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What is this summary about? This is a summary of an article about the Cincinnati study, which was published in the Journal of Comparative Effectiveness Research in January 2020. The Cincinnati study reviewed data from 435 males with Duchenne muscular dystrophy, also known as DMD, who were treated at the Cincinnati Children's Hospital Medical Center. DMD is a rare disease that worsens over time. People with DMD experience inflammation in their muscles and muscle loss over time. They also experience bone problems such as an abnormally bent spine, also known as scoliosis, as well as heart and lung problems. What happened in the Cincinnati study? Prednisone and deflazacort are steroids that help to reduce muscle inflammation and are used as treatments for DMD. The study researchers wanted to further understand the differences between using prednisone and deflazacort in males with DMD by reviewing data from past medical records of patients seen in clinics rather than in clinical studies. This is known as gathering real-world evidence. In the Cincinnati study, the researchers compared males with DMD who started taking prednisone as their first steroid treatment with males who started taking deflazacort as their first steroid treatment. What were the results? Overall, the researchers found that the participants who took deflazacort were able to walk until a later age before they needed to use a wheelchair, compared with those who took prednisone. They also had a lower risk of scoliosis and developed it at a later age. What do the results of the study mean? These results helped the researchers to learn more about the differences between how well prednisone and deflazacort work in males with DMD based on their medical records.

Computed tomography coronary angiography (CTCA) is an established imaging modality widely used for diagnosing coronary artery stenosis with expanding potential for comprehensive assessment of coronary artery disease (CAD). Lesion-based analyses of high-risk plaques (HRP) on CTCA may aid further in prognostication presenting with stable chest pain. We conduct qualitative and quantitative assessments to identify HRPs that are associated with acute coronary syndrome (ACS) on a medium to long term follow-up.Retrospective cohort study of patients who underwent CTCA for suspected CAD. Obstructive stenosis (OS) is defined as ≥50% and the presence of HRP and its constituents: positive-remodelling (PR), low-attenuation-plaque (LAP;56 HU), very-low-attenuation-plaque (vLAP;30 HU) and spotty-calcification (SC) were recorded. A cross-sectional quantitative analysis of HRP was performed at the site of minimum-luminal-area (MLA). The primary endpoint was fatal or non-fatal ACS on follow-up.A total of 1,257 patients were included (mean age 61±14 years old and 51% male) with a median follow-up of 7.24 years (interquartile range 5.5 to 7.7 years). The occurrence of ACS was significantly higher in HRP (+) patients compared to HRP (-) patients and patients with no plaques (20.5%The presence of OS and the LAP area at the site of MLA identify the HRP lesions that have the greatest association with development of future ACS.

Recent landmark discoveries have underpinned the physiological importance of intron retention (IR) across multiple domains of life and revealed an unexpected breath of functions in a large variety of biological processes. Despite significant progress in the field, some challenges remain. Once solved, opportunities will arise for discovering more functions of IR.

Anti-programmed death-1 (anti-PD-1) immunotherapy reinvigorates CD8 T cell responses in patients with cancer but PD-1 is also expressed by other immune cells, including follicular helper CD4 T cells (Tfh) which are involved in germinal centre responses. Little is known, however, about the effects of anti-PD-1 immunotherapy on noncancer immune responses in humans. To investigate this question, we examined the impact of anti-PD-1 immunotherapy on the Tfh-B cell axis responding to unrelated viral antigens. Following influenza vaccination, a subset of adults receiving anti-PD-1 had more robust circulating Tfh responses than adults not receiving immunotherapy. PD-1 pathway blockade resulted in transcriptional signatures of increased cellular proliferation in circulating Tfh and responding B cells compared with controls. These latter observations suggest an underlying change in the Tfh-B cell and germinal centre axis in a subset of immunotherapy patients. Together, these results demonstrate dynamic effects of anti-PD-1 therapy on influenza vaccine responses and highlight analytical vaccination as an approach that may reveal underlying immune predisposition to adverse events.

