Appropriateness of antibiotic use for patients with asymptomatic bacteriuria or urinary tract infection with positive urine culture: a retrospective observational multi-centre study in Korea.

BACKGROUND: Antibiotic resistance threatens public health worldwide, and inappropriate use of antibiotics is one of the main causes. AIM: To evaluate qualitative use of antibiotics in asymptomatic bacteriuria (ABU) and urinary tract infection (UTI). METHODS: Cases of positive urine culture (≥105 colony-forning units/mL) performed in inpatient, outpatient and emergency departments in April 2021 were screened in 26 hospitals in the Republic of Korea. The cases were classified as ABU, lower UTI and upper UTI. The appropriateness of antibiotic use was evaluated retrospectively by infectious disease specialists using quality indicators based on clinical guidelines for ABU and UTI. RESULTS: This study included a total of 2697 patients with ABU or UTI. The appropriateness of antibiotic use was assessed in 1157 patients with ABU, and in 677 and 863 patients with lower and upper UTI, respectively. Among the 1157 patients with ABU, 251 (22%) were prescribed antibiotics without appropriate indications. In 66 patients with ABU in which antibiotics were prescribed with appropriate indications, the duration was adequate in only 23 (34.8%) patients. The appropriateness of empirical and definite antibiotics was noted in 527 (77.8%) and 353 (68.0%) patients with lower UTI, and 745 (86.3%) and 583 (78.2%) patients with upper UTI, respectively. The duration of antibiotics was adequate in 321 (61.8%) patients with lower UTI and 576 (78.7%) patients with upper UTI. CONCLUSIONS: This nationwide qualitative assessment of antibiotic use in ABU and UTI revealed that antibiotics were often prescribed inappropriately, and the duration of antibiotics was unnecessarily prolonged.

Applicability and limitations of quality indicator-based assessment of appropriateness in antimicrobial use: a comparison with expert opinion.

BACKGROUND: The effective implementation of antimicrobial stewardship requires an a-priori assessment of the appropriateness of antimicrobial prescriptions. AIM: To evaluate the effectiveness of quality indicators (QIs) in determining the appropriateness of antimicrobial prescriptions compared to that of expert opinions. METHODS: The study assessed antimicrobial use in 20 hospitals in Korea, with infectious disease specialists rating the appropriateness based on QIs and expert opinions. The selected QIs were (1) taking two blood cultures, (2) taking cultures from suspected sites of infection, (3) prescribing empirical antimicrobials according to guidelines, and (4) changing from empirical to pathogen-directed therapy for hospitalized patients and (2, 3, and 4) for ambulatory patients. Applicability, compliance with QIs, and agreement between QIs and expert opinions were investigated. FINDINGS: Overall, 7999 therapeutic uses of antimicrobials were investigated at the study hospitals. The experts rated 20.5% (1636/7999) as inappropriate use. For hospitalized patients, antimicrobial use was assessed based on all four QIs in 28.8% (1798/6234) of the cases. For ambulatory care patients, only 7.5% (102/1351) of the antimicrobial use cases were assessed using all three QIs. The agreement between expert opinions and all four QIs for hospitalized patients was minimal (κ = 0.332), whereas that between expert opinions and all three QIs for ambulatory patients was weak (κ = 0.598). CONCLUSION: QIs have limitations in determining the appropriateness of antimicrobial use, and the degree of agreement with expert opinions was low. Therefore, these QI limitations should be considered when determining the appropriateness of antimicrobial use.

Multiple Mechanisms in Proton-Induced Nucleon Removal at ∼100 MeV/Nucleon.

We report on the first proton-induced single proton- and neutron-removal reactions from the neutron-deficient ^{14}O nucleus with large Fermi-surface asymmetry S_{n}-S_{p}=18.6 MeV at ∼100 MeV/nucleon, a widely used energy regime for rare-isotope studies. The measured inclusive cross sections and parallel momentum distributions of the ^{13}N and ^{13}O residues are compared to the state-of-the-art reaction models, with nuclear structure inputs from many-body shell-model calculations. Our results provide the first quantitative contributions of multiple reaction mechanisms including the quasifree knockout, inelastic scattering, and nucleon transfer processes. It is shown that the inelastic scattering and nucleon transfer, usually neglected at such energy regime, contribute about 50% and 30% to the loosely bound proton and deeply bound neutron removal, respectively. These multiple reaction mechanisms should be considered in analyses of inclusive one-nucleon removal cross sections measured at intermediate energies for quantitative investigation of single-particle strengths and correlations in atomic nuclei.

