A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17).

BACKGROUND: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. PATIENTS AND METHODS: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test. RESULTS: Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. CONCLUSIONS: Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Phase II study of a trastuzumab biosimilar in combination with paclitaxel for HER2-positive recurrent or metastatic urothelial carcinoma: KCSG GU18-18.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a widely explored therapeutic target in solid tumors. We evaluated the efficacy and safety of trastuzumab-pkrb, a biosimilar of trastuzumab, in combination with paclitaxel, in HER2-positive recurrent or metastatic urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled 27 patients; they were administered a loading dose of 8 mg/kg trastuzumab-pkrb on day 1, followed by 6 mg/kg and 175 mg/m2 paclitaxel on day 1 every 3 weeks, intravenously. All patients received six cycles of the combination treatment and continued to receive trastuzumab-pkrb maintenance until disease progression, unacceptable toxicity, or for up to 2 years. HER2 positivity (based on immunohistochemistry analysis) was determined according to the 2013 American Society of Clinical Oncology /College of American Pathologists HER2 testing guidelines. The primary endpoint was objective response rate (ORR); the secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. RESULTS: Twenty-six patients were evaluated via primary endpoint analysis. The ORR was 48.1% (1 complete and 12 partial responses) and the duration of response was 6.9 months [95% confidence interval (CI) 4.4-9.3 months]. With a median follow-up of 10.5 months, the median PFS and OS were 8.4 months (95% CI 6.2-8.8 months) and 13.5 months (95% CI 9.8 months-not reached), respectively. The most common treatment-related adverse event (TRAE) of any grade was peripheral neuropathy (88.9%). The most common grade 3/4 TRAEs were neutropenia (25.9%), thrombocytopenia (7.4%), and anemia (7.4%). CONCLUSIONS: Trastuzumab-pkrb plus paclitaxel demonstrates promising efficacy with manageable toxicity profiles in patients with HER2-positive recurrent or metastatic UC.

Nickel, chromium and methyl methacrylate monomer release from orthopaedic functional appliances.

AIM: This study was purposed to evaluate release of nickel and chromium ions and methyl methacrylate (MMA) monomers from functional appliances and their possible health effects. MATERIALS AND METHODS: Study design: Twin-block appliances and Bionators were immersed in artificial saliva and kept in a thermal incubator. Control group was established as artificial saliva without appliances. Artificial saliva was analysed after 7 days, 30 days and 90 days. Inductively coupled plasma mass spectrometry and gas chromatography-mass spectrometry was used for detection of nickel and chromium ions and MMA monomers. MTT assays and cytokine array were performed. STATISTICS: One way ANOVA with Tukey test and Dunnett's T3 for post-hoc analysis was used for evaluation of time-dependent changes and independent t-test was used for evaluation of MTT assay results. RESULTS: The results revealed that metal ions and MMA monomers are released from the appliances. Metal ion detection pattern was irregular and could not be analysed. Twin-block group showed significantly larger amount of MMA release. MTT assay revealed statistically significant but minimally reduced cellular activity on Bionator and twin-block groups compared to control groups. Cytokine array showed no or less inflammatory cytokine release on Bionator and twin-block groups. CONCLUSION: MMA monomer release was confirmed but the cytotoxic effect of functional appliance material release is minimal or negligible. General toxicity of the functional appliance from the MMA monomer release is likely to be minimal or negligible.

The Association with rhegmatogenous retinal detachment and paediatric atopic dermatitis: a 12-year Nationwide Cohort Study.

PURPOSE: Historically, atopic dermatitis (AD) is associated with an increased risk of rhegmatogenous retinal detachment (RRD). However, uncertainty remained regarding the effect of AD itself and comorbidities (e.g., allergic diseases, cataract surgery) on RRD occurrence in a large, population-based paediatric population. PATIENTS AND METHODS: We analysed the 12-year National Health Insurance Service database (2002-2013) covering the entire Korean population to estimate the association between AD and RRD in people aged under 20 years. RESULTS: We identified 3142 RRD patients, and matched 18,852 controls (six controls to each RRD patient); therefore, we included 21,994 peoples under aged 20 years in the analyses. AD was more prevalent in the RRD group (329 patients, 10.47%) than the control group (1043 patients, 5.53%; P < 0.001), and so were severe AD (153 patients [4.87%] and 223 patients [1.18%], respectively; P < 0.001). In conditional logistic regression analysis, AD was associated with RRD (OR, 1.61; 95% CI, 1.93-1.87) even after adjusting for allergic conditions, connective tissue disease, uveitis, and cataract surgery. In addition, severity of AD was associated with an increased risk of RRD (OR for non-severe AD and severe AD, 1.26 [95% CI, 1.05-1.51] and 2.88 [95% CI, 2.25-3.68]). CONCLUSION: This study suggests that AD itself is a risk factor of RRD in children by showing the association between AD and RRD occurrence and the biologic gradient even after adjustment for known confounders including allergic conditions, uveitis, and cataract surgery.

