Image findings of anti-neutrophil cytoplasmic antibody-associated vasculitis involving the skull base.

AIM: To investigate computed tomography (CT) and magnetic resonance imaging (MRI) features of skull bases involving anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). MATERIALS AND METHODS: A retrospective review was undertaken to identify an institutional historical cohort of 17 patients with confirmed AAV who underwent CT or MRI and had skull base involvement between 2002 and 2021. Two radiologists reviewed the extent and features of the lesions, bone changes, and other MRI findings. RESULTS: A total of 17 patients (12 men; mean age ± standard deviation, 46.5 ± 17.1 years) were selected. AAV presented as infiltrative lesions with involvement at various sites. Most cases involved the paranasal sinuses (PNS; 88%, 15/17), nasopharynx (88%, 15/17), pterygopalatine fossa (82%, 14/17), and parapharyngeal space (82%, 14/17), frequently accompanied by mucosal irregularity of the PNS and nasopharynx (71%, 12/17). Central skull base and temporal bone involvement were seen in 53% (9/17) and 38% (6/16) of cases, respectively. On T1-weighted imaging (WI) and T2WI MRI, all lesions (15/15) showed predominant signal iso-intensity to grey matter. CONCLUSIONS: Although radiological findings of AAV are non-specific and skull base involvement is less common, AAV may be considered if infiltrative lesions predominantly involving the PNS, nasopharynx, pterygopalatine fossa, and parapharyngeal space with combined bone changes of skull base are seen.

Effect of doping and loading Parameters on photocatalytic degradation of brilliant green using Sn doped ZnO loaded CSAC.

Sn doped ZnO loaded cotton stalk activated carbon (Sn-ZnO/CSAC) was prepared by chemical precipitation method, and the products were characterized. The XRD resultants confirm that the presence of hexagonal wurtzite phase of the bare ZnO. Furthermore, particular particle size gradually decreases (21.49 nm) due to doping and loading. UV-Vis absorption intensity of doped/loaded sample was red-shifted and then PL intensity is reduced. The photocatalytic performances of bare, Sn-doped ZnO and Sn-ZnO/CSAC was estimated by photodegradation of brilliant green (BG) under sunlight. The photodegradation of BG dye in 120 min over Sn-doped ZnO/CSAC is nearly 96.52%, which is considerably improved than bare ZnO (72.60%), respectively.

Vaginal compared with intramuscular progestogen for preventing preterm birth in high-risk pregnant women (VICTORIA study): a multicentre, open-label randomised trial and meta-analysis.

OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

[Ultrasound-guided peripheral venous puncture in patients with a poor venous status]. / Die ultraschallgesteuerte periphere Venenpunktion bei schlechtem Venenstatus.

BACKGROUND: In the case of a poor peripheral venous status the use of conventional approaches is associated with several failed attempts, delay of treatment, increased pain and escalation to more invasive techniques. Ultrasound-guided venous access has become increasingly popular for difficult venous access; however, in German-speaking countries it has not yet become as popular as in English-speaking countries. First attempt success rates are high, but the factors contributing to the time needed for ultrasound-guided venous access are not well investigated. It is hypothesized that body mass index (BMI), vein diameter and depth contribute to the time needed for successfully establishing a peripheral vein access in patients with a difficult venous status. METHODS: This study included 68 patients with a poor venous status. After written consent was obtained patient characteristics were documented and upper extremity veins eligible for access were scanned with ultrasound with the aim of performing an ultrasound-guided venous access. The following time periods were documented: 1) first skin contact with the ultrasound probe, 2) time to identify an accessible vein, 3) time for venous access. RESULTS: Of the patients 67 were successfully punctured by ultrasound-guided venous access, 65 at the first attempt and 2 at the second attempt. In one patient conventional venous access was obtained at the same time. A higher BMI was associated with a significantly shorter total puncture time (+1 BMI point ≙ -2.25 s) and a shorter vein identification time (+1 BMI point ≙ -1.82 s). A greater vein diameter correlated with a shorter total time (-14.23 s/mm) and a greater depth correlated with an increased total time (+1.65 s/mm). CONCLUSION: A greater vein diameter and a higher BMI contribute to a shorter time period for ultrasound-guided venous access. Obese patients with difficult venous access may benefit from ultrasound-guided venous access, which could be explained by the imaging contrast with a higher proportion of subcutaneous fatty tissue.

Patterns of prescription opioid use before total hip and knee replacement among US Medicare enrollees.

