Exploring the Role of Anatomical Imaging Techniques in Preoperative Planning for Orthopaedic Surgeries.

INTRODUCTION: The incorporation of a three-dimensional (3D) framework enables the surgeon to strategically plan their surgical intervention through the utilisation of the printed model. This encompasses the process of ascertaining the surgical approach, choosing the suitable reduction technique, finding the required implant dimensions, defining the ideal placement and alignment of the implant, and conducting a simulated practise of the procedure using a 3D printed duplicate of the anatomical structures. Therefore, we designed this study to evaluate the role of two imaging modalities (computed tomography (CT) and magnetic resonance imaging (MRI)) for pre-surgical planning for orthopaedic surgeries. METHODOLOGY: The present investigation entailed a prospective analysis of total knee arthroplasties (TKAs) that were performed using patient-specific instrumentation (PSI) from 2019 to 2022. After performing the bone resection operation utilising a customised cutting jig specific to each patient, the exact thickness of the resected bone was evaluated using a vernier calliper. In the MRI group, the researchers directly compared the cutting thickness during surgery with the consistency planned before the operation. In contrast, the CT group added the presumed cartilage thickness (2 mm) to the actual thickness of the bone that was removed from the lateral condyles. RESULTS:  The planned incision thickness in the distal femoral was 8.5 ± 0.8 in the CT group and 8.9 ± 0.5 in the MRI group, while the actual incision thickness was reported as 9.8 ± 0.54 in CT and 8.3 ± 1.1; however, no significant mean difference was found between both groups. The planned incision thickness was 2.6 ± 1.1 in the CT group and 2.43 ± 1.66 in the MRI group, while the actual thickness was observed as 2.5 ± 0.6 and 2.88 ± 1.12 without significant difference (p = 0.86). CONCLUSION: While magnetic resonance imaging (MRI) allows for the visualisation of cartilage, it has been observed that the MRI-based patient-specific instrumentation (PSI) system does not exhibit superior accuracy in projecting bone incision thickness compared to the computed tomography (CT)-based PSI system.

Neurocognitive Functions and Brain Volume in Patients with Endogenous Cushing's Syndrome Before and After Curative Surgery.

INTRODUCTION: Cushing's syndrome (CS) leads to various neuropsychiatric manifestations due to structural and functional changes of the brain and contributes significantly in the impairment of health-related quality of life. AIM AND OBJECTIVE: This study is conducted with aims to evaluate neurocognitive functions and brain volume in patients with endogenous Cushing's syndrome before and after curative surgery. METHODS: The diagnosis of CS was made by clinical features, abnormal cortisol dynamics, ACTH levels, and imaging studies. Neuropsychiatric tests (Beck depression Index, Spatial span test, PGI memory scale, Color trail test, Verbal fluency test), and Brain volume (Bi-caudate and third ventricular diameter) were done before and after curative surgery. RESULTS: Fifteen patients of CS were included for the study; all patients underwent curative surgery, neuropsychiatric assessment, and brain volume measurements. Nine patients were followed successfully till remission and repeat evaluation of these patients was done. Depression was the most common neuropsychiatric illness. Severity of depression positively correlated with 0800 h plasma cortisol and ACTH. Patients with higher severity of depression had maximum improvement after curative surgery. Significant decrease in the third ventricular, as well as bicaudate diameter, was observed after curative surgery (P < 0.01). CONCLUSION: Neuropsychiatric functions and structural brain changes reverse after curative surgery in patients with endogenous CS, however, long term follow-up is required to know whether these changes reverse completely or not.

N-cadherin adhesive interactions modulate matrix mechanosensing and fate commitment of mesenchymal stem cells.

During mesenchymal development, the microenvironment gradually transitions from one that is rich in cell-cell interactions to one that is dominated by cell-ECM (extracellular matrix) interactions. Because these cues cannot readily be decoupled in vitro or in vivo, how they converge to regulate mesenchymal stem cell (MSC) mechanosensing is not fully understood. Here, we show that a hyaluronic acid hydrogel system enables, across a physiological range of ECM stiffness, the independent co-presentation of the HAVDI adhesive motif from the EC1 domain of N-cadherin and the RGD adhesive motif from fibronectin. Decoupled presentation of these cues revealed that HAVDI ligation (at constant RGD ligation) reduced the contractile state and thereby nuclear YAP/TAZ localization in MSCs, resulting in altered interpretation of ECM stiffness and subsequent changes in downstream cell proliferation and differentiation. Our findings reveal that, in an evolving developmental context, HAVDI/N-cadherin interactions can alter stem cell perception of the stiffening extracellular microenvironment.

A pilot study with simvastatin and folic acid/vitamin B12 in preparation for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH).

