Sustained Functional Improvement Research Articles

MID-TERM OUTCOMES OF TROCHLEOPLASTY IN THE TREATMENT OF SEVERE TROCHLEAR DYSPLASIA

IntroductionTrochleoplasty is an effective surgical procedure for patients with severe trochlear dysplasia and recurrent patella instability. Previous work has suggested patients demonstrate early improvements in knee function and quality of life. However, concerns regarding longer term outcomes due to the development of stiffness and patellofemoral osteoarthritis remain a concern for these patients. Our aim was to assess mid-term patient-reported outcome and quality of life measures for trochleoplasty performed at a single centre for severe trochlear dysplasia.MethodsRetrospective review of 28 knees (23 patients) having undergone trochleoplasty for severe trochlear dysplasia were reviewed. Due to the non-parametric nature of the data, median and interquartile range (IQR) were determined for pre-operative and mid-term follow-up scores. Statistically significant differences between groups were assessed using paired Wilcoxon-signed rank test with statistical significance set at p<0.05. Data were analysed using a statistical software package (IBM® SPSS® Statistics 26.0).ResultsMedian time from surgery to follow-up for all patients in the series was 5.3 years (IQR 3.9 – 7.0 years). Median pre-operative Kujala score improved from 57.0 (IQR 45 – 66) to 96.3 (IQR 83 -100). Median pre-operative IKDC score improved from 42.6 (IQR 35.9 – 51.3) to 92.6 (IQR 71.6 – 98.7). Median EQ-5D score also improved from 0.691 (IQR 0.414 – 0.727) to 1.000 (IQR 0.8178 – 1.000). Improvement in Kujala scores, IKDC scores and EQ-5D were all statistically significant with p<0.001 in all domains.DiscussionOur data suggests patients experience significant improvements in knee function and quality of life following trochleoplasty surgery for severe dysplasia. We demonstrate an absolute improvement in scores at a mean of 5.3 years follow-up of 39.3 points for Kujala, 50 for IKDC and 0.309 for EQ-5D. Minimal clinically important differences (MCID) have been reported to be in the region of 10 for the Kujala score, 8.8–15.6 for IKDC and 0.085 for EQ-5D. Our data shows improvements which far exceed the published MCID, suggesting trochleoplasty confers a large treatment effect and patients benefiting from sustained improvements in knee function and overall quality of life at mid-term follow-up.ConclusionFollowing trochleoplasty for severe trochlear dysplasia, patient reported outcomes demonstrate continued improvements in knee function and quality of life at mid-term (5-year) follow-up. There is a large absolute treatment effect which likely impacts on both physical and psychological wellbeing for these patients. Continued surveillance of patient reported outcomes in this clinically complex cohort is indicated.

Evaluating purified exosome product and its role in neurologic and functional recovery following spinal cord injury in female rats

Introduction Exosomes represent extracellular vesicles that mediate intercellular interactions and have been extensively studied for their therapeutic potential. Purified exosomes product (PEP) from human plasma is reported to aid in tissue repair but has never been evaluated as a potential therapy for spinal cord injury (SCI). Objective We aim to investigate the effects of PEP on axon myelination, reduction in cavity size, and functional improvements in rats following SCI. Methods Following T9-T10 laminectomy and contusion to the spinal cord, female rats received either intrathecal (IT) PEP, IT ringer-lactate solution (RL), intravenous (IV) PEP, or IV RL one day post injury. Rats underwent behavioral assessments each week for 10 weeks following SCI. After 10 weeks, histological evaluations were performed to quantity axon myelination and cavity size. Results The IT PEP group had significantly (P ≤ 0.05) more myelinated axons 1000 μm rostral to the injury, at the epicenter, and 1000 μm caudal of the injury (34.3 ± 3.1, 27.7 ± 2.1, and 32.0 ± 1.7, respectively) compared to the IT RL group (27.3 ± 2.5, 17.3 ± 2.5, and 23.3 ± 2.5, respectively). In addition, IT PEP rats had significantly reduced cavity size at the injury epicenter compared to controls (28.31%±1.74% vs. 34.39%±3.78%, respectively). Lastly, functional improvements were observed and sustained beginning at the 31 days following injury. The IV PEP group did not show sustained functional improvement compared to the IV RL rats. Conclusion Our results suggest that IT PEP injection may yield beneficial effects following SCI. However, further studies are warranted to investigate the role of PEP following SCI and to optimize its potential for clinical translation.