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study.

OBJECTIVES: To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. METHODS: We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. RESULTS: Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05). CONCLUSIONS: Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

NAMPT Is an Essential Regulator of RA-Mediated Periodontal Inflammation.

Recent studies have indicated a potential correlation between rheumatoid arthritis (RA) and periodontal inflammation. We undertook this study to verify whether RA mediates periodontitis-like phenotypes in experimental mouse models of RA and to explore the role of nicotinamide phosphoribosyltransferase (NAMPT) in periodontal inflammation during RA pathogenesis. Periodontal inflammation and alveolar bone loss have been reported in mice with collagen-induced arthritis (CIA) and in genetically modified tumor necrosis factor-α (TNF-α) transgenic (TG) mouse models. Among the adipokines examined in our study, NAMPT expression was markedly upregulated in the periodontal ligament (PDL) tissues in RA mouse models and in human PDL cells stimulated by the proinflammatory cytokines, interleukin (IL) 1ß and TNF-α. When NAMPT was overexpressed with the Nampt-synthesizing adenovirus vector (Ad- Nampt), the PDL cells exhibited an increased expression of cytokines (IL6), chemokines (IL8 and chemokine [C-C motif] ligand 5 [CCL5]), inflammatory mediators (cyclooxygenase 2 [COX-2]), and matrix-degrading enzymes (matrix metalloproteinase [MMP] 1 and MMP3). Inhibition of NAMPT by the intracellular NAMPT (iNAMPT) inhibitor, FK866, or by the sirtuin inhibitor, nicotinamide, in PDL cells led to inhibition of the IL1ß or Ad- Nampt-induced upregulation of catabolic factors, whereas treatment with recombinant NAMPT protein or blockade of extracellular NAMPT (eNAMPT) with blocking antibody did not. Moreover, NAMPT inhibition by the intraperitoneal or intragingival injection of FK866 in CIA mice inhibited periodontal tissue damage, under conditions of RA. Thus, our results verified the co-occurrence of RA and periodontal inflammation using experimental mouse models of RA, suggesting that iNAMPT in PDL cells plays a pivotal role in the pathogenesis of RA-mediated periodontal inflammation by regulating the expression levels of catabolic genes, such as IL6, IL8, CCL5, COX-2, MMP1, and MMP3.

Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort.

Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 µg/ml with a high inoculum (∼5 × 107 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76-12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.

A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer.

PURPOSE: This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). METHODS: Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 µg/m2/day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. RESULTS: The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm3 and 161.75/mm3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. CONCLUSIONS: DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.

Successful outcome with minimally invasive plate osteosynthesis for periprosthetic tibial fracture after total knee arthroplasty.

INTRODUCTION: The incidence of periprosthetic fractures after total knee arthroplasty (TKA) is increasing, and treatment is becoming more necessary. In periprosthetic tibial fractures, the stem of the tibial component largely occupies the medullary canal of the proximal tibia, which limits the selection of implants. The purpose of this study was to evaluate the effectiveness of the minimally invasive plate osteosynthesis (MIPO) technique with locking plates for periprosthetic tibial fractures after TKA. MATERIALS AND METHODS: Sixteen patients with periprosthetic tibial fracture after TKA were included. There were 6 type II and 10 type III fractures according to the Felix classification. Ten patients had fractures in the proximal metaphysis, and 6 in the diaphysis. MIPO using locking plates was performed on the medial side in 4 cases, the lateral side in 2 cases, and both in 10 cases. Radiographic results included time to union, alignment, and malunion. Clinical results included range of motion (ROM), functional activity data, Knee Society scores, and complications. RESULTS: Fourteen of 16 fractures achieved union at 17.1 weeks (range, 14-24) postoperatively. There were 2 failures that required a secondary procedure. Except one for 1 case with varus malunion, all had acceptable alignment. Mean ROM at the final follow-up was 108.8° (range, 15-135°), and 15 patients recovered pre-injury knee joint activity. Mean knee and function scores were 88.9 (range, 77-100) and 83.3 (range, 60-100), respectively. Knees with fewer than 8 cortices giving purchase to screws in the proximal segment showed higher failure rates (P=0.025). DISCUSSION: MIPO with locking plates can achieve satisfactory results for periprosthetic tibial fractures after TKA. Rigid fixation of the proximal segment may be necessary for successful outcome. LEVEL OF EVIDENCE: IV.

