Long-term outcome of patients with primary or secondary tumors of the proximal femur treated by bipolar modular tumor prosthesis.

PURPOSE: The proximal femur is a common area for primary and also metastatic bone tumors. The objective of this study was to assess the long-term functional and oncological outcomes of patients with malignant primary or secondary tumors of the proximal femur, who underwent proximal femoral resection then reconstruction using bipolar modular tumor prosthesis. METHODS: Sixty patients with proximal femoral malignant tumors underwent resection and bipolar modular prosthesis between 2000 and 2016, were retrospectively reviewed. Based on diagnosis and presence or absence of pathological fracture, patients were divided into groups. The functional outcome of the patients was evaluated using the Musculoskeletal Tumor Society (MSTS) functional scoring system for the lower extremities. RESULTS: The mean age was 38 (9-80) years at the time of primary surgery. Pathological fracture was the presentation in 28 patients. The study included 44 patients with primary bone tumor and 16 patients with a secondary bone tumor. The mean MSTS functional score of the patients was 24.3 (range, 18-30) points with no significant difference in patients with primary or secondary tumors. The rate of complications in the present series was 45%. The most frequent complication was an infection in 10 patients (16.7%), followed by aseptic loosening in 7 patients (11.7%). Local recurrence of primary bone tumors occurred in three out of 44 patients (6.8%). CONCLUSION: Modular bipolar tumor prosthesis has a good long-term functional result in both primary and secondary tumors of the proximal femur, with no significant effect of age, presence or absence of pathological fracture or femoral resection length on the functional outcome. It was found that the only statistically significant variable regarding the risk of infection is previous surgeries. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Sucrose esters of aryldihydronaphthalene-type lignans, and antitumor activity of extracts of Moltkiopsis ciliata (Forssk.) aerial parts.

One new compound (3f-[(7'R,8'R)-4,4'-dihydroxy-5-methoxy-2,7'-cycloligna-7-en-9-methoxycarbonyl, 9'-carbonyl-O-] -ß- D-fructofuranosyl- (2→1)-α- D-glucopyranoside) (Moltkiopsin A) (2) was isolated and identified from the extract of aerial parts of the wild Egyptian plant Moltkiopsis ciliata (Frossk.), family Boraginaceae, for the first time, along with two aryldihydronaphthalene lignans 3f→9':6f→9-[(7'R,8'R)-4,4'- dihydroxy-3,3',5-trimethoxy-2,7'-cycloligna-7-en-9,9'-dicarbonyl]-6g-acetyl-α-D-gluco pyranosyl-(1→2) -ß-D-fructofuranoside (Trigonotin A) (1) which was reported for the first time from this plant species and a known compound 3f→9':6f→9-[(7'R,8'R)-4,4'- dihydroxy-3,3',5-trimethoxy-2,7'-cycloligna-7-en-9,9'-dicarbonyl]-α-D-gluco pyranosyl - (1→2)- ß-D- fructofuranoside (Trigonotin C) (3). These compounds were separated and purified using different chromatographic techniques and their structures were elucidated by extensive 1D (1H and 13C NMR), and 2D NMR (COSY, HSQC, and HMBC), besides ESI-MS spectral methods. Extracts were screened as antioxidant, antitumor and antibacterial. The different extracts showed moderate to strong antioxidant capacities in DPPH assays. Ethyl acetate, methylene chloride and crude methanol extracts exhibited the most significant free radicals scavenging activity when compared to the standard antioxidant vitamin C. Hexane and butanol fractions showed the highest cytotoxicity against the cancer cell lines HepG2 and MCF-7.

Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals.

AIMS: Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited. METHODS AND RESULTS: Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan + Amlodipine (ARR = 8.7% compared to untreated) and 14.3% for Ramipril + Amlodipine (ARR = 8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes. CONCLUSION: This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

Initial Experience with Unidirectional Barbed Suture for Abdominal Donor Site Closure in Deep Inferior Epigastric Perforator Flap Breast Reconstruction.

