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The prevalence of polycystic ovary syndrome (PCOS) among trans men has been reported as higher than among the cisgender population, which varies between 14.4% and 58%. In this cross-sectional study...

Thrombopoietin receptor agonists (TPO-RAs) are used to treat bone marrow failure in aplastic anemia (AA). Treatment with TPO-RAs, cyclosporine A (CsA) and anti-thymocyte globulin (ATG) induces remission and a sustained response. However, the efficacy of TPO-RAs without ATG remains unclear. We retrospectively assessed 45 patients with AA refractory to CsA and naïve for ATG treatment who received eltrombopag without ATG at our hospital during 2017-2021. Of these, 28 (62%) achieved a hematologic response in at least one lineage after six months of treatment, and 38 (84%) achieved best response at any point during the follow-up period. Four patients (25%) achieved trilineage responses during the follow-up period. Five patients switched from eltrombopag to romiplostim because of adverse events or lack of efficacy. Two developed hematologic malignancies. Eltrombopag was effective even in elderly ATG-ineligible patients with severe AA. The two-year overall survival rate was 84.3%, with a median follow-up of 26.3 months. Time from diagnosis to eltrombopag treatment initiation tended to affect the response (p = 0.0727), but no factors that significantly predicted hematologic response were identified. In conclusion, patients who are ineligible for ATG treatment because of age, complications, or even severe AA should nevertheless be considered for TPO-RA treatment.

Background We investigated the necessity of multiple core biopsies when performing transperineal template-guided mapping biopsy (TTMB) for patients with large prostates and no suspicious lesions on multiparametric magnetic resonance imaging (mpMRI). Materials and methods We retrospectively analyzed 304 patients on active surveillance (AS), 212 patients with previously negative transrectal ultrasound-guided biopsy (TRUS-Bx) and 67 biopsy naive patients who underwent TTMB between May 2017 and December 2020. The number of core biopsies and acute urinary retention (AUR) rates were analyzed in relation to the prostate volume (PV). Cancer detection rate according to the prostate volume and Prostate Imaging-Reporting and Data System (PI-RADS) scores were compared using the Pearson Chi-square test. Results AUR occurred more frequently in patients with PV over 39 cc (5.5% vs. 24.4%, P Conclusion Increasing the number of core biopsies of prostates measuring ≥39 cc with PI-RADS 1–2 on mpMRI does not significantly increase the detection rates of any prostate cancer or csPCA.

Background: Although hypertension is a well-known risk factor for chronic kidney disease (CKD), the blood pressure (BP) at which antihypertensive interventions should be initiated remains to be determined. Therefore, we investigated the association between BP and CKD in treatment-naïve individuals.Methods: This prospective cohort study considered 7,343 individuals in the Korean Genome and Epidemiology Study who were not taking antihypertensive medications. Subjects were categorized into six groups according to their systolic BP (SBP) and five groups according to their diastolic BP (DBP). The primary outcome was incident CKD, which was defined as an estimated glomerular filtration rate of

Information on microbiota dynamics in pulmonary tuberculosis (TB) in Africa is scarce. Here, we sequenced sputa from 120 treatment-naïve TB patients in Uganda, and investigated changes in microbiota of 30 patients with treatment-response follow-up samples. Overall, HIV-status and anti-TB treatment were associated with microbial structural and abundance changes. The predominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria, accounting for nearly 95% of the sputum microbiota composition; the predominant genera across time were Prevotella, Streptococcus, Veillonella, Haemophilus, Neisseria, Alloprevotella, Porphyromonas, Fusobacterium, Gemella, and Rothia. Treatment-response follow-up at month 2 was characterized by a reduction in abundance of Mycobacterium and Fretibacterium, and an increase in Ruminococcus and Peptococcus; month 5 was characterized by a reduction in Tannerella and Fusobacterium, and an increase in members of the family Neisseriaceae. The microbiota core comprised of 44 genera that were stable during treatment. Hierarchical clustering of this core’s abundance distinctly separated baseline (month 0) samples from treatment follow-up samples (months 2/5). We also observed a reduction in microbial diversity with 9.1% (CI 6–14%) of the structural variation attributed to HIV-status and anti-TB treatment. Our findings show discernible microbiota signals associated with treatment with potential to inform anti-TB treatment response monitoring.

We previously reported that t(14;18)-negative follicular lymphomas (FL) show a clear reduction of newly acquired N-glycosylation sites (NANGS) in immunoglobulin genes. We therefore aimed to investigate in-depth the occurrence of NANGS in a larger cohort of t(14;18)-positive and t(14;18)-negative FL, including early (I/II) and advanced (III/IV) stage treatment-naive and relapsed tumors. The clonotype was determined by using a next-generation sequencing approach in a series of 68 FL with fresh frozen material [36 t(14;18) positive and 32 t(14;18) negative]. The frequency of NANGS differed considerably between t(14;18)-positive and t(14;18)-negative FL stage III/IV, but no difference was observed among t(14;18)-positive and t(14;18)-negative FL stage I/II. The introduction of NANGS in all t(14;18)-negative clinical subgroups occurred significantly more often in the FR3 region. Moreover, t(14;18)-negative treatment-naive FL, specifically those with NANGS, showed a strong bias for IGHV4-34 usage compared with t(14;18)-positive treatment-naive cases with NANGS; IGHV4-34 usage was never recorded in relapsed FL. In conclusion, subgroups of t(14;18)-negative FL might use different mechanisms of B-cell receptor stimulation compared with the lectin-mediated binding described in t(14;18)-positive FL, including responsiveness to autoantigens as indicated by biased IGHV4-34 usage and strong NANGS enrichment in FR3.

BACKGROUND Insufficient and contradictory data are available about the relation between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV). AIM To analyze differences in basic clinical, radiological, and laboratory characteristics in addition to tumor behavior upon HCC diagnosis between patients with and without a previous history of DAAs exposure. METHODS This multicenter case-control study included 497 patients with chronic HCV-related HCC, allocated into one of two groups according to their history of antiviral treatment for their HCV. RESULTS Group I included 151 HCC patients with a history of DAAs, while 346 patients who had never been treated with DAAs were assigned to group II. A significant difference was observed between both groups regarding basic assessment scores (Child, MELD, and BCLC), which tended to have more advanced liver disease and HCC stage upon diagnosis in group I. However, serum albumin was significantly affected, and serum α-fetoprotein was significantly higher in group II (P < 0.001). In addition, group I showed significant HCC multicentricity than group II, while the incidence of portal vein thrombosis was significantly higher in group I (P < 0.001). CONCLUSION The basic clinical scores and laboratory characteristics of HCC patients are advanced in patients who are naïve to DAAs treatment; however, HCC behavior is more aggressive in DAA-treated patients.

