Subjective Functional Improvement Research Articles

MP18-08 NOVEL MACHINE LEARNING ALGORITHMS ARE ACCURATE AND NONINFERIOR TO HUMAN EXPERTS IN PREDICTING SUBJECTIVE PATIENT OUTCOMES FOLLOWING THIRD LINE THERAPY FOR OVERACTIVE BLADDER

You have accessJournal of UrologyCME1 May 2022MP18-08 NOVEL MACHINE LEARNING ALGORITHMS ARE ACCURATE AND NONINFERIOR TO HUMAN EXPERTS IN PREDICTING SUBJECTIVE PATIENT OUTCOMES FOLLOWING THIRD LINE THERAPY FOR OVERACTIVE BLADDER Glenn T. Werneburg, Eric Werneburg, Howard Goldman, Andrew Mullhaupt, and Sandip Vasavada Glenn T. WerneburgGlenn T. Werneburg More articles by this author , Eric WerneburgEric Werneburg More articles by this author , Howard GoldmanHoward Goldman More articles by this author , Andrew MullhauptAndrew Mullhaupt More articles by this author , and Sandip VasavadaSandip Vasavada More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002551.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We demonstrated machine learning (ML) algorithms accurately predict objective outcomes following third-line treatment for overactive bladder (OAB). Importantly, objective improvements (e.g. leak number) do not necessarily translate to subjective improvements, and thus here we developed ML algorithms to predict patient-reported subjective improvement in bladder leakage and function following OnabotulinumtoxinA (OBTX-A) or sacral neuromodulation (SNM) for OAB. We hypothesized algorithms would exhibit noninferiority to human experts. METHODS: ROSETTA datasets for OAB patients randomized to OBTX-A or SNM were obtained from NICHD. Novel ML algorithms, using reproducing kernel techniques, were trained and tasked to predict improvement in bladder leakage and function measured by Patient Global Impression of Improvement (PGI-I), a robust and valid patient-reported outcome measure of improvement following OAB treatment in a subset of patients in which algorithms were blinded to outcomes. Blinded expert FPMRS urologists given the same data also predicted outcomes. ROC curves with AUC and 95% CI were generated. RESULTS: Top algorithms exhibited excellent predictive accuracy for bladder function improvement in patients who underwent both OBTX-A (yellow; AUC 0.86, CI: 0.77–0.99, figure left) and SNM (AUC 0.96, CI: 0.88–1.0, figure right), and were noninferior to expert FPMRS urologists (purple and blue; Figure left: OBTX-A; Figure right: SNM). Top algorithms also exhibited excellent predictive accuracy for bladder leakage improvement in patients who underwent both OBTX-A (AUC 0.75, CI: 0.58–0.90) and SNM (AUC 0.80, CI: 0.62–0.98), and were noninferior to experts. CONCLUSIONS: Novel ML algorithms were accurate and noninferior to experts in prediction of patient-reported subjective improvements in bladder function and leakage in OAB. Objective outcomes do not necessarily translate to subjective improvement, and thus patient-reported outcomes are an optimal outcome measure. ML algorithms generated using the described novel techniques may complement clinical judgement in patient counseling, and their generalizability to other scenarios within and outside urology is promising and warrants investigation. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e298 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Glenn T. Werneburg More articles by this author Eric Werneburg More articles by this author Howard Goldman More articles by this author Andrew Mullhaupt More articles by this author Sandip Vasavada More articles by this author Expand All Advertisement PDF DownloadLoading ...

Age- and sex-related variations of individual retinal layer thickness in the foveal center of healthy eyes

Alterations of the visual function during life are associated with changes in the morphological parameters of the outer retinal layers of the fovea. We evaluated age- and sex-related variations of the mean thicknesses of the different retinal layers at the central foveola which provides the maximal visual acuity. The vertical expansions of the following structures were measured on spectral-domain optical coherence tomographic images of 2944 healthy eyes of 1990 subjects with ages between 5 and 85 years: the total thickness of the retinal tissue, the thickness of the retinal pigment epithelium, the lengths of photoreceptors (receptor segments), photoreceptor outer segments (POS), and photoreceptor inner segments (PIS), and the thicknesses of the ellipsoid zone (EZ), myoid zone (MZ), external limiting membrane, outer nuclear layer, Henle fiber layer, and the horizontal layer of the Müller cell cone. We found diverse morphologies of the central photoreceptor layer with different thicknesses of the EZ and interdigitation zone lines. The mean total thickness of the retinal tissue at the central foveola showed three periods: it increased between 5 and about 41 years of age, displayed a plateau until about 52 years, and decreased continuously thereafter. Photoreceptors, POS, and PIS displayed their maximal mean lengths between 5 and about 36 years of age; the lengths decreased continuously between 36 and 85 years of age. Whereas the mean thickness of the EZ did not alter across the life span, the mean thickness of MZ displayed three periods: it increased between 5 and about 21 years of age, showed a plateau until about 36 years, and decreased considerably thereafter. Sex differences were observed for five parameters in eyes of subjects aging between 55 and 85 years. We suggest that the MZ thickness reflects the level of the metabolic activity of photoreceptors. The increase in the MZ thickness, likely reflecting increasing metabolic activity of photoreceptors, might contribute to the improvement of visual function in young subjects. The decrease of the MZ thickness in the fovea of elderly might reflect a decrease of the metabolic activity perhaps resulting from mitochondrial dysfunction which is known to occur in photoreceptors of aged eyes.