Background The terminal ileum poses a predilection for Crohn’s disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER). Methods This is a post hoc analysis of patients with moderately to severely active CD, defined as Crohn’s disease activity index 220 to 450, and terminal ileal ulceration treated with antitumor necrosis factor (TNF)-α inhibitor adalimumab from the EXTEND trial. We studied whether baseline total Global Histologic Disease Activity Scores (GHAS), any individual histologic element, and specific immunohistochemical (IHC) markers of chronic inflammation from biopsy specimens were associated with postinduction (week 12) and maintenance (week 52) ER, defined as Simple Endoscopic Score for Crohn’s Disease of 0. Multivariable logistic regression models adjusted for confounders were used to assess the relationship between histologic markers and 1-year outcomes. Results Seventy-one adult patients with CD affecting the ileum were included in this analysis. Both baseline ileal GHAS scores and individual histologic components were not found to be associated with ER at weeks 12 or 52. Increased expression of interleukin-13 receptor (IL-13R) on IHC stains was associated with reduced likelihood of achieving 1-year ER (adjusted odds ratio, 0.06; 95% CI, 0.01-0.92; P = .044). No other biomarker assessed was associated with 1-year ER. Conclusions Ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not associated with 1-year ER. However, strong staining for IL-13 receptor in the ileum was associated with reduced odds of 1-year ER using adalimumab. Mucosal cellular disease profiles might pose an opportunity to guide treatment of CD.

Fibroblast activation protein (FAP) is a membrane-tethered serine protease overexpressed in the reactive stromal fibroblasts of >90% human carcinomas, which makes it a promising target for developing radiopharmaceuticals for the imaging and therapy of carcinomas. Here, we synthesized two novel (R)-pyrrolidin-2-yl-boronic acid-based FAP-targeted ligands: SB02055 (DOTA-conjugated (R)-(1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)glycyl)pyrrolidin-2-yl)boronic acid) and SB04028 (DOTA-conjugated ((R)-1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)-D-alanyl)pyrrolidin-2-yl)boronic acid). natGa- and 68Ga-complexes of both ligands were evaluated in preclinical studies and compared to previously reported natGa/68Ga-complexed PNT6555. Enzymatic assays showed that FAP binding affinities (IC50) of natGa-SB02055, natGa-SB04028 and natGa-PNT6555 were 0.41 ± 0.06, 13.9 ± 1.29 and 78.1 ± 4.59 nM, respectively. PET imaging and biodistribution studies in HEK293T:hFAP tumor-bearing mice showed that while [68Ga]Ga-SB02055 presented with a nominal tumor uptake (1.08 ± 0.37 %ID/g), [68Ga]Ga-SB04028 demonstrated clear tumor visualization with ~1.5-fold higher tumor uptake (10.1 ± 0.42 %ID/g) compared to [68Ga]Ga-PNT6555 (6.38 ± 0.45 %ID/g). High accumulation in the bladder indicated renal excretion of all three tracers. [68Ga]Ga-SB04028 displayed a low background level uptake in most normal organs, and comparable to [68Ga]Ga-PNT6555. However, since its tumor uptake was considerably higher than [68Ga]Ga-PNT6555, the corresponding tumor-to-organ uptake ratios for [68Ga]Ga-SB04028 were also significantly greater than [68Ga]Ga-PNT6555. Our data demonstrate that (R)-(((quinoline-4-carbonyl)-d-alanyl)pyrrolidin-2-yl)boronic acid is a promising pharmacophore for the design of FAP-targeted radiopharmaceuticals for cancer imaging and radioligand therapy.

