Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3.

BACKGROUND: In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with disease progression on prior endocrine therapy. In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3. PATIENTS AND METHODS: MONARCH 3 is a randomized, double-blind, phase III study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival was an exploratory endpoint. RESULTS: A total of 493 women were randomized 2 : 1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease, there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% confidence interval 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and chemotherapy-free survival numerically improved with the addition of abemaciclib. No new safety signals were observed. CONCLUSIONS: Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (intent-to-treat population: 13.1 months; subgroup with visceral disease: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.

Integrated Analysis of Microbiome and Metabolome Reveals Disease-Specific Profiles in Inflammatory Bowel Diseases and Intestinal Behçet's Disease.

The gut microbial and metabolic characteristics of intestinal Behçet's disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn's disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases.

A GLP-1/GLP-2 receptor dual agonist to treat NASH: Targeting the gut-liver axis and microbiome.

BACKGROUND AND AIMS: Currently there is no Food and Drug Administration-approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH. APPROACH AND RESULTS: C57BL/6J mice were fed a choline-deficient high-fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc fusion (GLP1/2-Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis. CONCLUSIONS: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

Bifidobacterium breve CBT BR3 is effective at relieving intestinal inflammation by augmenting goblet cell regeneration.

BACKGROUND AND AIM: Bifidobacterium breve was the first bacteria isolated in the feces of healthy infants and is a dominant species in the guts of breast-fed infants. Some strains of B. breve have been shown to be effective at relieving intestinal inflammation, but the modes of action have yet to be elucidated. In this study, we investigated the mechanisms of action of B. breve CBT BR3 isolated from South Korean infant feces in relieving colitis in vitro and in vivo. METHODS: Colitis was induced in mice with dextran sodium sulfate (DSS) and dinitrobenzene sulfonic acid (DNBS). Quantitative reverse-transcription polymerase chain reaction, in vitro FITC-dextran flux permeability assay, and aryl hydrocarbon receptor (AhR) luciferase assay are performed using Caco-2 cells and HT29-Lucia™ AhR cells. RESULTS: B. breve CBT BR3 was orally administered. B. breve CBT BR3 improved colitis symptoms in both DSS- and DNBS-induced colitis models. B. breve CBT BR3 increased the number of goblet cells per crypt. B. breve increased the mRNA expressions of Notch, Spdef, Muc5, and Il22. The mRNA expressions of Occludin, which encodes a membrane tight-junction protein, and Foxo3, which encodes a protein related to butyrate metabolism, were also increased in the DSS- and DNBS-induced colitis models. B. breve CBT BR3 protected inflammation-induced epithelial cell permeability and improved goblet cell function by inducing aryl hydrocarbon receptor in vitro. CONCLUSIONS: These results indicate that B. breve CBT BR3 is effective at relieving intestinal inflammation by augmenting goblet cell regeneration.

Frequency and risk factors for failed weaning from supplemental oxygen therapy after general anesthesia at a postanesthesia care unit: a retrospective cohort study.

BACKGROUND: Patients are administered supplemental oxygen upon emergence from general anesthesia against the risk of hypoxia. However, few studies have assessed the weaning from supplemental oxygen therapy. This study investigated the frequency and risk factors of failure to discontinue supplemental oxygen at a postanesthesia care unit (PACU). METHODS: This retrospective cohort study was conducted in a tertiary hospital. We reviewed the medical records of adult patients admitted to the PACU after general anesthesia for elective surgery between January 2022 and November 2022. The primary endpoint was the frequency of failed weaning from supplemental oxygen therapy at PACU. A failed weaning was defined as oxygen saturation (SpO2) < 92% after discontinuing oxygen administration. The rate of failed discontinuation of supplemental oxygen at the PACU was assessed. Demographics, intraoperative, and postoperative factors were explored to determine potential associations with failed weaning from supplemental oxygen therapy using logistic regression analysis. RESULTS: We analyzed 12,109 patients. We identified 842 cases of failed weaning from supplemental oxygen therapy, with a frequency of 1:14 (95% confidence interval [CI], 1:15-1:13). Risk factors that showed the strongest associations with failed weaning included postoperative hypothermia (odds ratio [OR], 5.42; 95% CI, 4.40-6.68; P < 0.001), major abdominal surgery (OR, 4.04; 95% CI, 3.29-4.99; P < 0.001), and preoperative SpO2 < 92% in room air (OR, 3.15; 95% CI, 2.09-4.64; P < 0.001). CONCLUSION: In the analysis of more than 12,000 general anesthetics, an overall risk of failed weaning from supplemental oxygen therapy of 1:14 was observed. The identified risk factors may help determine the discontinuation of supplemental oxygen administration at PACU. TRIAL REGISTRATION: Not applicable.