Relationship of Vitamin A and Thyroid Function in Individuals With Obesity and After Laparoscopic Sleeve Gastrectomy.

Vitamin A deficiency (VAD) occurs in obesity and may be associated with thyroid dysfunction. We aimed to investigate the association of VA with thyroid function in obesity and after laparoscopic sleeve gastrectomy (LSG). Nine hundred and seventy-six obese subjects were enrolled for this study and were divided into VAD, marginal vitamin A deficiency (MVAD), and vitamin A normal (NVA) groups. VAD was defined as VA ≤ 200 ng/ml, MVAD was defined as VA > 200 but <300 ng/ml, and NVA was defined as VA ≥ 300 ng/ml. Thyroid function was compared among groups and the relationship of VA and thyroid function was analyzed. Two hundred and forty-four of the 976 obese subjects underwent LSG, and the change in thyroid function and VA at 3, 6, and 12 months after surgery was measured. Results showed that 37% of all the subjects had subclinical hypothyroidism (SH), and the SH group had lower VA levels than the non-SH group (P = 0.008). Forty-nine percent of all the subjects had MVAD, 9% had VAD, while the MVAD or VAD group had lower FT4 than the NVA group (P = 0.005 and P = 0.001). The VAD group also had higher TSH than NVA group (P = 0.037). VA was significantly negatively associated with TSH (r = −0.151, P = 0.006) and positively associated with FT4 (r = 0.228, P < 0.001). TSH was significantly decreased at 3, 6, and 12 months (3M: from 4.43 ± 2.70 to 2.63 ± 1.46 mU/l, P < 0.001; 6M: from 4.43 ± 2.70 to 3.84 ± 2.34 mU/l, P = 0.041; 12M: from 4.43 ± 2.70 to 2.85 ± 1.68 mU/l, P = 0.024). After LSG surgery, VA levels were slightly increased, when compared to pre-surgery levels, at 3, 6, and 12 months (3M: from 262.57 ± 68.19 to 410.33 ± 76.55 ng/ml, P = 0.065; 6M: from 262.57 ± 68.19 to 281.36 ± 93.23 ng/ml, P = 0.343; 12M: from 262.57 ± 68.19 to 300.37 ± 86.03 ng/ml, P = 0.083). SH group also had lower TSH and higher VA than the non-SH group at 3 months post-surgery [TSH: −1.4(−2.3, −0.3) vs. −0.2(−0.8, −0.2) mU/l, P < 0.001; VA: 163.99 ± 32.58 vs. 121.69 ± 27.59 ng/ml, P = 0.044]. In conclusion VA, which is related to thyroid hormone production, protects against thyroid dysfunction in obese subjects. The improvement of thyroid function in subjects with SH after LSG may be related to the increased VA levels observed post-surgery.Clinical Trial RegistrationClinicalTrial.gov ID: NCT04548232.

Sorafenib in Dupuytren and Ledderhose Disease.

Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRβ, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.

307 The A to E (ABCDE) Pit Crew Model: A Novel Approach to Team-Based Care of Critical Patients in the Pre-Hospital Setting

This study aimed to evaluate the effectiveness of a novel team-based approach to care for a simulated critically ill out-of-hospital patient. Both subjective and objective data were collected and analyzed. The primary outcome of this study was a subjective improvement in communication and team function. Secondary outcomes included completion of critical actions and time to intervention.

Association of Visual Appearance on Outcomes After Hallux Valgus Surgery.