Adults with congenital heart disease and pulmonary arterial hypertension: Quantitative assessment of haemodynamic parameters under disease targeting therapy - A retrospective multicentre analysis

Abstract Background Pulmonary arterial hypertension (PAH) occurs in approximately 10% of adults with congenital heart disease (ACHD), usually develops secondary to intra- or extra-cardiac shunts resulting in pressure and/or volume overload in the pulmonary circulation, and is associated with increased morbidity and mortality. Treatment strategies for PAH-ACHD include disease targeting therapies (DTT), such as phosphodiesterase-5 inhibitors (PDE5i) and endothelin receptor antagonists (ERA). Data regarding the impact of DTT on cardiopulmonary haemodynamics in PAH-ACHD are scarce. Purpose Aim of this study was to quantify effects of DTT on cardiopulmonary haemodynamics (assessed by right heart catheterisation [RHC]) and on key non-invasive functional parameters contributing to ESC/ERS risk status in PAH-ACHD patients, as applied in real-world clinical practice. Methods We retrospectively analysed the effect of DTT in PAH-ACHD patients who had undergone RHC in adulthood at baseline (treatment-naïve) between 2000 and 2022, with at least one follow-up RHC during DTT, in six expert centres in Europe. Clinical characteristics (WHO functional class [WHO-FC], 6-minute walking distance [6MWD], N-terminal pro-brain natriuretic peptide [NTproBNP] and measures of RHC (systemic/ pulmonary cardiac output, systolic/diastolic/mean pulmonary arterial pressure [sPAP, dPAP, mPAP], and pulmonary arterial wedge pressure [PAWP]) were collected. Pulmonary vascular resistance/arterial compliance (PVR+PAC) and stroke volume index (SVI) were calculated. Results 44 patients (70% female, mean age 45±15 years) were included. Underlying CHD was a pre- or post-tricuspid shunt in 35% and 63%, respectively. 14% had complex CHD, 7% had innate left heart disease, and 21% presented with Eisenmenger´s syndrome. At baseline 71% were in WHO-FC III/IV, 6MWD was 371±105 m, and NTproBNP was 673 [446–1021] ng/l. On RHC, mPAP was 58±15 mmHg, PVR 11 [7–17] wood units (WU), SVI 32 [27–44] ml/min/m2, CI 2.7±1.0 l/min/m2, and PAC 1.0 [0.7–1.4] ml/mmHg. DTT was started in all patients after baseline RHC. 81% received monotherapy (34% PDE5i, 66% ERA) and 19% received upfront combination therapy (PDE5i+ERA). Follow-up RHC was performed 15 [5–33] months after baseline RHC. At follow-up, WHO-FC and NTproBNP (562 [428-762] ng/l) significantly improved (p<0.001 and p=0.021, respectively), as did hemodynamic measures: mPAP (53±15 mmHg, p<0.001), PVR (9 [5–10] WU, p<0.001), SVI (37 [30–49] ml/min/m2, p=0.010), PAC (1.3 [1.0–1.7] ml/mmHg, p<0.001), and CI (3.1±1.1 l/min/m2, p=0.001). In contrast, 6MWD showed subtle change (379±111 m, p=0.164). After follow-up RHC, DTT was escalated in 78% of patients. Conclusions In PAH-ACHD patients, DTT was associated with a moderate but sustained haemodynamic and functional improvement after 15 months. Repeat RHC triggered treatment escalation in most patients. Therefore, ongoing vigilance for PAH-ACHD patients and subsequent treatment optimisation is warranted.

Abstract 12927: Impact of AAV- MYBPC3 Gene Transfer on Heart Structure and Function in Human and Mouse Models of Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a life-threatening inherited heart disease characterized by left ventricular hypertrophy and diastolic dysfunction. The most common cause of HCM is genetic variants in MYBPC3 , encoding cardiac myosin binding protein C (cMyBP-C), a sarcomeric protein with structural and regulatory roles. The majority of MYBPC3 gene variants are truncating leading to protein haploinsufficiency. Hypothesis: Transfer of a functional copy of MYBPC3 to heart muscle deficient in cMyBP-C will lead to sustained improvements in cardiac function. Aims: To determine whether BMN 293 (AAV-hMYBPC3) can restore cMyBP-C levels in the sarcomere and halt and/or reverse disease progression in non-clinical models of genetic HCM due to MYPBC3 deficiency. Methods: BMN 293 is an adeno-associated virus (AAV) vector that encodes wild-type human MYBPC3 under the control of a cardiomyocyte-selective promoter. We transduced human iPSC-derived cardiomyocytes and engineered heart tissues (EHTs) carrying a compound heterozygous truncating MYBPC3 mutation (MYBPC3 -/- ) with BMN 293 and assessed cMyBP-C levels and contractile parameters. We also systemically administered BMN 293 to MYBPC3 -/- mice and assessed cardiac distribution of human cMyBP-C by molecular and histological methods and determined its impact on left ventricular hypertrophy and function by echocardiography and other imaging techniques. Results: BMN 293 transduction of human iPSC MYBPC3 -/- cardiomyocytes and EHTs resulted in high levels of human MYBPC3 mRNA and cMyBP-C protein, correct incorporation of cMyBP-C into the sarcomere, and complete normalization of contractile kinetics. BMN 293 was well tolerated in MYBPC3 -/- mice and resulted in uniform restoration of cMyBP-C expression throughout the heart and significant correction of structural and functional cardiac abnormalities. Conclusions: A single IV infusion of BMN 293 to MYBPC3 -/- mice resulted in early and sustained reduction in left ventricular hypertrophy and durable improvements in diastolic function.

