Early Flare Research Articles

Comparison of treatment outcomes between slow coagulation transscleral cyclophotocoagulation and micropulse transscleral laser treatment

This study compared treatment outcomes of slow coagulation transscleral cyclophotocoagulation (SC-CPC, 65 eyes) and micropulse transscleral laser treatment (MPL, 134 eyes) in patients with medically uncontrolled glaucoma. Success was defined as achieving an intraocular pressure (IOP) of 6–21 mmHg with a ≥ 20% reduction from baseline, no reoperation for glaucoma, and no loss of light-perception vision. Visual acuity, number of glaucoma medication, corneal endothelial cell count, aqueous flare values, and complications were analyzed. At 12 months, mean IOP decreased from 32.2 ± 13.4 to 17.9 ± 8.3 mmHg in the SC-CPC group and from 26.4 ± 10.8 to 16.5 ± 6.8 mmHg in the MPL group. No significant changes were observed in visual acuity, medication count, or corneal endothelial cell count. Aqueous flare values increased immediately after the procedure and gradually decreased in both groups, with greater changes at 1 week significantly associated with greater IOP reduction (p < 0.05). Pupillary abnormalities were found in 5 eyes (4.5%) of the MPL group, with no severe complications. The 12-month success rates were 50.1% for SC-CPC and 38.2% for MPL (p = 0.131). Both SC-CPC and MPL effectively controlled IOP, with early postoperative aqueous flare values predicting treatment outcomes.

Digital biomarkers for psoriatic arthritis: a qualitative focus group study on patient-perceived opportunities and barriers

ObjectivesThe widespread adoption of wearables, for example, smartphones and smartwatches in the daily lives of the general population, allows passive monitoring of physiological and behavioural data in the real world....

COVID-19 Vaccination and Gout Flare Risk in Patients With Infrequent or Frequent Flares: A Prospective Cohort Study.

To assess post-COVID-19 vaccination gout flare risk with differing baseline flare burden. We prospectively studied gout patients with infrequent or frequent flares, defined as ≤1 flare/year or ≥2 flares/year, respectively. COVID-19 vaccine-naive patients managed with urate-lowering therapy between February and June 2021 were included and voluntarily decided on vaccination. Participants were followed for 12 weeks after enrollment or first vaccine dose. Gout flares and risk factors were compared between groups. Of 530 participants, 308 (58.1%) had infrequent flares and 222 (41.9%) had frequent flares at baseline, with 248 (142 infrequent and 106 frequent) receiving two-dose COVID-19 vaccination. Vaccination increased cumulative flare incidence at 12 weeks in the infrequent but not the frequent flare group (26.1% vs 10.8%, P = 0.001, compared with 60.4% vs 65.5%, P = 0.428). Flare incidence in the final 4 weeks of observation decreased significantly only in the vaccinated infrequent flare group (4.3% vs 12.0%, P = 0.017). Multivariable analyses showed that vaccination (odds ratio [OR] 2.82, 95% confidence interval [95% CI] 1.50-5.30, P = 0.001), flare in the preceding year (OR 1.95, 95% CI 1.03-3.71, P = 0.04), and body mass index (OR 1.09, 95% CI 1.01-1.19, P = 0.03) were independently associated with increased flare risk in the infrequent flare group. Baseline serum urate (mg/dl) was an independent risk factor in the frequent flare group (OR 1.23, 95% CI 1.05-1.45, P = 0.012). COVID-19 vaccination was associated with increased early gout flares only in patients with previously infrequent flares.

Relationship of peak fluxes of solar radio bursts and X-ray class of solar flares: Application to early great solar flares