Discovery of Leishmania donovani topoisomerase IB selective inhibitors by targeting protein-protein interactions between the large and small subunits.

Visceral leishmaniasis (VL) is a fatal infectious disease caused by viscerotropic parasitic species of Leishmania. Current treatment options are often ineffective and toxic, and more importantly, there are no clinically validated drug targets available to develop next generation therapeutics against VL. Topoisomerase IB (TopIB) is an essential enzyme for Leishmania survival. The enzyme is organized as a bi-subunit that is distinct from the monomeric topoisomerase I of human. Based on this unique feature, we synthesized peptides composed of partial amino acid sequences of small subunit of Leishmania donovani (Ld) TopIB to confirm a decrease in catalytic activity by interfering the interaction between the two subunits. One of the synthetic peptides, covering essential amino acids for catalytic activity of LdTopIB, interrupted the enzymatic activity. Next, we examined 151 compounds selected from virtual screening in a functional assay and identified three LRL-TP compounds with a significant decrease in LdTopIB activity (IC50 of LRL-TP-85: 1.3 µM; LRL-TP-94: 2.9 µM; and LRL-TP-101: 35.3 µM) and no effects on Homo sapiens (Hs) TopIB activity. Based on molecular docking, the protonated tertiary amine of inhibitors formed key interactions with S415 of the large subunit. The EC50 values of LRL-TP-85, LRL-TP-94, and LRL-TP-101 were respectively 4.9, 1.4, and 27.8 µM in extracellular promastigote assay and 34.0, 53.7, and 11.4 µM in intracellular amastigote assay. Overall, we validated the protein-protein interaction site of LdTopIB as a potential drug target and identified small molecule inhibitors with anti-leishmanial activity.

Comparison of joint degeneration and pain in male and female mice in DMM model of osteoarthritis.

OBJECTIVE: While the prevalence of radiographic and symptomatic osteoarthritis (OA) is higher in women, male mice are more frequently used in animal experiments to explore its pathogenesis or drug efficacy. In this study, we examined whether sexual dimorphism affects pain and joint degeneration in destabilization of the medial meniscus (DMM) mouse model. METHODS: DMM or sham surgery was performed on the knee of male and female C57BL/6 mice. Joint damage was assessed by safranin O staining and scored using the Osteoarthritis Research Society International (OARSI) scoring system. Von Frey hair, incapacitance, and rotarod tests were conducted to measure joint pain. The analgesic effect of capsazepine (CPZ), a TRPV1 antagonist, was compared between male and female mice. RESULTS: Histology and OARSI scoring analysis showed that cartilage degeneration developed, and progressed in both male and female DMM groups, however, damage was less severe in females at the late stage of OA. Pain behavior, as measured by mechanical allodynia, was displayed for longer in male DMM mice compared to females. Incapacitance data showed that CPZ significantly reduced DMM-induced pain in male mice but not in female mice. Immunofluorescence microscopy analysis demonstrated that DMM surgery increased the expression of TRPV1 in both female and male dorsal root ganglion (DRG). Injection of CPZ significantly suppressed TRPV1 expression in the DRG of male mice only. CONCLUSION: Joint damage develops comparably in both female and male mice after DMM although it progresses less in females. There was a subtle sex difference in pain behaviors and analgesic efficacy of a TRPV1 antagonist, which was accompanied by a differential regulation of TPRV1.

Off-line learning in a rhythmic bimanual task: early feedback dependency is reduced over wakefulness.

Research has supported two distinct forms of motor skill consolidation that can occur between practice sessions: (1) off-line learning, and (2) memory stabilization. Off-line learning describes performance improvement between practice sessions that is above the gain observed at the end of practice, while memory stabilization describes a gain in performance that is maintained between practice sessions. This study used a Lissajous plot to provide concurrent feedback to train participants to produce a 90° relative phase between the index fingers (flexion/extension motion). Significant improvements in performance emerged after ten trials (5 min) of practice. At the end of training, participants were divided into two delay interval groups before retesting, 2-h and 6-h. The retesting session started with participants performing an interference task (10 trials, 5 min) that required training on a 45° relative phase between the fingers with concurrent feedback from the Lissajous plot. When training with the interference task was completed participants were retested with the 90° relative phase without the Lissajous plot feedback. In the retest of the 90° pattern, a performance loss was found in the 2-h delay group, whereas the 6-h delay group maintained the end of practice performance level. Maintenance of the same level of performance without the Lissajous plot represents memory stabilization of the initially trained 90° pattern. The findings are discussed within the context of current positions regarding procedural consolidation and the coordination dynamics framework wherein action and perception are linked through the informational nature of relative phase.