Background Neuroimaging studies in posttraumatic stress disorder (PTSD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these are localized to specific regions of fiber tracts, and what diagnostic value they might have. This study set out to explore the spatial profile of WM abnormalities along defined fiber tracts in PTSD. Methods Diffusion tensor images were obtained from 77 treatment-naive noncomorbid patients with PTSD and 76 demographically matched trauma-exposed non-PTSD (TENP) controls. Using automated fiber quantification, tract profiles of fractional anisotropy, axial diffusivity, mean diffusivity, and radial diffusivity were calculated to evaluate WM microstructural organization. Results were analyzed by pointwise comparisons, by correlation with symptom severity, and for diagnosis-by-sex interactions. Support vector machine analyses assessed the ability of tract profiles to discriminate PTSD from TENP. Results Compared to TENP, PTSD showed lower fractional anisotropy accompanied by higher radial diffusivity and mean diffusivity in the left uncinate fasciculus, and lower fractional anisotropy accompanied by higher radial diffusivity in the right anterior thalamic radiation. Tract profile alterations were correlated with symptom severity, suggesting a pathophysiological relevance. There were no significant differences in diagnosis-by-sex interaction. Tract profiles allowed individual classification of PTSD versus TENP with significant accuracy, of potential diagnostic utility. Conclusions These findings add to the knowledge of the neuropathological basis of PTSD. WM alterations based on a tract-profile quantification approach are a potential biomarker for PTSD.

Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disease that is characterized by accumulation of cysteine and formation of crystals within cells of different organs and tissues causing systemic manifestations in childhood that include poor linear growth, ocular involvement, hypothyroidism, and progressive kidney disease. This study was a long‐term, prospective open‐label evaluation of twice‐daily delayed release (DR) cysteamine capsules in cystinosis patients

BACKGROUND AND PURPOSE: Arterial sclerosis resulting from hypertension slows CSF transportation in the perivascular spaces, showing the intrinsic relationship between the CSF and the blood vasculature. However, the exact effect of hypertension on human CSF flow dynamics remains unclear. The present study aimed to evaluate CSF flow dynamics in treatment-naive patients with essential hypertension using phase-contrast cine MR imaging. MATERIALS AND METHODS: The study included 60 never-treated patients with essential hypertension and 60 subjects without symptomatic atherosclerosis. CSF flow parameters, such as forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, average flow, and net flow volume, were measured with phase-contrast cine MR imaging. Differences between the 2 groups were assessed to determine the independent determinants of these CSF flow parameters. RESULTS: Forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, and average flow in the patients with hypertension significantly decreased (all, P

Optimal resection of breast tumors requires removing cancer with a rim of normal tissue while preserving uninvolved regions of the breast. Surgical and pathological techniques that permit rapid molecular characterization of tissue could facilitate such resections. Mass spectrometry (MS) is increasingly used in the research setting to detect and classify tumors and has the potential to detect cancer at surgical margins. Here, we describe the ex vivo intraoperative clinical application of MS using a liquid micro-junction surface sample probe (LMJ-SSP) to assess breast cancer margins. In a midpoint analysis of a registered clinical trial, surgical specimens from 21 women with treatment naïve invasive breast cancer were prospectively collected and analyzed at the time of surgery with subsequent histopathological determination. Normal and tumor breast specimens from the lumpectomy resected by the surgeon were smeared onto glass slides for rapid analysis. Lipidomic profiles were acquired from these specimens using LMJ-SSP MS in negative ionization mode within the operating suite and post-surgery analysis of the data revealed five candidate ions separating tumor from healthy tissue in this limited dataset. More data is required before considering the ions as candidate markers. Here, we present an application of ambient MS within the operating room to analyze breast cancer tissue and surgical margins. Lessons learned from these initial promising studies are being used to further evaluate the five candidate biomarkers and to further refine and optimize intraoperative MS as a tool for surgical guidance in breast cancer.

Background/Aim: Thyroid hormones play an essential role in retinal development and physiological functions. Although the effects of hyperthyroidism on ocular circulation are well-defined, no studies report the effects of clinical hypothyroidism on retinal and choroidal circulation. We aimed to compare the macular vessel density and flow indexes of patients with treatment-naive hypothyroidism and healthy controls using optical coherence tomography angiography (OCTA).Methods: This case-control study included 104 eyes of 52 participants. Group 1 (n=24) consisted of patients with treatment-naive overt hypothyroidism, while Group 2 (n=28) consisted of age and sex-matched healthy controls. Images were obtained using AngioVue software 2.0 of the OCTA device in a 6 × 6 mm area centered on the macula. Foveal avascular zone (FAZ) area, macular retinal thickness, FAZ perimeter (PERIM), choroidal flow index (CF), outer retinal flow index (ORF) and macular vessel density (VD) in the superficial (SCP) and deep retinal capillary plexus (DCP) were recorded for all patients.Results: The whole [Group 1: 49.9 (7.0)%; Group 2: 54.6 (5.9)%], parafoveal [Group 1: 54.7 (4.8)%; Group 2: 58.6 (3.9)%] and perifoveal [Group 1: 51.5 (7.2)%; Group 2: 55.9 (6.8)% ] VD in DCP were significantly lower in Group 1 compared to Group 2 (P=0.012; P=0.002 and P=0.028 respectively). However, parafoveal VD in SCP was significantly higher in Group 1 [52.4 (2.26)] than in Group 2 [49.9 (6.87)] (P=0.032). The mean VD in DCP was significantly positively correlated with the choroidal (P=0.021) and outer retinal flow indexes (P=0.033). The mean foveal VD in DCP was significantly positively correlated with the mean foveal (P

AimTo evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME).MethodsThe open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that were treatment-naïve or non-responsive to antivascular endothelial growth factors. No eyes were excluded based on baseline best-corrected visual acuity (BCVA) or central subfield retinal thickness (CRT). After the initial DEX injection at the baseline visit, reinjection was permitted at ≥16-week intervals. Week-16 and week-52 visits were mandatory. Primary endpoints were changes in mean BCVA and CRT from baseline to 52 weeks.ResultsOf 200 eyes enrolled in the AUSSIEDEX study, 57 were treatment-naïve. Baseline mean BCVA was 58.8 letters and baseline mean CRT was 418.6 µm; changes in mean BCVA and CRT from baseline to 52 weeks in this subgroup were 3.4 letters (p=0.042) and –89.6 µm (pConclusionIn this largest prospective, real-world study of DEX monotherapy for DME to date, DEX significantly improved CRT and BCVA at 52 weeks in treatment-naïve eyes, without new safety concerns, supporting DEX use in treatment-naïve DME.Trial registration numberNCT02731911.