BACKGROUND AND AIM: This study was conducted in preparation for the Study Evaluating Additional Reduction in Cholesterol and Homocysteine (SEARCH). SEARCH is a 12,000 patient 2X2 factorial study in post-myocardial infarction patients that will compare simvastatin 20 mg with simvastatin 80 mg to evaluate whether greater LDL-C reductions with simvastatin provide greater coronary event reductions. SEARCH will also test the hypothesis that lowering plasma homocysteine with folic acid and vitamin B12 will reduce coronary events. This pilot study was performed to determine whether any clinically meaningful interaction between simvastatin and folic acid/vitamin B12 exists. METHODS AND RESULTS: Following a 2-week diet/placebo run-in period, 141 patients with primary hypercholesterolaemia were randomised to one of three treatments for 6 weeks: 80 mg/day simvastatin and 2 mg folic acid/0.8 mg vitamin B12 daily (combination group); or 80 mg/day simvastatin and placebo vitamins (simvastatin alone group); or 2 mg folic acid/0.8 mg vitamin B12 daily and placebo simvastatin (vitamins alone group). The combination group and simvastatin alone group experienced similar serum lipid changes with reductions in LDL-cholesterol of 55.2% and 51.5% respectively. The combination group and vitamins alone group experienced similar homocysteine lowering with reductions in homocysteine of 25.3% and 23.1% respectively. All therapies were well tolerated. CONCLUSIONS: There was no detectable antagonistic effect when simvastatin and folic acid/vitamin B12 were administered concomitantly.

Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia.

In view of the role of both the de novo biosynthesis and receptor-mediated uptake of cholesterol for normal steroidogenesis, we evaluated whether extending the therapeutic dose of the hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, to 80 mg/d would affect adrenal and gonadal steroid synthesis in men with hypercholesterolemia. To evaluate this question, we enrolled men into a multicenter randomized, placebo-controlled study lasting 12 weeks. Men with serum low-density lipoprotein cholesterol (LDL-C) more than 145 mg/dL after 6 weeks of a lipid-lowering diet were randomized to 80 mg simvastatin or placebo. Half of the subjects were asked to undergo a 6-hour infusion of corticotropin (ACTH) to evaluate cortisol synthesis, and the entire cohort received a human chorionic gonadotropin (hCG) stimulation test to assess gonadal hormone secretion using pooled serum samples taken 15 minutes apart. A total of 81 men (age, 45 +/- 11 years; 93% Caucasian) with baseline serum LDL-C of 197 mg/dL (placebo, n = 39) and 184 mg/dL (simvastatin 80 mg, n = 42) completed the study. After 12 weeks, serum LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) in the simvastatin group changed by -43%, -25%, and 8%, respectively (all P < .001). The basal cortisol level and the peak serum cortisol and area under the curve response to the 6-hour ACTH infusion were comparable between the two treatment groups at baseline and after 12 weeks. The pooled total testosterone level at baseline was 541 and 513 ng/dL in the placebo and simvastatin-treated groups, respectively, which declined to 536 +/- 20.5 ng/dL (-1.5%) and 474 +/- 30.4 ng/dL (-13.6%, P = .09) after treatment (mean +/- SD). The pooled free testosterone declined by 6.3% in the simvastatin group, versus a 4.9% increase in the placebo group (P = .588), while pooled bioavailable testosterone declined 10.2% in the simvastatin group and increased 1.4% in the placebo group (P = .035). There were no changes in serum gonadotropin levels or sex hormone-binding globulin (SHBG). After administration of hCG, there were no differences in the peak total pooled testosterone level before or after 12 weeks of treatment. Simvastatin 80 mg was well tolerated compared with placebo. In conclusion, basal and stimulated cortisol production was unaffected by the use of simvastatin 80 mg versus placebo. As reported with other statins and cholestyramine, there were small declines in the simvastatin-treated group for pooled total, free, and bioavailable testosterone after 12 weeks, although there was no compensatory increase in serum follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels.

Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia.

BACKGROUND AND AIM: Clinical data suggesting that larger decreases in low density lipoprotein cholesterol (LDL-C) result in greater reductions in coronary heart disease events have led to the establishment of aggressive LDL-C targets for the treatment of hypercholesterolemia. In view of this, the efficacy and safety of a new maximum dose of simvastatin, 80 mg, were evaluated in 9 studies involving 2819 hypercholesterolemic patients. This report focuses on the combined results from the 4 main or Pivotal studies in which a total of 1936 patients received simvastatin 40 or 80 mg for 36 to 48 weeks. METHODS AND RESULTS: The Pivotal studies had similar randomized, multicenter, controlled, double-blind, parallel-group designs. Their combined results demonstrated a significant advantage in the LDL-C-lowering effect for the 80 mg dose. At week 24, the mean percentage reductions (95% confidence intervals) from baseline in LDL-C for the 40 and 80 mg groups were -39.8% (-40.9, -38.7) and -45.7% (-46.5, -45.0) respectively (p < 0.001, between groups), and larger reductions in total cholesterol and triglycerides were also observed in the 80 mg group. Both doses were well tolerated. No new or unexpected adverse events were observed and the overall clinical event profiles were similar in the two groups. Clinically significant hepatic transaminase increases (> 3 times the upper limit of normal/ULN) and myopathy (muscle symptoms plus creatine kinase increase > 10 times ULN) occurred infrequently with both doses. Simvastatin 80 mg had a comparable efficacy and safety profile in women and men as well as in non-elderly and elderly patients. CONCLUSIONS: Simvastatin 80 mg provides additional LDL-C and triglyceride reductions compared to the 40 mg dose and has an excellent safety and tolerability profile.