Bone marrow aspirate concentration provided better results in cartilage regeneration to microfracture in knee of osteoarthritic patients.

PURPOSE: To determine whether microfracture with bone marrow aspirate concentrate (BMAC) improves functional outcome and cartilage regeneration better than microfracture alone in patients undergoing high tibial osteotomy (HTO) for medial unicompartmental osteoarthritis (OA). METHODS: Among 436 patients treated with HTO for medial unicompartmental OA with varus deformity between 2010 and 2016, clinical outcomes were retrospectively compared between the microfracture alone group (group I, 43 cases) and microfracture with BMAC augmentation group (group II, 48 cases). Of these, 64 patients underwent a second-look arthroscopic assessment. Clinical outcomes were compared based on the Knee Society Score (KSS), International Knee Documentation Committee (IKDC) subjective score, and Western Ontario and McMaster Universities Arthritis Index (WOMAC). Cartilage regeneration was assessed according to Koshino's staging system and the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. RESULTS: At the last follow-up, there were no significant intergroup differences in terms of KSS for pain and function (p > 0.05). Moreover, WOMAC scores were similar between the two groups (p > 0.05). Regarding second-look arthroscopy findings, according to Koshino's staging system, there was no significant intergroup difference in terms of defect coverage (p = 0.187). However, group II showed a significantly better mean CRA score than group I (p = 0.035). CONCLUSION: There were no significant differences in clinical outcomes and cartilage regeneration between the groups. However, the CRA score was significantly higher with BMAC augmentation and microfracture than microfracture alone. Therefore, BMAC augmentation had a synergistic effect for a better cartilage regeneration, although studies with a longer follow-up might help to confirm whether microfracture with BMAC augmentation would ensure better clinical outcomes than microfracture alone for the treatment of knee OA.

Mid-term results of total hip arthroplasty with modified trochanteric osteotomy in Crowe type IV developmental dysplasia of the hip.

BACKGROUND: This study aimed to explore mid-term clinical results of cementless total hip arthroplasty (THA) with modified trochanteric osteotomy in Crowe type IV developmental dysplasia of the hip (DDH). METHODS: Thirteen patients (13 hips) with Crowe type IV DDH who underwent THA with modified trochanteric osteotomy between May 2013 and October 2015 were retrospectively analyzed. The mean follow-up duration was 5.2 years (range, 4.9-6.1 years). RESULTS: The mean Harris Hip Score (HHS) significantly (p < 0.05) improved from 30.7 (range, 22-38) to 87.5 (range, 83-93). The mean leg length discrepancy (LLD) was 53.4 mm (range, 42.1-68.5 mm) preoperatively. The final LLD was 5.6 mm (range, 2.4-9.1 mm; p < 0.05). The mean leg length after surgery was 47.4 mm (range, 33.6-67.2 mm) and the femur shortening distance was 43.8 mm (range, 31.2-53.4 mm). The average duration of bone union for the greater trochanter (GT) was 2.5 months (range, 1.5-3.6 months). There was no infection, GT non-union, or loosening (septic or aseptic) of the stem or cup in any case. CONCLUSIONS: THA with modified trochanteric osteotomy with a cementless cup is an effective treatment for Crowe type IV DDH. It can rebuild complex biomechanics and biology of hip dysplasia without increasing complications.

Mouse-human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck.

BACKGROUND: Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs). METHODS: Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab. RESULTS: For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone. CONCLUSIONS: The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN. CLINICAL TRIAL REGISTRATION: NCT01527877.

Effect of diabetes mellitus on the outcomes of total ankle arthroplasty: is controlled diabetes mellitus a risk factor?

BACKGROUND: It is still uncertain whether diabetes mellitus (DM) is a risk factor for poor outcomes and increased complications after total ankle arthroplasty (TAA). The objective of this study was to compare clinical outcomes and complication rates of TAA in patients with and without DM. METHODS: This study enrolled patients with symptomatic end-stage ankle osteoarthritis with a minimum follow-up period of 24 months after TAA. A total of 252 patients (266 ankles) were classified into two groups according to the presence of DM: (1) DM group (59 patients, 67 ankles) and (2) non-DM group (193 patients, 199 ankles). We defined controlled diabetes as (1) HbA1c level < 7.0%, or (2) fasting glucose level < 130 mg/dL with HbA1c level ≥ 7.0% for hospitalization period. Clinical outcomes data (Ankle Osteoarthritis Scale, American Orthopedic Foot and Ankle Society ankle-hindfoot score, Short Form-36 Physical Component Summary score, and visual analog scale for pain) were compared preoperatively and at the final follow-up between the two groups. Complications following TAA were also compared between the two groups. RESULTS: All clinical variables had improved in both groups by the final follow-up (mean follow-up = 77.8 months). There was no significant difference in any clinical variable between the two groups at the final follow-up (P > 0.05). Of the 266 ankles, 73 ankles (19 in the DM group, 54 in the non-DM group) developed periprosthetic osteolysis. Although the DM group showed a higher prevalence of aseptic loosening or subsidence, the difference between the two groups was not statistically significant (P = 0.236). CONCLUSIONS: In the intermediate-term follow-up, TAA in patients with controlled DM showed clinical outcomes and complication rates comparable to patients without DM. Our results suggest that TAA can be done safely in diabetic patients if the DM is controlled in the perioperative period. LEVEL OF EVIDENCE: Therapeutic Level III.