Objectives DRAKO (NCT02850263) is a 24-month, prospective, non-interventional, multi-centre cohort study which enroled patients diagnosed with centre-involving diabetic macular oedema (DMO). The study aims to evaluate standard of care with intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the anti-vascular endothelial growth factor (anti-VEGF) treatment-naive patient cohort after 12-month follow-up. Methods Study eyes were treated with IVT-AFL as per local standard of care. The mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline at 12 months were measured and stratified by baseline factors. The number of injections and safety data were also evaluated. Results A total of 507 patients were enroled from 35 centres. Mean (SD) baseline BCVA was 71.4 (12.0) letters and CST was 448.7 (88.7) µm, with 63.1% of patients presenting with baseline BCVA ≥ 70 letters (mean 78.1). Mean (SD) change in BCVA of 2.5 (12.2) letters and CST of −119.1 (116.4) µm was observed at month 12. A 7.3 letter gain was observed in patients with baseline BCVA Conclusion Year one results indicated that IVT-AFL was an effective treatment for DMO in standard of care UK clinical practice, maintaining or improving visual acuity in treatment-naive patients with good baseline visual acuity, despite some patients being undertreated versus the summary of product characteristics. These results also demonstrated the clinical importance and meaningful impact of diabetic retinopathy screening in the UK.

Background: Most patients with HER2-positive metastatic breast cancer (MBC) receive first-line treatment with anti-HER2 agents and have already received anti-HER2 therapy as adjuvant or neoadjuvant therapy in the local setting of their disease presentation. Despite that, they constitute only a minority among clinical trials, and their response to reintroduction to anti-HER2 treatments is inconclusive based upon conflicting studies. We aimed to examine if previous exposure influences the clinical outcome of patients treated with anti-HER2 treatments compared to patients who were naïve to anti-HER2 agents. Methods: We conducted a retrospective observational study of HER2-positive MBC patients who were treated with trastuzumab and pertuzumab from 2014 to 2018. We collected and analyzed data including patients’ demographic characteristic as well as extracted data of previous treatment regimens and the efficiency of the anti-HER2 therapy measured by response rate (RR), time to tumor progression (TTP), and overall survival (OS). Results: Eighty patients met the inclusion criteria, 26 (32.5%) of them were previously exposed to anti-HER2 treatments and 54 (67.5%) were not previously exposed to anti-HER2 therapy. No significant differences were detected in RR after 3 months of treatment (p = 0.684). TTP was significantly better among patients with no previous exposure in comparison with patients with previous exposure to anti-HER2 therapy (21 vs. 14 months, p = 0.044) and we noted a trend in better OS (p = 0.056). Conclusion: Our analysis suggests that previous exposure to anti-HER2 agents might influence the clinical outcome of first-line treatment in metastatic HER2 patients. These findings justify further exploration of the benefit of reintroduction of anti-HER2 treatment enabling the optimal treatment for patients with previous anti-HER2 therapy exposure.

Objectives: The efficacy of new direct-acting antivirals (DAAs) in treating hepatitis C infection can depend on treatment adherence, which may be influenced by the patient's current lack of awareness of the disease. This study set out to understand the treatment naïve chronic hepatitis C patients' preferences for new DAAs (attributes) and to compile information about the diagnosis process. Material and method: Spanish quantitative market research study conducted between November 2018 and January 2019 to assess the posology preferences of treatment-naïve patients with chronic hepatitis C before starting treatment (seen by hepatologists and infectious diseases specialists). A telephone interview was carried out to collect demographic, diagnostic and treatment preference data, consisting of two dosing OPTIONS: 1) three tablets/day (single dose), at the same time, with food (8 weeks). 2) single tablet/day, at any time with/without food (12 weeks). A descriptive analysis of pooled results was performed. Results: 104 patients (mean age: 49 years) with hepatitis C diagnosed 7.3±9.7 years ago (average), mainly in primary care (PC) (42%). The most common reasons for not having started treatment were health problems/comorbidities (31%). Fifty-eight percent of patients were not informed about the available treatments. Seventy-two percent of patients preferred a simple tablet/day, at any time, with/without food (12 weeks), and considered compatibility with other treatments, side effects, ease of administration, treatment duration and the number of tablets to be very important. Discussion: Patient preferences are mainly driven by dosing flexibility and simplicity, including freedom to take the medication with/without food. The role of PC in the diagnosis should be taken into account. There are still patients who are untreated after diagnosis.

Introduction The MET pathway is a promising target in patients with non–small-cell lung cancer (NSCLC). Fluorescence in situ hybridization analysis has become a standard method to detect MET amplification. However, no consensus has been reached regarding the definition of MET amplification. We aimed to find clinically meaningful cutoffs for MET amplification that could be used as a prognostic marker and/or indication for MET inhibitor therapy. Patients and Methods We reviewed the fluorescence in situ hybridization results of MET/CEP7 (centromere of chromosome 7) for 2260 patients with treatment-naive NSCLC from 2014 to 2019. Clinical and pathologic data were collected from the medical records. Log-rank tests and Cox proportional hazard models were used to estimate the overall survival (OS) among patients with different MET/CEP7 ratios and/or MET copy numbers. Results Of the 2260 patients, 130 (5.8%) had had a MET/CEP7 ratio of ≥ 1.8 and 13 (0.6%) had had a ratio of ≥ 5.0. Of these 130 patients with a MET/CEP7 ratio of ≥ 1.8, 123 (95%) also had a MET copy number of ≥ 5. In general, a higher MET copy number and higher MET/CEP7 ratio were associated with advanced tumor stage. The OS was significantly shorter when the MET copy number was ≥ 10 and/or when the MET/CEP7 ratio was ≥ 1.8. A MET/CEP7 ratio of ≥ 1.8 remained a significant hazard to OS on multivariate analysis (hazard ratio, 1.63; P = .019). Conclusions Patients with a MET copy number of ≥ 10 and/or MET/CEP7 ratio of ≥ 1.8 showed significantly poorer survival, and a MET/CEP7 ratio of ≥ 1.8 was an independent poor prognostic factor.