A New Practical Desensitization Protocol for Oxaliplatin-Induced Immediate Hypersensitivity Reactions: A Necessary and Useful Approach.

BACKGROUND AND OBJECTIVE: Desensitization protocols for patients with immediate hypersensitivity reactions (IHSRs) have proven to be effective, but they are not widely used in clinical practice because of impracticalities such as high cost, long procedure duration, and a lack of trained personnel. We aimed to determine the clinical characteristics of oxaliplatin-induced IHSRs and assess measures to protect against these reactions and to validate a new practical desensitization protocol. METHODS: We retrospectively reviewed 2640 cases of oxaliplatin IHSRs in 271 oxaliplatin users and prospectively used a newly designed desensitization protocol 32 times in 12 patients with hypersensitivity to platinum-based chemotherapy. The protocol consisted of increases in infusion rate every 15 minutes, regardless of the concentration of the chemotherapy agent in the infusion bags. RESULTS: Of the 271 patients administered oxaliplatin, 45 (16.6%) experienced IHSRs. Of 39 patients who experienced an IHSR but needed to continue oxaliplatin, 6 (15.4%) stopped treatment due to the reaction, and 33 (84.6%) continued despite the risk of further reactions. The new desensitization protocol was successfully completed in 12 patients (100%), but it was ineffective in 3 patients (all with a negative skin prick test), who experienced fever without urticaria. CONCLUSIONS: Many patients who experience oxaliplatin-induced IHSRs are required to stop first-line oxaliplatin-based chemotherapy or to continue without desensitization, with the associated risks. Our new desensitization protocol is practical and easy to use in clinical practice.

Essential role of insulin-like growth factor 2 in resistance to histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors (HDIs) are promising anticancer therapies and have been clinically used for the treatment of hematological malignancy. However, their efficacy in solid tumors is marginal and drug resistance hampers their further clinical utility. To develop novel strategies for the HDI-based anticancer therapeutics in non-small cell lung cancer (NSCLC), in the present study, we investigated the mechanisms underlying resistance to HDI treatment in NSCLC cells. We show the STAT3-mediated IGF2/IGF-1R signaling cascade as a key modulator for both acquired and primary HDI resistance. The treatment with HDI upregulated IGF2 transcription in NSCLC cells carrying intrinsic or acquired drug resistance via direct binding of STAT3 in IGF2 P3 and P4 promoters. Acetylated STAT3 emerged upon HDAC inhibition was protected from the proteasome-mediated degradation of STAT3 and functioned as a direct transcription factor for IGF2 expression. Genomic or pharmacological strategies targeting STAT3 diminished the HDI-induced IGF2 mRNA expression and overcame the resistance to HDI treatment in HDI-resistant NSCLC- or patient-derived tumor xenograft models. These findings provide new insights into the role of acetylated STAT3-mediated activation of IGF2 transcription in HDI resistance, suggesting IGF2 or STAT3 as novel targets to overcome HDI resistance in NSCLC.

A surgical strategy for severe facial asymmetry due to unilateral condylar overgrowth.

Unilateral condylar overgrowth induces severe facial asymmetry. Therefore, treatment focuses on both elimination of the condyle lesion and correction of the facial asymmetry. The aim of this report is to present three patient cases, introducing a simpler surgical method, the indications for this surgical method, and a treatment planning flow that is consistently applicable regardless of the origin of the condylar lesion. Condylectomy was performed simultaneously with orthognathic surgery, with the vertical ramus osteotomy selected as the method of ramus surgery; ipsilateral ramus surgery was not performed on the condylectomy side. This method is applicable in cases in which facial asymmetry originates solely from unilateral condylar overgrowth, and the maxilla and mandible are presumed to have been in the normal class I anteroposterior position before the onset of condylar lesion growth. After surgery, temporomandibular joint pain and/or mouth limitations were resolved, the new condyle showed satisfactory bone remodelling, and favourable facial symmetry was attained. The postoperative results were maintained long-term and there was no recurrence on the condylectomy side. This simply modified surgical strategy for facial asymmetry due to unilateral condylar overgrowth may be used in selected patients, regardless of the origin of the condylar lesion.