Abstract Large solar flares occasionally trigger significant space-weather disturbances that affect the technological infrastructures of modern civilization, and therefore require further investigation. Although these solar flares have been monitored by satellite observations since the 1970s, large solar flares occur only infrequently and restrict systematic statistical research owing to data limitations. However, Toyokawa Observatory has operated solar radio observations at low frequencies (at 3.75 and 9.4 GHz) since 1951 and captured the early great flares as solar radio bursts. To estimate the magnitudes of flares that occurred before the start of solar X-ray (SXR) observations with the Geostationary Operational Environmental Satellite (GOES) satellites, we show the relationship between microwave fluxes at 3.75 and 9.4 GHz and X-ray fluxes of flares that occurred after 1988. In total, we explored 341 solar flares observed with the Nobeyama Radio Polarimeters and Toyokawa Observatory from 1988–2014 and compared them with the SXR observations recorded by the GOES satellites. The correlation coefficient was approximately 0.7. Therefore, the GOES X-ray class can be estimated from the peak flux at 3.75 and 9.4 GHz with a large variance and an error of factor of 3 (1σ). Thus, for the first time, we quantitatively estimated the light curves of two early solar flares observed in 1956 February by the Toyokawa solar radio observations using the relationship between SXR thermal radiation and microwave nonthermal radiation (Neupert, 1968, ApJ, 153, 59).

Effect of Top Sheet Materials on Joint Performance of Self-Piercing Riveting

Three types of self-piercing riveting (SPR) joints, i.e., steel/aluminum, carbon fiber reinforced polymer (CFRP)/ aluminum, and aluminum/aluminum, were constructed using three different top sheet materials with the same aluminum alloy as the bottom sheet. The effects of the top sheet material on the joint quality and mechanical behavior were evaluated. The top sheet materials’ characteristics dominate the rivet piercing process and the consequent interlock distance. The high-strength steel top sheet requires a comparatively higher rivet setting force and induces early flaring of the rivet tail, resulting in a larger interlock distance. Though the CFRP needs the highest rivet setting force to penetrate the rivet through the CFRP fibers, the CFRP/aluminum joint exhibits the smallest interlock distance because of the SPR process-induced damages to the CFRP and subsequently less flaring of the rivet tail. In strength tests, the damaged CFRP sheet resulted in rivet head pullout of the CFRP/aluminum joints, which exhibited the lowest lap-shear and cross-tension strengths. In contrast, the steel/aluminum joints demonstrated the highest strengths because of their comparatively larger interlock distances. In addition to the experimental analysis, simulations revealed the rivet penetration and flaring mechanisms with various top sheet materials, and their respective joint quality and strengths.

Photometric and Spectroscopic Observations of GRB 210104A: Bright Reverse-shock Emission and Dense Circumburst Environment

Early afterglow observations of gamma-ray bursts (GRBs) are valuable for exploring the properties of their jets and ambient medium. We report our photometric and spectroscopic observations of GRB 210104A and discuss its jet properties with multiwavelength data. Our spectroscopic observation reveals several absorption features and a tentative redshift of 0.46 is identified. A bright optical flare that has a peak brightness of R = 13 mag at 112 ± 7 s was observed in the R band during 67 ∼ 165 s post the GRB trigger. The flux of the R-band afterglow decays with a slope of α O = − 0.91 ± 0.03 at t > 650 s. The early X-ray afterglow lightcurve is a smooth bump, and it decays with a slope of α X = −1.18 ± 0.01 at late epoch. Our joint spectral fit to the optical-X-ray afterglows during (1.1–1.3) × 104 s yields a photon index ΓO,X = −1.82 ± 0.04. The derived host galaxy extinction is A R = 0.87. Attributing the early optical flare to the reverse-shock (RS) emission and the late optical-X-ray emission to the forward shock emission, the optical and X-ray lightcurves at t < 3 × 104 s can be well fit adopting a Markov Chain Monte Carlo algorithm. Comparing the properties of GRB 210104A with other GRBs that have detection of bright RS emission, we show that its jet is mildly magnetized (R B = 28), with high radiation efficiency (77%), is subenergetic (E k,iso = 4.5 × 1051 erg), and moderately relativistic (Γ0 ∼ 35) in a density medium (n 0 ∼ 417 cm−3). It follows the tight L γ,iso–E p,z–Γ0 relation as with typical GRBs.