Background Pancreatectomy is a necessary component of curative intent therapy for pancreatic cancer, and patients living in non-metropolitan areas may face barriers to accessing timely surgical care. We evaluated the intersecting associations of rurality, socioeconomic status (SES), and race on treatment and outcomes of Medicare beneficiaries with pancreatic cancer. Methods We conducted a retrospective cohort study, using fee-for-service Medicare claims of beneficiaries with incident pancreatic cancer (2016-2018). We categorized beneficiary place of residence as metropolitan, micropolitan, or small town/rural. Measures of SES were Medicare-Medicaid dual eligibility and the Area Deprivation Index (ADI). Primary study outcomes were receipt of pancreatectomy and one-year mortality. Exposure-outcome associations were assessed with competing risks and logistic regression. Results We identified 45,915 beneficiaries with pancreatic cancer, including 78.4%, 10.9%, and 10.7% residing in metropolitan, micropolitan, and rural areas, respectively. In analyses adjusted for age, sex, comorbidity, and metastasis, residents of micropolitan and rural areas were less likely to undergo pancreatectomy (adjusted subdistribution hazard ratio=0.88 for rural, 95%CI 0.81-0.95) and had higher one-year mortality (aOR=1.25 for rural, 95%CI 1.17-1.33), compared with metropolitan residents. Adjustment for measures of SES attenuated the association of non-metropolitan residence with mortality, and there was no significant association of rurality with pancreatectomy after adjustment. Black beneficiaries had lower likelihood of pancreatectomy than White, non-Hispanic beneficiaries (aSHR=0.80, 95%CI 0.72-0.89, adjusted for SES). One-year mortality in metropolitan areas was higher for Black beneficiaries (aOR=1.15 95%CI 1.05-1.26). Conclusions Rurality, socioeconomic deprivation, and race have complex interrelationships and are associated with disparities in pancreatic cancer treatment and outcomes.

Laptop use appears to contribute to poor working postures and neck pain among university students. Postural braces have the potential to improve upper back/neck posture and therefore might have a role as an ergonomic aid for this population. Therefore, the purpose of this study was to assess the short-term effects of scapular bracing on pain, fatigue, cervicothoracic posture, and the activity of the neck and upper-back muscles in healthy college students. A randomized controlled crossover trial was conducted to evaluate the self-reported pain and fatigue, the amplitude and median frequency of surface electromyography in neck extensors, upper trapezius, and lower trapezius, as well as the neck and shoulder sagittal alignment (measured by inertial sensors and digital photographs) during a 30-min typing task in a sample of young, healthy university students with or without a scapular brace. The brace condition resulted in significantly smaller levels of bilateral trapezius muscle activity (p < 0.01). Rounded shoulder posture was slightly better in the brace condition, but these differences were not significant (p > 0.05). There were no significant immediate differences in pain or fatigue scores, neck alignment, or the electromyographic activity of the other muscles tested between brace and non-brace conditions (all p > 0.05). However, bracing appears to immediately reduce the electromyographic activity of the lower trapezius muscles (p < 0.05). These findings shed some light on the possible advantages of scapular bracing for enhancing laptop ergonomics in this group of individuals. Future studies are warranted to evaluate the effects of different types of braces, the importance of matching the brace to the user, and the short- and long-term effects of brace use on computer posture and muscle activity.

Funding Acknowledgements Type of funding sources: None. Background Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for patients with hematologic malignancies, but is associated with life-threatening toxicities which contribute to prolonged hospitalization and chronic comorbidities. The presence of life-threatening toxicities results in variable length of survival. In this context, identifying appropriate prognostic biomarkers of HCT response is of clinical importance. Pre-treatment elevated resting heart rate (RHR) has been associated with increased risk of toxicities and worse survival in patients with solid tumors, but this has not been studies in patients undergoing HCT. Purpose To examine the association between pre-HCT RHR and outcomes after allogeneic HCT. Methods This was a retrospective cohort study of patients who underwent allogeneic HCT for acute leukemia or myelodysplastic syndrome as adults (≥18 years old). RHR was obtained from pre-HCT screening electrocardiogram or echocardiogram after a 5-minute rest in the supine position. RHR was first divided into quartiles: 50-66 beat per minutes (bpm), 67-75 bpm, 76-85 bpm, 86-163 bpm. There was no significant association between RHR and 2-year mortality among the three lowest quartiles, and they were combined in our analyses (lower RHR [ Results There were 792 consecutive patients who underwent HCT between 2007-2014. Median age was 51 years (range 18–74 years); 53.8% were male and 57.1% were non-Hispanic white. Average length of hospitalization was significantly longer in patients with elevated RHR compared to those with lower RHR (35.6 [21.2] vs 32.0 [18.7] days; P = 0.003). However, there was no association between RHR and the development of MACE after HCT. Patients with elevated RHR had significantly worse 2-year overall survival (50.2% vs. 66.1%, p Conclusion This study is the first to demonstrate the association between pre-treatment RHR and clinically important outcomes in patients with acute leukemia or myelodysplastic syndrome undergoing HCT. This information may be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT.

