Dabrafenib and steroids for the treatment of Erdheim-Chester disease with extensive CNS involvement: a case report.

Erdheim-Chester disease (ECD) is an exceedingly rare non-Langerhans cell CD68+ CD1a- S100- histiocytic multi-organ disease. Diagnosis of ECD is often delayed due to non-specific radiographic findings and heterogeneous lesional tissue. Increasingly, the role of genomic alterations is being recognized for both diagnosis and treatment of ECD. More than half of ECD patients harbor the BRAFV600E mutation. Evaluation for this mutation be can falsely negative on immunohistochemical staining and confirmation with molecular analyses is recommended. We present a case of the 44 year-old male with BRAFV600E-positive ECD treated successfully with steroids followed by single-agent dabrafenib.

Erdheim-Chester disease (ECD) is an exceedingly rare type of histiocytosis (a disorder of white blood cells). The diagnosis of ECD can be challenging because tissue biopsy may not provide a definitive diagnosis. Currently, genetic mutations can be used to support both diagnosis and treatment. We present a case of the 44 year-old male with BRAF V600E -positive ECD who was treated successfully with steroids followed by dabrafenib.

Defining recovery trajectories after shoulder arthroplasty: a latent class analysis of patient-reported outcomes.

BACKGROUND: Patients undergoing total shoulder arthroplasty (TSA) can have varying levels of improvement after surgery. As patients typically demonstrate a nonlinear recovery trajectory, advanced analysis investigating the degrees of variation in outcomes is needed. Latent class analysis (LCA) is a mixed and multilevel model that estimates random slope variance to evaluate heterogeneity in outcome patterns among patient subgroups and can be used to outline differing recovery trajectories. The purpose of this study was to determine recovery trajectory patterns after TSA and to identify factors that predict a given trajectory. METHODS: Data from a prospectively collected single institutional database of patients undergoing anatomic and reverse TSA were utilized. Patients were included if they had American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores preoperatively, as well as postoperative scores at 6 weeks, 6 months, 1 year, and 2 years. Patients were excluded if they underwent a revision procedure or hemiarthroplasty or had prior infection. LCA was used to subdivide the patient cohort into subclasses based on postoperative recovery trajectory. This was performed for all patients as well as anatomic TSA and reverse TSA as separate groups. Unpaired Student t tests, analysis of variance, and Fisher exact test were used to compare classes based on factors including age, body mass index, sex, preoperative diagnosis, and type of arthroplasty. RESULTS: A total of 244 TSAs were included in the final analysis, comprising 89 anatomic TSA and 155 reverse TSA. In the combined group, LCA modeling revealed 3 patterns for recovery: Resistant Responders had low baseline scores (ASES < 30) and poor final results (ASES < 50), Steady Progressors had moderate baseline scores (ASES 30-50) with moderate final results (ASES 50-75), and High Performers had moderate baseline scores (ASES > 50) with excellent final results (ASES > 75). For anatomic TSA, we identified Delayed Responders with moderate baseline scores and a delayed response before ultimately achieving moderate final results, Steady Progressors with moderate baseline scores and a steady progression to achieve moderate final results, and High Performers who had moderate baseline scores and excellent final results. For reverse TSA, we identified Late Regressors with low baseline scores and poor final results, Steady Progressors with moderate baseline scores and moderate final results, and High Performers with moderate baseline scores and excellent final results. CONCLUSIONS: Patients recover in a heterogenous manner following TSA. Through LCA, we identified different recovery trajectories for patients undergoing anatomic TSA and reverse TSA.

Do patient outcomes and follow-up completion rates after shoulder arthroplasty differ based on insurance payor?