The Role of Off-Therapy Viral Kinetics in the Timing and Severity of Flares in Hepatitis B e Antigen–Negative Patients

Hepatitis B flare occurs earlier and is more severe in patients stopping tenofovir (TDF) compared with entecavir (ETV). This study investigated relationship between hepatitis B virus (HBV) kinetics, onset timing, and the severity of flares. Hepatitis B e antigen-negative chronic hepatitis B patients who developed off-ETV or off-TDF hepatitis flare were recruited. Their HBV kinetics and the severity of flares were compared between patients with early (<6 months) and late (between 6 and 24 months) flares. Propensity score matching was performed at 1:1 adjusting for age, sex, cirrhosis, and end-of-treatment (EOT) hepatitis B surface antigen between off-ETV and off-TDF flares. After propensity score matching, 76% and 15% of each 107 off-TDF and off-ETV patients, respectively, developed early flare. A much steeper HBV DNA upsurge (ΔHBV DNA/month) was observed in off-TDF than off-ETV flares (2.12 vs 0.73 log10 IU/mL; P < .01). Greater ΔHBV DNA/month correlated with earlier timing and higher peak alanine aminotransferase levels of flares. ΔHBV DNA/month ≥2.5 log10 IU/mL was an independent factor for severe off-TDF flare, and ≥1 log10 IU/mL was a predictor for severe off-ETV flares. Greater HBV DNA upsurge rate (ΔHBV DNA/month) ≥1 log10 IU/mL is a key factor for an earlier onset and more severe flare. More frequent ΔHBV DNA/month ≥1 log10 IU/mL in off-TDF than off-ETV flares may explain why off-TDF flare mostly occurred early and was more severe. More stringent monitoring in those with ΔHBV DNA/month ≥1 log10 IU/mL at flare, especially ≥2.5 log10 IU/mL in early off-TDF flares, is important for timely retreatment to prevent decompensation.

Predictors of Early Response, Flares, and Long-Term Adverse Renal Outcomes in Proliferative Lupus Nephritis: A 100-Month Median Follow-Up of an Inception Cohort.

Objective: To define predictors of response, time to response, flares, and long-term renal outcome in an inception cohort of proliferative lupus nephritis (PLN). Methods: We included 100 patients (80% female; mean age 31 ± 13 years) with biopsy-proven PLN (III, IV, III/IV + V). Clinical, laboratory, histological and therapeutical parameters were recorded at baseline, 6, 9, 12, 18, 24, 36, 72 months, time of flare, and last follow-up visit. Logistic and Cox-regression models were applied. Results: After induction treatment (69% received cyclophosphamide (CYC) and 27% mycophenolic acid (MPA)), partial (PR) or complete (CR) response was achieved in 59% (26% CR, 33% PR) and 67% (43% CR, 24% PR) of patients at 3 and 6 months, respectively; median time to PR was 3 months (IQR 5) and median time to CR was 6 months (IQR 9). Baseline proteinuria <1.5 g/day correlated with a shorter time to CR (HR 1.77) and with CR at 3, 6, and 9 months (OR 9.4, OR 5.3 and OR 3.7, respectively). During 100-month median follow-up, 33% of patients had ≥1 renal flares (median time: 38 months). Proteinuria >0.8 g/day at 12 months was associated with a higher risk of flares (OR 4.12), while MPA and mixed classes with lower risk (OR 0.14 and OR 0.13, respectively). Baseline proteinuria >2 g/day and 12-month proteinuria >0.8 g/day correlated with a shorter time to flare (HR 2.56 and HR 2.57, respectively). At the end of follow-up, 10% developed stage 3–4 chronic kidney disease (CKD), and 12% end-stage renal disease (ESRD). Twelve-month proteinuria >0.8 g/day (OR 10.8) and interstitial fibrosis/tubular atrophy >25% (OR 7.7) predicted CKD or ESRD at last visit. Conclusions: Baseline proteinuria <1.5 g/day predicted time to CR. Twelve-month proteinuria >0.8 g/day correlated with flares (ever) and time to flare and, along with baseline interstitial fibrosis/tubular atrophy >25%, predicted CKD or ESRD at the last visit.