Deep Learning of Time-Signal Intensity Curves from Dynamic Susceptibility Contrast Imaging Enables Tissue Labeling and Prediction of Survival in Glioblastoma.

BACKGROUND AND PURPOSE: An autoencoder can learn representative time-signal intensity patterns to provide tissue heterogeneity measures using dynamic susceptibility contrast MR imaging. The aim of this study was to investigate whether such an autoencoder-based pattern analysis could provide interpretable tissue labeling and prognostic value in isocitrate dehydrogenase (IDH) wild-type glioblastoma. MATERIALS AND METHODS: Preoperative dynamic susceptibility contrast MR images were obtained from 272 patients with IDH wild-type glioblastoma (training and validation, 183 and 89 patients, respectively). The autoencoder was applied to the dynamic susceptibility contrast MR imaging time-signal intensity curves of tumor and peritumoral areas. Representative perfusion patterns were defined by voxelwise K-means clustering using autoencoder latent features. Perfusion patterns were labeled by comparing parameters with anatomic reference tissues for baseline, signal drop, and percentage recovery. In the validation set (n = 89), a survival model was created from representative patterns and clinical predictors using Cox proportional hazard regression analysis, and its performance was calculated using the Harrell C-index. RESULTS: Eighty-nine patients were enrolled. Five representative perfusion patterns were used to characterize tissues as high angiogenic tumor, low angiogenic/cellular tumor, perinecrotic lesion, infiltrated edema, and vasogenic edema. Of these, the low angiogenic/cellular tumor (hazard ratio, 2.18; P = .047) and infiltrated edema patterns (hazard ratio, 1.88; P = .009) in peritumoral areas showed significant prognostic value. The combined perfusion patterns and clinical predictors (C-index, 0.72) improved prognostication when added to clinical predictors (C-index, 0.55). CONCLUSIONS: The autoencoder perfusion pattern analysis enabled tissue characterization of peritumoral areas, providing heterogeneity and dynamic information that may provide useful prognostic information in IDH wild-type glioblastoma.

Magnetocaloric effect and Griffiths phase analysis in a nanocrystalline Ho2NiMnO6 and Ho2CoMnO6 double perovskite.

Rare-earth double perovskite oxides have intriguing magnetocaloric properties at cryogenic temperatures. In this study, Ho2NiMnO6 and Ho2CoMnO6 were synthesized using the sol-gel method, which crystallized in a monoclinic structure in the P21/n space group. The magnetic phase transition was observed at 81.2 K for Ho2NiMnO6 and 73.5 K for Ho2CoMnO6. The presence of a paramagnetic matrix and short-range ferromagnetic clusters causes magnetic disorder in these double perovskites, resulting in Griffiths phase formation. The Arrott plot confirms that compounds undergo second-order phase transition. At an applied magnetic field of 5 T, the maximum magnetic entropy change (-ΔS) for the studied compounds is 1.7 and 2.2 J kg-1 K-1, respectively. The transition metals Ni and Co in a double perovskite cause lattice distortion in the structural parameters and oxidation states of manganese (Mn3+/Mn4+), which changes the magnetic and magnetocaloric properties. The quantitative approach provides a systematic study of magnetocaloric properties of the rare earth double perovskite compounds with ferromagnetic 3d transition elements.

Detection efficiency calibration for an array of fourteen HPGe detectors.