Virilizer-like m6A methyltransferase-associated protein (VIRMA) maintains the stability of the m6A writer complex. Although VIRMA is critical for RNA m6A deposition, the impact of aberrant VIRMA expression in human diseases remains unclear. We show that VIRMA is amplified and overexpressed in 15–20% of breast cancers. Of the two known VIRMA isoforms, the nuclear-enriched full-length but not the cytoplasmic-localised N-terminal VIRMA promotes m6A-dependent breast tumourigenesis in vitro and in vivo. Mechanistically, we reveal that VIRMA overexpression upregulates the m6A-modified long non-coding RNA, NEAT1, which contributes to breast cancer cell growth. We also show that VIRMA overexpression enriches m6A on transcripts that regulate the unfolded protein response (UPR) pathway but does not promote their translation to activate the UPR under optimal growth conditions. Under stressful conditions that are often present in tumour microenvironments, VIRMA-overexpressing cells display enhanced UPR and increased susceptibility to death. Our study identifies oncogenic VIRMA overexpression as a vulnerability that may be exploited for cancer therapy.

Adaptation is defined as reduced neural activation following repeated stimulus presentation. While previous EEG studies used either one repetition or multiple repetitions to elicit adaptation in event-related potentials (ERP), it is unclear whether adaptation differs between initial and subsequent repetitions. In addition, multiple repetitions were used in mismatch negativity (MMN) experiments to measure deviance detection, but how adaptation contributes to the MMN remains unclear. Therefore, in the current study, 37 healthy adults participated in an EEG experiment with a pure tone roving paradigm and a random stimulus arrangement to minimize expectations. The amplitudes and latencies were traced along with the first ten tones in different components of the auditory ERP, including P1, N1, and P2, to examine the relationship between adaptation and the number of repetitions. Results showed a slight increasing adaptation effect in the P1, an L-shaped adaptation in the N1 with a large decrease after the first repetition, and a continuous, linear amplitude increase in the P2, possibly indicating memory trace formation. Regression results showed that the peak amplitudes of the N1 initial adaptation and the P2 subsequent adaptation significantly explained the variance in the MMN amplitude. The results indicate distinct adaptation patterns for multiple repetitions in different components and suggest that the MMN combines two processes as indicated by the initial adaptation in the N1 and a continuous memory trace effect in the P2. Separating the two processes may be relevant for models of cognitive processing and clinical disorders.

Introduction We developed and internally validated a prognostic scoring index for ulcerative colitis (UC) patients that includes baseline patient-reported outcomes (PROs), biomarkers, endoscopy, and histology for achieving 1-year endoscopic improvement (EI). Methods This post hoc analysis included 644 patients treated with ustekinumab induction therapy. Data were randomly split to obtain a 70% training and 30% testing cohort. Multivariate analyses assessed baseline variables and those with P < .05 were assigned weights based on their relative prognostic value from logistic regression modeling for predicting 1-year EI (Mayo endoscopic score ≤1). A cutoff was obtained by calculating the maximum Youden index and validated in the testing cohort. Results Prior biologic failure, albumin 5 mg/L, Mayo stool frequency subscore, endoscopic erosions/ulcerations, and chronic histologic structural/architectural changes demonstrated significant associations with 1-year EI and were included in the final model. The Ulcerative Colitis Severity Index (UCSI) had acceptable discriminative ability for 1-year EI in the training (area under the curve [AUC], 0.78; 95% confidence interval, 0.70-0.86) and testing cohort (AUC, 0.76; 95% CI, 0.68-0.85). Compared with the UCSI, the Mayo Clinic score demonstrated poor accuracy (AUC, 0.49; 95% CI, 0.40-0.58) for predicting 1-year EI (P = .0006). The UCSI predicted 1-year endoscopic healing (Mayo endoscopic score = 0), clinical remission (total Mayo Clinic score ≤2 and no subscore >1), partial Mayo score remission Discussion The UCSI is an internally validated prognostic scoring tool that accurately predicts 1-year EI at baseline among moderate-to-severe UC patients initiating therapy. Further validation with additional datasets is needed.