Ryan B Rush,1– 4 Sloan W Rush2,3 1Instituto de la Visión– Hospital La Carlota, Montemorelos, Nuevo León, 67530, México; 2Panhandle Eye Group, Amarillo, TX, 79106, USA; 3Department of Surgery, Texas Tech University Health Science Center, Amarillo, TX, 79106, USA; 4Southwest Retina Specialists, Amarillo, TX, 79106, USACorrespondence: Ryan B RushSouthwest Retina Specialists, 7411 Wallace Blvd, Amarillo, TX, 79106, USATel +1 806 351-1870Email ryan.rush.md@gmail.comPurpose: To report the outcomes in subjects undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for the management of treatment-naïve diabetic macular edema (DME).Methods: Ten treatment-naïve subjects with non-proliferative diabetic retinopathy prospectively underwent PPV with ILM peeling for the treatment of DME at a single university-affiliated institution. The preoperative features, intraoperative details and postoperative outcomes were collected and analyzed.Results: All 10 subjects underwent PPV with ILM peeling without significant intraoperative or postoperative complications at 6 months follow-up. Visual acuity improved from a baseline of 0.74 (95% CI: 0.48– 1.0) logMAR (Snellen 20/110) to 0.46 (95% CI: 0.3– 0.62) logMAR (Snellen 20/58) at 6 months follow-up (p=0.045). Optical coherence tomography central macular thickness reduced from a baseline of 456 (95% CI: 394.7– 516.4) microns to 316.8 (95% CI: 275.9– 357.7) microns at 6 months follow-up (p < 0.001).Conclusion: This pilot study suggests that PPV with ILM peeling may be a viable treatment option for the management of treatment naïve DME in subjects with non-proliferative diabetic retinopathy. Development of a randomized controlled trial may be justified to validate the results of this study.Clinicaltrials.gov Identifier #: NCT03660345.Keywords: vitrectomy, internal limiting membrane peeling, diabetic macular edema

Background: Transsexuality is explained and defined as a gender-identity disorder, characterised by very strong conviction of belonging to the opposite sex and has been associated with a distinct neuroanatomical pattern. Materials and methods: We performed a structural analysis in search of possible differences in grey matter structures based on magnetic resonance imaging scans of the brains of 26 individuals between 19 and 38 years of age. The participants were divided into two groups of 15 controls and 11 transgender individuals. The segmentation of subcortical grey matter was performed using FIRST model a model-based segmentation/registration tool, from FSL software package. Results: The results showed that the volume of the brain region called nucleus accumbens on the left side was significantly smaller in the group of transgender individuals compared to the control. It was the most important parameter which was shown to make distinction between two examined groups. Conclusions: The results also showed decreased volumes of the left thalamus, right hippocampus and right caudate nucleus.

Background Multivariable baseline factor analysis across cabotegravir + rilpivirine clinical trials showed that HIV-1 subtypes A6/A1 and the presence of rilpivirine resistance-associated mutations (RAMs) were associated with an increased risk of virological failure of this dual therapy. The aim of this study was to describe the prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients. Patients and methods From 2010 to 2020, 4212 sequences from ARV-naive patients were collected from three large Parisian academic hospital genotypic databases. Cabotegravir and rilpivirine RAMs were defined according to the ANRS algorithm. Results Among 4212 ARV-naive patients, 38.6% were infected with subtype B, 32.4% with CRF02_AG (32.4%) and 5.1% with subtype A (85.5% being A6/A1 subtype). Overall, the presence of at least one cabotegravir or rilpivirine RAM was 16.2% and 14.3%, respectively. Considering genotypic resistance interpretation, using the ANRS algorithm, 0.74% (n = 31), 6.2% (n = 261) and 0.09% (n = 4) of sequences were resistant to cabotegravir, rilpivirine or both, respectively. The overall prevalence of L74I in integrase and E138A in RT was 13.0% and 3.2%, respectively, and stable over the decade. Thus, adding 183 subtype A6/A1 sequences to 244 sequences interpreted as resistant to rilpivirine led to 427 (10.1%) sequences combining both baseline virological risk factors for cabotegravir + rilpivirine dual-therapy failure. Conclusions Among large sequence databases, when adding prevalence of rilpivirine-resistant viruses and HIV-1 subtype A6/A1 sequences, 10.1% of patients would not be eligible for cabotegravir + rilpivirine dual therapy. These data re-emphasize the need for a pre-therapeutic genotypic resistance test to detect polymorphisms and transmitted drug resistance and to define HIV-1 subtype.

PRCIS Reduction of intraocular pressure (IOP) by latanoprost in treatment-naive eyes is significantly correlated to an increase in vessel density (VD) at the optic nerve head (ONH). PURPOSE To evaluate the effect of topical latanoprost on ocular microvasculature using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS In this prospective case-control study, 26 eyes from 18 treatment-naive subjects in whom prostaglandin analogue (PGA) latanoprost 0.005% was initiated were included as cases. In 10 out of the 18 subjects, medication was initiated in only 1 eye; their contralateral untreated eyes were used as controls. OCTA (AngioVue, Optovue Inc., Fremont, CA) was performed at baseline and ≥3 weeks after commencing treatment. Main outcome measures were change in flow area and VD at the ONH, radial peripapillary capillaries (RPC), and macula. Comparison between the 2 visits was performed using a linear mixed model adjusted for intereye correlation and mean ocular perfusion pressure. RESULTS IOP decreased by 26.1%±11.3% (P

Kuo-Hsuan Hsu,1,2,* Jing-Wen Huang,2,3,* Jeng-Sen Tseng,2,4,5 Kuan-Wen Chen,6 Yih-Chyang Weng,7 Sung-Liang Yu,8– 12 Tsung-Ying Yang,4,5 Yen-Hsiang Huang,2,4 Jeremy JW Chen,2 Kun-Chieh Chen,4,13– 15 Gee-Chen Chang2,4,5,13– 15 1Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Institute of Biomedical Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 3Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; 4Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 5Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6Department of Radiation Oncology, Taichung Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation, Taichung, Taiwan; 7Radiation Oncology, Nantou Hospital of Ministry of Health and Welfare, Nantou City, Taiwan; 8Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; 9Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; 10Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 11Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan; 12Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 13Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 14Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 15School of Medicine, Chung Shan Medical University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Gee-Chen Chang; Kun-Chieh ChenDivision of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan, Republic of ChinaTel +886-4-24739595 ext. 34412Fax +886-4-24739595 #34710Email cshy1888@csh.org.tw; ckjohn@mail2000.com.twBackground: Whether radiotherapy only for primary lung tumor (RTPLT) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves survival of treatment naïve advanced EGFR-mutant lung adenocarcinoma (LAD) patients with/without polymetastasis.Materials and Methods: This was a retrospective, single-center, observational study. Patients with stage IIIB-IV EGFR-mutant LAD with disease control by EGFR-TKI therapy were divided into curative RTPLT, and control, without radiotherapy (WRTPLT) groups.Results: A total of 138 patients were enrolled; 46 in the RTPLT group and 92 in the WRTPLT group. Amongst them, 37% had oligometastasis, and 26.1% brain metastasis. The RTPLT group had both significantly longer progression-free survival (PFS) (27.5 months [95% CI 18.1– 36.9] vs 10.9 months [95% CI 6.3– 15.5], P< 0.001) and overall survivor (OS) (NR [95% CI NR-NR] vs 38.0 months [95% CI 31.2– 44.8], P< 0.001), respectively, when compared to the WRTPLT group. In multivariate analysis, the adjusted HR of radiotherapy on PFS was 0.30 (0.19– 0.47) and on OS, 0.11 (0.04– 0.30). Patients with oligometastasis had significantly longer PFS than those with polymetastasis with an HR of 0.35 (0.14– 0.85), P=0.02. Patients with either oligometastasis or polymetastasis had significant longer PFS when undergoing radiotherapy than those without (both P< 0.05). An EGFR-TKI to radiotherapy interval < 24 weeks seemed more beneficial (P=0.097). Radiation pneumonitis comprised 32 (69.6%), 12 (26.1%), and two (4.3%) cases of common terminology criteria grade I, II, and III, respectively.Conclusion: Curative RTPLT can prolong survival in patients with LAD following EGFR-TKI disease control, both involving oligometastasis and polymetastasis. RTPLT within 24 weeks after EGFR-TKI initiation appeared to be more beneficial with tolerable radiation pneumonitis.Keywords: radiotherapy to primary lung tumor, RTPLT, EGFR-TKI, lung adenocarcinoma, oligometastasis, polymetastasis