In this study, our aim was to determine the effect of cosmetic improvement on patient satisfaction and functional scores in hallux valgus (HV) surgery. Preoperative foot photographs of 105 patients who had undergone chevron osteotomy for HV between 2016 and 2018 were taken. The patients were divided into 2 groups. Twenty-four months after surgery, the preoperative foot photographs were shown to patients in group 1 (n = 52) but not to patients in group 2 (n = 53). The groups were then compared using the visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society Hallux Metatarsophalangeal-Interphalangeal (AOFAS Hallux MTP-IP), and the 36-Item Short Form Health Survey (SF-36) scores. Both groups were evaluated radiologically with preoperative and postoperative hallux valgus angles and intermetatarsal angles. There was no difference between the 2 groups in terms of radiologic parameters either pre- or postoperatively, or AOFAS Hallux MTP-IP scores postoperatively. However, for group 1, the VAS was lower (0.4±0.8 vs 1.8±1.6, P = .003) and both the SF-36 physical functioning (88.3±18.1 vs 79.1±23.2, P = .017) and SF-36 mental health scores were higher (78.8±19 vs 69.2±16.3, P = .022). Visualizing improvement in the cosmetic appearance of the foot appears associated with patients' perception of subjective pain and functional improvement. We recommend that preoperative foot photographs be taken and recorded. Level III, case-control study.

LGG-16. TO BE PRECISE - KNOW YOUR TARGETS: INSTITUTIONAL EXPERIENCE WITH TUMOR TARGETED THERAPY FOR RECURRENT/PROGRESSIVE PEDIATRIC LOW-GRADE GLIOMA AND PLEXIFORM NEUROFIBROMA

IntroductionThe oncogenic drivers of pediatric CNS tumors are rapidly being identified with the implementation of high throughput genetic screening. Precision medicine approaches to treatment have shown promising results, but data remains limited in the community oncology setting. We aim to describe our institutional experience using targeted therapies for plexiform neurofibroma and recurrent/progressive pediatric low-grade glioma (pLGG). MethodsWe performed a retrospective chart review of all patients treated with tumor targeted therapies for recurrent/progressive pLGG and plexiform neurofibroma over the past 5 years. ResultsTen patients treated with tumor targeted therapies were identified. Regimens included combination Dabrafenib and Trametinib (n=3), Trametinib monotherapy (n=2), Selumetinib (n=3), Vemurafenib (n=1), and Larotrectinib (n=1). Median age at therapy initiation was 11.5 years (range 1.1 - 18 years). Tumor molecular status included BRAFV600E mutation (n=4), NF1 mutation (n=2), KIAA1549-BRAF fusion (n=1), NACC-NTRK fusion (n=1), and FGFR1 mutation (n=1). Patients trialed an average of 2 treatment regimens prior to targeted therapy initiation (range 0–5). Mean duration of therapy was 14.5 months (range .5–33 months) with 8 patients remaining on treatment. Based on modified RANO criteria, responses included partial (n=1), stable disease (n=8), and progressive disease (n=1). Progressive disease was noted after 4 months of treatment with Dabrafenib and Trametinib combination therapy, but rate of tumor growth was decreased. Subjective functional improvement was seen in 50% of patients. The most common toxicities included rash (n=5) and pyrexia (n=2). Trametinib was discontinued in one patient due to intra-tumoral hemorrhage of unclear etiology. ConclusionTreatment of pediatric CNS tumors with targeted agents appears to be feasible and efficacious in the community oncology setting. Multi-institutional clinical trials are currently ongoing for each of these therapies. There remains a need for community oncology institutional data regarding their use.

Correlation Between Muscle Strength and Functional Improvement After a Neuromuscular Electrical Strengthening Associated with Undenatured Type II Collagen in Knee Osteoarthritis

Knee osteoarthritis (OA) is one of the most common musculoskeletal disorders, affecting 2693 out of every 100,000 women and 1770 out of every 100,000 men. The main treatment for OA is education and exercise. Aerobic and strengthening exercises are effective in reducing pain and disability. Moreover, the nutraceutical undenatured type II collagen (UC-II) has been studied in patients with knee OA. Knee muscle strength is shown to be related to physical function in people with knee OA. This study analyzed the correlation between muscle strength and function in patients with knee OA after a muscle strengthening exercise program and UC-II supplementation. A randomized, single-blinded, placebo-controlled trial of 100 patients with grade I to III knee OA. The groups were as follows: UC-II (CG), placebo UC-II (PCG), UC-II and NMES Strengthening (CNSG), placebo UC-II and NMES Strengthening (PCNSG), and NMES Strengthening (NSG), each with 20 participants. The following were evaluated: knee quadriceps muscle strength, objective function (6MWT and TUG), and subjective function (WOMAC and Lequesne), at 30 days, 90 days, and 6 months after the intervention. The CG improved function only 6 months after the interventions (p < 0.05). The CNSG and PG improved quadriceps strength and function in all reevaluations (p < 0.05). There was a moderate to strong correlation between bilateral quadriceps strength and objective function as assessed by TUG and 6MWT at 30 days in the CNSG and PG (p < 0.005), this effect remaining after 6 months of intervention (p < 0.05). There was a moderate to strong correlation between bilateral quadriceps muscle strength and objective function as assessed by WOMAC and Lequesne scores in the CNSG and NSG at all times of the study (p < 0.05). Muscle strength gain was significantly correlated with objective and subjective functional improvement in patients with knee OA. The combination of muscle strengthening and UC-II administration potentiated this functional gain. Brazilian Registry of Clinical Trials (REBEC): RBR-8ghcx3

PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation.

Extensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that elevated low-density lipoprotein cholesterol (LDL-C) concentrations play a central role in the pathophysiology of atherosclerotic cardiovascular disease. Apart from LDL-C, also triglycerides independently modulate cardiovascular risk. Reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma LDL-C, but it is also associated with a reduction in triglyceride levels potentially through modulation of the expression of free fatty acid transporters. Preclinical data indicate that PCSK9 is up-regulated in the ischaemic heart and decreasing PCSK9 expression impacts on infarct size, post infarct inflammation and remodeling as well as cardiac dysfunction following ischaemia/reperfusion. Clinical data support that notion in that PCSK9 inhibition is associated with reductions in the incidence of myocardial infarction, stroke, and coronary revascularization and an improvement of endothelial function in subjects with increased cardiovascular risk. The aim of the current review is to summarize the current knowledge on the importance of free fatty acid metabolism on myocardial ischaemia/reperfusion injury and to provide an update on recent evidence on the role of hyperlipidemia and PCSK9 in myocardial infarction and cardioprotection.

CTNI-48. NOVEL TREATMENT OF END STAGE RECURRENT GLIOBLASTOMA TREATED WITH A NONINVASIVE ONCOMAGNETIC DEVICE USING OSCILLATING MAGNETIC FIELDS – A NEW AND POWERFUL NONINVASIVE THERAPY

Abstract Noninvasive treatment with alternating electric fields at 200 kHz (Optune therapy) has been approved for recurrent and newly diagnosed glioblastoma (GBM). We have recently tested and confirmed in vitro, and in patient derived xenografted mouse models, the oncolytic potential of powerful newly developed device generating oscillating magnetic fields (OMF) using rotating magnets. This device is completely different and has different mechanisms of action than Optune therapy. We report the successful treatment of an endstage recurrent GBM in a 53-year-old man. The patient had undergone radical surgical excision and standard of care chemoradiotherapy, as well as experimental gene therapy for a left frontal tumor. 18 months after this treatment, there was recurrence with progressive enlargement and leptomeningeal spread, making the patient’s condition not suitable for further treatment. We conducted a 5-week treatment (followed by a pause of one week) consisting of daily exposure (on weekdays) with intermittent OMF. The patient tolerated the treatment well. At 4 weeks there was a progressive reduction of the contrast-enhanced tumor (CET) volume to less than 60% of the pre-treatment volume on magnetic resonance imaging scans. Caregiver report indicated mild subjective improvement in speech and cognitive function. The daily decrease in volume was correlated with the amount of daily treatment, with longer treatments showing an increase in shrinkage of the CET volume. After the treatment pause in the 6th week, there was an apparent increase in CET volume. However, a marked reduction in the choline peak and an increase in the lipid peak on a proton magnetic resonance spectrogram of the tumor at this timepoint documented that this represented necrotic tissue. We are excited about this new and powerful treatment for glioblastoma and will present the details of treatment and imaging studies during therapy.

Preexisting and treated concomitant ankle instability does not compromise patient-reported outcomes of solitary osteochondral lesions of the talus treated with matrix-induced bone marrow stimulation in the first postoperative year: data from the German Cartilage Registry (KnorpelRegister DGOU).

The purpose of this study was to compare the subjective ankle function within the first year following matrix-induced bone marrow stimulation (M-BMS) of patients with a solitary osteochondral lesion of the talus (OCLT) with and without concomitant chronic ankle instability (CAI). Data from the German Cartilage Registry (KnorpelRegister DGOU) for 78 patients with a solitary OCLT and a follow-up of at least 6months were included. All patients received M-BMS for OCLT treatment. The cohort was subdivided into patients with OCLT without CAI treated with M-BMS alone (n = 40) and patients with OCLT and CAI treated with M-BMS and additional ankle stabilisation (n = 38). The Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), and the Numeric Rating Scale for Pain (NRS) were used to assess patient-reported outcomes (median (minimum-maximum)). From preoperatively to 12months postoperatively, patients with OCLT without CAI treated with M-BMS alone had a significant improvement of all subscales in the FAAM [activity of daily living 64.3 (10-100) to 88.1 (39-100); sports 34.4 (0-100) to 65.6 (13-94), functional activities of daily life 50 (0-90) to 80 (30-100), functional sports 30 (0-100) to 70 (5-100)] and FAOS [pain 61.1 (8-94) to 86.1 (50-100), symptoms 60.7 (18-96) to 76.8 (29-100), activities of daily living 72.1 (24-100) to 91.9 (68-100), sport/recreational activities 30.0 (0-70) to 62.5 (0-95), quality of life 31.3 (6-50) to 46.9 (19-100)]. Within the first year, patients with OCLT and CAI treated with M-BMS and ankle stabilisation also showed significant improvement in the FAAM [activity of daily living 68.8 (5-99) to 90.5 (45-100); sports 32.8 (0-87.5) to 64.1 (0-94), functional activities of daily life 62.5 (25-100) to 80 (60-90), functional sports 30 (0-100) to 67.5 (0.95)] and the FAOS [pain 66.7 (28-92) to 87.5 (47-100), symptoms 57.1 (29-96) to 78.6 (50-100), activities of daily living 80.1 (25-100) to 98.5 (59-100), sport/recreational activities 35.0 (0-100) to 70.0 (0-100), quality of life 25.0 (0-75) to 50.0 (19-94)]. The pain level decreased significantly in both groups. No significant difference was found between both groups regarding the subscales of FAAM, FAOS and the NRS 1year postoperatively. Improvements in subjective ankle function, daily life activities and sports activities were observed within the first year following M-BMS. Our results suggest that preexisting and treated ankle instability did not compromise subjective outcome in patients treated with M-BMS in the first postoperative year. Level IV.