On the Nature of the Photospheric Horizontal Magnetic Field Increase in Major Solar Flares

The rapid increase of the horizontal magnetic field (B h ) around the flaring polarity inversion line is the most prominent photospheric field change during flares. It is considered to be caused by the contraction of flare loops, the details behind which is still not fully understood. Here we investigate the B h increase in 35 major flares using HMI high-cadence vector magnetograms. We find that the B h increase is always accompanied by the increase of field inclination. It usually initiates near the flare ribbons, showing a step-like change in between the ribbons. In particular, its evolution in the early flare phase shows a close spatiotemporal correlation to flare ribbons. We further find that the B h increase tends to have similar intensity in confined and eruptive flares but a larger spatial extent in eruptive flares in a statistical sense. Its intensity and timescale have inverse and positive correlations to the initial ribbon separations, respectively. The results altogether are well consistent with a recent proposed scenario that suggests that the reconnection-driven contraction of flare loops enhances the photospheric B h according to the ideal induction equation, providing statistical evidence of the reconnection-driven origin for the B h increase for the first time.

Statistical Properties of X-ray Flares in Gamma-ray Bursts

X-ray flares are frequently detected in the X-ray afterglow light curves and are highly correlated with the prompt emission of gamma-ray bursts (GRBs). We compile a comprehensive sample of X-ray flares up to 2021 April, comprising 697 flares. We classify the total sample into four types: early flares (tp≤103 s), late flares (tp&gt;103 s), long gamma-ray burst (LGRB) flares and short gamma-ray burst (SGRB) flares, and analyze the distributions and relationships of the flare parameters. It is found that the early flares have a higher frequency, shorter duration, and more asymmetrical structure. In addition, the distributions of the morphological parameters of the SGRB flares are similar to those of the LGRB flares. We also find that the durations and rising (decay) times of the early flares are positively correlated with the peak times, but the late flares follow the different dependent relations. There is a strong anti-correlation between the peak luminosities (LX,P) and the peak times of the flares, e.g., LX,p∝tp,z−1.45 for the LGRB flares, and LX,p∝tp,z−1.27 for the SGRB flares, respectively. Furthermore, the peak luminosity is highly dependent on the isotropic energy (EX,iso) for the early LGRB flares, the best fit is LX,p∝EX,iso1.06(r=0.89). We also find a tight three-parameter correlation, LX,p∝tp,z−1.03EX,iso0.92(r=0.96). All the late flares fall into the 3σ confidence region defined by the early flares. In terms of the point of kinematic arguments, both the SGRB and LGRB flares support a common scheme of internal origin. The SGRB flares have similar properties to the LGRB flares, suggesting that both of them share a similar physical mechanism from the late-time activity of central engine.

18F]Fluorothymidine(FLT)-PET imaging of thymidine kinase 1 pharmacodynamics in non-small cell lung cancer treated with pemetrexed.

3070 Background: Imaging of tumor proliferation has been studied with FLT-PET in various tumor types including NSCLC. Pemetrexed inhibits thymidylate synthase(TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). TS inhibition upregulates the thymidine salvage pathway including relocalisation of ENT1 to membrane and TK1 activation as a transient “flare” response. We hypothesise that this can be detected as an increase in FLT tumoral uptake that subsequently decreases with reduced proliferation. This study was conducted to assess FLT uptake as an early pharmacodynamics(PD) marker of pemetrexed response. Methods: This was an open-label imaging study in 21 patients with Stage 3/4 NSCLC treated with pemetrexed and platinum-based chemotherapy. Patients underwent FLT PET/CT scan at baseline and 4h after administration of pemetrexed. Platinum component of treatment was administered on the day after second FLT scan for cycle 1. Plasma for TK1 activity expression were collected before each scan time point and analysed by ELISA. Percentage change in standardized uptake value (%ΔSUV) was calculated as [SUV(PET2) – SUV(PET1)]/ SUV(PET1)*100. Treatment response calculated by RECIST 1. 1 and survival data were collected. Results: 17 patients had evaluable PET/CT scans for pemetrexed response. Median percentage difference for SUVmean and SUVmax in tumour lesions increased by 3% and 10.3% respectively. 5 patients showed homogeneous FLT flare at 4h after pemetrexed, 2 patients had decrease, 10 patients had heterogeneous FLT response (regardless of platinum doublet). There was no significant correlation between plasma TK1 activity and FLT flare. At 9 weeks, 4 patients had partial response, 9 stable disease and 4 progressive disease. Baseline and weighted average ΔSUVmax were not associated with survival. The 5 patients with FLT flare in all lesions showed a median OS of 31 months, unlike the group with heterogenous or decrease uptake(15 months). FLT uptake in bone marrow and small bowel significantly increased at 4h (t test p = 0.004, p = 0.004, respectively) indicating increased thymidine salvage activity. Early FLT uptake was not predictive for tumour RECIST response or OS. In multivariable cox regression analysis, pre-treatment TK1 activity, adjusted for performance status, smoking history and age, independently affected survival in this group (p = 0.011). Conclusions: Early FLT flare at 4h was seen in NSCLC post pemetrexed administration indicating activation of thymidine salvage pathway. Median overall survival of patients with an FLT flare response was more than twice longer than patients with mixed or no response. However, the small sample size lacked power to show statistical significance in the OS comparison. Further studies should evaluate this and the relationship to other prognostic variables in a larger cohort of patients. Clinical trial information: NCRI UK badge 9249.