Carl Erb,1 Ingeborg Stalmans,2 Milko Iliev,3 Francisco José Muñoz-Negrete4 1Eye Clinic Wittenbergplatz, Berlin, Germany; 2Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium; 3Ophthalmology Department, University of Bern, Inselspital, Bern, Switzerland; 4Servicio de Oftalmología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, IRYCIS, Madrid, EspañaCorrespondence: Francisco José Muñoz-NegreteServicio de Oftalmología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, IRYCIS, Madrid, EspañaTel +34 913 36 80 00Email franciscojmunoz@telefonica.netPurpose: Patient satisfaction is important in the treatment of glaucoma. Suboptimal compliance and impaired long-term outcome are a likely result of poor tolerability. The present multicentre, international, transverse, epidemiological survey was conducted to assess the satisfaction of patients who had received preservative-free latanoprost (PFL) for at least 3 months.Patients and Methods: A total of 1872 patients from 6 European countries, treated with PFL for at least 3 months, were included in this survey. Prior to PFL treatment, patients were to be treatment naïve or currently treated for their glaucoma. During a single routine consultation, patients completed a questionnaire concerning global satisfaction and satisfaction based on tolerability.Results: In total, 76.2% had been previously treated; 69.4% had received preserved and 6.8% preservative-free (PF) topical treatment. After 3 months of PFL treatment, a large majority of patients (95.3%) were satisfied or very satisfied with their PFL treatment and were, overall, significantly (p< 0.0001) more satisfied with PFL than with their previous treatment; 4.2% were either unsatisfied or very unsatisfied. Overall, 97.3% of originally treatment-naïve patients were satisfied (50.1%) or very satisfied (47.2%) with their PFL. Ocular surface disease was diagnosed in 9.2% of patients (n=173) and was mainly mild (76.9%). Patient satisfaction with PFL was very high.Conclusion: PFL may be considered a valuable first-choice treatment in glaucoma patients.Keywords: glaucoma, prostaglandin, preservative-free latanoprost, patient satisfaction, tolerability, tear substitutes, intra-ocular pressure, ocular surface disease, conjunctival hyperaemia

Objective: to conduct a cost-effectiveness study of major biologic disease-modifying antirheumatic drugs (bDMARDs) used for the treatment of ankylosing spondylitis (AS) in Russian health care system with the focus on the new effective drug netakimab (NTK).Patients and methods. Based on the available meta-analysis, a Markov model for therapy was constructed using reference drugs. Then, based on the simulation results, a Cost-Effectiveness Analysis (CEA) and a Budget Impact Analysis (BIA) were carried out. The robustness of the result has been confirmed by several sensitivity analyzes.Results and discussion. NTK showed an advantage in CEA, including the cases when the direct costs of therapy were lower for the reference drug (which shows the greater efficacy of NTK). According to the BIA, the extension of NTK administration in naive patients was consistently associated with a decrease in the budgetary burden. Sensitivity analyzes confirmed the robustness of the result.Conclusion. NTK has clinical and economic advantage in the treatment of AS, it is attractive in terms of both patient's and health care benefit in general. More extensive use of NTK can save more than 5 billion RUB.

Purpose. To evaluate the capability of swept source-optical coherence tomography angiography (SS-OCTA) in the detection and localization of treatment-naive macular neovascularization (MNV) secondary to exudative neovascular age-related macular degeneration (nAMD). Methods. In this prospective, observational case series, 158 eyes of 142 patients were diagnosed with exudative nAMD using fluorescein (FA) and indocyanine green angiography (ICGA) and evaluated by SS-OCTA in a tertiary retina center (Rudolf Foundation Hospital Vienna, Austria). The main outcome measure was the sensitivity of SS-OCTA compared to the standard multimodal imaging approach. Secondary outcome measure was the anatomic analysis of MNV in relation to the retinal pigment epithelium. Results. En-face SS-OCTA confirmed a MNV in 126 eyes (sensitivity: 79.8%), leaving 32 eyes (20.2%) undetected. In 23 of these 32 eyes (71.9%), abnormal flow in cross-sectional SS-OCTA B-scans was identified, giving an overall SS-OCTA sensitivity of 94.3%. Eyes with a pigment epithelium detachment (PED) ≥ 300 μm had a smaller probability for correct MNV detection ( p = 0.015 ). Type 1 MNV showed a trend ( p = 0.051 ) towards smaller probability for the correct detection compared to all other subtypes. Other relevant factors for the nondetection of MNV in SS-OCTA were image artifacts present in 3 of 32 eyes (9.4%). SS-OCTA confirmed the anatomic localization of 93 in 126 MNVs as compared to FA (sensitivity: 73.8%). There was no influence of age, gender, pseudophakia, visual acuity, central foveal thickness, or subfoveal choroidal thickness on the detection rate of MNV. Conclusions. SS-OCTA remains inferior to dye-based angiography in the detection rate of exudative nAMD consistent with type 1 MNV and a PED ≥300 µm. The capability to combine imaging modalities and distinguish the respective MNV subtype improves its diagnostic value.

