Ophthalmology

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend-based regimen (T&E) with up to every-16-week (Q16W) dosing in the YOSEMITE/RHINE (NCT03622580/NCT03622593) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg Q8W, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg Q8W. The T&E up to Q16W dosing regimen was based on central subfield thickness (CST) and best-corrected visual acuity (BCVA) change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE/RHINE (N=940/951), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92/96/100 average) with faricimab Q8W (YOSEMITE/RHINE, +10.7/+10.9 letters) or T&E (+10.7/+10.1 letters) were comparable with aflibercept Q8W (+11.4/+9.4 letters). The median number of study drug injections was lower with faricimab T&E (YOSEMITE/RHINE, 10/11 injections) versus faricimab Q8W (15 injections) and aflibercept Q8W (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was further improved during year 2, with >60% of patients on Q16W dosing and ∼80% on ≥Q12W dosing at week 96. Almost 80% of patients who achieved Q16W dosing at week 52 maintained Q16W dosing without an interval reduction through week 96. Mean CST reductions were greater, and more patients achieved absence of DME (CST <325μm) and absence of intraretinal fluid with faricimab Q8W or T&E versus aflibercept Q8W through year 2. Overall, faricimab was well tolerated, with a safety profile comparable to aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to Q16W were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2/VEGF-A inhibition to promote vascular stability and provide durable efficacy for patients with DME

Reconstruction versus conservative treatment after rupture of the anterior cruciate ligament: cost effectiveness analysis

BACKGROUND: The decision whether to treat conservatively or reconstruct surgically a torn anterior cruciate ligament (ACL) is an ongoing subject of debate. The high prevalence and associated public health burden of torn ACL has led to continuous efforts to determine the best therapeutic approach. A critical evaluation of benefits and expenditures of both treatment options as in a cost effectiveness analysis seems well-suited to provide valuable information for treating physicians and healthcare policymakers. METHODS: A literature review identified four of 7410 searched articles providing sufficient outcome probabilities for the two treatment options for modeling. A transformation key based on the expert opinions of 25 orthopedic surgeons was used to derive utilities from available evidence. The cost data for both treatment strategies were based on average figures compiled by Orthopaedic University Hospital Balgrist and reinforced by Swiss national statistics. A decision tree was constructed to derive the cost-effectiveness of each strategy, which was then tested for robustness using Monte Carlo simulation. RESULTS: Decision tree analysis revealed a cost effectiveness of 16,038 USD/0.78 QALY for ACL reconstruction and 15,466 USD/0.66 QALY for conservative treatment, implying an incremental cost effectiveness of 4,890 USD/QALY for ACL reconstruction. Sensitivity analysis of utilities did not change the trend. CONCLUSION: ACL reconstruction for reestablishment of knee stability seems cost effective in the Swiss setting based on currently available evidence. This, however, should be reinforced with randomized controlled trials comparing the two treatment strategies

Criticality in tailoring the treatment for tracheoesophageal fistulas in children.

Tracheo-oesophageal fistula (TOF) is a rare pathology. It can be congenital and concurrent with other congenital anomalies such as oesophageal atresia, laryngeal and tracheal agenesis, or it can be acquired. The purpose of this study was to analyse various management strategies and their outcomes in infants and children with TOF and identify potential areas for standardisation of the fistula repair procedures. At a single institution, a retrospective analysis of infants and children with congenital or acquired TOF between 2013 and 2019 was performed. Thirteen patients were identified. Data collection included: patient demography, associated congenital anomalies, details of fistula at the time of endoscopy, surgical approach and intra-operative findings, need for additional intervention(s), and outcomes. Thirteen patients underwent endoscopic or open surgeries for correction of TOF. The TOF was congenital in ten patients and acquired in three patients. Eight patients had associated aero-digestive comorbidities, and six patients had systemic comorbidities. Three patients underwent endoscopic procedures and nine patients underwent an open TOF repair. One patient had tracheal agenesis and was not offered any treatment. Two patients required multiple endoscopic interventions for recurrent TOFs. Among four patients with prior tracheostomy, three were decannulated and one awaits decannulation. Conclusıon Appropriate case selection and surgical ergonomics are essential for patients with TOF to avoid recurrences. Preoperative endoscopy to obtain precise details regarding associated laryngotracheal lesions and demographics of the fistula is crucial

The role of nesfatin-1 in impaired appetite in patients with major depressive disorder

Aim The aim of the present study was to explore whether plasma nesfatin-1 levels are associated with impaired appetite in major depressive disorder (MDD). Methods Patients were recruited from outpatients who consecutively sought treatment in the psychiatric outpatient clinic of the University Hospital since March 2012. All patients were diagnosed with major depressive disorder according to DSM-IV. The appetite of patients was assessed by specific questionnaire. We categorized patients into two groups according to their appetite. Study group consisted of 30 patients with increased appetite (MDD-IA), 28 patients with decreased appetite (MDD-DA) and 28 healthy controls. Plasma nesfatin-1 levels and body mass index (BMI) were measured. Results There was no statistically significant difference in nesfatin-1 between groups. The mean serum nesfatin-1 level did not show any correlation with age, BMI, HAM-D scores and fasting blood glucose in patients groups. Conclusion Our findings suggest that fasting plasma nesfatin-1 levels are unchanged in untreated MDD patients and there is no evidence for nesfatin-1 playing a role in impaired appetite in patients with MDD. © 2013 Elsevier GmbH

The utility of susceptibility-weighted imaging to evaluate the extent of iron accumulation in the choroid plexus of patients with beta-thalassaemia major

AIM: To assess iron accumulation in the choroid plexus of beta-thalassaemia patients using fast spin echo (FSE) T2-weighted, gradient echo (GRE) T2*-weighted, susceptibility-weighted imaging (SWI) and compare the results