP, SJ). The studies’ sampling methods were compared with respect to their inclusion criteria, assessment tools and methods used to identify the study population. Results We summarized case ascertainment methods from 64 studies. Study participants were identified based on a diagnosis that was evaluated during the study, or a recorded medical dementia diagnosis, or a recorded medical diagnosis either with additional cognitive screenings or using screening tests exclusively. The descriptions of the diagnostics that were applied to assess a diagnosis of dementia were not fully transparent in most of the studies with respect to either a clear reference definition of dementia or applied diagnostic criteria. If reported, various neuropsychological tests were used, mostly without a clear rationale for their selection. Conclusion Pragmatic considerations often determine the sampling strategy; they also may explain the variances we detected in the different studies. Variations in sampling methods impede the comparability of study results. There is a need to consent case ascertainment strategies in dementia studies in health service research in nursing homes. These strategies should consider resource constraints and ethical issues that are related to the vulnerable population of nursing home residents. Additionally, reporting about dementia studies in nursing homes need to be improved. If a diagnosis cannot be evaluated based on either ICD or DSM criteria, the study population may not be reported as having dementia. If a diagnosis is evaluated based on ICD or DSM criteria within the study, there is a need for more transparency of the diagnostic process. Electronic supplementary material The online version of this article (doi:10.1186/s12877-016-0249-7) contains supplementary material, which is available to authorized users.

Purpose To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS). Methods and Materials Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS). Results The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60–100). A KPS of ≥80 significantly influenced OS (median OS, 4.8 months for KPS ≤70 vs. 8.8 months for KPS ≥80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191–0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of ≤70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157–4.049, p = 0.0157). Conclusions Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with metastatic cancer, especially for patients previously treated with WBRT. A KPS of ≥80 predicts for an improved outcome.

Tissue-engineered septal cartilage may provide a source of autologous cartilage for repair of nasal defects. Production of clinically useful neocartilage involves multiple steps that include manipulating the culture environment. Partial pressure of oxygen (ppO(2) ) is a property that has been shown to influence cartilage development. Specifically, studies suggest low ppO(2) augments in vitro growth of articular cartilage. Although in vivo measurements of articular cartilage ppO(2) have demonstrated hypoxic conditions, measurements have not been performed in septal cartilage. The objective of this study was to determine the ppO(2) of septal cartilage in vivo.Prospective, basic science.The ppO(2) was measured in 14 patients (mean ± standard deviation age, 35.9 ± 14.5 years; range, 18-63 years) during routine septoplasty or septorhinoplasty using the OxyLab pO(2) monitor (Oxford Optronix Ltd., Oxford, UK). Measurements were taken from the septum and inferior turbinate. Each patient's age and sex were recorded.The average ppO(2) measured at the septum and inferior turbinate was 10.5 ± 10.1 mm Hg (1.4 ± 1.3%) and 27.6 ± 12.4 mm Hg (3.6 ± 1.6%), respectively. The ppO(2) of these locations was significantly different (P.005). Advancing age was positively correlated with septal ppO(2) (R(2) = 0.42; P.05). Septal ppO(2) showed no significant sex variation.This is the first report of in vivo measurement of ppO(2) in septal cartilage. The data demonstrate reduced oxygenation of septal cartilage relative to the inferior turbinate. This elucidates an important characteristic of the in vivo milieu that can be applied to septal cartilage tissue engineering.

BACKGROUND: High blood pressure (BP) is one of the most important risk factors for stroke, and antihypertensive therapy significantly reduces the risk of cardiovascular morbidity and mortality. However, achieving a regulated BP in hypertensive patients is still a challenge. OBJECTIVE: To evaluate the impact of an intervention targeting GPs' management of hypertension. METHODS: A cluster randomized trial comprising 124 practices and 2646 patients with hypertension. In the Capital Region of Denmark, the participating GPs were randomized to an intensive or to a moderately intensive intervention group or to a control group and in Region Zealand and Region of Southern Denmark, practices were randomized into a moderately intensive intervention and to a control group. The main outcome measures were change in proportion of patients with high BP and change in systolic BP (SBP) and diastolic BP (DBP) from the first to the second registration. RESULTS: The proportion of patients with high BP in 2007 was reduced in 2009 by ∼9% points. The mean SBP was reduced significantly from 2007 to 2009 by 3.61 mmHg [95% confidence interval (CI): -4.26 to -2.96], and the DBP was reduced significantly by 1.99 mmHg (95% CI: -2.37 to -1.61). There was no additional impact in either of the intervention groups. CONCLUSION: There was no impact of the moderate intervention and no additional impact of the intensive intervention on BP.