Comparison of outcomes between fungal and non-fungal periprosthetic joint infections in total knee arthroplasty.

Aims: Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy. Methods: We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation. Results: The fungal PJI group demonstrated a significantly worse treatment success rate at the final follow-up than the non-fungal PJI group (65.0% (26/40) vs 85.0% (34/40); p < 0.001). The mean prosthesis-free interval was longer in the fungal PJI group than in the non-fungal PJI group (6.7 weeks (SD 5.8) vs 4.1 weeks (SD 2.5); p = 0.020). The rate of survivorship free from reinfection was worse in the fungal PJI group (83.4% (95% confidence interval (CI) 64.1 to 92.9) at one year and 76.4% (95% CI 52.4 to 89.4) at two years) than in the non-fungal PJI group (97.4% (95% CI 82.7 to 99.6) at one year and 90.3% (95% CI 72.2 to 96.9) at two years), but the differences were not significant (p = 0.270). Cox proportional hazard regression analysis identified the duration of the prosthesis-free interval as a potential risk factor for failure (hazard ratio 1.128 (95% CI 1.003 to 1.268); p = 0.043). Conclusion: Fungal PJIs had a lower treatment success rate than non-fungal PJIs despite two-stage revision arthroplasty and appropriate antifungal treatment. Our findings highlight the need for further developments in treating fungal PJIs.

Comparison of Preoperative Bone Density in Patients With and Without Periprosthetic Osteolysis Following Total Ankle Arthroplasty.

BACKGROUND: Modern total ankle arthroplasty (TAA) prostheses are uncemented press-fit designs whose stability is dependent on bone ingrowth. Preoperative insufficient bone density reduces initial local stability at the bone-implant interface, and we hypothesized that this may play a role in periprosthetic osteolysis. We aimed to investigate the preoperative bone density of the distal tibia and talus and compare these in patients with and without osteolysis. METHODS: We enrolled 209 patients (218 ankles) who underwent primary TAA using the HINTEGRA prosthesis. The overall mean follow-up duration was 66 (range, 24-161) months. The patients were allocated into 2 groups according to the presence of periprosthetic osteolysis: the osteolysis group (64 patients, 65 ankles) and nonosteolysis group (145 patients, 153 ankles). Between the 2 groups, we investigated and compared the radiographic outcomes, including the Hounsfield unit (HU) value around the ankle joint and the coronal plane alignment. RESULTS: HU values of the tibia and talus measured at 5 mm from the reference points were higher than those at 10 mm in each group. However, comparing the osteolysis and nonosteolysis groups, we found no significant intergroup difference in HU value at every measured level in the tibia and talus (P > .05). Concerning the coronal plane alignment, there were no significant between-group differences in the tibiotalar and talar tilt angles (P > .05). CONCLUSION: Patients with osteolysis showed similar preoperative bone density of the distal tibia and talus compared with patients without osteolysis. Our results suggest that low bone density around the ankle joint may not be associated with increased development of osteolysis. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Intracranial failure after hippocampal-avoidance prophylactic cranial irradiation in limited-stage small-cell lung cancer patients.

We evaluated intracranial failure after hippocampus-avoidance-prophylactic cranial irradiation (HA-PCI) for limited-stage small-cell lung cancer (SCLC). Data of 106 patients who received PCI with 25 Gy were retrospectively reviewed. The patients were divided into two groups based on whether they underwent HA-PCI: the HA-PCI group (n = 48) and the conventional PCI (C-PCI) group (n = 58). Twenty-one patients experienced intracranial failure: 11 and 10 patients in the C-PCI and HA-PCI groups, respectively. Using the log-rank test, the intracranial failure rate was not significantly different between the groups (p = 0.215). No clinical factor was significantly associated with intracranial failure in multivariate Cox regression analysis, but HA-PCI tended to be associated with increased incidence of intracranial failure (HR 2.87, 95% CI 0.86-9.58, p = 0.087). Among patients who received HA-PCI, two developed peri-hippocampal recurrence. A higher thoracic radiotherapy dose (≥ 60 Gy) was significantly associated with DFS (HR 0.52, p = 0.048) and OS (HR 0.35, p = 0.003). However, HA-PCI was associated with neither DFS nor OS. Although HA-PCI may be associated with an increased risk of intracranial failure, HA-PCI did not impair disease control or survival. Future prospective randomized trials are needed to reach a definite conclusion.

