Search

A 75-year-old Caucasian woman presented with sudden-onset multifocal scotomas in her right eye's central vision for 1 day. There were subtle white intraretinal foveal lesions that correlated with patchy inner retinal hyperreflectivity on optical coherence tomography, suggestive of paracentral acute middle maculopathy. Initial cerebrovascular work-up was negative. Review of systems was positive for lethargy and jaw claudication. The sedimentation rate and c-reactive protein were elevated, but platelet count was normal. The patient was started on 60 mg oral prednisone daily and underwent bilateral temporal artery that confirmed the diagnosis of giant cell arteritis.

1) To report minimum 2- and 5-year outcomes of high-level athletes who did not return to sport (RTS) after hip arthroscopy for reasons unrelated to their hip (T athletes) and 2) to benchmark these findings against a propensity-matched control group of high-level athletes who returned to sport (RTS athletes).Data were prospectively collected and retrospectively reviewed for professional, collegiate, and high school athletes between April 2008 and October 2015, who underwent primary hip arthroscopy. Athletes were considered eligible if they did not return to sport for reasons unrelated to their hip such as loss of interest, graduation, or a lifestyle transition (T athletes). Inclusion criteria were preoperative and minimum 5-year postoperative patient-reported outcomes (PROs) for the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score-Sports Specific Subscale (HOS-SSS), and the visual analog scale (VAS) for pain. Clinical outcomes were assessed using the minimal clinically important difference (MCID) and maximum outcome improvement satisfaction threshold (MOIST). T athletes were then propensity-matched to a control group of high-level athletes who returned to sport after hip arthroscopy (RTS athletes) for comparison.Twenty-seven T hips (25 patients) were included in the analysis with a mean follow-up time of 38.9 ± 16.8 and 72.1 ± 16.8 months for minimum 2- and 5-year outcomes, respectively. They demonstrated significant improvement in all measured PROs. When compared to a propensity-matched control group of RTS athletes, T athletes demonstrated similar improvement in PROs (mHHS, NAHS, and HOS-SSS) and achieved MCID at similar rates for NAHS (T: 77.8% vs RTS: 68.8%; P = .570) and HOS-SSS (T: 70.3% vs RTS: 76.6%, P = .824) compared to RTS athletes; however T athletes demonstrated higher rates of achieving MCID for mHHS (T: 88.9% vs RTS: 72.9% P = .033).Athletes who did not return to sport for reasons unrelated to their hip demonstrated favorable outcomes at minimum 2- and 5-year follow-up. They had similar PROs and rates of achieving MCID for HOS-SSS compared to a propensity-matched control group of high-level athletes who returned to sport. Return to sport status may not necessarily be correlated to the patient's perception of their own outcome.III, retrospective cohort study.

Background The ideal cardiac risk stratification strategy for orthotopic liver transplantation (OLT) is unknown. Our institution performed coronary angiography for asymptomatic OLT candidates at high risk for CAD : ≥65 years of age, diabetic and ≥55 years of age or diagnosed ≥5 years, abnormal stress test, or at the discretion of the OLT committee. Methods The analysis included 301 consecutive, asymptomatic OLT candidates who underwent coronary angiography. The primary outcome was the prevalence of obstructive CAD. Results At 2-year follow-up, OLT was performed in 44.9%, and 42.2% died. The prevalence of obstructive CAD, involvement of the proximal or mid LAD, and 3-vessel CAD were 10.3%, 6.6%, and 0.7%, respectively. Percutaneous and surgical revascularization were performed in 7.0% and 1.3%, respectively. Stress test was performed in 54.8%. The sensitivity and specificity of stress testing were 0% and 87.1%, respectively. The negative and positive predictive values of stress testing were 91.4% and 0%, respectively. Chest computed tomography (CT) was performed in 83.1%. Moderate or severe coronary artery calcification (CAC) was present in 47.8%. The sensitivity and specificity of moderate or severe CAC were 88.9% and 57.3%, respectively. The negative and positive predictive values of moderate or severe CAC were 97.7% and 20.2%, respectively. Multivariate analysis demonstrated that CAC was an independent predictor of obstructive CAD (HR 10.7; 95% CI 3.2–37.9; p Conclusions The prevalence of obstructive CAD in asymptomatic OLT candidates at high risk was uncommon. Alternative diagnostic strategies may be preferred to coronary angiography.

Predictors of outcomes in adolescent athletes undergoing hip arthroscopy have not been established. The purpose of this study was to identify factors correlated with achieving the Patient Acceptable Symptomatic State (PASS) for the Hip Outcome Score-Sports Specific Subscale (HOS-SSS) at a minimum 5-year follow-up in adolescent athletes undergoing primary hip arthroscopy.Data were reviewed on adolescent (below 18 y old) athletes who underwent primary hip arthroscopy for femoroacetabular impingement syndrome between March 2008 and October 2015. Patients were included if they participated in sport within 1 year before surgery and had preoperative, 2-year, and minimum 5-year postoperative patient-reported outcome (PRO) scores for the modified Harris Hip Score, HOS-SSS, Visual Analog Scale for pain (VAS), and Non-Arthritic Hip Score (NAHS). Patients were divided into 2 groups based on whether they achieved PASS for HOS-SSS. Demographics, intraoperative findings, radiographic variables, surgical treatments, and PRO were compared. Multivariate logistic regression with corresponding odds ratios (ORs) quantified the correlation between variables and achievement of the PASS.A total of 123 athletes with a mean age of 16.2±1.1 years were included. These athletes demonstrated significant imrpovement from preoperative to minimum 5-year follow-up for all recorded PROs (P0.001). The multivariate logistic regression model identified preoperative NAHS (P=0.019, OR: 1.033), 2-year postoperative HOS-SSS (P=0.014, OR: 1.037), and 2-year postoperative VAS (P=0.003, OR: 0.590) as statistically significantly correlated with achieving the PASS. Athletes with a 2-year postoperative VAS pain score ≤2 achieved PASS at a rate of 81.9%, while those with a score2 achieved PASS at a rate of 24.1% (P0.001, OR: 14.2, 95% confidence interval: 5.23-38.7).Favorable outcome were achieved at mid-term follow-up in adolescent athletes undergoing primary hip arthroscopy. Preoperative NAHS, 2-year postoperative HOS-SSS, and 2-year postoperative VAS pain scores were correlated with achieving the PASS for HOS-SSS at a minimum 5-year follow-up. Patients with 2-year postoperative VAS ≤2 were significantly more likely to achieve the PASS at 5-year follow-up than those with scores2.Level III-case-control study.