Effects of acupuncture versus cognitive behavioral therapy on cognitive function in cancer survivors with insomnia: A secondary analysis of a randomized clinical trial.

Cancer-related cognitive impairment is a prevalent, disruptive condition potentially exacerbated by sleep disturbances. The current study was performed to evaluate the effects of acupuncture versus cognitive behavioral therapy for insomnia (CBT-I) on objective and subjective cognitive function in cancer survivors with insomnia. Using data from a randomized clinical trial (160 survivors) that compared acupuncture versus CBT-I for insomnia occurring in cancer survivors, the authors analyzed cognitive outcomes and their relationship to insomnia symptoms. Analysis was limited to 99 patients who reported baseline cognitive difficulties. Interventions were delivered over 8weeks. Objective attention, learning, and memory were evaluated using the Buschke Selective Reminding Test. Subjective cognitive function was assessed using the Brown Attention-Deficit Disorder Scales. Insomnia symptoms were assessed using the Insomnia Severity Index. All outcomes were collected at baseline, week 8, and week 20. From baseline to week 8, acupuncture produced statistically significant within-group improvements in objective attention (Cohen D, 0.29), learning (Cohen D, 0.31), and memory (Cohen D, 0.33) that persisted to week 20 (all P<.05), whereas CBT-I produced a statistically significant within-group improvement in objective attention from baseline to week 20 (Cohen D, 0.50; P<.05); between-group differences were not statistically significant. Both interventions produced statistically significant within-group improvements in subjective cognitive function at weeks 8 and 20 compared with baseline (all P<.001); between-group differences were not statistically significant. In the acupuncture group, patients with clinically meaningful responses with regard to insomnia symptoms demonstrated a significantly greater improvement in subjective cognitive function compared with those without clinically meaningful insomnia responses (P=.006). Among cancer survivors with insomnia, both acupuncture and CBT-I produced significant improvements in objective and subjective cognitive function. However, the effect sizes varied and only survivors in the acupuncture group demonstrated a significant relationship between cognitive and sleep outcomes. These preliminary findings warrant further investigation to guide the personalized management of patients with cancer-related cognitive impairment.