Background Limb-threatening lower extremity injuries often require secondary bone grafting after soft tissue reconstruction. We hypothesized that there would be fewer wound complications when performing secondary bone grafting via a remote surgical approach rather than direct flap elevation. Methods A retrospective cohort study was performed at a single Level 1 trauma center comparing complications after secondary bone grafting in patients who had undergone previous soft tissue reconstruction after open tibia fractures between 2006 and 2020. Comparing bone grafting via a remote surgical incision versus direct flap elevation, we evaluated wound dehiscence requiring return to the operating room as the primary outcome. Secondary outcomes were deep infection and delayed amputation. Results We identified 129 patients (mean age: 40 years, 82% male) with 159 secondary bone grafting procedures. Secondary bone grafting was performed via a remote surgical approach in 54% (n = 86) and direct flap elevation in 46% (n = 73) of cases. Wound dehiscence requiring return to the operating room occurred in one patient in the flap elevation group (1%) and none of the patients in the remote surgical approach. The odds of deep wound infection (OR, 1.77; p = 0.31) or amputation (OR, 1.43; p = 0.73) did not significantly differ between surgical approaches. No significant differences were found in complications between the reconstructive surgeon elevating and re-insetting the flap and the orthopaedic trauma surgeon performing the flap elevation and re-inset. Conclusion Direct flap elevation for secondary bone grafting after soft tissue reconstruction for open tibia fractures did not result in more complications than bone grafting via a remote surgical approach. These findings should reassure surgeons to allow other clinical factors to influence the surgical approach for bone grafting.

Singapore grouper iridovirus (SGIV), one of the nucleocytoviricota viruses (NCVs), is a highly pathogenic iridovirid. SGIV infection results in massive economic losses to the aquaculture industry and significantly threatens global biodiversity. In recent years, high morbidity and mortality in aquatic animals have been caused by iridovirid infections worldwide. Effective control and prevention strategies are urgently needed. Here, we present a near-atomic architecture of the SGIV capsid and identify eight types of capsid proteins. The viral inner membrane-integrated anchor protein colocalizes with the endoplasmic reticulum (ER), supporting the hypothesis that the biogenesis of the inner membrane is associated with the ER. Additionally, immunofluorescence assays indicate minor capsid proteins (mCPs) could form various building blocks with major capsid proteins (MCPs) before the formation of a viral factory (VF). These results expand our understanding of the capsid assembly of NCVs and provide more targets for vaccine and drug design to fight iridovirid infections.

Maintenance of CTL-, Th1-, and NK cell–mediated type-1 immunity is essential for effective antitumor responses. Unexpectedly, we observed that the critical soluble mediators of type-1 immune effector cells, IFNγ and TNFα, synergize in the induction of cyclooxygenase 2 (COX2), the key enzyme in prostaglandin (PG)E2 synthesis, and the subsequent hyperactivation of myeloid-derived suppressor cells (MDSC) within the tumor microenvironment (TME) of ovarian cancer patients. MDSC hyperactivation by type-1 immunity and the resultant overexpression of indoleamine 2,3-dioxygenase (IDO), inducible nitric oxide synthase (iNOS/NOS2), IL10, and additional COX2 result in strong feedback suppression of type-1 immune responses. This paradoxical immune suppression driven by type-1 immune cell activation was found to depend on the synergistic action of IFNγ and TNFα, and could not be reproduced by either of these factors alone. Importantly, from a therapeutic standpoint, these negative feedback limiting type-1 responses could be eliminated by COX2 blockade, allowing amplification of type-1 immunity in the ovarian cancer TME. Our data demonstrate a new mechanism underlying the self-limiting nature of type-1 immunity in the human TME, driven by the synergistic induction of COX2 by IFNγ and TNFα, and provide a rationale for targeting the COX2–PGE2 axis to enhance the effectiveness of cancer immunotherapies. Cancer Immunol Res; 4(4); 303–11. ©2016 AACR.

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Supplemental Table 1 provides the information about the clinical status of patients(donors of ovarian cancer ascites). Supplemental Figures S1-S6 provide the characterization of the immune cells and experimental systems involved in the study and additional data from complementary assays and individual donors. Figure legends are provided under each Figure.

