Pinhole amniotic membrane for peripheral corneal defects in patients with a single eye or low vision.

AIMS: To describe the efficacy of a new pinhole amniotic membrane placement technique in cases of peripheral epithelial defects in patients with a single eye or low vision in the contrye. METHODS: This technique is based on a small central hole done with a dermatological 3 to 4 mm punch (according to pupillary diameter in mesoscopic conditions) and a continuous suture in the perilimbal cornea to fix the amniotic membrane. We performed this technique in 6 patients. Patients were followed clinical and photographically. RESULTS: No changes in the visual acuity before and after the surgery were observed. During follow-up, a complete re-epithelialization was observed with no need for reinterventions. CONCLUSIONS: Amniotic membrane transplantation is a very useful option in patients with persistent epithelial defects; however, its use is limited by the subsequent visual acuity. The use of the pinhole amniotic membrane technique allows us to treat peripheral persistent corneal lesions without modifying patients' visual acuity. This new technique may become especially useful in patients with functional single eye of low vision in the contralateral eye.

Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn's Disease.

BACKGROUND & AIMS: The magnetic resonance index of activity (MARIA) for Crohn's disease (CD) is used to assess the activity of luminal CD. However, it has a number of practical limitations. We aimed to develop and validate a simplified MARIA to more easily and quickly assess CD activity and response to therapy. PATIENTS AND METHODS: We performed a retrospective analysis of magnetic resonance imaging data from 98 participants in 2 studies. We used logistic regression analysis to identify magnetic resonance imaging parameters independently associated with CD endoscopic index of severity (CDEIS) scores (the reference standard). We validated the responsiveness and reliability of the simplified MARIA in an independent cohort of 37 patients who underwent magnetic resonance imaging and endoscopy before and after a therapeutic intervention. RESULTS: Logistic regression analysis showed that dichotomous qualitative assessment of wall thickening (>3 mm), presence of mural edema, perienteric fat stranding, and ulcers were independently associated with CDEIS scores; we used these factors to create a simplified MARIA. Simplified MARIA scores greater than 1 identified segments with active CD with 90% sensitivity and 81% specificity (area under the curve 0.91; 95% confidence interval 0.88-0.94). Simplified MARIA scores of 2 or more detected severe lesions (ulcers) with 85% sensitivity and 92% specificity (area under the curve 0.94; 95% confidence interval 0.91-0.96). For each patient, there was a high level of correlation between simplified MARIA scores and CDEIS scores (r = 0.83) and simplified MARIA scores and original MARIA scores (and r = 0.93) (P < .001). The simplified MARIA score accurately detected changes in lesion severity in response to therapy and was as reliable as endoscopy for the assessment of mucosal healing. CONCLUSION: We developed and validated a simplified MARIA for easier and faster assessment of CD activity and severity. This index identifies patients with a response to therapy with a high level of accuracy. These findings require confirmation in independent, multireader studies.

Identification of potential inhibitors of SARS-CoV-2 papain-like protease from tropane alkaloids from Schizanthus porrigens: A molecular docking study.

This paper presents identification of potential inhibitors of SARS-CoV-2 papain-like protease from tropane alkaloids from Schizanthus porrigens, using molecular docking method. Binding affinities were compared with those obtained with Lopinavir as a SARS-CoV-2 papain-like protease inhibitor. Overall, our findings indicate that Schizanthine Z binds to the SARS-CoV-2 papain-like protease with relatively high affinity and favorable ADME properties. Therefore, Schizanthine Z may represent an appropriate compound for further evaluation in antiviral assays.

Treatment of gingival pigmentation with a 755-nm alexandrite picosecond laser.

Hyperpigmentation of the gums can be associated to several etiological factors. Although it is physiological in most cases it can cause esthetic concerns in some patients. The objective of our study was to evaluate the clinical efficacy and patient satisfaction with the treatment of gingival hyperpigmentation with picosecond alexandrite laser of 755 nm. We selected two patients with gingival hyperpigmentation on the anterior face of the upper and lower gums of years of evolution. Malignancy, drug ingestion, exposure to tobacco and underlying genetic and endocrine alterations were ruled out. Clinical photographs were taken before treatment and 2 weeks after the procedure. In both cases, anterior gingival areas were depigmented with satisfaction. The patients did not complain of severe pain or discomfort. Two weeks after the procedure the gingiva showed almost complete depigmentation. In conclusion, the 755-nm alexandrite picosecond laser seems to be safe and effective for the esthetic treatment of gingival hyperpigmentation.

A human cellular system for analyzing signaling during corneal endothelial barrier dysfunction.