Background The ideal drug-eluting stent (DES) for the treatment of unprotected left main coronary artery (ULMCA) is unknown. We compared percutaneous coronary intervention (PCI) using durable polymers versus early-generation, thicker strutted and coated bioabsorbable polymers for ULMCA disease. Methods Patients who underwent ULMCA PCI (893 patients) from April 2008 to November 2014 were identified from the Grand-DES registry. The primary end point was 3-year target lesion failure (TLF) after propensity score matching. Results The final analysis included 754 patients (84.4%) and 139 patients (15.6%) in the durable and bioabsorbable polymer group, respectively. The groups differed significantly in lesion and procedural characteristics. Propensity score-matched analysis revealed a trend toward a lower 3-year TLF in the durable polymer group (log rank p=0.071). Independent predictors of 3-year TLF were chronic kidney disease, presentation with acute myocardial infarction, and a two-stenting technique for ULMCA lesions. Definite/probable stent thrombosis rates at 3-years were low in both groups (0.8% vs. 0.7%, p=0.925). Conclusions The safety of ULCMA PCI was excellent, and durable and bioabsorbable polymer DES provided similar clinical outcomes at 3-year follow-up. Landmark analysis revealed that the durable polymer group had a lower TLF rate from 9 months. Further studies are needed to confirm these results.

A healthy 7-year-old girl underwent a routine eye examination and was referred for unilateral, left optic nerve swelling. Best-corrected visual acuity in the affected eye was 20/20 with full Ishihara color plates and no relative afferent pupillary defect. Initial extensive workup was normal for any cause of unilateral disk swelling. When the patient returned a few years later with decreased vision, a thickened, gray-white preretinal tissue with surrounding retinal contraction and a surrounding charcoal gray lesion had developed in her optic nerve. Spectral-domain optical coherence tomography over the optic nerve demonstrated distortion of the inner retinal architecture, a dense epiretinal membrane, and high internal reflectivity. Clinical examination and imaging revealed a diagnosis of combined hamartoma of the retina and retinal pigment epithelium.

Objectives The safety and efficacy of an initial intravenous bolus of low-dose heparin (40 IU/kg) was evaluated in biomarker negative patients undergoing percutaneous coronary intervention (PCI). Background A bolus of 70–100 IU/kg of heparin is currently recommended for patients undergoing PCI. However, the ideal dose of heparin has not been evaluated in a randomized trial. The higher dose of 100 IU/kg may increase the risk of bleeding. An initial bolus of low-dose heparin may be advantageous to avoid supratherapeutic activating clotting times (ACT) while still allowing for the administration of additional heparin if the ACT is subtherapeutic. Methods From January 2008 to February 2020, 904 patients undergoing elective transfemoral PCI received an initial bolus of 40 IU/kg of heparin. Patients who underwent transradial PCI were not included. Patients were routinely pretreated with dual antiplatelet therapy. The primary end point was the composite of cardiac death, myocardial infarction (MI), urgent target vessel revascularization (TVR) for ischemia, or major bleeding within 30 days after PCI. Results The initial mean activating clotting time was 235.4 ± 26.6 s. The clinical event rates were low: the primary end point occurred in 5.3%, cardiac death in 1.0%, MI in 3.1%, urgent TVR in 0.7% and major bleeding in 1.9%. Stent thrombosis was uncommon (0.2%). No patients developed profound thrombocytopenia. Three patients (0.3%) had acute limb ischemia that required revascularization. Conclusion An initial strategy of low-dose heparin is associated with low ischemic and bleeding complications in biomarker negative patients who undergo transfemoral PCI.

Purpose: The COMBO biodegradable polymer sirolimus-eluting stent includes endothelial progenitor cell capture (EPC) technology for rapid endothelialization, which may offer advantage in acute coronary syndromes (ACS). We sought to analyze the performance of the COMBO stent by ACS status and ACS subtype. Methods: The COMBO collaboration (n = 3614) is a patient-level pooled dataset from the MASCOT and REMEDEE registries. We evaluated outcomes by ACS status, and ACS subtype in patients with ST segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) versus unstable angina (UA). The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Secondary outcomes included stent thrombosis (ST). Results: We compared 1965 (54%) ACS and 1649 (46.0%) non-ACS patients. ACS presentations included 40% (n = 789) STEMI, 31% (n = 600) NSTEMI, and 29% (n = 576) UA patients. Risk of 1-year TLF was greater in ACS patients (4.5% vs. 3.3%, HR 1.51 95% CI 1.01–2.25, p = 0.045) without significant differences in definite/probable ST (1.1% vs 0.5%, HR 2.40, 95% CI 0.91–6.31, p = 0.08). One-year TLF was similar in STEMI, NSTEMI, and UA (4.8% vs 4.8% vs. 3.7%, p = 0.60), but definite/probable ST was higher in STEMI patients (1.9% vs 0.5% vs 0.7%, p = 0.03). Adjusted outcomes were not different in MI versus UA patients. Conclusions: Despite the novel EPC capture technology, COMBO stent PCI was associated with somewhat greater risk of 1-year TLF in ACS than in non-ACS patients, without significant differences in stent thrombosis. No differences were observed in 1-year TLF among ACS subtypes.

