Are Outcomes Comparable for Repair of AO/OTA Type 13C1 and Type 13C2 Distal Humeral Fractures Using the Paratricipital Approach?

Background: Studies have reported favorable outcomes using the paratricipital approach for fixation of distal humeral intra-articular fractures. However, literature evaluating the clinical results of the approach remains limited. The objective of this study was to compare clinical outcomes between type 13C2 and type 13C1 distal humeral fractures after open reduction and internal fixation performed using the same approach and same type of plate. Methods: A total of 52 adults with type 13C1 or 13C2 distal humeral fractures were treated surgically at our institution during 2006 to 2018. We retrospectively analyzed data from 29 of these patients (19 with type 13C1 fractures and 10 with 13C2 fractures) who met the inclusion criteria. All subjects were followed for a minimum of 2 years postoperatively. Clinical and radiologic results were analyzed to determine differences in outcomes between the two types of fractures. Clinical results were evaluated using elbow range of motion (ROM), Mayo Elbow Performance Score (MEPS), and Quick Disabilities of the Arm, Shoulder and Hand (Q-DASH) score. Alignment, fracture union, and presence of posttraumatic arthritis were evaluated radiologically. Results: The patients' mean age was 51 years, and the mean duration of follow-up was 29 months. Mean ROM was 129.5° ± 21.5° in the type 13C1 group and 123.0° ± 20.6° in the 13C2 group (p = 0.20). Mean Q-DASH score was 12.6 ± 11.7 in the 13C1 group and 16.2 ± 19.8 in the 13C2 group (p = 0.60). Mean MEPS was 92.9 ± 8.5 in the 13C1 group and 85.0 ± 14.1 in the 13C2 group (p = 0.09). Carrying angle did not differ significantly between the 13C1 and 13C2 groups. No patient in either group exhibited nonunion or posttraumatic arthritis. Conclusions: Although the paratricipital approach has the disadvantage of limited visualization of articular surfaces, there were no differences in surgical outcomes between type 13C1 and type 13C2 distal humeral fractures after fixation using this approach. Thus, surgeons may need to consider using the paratricipital approach for open reduction and internal fixation of 13C2 distal humeral fractures.

Recapitulation of First Pass Metabolism Using 3D Printed Microfluidic Chip and Organoid.

The low bioavailability of oral drugs due to first pass metabolism is a major obstacle in drug development. With significant developments in the field of in vitro organ modeling and microfluidic chip three-dimensional (3D) printing, the challenge is to apply these for the production and evaluation of new drug candidates. This study aimed to produce a microfluidic chip to recapitulate and assess the feasibility of the first pass metabolism. The infill condition of the polycarbonate transparent filament and layer height was optimized to visualize and maintain the organoid or spheroid on the chip. Next, the chip was fabricated using a 3D printer after a computer-aided design (CAD). The chip consisted of three wells of different heights. The small intestinal (SI) organoid and colorectal adenocarcinoma spheroids were placed on the second and third wells, respectively. No additional equipment was assembled, and the tilted tunnel was connected to each well to transport the material by gradient force. The chip was fabricated using 50% and 0.1 um thickness. Among the three different prototypes of chip (chips 1, 2, and 3), the highest distribution of plasmids in the Matrigel of the second well was observed in Chip 2 at 48 h. The effect of first pass metabolism was analyzed using docetaxel. In the chip without an SI organoid, there was a marked decrease in the viability of colorectal adenocarcinoma spheroids due to drug efficacy. However, in the chip with the SI organoid, no significant change in viability was observed because of first pass metabolism. In conclusion, we presented a simple, fast, and low-cost microfluidic chip to analyze the efficacy change of candidate drug by the first pass metabolism.

Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model.

Foxp3 is a master regulator of CD4(+)CD25(+) regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4(+) or CD8(+) cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3(DTR) mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma.

Perioperative Risk Assessment in Patients Aged 75 Years or Older: Comparison between Bilateral and Unilateral Total Knee Arthroplasty.

PURPOSE: The purpose of this study is to evaluate the risk of sequential bilateral total knee arthroplasty (TKA) under 1 anesthesia in patients 75 years or older. MATERIALS AND METHODS: Patients aged 75 years or older who underwent sequential bilateral TKA (bilateral group, n=159) and unilateral TKA (unilateral group, n=159) between 2002 and 2012 were selected. All patients were evaluated for underlying medical diseases, such as cardiac, pulmonary, and renal problems, and high-risk patients were recommended to postpone the surgery. We compared the underlying diseases, major postoperative complications, and the length of hospital stay between bilateral and unilateral groups. RESULTS: The prevalence of underlying diseases of the bilateral group was 74.8% and major complications occurred in 6 patients (3.8%). The prevalence of underlying diseases of the unilateral group was 52.4% and complications were observed in 4 patients (2.4%). Although the complication rate of the bilateral group was slightly higher than that of the unilateral group, the difference was not statistically meaningful (p=0.204). The length of hospital stay was 21.9 days for the bilateral group and 24.9 days for the unilateral group. CONCLUSIONS: There was no significant difference in postoperative complications between groups. The result shows that bilateral TKA can be relatively safe compared with unilateral TKA in patients 75 years or older. However, careful selection of low-risk patients is advised.