Increased risk of chronic otitis media in chronic rhinosinusitis patients: a longitudinal follow-up study using a national health screening cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) and chronic otitis media (COM) share pathophysiological mechanisms such as bacterial infection, biofilm, and persistence of the obstruction state of ventilation routes. However, only a few studies have investigated the relationship between these two diseases nationwide and in the general population. The purpose of this study was to determine whether the incidence of COM in patients with CRS differed from that of a matched control from the national health screening cohort. METHODS: Data from the Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2015. Participants who were treated ≥ ≥ ≥2 times and underwent head and neck computed tomography evaluation were selected. A 1:4 matched CRS group (n=8,057) and a control group (n=32,228) were selected. The control group included participants who were never treated with the ICD-10 code J32 from 2002 to 2015. The CRS group included CRS patients with/without nasal polyps. RESULTS: The incidence of COM was significantly higher in the CRS group than in the control group. In a subgroup analysis, the incidence of COM in all age groups and in men and women was significantly higher in the CRS group than in the control group. More, CRS increased the risk of COM. CONCLUSIONS: A significant association was observed between CRS and COM. This indicates that CRS patients have a high risk of developing COM.

Identification of inhibitors of Bcl-2 family protein-protein interaction by combining the BRET screening platform with virtual screening.

Bcl-2 family proteins play key roles in tumor initiation, progression, and resistance to therapy. Therefore, the protein-protein interactions (PPIs) between the pro-survival proteins, B-cell lymphoma (Bcl)-2 and Bcl-xL, and the pro-apoptotic proteins, Bax and Bak, could be attractive therapeutic targets for anti-cancer drug discovery. Here, we found new small molecules, BIP-A1001 and BIP-A2001 that modulated Bak/Bax and Bcl-xL interactions by combining the Nanoluc/YFP-based bioluminescence resonance energy transfer (BRET) assay with structure based virtual screening. In addition, we chose compounds with similar structures to BIP-A1001 and BIP-A2001 and tested their inhibitory effects using the BRET assay as a dose-response function. The results indicated that identifying compounds that inhibit interactions between Bak/Bax and Bcl-xL could be a promising approach to enhance cancer therapy.

Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model.

BACKGROUND: Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. RESULTS: All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17). CONCLUSION: We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.

Impact of Epidermal Growth Factor Receptor Mutation on Clinical Outcomes of Nintedanib Plus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer from the Korean Named Patient Program.

OBJECTIVES: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program. METHODS: Docetaxel was administered either 75 or 37.5 mg/m2 on D1, D8 q every 3 weeks for 4-6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity. RESULTS: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(-), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(-), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression. CONCLUSIONS: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC.

ALK-positive anaplastic large cell lymphoma with a monomorphic small-cell pattern masquerading as inflammatory gastric lesions.

INTRODUCTION: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)-pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions. CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered. DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

Design, fabrication and space suitability tests of wide field of view, ultra-compact, and high resolution telescope for space application.

We report on the design, manufacture, and testing of an ultra-compact telescope for 16 unit (16U) CubeSats for Earth and space observation. This telescope provides 1 arcsec resolution at a 2.9 degree field of view. Dimensions are optimized to 230 × 230 × 330mm3 with a mass of less than 6kg including support structure. Our catadioptric 5-element design consists of a full-aperture corrector, a Mangin primary mirror (PM), a secondary mirror (SM), and a 2-lens field corrector. The focal length is 745mm, and squared-circular aperture has an equivalent diameter of 241mm. The designed modulation transfer function (MTF) is 0.275 for the entire unit including baffles at a Nyquist frequency of 161 cycles/mm for the 450-800nm band. As one of the distinguishing features of our state-of-the-art design, all optical surfaces are spherical to simplify adjustment. For the best thermal stability, all optical elements are produced from fused silica. We describe the details of design, adjustment, and laboratory performance tests for space environments in accordance with the requirements for in-orbit operation onboard Earth-observation micro-satellites to be launched in 2018.

Magnetic resonance tumour regression grade and pathological correlates in patients with rectal cancer.