The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplastic cells1,2. STING is also a robust driver of antitumour immunity, which has led to the development of STING activators and small-molecule agonists as adjuvants for cancer immunotherapy3. Pain, transmitted by peripheral nociceptive sensory neurons (nociceptors), also aids in host defence by alerting organisms to the presence of potentially damaging stimuli, including pathogens and cancer cells4,5. Here we demonstrate that STING is a critical regulator of nociception through IFN-I signalling in peripheral nociceptors. We show that mice lacking STING or IFN-I signalling exhibit hypersensitivity to nociceptive stimuli and heightened nociceptor excitability. Conversely, intrathecal activation of STING produces robust antinociception in mice and non-human primates. STING-mediated antinociception is governed by IFN-Is, which rapidly suppress excitability of mouse, monkey and human nociceptors. Our findings establish the STING-IFN-I signalling axis as a critical regulator of physiological nociception and a promising new target for treating chronic pain.

An 84-year-old female presented with bilateral scotomas and progressive nyctalopia over 1 year. Best-corrected visual acuity was 20/50 in both eyes with reduced color vision. Goldmann visual field showed bilateral cecocentral scotomas and generalized constriction of the visual fields. This led to an electroretinogram showing an electronegative pattern consistent with autoimmune retinopathies. Infectious workup was negative. Anti-retinal antibodies were positive, leading to a presumed diagnosis of cancer-associated retinopathy (CAR). Imaging showed a previously unknown left renal lower pole mass, and she underwent a radical nephrectomy. Biopsy showed nuclear grade-3 clear cell renal carcinoma staged T1. The patient was treated with oral prednisone with no ocular improvement. We report on a rare case of clear cell renal carcinoma causing CAR. CAR is an important paraneoplastic syndrome to diagnose since the majority of ocular cases precede other manifestations of malignancy. Therefore, a timely diagnosis of CAR can be lifesaving or at least life-extending.

Calcified coronary lesions are notorious for posing technical difficulty during angioplasty. Fortunately, more devices are available to tackle coronary calcifications. However, there remain difficult cases whereby a single modality is insufficient. Here we report the feasibility and success of a case, using Novo combination of Shockwave Lithotripsy after Orbital Atherectomy. (Level of Difficulty: Intermediate.), Graphical abstract

Regorafenib is a tyrosine kinase inhibitor approved by the FDA for the treatment of patients with chemotherapy refractory metastatic colorectal cancer (mCRC). Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasis, and tumor immunity. Here, we report biomarker results from LCCC1029, a randomized, placebo-controlled, phase II trial of chemotherapy ± regorafenib in patients with second-line mCRC. A panel of 20 soluble protein biomarkers (termed the Angiome) was assessed in the plasma of 149 patients from the LCCC1029 trial both at baseline and along the treatment continuum. Baseline protein levels were analyzed for prognostic and predictive value for progression-free survival (PFS) and overall survival (OS). Changes in protein levels during treatment were analyzed for potential pharmacodynamic effects. Six markers (HGF, IL6, PlGF, VEGF-R1, OPN, and IL6R) were found to be prognostic for PFS. Nine markers (IL6, TIMP-1, PlGF, VCAM-1, ICAM-1, OPN, TSP-2, HGF, and VEGF-R1) were prognostic for OS. Higher baseline levels of OPN (Pintx = 0.0167), VCAM-1 (Pintx = 0.0216), and PDGF-AA (Pintx = 0.0435) appeared to predict for PFS benefit from regorafenib compared with placebo. VCAM-1 was also potentially predictive of OS benefit from regorafenib compared with placebo (Pintx = 0.0124). On-treatment changes of six markers reflected potential on-target effect of regorafenib. Consistent results were observed in an Italian cohort where 105 patients with late-stage mCRC received regorafenib monotherapy. The key findings of this study suggest that VCAM-1 may be a predictive biomarker for regorafenib benefit, while multiple protein markers may be prognostic of outcome in patients with mCRC.

Purpose Claudin-low molecular subtypes have been identified in breast and bladder cancers and are characterized by low expression of claudins, enrichment for epithelial-to-mesenchymal transition (EMT), and tumor-initiating cell (TIC) features. We evaluated whether the claudin-low subtype also exists in gastric cancer. Materials and Methods Four hundred fifteen tumors from The Cancer Genome Atlas (TCGA) gastric cancer mRNA data set were clustered on the claudin, EMT, and TIC gene sets to identify claudin-low tumors. We derived a 24-gene predictor that classifies gastric cancer into claudin-low and non–claudin-low subtypes. This predictor was validated with the Asian Cancer Research Group (ACRG) data set. We characterized molecular and clinical features of claudin-low tumors. Results We identified 46 tumors that had consensus enrichment for claudin-low features in TCGA data set. Claudin-low tumors were most commonly diffuse histologic type (82%) and originally classified as TCGA genomically stable (GS) subtype (78%). Compared with GS subtype, claudin-low subtype had significant activation in Rho family of GTPases signaling, which appears to play a key role in its EMT and TIC properties. In the ACRG data set, 28 of 300 samples were classified as claudin-low tumors by the 24-gene predictor and were phenotypically similar to the initially derived claudin-low tumors. Clinically, claudin-low subtype had the worst overall survival. Of note, the hazard ratios that compared claudin-low versus GS subtype were 2.10 (95% CI, 1.07 to 4.11) in TCGA and 2.32 (95% CI, 1.18 to 4.55) in the ACRG cohorts, with adjustment for age and pathologic stage. Conclusion We identified a gastric claudin-low subtype that carries a poor prognosis likely related to therapeutic resistance as a result of its EMT and TIC phenotypes.

Objective:To determine the percentage of the healthy population that responds asymmetrically to the red desaturation test, and to approximate the degree of red desaturation in those individuals. We also sought to elucidate any correlation between demographic variables and red desaturation prevalence and severity.Methods:Adults aged 18 and older with a normal eye exam, including confrontation fields and best-corrected visual acuity of ≥ 20/25 OU, were eligible for this prevalence study. Those with objective or subjective afferent visual dysfunction were excluded. A total of 101 eligible participants (31.7% male; 77.2% white race; mean (SD) age: 41.5 (15.3) years) were queried whether monocular perception of redness of a standardized tropicamide bottle cap was the same and to estimate the interocular percentage difference, with one eye perceiving the bottle cap at “100% redness.”Results:Twenty-four participants (23.8%) experienced some degree of red desaturation. For these individuals with red desaturation, the average interocular difference was 9.0% (range 2-25%, 95% CI: 6.0-12.0%). There was no statistical evidence for a relationship between red desaturation and race, sex, or age.Conclusion:This study shows that nearly a quarter of healthy patients without apparent optic nerve or macular dysfunction may recognize red desaturation. This deserves consideration when interpreting red desaturation testing in patients suspected to have unilateral optic neuropathy. Further research with larger sample sizes may identify predictors of red desaturation in healthy patients, establish the red desaturation threshold separating pathologic from physiologic phenomena, and assess the repeatability of red desaturation over time in affected individuals.