Purpose of this study is to determine the types, incidence, and severity of acute complications of intracranial stereotactic radiosurgery (SRS), specifically Gamma Knife (GK). Patients who had never had previous SRS were eligible for this prospective IRB-approved study. The questionnaire used applicable questions from CTCAE v.3.0, the Brief Pain Questionnaire (Short Form), Brief Fatigue Inventory, and the Tinnitus Handicap Inventory. Questionnaires were obtained prior to Gamma Knife (GK), 1 week, 1 month, and 2 months to assess complications. Seventy-six eligible patients (median age of 62 years) had complete data and were analyzed. Diagnoses included: 26 (34%) with brain metastases, 15 (20%) with trigeminal neuralgia, 12 (16%) with schwannoma, 10 (13%) with meningioma, 7 (9%) with arteriovenous malformation, 3 (4%) with pituitary adenoma, and 3 (4%) with other. At 1 week, 24% developed minimal scalp numbness (p = 0.0004 baseline compared to 1 week). Only 13% had minimal scalp numbness at 1 month and 2% at 2 months (both p = NS compared to baseline). There was no difference in scalp tingling between baseline and the various time points. Thirteen percent developed pin site pain at 1 week with a median intensity level of 2 out of 10. By one month, only 3% had pin site pain with a median intensity level of 3 out of 10. Four percent developed pin-site infection at 1 week and none at 1 and 2 months. There was no significant difference in nausea from baseline at 1 week, but there was worsening nausea at 1 month (p = 0.0114). By 1 month, 10% reported new local hair loss. 23%, 16%, and 15% complained of new/worsening fatigue at 1 week, 1 month, and 2 months, respectively, but 40% reported fatigue at baseline. Balance improved following SRS over all time periods (for all comparisons, p < 0.009). 1%, 6%, and 3% developed new tinnitus at 1 week, 1 month, and 2 months, respectively, which was significant when comparing baseline to non-baseline (p = 0.0269). Thirty-two patients were employed prior to SRS. Three (9%) patients did not return to work. Twenty-seven (84%) patients returned to work a median of 4 days after SRS. Two people did not report their employment status after SRS. There was no significant difference in face swelling, headache, eye pain, vomiting, seizures, or passing out at any intervals compared to baseline. This prospective study demonstrates that GK is well tolerated with few patients developing major acute effects. Many patients are able to return to work shortly after GK.

The comorbidity of posttraumatic stress disorder (PTSD) and psychotic symptoms is higher than what might be expected based on the prevalence of either disorder alone. Furthermore, the presence of psychotic symptoms is evident in PTSD patients who do not otherwise meet criteria for a psychotic spectrum disorder. The current paper discusses three existing hypotheses regarding the relation of PTSD and psychosis and presents a series of case studies that illustrates this phenomenon across a diverse group of patients and scenarios. Clinical implications in light of these case studies are offered, including the suggestion that the next edition of the Diagnostic and Statistical Manual of Mental Disorders includes a specifier of PTSD with psychotic features.

Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in patients with multiple sclerosis (MS). A subject is considered CCSVI positive if ≥ 2 venous hemodynamic (VH) criteria are fulfilled.To determine prevalence of CCSVI in a large cohort of patients with MS, clinically isolated syndrome (CIS), other neurologic diseases (OND), and healthy controls (HC), using specific proposed echo-color Doppler (ECD) criteria.Transcranial and extracranial ECD were carried out in 499 enrolled subjects (289 MS, 163 HC, 26 OND, 21 CIS). Prevalence rates for CCSVI were calculated in 3 ways: first, using only the subjects for whom diagnosis was certain (i.e., borderline subjects were excluded); secondly, including the borderline subjects in the "no CCSVI" group; and finally, taking into account subjects who presented any of the VH criteria.CCSVI prevalence with borderline cases included in the "no CCSVI" group was 56.1% in MS, 42.3% in OND, 38.1% in CIS, and 22.7% in HC (p0.001). The CCSVI prevalence figures were 62.5% for MS, 45.8% for OND, 42.1% for CIS, and 25.5% for HC when borderline cases were excluded (p0.001). The prevalence of one or more positive VH criteria was the highest in MS (81.3%), followed by CIS (76.2%), OND (65.4%), and HC (55.2%) (p0.001). CCSVI prevalence was higher in patients with progressive than in nonprogressive MS (p = 0.004).Our findings are consistent with an increased prevalence of CCSVI in MS but with modest sensitivity/specificity. Our findings point against CCSVI having a primary causative role in the development of MS.