Skeletal stability of surgery-first bimaxillary orthognathic surgery for skeletal class III malocclusion, using standardized criteria.

The purpose of this study was to compare the postoperative stability following bimaxillary surgery performed either with or without preoperative orthodontic treatment, in class III malocclusion patients. These patients were enrolled using standardized inclusion criteria. Forty patients with a class III malocclusion were included in this retrospective study. Inclusion criteria were class III malocclusion with and without premolar extraction, <3mm midline deviation, and <5mm arch width discordance. Patients were assigned to the conventional bimaxillary surgery group (n=20) or the surgery-first bimaxillary surgery group (n=20). Serial cephalometric radiographs obtained before surgery (T0), at 2 months after surgery (T1), and at 6 months after surgery (T2) were used to assess the variation in surgical change (T0 to T1) and postsurgical change (T1 to T2). Eight linear and three angular parameters were used to evaluate postoperative stability. With respect to postsurgical changes, significant differences were observed in the changes for the vertical reference plane to the posterior nasal spine, horizontal reference plane to B-point, and occlusal plane angle in both groups. No statistically significant differences in the relapse rates were observed between the two groups. No significant differences were observed between the two groups in terms of the postoperative stability.

Comparison of short wrist transverse open and limited open techniques for carpal tunnel release: a randomized controlled trial of two incisions.

UNLABELLED: The purpose of this randomized controlled trial was to compare outcomes of limited open and short wrist transverse techniques in patients with carpal tunnel syndrome. In a single centre randomized controlled trial, 84 patients with idiopathic carpal tunnel syndrome were randomized before surgery to limited open or short wrist transverse open carpal tunnel release. The patients were evaluated at 6 weeks, 3 months, 6 months, and 1 and 2 years after surgery. At every follow-up, the Brigham and Women's Carpal Tunnel Questionnaire scores, scar discomfort, and subjective patient satisfaction were evaluated. Two years after surgery, five patients were lost to follow-up. The groups had similar Brigham and Women's Carpal Tunnel Questionnaire Symptom Severity and Functional Status scores and subjective satisfaction scores. The incidence of scar discomfort was not significantly different between the two groups on serial postoperative follow-up. Short wrist transverse open release surgery showed similar early postoperative symptoms and subjective and functional outcomes to limited open release. LEVEL OF EVIDENCE: II.

Dual Role of Cyanidin-3-glucoside on the Differentiation of Bone Cells.

Cyanidin-3-glucoside (C3G) is one of the major components of anthocyanin, a water-soluble phytochemical. Recent studies demonstrated the chemopreventive and chemotherapeutic activities of C3G in various conditions, including cancer, although the precise effects of C3G on osteoclast and osteoblast differentiation remain unclear. Here, we investigated the role of C3G in the differentiation of bone-associated cells and its underlying mechanism. C3G inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation and formation in a dose-dependent manner and downregulated the expression of osteoclast differentiation marker genes. Pretreatment with C3G considerably reduced the induction of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated kinases activation by RANKL in osteoclast precursor cells. Furthermore, C3G dramatically inhibited the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1, which are important transcription factors for osteoclast differentiation and activation. The formation of osteoclasts in coculture of bone marrow cells and calvaria-derived osteoblasts was also inhibited by C3G treatment, although the expression of macrophage colony-stimulating factor and RANKL (master factors for osteoclast differentiation and formation) and osteoprotegerin (a decoy receptor for RANKL) on osteoblasts was unaffected. The inhibitory effect of C3G on osteoclastogenesis is therefore targeted specifically to osteoclasts but not osteoblasts. Moreover, analysis of the expression levels of osteoblast differentiation marker genes and alizarin red staining showed that osteoblast differentiation and matrix formation increased after C3G treatment. Taken together, these results strongly suggest that C3G has a dual role in bone metabolism, as an effective inhibitor of osteoclast differentiation but also as an activator of osteoblast differentiation. Therefore, C3G may be used as a potent preventive or therapeutic agent for bone-related diseases, such as osteoporosis, rheumatoid arthritis, and periodontitis.