BACKGROUND: Disparities associated with socioeconomic status (SES) and insurance coverage have been shown to affect outcomes in different medical conditions and surgical procedures. We hypothesized that patients insured by Medicaid will be associated with lower follow-up rates and inferior outcomes relative to those with Medicare or private insurance. METHODS: Patients undergoing shoulder arthroplasty, including anatomic total shoulder arthroplasty, reverse arthroplasty, and hemiarthroplasty, were enrolled preoperatively in an institutional database. Preoperative demographics, payor (Medicaid, Medicare, or private insurance), and baseline American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores were recorded. Postoperatively, patients completed ASES scores at multiple time points. Follow-up completion rate was calculated as the number of follow-up visits completed relative to possible visits. Continuous variables were compared between groups with 1-way analyses of variance, and chi-squared tests were used for categorical variables. Significance was defined as P < .05. RESULTS: There were 491 shoulder replacements performed for 438 patients from 2012-2017. The mean follow-up completed percentage was significantly lower (P < .001) for Medicaid patients (62.6% ± 33.7%) relative to Medicare patients (80.2% ± 26.7%; P < .001) and private insurance patients (77.8% ± 22.1%; P = .001). The ASES Composite score increased significantly for all patients from baseline to final follow-up. At each time point, including before surgery and each postoperative time point, patients with Medicaid insurance had significantly lower ASES Composite scores. The final ASES Composite score was significantly lower in the Medicaid patients (66.1 ± 28.7) relative to private insurance patients (78.3 ± 20.8; P = .023). Medicaid patients had significantly lower preoperative (P < .001) and postoperative (P = .018) ASES Pain subscores. In multivariate regression analysis, Medicaid insurance was associated with both inferior preoperative and postoperative ASES scores relative to patients with Medicare or private insurance. CONCLUSIONS: We observed that all patients, regardless of insurance payor, improved by similar magnitudes after shoulder arthroplasty, though patients with Medicaid insurance had significantly lower preoperative and postoperative ASES scores, primarily because of the ASES Pain subscore. Patients with Medicaid insurance also have lower follow-up rates than other payors.

Treatment of Labral Calcification in the Setting of Femoroacetabular Impingement Syndrome With Arthroscopic Calcification Excision, Labral Repair, and Osteoplasty Improves Outcomes.

PURPOSE: To describe the diagnosis and 2-year outcomes of arthroscopic treatment for labral calcification in the setting of femoroacetabular impingement syndrome (FAIS). METHODS: A retrospective analysis was performed from a prospectively collected database of patients with FAIS undergoing hip arthroscopy. Patients with FAIS with labral calcification were differentiated radiographically from patients with other paralabral radiopaque densities such as os acetabuli, acetabular rim fractures, and labral ossification. Patients with FAIS with labral calcification were treated with arthroscopic calcification excision, labral repair, and osteoplasty and matched by age, sex, and body mass index with a cohort of patients with FAIS without labral calcifications who underwent labral repair and osteoplasty. Pre- and 2 years postoperatively, patients completed patient-reported outcome (PRO) scores including the modified Harris Hip Score, Hip disability and Osteoarthritis Outcome Score (HOOS), 12-item Short-Form survey, and visual analog scale. RESULTS: In total, 40 hips (21 male, 19 female) with FAIS and labral calcification were included (age 36.8 ± 8.1, body mass index, 25.9 ± 4.5). Patients with FAIS with labral calcification demonstrated similar significant PRO score improvements compared with a matched cohort of patients with FAIS without labral calcification at 2 years after surgery (visual analog scale: (-)2.3 ± 0.4, (-)2.7 ± 0.5, modified Harris Hip Score: 16.1 ± 2.6, 17.1 ± 3.2; HOOS symptoms: 21.9 ± 3.7, 18.6 ± 3.6; HOOS pain: 22.1 ± 3.0, 25.0 ± 3.5; HOOS activities of daily living: 20.2 ± 2.8, 23.8 ± 3.3; HOOS sport: 35.6 ± 5.0, 35.6 ± 4.1; HOOS quality of life: 36.9 ± 4.5, 37.5 ± 4.4; 12-item Short-Form survey physical component summary: 15.5 ± 2.3, 20.1 ± 2.1, respectively). Both cohorts achieved minimal clinically important differences at equivalent rates (60%-82.5%) for all PRO scores. CONCLUSIONS: Patients with labral calcification in the setting of FAIS can be effectively treated with arthroscopic calcification excision, labral repair, and osteoplasty. These patients demonstrate significant improvements in patient-reported outcomes and achievement of minimal clinically important differences at 2 years similar to patients undergoing arthroscopic treatment for FAIS without labral calcification. LEVEL OF EVIDENCE: Level III, matched cohort study.

Modified manual small incision cataract surgery technique for phacoemulsification-trained surgeons.