The CUP array of germanium (CAGe) is an array of fourteen high-purity germanium (HPGe) detectors. The detection efficiency of full-energy-peak emitted from the various samples assayed on the CAGe was calculated using the Monte Carlo simulation toolkit GEANT4. If the dead layer on the surface of the crystal is treated in the simulation as a continuous part of the active crystal, then the detection efficiency will be overestimated. Thus, the detection efficiency of the CAGe was adjusted using multi-nuclide source data and Monte Carlo simulations. The gamma spectra of the known activity source were obtained for each HPGe detector of the CAGe. The detection efficiency measured by the multi-source data was smaller than that of simulation data if the simulation treated the whole volume of germanium crystals as active for gamma detection. By optimizing the dead layers' thicknesses in the simulation, the detection efficiency calculated by the simulation could be matched to that of multi-source data.

The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Stachydrine alleviates lipid-induced skeletal muscle insulin resistance via AMPK/HO-1-mediated suppression of inflammation and endoplasmic reticulum stress.

OBJECTIVE: Insulin resistance develops due to skeletal muscle inflammation and endoplasmic reticulum (ER) stress. Stachydrine (STA), extracted from Leonurus heterophyllus, has been shown to suppress proliferation and induce apoptosis in breast cancer cells and exert anti-inflammatory properties in the brain, heart, and liver. However, the roles of STA in insulin signaling in skeletal muscle remain unclear. Herein, we examined the impacts of STA on insulin signaling in skeletal muscle under hyperlipidemic conditions and its related molecular mechanisms. METHODS: Various protein expression levels were determined by Western blotting. Levels of mouse serum cytokines were measured by ELISA. RESULTS: We found that STA-ameliorated inflammation and ER stress, leading to attenuation of insulin resistance in palmitate-treated C2C12 myocytes. STA dose-dependently enhanced AMPK phosphorylation and HO-1 expression. Administration of STA attenuated not only insulin resistance but also inflammation and ER stress in the skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, STA-ameliorated glucose tolerance and insulin sensitivity, as well as serum TNFα and MCP-1, in mice fed a HFD. Small interfering (si) RNA-associated suppression of AMPK or HO-1 expression abolished the effects of STA in C2C12 myocytes. CONCLUSIONS: These results suggest that STA activates AMPK/HO-1 signaling, resulting in reduced inflammation and ER stress, thereby improving skeletal muscle insulin resistance. Using STA as a natural ingredient, this research successfully treated insulin resistance and type 2 diabetes.

Thin-Slice Pituitary MRI with Deep Learning-Based Reconstruction for Preoperative Prediction of Cavernous Sinus Invasion by Pituitary Adenoma: A Prospective Study.

BACKGROUND AND PURPOSE: Accurate radiologic prediction of cavernous sinus invasion by pituitary adenoma remains challenging. We aimed to assess whether 1-mm-slice-thickness MRI with deep learning-based reconstruction can better predict cavernous sinus invasion by pituitary adenoma preoperatively and to estimate the depth of invasion and degree of contact in relation to the carotid artery, compared with 3-mm-slice-thickness MRI. MATERIALS AND METHODS: This single-institution, prospective study included 67 consecutive patients (mean age, 53 [SD, 12] years; 28 women), between January and August 2020, who underwent a combined contrast-enhanced T1-weighted imaging protocol of 1-mm-slice-thickness MRI + deep learning-based reconstruction and 3-mm-slice-thickness MRI. An expert neuroradiologist who was blinded to the imaging protocol determined cavernous sinus invasion using the modified Knosp classification on 1-mm-slice-thickness MRI + deep learning-based reconstruction and 3-mm-slice-thickness MRI, respectively. Reference standards were established by the consensus of radiologic, intraoperative, pathologic, and laboratory findings. The primary end point was the diagnostic performance of each imaging protocol, and the secondary end points included depth of invasion and degree of contact in relation to the carotid artery. RESULTS: The diagnostic performance of 1-mm-slice-thickness MRI + deep learning-based reconstruction (area under the curve, 0.79; 95% CI, 0.69 - 0.89) in predicting cavernous sinus invasion by pituitary adenoma was higher than that of 3-mm-slice-thickness MRI (area under the curve, 0.61; 95% CI, 0.52-0.70; P < .001). One-millimeter-slice-thickness MRI + deep learning-based reconstruction demonstrated greater depth of invasion by pituitary adenomas from the medial intercarotid line than 3-mm-slice-thickness MRI (4.07 versus 3.12 mm, P < .001). A higher proportion of cases were in a greater degree of contact with the intracavernous ICA with 1-mm-slice-thickness MRI + deep learning-based reconstruction than with 3-mm-slice-thickness MRI (total encasement, 37.3% versus 13.4%, P < .001; >270°, 38.8% versus 16.4%, P < .001). CONCLUSIONS: Compared with 3-mm-slice-thickness MRI, 1-mm-slice-thickness MRI + deep learning-based reconstruction showed a higher diagnostic performance in preoperatively predicting cavernous sinus invasion by pituitary adenomas and demonstrated a greater depth and degree of contact in relation to the carotid artery.