Triple negative breast cancer (TNBC) is an aggressive and difficult-to-treat subtype of breast cancer that typically exhibits rapid growth rates, high rates of metastasis, and resistance to commonly used oncological drugs. Historically, cell lines have been utilized in order to study TNBC; recently, however, patient derived xenografts (PDX) models have evolved as the new standard that offers a translational approach to the research and subsequent treatment of breast cancer. Here, we characterize two novel PDX models for TNBC: TU-BcX-4QA and TU-BcX-4QAN. The former derived from a biopsy specimen prior to any therapies, and the latter derived from a mastectomy of the same patient after three rounds of AC-T therapy (doxorubicin and cyclophosphamide followed by paclitaxel). In establishing a treatment naïve and post-neoadjuvant therapy PDX model pair, we created a prime model that examines the effects of chemotherapy on tumor heterogeneity, clonal selection, and the overall characteristics of a tumor. Furthermore, we examined the evolution of the characteristics of the post-neoadjuvant therapy PDX model after continual passaging within the SCID/Beige murine models. Through serial implantation in SCID/Beige murine models for tissue propagation, we observed that TU-BcX-4QAN consistently had a higher tumor growth rate and a smaller number of metastatic lesions that developed on the lungs and liver in comparison to the TU-BcX-4QA model. In treating the tumor derived cell lines with NCI-approved oncological drugs, we distinguished the variations in their responses to various, commonly used therapies, and determined that TU-BcX-4QAN had a more resistant profile. Using qRT-PCR, we further discovered the differences between the two models in their contrasting gene expression; preliminary data indicates an increase in certain mesenchymal genes (CDH2, VIM, and ZEB2), a decrease in cell cycle genes (p21, p53), and an increase in proliferation genes (MK167) in TU-BcX-4QAN compared to TU-BcX-4QA. Additionally, serial passages are correlated with a decrease trend in human gene expression within TU-BcX-4QAN. This suggest that treatment can select for certain cancer cells within the primary tumor that allows for the growth of a different tumor altogether and illustrates both the advantages and limitations of the TU-BcX-4QA andTU-BcX-4QAN model pair in translational research. Citation Format: Gabrielle Olivia Windsor, Margarite Matossian, Maryl Wright, Steven Elliott, Khoa Nguyen, Bridgette Collins-Burow, Matthew Burow. Treatment naïve patient-derived xenograft model compared to the post-neoadjuvant model from the same patient diagnosed with triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-47.

Objective: In this study, we compared the serum zonulin levels in patients diagnosed for the first time with active ulcerative colitis with those in healthy cases and attempted to determine whether serum zonulin levels were different in the active ulcerative colitis. Material and Methods: A total of 53 naive patients admitted to our hospital between 2019 and 2020 and diagnosed with active ulcerative colitis by colonoscopy were included as a group of cases and 37 patients with no acute or chronic diseases whose colonoscopy was normal as the control group. Results: The study was conducted on 90 cases, 65.5% male and 34.5% female. The patients with ulcerative colitis were compared with the control group in terms of serum zonulin levels. Average serum zonulin levels of the patients with ulcerative colitis (16.73 ± 5.49 ng/ml) were not significantly different than those in the control group 17.48 ± 8.31 ng/ml). Serum zonulin levels of the patients were also compared according to location and severity of disease and did not differ statistically significantly between the groups in terms of the Montreal Classification. When serum zonulin levels were grouped according to the Truelove and Witts criteria, there was no statistically significant difference between the patient groups themselves and the control group. Conclusion: Serum zonulin levels were not greater in the patients with naive active ulcerative colitis compared to the healthy controls. Several previous studies have shown that serum zonulin levels are elevated in patients with ulcerative colitis, but more studies are needed on this subject.

Mixed phenotype acute leukemia (MPAL) is a rare hematological malignancy that lacks consensus on optimal management. We report for the first time two cases of treatment-naïve B/myeloid MPAL patients treated with a novel chemo-free regimen using venetoclax combined with hypomethylating agents, which successfully induced complete remission with tolerable toxicities.

Objectives: This study was conducted to test the efficacy of Sofosbuvir in patients of genotype 3a who are treatment-naïve which represents the most common setting in Pakistan. Study Design: Experimental study. Setting: Mayo Hospital, Lahore, Punjab, Pakistan. Period: August 2016 to September 2017. Material & Methods: We used an Open label and Quasi Experimental Study Design to test the efficacy of Sofosbuvir in 262 treatment-naïve patients. The duration of the therapy was 24 weeks. All patients were treated with Sofosbuvir 400mg once daily and Ribavirin 400 mg thrice daily. The end of treatment response i.e. ETR was noted at the end by determining the viral load by Polymerase Chain Reaction (PCR). Results: Of the 262 patients included in the study, 43 patients left the treatment either due to financial constraints barring them from following up or due to non-compliance. 11 patients left the treatment due to adverse events. 208 patients completed the 24-week therapy from which 201 (96.6 %) patients showed +Ve ETR. Two patients showed relapse both of whom had high viral load. Five patients were non-responders. The rate of discontinuation of Sofosbuvir due to adverse effects was low (4-5%). Conclusion: Patients with HCV genotype 3a have shown promising improvement in treatment response with Sofosbuvir as compared to the older treatment regimes. In contrast to the long duration of treatment and more disabling adverse effects profile of conventional regimes, Sofosbuvir, with its greater therapeutic efficacy and relatively well-tolerated adverse effects, is expected to provide a break-through in treating Hepatitis C and minimizing the incidence of its complications.

Purpose To compare visual improvements between initial intravitreal t-PA with gas injection before anti-vascular endothelial growth factor (VEGF) and anti-VEGF injection monotherapy for submacular haemorrhage (SMH) associated with age-related macular degeneration (AMD). Methods We retrospectively reviewed medical records of naive patients treated with intravitreal t-PA with gas injection before anti-VEGF (Group 1) or only with intravitreal anti-VEGF injection (Group 2) for SMH [disc area (DA) ≥ 2] associated with AMD from two institutions. Both groups received 3 monthly loads of anti-VEGF injections followed by injections as needed for AMD treatment. Changes in best-corrected visual acuity (BCVA, logMAR) between the initial visit and after 6 months of treatment were compared between two groups. Results A total of 82 patients were enroled. Of these, 32 patients and 50 patients were grouped in Groups 1 and 2, respectively. The mean change in BCVA over 6 months for Group 1 was -0.52 ± 0.88, which was significantly larger (p = 0.044) than the mean change for Group 2 (-0.15 ± 0.58). We compared visual improvements between the two groups based on the following SMH size categories: ≤5, >5, and ≤15, and >15 DA. When the SMH size was ≤5, or >5 and ≤15 DA, the mean change in BCVA was larger for Group 1 than for Group 2, but this difference was not significant. When SMH size was >15 DA, Group 1 patients exhibited a mean visual improvement of -0.79 ± 0.80, which was significantly greater (p = 0.029) than that of Group 2 (-0.06 ± 0.67). Conclusions Patients that were primarily treated for SMH associated with AMD using t-PA and gas injection (followed by anti-VEGF injection) exhibited better visual improvement than those treated with anti-VEGF monotherapy, especially in patients exhibiting larger SMH sizes (>15 DA) at the initial visit.