PURPOSE: To present the technique and outcomes of a modified manual small incision cataract surgery designed for the phacoemulsification surgeons who are learning to perform manual small incision cataract surgery. METHODS: This was a retrospective, single-centred, comparative study. We included all the patients who underwent the modified manual small incision cataract surgery for visually significant cataract at Singapore National Eye Centre. All surgeries were performed by either a senior phaco-trained surgeon (M.A.) who had performed more than 500 manual small incision cataract surgery or a junior phaco-trained surgeon (D.C.) who had performed around 500 phacoemulsification but never performed any manual small incision cataract surgery. The main modification of this technique lies in the creation of an additional phaco-like main wound at 90° to the scleral tunnel wound, with most surgical steps performed through this additional wound. The outcomes were analysed and compared between the senior and junior surgeons. The main outcome measures were visual outcome and major intraoperative complications such as posterior capsular rupture and zonular dialysis. RESULTS: A total of 132 cases were included; 102 (77.3%) and 30 (22.7%) cases were performed by the senior and junior surgeons, respectively. Pre-operatively, 85.6% eyes had best-corrected visual acuity of counting fingers or worse. Postoperatively, the visual outcome at 1 month was similar between the senior and junior surgeons, with 68.7% eyes achieving a best-corrected visual acuity of ⩾6/12 (p = 0.17). No posterior capsular rupture, zonular dialysis or endophthalmitis was observed during the study period. CONCLUSIONS: This modified technique may serve as a useful transition technique for the phaco-trained surgeons to develop skills in manual small incision cataract surgery, with demonstrable good visual outcome and safety.

Onset hyperalgesia and offset analgesia: Transient increases or decreases of noxious thermal stimulus intensity robustly modulate subsequent perceived pain intensity.

Reported pain intensity depends not only on stimulus intensity but also on previously experienced pain. A painfully hot temperature applied to the skin evokes a lower subjective pain intensity if immediately preceded by a higher temperature, a phenomenon called offset analgesia. Previous work indicated that prior pain experience can also increase subsequent perceived pain intensity. Therefore, we examined whether a given noxious stimulus is experienced as more intense when it is preceded by an increase from a lower temperature. Using healthy volunteer subjects, we observed a disproportionate increase in pain intensity at a given stimulus intensity when this intensity is preceded by a rise from a lower intensity. This disproportionate increase is similar in magnitude to that of offset analgesia. We call this effect onset hyperalgesia. Control stimuli, in which a noxious temperature is held constant, demonstrate that onset hyperalgesia is distinct from receptor or central sensitization. The absolute magnitudes of offset analgesia and onset hyperalgesia correlate with each other but not with the noxious stimulus temperature. Finally, the magnitude of both offset analgesia and onset hyperalgesia depends on preceding temperature changes. Overall, this study demonstrates that the perceptual effect of a noxious thermal stimulus is influenced in a bidirectional manner depending upon both the intensity and direction of change of the immediately preceding thermal stimulus.

Patellar tendon reconstruction with hamstring autograft for the treatment of chronic irreparable patellar tendon injuries.

BACKGROUND: Patellar tendon injuries not amenable to primary repair present a challenging problem for surgeons and patients alike. No standard surgical technique exists for these injuries and few studies report outcomes after surgical treatment. METHODS: A retrospective analysis was conducted for patients undergoing surgical treatment for irreparable patellar tendon tears. Patients were treated with an indirect tendon reconstruction technique using high-strength suture to set initial patellar height and hamstring autograft for biologic augmentation. Patients who underwent this procedure between 2012 and 2018 and met minimum two-year follow-up with completion of all outcome measurements including KOOS, PROMIS, VAS pain and satisfaction scores were included. RESULTS: Eleven patients met inclusion criteria. Ten of eleven patients (91%) had intact repairs and final patient outcomes were collected at a mean of 54.9 ± 23.1 months after surgery. Only one patient experienced extensor lag at final follow-up (p < 0.001). The preoperative Caton-Dechamps ratio was 1.77 ± 0.58, which decreased to 0.98 ± 0.25 after surgery (p < 0.001). The mean postoperative KOOS ADL score was 61.5. The mean postoperative PROMIS Global Mental and Physical Health scores were 46.9 ± 8.7 and 42.0 ± 9.8. Post-operative mean VAS satisfaction score was 5.6 ± 3.4. CONCLUSIONS: Patellar tendon reconstruction with autologous hamstring tendon graft and suture augmentation allows for acceptable outcomes in the setting of patellar tendon disruption with segmental defects when direct repair is not possible.

Human Rotator Cuff Tears Have an Endogenous, Inducible Stem Cell Source Capable of Improving Muscle Quality and Function After Rotator Cuff Repair.