BACKGROUND: Evidence to support the specific use of magnetic resonance tumour regression grade (mrTRG) is inadequate. The aim of this study was to investigate the pathological characteristics of mrTRG after chemoradiotherapy (CRT) for rectal cancer and the implications for surgery. METHODS: Patients undergoing long-course CRT (45-50 Gy plus a booster dose of 4-6 Gy) for mid or low rectal cancer (cT3-4 or cN+ without metastasis) between 2011 and 2015 who had post-CRT rectal MRI before surgery were included retrospectively. Three board-certified experienced radiologists assessed mrTRG. mrTRG was correlated with pathological tumour regression grade (pTRG), ypT and ypN. In a subgroup of patients with mrTRG1-2 and no tumour spread (such as nodal metastasis) on MRI, the projected rate of completion total mesorectal excision (TME) if they underwent transanal excision (TAE) and had a ypT status of ypT2 or higher was estimated, and recurrence-free survival was calculated according to the operation (TME or TAE) that patients had actually received. RESULTS: Some 439 patients (290 men and 149 women of mean(s.d.) age 62·2(11·4) years) were analysed. The accuracy of mrTRG1 for predicting pTRG1 was 61 per cent (40 of 66), and that for ypT1 or less was 74 per cent (49 of 66). For mrTRG2, these values were 22·3 per cent (25 of 112) and 36·6 per cent (41 of 112) respectively. Patients with mrTRG1 and mrTRG2 without tumour spread were ypN+ in 3 per cent (1 of 29) and 16 per cent (8 of 50) respectively. Assuming mrTRG1 or mrTRG1-2 with no tumour spread on post-CRT MRI as the criteria for TAE, the projected completion TME rate was 26 per cent (11 of 43) and 41·0 per cent (41 of 100) respectively. For the 100 patients with mrTRG1-2 and no tumour spread, recurrence-free survival did not differ significantly between TME (79 patients) and TAE (21) (adjusted hazard ratio 1·86, 95 per cent c.i. 0·42 to 8·18). CONCLUSION: Patients with mrTRG1 without tumour spread may be suitable for TAE.

The Effect of Intraoperative Nefopam Administration on Acute Postoperative Pain and Chronic Discomfort After Robotic or Endoscopic Assisted Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Acute postoperative pain and chronic discomfort are reported after robotic or endoscopic thyroidectomy. The purpose of this prospective, randomized, and double-blinded clinical trial was to investigate whether intraoperative infusion of nefopam decreases acute postoperative pain and chronic discomfort following either a robotic or endoscopic thyroidectomy via the bilateral axillo-breast approach (BABA). METHODS: Patients were randomized into two groups: The control group (n = 29) or the nefopam group (n = 29). Patients in each group were infused with the same volume of saline or nefopam (0.2 mg/kg bolus, 120 µg/kg/h continuous infusion) during surgery. Acute postoperative pain, the need for rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Chronic pain and discomfort was recorded at 3 months after surgery. RESULTS: Patients in the nefopam group reported lower pain scores in the neck, as well as the axilla and anterior chest areas at 1, 6, 24, and 48 h postoperatively, when compared with the control group (P < 0.05 at each time points). Rescue analgesics were required less in the nefopam group than in the control group (1.4 [1] vs. 2.3 [1.5]; P = 0.001). The degree of chronic pain and discomfort were relatively lower in the nefopam group (P < 0.05). CONCLUSION: We report that intravenous nefopam infusion during surgery decreased acute postoperative pain and the need for rescue analgesics, as well as chronic discomfort, following BABA robotic or endoscopic thyroidectomy without adverse events.

Risk factors for Korean women to develop an isthmocele after a cesarean section.

BACKGROUND: The increase in number of cesarean section (CS) operations has resulted in an increase in cases of isthmocele development. The objective of this study is to determine the risk factors for isthmocele development after CS. METHODS: Isthmocele measurements were taken for 404 women with a history of at least one low transverse CS. The following potential risk factors were investigated: patient's age at CS, cause of CS, weeks of gestation at CS, premature rupture of membrane (PROM), phase of labor, type suture (single/double layer), operation time, uterine flexion (anteversion/retroversion), and blood transfusion during operation. A transvaginal ultrasound was carried out to examine the isthmocele in the uterus after CS, including the shape of the isthmocele, residual myometrial thickness, depth and width of isthmocele, cervical thickness, location of the isthmocele, and clinical characteristics. RESULTS: In our study population, the isthmocele had a prevalence of 73.8%. Most isthmocele had a triangular (65.4%) or semicircular shape (10.4%). The presence of an isthmocele was significantly associated with repeat CS, premature rupture of membrane (PROM), short operation time, and extent of cervix dilatation at CS. The risk of isthmocele was low in women who had placenta previa totalis (PPT), twin, a long operation time, or a transfusion during the operation. CONCLUSIONS: In our study, isthmocele development was significantly associated with repeat CS, PROM, a short operation time, and the extent of cervix dilatation at CS. Therefore, PROM prevention and a more careful uterine closure are needed to reduce the risk of developing an isthmocele after CS.