Sirolimus Long-Term Tolerability and Impact on Kidney Function in Lung Transplantation: A Single-Center Experience

After lung transplant, 2 common complications are calcineurin inhibitor (CNI) induced nephrotoxicity and bronchiolitis obliterans syndrome. The objective of this study was to investigate the long-term effects of sirolimus conversion after lung transplantation. This was a retrospective cohort study of patients who had undergone lung transplantation at a single center from June 2003 to December 2016. We compared patients converted to a sirolimus-based regimen to those maintained on our standard tacrolimus-based regimen. Kidney function, pulmonary function, and immunosuppression concentrations were compared between the groups. Additionally, indications, toxicity monitoring parameters, and discontinuation rates for sirolimus were collected. During the study period, 176 of the 205 patients who underwent lung transplants were converted to a sirolimus-containing regimen (86%). The most common reason for sirolimus initiation was impairment of kidney function or CNI-associated neurotoxicity. Sirolimus was initiated at a median of 150 days post-transplantation and continued for a medium time of 5.02 (2.27-7.85) years. Of those patients converted to sirolimus, 39 (22%) had sirolimus subsequently discontinued secondary to an adverse event. No difference in pulmonary function was found between the groups at 1- and 3-years post-transplantation. In the sirolimus group, the median estimated glomerular filtration rate improved by 8.6 mL/min/1.73 m2 at 3 months post-conversion (P < .001), which was maintained at both 1 and 3 years (P=.014 and .025, respectively). Sirolimus is a viable immunosuppressant option after lung transplant, which successfully allows for the reduction or withdrawal of the CNI, resulting in sustained improvement in kidney function.

Long-term clinical outcomes of elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis and advanced pulmonary disease

BackgroundThe combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators elexacaftor, tezacaftor and ivacaftor (ELX/TEZ/IVA) has been approved for treatment of cystic fibrosis (CF) patients (pwCF) homozygous and heterozygous for Phe508del. We aim to assess the long-term effects of ELX/TEZ/IVA therapy on clinical outcomes in severe pwCF. MethodsLung function, pulmonary exacerbation (PEx), sweat chloride concentration, body mass index (BMI) and the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R RD) were prospectively evaluated in a cohort of pwCF who were candidates for inclusion in a compassionate program of ELX/TEZ/IVA therapy. All procedures were performed at baseline and then at 12 and 24 months after initiation of modulator therapy. The number of PExs in the year before the study enrollment was collected from our records. ResultsThirty-six adult pwCF (median age 36.7 years; BMI 19.8 kg/m2; FEV1 36.5% predicted) were recruited from 2019. At 12 and 24 months after initiation, the absolute change in ppFEV1 (percent predicted forced expiratory volume in 1 s) from baseline was +12.5% (p < 0.0001) and +13% (p < 0.0001), respectively. A median of 4.0 exacerbations per patient was reported in the preceding year, while the median number of PExs was 0.0 and 1.0 after 12 and 24 months, respectively, of modulator therapy (both p < 0.0001). After 12 and 24 months of ELX/TEZ/IVA therapy, the CFQ-R RD score improved by 22.4 points (p < 0.0001) and 16.7 points (p < 0.0001), and sweat chloride levels decreased by 65.5 mmol/L (p < 0.0001) and 60 mmol/L (p < 0.0001), respectively. BMI significantly increased. ConclusionsLong-term ELX/TEZ/IVA combination therapy markedly impacts the clinical status of patients with severe CF, showing a sustained improvement in lung function and PEx rate.

Deep brain stimulation in multiple sclerosis-associated tremor. A large, retrospective, longitudinal open label study, with long-term follow-up

BackgroundTremor affects up to 25%-58% in multiple sclerosis (MS) population. Deep-brain stimulation (DBS) of the ventral-intermediate nucleus (VIM) of the thalamus is considered as a potential option following medical treatments. Long term DBS efficacy is not well known in these patients with a poor outcome mostly related to disease progression. ObjectiveTo report a large and retrospective study of thalamic DBS in MS tremor. MethodsWe conducted a large and retrospective study of patients with MS disabling and pharmacologically resistant upper limb tremor, who underwent thalamic DBS procedure from January 1992 to January 2015 in University Hospital of Henri Mondor, France. Demographic data, clinical assessment and activity daily living were collected. A three-month and twelve-month post-operative assessment with clinical and functional rating scales have been achieved, as well as long term follow-up for most patients. ResultsOne hundred and four patients underwent DBS procedure. There were 71 female (68%) and 33 male (32%). At three-month post-operative assessment, 64% patients were improved clinically and functionally. Among these, 93% of patients kept a good efficacy at one-year post-operative assessment. Mean duration of follow-up for these patients was 6 years. ConclusionWe described a long-term sustained clinical and functional improvement in this large and retrospective report of thalamic DBS. This neuromodulation approach could be a therapeutic option for all severe upper extremity refractory tremor in MS patients.