The additional use of end-tidal alveolar dead space fraction following D-dimer test to improve diagnostic accuracy for pulmonary embolism in the emergency department.

PURPOSE: To determine the diagnostic performance of bedside assessment of end-tidal alveolar dead space fraction (ADSF) for pulmonary embolism (PE) and whether the use of additional ADSF assessment following D-dimer assay can improve the diagnostic accuracy in suspected PE patients in the emergency department. METHODS: A prospective observational study of 112 consecutive adult patients suspected of PE of whom 102 were eligible for analysis. ADSF was calculated using arterial carbon dioxide and end-tidal carbon dioxide. An ADSF less than 0.2 was considered normal. RESULTS: PE was confirmed in 11 (10.8%) of 102 patients. D-dimer assay alone as a reference standard test for PE had a sensitivity of 100%, specificity of 38.5% and false negativity of 0%. Area under the receiver-operator characteristic curve for the diagnosis of PE using ADSF values alone was 0.894, Sensitivity, specificity and false negativity for the combined results of a positive D-dimer test and abnormal ADSF were 100%, 78.0% and 0% for the presence of PE, respectively. Of 65 patients with a low or intermediate clinical probability and a positive D-dimer assay, 36 (55.4%) patients displayed normal ADSF and had no PE. CONCLUSIONS: By itself ADSF assessment performed well in diagnosis of PE. The combined result of a positive D-dimer and abnormal ADSF increased the specificity for diagnosing PE compared with the D-dimer test alone. The use of additional bedside ADSF assessment following a positive D-dimer test may reduce the need for further imaging studies to detect PE in patients with a low or intermediate clinical probability.

The results of screw augmentation of acetabular cement spacers for the treatment of periprosthetic hip joint infection.

INTRODUCTION: Prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) is widely used in two-stage revision arthroplasty in periprosthetic joint infection (PJI) after total hip arthroplasty (THA). In our institution, we encountered several cases of acetabular cement spacer dislodgement. The aim of this study was to compare the results of two-stage revision arthroplasties with antibiotic-loaded cement spacers with or without screws on the acetabulum for PJI. PATIENTS AND METHODS: This retrospective study included 44 patients who underwent a two-stage revision THA for PJI from June 2007 to May 2017. We divided the patients into two groups: group 1 consisted of 21 patients (21 hips) who underwent two-stage revision arthroplasty with screw augmentation, while group 2 consisted of 23 patients (23 hips) who underwent the same surgery without screw augmentation at the acetabular cement spacer. We compared the migration and dislodgement of the acetabular cement spacer between the two groups. RESULTS: Before the second-stage surgery, there was less vertical migration of the cement spacer in group 1 compared to group 2 (1.2 mm vs 3.1 mm, p < 0.001). There was also less medial migration of the cement spacer in group 1 (0.6 mm vs 1.6 mm, p = 0.001). After the first stage, the mean Harris Hip score was significantly higher in group 1 than in group 2 (75 vs 65, p = 0.033). Cement spacer rotation or total movement out of the acetabular area occurred in six patients, all in group 2. After first stage reinfection occurred in two patients, one in each group. CONCLUSIONS: Screw augmentation to the acetabulum in the first-stage surgery provides better stability of acetabular antibiotic cement spacers without increasing reinfection rate.

Treatment for gastric 'indefinite for neoplasm/dysplasia' lesions based on predictive factors.

BACKGROUND: Gastric 'indefinite for neoplasm/dysplasia' (IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management. AIM: To determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions. METHODS: In total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection (n = 134), surgery (n = 22), and follow-up endoscopic biopsy (n = 305) were performed to confirm the diagnosis. The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia (60%) or atypical epithelia (40%) at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases. RESULTS: Four clinical factors [age ≥ 60 years (2.445, 95%CI: 1.305-4.580, P = 0.005), endoscopic size ≥ 10 mm (3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion (5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding (4.056, 95%CI: 1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium (25.575, 95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI: 1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were 91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change (5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review. CONCLUSION: More than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.

Baseline Renal Function Predicts Hyponatremia in Liver Cirrhosis Patients Treated with Terlipressin for Variceal Bleeding.