An animal model of chronic tympanic membrane (TM) perforation is needed for experiments on supporting healing of TM perforations. The basic fibroblast growth factor is important in TM wound healing. The object of this study was to investigate the efficacy of fibroblast growth factor receptor 1 (FGFR1) inhibition to arrest wound healing of experimental TM perforation. Bilateral instrumental myringotomies were performed in 12 rats. A specific inhibitor of the FGFR1 tyrosine kinase (SU5402) was applied to the left TM (2 mg/ml) and to the right TM (10 mg/ml) of each animal daily for 12 consecutive days. Thereafter, TMs were observed weekly for a total of 30 days. TM healing was delayed in a dose-dependent manner. We observed differences in the histologic parameters between both groups. SU 5402 is a strong inhibitor of TM healing but seems not to be suitable to create a chronic TM perforation in rat.

Purpose Comparing the chromosomal radiosensitivity of prostate cancer patients with that of healthy donors. Materials and methods The study was performed on 81 prostate cancer patients characterised by a clinical stage of predominantly pT2c or pT3a and a median age of 67years. As healthy donors 60 male monozygotic twin pairs were recruited with a median age of 28years. Chromosomal radiosensitivity was measured using both G0- and G2-assay. Results No difference between healthy donors and prostate cancer patients was detected concerning G0-radiosensitivity, since medians were similar (Hodges–Lehmann estimate: −0.05, 95% CI: −0.18–0.08, p =0.4167). However, a pronounced difference was determined for G2-radiosensitivity with prostate cancer patients showing a significantly higher sensitivity compared to healthy donors (Hodges–Lehmann estimate: −0.41, 95% CI: −0.53 to −0.30, p =1.75 −9 ). Using the 90% quantile of G2-radiosensitivity in healthy donors as a threshold for discrimination the fraction of prostate cancer patients with elevated radiosensitivity increased to 49%. Conclusion G2-, but not G0-radiosensitivity is a promising marker for predisposition of prostate cancer.

In this multicentre study, data on 102 shoulder hemiarthroplasties for the treatment of fractures were analysed retrospectively with regard to tuberosity healing and functional outcome. Methods Clinical outcome was assessed using the constant score (CS) and the American Shoulder and Elbow Score (ASES). The mean follow-up time was 28.1 months. The proportion of patients presenting tuberosity healing was 35.3% (36 out of 102). Results Anatomical tuberosity healing has a significant effect on CS, especially for lateral elevation (p = 0.0076), forward elevation (p = 0.0002), power (p = 0.0023) and the ASES (p = 0.017). However, the pain value of the CS was not influenced by tuberosity healing (p = 0.34). In patients with anatomically healed tuberosities, the CS averaged 53.0 points, whereas in the group of patients with non-anatomical tuberosity healing, the score averaged 40.1 points (p = 0.0004). There was an 11-fold increase in tuberosity nonunion in females compared with males (p = 0.0045). Further, nonunion was seen to be associated with advanced age of >70 years (p = 0.037) and the presence of osteoporosis (p = 0.034). Conclusion In this study, we found that anatomical tuberosity healing around the prosthesis improved functional outcome and range of motion.

Recently, a report on a bilateral tympanic membrane (TM) perforation in a patient after long-term treatment with erlotinib was published. The object of this study was to investigate the destructive potential of topical applied epidermal growth factor receptor (EGFR) inhibitors on wound healing of experimental TM perforation in rats by evaluating closure rates and histology. In 12 rats, erlotinib (10#x00A0;mg/ml) was applied to one TM of each animal and cetuximab (5#x00A0;mg/ml) to the other side daily for 12 consecutive days. Both the erlotinib group (11.8 days) and cetuximab group (9 days) had prolonged healing latencies compared to a reference value (7 days). We observed differences in the histologic parameters between both groups. Our results suggest that in normal TM, the inhibition of EGFR does not lead to a persistent perforation. However, in case of preexisting TM pathology, a spontaneous perforation in patients under long-term treatment of EGFR inhibitors seems to be possible.