Atrial septal defect-associated pulmonary hypertension with decompensated heart failure: outcomes after fenestrated device closure.

Up to 90% of adults with untreated atrial septal defect will be symptomatic by 4th decade, and 30-49% will develop heart failure. 8-10% of these patients have pulmonary arterial hypertension with a female predominance regardless of age. We aimed to demonstrate that fenestrated closure can be safely performed in patients with decompensated heart failure and atrial septal defect-associated pulmonary arterial hypertension with improved outcome. Transcatheter fenestrated atrial septal defect closures (Occlutech GmbH, Jena, Germany) were performed on a compassionate-use basis in 5 consecutive adult patients with atrial septal defect-associated pulmonary arterial hypertension and severe heart failure with prohibitive surgical mortality risks. Change in systemic oxygen saturation, 6-minute walk test, NYHA class, echocardiographic and haemodynamic parameters were used as parameters of outcome. All patients were female, mean age 48.8 ± 13.5 years, followed up for a median of 29 months (max 64 months). Significant improvements observed in the 6-minute walk test, and oxygen saturation comparing day 0 time point to all other follow-up time points data (B = 1.32, SE = 0.28, t (22.7) = -4.77, p = 0.0001); and in the haemodynamic data (including pulmonary vascular resistance and pulmonary pressure) (B = -0.60, SE = 0.22, t (40.2) = 2.74, p = .009). All patients showed improved right ventricular size and function along with NYHA class. There were no procedure-related complications. Fenestrated atrial septal defect closure is feasible in adults with decompensated heart failure and atrial septal defect-associated pulmonary arterial hypertension. It results in sustained haemodynamic and functional improvement.

Chronic PCSK9 inhibitor therapy leads to sustained improvements in endothelial function, arterial stiffness, and microvascular function.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively decrease low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events in patients at very high cardiovascular risk. Recent short-term studies suggest a partially LDL-C independent beneficial effect of PCSK9 inhibitor (PCSK9i) therapy on endothelial function and arterial stiffness, whereas it is unknown if this effect persists and what the effect is on microcirculation. To investigate the effects of PCSK9i therapy on vascular parameters beyond its lipid lowering effect. In this prospective trial, 32 patients at very high cardiovascular risk and indication for PCSK9i therapy were included. Measurements were performed at baseline and after 6 months of PCSK9i treatment. Endothelial function was assessed as flow-mediated dilation (FMD). Arterial stiffness was measured as pulse wave velocity (PWV) and aortic augmentation index (AIx). Peripheral tissue oxygenation (StO2) as a marker of microvascular function was assessed at the distal extremities using near-infrared spectroscopy camera. Six months of PCSK9i therapy decreased LDL-C levels from 141 ± 54 to 60 ± 30 mg/dl (-56 ± 21 %, p < 0.001), FMD significantly increased from 5.4 ± 1.7 % to 6.4 ± 1.9 % (+19 ± 10 %, p < 0.001), PWV decreased in male patients significantly from 8.9 ± 2.1 to 7.9 ± 1.5 m/s (-12 ± 9 %, p = 0.025). AIx decreased from 27.1 ± 10.4 % to 23.0 ± 9.7 % (-16 ± 14 %, p < 0.001), StO2 significantly increased from 67 ± 12 % to 71 ± 11 % (+7 ± 6 %, p = 0.012). Brachial and aortic blood pressure showed no significant changes after six months. There was no correlation between LDL-C reduction and changes in vascular parameters. Chronic PCSK9i therapy is associated with sustained improvements in endothelial function, arterial stiffness, and microvascular function independent from lipid lowering.

A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis

Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis. To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis. The Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia. Individuals aged 12 to 25 years who were seeking treatment and met criteria for ultrahigh risk of psychosis according to the Comprehensive Assessment of At-Risk Mental States were recruited between April 2016 and January 2019. Of 1343 individuals considered, 342 were recruited. Step 1: 6 weeks of support and problem solving (SPS); step 2: 20 weeks of cognitive-behavioral case management (CBCM) vs SPS; and step 3: 26 weeks of CBCM with fluoxetine vs CBCM with placebo with an embedded fast-fail option of ω-3 fatty acids or low-dose antipsychotic medication. Individuals who did not remit progressed through these steps; those who remitted received SPS or monitoring for up to 12 months. Global Functioning: Social and Role scales (primary outcome), Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Montgomery-Åsberg Depression Rating Scale, quality of life, transition to psychosis, and remission and relapse rates. The sample comprised 342 participants (198 female; mean [SD] age, 17.7 [3.1] years). Remission rates, reflecting sustained symptomatic and functional improvement, were 8.5%, 10.3%, and 11.4% at steps 1, 2, and 3, respectively. A total of 27.2% met remission criteria at any step. Relapse rates among those who remitted did not significantly differ between SPS and monitoring (step 1: 65.1% vs 58.3%; step 2: 37.7% vs 47.5%). There was no significant difference in functioning, symptoms, and transition rates between SPS and CBCM and between CBCM with fluoxetine and CBCM with placebo. Twelve-month transition rates to psychosis were 13.5% (entire sample), 3.3% (those who ever remitted), and 17.4% (those with no remission). In this sequential multiple assignment randomized trial, transition rates to psychosis were moderate, and remission rates were lower than expected, partly reflecting the ambitious criteria set and challenges with real-world treatment fidelity and adherence. While all groups showed mild to moderate functional and symptomatic improvement, this was typically short of remission. While further adaptive trials that address these challenges are needed, findings confirm substantial and sustained morbidity and reveal relatively poor responsiveness to existing treatments. ClinicalTrials.gov Identifier: NCT02751632.