The Nascent Milliquasar VT J154843.06+220812.6: Tidal Disruption Event or Extreme Accretion State Change?

We present a detailed multiwavelength follow-up of the nuclear radio flare VT J154843.06+220812.6, hereafter VT J1548. VT J1548 was selected as a ∼1 mJy radio flare in 3 GHz observations from the Very Large Array Sky Survey. It is located in the nucleus of a low-mass () host galaxy with weak or no past active galactic nuclei (AGN) activity. VT J1548 is associated with a slow rising (multiple year), bright mid-IR flare in the Wide-field Infrared Survey Explorer survey, peaking at ∼10%L edd.. No associated optical transient is detected, although we cannot rule out a short, early optical flare given the limited data available. Constant late-time (∼3 yr post-flare) X-ray emission is detected at ∼1042 erg s−1. The radio spectral energy distribution is consistent with synchrotron emission from an outflow incident on an asymmetric medium. A follow-up, optical spectrum shows transient, bright, high-ionization coronal line emission ([Fe x i] λ6375, [Fe x i] λ7894, [S x i i] λ7612). Transient broad Hα is also detected but without corresponding broad Hβ emission, suggesting high nuclear extinction. We interpret this event as either a tidal disruption event or an extreme flare of an AGN, in both cases obscured by a dusty torus. Although these individual properties have been observed in previous transients, the combination is unprecedented. This event highlights the importance of searches across all wave bands for assembling a sample of nuclear flares that spans the range of observable properties and possible triggers.

Neutrophil/lymphocyte ratio but not platelet/lymphocyte ratio and mean platelet volume can be an indicator of subclinical inflammation in patients with Familial Mediterranean Fever

Aim of the work: To evaluate the value of three hematological indices to determine subclinical inflammation in Familial Mediterranean Fever (FMF) patients during attack-free period. Patients and methods: This study included 60 FMF patients without FMF-related symptoms or signs in the preceding month and 50 age and sex matched healthy control. Subclinical inflammation was defined as the presence of elevated C-reactive protein (CRP) > 5 mg/dL and/or serum amyloid A (SAA) levels > 6.4 mg/L in the absence of any FMF related clinical signs and symptoms. The neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR) and mean platelet volume (MPV) were evaluated. Results: The median age of the patients was 32 and 80% were females. They were 12 (80%) with subclinical inflammation and 48 (80%) without. Mutations of MEFV gene were analyzed in 43 (56.6%) patients and were homozygous in 21, heterozygous in 12 and compound heterozygous in 10. The most common mutation was of M694V. The NLR and PLR were significantly higher and MPV lower in patients with inflammation (p = 0.002, p = 0.02, p = 0.03, respectively) but was comparable to the values in the control. Only NLR was significantly higher in those with inflammation compared to those without (p = 0.009) whereas MPV and PLR were similar (p = 0.45 and p = 0.22, respectively). The best cut-off value for NLR in predicting subclinical inflammation in patients was 2.94 (sensitivity 66.7%, specificity 94.9%;p = 0.009). Conclusions: Only NLR increased in FMF patients with subclinical inflammation which may be used as a marker in determining early activity or flare in addition to other markers.