Preoperative radiochemotherapy has been reported to enhance tumor response and to improve long-term survival in advanced squamous cell carcinoma of the head and neck. This retrospective study evaluates regression rate and long-term survival in 228 patients with primary oral squamous cell carcinoma treated by neoadjuvant radiochemotherapy and radical surgery. All patients with biopsy-proven, resectable oral squamous cell carcinoma – TNM stages II–IV without distant metastasis – received preoperative treatment consisting of fractioned irradiation of the primary and the regional lymph nodes with a total dose of 40 Gy and additional cisplatin (n = 160) or carboplatin (n = 68) during the 1st week of treatment. Radical surgery and neck dissection followed after a delay of 10–14 days. The study only included cases with histologically negative resection margins. After a median follow-up of 5.2 years, 53 patients (23.2%) had experienced local-regional recurrence. The median 2-year disease-specific survival (DSS) rate was 86.2%. 5-year DSS and 10-year DSS were 76.3% and 66.7%, respectively. Complete histological local tumor regression after surgery (ypT0) was observed in 50 patients (21.9%) and was independent of pretreatment tumor classification. Uni- and multivariate survival analysis revealed that ypT- and ypN-stage were the most decisive predictors for DSS. Preoperative radiochemotherapy with cisplatin/carboplatin followed by radical surgery attains favorable long-term survival rates. This applies especially to cases with complete histological tumor regression after radiochemotherapy, which can be assumed for one of five patients.

The independent prognostic importance of microscopic bladder neck involvement by prostate cancer in radical prostatectomy is questionable. We studied a cohort of 1845 patients to determine the significance of microscopic bladder neck involvement. Bladder neck involvement was defined as prostate cancer present within the coned bladder neck. We further categorized the cases as 'true bladder neck involvement' and 'false bladder neck involvement.' True bladder neck involvement required prostate cancer within thick smooth muscle bundles without intermixed benign prostatic glands. False bladder neck involvement was characterized by prostate cancer intermixed with benign prostatic glands. Bladder neck involvement was analyzed in relation to preoperative serum prostate-specific antigen (PSA) level, extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, radical prostatectomy Gleason score, and tumor volume. Of the 90 patients (4.9%) with microscopic bladder neck involvement, 63 were further classified as true bladder neck involvement and 27 as false bladder neck involvement. In univariate model, both types of bladder neck involvement (P

BACKGROUND. The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole-brain radiation therapy (WBRT). METHODS. The records of 1789 BM patients from August 1989 to November 2004 were reviewed. Of these, 111 underwent WBRT as part of their initial management and SRS as salvage. Patients were stratified by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, primary disease, dimension of the largest metastases and number of BM at initial diagnosis, and time to first brain recurrence after WBRT. Overall survival, survival after SRS, and time to local and distant failure were analyzed. RESULTS. The median OS from the initial diagnosis of BM was 17.7 months. Median survival after salvage SRS for the entire cohort was 9.9 months. Median survival after salvage SRS was 12.3 months in patients who had their first recurrence >6 months after WBRT versus 6.8 months for those who developed disease recurrence ≤6 months after (P = .0061). Primary tumor site did not appear to affect survival after SRS. Twenty-eight patients (25%) developed local recurrence after their first SRS with a median time of 5.2 months. A dose 2 cm were found to be predictive of local failure. CONCLUSIONS. In this study, patients who recurred after WBRT and were treated with salvage SRS were found to have good local control and survival after SRS. WBRT provided good initial control, as 45% of these patients failed >6 months after WBRT. Those with a longer time to failure after WBRT had significantly longer survival after SRS. Cancer 2008. © 2008 American Cancer Society.

The Partin tables were updated in 2007. However, to our knowledge their accuracy and performance characteristics have not been confirmed in an external validation cohort.We examined the discrimination and calibration properties of the 2007 Partin tables in 1,838 men treated with radical prostatectomy between 2001 and 2005 at Cleveland Clinic Foundation. The ROC derived AUC and the Brier score were used to quantify the discriminant properties of the predictions of the 2007 Partin tables for extraprostatic extension, seminal vesical invasion and lymph node invasion. Loess based calibration plots were used to examine the relationship between the predicted and observed rates of extraprostatic extension, seminal vesical invasion and lymph node invasion.The rates of extraprostatic extension, seminal vesical invasion and lymph node invasion were 26.9%, 5.5% and 1.8%. The accuracy of extraprostatic extension, seminal vesical invasion and lymph node invasion prediction was 71%, 80% and 75% according to the AUC method, and 0.176, 0.051 and 0.037 according to the Brier score, respectively. Extraprostatic extension predictions between 0% and 25%, and lymph node invasion predictions between 0% and 5% correlated well with observed extraprostatic extension and lymph node invasion rates, respectively. Conversely a suboptimal correlation was recorded between predicted and observed seminal vesical invasion rates as well as between predicted and observed rates of extraprostatic extension and lymph node invasion for predicted extraprostatic extension and lymph node invasion values above 25% and 5%, respectively.In this examined validation cohort the overall accuracy (AUC) of the Partin tables was comparable to results reported in the original 2007 development cohort. However, performance characteristics indicate that predictions within specific probability ranges should be interpreted with caution.