6- VS 9-MONTH RETURN TO SPORT TESTING RESULTS AFTER ACL RECONSTRUCTION WITH QUADRICEPS AUTOGRAFT IN ADOLESCENT PATIENTS

Background:Recently, anterior cruciate ligament reconstruction (ACLR) using quadriceps tendon autograft has gained in popularity, particularly in adolescent patients. Studies are lacking that evaluate return to sport (RTS) testing after ACLR with quadriceps tendon autograft (QT).Hypothesis/Purpose:To investigate differences between the 6-month and 9-month RTS assessment in adolescent patients undergoing ACLR with QT.Methods:A retrospective review of adolescent patients who underwent primary ACLR with all soft-tissue QT identified 18 patients with formal RTS testing data at 6 and 9 months. Surgeries were performed between June 2017 and October 2018 by single surgeon using an all-inside technique. Concomitant meniscus repairs were performed in 38.9% of patients. All patients followed the same standardized rehabilitation protocol and completed a structured RTS test 6 and 9 months after surgery. The RTS test consisted of isometric and isokinetic strength testing, the Lower Quarter Y-Balance Test (YBT-LQ), and single-legged hop testing. The recovery of muscle strength, assessed via isometric/isokinetic and hop testing, was defined by a limb symmetry index (LSI) ≥ 90%. Differences were compared between the two RTS time points.Results:The mean age at the time of surgery was 15.2 years (range, 13-17 years). There were statistically significant improvements in the Pedi-IKDC (92.1 ± 8.4 vs. 82.9 ± 8.7; P = 0.001) and Tegner activity scale (7.1 ± 2 vs. 5.1 ± 2; P = 0.001). There were statistically significant improvements in isometric quadriceps strength (LSI, 82.6 ± 16.8 vs. 93.1 ± 11; P = 0.03) and hamstring strength (LSI, 86.4 ± 11.3 vs. 98.2 ± 9.6; P = 0.001). There were improvements in isokinetic knee extension at both 60 deg/sec (LSI, 75 ± 16.9 vs. 82.8 ± 13.9) and 180 deg/sec (LSI, 79.1 ± 14.8 vs. 84.6 ± 10.9), but the differences were not statistically significant (P = 0.08 and P = 0.11, respectively). There were no significant differences in isokinetic testing of knee flexion at either 60 deg/sec or 180 deg/sec. There were no statistically significant differences in the anterior reach component of the YBT-LQ at 6 and 9 months. Patients demonstrated statistically significant improvements on single-legged hop testing with mean LSIs > 95% for each of the four tests at 9 months postop.Conclusion:Adolescent patients undergoing ACLR with QT demonstrated significant improvements in subjective function and quadriceps strength between 6 and 9 months postop. This data supports delaying RTS beyond 9 months in this at-risk population.Table 1.Patient Reported Outcomes and RTS Test Results 6 Months 9 Months P* Pedi-IKDC82.9 ± 8.792.1 ± 8.40.001*Lysholm93.4 ± 6.897.2 ± 3.70.075Tegner5.1 ± 27.1 ± 20.001*Isometric-Q (LSI)82.6 ± 16.893.1 ± 110.03*Isometric-HS (LSI)86.4 ± 11.398.2 ± 9.60.001*Isometric-Hip (LSI)104.9 ± 11.1105.4 ± 7.90.74Isokinetic-Q60 (LSI)75 ± 16.982.8 ± 13.90.08Isokinetic-HS60 (LSI)105.5 ± 20.9104.4 ± 24.80.33Isokinetic-Q180 (LSI)79.1 ± 14.884.6 ± 10.90.11Isokinetic-HS180 (LSI)97.9 ± 20.594.7 ± 15.20.7YBT-LQ Anterior Reach (cm)3.8 ± 52.3 ± 3.20.06Single Hop (LSI)90.1 ± 11.695.1 ± 5.70.01*Triple Hop (LSI)90.3 ± 8.296.6 ± 4.10.01*Crossover Hop (LSI)92.9 ± 13.297.3 ± 3.20.01*Timed Hop (LSI)95.7 ± 10.998.4 ± 5.60.01**statistically significant (P < 0.05)Data reported as mean ± SDRTS, Return to Sport; Q, Quadriceps; HS, Hamstring; LSI, Limb Symmetry Index; YBT-LQ, Lower Quarter Y-Balance Test

Functional and Aesthetic Outcomes of Extracorporeal Septoplasty: A Systematic Review and Meta-Analyses.

The safety and efficacy of extracorporeal septoplasty (ECS) has long been debated. Our objective was to determine this technique's functional and aesthetic outcomes and complications through a systematic review of the literature. PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science databases were evaluated for studies detailing functional or aesthetic outcomes of ECS. Bias was evaluated using the Cochrane Risk of Bias Tool and the Methodological Index for Non-randomized Studies (MINORS) score. Aesthetic and functional outcomes in addition to complications were evaluated using subjective and objective measures. Meta-analyses were performed when appropriate. Seventeen studies encompassing 1418 patients were included. The average MINORS score for observational studies was 9.2. Overall there was a significant improvement in subjective nasal function with a preoperative average Nasal Obstruction Symptom Evaluation (NOSE) score of 75 (±16) decreasing to 19.5 (±16.5) postoperatively for a mean difference (MD) of -55 (95% confidence interval (CI): -60 to -49.5). In terms of objective nasal function, at 6 months postoperatively, there was an improvement of nasal flow measured by rhinometry ranging from 70 to 71% across studies. Anthropometric measurements were utilized for objective aesthetic outcomes. There was a significant improvement in I-shaped deviations (MD: -2.7°, 95% CI: -5.6 to -0.16) and C-shaped deviations improved by 11.9° (95% CI +2.8-+21.2). Complication rates ranged from 0 to 18%. ECS can achieve significant improvements in the subjective and objective function of the nose. The associated complication rate is low but variable between surgeons.

How Much Time Is Needed Between Serial “Return to Play” Assessments to Achieve Clinically Important Strength Gains in Patients Recovering From Anterior Cruciate Ligament Reconstruction?