Chlorophyll content estimation based on cascade spectral optimizations of interval and wavelength characteristics

Spectroscopy is an efficient way to estimate the chlorophyll content of crop canopy in the visible and near-infrared region to indicate the photosynthesis capacity and growth status. Although hyperspectral data of crop canopy provide a lot of information, a critical issue is that the subsequent redundant and interference wavelengths could reduce the accuracy and robustness of the estimated results in the field. Therefore, a cascade method of interval-wavelength screening was proposed to reduce the data dimension and improve the crop estimation accuracy and robustness for the chlorophyll content diagnosis of maize crops. In the experiments, spectral reflectance data of maize canopy within 325–1075 nm were obtained, and chlorophyll contents were measured under the conditions of six nitrogen application rates and three growth periods following the early flaring, flaring, and tasseling stages. First, the backward interval partial least squares (BiPLS) method was used to optimize the spectrum interval. Then, competitive adaptive reweighted sampling (CARS) and genetic algorithm (GA) were used for secondary wavelength screening, and the partial least squares regression (Bi-CARS-PLSR and Bi-GA-PLSR) model was established with the chlorophyll content. Compared with the full-spectrum modeling (Full-PLSR) results and the GA and CARS screening wavelength modeling (Full-CARS-PLSR and Full-GA-PLSR) results in the full-spectrum range, the number of wavelengths in the Full-PLSR model was 751. The accuracy of the Full-PLSR model with the coefficient of determination was 0.88 for the calibration set (Rc2) and 0.66 for the verification set (Rv2). The root mean square error (RMSE) was 2.05 mg/L. The wavelength numbers of Full-CARS-PLSR and Full-GA-PLSR were 125 and 99, and their Rc2 and Rv2 were 0.88 and 0.67, respectively. The RMSE values of Full-CARS-PLSR and Full-GA-PLSR were 2.04 and 1.89 mg/L, respectively. By using the proposed cascade method, the wavelength numbers of the Bi-CARS-PLSR model and Bi-GA-PLSR model after interval optimization were 60 and 49, respectively. Their accuracy values for the calibration set (Rc2) were both 0.87, while those for the verification set (Rv2) were 0.7 and 0.78, respectively. The RMSE values of both models were 1.97 and 1.86 mg/L, respectively. The results showed that the proposed cascaded interval-wavelength screening method could eliminate redundant and collinearity variables and improve model performances. At the same time, the Bi-GA-PLSR modeling result was used for field prediction to establish a chlorophyll distribution map, which had a high consistency with the real chlorophyll distribution, and showed the potential to detect chlorophyll content of maize in the field.

The susceptibility of attaining and maintaining DMARD-free remission in different (rheumatoid) arthritis phenotypes.

To compare (sustained) DMARD-free remission rates((S)DFR), defined as respectively ≥6 months and >1 year, after 2 and 5 years between three clinical arthritis phenotypes; undifferentiated arthritis(UA), autoantibody-negative(RA-) and positive rheumatoid arthritis(RA+). All UA(n = 130), RA-(n = 176) and RA + (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. (S)DFR comparisons between phenotypes after 2 and 5 years were performed with Logistic regression. Medication use and early and late flares(DAS ≥ 2.4), respectively defined as < 12 and >12 months after reaching DFR, were also compared. Cox proportional hazard models were used to evaluate potential predictors for (S)DFR. Within 2 and 5 years less DFR was seen in RA + (17.2-25.7%), followed by RA-(28.4-42.1%) and UA patients(43.1-58.5%). This also applied for SDFR within 2 and 5 years (respectively 7.6% and 21.4%; 20.5% and 38.1%; and 35.4% and 55.4%). A flare during tapering was seen in 22.7% of patients. Of the patients in DFR 7.5% had an early flare and 3.4% a late flare. Also more treatment intensifications occurred in RA+ compared with RA- and UA. We found that higher baseline DAS, ACPA positivity, BMI and smoking were negatively associated with (S)DFR, while clinical phenotype(reference RA+), short symptom duration(<6 months) and remission within 6 months were positively associated. (Long-term) clinical outcomes differ between undifferentiated arthritis, autoantibody-negative and positive rheumatoid arthritis(RA). These data reconfirm that RA can be subdivided into aforementioned clinical phenotypes and that treatment might be stratified upon these phenotypes, although validation is needed. ISRCTN, https://www.isrctn.com/, ISRCTN26791028.