Characterization of the reference wave in a compact digital holographic camera.

A hologram is a recording of the interference between an unknown object wave and a coherent reference wave. Providing the object and reference waves are sufficiently separated in some region of space and the reference beam is known, a high-fidelity reconstruction of the object wave is possible. In traditional optical holography, high-quality reconstruction is achieved by careful reillumination of the holographic plate with the exact same reference wave that was used at the recording stage. To reconstruct high-quality digital holograms the exact parameters of the reference wave must be known mathematically. This paper discusses a technique that obtains the mathematical parameters that characterize a strongly divergent reference wave that originates from a fiber source in a new compact digital holographic camera. This is a lensless design that is similar in principle to a Fourier hologram, but because of the large numerical aperture, the usual paraxial approximations cannot be applied and the Fourier relationship is inexact. To characterize the reference wave, recordings of quasi-planar object waves are made at various angles of incidence using a Dammann grating. An optimization process is then used to find the reference wave that reconstructs a stigmatic image of the object wave regardless of the angle of incidence.

Prognostic significance of cachexia score assessed by CT in male patients with small cell lung cancer.

To determine the prognostic significance of CT-determined cachexia scores (CSs) in 127 consecutive male small cell lung cancer (SCLC) patients, cross-sectional areas of muscle and fat tissues at the third lumbar vertebra (L3) were retrospectively measured on baseline CT images. CSs were determined based on the presence of sarcopenia and/or adipopenia. According to the presence of sarcopenia (L3 muscle index <55 cm2 /m2 , 86.8%) and adipopenia (L3 fat index <22 cm2 /m2 , 11.8%), CSs were defined as follows: CS2 (sarcopenia and adipopenia, 11.8%), CS1 (sarcopenia only, 74.8%) and CS0 (13.4%). CS2 was significantly related to lower body mass index (p < .001) and poor performance status (p = .002), and patients with CS2 had shorter OS than patients with CS1 or CS0 (median OS, 5.0 months vs. 8.9 months vs. 18.3 months; p = .007). Multivariable analysis revealed that CS was an independent prognostic factor of poor survival (HR, 1.99 for CS1 and 2.59 for CS2, p = .036 and .023, CS0 as a reference), along with extensive stage (p < .001), supportive care only (p < .001) and an elevated lactate dehydrogenase (p = .005). CT-determined CSs, based on the presence of sarcopenia and/or adipopenia, could be used to predict prognosis in male SCLC.

Patterns, predictive factors and prognostic impact of multilevel metastasis in N1b papillary thyroid carcinoma.

BACKGROUND: The patterns, predictive factors and prognostic impact of multilevel metastasis in patients with N1b papillary thyroid carcinoma (PTC) were investigated. METHODS: A retrospective review of patients with N1b PTC from a tertiary referral centre in Korea who underwent unilateral modified radical neck dissection was undertaken. RESULTS: Of 658 patients, multilevel metastasis was found in 73·9 per cent; the most common type was metastasis in two levels. Tumour size per 0·1-cm increment (adjusted odds ratio (OR) 1·33, 95 per cent c.i. 1·08 to 1·64), microscopic extrathyroidal extension (adjusted OR 1·72, 1·10 to 2·71), gross extrathyroidal extension (adjusted OR 2·35, 1·24 to 4·46), unilateral central lymph node metastasis (adjusted OR 2·45, 1·53 to 3·92) and bilateral central lymph node metastasis (adjusted OR 4·06, 2·29 to 7·18) were independent predictors of multilevel metastasis. Only four-level metastasis significantly increased the risk of overall locoregional recurrence (LRR) (adjusted hazard ratio (HR) 7·41, 95 per cent c.i. 2·20 to 24·53) and lateral neck LRR (adjusted HR 7·22, 1·82 to 28·65), compared with one-level metastasis. Two subgroup analyses were conducted, showing that only three-level metastasis including metastasis in level V significantly increased the risk of overall LRR (adjusted HR 5·66, 1·20 to 26·75). In addition, having level V metastasis was an independent predictor of both overall (adjusted HR 3·26, 1·72 to 6·18; P < 0·001) and lateral neck (adjusted HR 3·28, 1·50 to 7·16; P = 0·003) LRR. CONCLUSION: Level V metastasis rather than multilevel metastasis itself is associated with an increased risk of LRR. Patients with N1b PTC and level V metastasis require risk restratification and meticulous follow-up.