Background: Pass rates for return-to-play evaluations are alarmingly low for patients after anterior cruciate ligament reconstruction (ACLR). Since timing of return to play is a complicated decision, it is important that patients be given optimal time to realize meaningful improvements in strength that warrant additional testing. Purpose: To (1) compare outcomes among patients assessed at different time points after ACLR, (2) determine strength gains indicative of improvements in subjective function, and (3) determine the amount of time necessary to achieve meaningful strength gains. Study Design: Cross-sectional/case-control study; Level of evidence, 3. Methods: A total of 293 patients participated in the study after ACLR (mean ± SD, 23.2 ± 10.1 years old; n = 142 female participants; 6.4 ± 0.9 months after ACLR). Participants were stratified on the month of their evaluation after ACLR: 5 to 6 months (n = 122), 6 to 7 months (n = 102), 7 to 8 months (n = 43), and 8 to 9 months (n = 26). The International Knee Documentation Committee (IKDC) subjective form and knee extensor and flexor torque and symmetry, as assessed through an isokinetic dynamometer, were compared among groups. Forty patients (20 female participants, 20.4 ± 7.1 years old) were referred for subsequent testing (2.14 ± 0.78 months after initial visit). Subjective improvement between visits was defined as a ≥9-point change of the IKDC score. Thresholds of knee extensor torque and symmetry indicative of subjective improvement and the time between assessments needed to achieve these strength improvements were determined. Results: Patients between 5 and 6 months (IKDC, 79.7; interquartile range [IQR], 70.1-88.5) had lower subjective function compared to patients between 6 and 7 months (IKDC, 83.9; IQR, 74.5-92.0; P = .019) and 8 and 9 months after ACLR (IKDC, 89.1; IQR 75.8-92.3; P = .026). Patients between 5 and 6 months (1.41 N·m/kg; IQR, 1.16-1.73 N·m/kg]) had lower knee extensor torque compared to patients 6 and 7 months (1.59 N·m/kg; IQR, 1.23-1.95 N·m/kg; P = .013) and 7 and 8 months after ACLR (1.62 N·m/kg; IQR, 1.30-1.86 N·m/kg; P = .046). Patients between 5 and 6 months (66.4%; IQR, 54.2-78.6) had lower symmetry compared to patients between 6 and 7 months (71.8%; IQR,61.1-82.9; P = .019) and 8 and 9 months afterACLR (75.2%; IQR, 66.6-87.7; P = .014). Of the 40 patients that completed follow-up assessments, an increase in knee extensor torque of 0.22 N·m/kg and symmetry of 5.75% discriminated patients that achieved subjective improvement. A period of 1.97 months between assessments discriminated those that achieved the established symmetry threshold. Conclusion: Patients demonstrate increasing subjective and quadriceps function when tested at later time points from surgery; however, the observed values are low, suggesting that at 9 months patients are demonstrating deficits that may be improving. Approximately 2 months is needed to observe clinically meaningful improvements.

Arthroscopic repair of isolated subscapularis tears: clinical outcome and structural integrity with a minimum follow-up of 4.6 years

After isolated subscapularis repair, improvement in shoulder function has been reported at short-term review. The purpose of this study was to determine whether arthroscopic subscapularis repair provides durable improvement in objective and subjective shoulder function with a low structural retear rate. All patients treated with arthroscopic repair of an isolated subscapularis tear between August 2003 and December 2012 with a minimum follow-up period of 4.6 years were identified from our database. A number of patients in our study cohort underwent a prior complete midterm assessment, which allowed a subgroup analysis to detect changes in structural integrity and corresponding function. Clinical and radiographic outcomes, including outcomes on conventional radiography and magnetic resonance imaging or ultrasound, were assessed. The study enrolled 36 shoulders with a mean patient age of 57.7 years (range, 31-75 years; standard deviation, 10.6 years). The mean follow-up period was 8.6 years (range, 4.6-13.9 years; standard deviation, 2.44 years). Internal rotation to the thoracic vertebrae was achieved in 94% of cases and was significantly improved (P < .001) compared with the preoperativesituation. The mean relative Constant score improved from 68% preoperatively to 93% at final follow-up (P < .001). Magnetic resonance imaging evaluation showed a rerupture rate of 2.7% (1 of 36 shoulders). Twenty patients underwent previous complete midterm assessment (mean, 2.9 years; range, 1-4.5 years), with comparisons between midterm and long-term follow-up showing comparable results without statistically significant deterioration. Functional and subjective improvements in shoulder function are maintained at a mean follow-up of more than 8 years after isolated subscapularis repair and are associated with a low structural failure rate of the repair.