OBJECTIVE: To examine patterns of prescription opioid use before total joint replacement (TJR) and factors associated with continuous use of opioids before TJR. DESIGN: We conducted an observational cohort study among Medicare enrollees aged ≥65 years who underwent TJR between 2010 and 2014. Preoperative opioid use was defined as having any opioid prescription in the 12-month period before TJR. Patients who had an opioid prescription every month for a 12-month period were defined as continuous users. We examined patients' demographics, pain-related conditions, medication use, other comorbidities, healthcare utilization and their association with use of opioids before TJR. RESULTS: A total of 473,781 patients underwent TJR:,155,516 THR and 318,265 TKR. Among the total cohort, 60.2% patients had any use of opioids and of those, 12.4% used opioids at least once a month continuously over the 12-month baseline period. Correlates of continuous opioid use included African American race (OR = 2.14, 95% confidence intervals (CI) = 2.01-2.28, compared to White patients), history of drug abuse (OR = 5.18, 95% CI = 3.95-6.79) and back pain (OR = 2.32, 95% CI = 2.24-2.39). CONCLUSIONS: In this large cohort of patients undergoing TJR, over 60% ever used opioids and 12.4% of them continuously used opioids in the 12-month prior to surgery. Utilization of opioids became more frequent and high-dosed near the surgery. History of drug abuse, back pain, and African American race were strongly associated with continuous use of opioids preoperatively. Further research is needed to determine short-term and long-term risks of preoperative use of opioids in TJR patients and to optimize pre- and post-TJR pain management of patients with arthritis.

Management of isolated recurrence after surgery for pancreatic adenocarcinoma.

BACKGROUND: Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well established. METHODS: Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large-volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities. RESULTS: Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non-surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection. CONCLUSION: Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.

Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an international consensus on the diagnosis of EBA essential. OBJECTIVES: To obtain an international consensus on the clinical and diagnostic criteria for EBA. METHODS: The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re-voting carried out. RESULTS: In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed. CONCLUSIONS: This first international consensus conference established generally agreed-upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.

Trends in use of hydroxychloroquine during pregnancy in systemic lupus erythematosus patients from 2001 to 2015.

BACKGROUND: Evidence suggests that continuing hydroxychloroquine (HCQ) during pregnancy in women with systemic lupus erythematosus (SLE) improves outcomes. We sought to describe time trends in the continuation, initiation, and duration of HCQ in a large population-based cohort of pregnant SLE women. METHODS: A cohort of pregnant women with SLE enrolled continuously in public (Medicaid, 2001-2010) or private (Optum Clinformatics, 2003-2015) health insurance between three months prior to conception and one month after delivery was identified. We assessed the proportion of women initiating or continuing HCQ and the duration of therapy during each calendar year in the study. RESULTS: A total of 5300 women with SLE were included. Of these, 852 (16.1%) were on HCQ treatment in the three-month period prior to their pregnancy. During pregnancy, the overall proportion of women with SLE taking HCQ increased from 12.4% in 2001 to 37.7% in 2015. Initiation of HCQ therapy during pregnancy increased from 2.7% in 2001 to 7.5% in 2010 ( p = 0.0002) (Medicaid) and from 4.9% in 2003 to 13.6% in 2015 ( p = 0.0001) (Clinformatics). Continuation of HCQ during pregnancy did not change significantly over time in either data set. The average cumulative day-supply of HCQ prescriptions during pregnancy increased from 37 days in 2001 to 77 days in 2010 ( p = 0.05) among HCQ initiators and from 79 days in 2001 to 125 days in 2010 ( p = 0.0009) among HCQ continuers in Medicaid. Among privately insured women, the average cumulative day-supply of HCQ prescriptions among HCQ continuers increased from 84 in 2004 to 163 in 2015 ( p = 0.0006) but did not change significantly among HCQ initiators. CONCLUSION: The proportion of women initiating HCQ during pregnancy and the average cumulative day-supply of HCQ increased from 2001 to 2015. While these findings are encouraging, overall HCQ use during pregnancy remains low.

Belatacept-Resistant Rejection Is Associated With CD28+ Memory CD8 T Cells.

Recently, newer therapies have been designed to more specifically target rejection in an effort to improve efficacy and limit unwanted toxicity. Belatacept, a CD28-CD80/86 specific reagent, is associated with superior patient survival and graft function compared with traditional therapy, but its adoption as a mainstay immunosuppressive therapy has been tempered by increased rejection rates. It is essential that the underlying mechanisms associated with this rejection be elucidated before belatacept is more widely used. To that end, we designed a study in a nonhuman primate kidney transplant model where animals were treated with either a belatacept- or a tacrolimus-based immunosuppressive regimen. Interestingly, we found that elevated pretransplant frequencies of CD28+ CD8+ TEMRA cells are associated with rejection on belatacept but not tacrolimus treatment. Further analysis showed that the CD28+ CD8+ TEMRA cells rapidly lose CD28 expression after transplant in those animals that go on to reject with the allograft infiltrate being predominantly CD28- . These data suggest that CD28+ memory T cells may be resistant to belatacept, capable of further differentiation including loss of CD28 expression while maintaining effector function. The unique signaling requirements of CD28+ memory T cells provide opportunities for the development of targeted therapies, which may synergize with belatacept to prevent costimulation-independent rejection.

Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection.

The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004). The anti-CD154 dAb effectively blocked CD40-CD154 interactions but lacked crystallizable fragment (Fc) binding activity and resultant platelet activation. In a nonhuman primate kidney transplant model, anti-CD154 dAb was safe and efficacious, significantly prolonging allograft survival without evidence of thromboembolism (Median survival time 103 days). The combination of anti-CD154 dAb and conventional immunosuppression synergized to effectively control allograft rejection (Median survival time 397 days). Furthermore, anti-CD154 dAb treatment increased the frequency of CD4+ CD25+ Foxp3+ regulatory T cells. This study demonstrates that the use of a novel anti-CD154 dAb that lacks Fc binding activity is safe without evidence of thromboembolism and is equally as potent as previous anti-CD154 agents at prolonging renal allograft survival in a nonhuman primate preclinical model.

Patterns and predictors of persistent opioid use following hip or knee arthroplasty.

OBJECTIVE: The relationship between arthroplasty and long-term opioid use in patients with knee or hip osteoarthritis is not well studied. We examined the prevalence, patterns and predictors of persistent opioid use after hip or knee arthroplasty. METHOD: Using claims data (2004-2013) from a US commercial health plan, we identified adults who underwent hip or knee arthroplasty and filled ≥1 opioid prescription within 30 days after the surgery. We defined persistent opioid users as patients who filled ≥1 opioid prescription every month during the 1-year postoperative period based on group-based trajectory models. Multivariable logistic regression was used to determine preoperative predictors of persistent opioid use after surgery. RESULTS: We identified 57,545 patients who underwent hip or knee arthroplasty. The mean ± SD age was 61.5 ± 7.8 years and 87.1% had any opioid use preoperatively. Overall, 7.6% persistently used opioids after the surgery. Among patients who used opioids in 80% of the time for ≥4 months preoperatively (n = 3023), 72.1% became persistent users. In multivariable analysis, knee arthroplasty vs hip, a longer hospitalization stay, discharge to a rehabilitation facility, preoperative opioid use (e.g., a longer duration and greater dosage and frequency), a higher comorbidity score, back pain, rheumatoid arthritis, fibromyalgia, migraine and smoking, and benzodiazepine use at baseline were strong predictors for persistent opioid use (C-statistic = 0.917). CONCLUSION: Over 7% of patients persistently used opioids in the year after hip or knee arthroplasty. Given the adverse health effects of persistent opioid use, strategies need to be developed to prevent persistent opioid use after this common surgery.

Identification of phenotypic clusters of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease.

BACKGROUND: Clinical presentation of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease (NERD) is found to be heterogeneous. This study classified phenotypic clusters to determine NERD subtypes. METHODS: We performed two-step cluster analysis using urticaria, chronic rhinosinusitis (CRS), and atopy, in a NERD cohort comprising 302 patients. Asthma exacerbation was defined as receiving at least one burst of intravenous steroid treatment and/or at least two bursts of oral steroid use (≥ 45 mg/3 days) per year. The possession rate of anti-asthmatic medications was estimated during the follow-up period. RESULTS: There were four subtypes: subtype 1 (NERD with CRS/atopy and no urticaria), subtype 2 (NERD with CRS and no urticaria/atopy), subtype 3 (NERD without CRS/urticaria), and subtype 4 (NERD with urticaria). Significant differences were found between the four subtypes in the female proportion, baseline FEV1%, serum total IgE level, and sputum/peripheral eosinophil count. A higher frequency of asthma exacerbations was noted in subtype 1 compared to subtype 3. The possession rates of medium- to high-dose inhaled corticosteroids/long-acting beta2 -agonists showed significant differences among the four subtypes. Metabolomic analysis showed that the four subtypes of NERD had a higher serum leukotriene E4 (LTE4) level than those with aspirin-tolerant asthma. The patients with subtypes 1 and 3 had a higher urine LTE4 level than those with subtype 2. CONCLUSION: We found four distinct subtypes with different clinical/biochemical findings and asthma exacerbations in a NERD cohort. These findings suggest that stratified strategies by applying subtype classification may help achieve better outcomes in the management of NERD.