Purpose of review Eye pain is one of the most common presenting symptoms in ophthalmology. It can range from bothersome to debilitating for patients, and it can be vexing for clinicians, especially in the white and quiet eye. The purpose of this review is to provide updates of recent literature regarding eye pain and to communicate our current understanding regarding the evaluation and management of conditions that cause eye pain with a relatively normal examination. Recent findings This review concerns recent literature regarding eye pain in the white and quiet eye. It is arranged by cause of pain and discusses dry eye syndrome, recurrent corneal erosion, postrefractive surgical pain, eye strain, intermittent angle closure, benign essential blepharospasm, trochleodynia, trochleitis and trochlear headache, and posterior scleritis. Summary Eye pain in the white and quiet eye remains a difficult-to-navigate topic for practitioners. However, a careful history and focused physical examination can elucidate the diagnosis in many cases. Recent updates to the literature have advanced our knowledge of how to identify and treat the underlying causes of eye pain.

Older patients who undergo coronary interventions are at greater risk of ischemic events and less likely to tolerate prolonged dual antiplatelet therapy (DAPT) due to bleeding risk. The COMBO biodegradable polymer sirolimus-eluting stent promotes rapid endothelialization through endothelial progenitor cell capture technology which may be advantageous in elderly patients. We compared 1-year clinical outcomes and DAPT cessation events in patients >75 versus ≤75 years from the MASCOT registry. MASCOT was a prospective, multicenter cohort study of all-comers undergoing attempted COMBO stenting. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a nontarget vessel or clinically driven target lesion revascularization. Bleeding was adjudicated using the Bleeding Academic Research Consortium criteria. Adjusted outcomes were analyzed using Cox regression methods. The study included 18% (n = 479) patients >75 years and 72% (n = 2,135) patients ≤75 years. One-year TLF occurred in 4.6% patients >75 years versus 3.1% patients ≤75years of age, p = 0.10; adj hazard ratio 1.36, 95% confidence intervals 0.77 to 2.38, p = 0.29. There were no significant differences in cardiac death (1.7% vs 1.3%, p = 0.55), MI (2.1% vs 1.2%, p = 0.14), target lesion revascularization (1.7% vs 1.4%, p = 0.60) and definite stent thrombosis (0.8% vs 0.4%, p = 0.19). Major Bleeding Academic Research Consortium 3,5 bleeding (3.1% vs 1.5%, p = 0.01) and DAPT cessation rates (32.4% vs 23.0%, p 75 years treated with COMBO stents had similar TLF but significantly greater incidence of bleeding than younger patients and DAPT cessation in one-third of patients over 1 year.

Summary Background Dual blockade of PD-L1 and VEGF has enhanced anticancer immunity through multiple mechanisms and augmented antitumour activity in multiple malignancies. We aimed to assess the efficacy and safety of atezolizumab (anti-PD-L1) alone and combined with bevacizumab (anti-VEGF) in patients with unresectable hepatocellular carcinoma. Methods GO30140 is an open-label, multicentre, multiarm, phase 1b study that enrolled patients at 26 academic centres and community oncology practices in seven countries worldwide. The study included five cohorts, and the two hepatocellular carcinoma cohorts, groups A and F, are described here. Inclusion criteria for these two groups included age 18 years and older; histologically, cytologically, or clinically (per American Association for the Study of Liver Diseases criteria) confirmed unresectable hepatocellular carcinoma that was not amenable to curative treatment; no previous systemic treatment; and Eastern Cooperative Oncology Group performance status of 0 or 1. In group A, all patients received atezolizumab (1200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks. In group F, patients were randomly assigned (1:1) to receive intravenous atezolizumab (1200 mg) plus intravenous bevacizumab (15 mg/kg) every 3 weeks or atezolizumab alone by interactive voice-web response system using permuted block randomisation (block size of two) and stratification factors of geographical region; macrovascular invasion, extrahepatic spread, or both; and baseline α-fetoprotein concentration. Primary endpoints were confirmed objective response rate in all patients who received the combination treatment for group A and progression-free survival in the intention-to-treat population in group F, both assessed by an independent review facility according to Response Evaluation Criteria in Solid Tumors version 1.1. In both groups, safety was assessed in all patients who received at least one dose of any study treatment. This study is registered with ClinicalTrials.gov , NCT02715531 , and is closed to enrolment. Findings In group A, 104 patients were enrolled between July 20, 2016, and July 31, 2018, and received atezolizumab plus bevacizumab. With a median follow-up of 12·4 months (IQR 8·0–16·2), 37 (36%; 95% CI 26–46) of 104 patients had a confirmed objective response. The most common grade 3–4 treatment-related adverse events were hypertension (13 [13%]) and proteinuria (seven [7%]). Treatment-related serious adverse events occurred in 25 (24%) patients and treatment-related deaths in three (3%) patients (abnormal hepatic function, hepatic cirrhosis, and pneumonitis). In group F, 119 patients were enrolled and randomly assigned (60 to atezolizumab plus bevacizumab; 59 to atezolizumab monotherapy) between May 18, 2018, and March 7, 2019. With a median follow-up of 6·6 months (IQR 5·5–8·5) for the atezolizumab plus bevacizumab group and 6·7 months (4·2–8·2) for the atezolizumab monotherapy group, median progression-free survival was 5·6 months (95% CI 3·6–7·4) versus 3·4 months (1·9–5·2; hazard ratio 0·55; 80% CI 0·40–0·74; p=0·011). The most common grade 3–4 treatment-related adverse events in group F were hypertension (in three [5%] patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group) and proteinuria (in two [3%] patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group). Treatment-related serious adverse events occurred in seven (12%) patients in the atezolizumab plus bevacizumab group and two (3%) patients in the atezolizumab monotherapy group. There were no treatment-related deaths. Interpretation Our study shows longer progression-free survival with a combination of atezolizumab plus bevacizumab than with atezolizumab alone in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy. Therefore, atezolizumab plus bevacizumab might become a promising treatment option for these patients. This combination is being compared with standard-of-care sorafenib in a phase 3 trial. Funding F Hoffmann-La Roche/Genentech.