Early locking plate removal following open reduction and internal fixation of proximal humeral fractures could prevent secondary implant-related complications

IntroductionProximal humeral fracture is a common cause of morbidity in the elderly and poses a challenge for the orthopedic surgeon. Open reduction and internal fixation (ORIF) with a locking plate is associated with high rate of secondary implant-related complications (IRC). Early implant removal could potentially reduce the risk of IRC and further improve the outcome in relatively asymptomatic patients. The purpose of this study was to evaluate the clinical and radiologic outcomes following implant removal. MethodsA total of 56 patients with an average age of 63 ± 13 years and a mean follow-up of 29 months were evaluated retrospectively following removal of a locking plate in the proximal humerus. Postoperative functional outcomes were evaluated with the Constant-Score, Subjective shoulder value and Quick-DASH score. ResultsEarly implant removal resulted in high functional outcomes with 96% of the patients reporting an improvement of their shoulder function following implant removal. No intraoperative complications were reported. Avascular necrosis (AVN) of the humeral head occurred in 12.5% of the patients, but no secondary screw cut-out was reported. ConclusionEarly implant removal might be a safe option to avoid secondary IRC with significant subjective functional improvement also in asymptomatic patients. Although early implant removal cannot reverse the process of AVN, it could potentially prevent secondary IRC and subsequent glenohumeral cartilage destruction.

Arthroscopic evidence of cartilage regeneration in severe knee cartilage defects and osteoarthritis following treatment with allogeneic umbilical cord-derived mesenchymal stromal cells (Chondrocell-Ex)

Background & Aim Background Knee cartilage defect is a difficult condition to treat. Currently, there are no satisfactory treatments for grade 3 International Cartilage Repair Society (ICRS) defect. Allogeneic umbilical cord-derived mesenchymal stromal cells (UC-MSCs) offers a safe and convenient potential therapeutic option for ICRS grade 3 knee articular cartilage defect because of their immunomodulatory functions and ability to promote cartilage differentiation. Despite subjective functional improvements reported by patients in many studies, objective arthroscopic images of gross cartilage regeneration are rarely obtained and it is not known if the improvement is merely due to reduction of joint inflammation or associated with cartilage regeneration. Objective The aim of this study was to assess the efficacy of allogeneic umbilical cord-derived mesenchymal stromal cells in patient with knee articular cartilage defects and to demonstrate cartilage regeneration using follow-up arthroscopy. Methods, Results & Conclusion Method This is a single-arm, open-label, compassionate study at the Universiti Kebangsaan Malaysia Medical Centre (UKKMC) with 12 months follow-up period. Subjects with knee articular cartilage defect ICRS 3 diagnosed via diagnostic arthroscopy were treated with allogeneic UC-MSCs (Chondrocell-Ex, Cytopeutics, Malaysia) and assessed in five subsequent visits. During the visits, assessment was done following Visual Analog Score (VAS), International Knee Documentation Committee (IKDC), Tegner Activity Score (TAS), and Knee injury and Osteoarthritis Outcome Score (KOOS) scoring. At the end of the study, subjects underwent another arthroscopy and gross morphology of the knee articular cartilage was directly visually reassessed. Results Six female subjects (mean age of 46.8±5.4 years) with single knee injury received the treatment. All patients had knee cartilage defect of 2.5cm2 or larger. We observe no procedure or stromal cell related adverse events during the 1 year follow up. VAS, IKDC, TAS and KOOS significantly improved in these subjects with VAS/KOOS, and TAS/IKDC score at 3 months and 6 months post therapy onwards until 12 months. Direct visualization during follow-up arthroscopy confirmed total coverage of previously defected articular cartilage in all patients. Conclusion Allogeneic UC-MSCs (Chondrocell-Ex) is well tolerated and feasible as a treatment in patients with moderately-severe knee articular cartilage defect, with arthroscopic evidence of total cartilage regeneration.

Diagnostic Challenges Associated with GLUT1 Deficiency: Phenotypic Variabilities and Evolving Clinical Features.

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.

Hippotherapy in Rehabilitation Care for Children With Neurological Impairments and Developmental Delays: A Case Series.

This report assesses functional mobility in children with neurological impairments and documented gross motor delays, before and after receiving either hippotherapy or standard outpatient physical therapy (PT). This is a case-series report using data previously collected for a discontinued randomized controlled trial, in which participants received hippotherapy or standard outpatient clinic PT for a 12-week treatment period. Results demonstrated both subjective and objective functional mobility improvements after treatment in participants receiving hippotherapy and standard outpatient PT, as determined by the Peabody Developmental Motor Scales-2, the Pediatric Evaluation of Disability Inventory, and the Goal Attainment Scaling. STATEMENT OF CONCLUSION AND RECOMMENDATIONS FOR CLINICAL PRACTICE:: When compared with standard outpatient PT, hippotherapy appears to be a viable treatment strategy for children aged 2 to 5 years with neurological impairments and gross motor delays, but additional research in this area is needed to validate findings.