We previously demonstrated that there is a learning curve for open radical prostatectomy. We sought to determine whether the effects of the learning curve are modified by pathologic stage.The study included 7765 eligible prostate cancer patients treated with open radical prostatectomy by one of 72 surgeons. Surgeon experience was coded as the total number of radical prostatectomies conducted by the surgeon prior to a patient's surgery. Multivariable regression models of survival time were used to evaluate the association between surgeon experience and biochemical recurrence, with adjustment for PSA, stage, and grade. Analyses were conducted separately for patients with organ-confined and locally advanced disease.Five-year recurrence-free probability for patients with organ-confined disease approached 100% for the most experienced surgeons. Conversely, the learning curve for patients with locally advanced disease reached a plateau at approximately 70%, suggesting that about a third of these patients cannot be cured by surgery alone.Excellent rates of cancer control for patients with organ-confined disease treated by the most experienced surgeons suggest that the primary reason such patients recur is inadequate surgical technique.

A significant proportion of patients with prostate cancer with Gleason score 6 disease at biopsy is upgraded to Gleason score 7 or higher after radical prostatectomy, increasing the risk of adverse outcome. We identified clinical and pathological parameters that predict pathological upgrading in this population.A total of 268 patients with biopsy Gleason score 6 prostate cancer who underwent biopsy and radical prostatectomy between October 1999 and January 2007 were included in the study. Pretreatment characteristics were used to identify predictors of pathological upgrading. Upgrading significance was established by comparing radical prostatectomy pathology between cases that were and were not upgraded.A total of 134 patients (50%) were upgraded postoperatively to Gleason score 7 or higher. Preoperative prostate specific antigen greater than 5.0 ng/ml (p = 0.036), prostate weight 60 gm or less (p = 0.004) and more cancer volume at biopsy, defined by cancer involving greater than 5% of the biopsy tissue (p = 0.002), greater than 1 biopsy core (p0.001) or greater than 10% of any core (p = 0.014), were associated with pathological upgrading. Upgraded patients were more likely to have extraprostatic extension and positive surgical margins at radical prostatectomy (p0.001 and 0.001, respectively).Prostate specific antigen, prostate volume and biopsy cancer volume predict clinically significant upgrading in patients diagnosed with Gleason score 6 disease. These parameters may be valuable in the pretreatment risk assessment of this patient population.

We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000.Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined.The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series.Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

Objectives Serum prostate specific antigen (PSA) screening has led to clinical and pathologic stage migration. We examined patients treated by radical prostatectomy between 1987 and 2005 to establish temporal trends in pathologic stage migration as assessed by the proportion of patients with nonorgan-confined disease (NOCD). Methods Step-sectioned prostatectomy specimens of 3364 consecutively treated patients were evaluated by year. The data were modeled by joinpoint regression, and the optimal model was selected by a Bayesian information criterion. Results From 1987 to 2005, the population underwent pathologic stage migration toward more organ-confined tumors (P

Background The learning curve for surgery — i.e., improvement in surgical outcomes with increasing surgeon experience — remains primarily a theoretical concept; actual curves based on surgical outcome data are rarely presented. We analyzed the surgical learning curve for prostate cancer recurrence after radical prostatectomy. Methods The study cohort included 7765 prostate cancer patients who were treated with radical prostatectomy by one of 72 surgeons at four major US academic medical centers between 1987 and 2003. For each patient, surgeon experience was coded as the total number of radical prostatectomies performed by the surgeon before the patient ’ s operation. Multivariable survival – time regression models were used to evaluate the association between surgeon experience and prostate cancer recurrence, defined as a serum prostatespecific antigen (PSA) of more than 0.4 ng/mL followed by a subsequent higher PSA level (i.e., bio che mical recurrence ), with adjustment for established clinical and tumor characteristics. All P values are two-sided. Results The learning curve for prostate cancer recurrence after radical prostatectomy was steep and did not start to plateau until a surgeon had completed approximately 250 prior operations. The predicted probabilities of recurrence at 5 years were 17.9% (95% confidence interval [CI] = 12.1% to 25.6%) for patients treated by surgeons with 10 prior operations and 10.7% (95% CI = 7.1% to 15.9%) for patients treated by surgeons with 250 prior operations (difference = 7.2%, 95% CI = 4.6% to 10.1%; P