This study aimed to assess effectiveness and safety of Evogliptin 5 mg in patients with T2DM who were prescribed Evogliptin alone or with other oral hypoglycemic agents in real world scenario. Overall 20 patients who received Evogliptin as routine clinical practice in management of T2DM were analyzed retrospectively from single center. Data collected from past medical records. Primary endpoint was mean changes in HbA1c from baseline to weeks 24 and secondary endpoints were Change in HbA1c from baseline to weeks 12 Change from baseline in FPG & PPG at weeks 12 & 24.Significant reduction in HbA1c at the end of 12 and 24 weeks of Evogliptin therapy was - 0.9% and -1.45% respectively from the baseline of HbA1c 8.6% (p value At the end of 12 and 24 weeks of addition of Evogliptin, significant reduction in FBG were seen i.e -49.5 mg/dl and -90.7mg/dl respectively from base line of 182 mg/dl and reduction in PPG was -79.4mg/dl and -116.6mg/dl respectively from base line 277 mg/dl (p value Evogliptin was found to be effective when added to the patients who were uncontrolled on dual / triple oral anti-diabetic medications and even in treatment naïve patient. It effectively showed reduction in HbA1c, FBG and PPG and the end of 12 and 24 weeks when added to existing anti-diabetic medications & well tolerated in type 2 diabetes Indian patients.Small sample size and retrospective study

Aim.To study predictive factors for functional outcome of aflibercept intravitreal antiangiogenic therapy in patients with neovascular age-related macular degeneration (nAMD). Material and methods.Thirty-six treatment naive nAMD patients (45 eyes, 26 females and 10 males, with a mean age of 74.4 10.9 years) were included in this study. All patients received 3 monthly aflibercept injections followed by 4 bimonthly aflibercept injections. Demographic characteristics, baseline best corrected visual acuity (BCVA), central retinal thickness (CRT), and structural retinal changes on optical coherence tomography (OCT) scans were evaluated for the correlation with BCVA after 10 months follow-up. Results.At the end of the follow-up period, the mean BCVA increased statistically significantly from 31 15 (~0.32) letters at baseline to 37 14 (~0.4) letters (p= 0.003). CRT at baseline and at the end of follow-up was 357 110 and 269 70 m (p 0.001), respectively. Final BCVA correlated statistically significantly with baseline BCVA (r= 0.62,p 0.0001), baseline CRT (r= 0.48,p= 0.001), and disease duration from the appearance of complaints until the therapy start (r= 0.32,p= 0.03). Structural macular changes on the OCT scans were not related to final BCVA (p 0.05) apart from the status of the ellipsoid zone (p 0.001). Final BCVA was statistically significantly lower in males than in females (34.7 14.0 (~0.4) and 45.0 9.2 (~0.63) letters, respectively,p= 0.03). Conclusion.Baseline visual acuity, gender, CRT, disease duration from the appearance of complaints until the therapy start, and status of the ellipsoid zone are predictive for the functional outcome in wet AMD patients.

Background: Although radiofrequency ablation (RFA) is a minimally invasive treatment for early-stage hepatocellular carcinoma (HCC), it remains unclear whether RFA achieves favorable outcomes in patients aged ≥80 years. This study aimed to determine the efficacy and safety of RFA for HCC in patients aged ≥80 years. Methods: A total of 512 naïve patients with HCC who had undergone RFA from January 2001 to December 2016 were enrolled. They were categorized into the ≥80-year-old group and the control group (aged

Background Endoscopic resection of non-invasive lesions is now the standard of care for lesions in the GI tract. However, resection techniques require extensive training, are not available in all endoscopy centers and are prone to complications. Endoscopic mucosal ablation (EMA) is a combination of resection and ablation techniques and it may offer an alternative in the management of such lesions. Case summary In this case series we report the successful treatment of three flat colonic polyps using the EMA technique. Two lesions were treatment naive and 1 was a recurrence after an endoscopic mucosal resection. The sizes ranged from 2 to 4 cm. All three polyps were ablated successfully with no immediate or delayed complications. The recurrence rate at 1 year of follow up was 0%. Conclusion Based on this initial experience, we conclude that EMA is a safe and effective technique for the treatment of non-invasive colonic polyps when endoscopic resection techniques are not available.

BACKGROUND Anastomotic stenosis (AS) after colorectal surgery was treated with balloon dilation, endoscopic procedure or surgery. The endoscopic procedures including dilation, electrocautery incision, or radial incision and cutting (RIC) were preferred because of lower complication rates than surgery and are less invasive. Endoscopic RIC has a greater success rate than dilation methods. Most reports showed that repeated RICs were needed to maintain patency of the anastomosis. We report that single session RIC was applied only to treatment-naive patients with AS. CASE SUMMARY Two female patients presented with AS. One patient had advanced rectal cancer and the other had a refractory stenosis following surgery for endometriosis at sigmoid colon. The endoscopic RIC procedure was performed as follows. A single small incision was carefully made to increase the view of the proximal colon and the incision was expanded until the surgical stapling line. Finally, we made a further circumferential excision with endoscopic knife along the inner border of the surgical staple line. At the end of the procedure, the standard colonoscope was able to pass freely through the widened opening. All patients showed improved AS after a single session of RIC without immediate or delayed procedure-related complications. Follow-up colonoscopy at 7 and 8 mo after endoscopic RIC revealed intact anastomotic sites in both patients. No treatment-related adverse events or recurrence of the stenosis was demonstrated during follow-up periods of 20 and 23 mo. CONCLUSION The endoscopic RIC may play a role as one of treatment options for treatment-naive AS with short stenotic lengths.