Denosumab-induced hypocalcemia in a patient with hyperthyroidism: a case report.

Denosumab is a humanized monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab is an effective treatment for osteoporosis but can cause hypocalcemia. We present a case of denosumab-induced hypocalcemia in a patient with hyperthyroidism with a high bone turnover state. A 48-year-old postmenopausal woman was diagnosed with hyperthyroidism and osteoporosis and received antithyroid drugs (propylthiouracil 200 mg/day) and denosumab. After 2 months of taking medication, the patient complained of numbness and tingling in the hands and feet and was diagnosed with hypocalcemia (calcium, 5.8 mg/dL; ionized calcium, 0.83 mmol/L). Alfacalcidol (0.5 µg/day) and calcium carbonate (3000 mg/day) were prescribed. Subsequently, the patient's symptoms improved, and her serum calcium level normalized. The risk of denosumab-induced hypocalcemia may be increased in patients with diseases related to high bone turnover, such as hyperthyroidism; therefore, caution is needed.

Structural, magnetic, and magnetocaloric properties of R2NiMnO6 (R = Eu, Gd, Tb).

The crystal structure, cryogenic magnetic properties, and magnetocaloric performance of double perovskite Eu2NiMnO6 (ENMO), Gd2NiMnO6 (GNMO), and Tb2NiMnO6 (TNMO) ceramic powder samples synthesized by solid-state method have been investigated. X-ray diffraction structural investigation reveal that all compounds crystallize in the monoclinic structure with a P21/n space group. A ferromagnetic to paramagnetic (FM-PM) second-order phase transition occurred in ENMO, GNMO, and TNMO at 143, 130, and 112 K, respectively. Maximum magnetic entropy changes and relative cooling power with a 5 T applied magnetic field are determined to be 3.2, 3.8, 3.5 J/kgK and 150, 182, 176 J/kg for the investigated samples, respectively. The change in structural, magnetic, and magnetocaloric effect attributed to the superexchange mechanism of Ni2+-O-Mn3+ and Ni2+-O-Mn4+. The various atomic sizes of Eu, Gd, and Tb affect the ratio of Mn4+/Mn3+, which is responsible for the considerable change in properties of double perovskite.

Initial experience with a suprapubic single-port robotic right hemicolectomy in patients with colon cancer.

BACKGROUND: We developed a novel suprapubic single-port robotic right hemicolectomy (spRHC) procedure for patients with right colon cancer using a da Vinci SP Surgical System. The aim of this study was to determine the safety and feasibility of this technique. METHODS: We performed the spRHC procedure on five patients with right colon cancers between July and September 2020. All procedures including colon mobilization, D3 lymphadenectomy, and intracorporeal anastomosis were completed using the single-port robotic platform through a mini-transverse suprapubic incision and an additional assistant port. Data regarding patient characteristics, perioperative outcomes and pathologic results were analyzed. RESULTS: Four of the five patients were males. The median age was 69 years (range, 58-77 years).Two patients received preoperative chemotherapy for advanced colon cancer. The median total operative time was 160 min (range, 150-240 min). The median docking time was 4 min 40 s (range, 2 min 10 s-5 min 10 s). The median console time was 105 min (range, 100-120 min). There were no conversions to multiport or open surgeries. The median hospital stay was 7 days (range, 5-12 days). One patient experienced a wound infection. The median number of harvested lymph nodes was 41 (range, 39-50 lymph nodes). CONCLUSIONS: SpRHC is safe and feasible. However, further comparative studies are needed to assess whether this procedure can provide patients with significant benefits compared with multiport robotic surgery.