Summary Treatment of mandibular condylar process fractures may be conservative or surgical. Both treatment approaches aim to reconstruct the articulating joint surfaces in a physiological position to the discoligamentary structures. The study comprised 1812 patients of Wuerzburg University who presented with a fracture of the mandibular condylar process between 1981 and 2001. Besides conservative management options, surgical interventions using mini-plate osteosynthesis and the Wuerzburg lag screw plate were studied for post-treatment changes. Statistical analysis revealed that surgical osteosynthesis is superior to merely conservative therapy in terms of post-treatment dysgnathic severity. Hence, surgical osteosynthesis is advocated especially in patients with high condylar fractures or dislocated fractures in order to ideally achieve ‘restitutio ad integrum’.

OBJECTIVE To investigate the detection rate and extent of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands (AG) suspicious for prostate cancer, and the cancer risk in subsequent biopsies, diagnosed by a first 24-core saturation biopsy, as although the optimum extent of biopsy is controversial there is a trend to increase the number of cores taken, and apart from detecting prostate cancer, identifying HGPIN and AG is associated with a greater risk of finding cancer in subsequent biopsies, thus warranting a closer follow-up. PATIENTS AND METHODS The study included 100 men with consecutive first-time saturation biopsies; the indications for biopsy were an abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level of >2.5 ng/mL. Each biopsy specimen was reviewed retrospectively by two pathologists to confirm the histological diagnosis. The number and percentage of cores positive for HGPIN, bilateral involvement and multifocality (HGPIN involving two or more cores) were recorded in each case. The presence of AG and cancer was also recorded. An extended (10–12 cores) repeat biopsy was available in 23 patients. RESULTS The median (range) age and PSA level of the patients was 63 (41–80) years and 4.9 (1.5–67.0) ng/mL, respectively. Of the 100 patients, 34% had normal findings (benign prostatic tissue, BPT), 39% had cancer, 26% had HGPIN and cancer, 22% had HGPIN alone, and 5% had AG. Repeat biopsies were available in nine of the 22 (41%) patients with HGPIN, four of five with AG, and 10 of the 34 (29%) with BPT. The median (range) interval between the first and second biopsy was 13 (4–36) months. Prostate cancer was detected at the second biopsy in a third of patients with isolated HGPIN on the first biopsy, and one of the four with AG. None of the patients with BPT had cancer on re-biopsy. The cancer detection rate was significantly greater in patients with multifocal than in those with unifocal HGPIN (80% vs none, P = 0.010). The median number of cores and percentage of tissue involved by HGPIN was 3.5 (2–5) and 1.0 (0.5–1.2)%, respectively, in patients with cancer detected in repeat biopsies, compared to 1.0 (1–3) and 0.2 (0.2–0.6)% in patients without cancer on repeat biopsy (P = 0.023 and 0.015, respectively). CONCLUSION Identifying multifocal HGPIN on first saturation biopsy is associated with an overall cancer detection rate of 80% on repeat 10–12-core biopsy. Although there were few patients, the detection of multifocal HGPIN warrants additional searches for concurrent invasive carcinoma by repeated biopsy.

Objective To prospectively assess the health-related quality of life (HrQoL) in Parkinson's disease (PD) during 12 months. Methods HrQoL was assessed in 145 PD patients using the PD-specific PDQ-39, PDQL and the generic EQ-5D. In addition, clinical rating-scales were used. Results All scales showed a pronounced effect of PD. In comparison to an age-matched population the EQ-5D was considerably affected. In comparison to baseline, however, there was no significant change in the generic scale but a significant change in the sum-score of disease-specific HrQoL-scales. Conclusions Only disease-specific scales were sensitive to change. Further studies are necessary to evaluate the time-dependent change in HrQoL.