Correct corneal endothelial barrier function is essential for maintaining corneal transparency. However, research on cell signaling pathways mediating corneal endothelial barrier dysfunction has progressed more slowly than that involving other cellular barriers because of the lack of human corneal endothelial cell models. Here we have optimized the culture of the human corneal endothelial cell (HCEC) line B4G12 as a model for studying paracellular permeability. We show that B4G12-HCECs form confluent monolayers with stable cell-cell junctions when cultured on plastic, but not glass, surfaces precoated with various extracellular matrix components. Cell morphometry and measuring intercellular spaces and transendothelial electric resistance indicate that B4G12-HCECs form optimal monolayers on collagen and fibronectin. Based on the use of specific inhibitors, it has been proposed that the Rho-regulated kinases, ROCK-I and ROCK-II, mediate actomyosin-induced contraction in corneal endothelial cell barriers. ROCKs are effectors of RhoA, RhoB and RhoC. We show that the GTPase RhoA and its effector ROCK-II are predominantly expressed in B4G12-HCECs and primary human corneal endothelial cells. The activation of Rho GTPases during acute barrier disruption has not been investigated in corneal endothelial cells. RhoA, but not other related GTPases that are highly expressed in B4G12-HCECs, such as Rac1 and Cdc42, is transiently activated during barrier disruption in response to the inflammatory mediator thrombin. Pharmacological inhibition of RhoA and ROCK reduces B4G12-HCEC acute contraction. We propose that exploiting B4G12-HCECs is a useful experimental strategy for gaining further insight into the signaling pathways involved in human corneal endothelial barrier function.

Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections.

BACKGROUND & AIMS: Infections in cirrhosis are frequently complicated by kidney dysfunction that entails a poor prognosis. Urinary biomarkers may be of potential clinical usefulness in this setting. We aimed at assessing the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker overexpressed in kidney tubules during kidney injury, in predicting clinical outcomes in cirrhosis with infections. METHODS: One-hundred and thirty-two consecutive patients hospitalized with infections were evaluated prospectively. Acute kidney injury (AKI) was defined according to AKIN criteria. uNGAL was measured at infection diagnosis and at days 3 and 7 (ELISA, Bioporto, DK). RESULTS: Patients with AKI (n=65) had significantly higher levels of uNGAL compared to patients without AKI (203 ± 390 vs. 79 ± 126 µg/g creatinine, p<0.001). Moreover, uNGAL levels were significantly higher in patients who developed persistent AKI (n=40), compared to those with transient AKI (n=25) (281 ± 477 vs. 85 ± 79 µg/g creatinine, p<0.001). Among patients with persistent AKI, uNGAL was able to discriminate type-1 HRS from other causes of AKI (59 ± 46 vs. 429 ± 572 µg/g creatinine, respectively; p<0.001). Moreover, the time course of uNGAL was markedly different between the two groups. Interestingly, baseline uNGAL levels also predicted the development of a second infection during hospitalization. Overall, 3-month mortality was 34%. Independent predictive factors of 3-month mortality were MELD score, serum sodium, and uNGAL levels at diagnosis, but not presence or stage of AKI. CONCLUSIONS: In patients with cirrhosis and infections, measurement of urinary NGAL at infection diagnosis is useful in predicting important clinical outcomes, specifically persistency and type of AKI, development of a second infection, and 3-month mortality.

Description of a new family with cryopyrin-associated periodic syndrome: risk of visual loss in patients bearing the R260W mutation.

OBJECTIVE: The aim of this study was to describe a family with cryopyrin-associated periodic syndrome (CAPS) in which the disease was unveiled after the ophthalmologic evaluation. METHODS: Family and personal histories from each of the patients were recorded. Each underwent a full ophthalmological examination along with the physical examination. The mutational analysis of the NLRP3 gene was performed by means of direct sequencing. RESULTS: The proband was admitted during an episode of unilateral anterior uveitis. She had a history of recurrent red eye and had been suffering episodes of skin rash and arthralgia induced by cold since childhood. At examination, she showed a reticulated corneal mid-stroma. Her mother and her younger sister also suffered from relapsing episodes of skin rash and fever triggered by cold as well as flares of red eye. They had developed premature hearing loss. In both cases, opacities in the corneal mid-stroma were evidenced with a slit lamp. The genetic analysis detected the heterozygous germline p.R260W mutation in the NLRP3 gene in the three women, confirming the diagnosis of CAPS. Treatment with anakinra resulted in complete remission of flares. CONCLUSION: In this family, a structural NLRP3 mutation was associated with classic MuckleWells features of different degrees of severity. Interstitial keratitis with corneal opacification, usually ascribed to neonatal-onset multisystem inflammatory disease, was found. We underscore that ocular involvement in MuckleWells syndrome should be carefully assessed, since it can lead to visual impairment.