An initial experience with a novel technique of single-port robotic resection for rectal cancer.

BACKGROUND: The da Vinci single-port (SP) system is designed to facilitate single-incision robotic surgery in a narrow space. We developed a new procedure of rectal resection using this system. The aim of the present study was to evaluate the technical feasibility and safety of SP robotic rectal resection for rectal cancer patients based on our initial experience. METHODS: A study was conducted on consecutive patients with mid or low rectal cancer who had SP robotic resection at our institution between July and September 2020. The demographic characteristics, perioperative data, and pathology results of the patients were retrospectively analyzed. RESULTS: There were 5 patients (3 males, 2 females, median age 57 years (range 36-73 years). The median tumor height from the anal verge was 4 cm (range 3-5 cm). Two patients received preoperative chemoradiotherapy for advanced rectal cancer. A single docking was conducted, and the median docking time was 4 min 20 s (range 3 min 30 s to 5 min). The median total operation time was 195 min (range 155-240 min), and the median time of pelvic dissection was 45 min (range 36-62 min). All patients had circumferential and distal tumor-free resection margins. One patient experienced an anastomosis-related complication. The median duration of hospital stay was 7 days (range 7-8 days). CONCLUSIONS: Our initial experience suggests that SP robotic rectal resection is safe and feasible. Further clinical trials comparing SP and multiport robotic rectal resection should be conducted to verify the superior aspects of this new system.

Long-term clinical outcomes of total mesorectal excision and selective lateral pelvic lymph node dissection for advanced low rectal cancer: a comparative study of a robotic versus laparoscopic approach.

BACKGROUND: The long-term outcomes of minimally invasive lateral pelvic lymph node dissection (LPND) are not completely known. The aim of this study was to compare long-term outcomes between robotic and laparoscopic LPND in low rectal cancer patients with suspected lymph node metastasis in the pelvic sidewall. METHODS: We retrospectively reviewed the records of all rectal cancer patients who had laparoscopic or robotic total mesorectal excision (TME) with LPND between March 2006 and June 2016. Stage IV patients were excluded. The outcomes of patients who had laparoscopic and robotic TME with LPND were compared. RESULTS: Twenty-nine patients had laparoscopic LPND and 70 had robotic LPND. No significant differences in patient characteristics were observed between the two groups. The urinary retention rate was lower in the robotic group than in the laparoscopic group (7.1% vs. 24.1%; p = 0.043). During a median follow-up of 44.3 months, the overall recurrence rates were 48.3% and 31.4% in the laparoscopic and robotic groups, respectively (p = 0.175). The 5-year disease-free survival rates were 50.4% and 67.0% in the laparoscopic and robotic groups, respectively (p = 0.227). The 5-year overall survival rates were 65.0% and 92.2% in the laparoscopic and robotic groups, respectively (p = 0.017). CONCLUSIONS: Robotic TME with LPND is safe and feasible. In particular, it is associated with lower urinary retention. Robotic TME with LPND might yield a similar local recurrence rate and 5-year disease-free survival, but favorable long-term overall survival as compared to the laparoscopic approach. However, considering the retrospective nature and both major variables of TME and LPND involved together, this should be cautiously interpreted.

Investigation of the optimal medium and application strategy for foot-and-mouth disease vaccine antigen production.

AIMS: For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive and economically affordable for the large-scale production of FMD vaccine. METHODS AND RESULTS: Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. CONCLUSIONS: Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labour involved in spent media removal. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.

Incidence of subsequent osteoporotic fractures after distal radius fractures and mortality of the subsequent distal radius fractures: a retrospective analysis of claims data of the Korea National Health Insurance Service.