Pyrocarbon hemiprostheses show little glenoid erosion and good clinical function at 5.5 years of follow-up

The success of traditional shoulder hemiarthroplasty with cobalt-chromium (CoCr) heads is limited by a painful glenoid erosion with problematic bone loss. Hemiprostheses with pyrolytic carbon (PyC) heads have shown reduced glenoid erosion in experimental laboratory studies. Few in vivo data are available. Single-center consecutive cohort study of 31 of 34 patients (91%) who underwent PyC hemiarthroplasty between 09.2013 and 06.2018. For eleven of these concentric glenoid reaming was additionally performed. The mean follow-up was 5.5 (range 3.5 - 7) years. Standardized x-rays were taken and clinical function (Constant score) and pain on the visual analogue scale (VAS) were recorded. AP x-rays were analyzed according to an established method by 2 independent observers: A line parallel to the superior and inferior glenoid rim was translated to the most medial point of the glenoid surface. A further parallel line was placed on the spinoglenoid notch (SGN) and the distance between the two lines was measured. Measurements were scaled using the known diameter of the implanted humeral head component. To assess eccentric erosion AP and axial images were classified according to Favard and Walch respectively. The mean medial glenoid erosion was 1.4 mm over 5.5 years. In the first year there was 0.8 mm of erosion, significantly more than the average erosion per year of 0.3 mm (p < 0.001). Mean erosion per year of patients with glenoid reaming was 0.4 mm, without reaming 0.2 mm (p = 0.09). An evolution of glenoid morphology was observed in 6 patients, of which 4 had a progression of the erosion grade. Prosthesis survival rate was 100%. The Constant score improved from 45.0 preoperatively to 78.0 2-3 years postoperatively and 78.8 at latest follow-up 5.5 years postoperatively (p < 0.001). Pain decreased from VAS 6.7 (3 - 9) preoperatively to 2.2 (0 - 8) at latest follow-up (p < 0.001). There was a weak correlation (r = 0.37) between erosion and pain improvement (p = 0.039) and no correlation between erosion and delta Constant score (r = 0.06). PyC HA caused little glenoid erosion and a sustained improvement in clinical function in our cohort at mid-term follow-up. PyC demonstrates a biphasic development of glenoid erosion, with a reduced rate after the first year. PyC hemiarthroplasty should therefore be considered as an alternative to total shoulder arthroplasty or CoCr hemiarthroplasty for patients with a high risk of glenoid component complications.

Raising Awareness Towards Underdiagnosed Renal Hypouricemia: A Case Report

Renal hypouricemia (RHUC) is an autosomal recessive disease caused by the dysfunction of uric acid (UA) transporters in the proximal tubule causing increased fractional excretion of uric acid (FEUA). It is associated with mutations of SLC22A12 that codifies for URAT1, involved in RHUC type 1, or SLC2A9 which codifies for GLUT9 and is involved in RHUC type 2. We present the case of a man diagnosed with RHUC type 2 following hospitalization for acute kidney injury (AKI). A 43-year-old was hospitalized due to AKI after a 20 km walk at an outdoor temperature of 30°C. On the objective examination, he was dehydrated. Blood tests presented severe azotemia (creatininemia 16.43 mg/dL, uremia 254 mg/dL), UA 3.6 mg/dL, fosfatemia 6 mg/dL, Na 138 mEq/L, K 4.2 mEq/L, Cl 102 mEq/l, arterial gasometry with pH 7.35, pCO2 36 mmHg, HCO3 20 mmol/L, lactates 1.4 mmol/L. Urine test with proteinuria and unremarkable sediment. His kidneys had foci of microlithiasis. He started vigorous fluid therapy and sustained improvement in renal function was seen, with no need for renal function replacement therapy. The subsequent evaluation showed hypouricemia &lt;1.5 mg/dL and FEUA of 32.5% (normal range 5.5%-8.5%). The molecular study identified the variant c.1221del p.(His407Glnfs*8) in the SLC2A9 gene in homozygosis, which established the diagnosis of RHUC type 2. This case highlights the importance of recognizing hereditary RHUC to prevent its manifestations, including exercise-induced AKI, nephrolithiasis, nephrocalcinosis, and more rarely, progression to stage 5 CKD. Its diagnosis should be considered in individuals with serum UA &lt;2 mg/dL and elevated FEUA. Additionally, it should be confirmed by the identification of mutations in homozygous or compound heterozygous in SLC22A12 or SCL2A9. Treatment includes xanthine oxidoreductase inhibitors and adequacy of physical activity. The use of uricosuric antihypertensive drugs whose mechanism of action involves blocking the URAT1 transporter should be avoided.