We report on intra- and inter-modal four-wave-mixing (FWM) in N-fold rotationally symmetric (C_N) single- and multi-core chiral photonic crystal fiber (PCF), created by spinning the preform during fiber drawing. The non-circular modal field is forced to rotate as it propagates along the fiber, resulting in circular birefringence and robust maintenance of circular polarization state. Multi-core chiral C_N PCF supports vortex-carrying helical Bloch modes (HBMs) in which the degeneracy between clockwise and counter-clockwise vortices is lifted. This makes possible new kinds of intermodal polarization modulational instability (PMI). We develop PMI theory for vortex HBMs, and illustrate the results by a series of experiments in which two or more PMI sidebands with different vorticities and polarization states are selectively generated by adjusting the polarization state and topological charge of the pump light. In every case both the topological charge and the spin of the pump light are conserved. We also report generation of a broadband supercontinuum in a single circularly polarized vortex mode.

The liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors (rAAV). Multiple clinical trials have been undertaken for this target in the past 15 years, however we are still to see market approval of the first liver-targeted AAV-based gene therapy. Inefficient expression of the therapeutic transgene, vector-induced liver toxicity and capsid, and/or transgene-mediated immune responses reported at high vector doses are the main challenges to date. One of the contributing factors to the insufficient clinical outcomes, despite highly encouraging preclinical data, is the lack of robust, biologically- and clinically-predictive preclinical models. To this end, this study reports findings of a functional evaluation of six AAV vectors in twelve preclinical models of the human liver, with the aim to uncover which combination of models is the most relevant for the identification of AAV capsid variant for safe and efficient transgene delivery to primary human hepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepatocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses of each system. This should allow the development of novel gene therapies targeting the human liver.

Background. Social support is important for stroke rehabilitation. Conventionally, social support is evaluated from the level of support received. However, the bidirectional support hypothesis postulated that self-perceived social support is optimized if individuals provide and receive social support in a balanced manner. The Brief 2-Way Social Support Scale (Brief 2-Way SSS) is a social support instrument measuring the reciprocity of receiving and giving emotional and instrumental social support. Objective. (1) To translate and culturally adapt the English version of the Brief 2-Way SSS into Chinese (Cantonese) (Brief 2-Way SSS-C), (2) to report the results of validation of the Brief 2-Way SSS-C, and (3) to investigate the level of social support in people with stroke in Hong Kong. Methods. The Brief 2-Way SSS-C was produced following the standard forward-backward translation model. People with stroke ( n = 109 ) and age-matched controls ( n = 53 ) were recruited through a university-affiliated neurorehabilitation laboratory. Results. The Brief 2-Way SSS-C demonstrated excellent content validity, acceptable to good internal consistency (Cronbach’s alpha of 0.74–0.88), and good test-retest reliability (intraclass correlation coefficient of 0.76–0.81). There were no ceiling or floor effects, and the MDC95 across all subscales was 4. The Brief 2-Way SSS-C subscales had significant correlations with various health-related outcome measures. People with stroke had a lower level of social support than the age-matched healthy controls. Conclusions. The Brief 2-Way SSS-C is a culturally relevant, reliable, and valid outcome measure for the level of social support in community-dwelling people with stroke.