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving hydroxychloroquine alone.

Prognostic clinical factors associated with remission and relapse in bullous pemphigoid.

BACKGROUND: Prognostic factors for remission and relapse of bullous pemphigoid (BP) remain uncertain. OBJECTIVE: To evaluate clinical factors associated with remission and relapse in Korean patients with BP. METHODS: A retrospective analysis was conducted of 174 patients diagnosed with BP between 1993 and 2014 at Gangnam Severance Hospital in Seoul, Korea. RESULTS: Of the 174 identified patients, 131 (75.29%) achieved remission after a mean treatment duration of 393.69 days. Prognostic factors for remission were older age (≥70 years) and the absence of an admission history. Of 131 patients who achieved remission, 40 patients (30.53%) experienced relapse after a mean duration of 335.65 days. However, no statistically significant factors were predictive of relapse by multivariate analysis. CONCLUSIONS: This study suggests BP patients who are older and have no admission history tend to achieve remission.

Optimization of a nanotip on a surface for the ultrafast probing of propagating surface plasmons.

We theoretically analyze a method for characterizing propagating surface plasmon polaritons (SPPs) on a thin gold film. The SPPs are excited by few-cycle near-infrared pulses using Kretschmann coupling, and a nanotip is used as a local field sensor. This geometry removes the influence of the incident excitation laser from the near fields, and enhances the plasmon electric field strength. Using finite-difference-time-domain studies we show that the geometry can be used to measure SPP waveforms as a function of propagation distance. The effects of the nanotip shape and material on the field enhancement and plasmonic response are discussed.

Comparative cardiovascular safety of glucagon-like peptide-1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study.

AIMS: To evaluate the comparative cardiovascular disease (CVD) safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM). METHODS: Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score-matched cohorts of patients with T2DM aged ≥18 years treated with metformin who initiated a GLP-1 RA or a comparator, i.e. DPP-4 inhibitor (n = 35 534), second-generation sulphonylureas (n = 28 138) or insulin (n = 47 068), between 2005 and 2013. We examined the association between drug initiation and a composite CVD endpoint, comprising hospitalizations for acute myocardial infarction, unstable angina, stroke or coronary revascularization. RESULTS: During the course of 1 year, there were 13.9 and 13.7 CVD events per 1000 person-years among propensity-score-matched initiators of GLP-1 RAs versus DPP-4 inhibitors [hazard ratio (HR) 1.02; 95% confidence interval (CI) 0.84-1.24]; and 12.1 versus 14.0 events among initiators of GLP-1 RAs versus sulphonylureas (HR 0.86; 95% CI 0.69-1.08). The effect estimates for GLP-1 RAs versus insulin were sensitive to the adjustment for glycated haemoglobin, after which the HR was 1.01 (95% CI 0.73-1.41). Results were robust across several sensitivity analyses, including an as-treated analysis considering up to 8.7 years of follow-up. CONCLUSIONS: This large study, performing head-to-head comparisons of GLP-1 RAs with other antidiabetic agents in real-world patients, provides estimates of relative safety precise enough to exclude large differences in CVD risk and adds further understanding to results from recent clinical trials.

Comparison of mechanical artificial shrinkage methods in mouse blastocyst vitrification.

PURPOSE OF INVESTIGATION: This study was designed to determine which mechanical artificial shrinkage (AS) method, conducted by puncture, pipetting, or aspiration, was effective in increasing the re-expansion rate of mouse blastocysts. MATERIALS AND METHODS: In each group, 30 mouse blastocysts were used. Before vitrification, the blastocoelic cavity was collapsed by puncture with a micro-needle, pipetting with a micro-glass pipette, and direct aspiration with an ICSI pipette. After thawing, the re-expansion rate of blastocysts was examined for each AS method. Re-expansion rate was checked at three, five, and seven hours after thawing. RESULTS: The number of re-expanded mouse blastocysts at five hours after thawing was 12 in the puncture with a micro-needle group, 11 in the pipetting with a micro-glass pipette group, and 24 in the direct aspiration with an ICSI pipette group. The cumulative number of re-expanded mouse blastocysts at seven hours after thawing was 20 in the puncture with a micro-needle group, 20 in the pipetting with a micro-glass pipette group, and 28 in the direct aspiration with an ICSI pipette group. There were statistically significant differences in the cumulative number of re-expanded mouse blastocysts between five and seven hours after thawing (p = 0.001 and 0.021, respectively). CONCLUSIONS: Direct aspiration with an ICSI pipette resulted in a higher re-expansion rate than the puncture and pipetting methods. It can be considered that the direct aspiration method is more convenient and simpler than the other two methods.