Outcomes and Survivorship 5 Years After Arthroscopic Rotator Cuff Repair in Active Patients 70 Years and Older.

Rotator cuff tears are common in the elderly population and are associated with increased pain, decreased function, and decreased enjoyment of recreational activities. To evaluate clinical outcomes at a minimum of 5 years after arthroscopic repair of full-thickness rotator cuff tears in recreational athletes aged ≥70 years at the time of surgery. Case series; Level of evidence, 4. Included were recreational athletes aged ≥70 years who underwent arthroscopic rotator cuff repair (RCR) from December 2005 to January 2016. Patient and surgery characteristics were collected prospectively and retrospectively reviewed. Patient-reported outcome (PRO) scores utilized were the American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), the shortened version of Disabilities of the Arm, Shoulder and Hand score (QuickDASH), 12-Item Short Form Health survey (SF-12) questionnaire (Physical Component Summary and Mental Component Summary), and patient satisfaction. Kaplan Meier survivorship analysis was performed, with failure defined as revision RCR or retear on magnetic resonance imaging (MRI). Overall, 71 shoulders (n = 67 patients [44 men, 23 women]; mean age, 73.4 years [range, 70.1-81.3 years]) were included in this study. Follow-up data was obtained for 65 of the 69 available shoulders (94%) at a mean of 7.8 years (range, 5-15.3 years). Mean age at follow-up was 81.2 years (range, 75.7-91.0). One RCR was revised after a traumatic accident, and another had a symptomatic, MRI-confirmed retear. One patient had lysis of adhesions for stiffness 3 months postoperatively. All PRO scores improved from pre- to postoperatively-ASES, from 55.3 to 93.6; SANE, from 62 to 89.6; QuickDASH, from 32.9 to 7.3; and SF-12 Physical Component Summary, from 43.3 to 53 (P < .001 for all)-and the median satisfaction score was 10 out of 10. Postoperatively, 63% of the patients returned to their original fitness program and 33% of patients modified their recreational activity. Survivorship analysis showed a 98% survival rate at 5 years and a 92% rate at 10 years. Sustained improvement in function, reduced pain, and return to activities was seen after arthroscopic RCR in active patients ≥70 years old. Despite one-third of patients modifying their recreational activity, the cohort reported high levels of satisfaction and general health.

Spinraza in Adults with Spinal Muscular Atrophy (SAS) – 14 month results (S33.010)

Spinraza in Adults with Spinal Muscular Atrophy (SAS) – 14 month results (S33.010)

The Baveno VII concept of cirrhosis recompensation.

Traditionally, the progression from compensated to decompensated cirrhosis has been regarded as a point of no return in the natural history of the disease. However, this point of view is increasingly being challenged by new evidence on disease regression and hepatic recompensation upon suppression/cure of the underlying aetiology. In order to create a uniform definition of recompensated cirrhosis, standardised criteria have been set out by the Baveno VII consensus, which include the removal of the primary aetiological factor, the resolution of any decompensating events and a sustained improvement in hepatic function. Initial insights into the concept of hepatic recompensation come from previous studies, which have demonstrated that a cure/suppression of the underlying aetiology in patients with prior decompensation leads to significant clinical improvements and favourable outcomes and can even enable the delisting of transplant candidates. Nevertheless, future studies are required to shed light on the natural history of hepatic recompensation, assess modifying factors and potential non-invasive biomarkers of recompensation and explore the molecular mechanisms of disease regression.

Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study

BackgroundPhase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele. To assess long-term effects of ELX/TEZ/IVA under real-world conditions of use, a 5-year observational registry-based study is being conducted. We report interim results from the first 2 years of follow-up. MethodsThe study included people with CF in the US Cystic Fibrosis Foundation Patient Registry (CFFPR) who initiated ELX/TEZ/IVA between October 2019 and December 2020. Pulmonary exacerbations (PEx), percent predicted forced expiratory volume in 1 second (ppFEV1), hospitalizations, bacterial pathogens, body mass index (BMI), CF complications and comorbidities, and liver function tests (LFTs) after treatment initiation were compared with the 5-year pre-treatment period. Death and lung transplantation were assessed relative to 2019 CFFPR data. Results16,116 people with CF were included (mean treatment duration 20.4 months). Among those with 5 years of pre-treatment data, mean PEx/patient/year declined to 0.18 (95% CI: 0.17, 0.19) in Years 1 and 2 post-treatment from 0.86 (95% CI: 0.83, 0.88) in the baseline year (79% reduction), after a continued increase observed pre-treatment. Similarly, a decline in mean hospitalizations/patient/year was observed in Year 1 that was sustained in Year 2 (74% reduction from baseline year). The mean absolute change in ppFEV1 from baseline was +8.2 percentage points (95% CI: 8.0, 8.4) in Year 1 and +8.9 percentage points (95% CI: 8.7, 9.1) in Year 2, after a continued decline observed pre-treatment. Positive bacterial cultures decreased for all evaluated pathogens, and mean BMI increased by 1.6 kg/m2 (95% CI: 1.5, 1.6) by Year 2. No new safety concerns were identified based on evaluation of CF complications, comorbidities, and LFTs. The annualized rates of death (0.47% [95% CI: 0.39, 0.55]) and lung transplantation (0.16% [95% CI: 0.12, 0.22]) were considerably lower than reported in 2019 (1.65% and 1.08%, respectively). ConclusionsELX/TEZ/IVA treatment was associated with sustained improvements in lung function, reduced frequency of PEx and all-cause hospitalization, increased BMI, and lower prevalence of positive bacterial cultures. Additionally, there was a 72% lower rate of death and 85% lower rate of lung transplantation relative to the year before ELX/TEZ/IVA availability. These results, from the largest cohort of ELX/TEZ/IVA-treated people to date, extend our understanding of the broad clinical benefits of ELX/TEZ/IVA.

Abstract PD8-04: The role of Yoga as a complementary therapy in women undergoing treatment for breast cancer: A randomized controlled trial

Abstract Background: Yoga has been tested in multiple small-randomized studies for its impact on quality of life (QOL) on breast cancer (BC). We conducted a randomized controlled trial, to study the effect of yoga on disease free survival as the primary endpoint in women with operable breast cancer. (NCT02161900). Methods: Women with non-metastatic BC during and after standard treatment, were randomized to yoga and conventional exercise(YCE) versus conventional exercise only(CE). The primary endpoint was disease free survival (DFS) with secondary endpoints of overall survival (OS) and QOL, which was assessed using the EORTC QLQC30, BR23, Brief fatigue inventory (BFI), Visual pain scores (VPS) and a spirituality questionnaire (SQ). EORTC QLQ was assessed at baseline (BL), 6-9 months (mo), 18-21 mo. BFI and VPS at BL, 6-8 mo and 12-15 mo and SQ at BL and 12-15 mo. We report the final analysis of DFS, OS and QOL in 850 women randomized to the study. The groups were balanced for clinic-pathologic factors in both arms. Results: Of the 850 women randomized on the study, 426 were on YCE arm and 424 on CE arm. The median age was 47 versus (vs) 48 years, median pT size was 3 vs 2.85cm, grade 3 tumors were 82.7 vs 82.1%, hormone receptor positive was in 69% vs 69.4% and HER2neu positive was in 14.4 vs13.7% in YCE and CE arms respectively. At a median follow-up of 80 months the disease fee survival was 80% vs 76.7% (HR= 0.85, 95% CI= 0.64 – 1.14, p=0.28), and overall survival was 85.4% vs 83.1% (HR= 0.86, 95%CI = 0.61 – 1.21, p=0.38) in YCE and CE respectively. Physical(p=0.043) and emotional function (0.017), fatigue (p=0.002), pain (p=0.031), appetite loss (&amp;lt; 0.001) arm symptoms (0.035) and systemic therapy side effects (0.036) reduced at 6-9mo in YCE, with sustained improvements in physical (p=0.036) and emotional function (p=0.008) at 54mo. The median score of fatigue after adjuvant therapy measured by QLQ C30 was lower in YCE compared to CE (11.11vs 22.22, p = 0.002). Similarly, in BFI the baseline median scores of severity of fatigue were 5 in YCE and 6 in CE which reduced to 3 at one year in both groups. A further reduction to 0 was observed in the YCE arm at 2 years and then sustained till 4 years compared to the median score of fatigue in CE which stayed at 3. (p=0.04, 0.03 2 and 4 years respectively). In VPS the number of patients experiencing severe pain in YCE group were less than CE group with specific reduction noted in pain over the breast/chest wall (p=0.018 at 24mo). Lastly SQ assessed spirituality and showed no difference, but less deterioration compared to baseline scores were noted in YCE. Fifty-three percent women on YCE showed an improvement in QOL from baseline compared to 47% in CE, however the global score of QOL did not differ significantly between the two arms. This cohort had overall compliance of 61% to yoga and physiotherapy in YCE with 91.75% compliance among those who did yoga for 6-9mo and 85% to physiotherapy alone in CE. Conclusions: Yoga resulted in a 15% relative improvement in DFS and 14% in OS, that did not reach statistical significance in this trial. Yoga is a low-risk, low-cost therapy that improves day-to-day activity, including pain, fatigue and quality of life in women with breast cancer.This is the first study where the long term benefits in quality of life have been noted with the addition of yoga for women undergoing treatment for breast cancer. Citation Format: Nita S. Nair, Nishu S. Goel, Vani Parmar, Ashwini Dewade, Shabina Siddique, Aarti Pandey, Rohini Hawaldar, Rajendra Badwe. The role of Yoga as a complementary therapy in women undergoing treatment for breast cancer: A randomized controlled trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD8-04.

