Old World Screwworm myiasis: First report of auricular Chrysomya bezziana myiasis in a dog in Singapore.

A German Shepherd dog was presented to a referral practice for screwworm myiasis affecting the ear. The successful management involved killing the larvae with afoxolaner plus milbemycin oxime and using video otoscopy to completely remove dead larvae. To the best of our knowledge, this is the first case report of auricular myiasis by Chrysomya bezziana in a dog in Singapore and the first report of video otoscopic management of myiasis.

Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer: results of exploratory analyses from the phase III BROCADE3 trial.

BACKGROUND: In the BROCADE3 trial, addition of the poly(ADP-ribose) polymerase inhibitor, veliparib, to carboplatin/paclitaxel improved progression-free survival (PFS) (hazard ratio 0.71, 95% confidence interval 0.57-0.88; P = 0.002) in patients with advanced human epidermal growth factor receptor 2-negative, germline BRCA1/2-mutated breast cancer. A subset of patients discontinued both carboplatin and paclitaxel before progression and continued on veliparib/placebo maintenance monotherapy until progression. Analyses in this patient subgroup are reported. PATIENTS AND METHODS: Patients were randomized 2 : 1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Veliparib (120 mg twice daily) or placebo was given on days -2 to 5, carboplatin (area under the curve 6 mg/ml) on day 1, and paclitaxel (80 mg/m2) on days 1, 8, and 15 of 21-day cycles. Patients who discontinued both carboplatin and paclitaxel before progression received blinded study drug monotherapy at an increased dose of 300-400 mg twice daily continuously. PFS was the primary endpoint. Exploratory analyses were carried out in the subgroup of patients who received blinded study drug as monotherapy. A time-varying Cox model including data from all patients was also used to evaluate treatment effect in the combination and monotherapy phases. RESULTS: A total of 136 of 337 patients randomized to veliparib plus carboplatin/paclitaxel and 58/172 patients randomized to placebo plus carboplatin/paclitaxel discontinued both carboplatin and paclitaxel before progression and continued on blinded veliparib or placebo monotherapy. In this blinded monotherapy subgroup, investigator-assessed median PFS from randomization was 25.7 months with veliparib versus 14.6 months with placebo. Hazard ratios from a time-varying Cox model favored veliparib during both combination therapy and monotherapy. Any-grade adverse events occurring in the monotherapy phase were primarily gastrointestinal. The most common grade ≥3 adverse events were neutropenia and anemia (4% each with veliparib; 5% and 2%, respectively, with placebo). CONCLUSIONS: Veliparib maintenance monotherapy had a tolerable safety profile and may extend PFS following combination chemotherapy.

Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Randomized, double-blind, active-controlled, multicentre, phase III clinical trial with two stages to assess the safety and efficacy of letibotulinum toxin a vs. onabotulinum toxin a for subjects with moderate to severe crow's feet.

BACKGROUND: Letibotulinum toxin A (LeBA) was approved by the Ministry of Food and Drug Safety (known as the Korea Food & Drug Administration) for cosmetic indications in 2012. However, the efficacy and safety of this newly introduced LeBA have not been investigated in crow's feet lines (CFL) treatment and standardization before its universal use. OBJECTIVE: The aim of this multicentre, double-blind, randomized, parallel, active-controlled Phase III clinical trial with two stages (ClinicalTrials.gov identifier: NCT03408236) was to investigate the non-inferiority of LeBA vs. the existing onabotulinum toxin A (OnBA) for the treatment of CFL. METHODS: A total of 240 subjects were randomized to either the test (LeBA) or control (OnBA) group. At the baseline and at weeks 4 while maximum smiling (primary efficacy assessment), 8, 12 and 16, investigator's on-site evaluation, independent evaluator, evaluation by the subjects, subjects' satisfaction assessment and safety assessment were performed. RESULTS: At week 4, the response rate of primary efficacy assessment was 69.75% and 68.33% in the test (LeBA) and control (OnBA) groups, respectively, without a significant difference. Other minor secondary evaluation results showed significant differences suggesting that LeBA offered better improvement than OnBA, but the overall results did not show significant differences between the two groups. CONCLUSION: This study showed that LeBA was as effective and safe as OnBA for the treatment of CFL at the same doses.

Creation and annihilation of topological meron pairs in in-plane magnetized films.

Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction.

Identifying key gait features associated with the radiological grade of knee osteoarthritis.