Rosacea with persistent facial erythema and high Demodex density effectively treated with topical ivermectin alone or combined with oral carvedilol.

Topical ivermectin is effective in treating papulopustular rosacea, but its effect on persistent facial erythema of rosacea with high Demodex densities has not been well documented. We retrospectively reviewed 39 rosacea patients with persistent facial erythema and high Demodex densities. Clinician's erythema assessment (CEA) and Demodex density were evaluated before and after topical ivermectin alone or combined with oral carvedilol. Three patients (all with papulopustular rosacea, in ivermectin group) dropped out due to early ivermectin-induced local flare of rosacea. In the remaining patients (ivermectin group n = 14; ivermectin-carvedilol group n = 22), the CEA grade and Demodex density were significantly reduced, both P < .01. There was no statistically significant difference between the two groups in CEA before and after treatment (P = .07 and P = .23, respectively), and in Demodex density (P = .82 and .10, respectively). Both regimens markedly improved the persistent facial erythema with response being excellent in 26 of 36 patients (72%), good in 2, fair in 4 and none in 4. There was a correlation between the reduction of CEA and Demodex density after treatment (rho = 0.50, P = .002). The results showed that topical ivermectin was effective in reducing persistent facial erythema of rosacea with Demodex overgrowth.

Early Changes in [18F]FDG Uptake as a Readout for PI3K/Akt/mTOR Targeted Drugs in HER-2-Positive Cancer Xenografts.

We investigated the potential use of [18F]FDG PET as a response biomarker for PI3K pathway targeting therapies in two HER-2-overexpressing cancer models. Methods. CD-1 nude mice were inoculated with HER-2-overexpressing JIMT1 (trastuzumab-resistant) or SKOV3 (trastuzumab-sensitive) human cancer cells. Animals were treated with trastuzumab, everolimus (mTOR inhibitor), PIK90 (PI3K inhibitor), saline, or combination therapy. [18F]FDG scans were performed at baseline, two, and seven days after the start of the therapy. Tumors were delineated on CT images and relative tumor volumes (RTV) and maximum standardized uptake value (SUVmax) were calculated. Levels of pS6 and pAkt on protein tumor lysates were determined with ELISA. Results. In the SKOV3 xenografts, all treatment schedules resulted in a gradual decrease in RTV and delta SUVmax (ΔSUVmax). For all treatments combined, ΔSUVmax after 2 days was predictive for RTV after 7 days (r = 0.69, p = 0.030). In JIMT1 tumors, monotherapy with everolimus or PIK90 resulted in a decrease in RTV (−30% ± 10% and −20% ± 20%, respectively) and ΔSUVmax (−39% ± 36% and −42% ± 8%, respectively) after 7 days of treatment, but not earlier, while trastuzumab resulted in nonsignificant increases compared to control. Combination therapies resulted in RTV and ΔSUVmax decrease already at day 2, except for trastuzumab+everolimus, where an early flare was observed. For all treatments combined, ΔSUVmax after 2 days was predictive for RTV after 7 days (r = 0.48, p = 0.028), but the correlation could be improved when combination with everolimus (r = 0.59, p = 0.023) or trastuzumab (r = 0.69, p = 0.015) was excluded. Conclusion. Reduction in [18F]FDG after 2 days correlated with tumor volume changes after 7 days of treatment and confirms the use of [18F]FDG PET as an early response biomarker. Treatment response can however be underestimated in schedules containing trastuzumab or everolimus due to temporary increased [18F]FDG uptake secondary to negative feedback loop and crosstalk between different pathways.