Objectives To investigate the value of contrast-enhanced (CE) turbo spin echo black blood (BB) sequences for imaging of therapy-naive high-grade gliomas (HGGs). Methods Consecutive patients with histopathologically confirmed World Health Organization (WHO) grade III or IV gliomas and no oncological treatment prior to index imaging (March 2019 to January 2020) were retrospectively included. Magnetic resonance imaging (MRI) at 3 Tesla comprised CE BB and CE turbo field echo (TFE) sequences. The lack/presence of tumor-related contrast enhancement and satellite lesions were evaluated by two readers. Sharper delineation of tumor boundaries (1, bad; 2, intermediate; 3, good delineation) and vaster expansion of HGGs into the adjacent brain parenchyma on CE BB imaging were the endpoints. Furthermore, contrast-to-noise ratios (CNRs) were calculated and compared between sequences. Results Fifty-four patients were included (mean age: 61.2 ± 15.9 years, 64% male). The vast majority of HGGs (51/54) showed contrast enhancement in both sequences, while two HGGs as well as one of six detected satellite lesions were depicted in CE BB imaging only. Tumor boundaries were significantly sharper (R1: 2.43 ± 0.71 vs. 2.73 ± 0.62, p p = 0.001), while the spread of HGGs into the adjacent parenchyma was larger when considering CE BB sequences according to both readers (larger spread in CE BB sequences: R1: 23 patients; R2: 20 patients). The CNR for CE BB sequences significantly exceeded that of CE TFE sequences (43.4 ± 27.1 vs. 32.5 ± 25.0, p = 0.0028). Conclusions Our findings suggest that BB imaging may considerably improve delineation of therapy-naive HGGs when compared with established TFE imaging. Thus, CE BB sequences might supplement MRI protocols for brain tumors. Key Points • This study investigated contrast-enhanced (CE) T1-weighted black blood (BB) sequences for improved MRI in patients with therapy-naive high-grade gliomas (HGGs). • Compared with conventionally used turbo field echo (TFE) sequences, CE BB sequences depicted tumor boundaries and spread of HGGs into adjacent parenchyma considerably better, which also showed higher CNRs. • Two enhancing tumor masses and one satellite lesion were exclusively identified in CE BB sequences, but remained undetected in conventionally used CE TFE sequences.

We report two treatment-naïve cases, a 26-year-old female patient and a 59-year-old male patient who were followed up for chronic hepatitis B (CHB) at the Department of Infectious Diseases and Clinical Microbiology. A partial response subsequent to 12 months of Tenofovir Disoproksil (TDF) monotherapy presumably due to an antiviral-drug resistance was noted. A sustained viral response with TDF (245 mg) or Tenofovir Alafenamide (TAF, 25 mg) + Entecavir (ETV, 1 mg) combination therapy was observed after failure with TDF monotherapy. A combination therapy with TDF (245 mg) or TAF (25 mg) +ETV (1 mg) is efficacious in naïve patients with a partial response to TDF monotherapy. Keywords: Chronic hepatitis B, Tenofovir, partial response, Entecavir, combination therapy

Higher tumor mutational burden (TMB) has been correlated with response to checkpoint blockade immunotherapy. However, it is unclear whether TMB independently serves as a prognostic biomarker for outcomes in immunotherapy-naïve patients. Here, we evaluated the relationship between TMB and overall survival in 1,415 immunotherapy-naïve patients with diverse advanced malignancies. TMB was studied both as a tiered variable (low ≤5 mutations/Mb, intermediate >5 and

Polypoidal choroidal vasculopathy (PCV) is a common choroidal vascular disease particularly in Asians. However, the underlying pathogenesis of PCV is still yet to be fully elucidated, and the correlation between choroidal vasculature and treatment response of PCV are poorly understood. Accordingly, we sought to find clues to understand the pathogenesis and prognosis of PCV by quantitatively evaluating choroidal vasculature from the entire fundus using ultra-widefield (UWF) indocyanine green angiography (ICGA). In this study, 32 eyes from 29 patients with treatment naïve PCV and 30 eyes from 30 healthy control participants were enrolled. Choroidal vascular density (CVD) of PCV eyes was higher than normal eyes in majority regions including the periphery. CVD was positively correlated with choroidal thickness and choroidal hyperpermeability, supporting that the pathogenesis of PCV may include choroidal congestion and dilatation. Thicker choroid and higher CVD were also correlated with poor treatment response after anti-VEGF injections. The CVD, quantified from UWF ICGA can also be used as an effective image biomarker to predict the treatment response in PCV.

Patients often rely on the advice of their general practitioner (GP) to decide which treatment best fits their needs. Hospitals, in turn, might influence GPs’ referral decision through kickbacks. We present a model with a monopolistic hospital and competitive GPs who vary in the degree of altruism towards their heterogeneous patients and show that an equilibrium without crowding out exists that separates GPs into referrers and care providers. Naïve patients visit purely selfish (referring) GPs, while rational patients sort themselves between the two groups of GPs. Finally, we investigate the scope for regulation, including an optimal coinsurance rate.

Background/AimsTo investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME).MethodsRetrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C).ResultsThe mean 2-year improvement of BCVA was −0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was −0.09±0.39, –0.02±0.40 and −0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively.ConclusionFollowing 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.

Purpose Compare treatment switching rates and costs among biologic-naive psoriasis patients initiating apremilast or biologics. Methods This retrospective claims analysis used IBM MarketScan Commercial and Medicare Supplemental databases to identify patients who initiated apremilast or a biologic (ie, tumor necrosis factor [TNF] or interleukin [IL] inhibitor) for psoriasis treatment between January 1, 2015, and December 31, 2016. A 1:1 propensity score matching was used to adjust for possible selection bias and maximize the number of patients available for analysis. Treatment switching, days to switch, and healthcare costs were assessed at 12 months. T-test and chi-square test were used to evaluate differences between cohorts for continuous and categorical variables as appropriate; Wilcoxon rank-sum tests were used to assess cost differences. Results In total, 88,025 patients newly initiated apremilast, a TNF inhibitor, or an IL inhibitor. After inclusion/exclusion criteria were applied and patients were propensity score matched, 1645 (apremilast), 1207 (TNF inhibitor), and 438 (IL inhibitor) patients were included in this analysis. Twelve-month switch rates were significantly lower for apremilast initiators compared with TNF inhibitor initiators (14% vs 25%; p 0.05). No statistical difference was observed in days to switch at 12 months for any treatment group. Total healthcare costs were lower for apremilast initiators compared with TNF and IL inhibitor initiators ($34,028 vs $55,973 and $64,430; p

Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides include granulomatosis with polyangiitis (GPA, previously called Wegener's), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss). In this report we used mycophenolate mofetil (MMF) and steroids to induce and maintain remission in two newly diagnosed cases with c-ANCA associated GPA. The two patients' maintained remission with no disease relapses during one year follow-up.Copyright © 2018 Sociedad Espanola de Reumatologia y Colegio Mexicano de Reumatologia. Publicado por Elsevier Espana, S.L.U. All rights reserved.

Eliglustat is a first‐line oral therapy for adults with Gaucher disease type 1 (GD1) with extensive, intermediate, or poor CYP2D6‐metabolizer phenotypes (90% of patients). We report real‐world outcomes after 2 years of eliglustat therapy in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943). As of January 2019, baseline and 2‐year data (±1 year) were available for 231 eliglustat‐treated GD1 patients: 19 treatment‐naïve (zero splenectomized) and 212 ERT patients who switched to eliglustat (36 splenectomized). Most patients (89%) were from the United States, where eliglustat was first approved. In treatment‐naïve patients, mean hemoglobin increased from 12.4 to 13.4 g/dL (P = .004, n = 18), mean platelet count increased from 113 to 156 × 109/L (P