Background The COMBO drug-eluting stent combines sirolimus-elution from a biodegradable polymer with an anti-CD34+ antibody coating for early endothelialization. Objective We investigated for geographical differences in outcomes after percutaneous coronary intervention (PCI) with the COMBO stent among Asians and Europeans. Methods The COMBO Collaboration is a pooled patient-level analysis of the MASCOT and REMEDEE registries of all-comers undergoing attempted COMBO stent PCI. The primary outcome was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR). Results This study included 604 Asians (17.9%) and 2775 Europeans (82.1%). Asians were younger and included fewer females, with a higher prevalence of diabetes mellitus but lower prevalence of other comorbidities than Europeans. Asians had a higher prevalence of ACC/AHA C type lesions and received longer stent lengths. More Asians than Europeans were discharged on clopidogrel (86.5% vs 62.8%) rather than potent P2Y12 inhibitors. One-year TLF occurred in 4.0% Asians and 4.1% of Europeans, p = 0.93. The incidence of cardiac death was higher in Asians (2.8% vs. 1.3%, p = 0.007) with similar rates of TV-MI (1.5% vs. 1.2%, p = 0.54) and definite stent thrombosis (0.3% vs. 0.5%, p = 0.84) and lower incidence of TLR than Europeans (1.0% vs. 2.5%, p = 0.025). After adjustment, differences for cardiac death and TLR were no longer significant. Conclusions In the COMBO collaboration, although 1-year TLF was similar regardless of geography, Asians experienced higher rates of cardiac death and lower TLR than Europeans, while incidence of TV-MI and ST was similar in both regions. Adjusted differences did not reach statistical significance. Clinicaltrial.gov identifier-numbers NCT01874002 (REMEDEE Registry), NCT02183454 (MASCOT registry).

Schizophrenia is a complex disorder that is diagnosed mainly with clinical observation and evaluation. Recent studies suggest that many people with schizophrenia have abnormalities in the function of the N-methyl- d -aspartate receptor (NMDAR). The retina is part of the central nervous system and expresses the NMDAR, raising the possibility of the early detection of NMDAR-related schizophrenia by detecting differences in retinal function. As a first-step, we used two non-invasive outpatient tests of retinal function, the photopic negative response (PhNR) of the light-adapted flash-electroretinogram (PhNR-fERG) and the pattern ERG (PERG), to test individuals with schizophrenia and controls to determine if there were measurable differences between the two populations. The PhNR-fERG showed that males with schizophrenia had a significant increase in the variability of the overall response, which was not seen in the females with schizophrenia. Additionally at the brightest flash strength, there were significant increases in the PhNR amplitude in people with schizophrenia that were maximal in controls. Our results show measurable dysfunction of retinal ganglion cells (RGCs) in schizophrenia using the PhNR-fERG, with a good deal of variability in the retinal responses of people with schizophrenia. The PhNR-fERG holds promise as a method to identify individuals more at risk for developing schizophrenia, and may help understand heterogeneity in etiology and response to treatment.

Purpose of review Ocular myasthenia gravis (OMG) is a complex condition with heterogenous phenotypes and ill-defined diagnostic criteria. Understanding concomitant risk factors and autoimmune serology can help inform prognosis for generalization and guide treatment. Recent findings Although antibodies to acetylcholine receptors or muscle-specific kinase likely increase risk of generalization, they are less frequent in OMG. Patients without either antibody tend to have a milder disease process and often have variable antibodies to other end-plate proteins such as LRP4, agrin, or cortactin. The treatment of OMG begins with pyridostigmine and is supplemented by oral prednisone if treatment-resistant or high risk for generalization. Variable oral prednisone regimens have been used with success and further immunosuppression may be best achieved with mycophenolate mofetil and azathioprine. Checkpoint inhibitor-induced myasthenia gravis is increasingly recognized and likely has high rates of mortality associated with myocarditis. Summary Our understanding of OMG and its variable phenotypes continues to evolve. Autoantibody testing increasingly provides valuable diagnostic and prognostic information. Despite these improvements, a lack of quality treatment trials creates significant challenges for evidence-based management guidelines.

Endovascular therapy is a viable treatment option for symptomatic peripheral artery disease (PAD). Diabetes mellitus is a major risk factor for PAD. We evaluated the long-term impact of diabetes mellitus in patients with PAD who underwent endovascular therapy. In this prospective registry of 765 patients who underwent endovascular therapy for symptomatic PAD, 560 had diabetes and 205 did not have diabetes. Propensity score matching (PSM) analysis was performed to adjust for any potential confounders. The primary endpoints were 5-year major adverse cardiac and cerebrovascular events (MACE) and major adverse limb events (MALE). After PSM analysis, baseline clinical and limb characteristics were similar in patients with diabetes and in patients without diabetes. Patients with diabetes had a higher rate of major hematoma (> 4 cm) (9.9% vs 3.3%, p = 0.038). At 5-year clinical follow-up, patients with diabetes and patients without diabetes had similar rates of MACE (20.7% vs 20.7%, log rank p = 0.989) and MALE (19.8% vs 24.5%, log rank p = 0.312), as well as the individual endpoints. In subgroup analysis adjusted by PSM, female patients with diabetes had a higher risk of MALE (hazard ratio 0.31, 95% CI 0.13–0.69, p = 0.004). Although there was a higher rate of major hematoma, patients with diabetes who underwent endovascular therapy had similar 5-year cardiac and vascular outcomes compared with patients without diabetes. Bleeding avoidance strategies, including optimal antiplatelet and antithrombotic therapy, and meticulous vascular access techniques, are needed in patients with diabetes to reduce the risk of bleeding and its deleterious impact on morbidity and mortality.