Early Flare Root Development on Nursery Field-Grown Seedling Stock

Field production of seedlings used to create nursery stock liners involves transplanting and root pruning that can alter root system architecture. Seedlings of eight species of trees commonly used in urban landscapes were selected based on the configuration of their woody lateral roots; Preferred (maximum gap between roots ≤90 degrees), Acceptable (maximum gap 120–150 degrees), and Inferior (≥180 degree gap—no lateral roots on one side). The lateral root configuration (LRC) of the seedlings was compared to the LRC one year after replanting. The number of lateral or regenerated roots alone was generally adequate to form an acceptable root flare (≥3 roots) one year after seedlings were replanted. The maximum gap in lateral roots as a seedling was not consistent with the maximum gap one year after the seedlings were replanted in most species. It often became larger. Neither lateral roots nor regenerated roots alone could reliably produce a root structure with an acceptable maximum gap between roots. Lateral roots and roots regenerated from the pruned end of the main root, together produced enough flare roots one year after replanting with a small enough maximum gap in the radial distribution for good stability. This information may be an initial step in developing criteria for seedling grading systems that will improve root systems of nursery stock grown for planting in urban landscapes.

Segmental Colectomy for Ulcerative Colitis: Is There a Place in Selected Patients Without Active Colitis? An International Multicentric Retrospective Study in 72 Patients

The aim of this study was to report a multicentric experience of segmental colectomy [SC] in ulcerative colitis [UC] patients without active colitis, in order to assess if SC can or cannot represent an alternative to ileal pouch-anal anastomosis [IPAA]. All UC patients undergoing SC were included. Postoperative complications according to ClavienDindo's classification, long term results, and risk factors for postoperative colitis and reoperation for colitis on the remnant colon, were assessed. 72 UC patients underwent: sigmoidectomy [n = 28], right colectomy [n = 24], proctectomy [n = 11], or left colectomy [n = 9] for colonic cancer [n = 27], 'diverticulitis' [n = 17], colonic stenosis [n = 5], dysplasia or polyps [n = 8], and miscellaneous [n = 15]. Three patients died postoperatively and 5/69 patients [7%] developed early flare of UC within 3 months after SC. After a median followup of 40 months, 24/69 patients [35%] were reoperated after a median delay after SC of 19 months [range, 2-158 months]: 22/24 [92%] underwent total colectomy and ileorectal anastomosis [n = 9] or total coloproctectomy [TCP] [n = 13] and 2/24 [8%] an additional SC. Reasons for reoperation were: colitis [n = 14; 20%], cancer [n = 3] or dysplasia [n = 3], colonic stenosis [n = 1], and unknown reasons [n = 3]. Endoscopic score of colitis before SC was Mayo 23 in 5/5 [100%] patients with early flare vs 15/42 without early flare [36%; p = 0.0101] and in 9/12 [75%] patients with reoperation for colitis vs 11/35 without reoperation [31%; p = 0.016]. After segmental colectomy in UC patients, postoperative early colitis is rare [7%]. Segmental colectomy could possibly represent an alternative to IPAA in selected UC patients without active colitis.

Antibodies to synthetic citrullinated peptide epitope correlate with disease activity and flares in rheumatoid arthritis.

Rheumatoid arthritis (RA), caused by the abnormal recognition of human joint cells by autoimmune antibodies, remains the world’s most prevalent autoimmune disease, with over five million people affected and as much as 4% of the population at risk of RA. To prevent rapid disease development, hormonal and anti-inflammatory therapies require fast and reliable RA diagnosis. However, difficulty in detecting early specific biomarkers for RA means that it is unclear when treatment needs to begin. Here, we combined synthesis of citrullinated peptide epitopes with molecular diagnostics to verify a new specific biomarker for early RA diagnosis and flare prediction. A fibrinogen-derived 21-amino-acid-long citrullinated peptide showed high reactivity toward autoantibodies in RA samples. Additionally, the level of antibodies to this epitope was elevated prior to flares. In contrast, other citrullinated protein variants had lower reactivity and poorer sensitivity to disease activity. In conclusion, fibrinogen-derived epitope E2 subjected to citrullination facilitated a reliable RA diagnosis with a strong correlation to disease activity. This is of a high value for the diagnosis and management of RA patients who respond poorly to treatment.