PURPOSE: Knee osteoarthritis (KOA) is characterized by pain and decreased gait function. This study assessed key features that can be used as mechanical biomarkers for KOA severity and progression. The identified features were validated statistically and were further examined by developing a classification model based on a machine-learning algorithm. METHODS: The study included 227 volunteers with various grades of KOA. The severity of KOA was graded using the Kellgren-Lawrence (KL) system. A total of 165 features were extracted from the gait data. The key features were selected using neighborhood component analysis. The selected features were validated using the t-test. Then, the features were examined by building a classification model using a random forest algorithm. RESULTS: Twenty features were identified that could discriminate the grade of KOA, including nine features extracted from the knee joint, seven from the hip, two from the ankle and two from the spatiotemporal gait parameters. The t-test showed that some features differed significantly between health and sever group, while some were significantly different among the severe group, and others were significantly different for all KL grades. The areas under the receiver operating characteristic curves for classification were 0.974, 0.992, 0.845, 0.894, and 0.905 for KL grades 0 through 4, respectively. CONCLUSION: Key gait features reflecting the grade of KOA were identified. The results of the statistical analysis and machine-learning algorithm show that the features can discriminate the severity of disease according to the KL grade.

Imputation of faulty magnetic sensors with coupled Bayesian and Gaussian processes to reconstruct the magnetic equilibrium in real time.

A Bayesian with Gaussian process-based numerical method to impute a few missing magnetic signals caused by impaired magnetic probes during tokamak operations is developed such that the real-time reconstruction of magnetic equilibria, whose performance strongly depends on the measured magnetic signals and their intactness, is affected minimally. Likelihood of the Bayesian model constructed with Maxwell's equations, specifically Gauss's law for magnetism and Ampère's law, results in an infinite number of solutions if two or more magnetic signals are missing. This undesirable characteristic of the Bayesian model is remediated by coupling the model with the Gaussian process. Our proposed numerical method infers nine non-consecutive missing magnetic signals correctly in less than 1 ms suitable for the real-time reconstruction of magnetic equilibria during tokamak operations.

Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study.

Background: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer. Patients and methods: Eligible patients ≥18 years with locally recurrent or metastatic breast cancer and a deleterious BRCA1/2 germline mutation were randomized 1 : 1 : 1 to VCP, VT, or placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and overall response rate (ORR). Results: Of 290 randomized patients, 284 were BRCA+, confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3 months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227], interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156), and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4 months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P < 0.001). Safety profile was comparable between carboplatin/paclitaxel arms. Adverse events (all grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with VT versus PCP. Conclusion: Numerical but not statistically significant increases in both PFS and OS were observed in patients with BRCA1/2-mutated recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional continuation single-agent therapy with veliparib/placebo if chemotherapy is discontinued without progression, in this patient population. Clinical trial information: NCT01506609.

Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.

PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab. Study endpoints included safety/tolerability and antitumour activity. The study was extended to include a Phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine. RESULTS: In the Phase II portion, of 50 patients treated with buparlisib and trastuzumab, the most common (≥ 30%) all-grade adverse events (AEs) were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved complete response and four (8%) patients had confirmed partial responses [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint (ORR ≥ 25%) was therefore not met. In the Phase Ib portion, all patients with measurable brain lesions at baseline showed tumour shrinkage to some degree; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined. CONCLUSION: Buparlisib plus trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety profile but limited efficacy in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine.

Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase III randomized trial.

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

Relationship between Total Fruit and Vegetable Intake and Self-Reported Knee Pain in Older Adults.

OBJECTIVES: Knee pain is one of the most common symptoms of knee osteoarthritis (OA) that affects the quality of life in the older adults, and identifying the contributing factors of knee pain is important. We hypothesized that higher fruit and vegetable consumption might be associated with the severity of knee pain lower prevalence of severe knee pain by affecting pain perception in the knee joint. Therefore, we investigated the relationship between self-reported knee pain and the consumption of fruits vegetables, carotenoids and vitamin C and self-reported knee pain. DESIGN: Nationally representative cross sectional study. SETTING: 2010-2011 rounds of the Korean National Health and Nutrition Examination Survey. PARTICIPANTS: A total of 6588 subjects aged ≥50 years were participated. METHODS: Severity of knee pain was estimated using a 10-point numeric rating scale (NRS). Daily intake of fruits, vegetables, and vitamins were estimated using data from 24-hour recalls and food frequency questionnaires. RESULTS: The NRS scores of knee pain decreased significantly with increasing fruit and vegetable intake quartiles. A multivariate logistic regression analysis showed that the fourth quartile of vegetable and fruit consumption was associated with decreased prevalence of severe knee pain (OR 0.59, 95% CI 0.48-0.73) compared with first quartile of vegetable and fruit consumption; however, carotenoids and vitamin C consumption was not associated with the severity of knee pain. CONCLUSIONS: In conclusion, severe knee pain was independently associated with fruit and vegetable consumption. Our findings suggest that intake of whole fruits and vegetables may help improve knee pain in older adults.