Typical optic neuritis is an idiopathic demyelinating condition that is often associated with multiple sclerosis. This has been well characterized and has an excellent prognosis. Atypical optic neuritis can result from an inflammatory, infectious, or autoimmune disorder. Differentiating the two types of optic neuritis is paramount and may be challenging early on in the clinical course. This review describes the recent literature describing the pathophysiology, clinical presentation, neuroimaging, and management of these disorders.

We sought to determine effect of signal strength on mean retinal nerve fibre layer (RNFL) using Spectralis optical coherence tomography (S-OCT). Thirty normal subjects (18 female, mean 37.9 years, range 24-61) were imaged with S-OCT using variably dense Bangerter foils to alter Q value (1 unit signal strength = 4 units Q). We found a statistically significant (p < 0.01) linear relationship (R = 0.8643) between Q and RNFL (1 unit decrease Q = 0.181 um mean RNFL increase). Unlike previous observations of Cirrus and Stratus OCT, we found RNFL thickness does not decrease with decreasing signal strength in S-OCT.

Background The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy are noninferior to 6 months. Our study objectives were to characterize medical oncologists’ perspectives toward the results of the IDEA collaboration and to evaluate how IDEA impacted prescribing patterns of adjuvant FOLFOX and CAPOX in colon cancer. Materials and Methods A list of questions developed by four medical oncologists regarding IDEA results were formulated and distributed online to gastrointestinal medical oncologists globally. Descriptive statistics and chi-square tests were used to summarize information. Results Of 174 responses, 145 were complete and analyzed. Responses were obtained globally from South America (53%); the U.S. and Canada (28%); Europe, Australia, and New Zealand (12%); and Asia (7%). Most clinicians (98%) were aware of the IDEA study. Prior to IDEA, clinicians preferred FOLFOX over CAPOX (81% vs. 19%). Subsequent to IDEA, 55% of clinicians preferred CAPOX over FOLFOX (odds ratio, 5.0; 95% confidence interval, 3.0–8.5; p < .01 compared with pre-IDEA). Two thirds (68%) of responders tailored duration of adjuvant therapy based on risk stratification. Most oncologists (76%) were more willing to discontinue oxaliplatin early if toxicities develop after the results of IDEA. Half of responders (50%) found that IDEA increased their confidence in decision making for adjuvant treatment; 36% were unchanged, and 15% indicated decreased confidence. Less than half (48%) were comfortable communicating the study results and the concept of a noninferiority trial with patients. Conclusion IDEA appears to have shifted clinician preference from FOLFOX to CAPOX for adjuvant therapy, and most clinicians now use a risk-stratified approach in determining duration of adjuvant therapy. Patient education resources may facilitate better communication of IDEA results to patients.

ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer. In this study, we observed elevated expression of full-length ECT2 protein in preneoplastic colon adenomas, driven by increased ECT2 mRNA abundance and associated with APC tumor-suppressor loss. Elevated ECT2 levels were detected in the cytoplasm and nucleus of colorectal cancer tissue, suggesting cytoplasmic mislocalization as one mechanism of early oncogenic ECT2 activation. Importantly, elevated nuclear ECT2 correlated with poorly differentiated tumors, and a low cytoplasmic:nuclear ratio of ECT2 protein correlated with poor patient survival, suggesting that nuclear and cytoplasmic ECT2 play distinct roles in colorectal cancer. Depletion of ECT2 reduced anchorage-independent cancer cell growth and invasion independent of its function in cytokinesis, and loss of Ect2 extended survival in a KrasG12D Apc-null colon cancer mouse model. Expression of ECT2 variants with impaired nuclear localization or guanine nucleotide exchange catalytic activity failed to restore cancer cell growth or invasion, indicating that active, nuclear ECT2 is required to support tumor progression. Nuclear ECT2 promoted ribosomal DNA transcription and ribosome biogenesis in colorectal cancer. These results support a driver role for both cytoplasmic and nuclear ECT2 overexpression in colorectal cancer and emphasize the critical role of precise subcellular localization in dictating ECT2 function in neoplastic cells. Significance: ECT2 overexpression and mislocalization support its role as a driver in colon cancer that is independent from its function in normal cell cytokinesis.

Purpose of review This review will extensively cover the clinical manifestations, causes, diagnostic evaluation, and management strategies of downbeat nystagmus (DBN). Recent findings Historically, MRI to assess for structural lesions at the cervicomedullary junction has been the primary diagnostic test in the evaluation of DBN since the 1980s. In recent years, there is increasing awareness of nonstructural causes of DBN including gluten ataxia, nutritional deficiencies, and paraneoplastic syndromes, among others. Medical management with aminopyridines has become first-line therapy in addition to disease-specific therapies. Summary DBN is a common form of acquired nystagmus and the differential diagnosis remains broad, including both benign and potentially fatal causes. For practical purposes, the causes can be categorized as structural vs. nonstructural with MRI as the ideal, initial diagnostic study to differentiate the two. General therapeutic options include pharmacotherapy to enhance Purkinje cell function, strabismus surgery or prisms to shift null points, and behavioural changes. Disease-specific treatment is necessarily broad, though a significant proportion of patients will be idiopathic.

BACKGROUND: Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase–inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown. METHODS: Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided. RESULTS: Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P

Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immune regulator STING (stimulator of interferon genes) confer remarkable protection against cancer pain, bone destruction, and local tumor burden. Repeated systemic administration of STING agonists robustly attenuates bone cancer-induced pain and improves locomotor function. Interestingly, STING agonists produce acute pain relief through direct neuronal modulation. Additionally, STING agonists protect against local bone destruction and reduce local tumor burden through modulation of osteoclast and immune cell function in the tumor microenvironment, providing long-term cancer pain relief. Finally, these in vivo effects are dependent on host-intrinsic STING and IFN-I signaling. Overall, STING activation provides unique advantages in controlling bone cancer pain through distinct and synergistic actions on nociceptors, immune cells, and osteoclasts., There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone cancer tumor burden, but also attenuate bone pain and reduce cancer-induced bone destruction.