Which tissues are best for microbiological diagnosis in patients with pyogenic vertebral osteomyelitis undergoing needle biopsy?

Identification of the causative microorganism is important in the management of pyogenic vertebral osteomyelitis (PVO). The aim of this study was to investigate whether culture positive rates differ between needle biopsy sites in patients with PVO, and which tissues are best for microbiological diagnosis. Between January 2005 and December 2013, we conducted a retrospective cohort study of PVO patients who had soft-tissue abscesses (paraspinal or psoas abscesses) and who received needle biopsy for microbiological diagnosis. Needle biopsy sites were classified into two anatomical categories: vertebral bodies, or soft tissues (intervertebral discs, paraspinal abscesses, or psoas abscesses). A generalized estimating equation model was developed to identify factors associated with tissue-culture positivity. During the study period a total of 136 tissues were obtained by needle biopsy from 128 PVO patients with soft-tissue abscesses. The culture positive rates of vertebral bodies and soft tissues were 39.7% (29/73), and 63.5% (40/63), respectively (p < 0.05). In a multivariate analysis, male gender (adjusted odds ratio (aOR) 2.24, 95% CI 1.00-5.02), higher C-reactive protein (aOR 1.07, 95% CI 1.01-1.15), positive blood culture (aOR 2.57, 95% CI 1.01-6.59), and soft tissues as biopsy site compared with vertebral bodies (aOR 2.28, 95% CI 1.08-4.78) were independent factors associated with tissue culture positivity. Soft tissues were the best sites for microbiological diagnosis in PVO patients undergoing needle biopsy.

Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model.

PURPOSE: To determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model. METHODS: VEGF-Trap was intravitreally injected in 18 rabbit eyes. Eyes were enucleated 1 h and 1, 2, 5, 14, and 30 days after injections and immediately frozen at -80 °C. Concentration of VEGF-Trap in vitreous, aqueous humor, and retina/choroid was determined using an indirect enzyme-linked immunosorbent assay and analyzed to obtain pharmacokinetic properties. RESULTS: Maximum concentration of VEGF-Trap was achieved at 1 h in all three tissues. A one-compartment model of distribution was selected as the final model for all tissues studied. Estimated half-life of VEGF-Trap in vitreous, aqueous humor, and retinal/choroid was 87.1, 36.8, and 35.0 h, respectively, and estimated mean residence time was 125.7, 53.1, and 50.5 h, respectively. Area under the curve from time 0 to the end point was 10009.8, 3945.1, and 1189.3, respectively. Total exposure of the aqueous humor and retina/choroid to VEGF-Trap was 39.4% and 11.9% of vitreous exposure, respectively. CONCLUSION: The vitreous half-life of VEGF-Trap is 3.63 days. This is shorter than that of bevacizumab (6.99 days) and longer than that of ranibizumab (2.51 days), as shown in studies using the same experimental settings. The concentration of VEGF-Trap peaked at 1 h after injections in all eye tissues studied.

Process development for recovery of vanadium and nickel from an industrial solid waste by a leaching-solvent extraction technique.

A process for recovering V(V) and Ni(II) from an industrial solid waste using sulfuric acid leaching, solvent extraction, precipitation and crystallization has been developed. The leaching parameters investigated were time, temperature and H2SO4 concentration. To quantify the linear and interaction coefficients a 2(3) full factorial experimental design was used. Regression equations for the extraction of V(V) and Ni(II) were determined and the adequacy of these equations was tested by Student's t-Test. More than 98% of both V(V) and Ni(II) were extracted in 90 min using 1.35 M H2SO4 at 40 °C. In addition, solvent extraction of V(V) with LIX 84-I in kerosene from the acidic leach liquor bearing 10.922 g/L V(V) and 18.871 g/L of Ni(II) was investigated. V(V) was extracted selectively using 40% LIX 84-I followed by stripping with NH4OH solution. McCabe-Thiele plots at O:A = 2:3 with 40% LIX 84-I and O:A = 3:1 with 15% (v/v) NH4OH showed two and three theoretical stages are needed for quantitative extraction and stripping of V(V), respectively. Ni(II) was selectively recovered from the V(V) free raffinate by adding ammonium oxalate at 60 °C. The purity of different products such as ammonium vanadate, nickel oxalate and nickel oxide obtained during the processes were analyzed and confirmed from the XRD studies.