Background: The deep inferior epigastric perforator (DIEP) flap is a predominant technique for autologous breast reconstruction. However, the best method of abdominal fascial closure in this technique is not well defined. This study details our initial experience with unidirectional barbed suture-only repair of abdominal donor site fascia. Methods: Patients who underwent DIEP flap breast reconstruction and abdominal fascial closure with Stratafix Symmetric Polydioxanone PDS Plus were retrospectively reviewed. Information regarding pertinent patient history, medical comorbidities, risk factors, and surgical technique was extracted, along with the incidence of eight separate postoperative abdominal surgical site occurrences. Results: Retrospective review identified 43 patients who underwent 19 unilateral and 24 bilateral DIEP flap breast reconstruction procedures (n = 67). Average patient follow-up was 791 days (range 153-1769). Six patients (14%) had a complication of the donor site. Seroma was most frequent (n = 3, 7%), followed by surgical site infection (n = 2, 5%). One patient had incisional dehiscence (2%) and another patient developed bulging (2%). No patients had chronic pain, weakness, hematoma, or hernia postoperatively. Patients with donor site complications had a history of abdominal/pelvic surgery significantly more often than the patients without donor site complications (100% versus 49%; P = 0.032). Conclusions: Abdominal fascial repair with Stratafix Symmetric suture alone led to low rates of abdominal donor site morbidity, including no hernia and rare bulging, following DIEP flap breast reconstruction. Additional advantages of this technique may be reduced operative times and lower operative costs compared with alternative methods of fascial repair, although prospective and randomized studies are warranted.

Pharmacokinetic Interactions and Tolerability of Rosuvastatin and Ezetimibe: A Randomized, Phase 1, Crossover Study in Healthy Chinese Participants.

BACKGROUND AND OBJECTIVE: The combination of rosuvastatin and ezetimibe has promising clinical benefits with a significant safety and tolerability profile. However, there is a lack of clinical data supporting the drug-drug interaction (DDI) in Chinese population. Thus, the aim of this study is to assess the potential pharmacokinetic DDI between rosuvastatin and ezetimibe in a Chinese population. METHODS: In this randomized, open-label, phase 1 study, 12 healthy volunteers were randomized to three treatment groups: 10 mg rosuvastatin plus 10 mg ezetimibe, 10 mg rosuvastatin alone, and 10 mg ezetimibe alone under fasting conditions. The plasma concentrations of rosuvastatin and ezetimibe were determined, and the pharmacokinetic parameters were calculated. Primary endpoints were peak plasma concentration (Cmax), area under the curve from zero to last measurement (AUC0-t), and area under the curve from zero to infinity (AUC0-∞) that were log-transformed, and co-administration was compared with monotherapy to evaluate the DDI. RESULTS: The geometric mean ratios (GMRs) of rosuvastatin with 90% confidence intervals (CIs) were 0.94 (0.80-1.12) for Cmax, 0.96 (0.85-1.08) for AUC0-t, and 0.96 (0.86-1.07) for AUC0-∞ when administered in combination with ezetimibe versus administered alone. The GMRs of unconjugated ezetimibe and total ezetimibe with 90% CIs were 1.15 (1.00-1.32) and 0.93 (0.80-1.07) for Cmax, 0.96 (0.84-1.10) and 0.95 (0.83-1.08) for AUC0-t, and 1.06 (0.96-1.18) and 0.94 (0.80-1.11) for AUC0-∞, respectively, when administered in combination with rosuvastatin versus administered alone. CONCLUSION: Co-administration of rosuvastatin and ezetimibe showed no clinically significant pharmacokinetic interactions in a healthy Chinese population.

A Bioequivalence Study of Ezetimibe/Rosuvastatin Fixed Dose Combination (10 mg/10 mg) Versus the Individual Formulations Taken Concomitantly.

INTRODUCTION: This study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and rosuvastatin) in Chinese healthy subjects under fasting conditions. METHODS: This was a phase I, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions. Cmax, AUC0-t, and AUC0-∞ from test and individual reference formulations were evaluated to assess bioequivalence. The safety assessments included adverse events (AEs)/treatment-emergent adverse events (TEAEs), potential clinically significant abnormalities (PCSAs) in vital signs, 12-lead electrocardiogram (12-ECG), and clinical laboratory parameters. RESULTS: Of the 68 subjects enrolled, 67 were treated. Systemic exposure to rosuvastatin based on Cmax, AUC0-t, and AUC0-∞ was similar in both treatments, with respective arithmetic values 12.4 ng/ml, 117 ng·h/mL, and 120 ng·h/mL for test formulation and 12.7 ng/ml, 120 ng·h/mL, and 123 ng·h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe was 4.14 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for the test formulation and 3.80 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for reference formulations. Systemic exposure to total ezetimibe was 70.5 ng/ml, 664 ng·h/mL, and 718 ng·h/mL for test formulation and 60.2 ng/ml, 648 ng·h/mL, and 702 ng·h/mL for reference formulations. The point estimates for rosuvastatin unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80-1.25. No deaths or serious adverse events were reported. CONCLUSIONS: Fixed dose combination of ezetimibe/rosuvastatin (10 mg/10 mg) achieved bioequivalence with reference to commercial tablets. TRIAL REGISTRATION NUMBER: CTR20202108.