Toxicity profile differences of adjuvant docetaxel/cyclophosphamide (TC) between Asian and Caucasian breast cancer patients.

AIM: For early-stage breast cancer, four cycles of docetaxel and cyclophosphamide (TC) was proven superior to doxorubicin plus cyclophosphamide in the US Oncology 9375 trial. Given primary prophylactic antibiotics, 5% febrile neutropenia was recorded in a population comprising 75.5% Caucasians. Smaller trials and retrospective studies reviewing TC use in Asian patients did not produce similar incidence rates. This study aims to discover the variable hematological toxicities with TC use in Caucasian and Asian patients. METHODS: Breast cancer data was retrospectively reviewed for patients receiving adjuvant docetaxel 60-75 mg/m2 plus cyclophosphamide 600 mg/m2 from six countries (China, Hong Kong, Japan, Taiwan, Italy, and United States). Similar number of patients with relatively balanced baseline characteristics were chosen for analysis of hematological and nonhematological toxicities and survival data. RESULTS: From March 2004 to July 2013, data of 227 patients (127 Asians and 100 Caucasian) patients were analyzed for treatment-related toxicities. During the four cycles of TC, Asians had a significantly higher rate of grade ≥2 neutropenia than Caucasians (45.7% vs 6.0%; P <0.001) and significantly more grade ≥3 neutropenia events were documented (respectively 30.7% vs 4.0%, P <0.001). The prophylactic use of G-CSF was similar; 26.0% in Asians and 28.0% in Caucasian (P = 0.764). There were no differences in nonhematological toxicities. No significant difference in disease-free survival was observed between Asians and Caucasians (log-rank P = 0.910). CONCLUSIONS: Ethnic differences in toxicity profile exist between Asian and Caucasian patients given adjuvant TC. Over 30% Asians but less than 5% Caucasians experienced grade ≥3 neutropenia.

Adnexal torsion in early pregnancy after assisted reproduction: can the adnexa be saved?.

Adnexal torsion occurs when the ovary and fallopian tube twist on the axis created between the infundibulopelvic ligament and the utero-ovarian ligament. The symptoms are mostly unspecific and diagnosis is therefore not simple. Early diagnosis is essential to preserve organ function and fertility. The increased use of assisted reproductive technologies has led to an increase in the risk of adnexal torsion, particularly in pregnant women or women with ovarian hyperstimulation syndrome (OHSS). A gestational age eight-week pregnant woman who received in vitro fertilization (IVF) came to the clinic and was suspected of adnexal torsion. The patient underwent an operation and the biopsy histologically confirmed ischemia. Here the authors report a case with comparison to other studies, the early diagnosis, and early operation that could save adnexa.

A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients.

BACKGROUND: Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. METHODS: Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. KEY RESULTS: Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). CONCLUSIONS & INFERENCES: Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.

Effects of intraoperative protective lung ventilation on postoperative pulmonary complications in patients with laparoscopic surgery: prospective, randomized and controlled trial.

BACKGROUND: Respiratory functions are usually impaired during pneumoperitoneum for laparoscopic surgery. This randomized, controlled and single-blinded study was performed to evaluate whether intraoperative protective lung ventilation influences postoperative pulmonary complications after laparoscopic hepatobiliary surgery. METHODS: Sixty-two patients were randomized to receive either conventional ventilation with alveolar recruitment maneuver (tidal volume of 10 ml/kg with inspiratory pressure of 40 cmH2O for 30 s after the end of pneumoperitoneum, group R), or protective lung ventilation (low tidal volume of 6 ml/kg with positive end-expiratory pressure [PEEP] of 5 cmH2O, group P). Induction and maintenance of anesthesia were done with balanced anesthesia. Respiratory complications such as atelectasis, pneumonia or desaturation were observed postoperatively. The length of hospital stay, arterial blood gas analysis, peak inspiratory pressure and hemodynamic variables were also recorded. Results are presented as mean ± SD or number of patients (%). RESULTS: Postoperative pulmonary complications (P = 0.023) and desaturation below 90 % (P = 0.016) occurred less frequently in group P than in group R. Eight patients of group R and 3 patients of group P showed atelectasis. Pneumonia was diagnosed in 1 patient of group R. No differences were observed in the length of hospital stay, arterial blood gas analysis (pH, PaO2, PaCO2 and PAO2) and hemodynamic variables except PAO2, AaDO2 and peak inspiratory pressure between the two groups. CONCLUSION: Protective lung ventilation (low tidal volume with PEEP) during pneumoperitoneum was associated with less incidences of pulmonary complications than conventional ventilation with alveolar recruitment maneuver after laparoscopic hepatobiliary surgery.