Effects of bariatric surgery on testosterone level and sexual function in men with obesity: A retrospective study.

Bariatric surgeries induce well-documented weight loss and resolve obesity comorbidities. Sexual function is one of the aspects of life quality and may benefit from surgery. Few studies have revealed the impact of bariatric surgeries on sexual function in Chinese men with obesity. This is a retrospective cohort study of patients undergoing bariatric surgery [laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB)]. Data were collected between September 2017 and February 2022. The International Index of Erectile Function (IIEF) questionnaire was used to evaluate erectile function, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. Sex hormones and other blood tests were evaluated before and at least 1 year after the surgery. Fifty-nine Chinese male patients completed the IIEF questionnaire. The multivariate logistic regression analysis revealed that body mass index (BMI) was the single independent risk factor of the severity of erectile dysfunction (ED). Preoperative testosterone levels had negative correlations with BMI and waist circumference. Thirty-seven patients completed the postoperative questionnaire with a mean follow-up of 23.2 months. BMI and waist circumference were negatively correlated with testosterone levels. BMI was an independent risk factor for the severity of ED. LSG and LRYGB led to positive and sustained improvement in sexual function of men with obesity. The two procedures had a comparable effect, more subjects being needed. Sex hormone levels also could be reversible. However, more weight loss did not predict a positive change in sexual function. A greater BMI loss might predict a greater increase in testosterone.

Comparison of Ultrasound-Guided versus Anatomical Landmark-Guided Approach for Perineural Steroid Infiltration in Carpal Tunnel Syndrome: A Prospective Randomised Controlled Trial

Background: Carpal tunnel syndrome (CTS), a compressive neuropathy is usually managed by conservative treatment and/or decompressive surgery. Minimally invasive perineural steroid injections have been shown to be very effective in early-onset CTS. We evaluated the clinical efficacy and safety of ultrasound (USG)-guided steroid injection over anatomical landmark-guided approach in CTS. Methodology and Results: Eighty-four consecutive Stage I-II primary CTS patients enrolled between August 2017 and December 2018 were randomised prospectively into two groups in 1:1 fashion. In Group I, anatomical landmark guided and in Group II, USG guided 1 ml steroid (40 mg methylprednisolone) was injected perineurally. Symptom and functional assessments were done using Boston Carpal Tunnel Questionnaire (BCTQ) and Visual Analogue Scale (VAS) score at 3, 6 and 12 weeks’ follow-up. Significant improvement was seen in BCTQ and VAS scores of both groups at 3 weeks follow-up. At subsequent follow-ups (at 6 and 12 weeks), marked improvement of BCTQ and VAS scores in USG-guided group was observed. Conclusion: USG-guided perineural steroid injections had early-onset significant and sustained symptom reduction and functional improvement at 6- and 12-weeks follow-up when compared to anatomical landmark-guided approach with both the techniques being equally safe.

Long-Term Rehabilitation Outcomes of Neurological Patients: A Multicenter Study

Objective: To evaluate functional outcomes in patients three years after rehabilitation and to identify factors significantly associated with improvement.Materials and Methods: This prospective cohort study was carried out in nine tertiary centers to compare functional outcomes (Barthel Index; BI) at discharge with scores at three-year follow-up among various diagnoses and types of admissions. Related factors were evaluated for association with improvement in functional score.Results: Three hundred and eighteen patients (mean age: 54 years; 60% male) were included. More than half of all patients suffered from a spinal cord injury. After three years, 35% of patients were still receiving physical therapy. Only those who were admitted for intensive rehabilitation showed significant improvement after three years. One hundred and ten patients or 35.8% showed significant improvement over time. A univariate analysis showed type of diagnosis, type of admission, onset to admission interval, BI at discharge, and presence of depression and complications at follow-up to be significantly associated with improvements in functional score in the follow-up period. Using a multivariate analysis, only the type of diagnosis, low BI at discharge, and absence of depression and complications at follow-up related to functional improvement.Conclusion: One-third of patients had sustained functional improvements from rehabilitation three years after discharge. Participants admitted into intensive rehabilitation showed significant improvements in functional scores between discharge and follow-up. TBI diagnosis, low BI at discharge, absence of depression and complications at follow-up related to long-term functional improvement at the three-year mark.