We report novel case of a 57-year-old woman who developed bilateral ocular ischemic syndrome in the setting of chronic angle closure glaucoma without associated angle neovascularization. Detailed is a course in which markedly prolonged, elevated intraocular pressure led to significantly reduced arterial perfusion at the level of the central retinal artery, leading to the clinical picture of ocular ischemic syndrome.

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%, HR, 2.93, 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

Purpose To identify clinical and radiographic factors that predict return to sport in athletes undergoing hip arthroscopy and to determine thresholds for significant predictors. Methods Data were reviewed on all patients who underwent primary hip arthroscopy between November 2008 and August 2018. Patients were included if they played professional, college, or high school sports within 1 year before surgery and had preoperative, 3-month, 1-year, and 2-year postoperative patient-reported outcome scores for modified Harris Hip Score, Hip Outcome Score-Sport Specific-Subscale, and Nonarthritic Hip Score. Rates of achieving the minimal clinically important difference also were evaluated. Patients were divided into groups based on whether they returned to sport at the same or greater level. Multivariate logistic regression and receiver operator characteristic analysis were used to evaluate the correlation between significant variables and return to sport. Results A total of 136 patients with a mean age of 20.8 ± 7.07 years were included. Among athletes who attempted to return, professional and collegiate athletes returned to sport at any level at a rate of 85.0% (51/60), and high-school athletes returned at a rate of 88.1% (52/59). Competition level, postoperative alpha angle, change in alpha angle, and postoperative patient-reported outcomes were significantly different between groups. Athletes who returned to sport achieved the minimal clinically important difference for Hip Outcome Score–Sport Specific-Subscale at significantly higher rates than athletes who did not return to sport (91.6% vs 71.7%, P = .002, S = 8.97). The multivariate logistic regression model identified postoperative alpha angle as a statistically significant predictor of return to sport (P 9.97 [odds ratio 0.85, 95% confidence interval 0.79-0.91]). The receiver operator characteristic curve for postoperative alpha angle demonstrated acceptable discrimination between patients returning to sport and patients not returning to sport with an area under the curve of 0.71 and a threshold value of 46°. Athletes with a postoperative alpha angle ≤46° returned to sport at significantly higher rates than those with a postoperative alpha angle >46° [(P 9.97 [odds ratio 6.3, 95% confidence interval 2.6-15.2]). Conclusions Postoperative alpha angle was identified as a predictor of return to sport in athletes. The odds of returning to sport were 6.3 times greater in athletes with postoperative alpha angles ≤46° compared with athletes with angles >46°. Level of Evidence III, retrospective cohort study.

Performing germline and somatic sequencing in locally advanced and metastatic pancreatic cancer can identify potentially targetable genomic aberrations that impact current standard treatment options or eligibility for biomarker-targeted clinical trials. Testing for deleterious germline mutations in BRCA1/2 impacts patient selection for platinum-based chemotherapy regimens and selection of patients who are candidates to receive maintenance therapy with olaparib. Additional germline mutations also similarly introduce potential vulnerabilities to the cancers that arise and may be targeted by clinical trials. Somatic mutation testing also provides opportunities for optimal selection of patients for biomarker-driven clinical trials. Although KRAS mutations are found in 90% to 93% of pancreatic cancers, there are increasing opportunities for therapies against particular mutant KRAS isoforms, especially with the advent of KRAS G12C–specific small molecule inhibitors, and KRAS targeting trials will increasingly require identification of the specific KRAS mutation present. There are also a range of tumor site–agnostic molecular features, such as microsatellite instability and NTRK fusions that, although rarely found in pancreatic cancers, impact selection of patients who have the potential for dramatic benefit with immune checkpoint inhibitors such as pembrolizumab or TRK inhibitors such as larotrectinib or entrectinib, respectively, and thus motivate broader somatic mutation and fusion testing for patients with locally advanced and metastatic pancreatic cancers. Multiple other rare actionable aberrations, particularly gene fusions in the 8% to 10% of KRAS wild-type pancreatic cancers, are also known, and enrollment in basket trials for these rare patient cohorts is highly encouraged.

A 65-year-old man with end-stage renal disease on peritoneal dialysis was admitted for new onset binocular double vision, failure to thrive, and debilitating right-sided headaches. Medical history was significant for tympanomastoidectomy for polymicrobial mastoiditis and treatment with IV antibiotics. MRI brain without contrast was read by radiology initially as showing expected postsurgical changes; however, given patient's history of mastoiditis infection, there was a high clinical suspicion for Gradenigo syndrome. MRI brain was repeated with gadoxetate contrast to minimize the risk of nephrogenic systemic fibrosis (NSF) in a patient with severe renal disease and this revealed an intracranial empyema involving both the trigeminal and abducens nerves confirming the diagnosis of Gradenigo syndrome. This case presented a diagnostic challenge because of suboptimal visualization on initial nonenhanced MRI. Gadoxetate was chosen because of its unique properties including high hepatobiliary excretion making it a safer form of gadolinium-based contrast agent that may not have the potential to precipitate NSF.

BACKGROUND The COMBO drug eluting stent is a novel device with luminal endothelial progenitor cell capture technology for rapid homogeneous endothelialization. METHODS AND RESULTS We examined for sex differences in 1-year outcomes after COMBO stenting from the COMBO collaboration, a pooled patient-level dataset from the MASCOT and REMEDEE multicenter registries. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI), or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods. The study included 861 (23.8%) women and 2,753 (76.2%) men. Women were older with higher prevalence of several comorbidities including diabetes mellitus. Risk of 1-year TLF was similar in both sexes (3.8% vs. 3.9%, HR 0.92, 95% CI 0.59-1.42, p = .70), without sex differences in the incidence of cardiac death (1.6% vs. 1.5%, p = .78), TV-MI (1.5% vs. 1.1%, p = .32), or CD-TLR (2.0% vs. 2.2%, p = .67). Definite or probable ST occurred in 0.4% women and 1.0% men (HR 0.26, 95% CI 0.06-1.11, p = .069). CONCLUSIONS Despite greater clinical risks at baseline, women treated with COMBO stents had similarly low 1-year TLF and other ischemic outcomes compared to men.