OBJECTIVES: Terlipressin is safely used for acute variceal bleeding. However, side effects, such as hyponatremia, although very rare, can occur. We investigated the development of hyponatremia in cirrhotic patients who had acute variceal bleeding treated with terlipressin and the identification of the risk factors associated with the development of hyponatremia. DESIGN AND METHODS: This retrospective, case-control study investigated 88 cirrhotic patients who developed hyponatremia and 176 controls that did not develop hyponatremia and were matched in terms of age and gender during the same period following terlipressin administration. RESULTS: The overall change in serum sodium concentration and the mean lowest serum sodium concentration were 3.44 ± 9.55 and 132.44 ± 8.78 mEq/L during treatment, respectively. Multivariate analysis revealed that baseline serum sodium was an independent positive predictor, and the presence of baseline serum creatinine, HBV, DM, creatinine, and shock on admission was independent negative predictors of hyponatremia (P < 0.05). CONCLUSION: The presence of HBV, DM, the baseline serum sodium, shock on admission, and especially baseline creatinine may be predictive of the development of hyponatremia after terlipressin treatment. Therefore, physicians conduct vigilant monitoring associated with severe hyponatremia when cirrhotic patients with preserved renal function are treated with terlipressin for variceal bleeding.

Exercise-Induced Intrapulmonary Arteriovenous Shunt in a Patient Complaining of Dyspnea during Strenuous Exercise.

A 51-year-old highly fit man presented for dyspnea with strenuous aerobic exercise. The patient was asymptomatic and all tests were normal at rest. With increasing exercise intensity, he suddenly complained of dyspnea and showed a severe exercise-induced hypoxemia with an excessive alveolar-arterial oxygen tension difference. In agitated saline contrast echocardiography at peak exercise, a large amount of left to right shunt was identified after > 5 cardiac cycles, which suggests the presence of exercise-induced intrapulmonary arteriovenous shunt in this patient.

Chemical properties and oxidative stability of perilla oils obtained from roasted perilla seeds as affected by extraction methods.

The chemical properties and oxidative stability of perilla oils obtained from roasted perilla seeds as affected by extraction methods (supercritical carbon dioxide [SC-CO(2)], mechanical press, and solvent extraction) were studied. The SC-CO(2) extraction at 420 bar and 50 °C and hexane extraction showed significantly higher oil yield than mechanical press extraction (P < 0.05). The fatty acid compositions in the oils were virtually identical regardless of the extraction methods. The contents of tocopherol, sterol, policosanol, and phosphorus in the perilla oils greatly varied with the extraction methods. The SC-CO(2) -extracted perilla oils contained significantly higher contents of tocopherols, sterols, and policosanols than the mechanical press-extracted and hexane-extracted oils (P < 0.05). The SC-CO(2) -extracted oil showed the greatly lower oxidative stability than press-extracted and hexane-extracted oils during the storage in the oven under dark at 60 °C. However, the photooxidative stabilities of the oils were not considerably different with extraction methods.

A gas chromatography-tandem quadrupole mass spectrometric analysis of policosanols in commercial vegetable oils.

UNLABELLED: Reportedly policosanols (PCs) have various beneficial functionalities on health. A gas chromatography-tandem mass spectrometry (GC-MS/MS) with a low limit of detection (LOD), and high specificity, recovery, and precision was successfully established for the PC analysis in vegetable oils. The LODs for the PCs were in the range of 0.002 to 0.016 µg/mL. The relative standard deviation (RSD) for the repeated analysis of PCs was less than 3.356%. The mean recoveries for spiked heptacosanol and octacosanol in vegetable oil were 102.3% and 106.3%, respectively. The total PC contents in the vegetable oils varied from 3.01 to 427.83 mg/kg oil. Perilla seed, grape seed, and rice bran oils were found to be highly rich sources of PCs, containing 427.83, 245.15, and 171.17 mg PCs/kg oil, respectively. Corn, sesame, and soybean oils contained only a negligible quantity of PCs. The PC composition in vegetable oils was greatly source dependent. In perilla seed oil, octacosanol was the single most predominant component, representing 55.93% of the total PC. In grape seed oil, however, hexacosanol is the most abundant PC, followed by octacosanol, tetracosanol, and triacontanol in a decreasing order. The major PCs in rice bran oil were triacontanol, octacosanol, hexacosanol, and tetracosanol, which constituted over 87.3% of the total PC. This represents the 1st report on the composition and contents of PC in most vegetable oils analyzed here. PRACTICAL APPLICATION: The information might be used for the development of vegetable oil products with beneficial functionality.