Background We compared the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Modified Multiplied SES-CD (MM-SES-CD) scores with the Rutgeerts score for predicting clinical recurrence (CR) of postoperative Crohn’s disease (CD). Methods This post hoc analysis of the prospective, multicenter, randomized, double-blind, placebo-controlled trial comparing remicade and placebo in the prevention of recurrence in Crohn’s disease patients undergoing surgical resection who are at an increased risk of recurrence (PREVENT) study used receiver operating characteristic curve analyses to compare the Rutgeerts, SES-CD, and MM-SES-CD scores at week 76 for subsequent CR by week 104 in 208 participants. Multivariate logistic regression models evaluated cutoffs for the odds of experiencing CR by week 104, after adjustment for confounders. CR was defined as Crohn’s Disease Activity Index score ≥200 and ≥70-point increase from baseline (or development of fistulas, abscesses, or treatment failure) and endoscopic recurrence by week 104, defined as Rutgeerts score ≥i2. Results The week 76 Rutgeerts score predicted CR by week 104 with fair accuracy (area under the receiver-operating characteristic curve [AUC], 0.74; 95% confidence interval [CI], 0.65-0.83), which was similar to the SES-CD ileum score (AUC, 0.72; 95% CI, 0.64-0.80) and the MM-SES-CD ileum score (AUC, 0.72; 95% CI, 0.63-0.80). Compared with cutoffs by the other scores, the MM-SES-CD total score ≥26 at week 76 had the highest odds ratio to predict CR by week 104. Patients with a week 76 MM-SES-CD total score ≥26 were 4.41 times (95% CI, 2.06-9.43, P < .001) more likely to have CR by week 104 compared with those with an MM-SES-CD total score Conclusions The SES-CD and MM-SES-CD perform similarly to the Rutgeerts score for predicting subsequent CR of postoperative CD. The MM-SES-CD threshold of ≥26 was predictive of postoperative CR. Clinicians and trialists could consider using the SES-CD or MM-SES-CD to assess postoperative CD given their ability to capture colonic disease recurrence and predict CR.

SM03, an anti-CD22 recombinant IgG1 mAb, is currently in a phase III clinical trial for the treatment of rheumatoid arthritis (NCT04312815). SM03 showed good safety and efficacy in phase I systemic lupus erythematosus and phase II moderate to severe rheumatoid arthritis clinical trials. We propose the success of SM03 as a therapeutic to systemic autoimmune diseases is through the utilization of a novel mechanism of action unique to SM03. CD22, an inhibitory coreceptor of the BCR, is a potential immunotherapeutic target against autoimmune diseases. SM03 could disturb the CD22 homomultimeric configuration through disrupting cis binding to α2,6-linked sialic acids, induce rapid internalization of CD22 from the cell surface of human B cells, and facilitate trans binding between CD22 to human autologous cells. This in turn increased the activity of the downstream immunomodulatory molecule Src homology region 2 domain-containing phosphatase 1 (SHP-1) and decreased BCR-induced NF-κB activation in human B cells and B cell proliferation. This mechanism of action gives rationale to support the significant amelioration of disease and good safety profile in clinical trials, as by enabling the “self” recognition mechanism of CD22 via trans binding to α2,6 sialic acid ligands on autologous cells, SM03 specifically restores immune tolerance of B cells to host tissues without affecting the normal B cell immune response to pathogens.

BACKGROUND: Quantitative flow ratio (QFR) may be used to assess the functional significance of coronary lesions. Only limited validation exists for this technology in the setting of severe aortic stenosis. METHODS: A prospective study was performed on patients who were being considered for transcatheter aortic valve implantation. QFR analysis was performed (Medis Medical Imaging System, Leiden, The Netherlands) and compared to invasive measurements of haemodynamic assessment [fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), diastolic pressure ratio during the wave-free period (dPR) and distal arterial pressure/arterial pressure (Pd/Pa)]. RESULTS: A total of 35 patients were included in the study. Mean age was 75.5±6.5 and mean aortic valve gradient was 44.3±11.8 mmHg. There were 57 vessels analysed. The mean FFR was 0.83±0.10 and 22 vessels (39%) had a functionally significant FFR ≤0.80. QFR demonstrated a discriminatory power to predict functionally significant FFR [area under the receiver operating characteristic curve (AUC), 0.92; 95% confidence interval (CI): 0.84 to 1.00], representing a sensitivity of 73%, specificity of 91%, positive predictive value of 84%, negative predictive value of 84% and an accuracy of 84%. QFR also demonstrated a discriminatory power to predict functionally significant iFR ≤0.89 (AUC =0.92; 95% CI: 0.85 to 0.99), dPR ≤0.89 (AUC =0.90; 95% CI: 0.83 to 0.98) and Pd/Pa ≤0.92 (AUC =0.89; 95% CI: 0.80 to 0.97). CONCLUSIONS: QFR demonstrates acceptable diagnostic performance in patients with severe aortic stenosis when both FFR and non-hyperaemic pressure indices are used as reference standards.