Cycline antibiotics (CAs) are commonly used to treat acne, blepharitis, and dry eye syndrome. Prescribers or patients may hesitate to use Cas because they may increase the risk of pseudotumor cerebri syndrome (PTCS).We sought to assess whether CA use is associated with an increased risk of PTCS or papilledema and whether the risk depends upon dosage or duration of CA intake.We studied patients 12 to 65 years of age who were diagnosed with acne, blepharitis, or dry eye syndrome, who were enrolled in a nationwide managed care network between January 1, 2001 and December 31, 2015, and who had no preexisting diagnosis of papilledema or PTCS. Multivariable Cox regression modeling was used to assess the risk of developing papilledema or PTCS from exposure to CAs.Among the 728,811 eligible enrollees (mean age, 34.7 years; 72% female), 42.0% filled ≥1 CA prescription. Of the 305,823 CA users, 170 (0.06%) were diagnosed with papilledema or PTCS. By comparison, of the 57.0% with no record of CA use, 121 (0.03%) were diagnosed with papilledema or PTCS (P .0001). In the unadjusted model, every additional year of CA use was associated with a 70% (doxycycline: hazard ratio, 1.70 [95% confidence interval 0.98-2.97]; P = .06) or 91% (minocycline: hazard ratio, 1.91 [95% confidence interval 1.11-3.29]; P = .02) increased hazard of papilledema/PTCS relative to nonusers of CAs. After adjustment for confounders, the increased hazard of PTCS/papilledema with CA use was no longer statistically significant (P = .06, doxycycline; P = .08, minocycline).This study relies on claims data, which lack clinical data.This study offers some evidence that CAs may increase the risk of PTCS/papilledema. However, after accounting for confounding factors in our multivariable models, we found no statistically significant association between CA use and the development of PTCS. Moreover, there was no dose-response effect whereby greater CA use was associated with a higher PTCS risk.

Background Direct stenting offers many potential advantages in appropriately selected lesions. Coronary artery calcification increases the complexity and risk of adverse events associated with percutaneous coronary intervention. This study aimed to examine the feasibility of direct stenting after treatment with orbital atherectomy (OA). Methods ORBIT II was a single-arm trial enrolling 443 subjects with de novo severely calcified coronary lesions treated with OA; direct stenting was utilized in 59.0% of cases. Procedural outcomes and 3-year major adverse cardiac event (MACE) rates were compared in subjects treated with pre-stent balloon dilatation versus direct stenting after OA. Results Procedural success (84.2% vs. 93.3%; p = 0.004) was significantly higher in the direct stenting cohort. 3-year MACE occurred less frequently in the direct stenting cohort (29.9% vs. 19.1%; p = 0.006), driven by lower rates of myocardial infarction and target lesion revascularization . In a propensity matched analysis, procedural success and 3-year MACE rates were similar in the pre-stent balloon dilatation and direct stenting groups (85.0% vs. 91.8%; p = 0.122 and 28.2% vs. 19.6%; p = 0.078, respectively). Conclusions Orbital atherectomy facilitates direct stenting and is associated with high procedural success and favorable 3-year outcomes in carefully selected patients. Randomized studies are needed to assess the optimal strategy after lesion preparation with OA.

Background A balance between autonomy and supervision can be difficult to obtain in medical education. In this study, we sought to determine whether the presence and level of supervision of ophthalmology resident outpatient clinic correlates with metrics of resident success, professionalism and stress. Methods A survey was emailed to all US ophthalmology program directors requesting it be forwarded to PGY4 residents. Questions included whether their program provided a resident-hosted outpatient clinic, and if so, whether residents were mandated to discuss every patient with faculty. Residents were assigned to three categories based on this question (0: no clinic, 1: mandated faculty input, 2: discretionary faculty input). Success metrics included numbers of manuscripts submitted, OKAP scores and success in obtaining fellowships. Professionalism metrics included rating comfort obtaining informed consent, breaking bad news, managing time in clinic, and confidence in providing care in various settings. Residents affirming participation in a continuity clinic also provided perceptions of the level of supervision and how the clinic affected stress. Results Category 1 residents perceived somewhat too much supervision, while category 2 residents felt that they had somewhat insufficient supervision. The majority of residents in either category did not feel that the continuity clinic affected their overall stress, although those who reported a change in stress usually indicated that the presence of the clinic increased stress. There were no other statistically significant differences between the responses from any category. Conclusions The presence of a resident-hosted continuity clinic neither adds nor detracts from the success or sense of professionalism of ophthalmology residents. However, when such a clinic is present, the degree of supervision appears to correlate inversely with resident perception of autonomy. These results suggest that the decision of a training program to offer a clinic hosted by residents offering comprehensive continuity care can be informed primarily by faculty and trainee philosophy and personal preferences without comprising education quality, clinical efficiency, residents’ perception of stress or their success in fellowship matching. Electronic supplementary material The online version of this article (10.1186/s12909-019-1620-0) contains supplementary material, which is available to authorized users.

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.

Purpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods...

Successful percutaneous coronary intervention (PCI) can be challenging in the presence of heavily calcified lesions. Severely calcified lesions are associated with worse clinical outcomes. Recognition of calcification is important before stenting to ensure adequate stent expansion can be attained. Orbital atherectomy is a safe and effective method to ablate calcified plaque. Lesion preparation through plaque modification with orbital atherectomy before stent implantation can help to optimize the results of PCI in these complex lesions.

The authors report the case of a 75-year-old man with preexisting glaucoma and recurrent retinal detachment who underwent intraocular silicone oil placement OD resulting in subsequent retrolaminar silicone oil migration to the optic chiasm and vision loss OS. MRI showed silicone oil tracking posteriorly along the right optic nerve to the chiasm. He was placed on high-dose corticosteroids and underwent a successful optic nerve sheath fenestration with improvement of vision in the contralateral eye. Clinicians should be cognizant of the potential for translaminar posterior migration of intraocular silicone oil, as well as the utility of optic nerve sheath fenestration to decompress the anterior visual pathways and restore vision.