BACKGROUND: The muscle quality of the rotator cuff (RC), measured by atrophy and fatty infiltration (FI), is a key determinant of outcomes in RC injury and repair. The ability to regenerate muscle after repair has been shown to be limited. PURPOSE: To determine if there is a source of resident endogenous stem cells, fibroadipogenic progenitor cells (FAPs), within RC injury patients, and if these cells are capable of adipogenic, fibrogenic, and pro-myogenic differentiation. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 patients between the ages of 40 and 75 years with partial- or full-thickness RC tears of the supraspinatus and evidence of atrophy and FI Goutallier grade 1, 2, or 3 were selected from 2 surgeons at an orthopaedic center. During the surgical repair procedure, supraspinatus muscle biopsy specimens were obtained for analysis as were deltoid muscle biopsy specimens to serve as the control. FAPs and satellite cells were quantified using fluorescence-activated cell sorting. Muscle FI and fibrosis was quantified using Oil Red O and Masson trichrome staining. FAP differentiation and gene expression profiles were compared across tear sizes after culture in adipogenic, fibrogenic, and beta-3 agonist (amibegron) conditions. Analysis of variance was used for statistical comparisons between groups, with P < .05 as statistically significant. RESULTS: Histologic analysis confirmed the presence of fat in biopsy specimens from patients with full-thickness tears. There were more FAPs in the full-thickness tear group compared with the partial-thickness tear group (9.43% ± 4.25% vs 3.84% ± 2.54%; P < .01). Full-thickness tears were divided by tear size, with patients with larger tears having significantly more FAPs than those with smaller tears. FAPs from muscles with full-thickness tendon tears had more adipogenic and fibrogenic potential than those with partial tears. Induction of a beige adipose tissue (BAT) phenotype in FAPs was possible, as demonstrated by increased expression of BAT markers and pro-myogenic genes including insulin-like growth factor 1 and follistatin. CONCLUSION: Endogenous FAPs are present within the RC and likely are the source of FI. These FAPs were increased in muscles with in larger tears but are capable of adopting a pro-myogenic BAT phenotype that could be utilized to improve muscle quality and patient function after RC repair.

Diabetic retinopathy screening and treatment in Myanmar: a pilot study.

BACKGROUND/AIMS: The goals of this pilot study were (a) to demonstrate the feasibility of identifying patients with vision-threatening diabetic retinopathy (DR) in a provincial area of Myanmar and treating them with portable lasers and (b) to gather data specific to Myanmar to help design larger cross-sectional studies of DR prevalence in Myanmar. METHODS: 97 consecutive patients with diabetes mellitus (DM) were identified by local ophthalmologists over a period of 1 month in Pyinmana, Myanmar and were referred to the pilot screening programme. Patients' demographics were recorded and their eyes were examined. Those with vision-threatening DR were treated with panretinal photocoagulation (PRP). RESULTS: Of the 97 patients with DM, 33 (34%) had evidence of DR, 23 (23.5%) had evidence of vision-threatening DR including 13 (13.5%) with proliferative DR and 33 eyes in 23 patients (23.5%) had PRP with portable green wavelength laser. Hypertension was a significant cofactor in the development of vision-threatening DR (p<0.01). The average time since diagnosis of DM was 6.0 years in patients with vision-threatening DR. CONCLUSIONS: This study demonstrates the feasibility of identifying and treating patients with vision-threatening DR in a provincial area of Myanmar and provides initial data to plan a larger study to assess true prevalence, a prerequisite for establishing broader screening/treatment programs.

Awareness of diabetic eye disease among general practitioners and diabetic patients in Yangon, Myanmar.

BACKGROUND: Diabetes is an increasing problem in Myanmar with more than three million people affected. There are no data on awareness of diabetic retinopathy among the general practitioners (GPs) or diabetic population of Myanmar. This study aims to evaluate the awareness of diabetes-related eye disease among GPs and diabetic patients in Yangon, Myanmar. DESIGN: A cross-sectional survey. METHODS: From the Myanmar Medical Association Registry of 978 practicing GPs in Yangon, 200 were randomly selected and a structured questionnaire was sent to each. Each GP was asked to give a separate questionnaire to the first five diabetic patients who attended their practice. RESULTS: One hundred GPs and 480 patients returned the questionnaires. Although 99% of GPs were aware that diabetes could result in loss of vision, 49% never examined the fundi of their diabetic patients. Of the diabetic patients, 86% were aware that diabetes could damage their eyesight. Although 92% realized they should visit an ophthalmologist regularly, only 57% had seen an ophthalmologist. Patients who never attended school were less likely to visit an ophthalmologist than those with tertiary education (odds ratio 0.24; 95% confidence interval 0.09, 0.66). Patients with diabetes for less than 2 years were less likely to visit an ophthalmologist than those with diabetes for more than 10 years (odds ratio 0.21; 95% confidence interval 0.9, 0.44). There was no association between age, gender or work status and the likelihood of having seen an ophthalmologist. CONCLUSION: Although both GPs and diabetic patients are aware of the need for regular fundal screening, just over half the patients had been screened. There exists a need for programmes in Myanmar to induce a behavioural change in diabetic patients with regards to screening examinations.