Accuracy and limitations of computer-guided curettage of benign bone tumors.

Adequate curettage of benign bone tumors located close to articular joints or neurovascular tissue is difficult without damaging those tissues. The purpose of this study was to evaluate the adequacy of tumor removal in computer-assisted curettage of benign bone tumors. The study is a prospective case series involving eight patients with benign bone tumors located near an articular joint or major neurovascular tissue. Image-to-patient registration with the navigation system was performed using paired-points methods in conjunction with CT images. A cortical window was created to visualize the tumor cavity. After removal of the gross tumor with sharp curettes, a specially designed burr attached to a navigation probe was used to monitor the location of the burr tip in real time. The high-speed burr extended the bony margin a few millimeters over the cavity wall. The empty cavity was then filled with bone cement. We assessed the accuracy of curettage and articular involvement by comparing pre- and post-operative CT images. In all cases, deeply seated or multi-cystic tumors were sufficiently removed according to the pre- and post-operative fusion CT images. The subchondral bone was punctured when the initial thickness of the subchondral bone was less than 2.5 mm. However, use of the computer-guided burr was safe if the thickness of the subchondral bone was greater than 3 mm. Computer-assisted curettage is a safe and useful method for localizing deeply seated benign bone tumors. However, use of the burr should be avoided when the bone thickness is less than 3 mm to avoid major tissue damage.

The role of TLE1 in synovial sarcoma.

The treatment outcome of synovial sarcoma is poor owing to its resistance to radiation and chemotherapy. The transducin-like enhancer of split 1 (TLE1) is a co-repressor that involves many signaling pathways like cell survival, hematopoiesis and differentiation. Although TLE1 is uniquely expressed in synovial sarcomas, the biological role of TLE1 is not completely understood. This study evaluated the function of TLE1 in synovial sarcomas using knock-down of TLE1, and examined whether the inhibition of TLE1 suppresses the proliferation of synovial sarcomas and enhances the cytotoxicity caused by doxorubicin (doxo). The over-expression of TLE1 was first confirmed in synovial sarcoma cells (HS-SYII). When the HS-SYII cells and normal fibroblast were transiently transfected with TLE1 siRNA, the MTT assay revealed growth inhibition in the HS-SY-11 cells but not in the normal fibroblast. TLE1 silencing also potentiated the cytotoxic effects of doxo against HS-SYII cells. This effect of TLE1 silencing was attributed mainly to the induction of apoptosis. Subsequent analysis revealed that Bcl-2 is a possible downstream target of TLE1 signaling. This study demonstrated that TLE1 is a critical factor for the survival of synovial sarcomas. Overall, the inhibition of TLE1 affects cell proliferation and the apoptosis pathway by suppressing the expression of Bcl-2.

Improvement of cardiovascular risk factors in patients with type 2 diabetes after long-term continuous subcutaneous insulin infusion.

BACKGROUND: The effects of long-term continuous subcutaneous insulin infusion (CSII) on cardiovascular risk factors such as hyperglycaemia, dyslipidaemia, and proinflammatory cytokine levels have not been assessed so far in type 2 diabetes. METHODS: We analysed the levels of HbA(1c), serum lipids, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) at 0, 2, and 30 weeks after CSII in 15 patients with type 2 diabetes (mean age, 53.3+/-10.1 years; disease duration, 9.4+/-5.3 years) without previous history of major cardiovascular events. RESULTS: At week 30, CSII significantly lowered HbA(1c) by 5.0+/-0.9% compared to baseline (7.9+/-1.9%, p<0.001) and improved high-density lipoprotein cholesterol (HDLc; 1.09+/-0.16 at baseline vs 1.25+/-0.15 mmol/L at week 30; p<0.05) and low-density lipoprotein cholesterol (LDLc)/HDLc ratios (2.8+/-1.4 at baseline vs 2.2+/-0.9 at week 30; p<0.05). CSII also decreased the proportion of patients with dyslipidaemia at week 30. At baseline, TNF-alpha and IL-6 levels were up-regulated (2.65+/-4.04 and 2.82+/-1.81 pg/mL, respectively) compared to the normal control (p<0.01 and p<0.05, respectively); however, cytokine levels decreased significantly at week 30 (1.44+/-2.25 and 1.99+/-1.05 pg/mL, respectively; p=NS vs control). CONCLUSIONS: Long-term CSII alone decreased cardiovascular risk factors in poorly controlled type 2 diabetes, suggesting that the synchronization of sufficient insulin peaks with meal ingestion and continuous pulsatile infusion of basal insulin corrects metabolic derangements.