A better understanding of the features of subsequent fractures after distal radius fracture (DRF) is important for the prevention of further osteoporotic fractures. This study found that the cumulative incidence of subsequent osteoporotic fractures in South Korea increased over time and that the mortality rates of subsequent DRFs were lower than those of first-time DRFs. INTRODUCTION: We examined the incidence of osteoporotic fractures following distal radius fractures (DRFs) and the mortality rate after subsequent DRFs using claims data from the Korea National Health Insurance (KNHI) Service. METHODS: We identified records for 41,417 patients with first-time DRFs in 2012. The occurrence of osteoporotic fractures of the spine, hip, wrist, and humerus at least 6 months after the index DRF was tracked through 2016. All fractures were identified by specific diagnosis and procedure codes. One-year mortality rates and standardized mortality ratios (SMRs) for initial and subsequent DRFs were calculated for all patients. RESULTS: The 4-year cumulative incidence of all subsequent osteoporotic fractures was 14.74% (6105/41,417; 9.47% in men, 15.9% in women). The number of associated subsequent fractures was 2850 for the spine (46.68%), 2271 for the wrist (37.2%), 708 for the hip (11.6%), and 276 for the humerus (4.52%). The cumulative mortality rate 1 year after the first-time and subsequent DRF was 1.47% and 0.71%, respectively, and the overall SMR was 1.48 (95% CI: 1.37-1.61) and 0.71 (95% CI: 0.42-1.21), respectively. CONCLUSION: The cumulative incidence of osteoporotic fractures following DRFs increased over the study period and was higher among women. The cumulative mortality rates and SMRs of subsequent DRFs were lower than those of first-time DRFs at the 1-year follow-up. Given the increasing incidence rate of DRFs, the incidence of subsequent osteoporotic fractures may also increase.

A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial.

BACKGROUND: Significantly more patients with moderate-to-severe plaque psoriasis treated with the interleukin (IL)-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab in the IXORA-R head-to-head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. OBJECTIVES: To compare skin and nail clearance and patient-reported outcomes for ixekizumab vs. guselkumab, up to week 24. METHODS: IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran-Mantel-Haenszel test stratified by pooled site. Time-to-first-event comparisons were performed using Kaplan-Meier analysis, and P-values were generated using adjusted log-rank tests stratified by treatment group. Cumulative days at clinical and patient-reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). RESULTS: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference -2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. CONCLUSIONS: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate-to-severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab.

High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). OBJECTIVES: To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. RESULTS: Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. CONCLUSIONS: In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

All-cause mortality, cardiovascular mortality, and incidence of cardiovascular disease according to a screening program of cardiovascular risk in South Korea among young adults: a nationwide cohort study.

OBJECTIVES: We aimed to determine whether there are any differences in all-cause and cause-specific mortality with cardiovascular disease (CVD) risk between health screening attenders and non-attenders among young adults. STUDY DESIGN: We performed a retrospective cohort study using claim data from the Korean National Health Insurance Service database. METHODS: Individuals aged 20-39 years who had received health screening at least once between 2002 and 2005 were classified as attenders, and the others were classified as non-attenders. After propensity score matching according to attendance of health screening, 2,060,409 attenders and 2,060,409 non-attenders were included. We estimated adjusted hazard ratios (HRs) and 95% confidence interval (CI) for all-cause mortality, cause-specific mortality, and hospitalization of CVD from 2006 to 2015. RESULTS: Survival from all-cause mortality was greater among attenders than among non-attenders (log rank P < 0.001). Similarly, death from CVD (log rank P = 0.007) and CVD events (log rank P < 0.001) were less likely among attenders. The risk for all-cause mortality in attenders was significantly lower than that in non-attenders (HR = 0.83, 95% CI = 0.81 to 0.84). The risk for CVD mortality (HR = 0.80, 95% CI = 0.73 to 0.87) and hospitalization of CVD (HR = 0.92, 95% CI = 0.91 to 0.94) were lower in attenders. In stratified analyses, the risk for all-cause and cause-specific mortalities was lower among attenders regardless of insurance type. CONCLUSIONS: Among young adults, the risk for all-cause mortality, CVD mortality, and hospitalization of CVD were lower for those who underwent health screenings. Future studies that evaluate the cost-effectiveness of health screening with additional consideration of psychosocial aspects are needed.