Three-dimensional evaluation of accommodating intraocular lens shift and alignment in vivo.

OBJECTIVE: To quantify 3-dimensionally the anterior segment geometry, biometry, and lens position and alignment in patients before and after implantation of the Crystalens-AO (Bausch & Lomb, Rochester, NY) accommodating intraocular lens (A-IOL). DESIGN: Prospective, observational study. PARTICIPANTS: Ten patients (20 eyes) with cataract before and after implantation of the Crystalens-AO A-IOL. METHODS: Custom full anterior segment 3-dimensional (3-D) spectral optical coherence tomography (OCT) provided with quantification tools was used to image the cornea, iris, and natural lens preoperatively and intraocular lens postoperatively. Measurements were obtained under phenylephrine preoperatively and under natural viewing conditions and phenylephrine (for accommodative efforts ranging from 0 to 2.5 diopters [D]) and pilocarpine postoperatively. MAIN OUTCOME MEASURES: Three-dimensional quantitative anterior segment images, corneal geometry and power, anterior chamber depth (ACD), lens thickness, pupil diameter, A-IOL shift with accommodative effort or drug-induced accommodation, and A-IOL alignment. RESULTS: Crystalline lens and IOLs were visualized and quantified 3-dimensionally. The average ACD were 2.64±0.24 and 3.65±0.35 mm preoperatively and postoperatively (relaxed state), respectively, and they were statistically significantly correlated (although their difference was not statistically correlated with lens thickness). The A-IOL did not shift systematically with accommodative effort, with 9 lenses moving forward and 11 lenses moving backward (under natural conditions). The average A-IOL shift under stimulated accommodation with pilocarpine was -0.02±0.20 mm. The greatest forward shift occurred bilaterally in 1 patient (-0.49 mm in the right eye and -0.52 mm in the left eye, under pilocarpine). The high right/left symmetry in the horizontal tilt of the crystalline lens is disrupted on IOL implantation. Accommodative IOLs tend to be slightly more vertically tilted than the crystalline lens, with increasing tendency with accommodative effort. Two subjects showed postoperative IOL tilts >9 degrees. Changes in pupillary diameter correlated with pilocarpine-induced A-IOL axial shift. Intermediate accommodative demands (1.25 D) elicited the greater shifts in axial A-IOL location and tilt and pupil diameter. CONCLUSIONS: Quantitative 3-D anterior segment OCT allows full evaluation of the geometry of eyes implanted with A-IOLs preoperatively and postoperatively. High-resolution OCT measurements of the Crystalens 3-D positioning revealed small (and in many patients backward) A-IOL axial shifts with both natural or drug-induced accommodation, as well as tilt changes with respect to natural lens and accommodative effort.

Viral hepatitis and liver transplantation: pathogenesis, prevention and therapy of recurrent disease.

Cirrhosis secondary to hepatitis C virus infection is the leading cause of liver transplantation in most countries. Hepatitis C has an accelerated course after transplantation, and for this reason graft and patient survival are decreased in comparison with other indications of liver transplantation. The development of direct-acting antivirals has been a major step in the management of hepatitis C and in a few years from now the infection will be eradicated with the combination of oral drugs with a good safety profile. This will likely allow prevention of hepatitis C recurrence in most cases. Meanwhile, management of hepatitis C virus infection still relies on the combination of interferon, ribavirin and the first-generation protease inhibitors telaprevir and boceprevir.

[Future prospects for hepatitis C treatment: without interferon and ribavirin?]. / Perspectivas futuras del tratamiento de la hepatitis C, ¿sin interferón y sin ribavirina?

The hepatitis C virus is an important health problem worldwide. Currently, the standard treatment of genotype 1 chronic hepatitis C is the combination of pegylated interferon, ribavirin and a first-generation protease inhibitor: telaprevir or boceprevir. This triple therapy has improved the efficacy of treatment but has also increased regimen complexity, costs, and the number of adverse effects (mainly hematological and cutaneous). Unfortunately, viral response rates are still suboptimal in patients with cirrhosis, particularly those with a prior null response. Moreover, studies carried out in clinical practice have shown that the presence of advanced fibrosis confers a high risk of developing severe adverse effects during treatment (infection, decompensation and even death). It is therefore essential to select candidates for triple therapy according to their risk of complications and possibilities for cure. In this scenario, interferon (and ribavirin)-free combinations are very safe and well tolerated first-line treatments. This review describes the current treatment of hepatitis C as well as the latest results of studies combining distinct direct antiviral agents without interferon. It is hoped that these drugs will be available shortly, although their cost may be high. Consequently, it is essential to identify those patients who could derive the greatest benefit from these treatments.

A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis.

BACKGROUND & AIMS: The Acute Kidney Injury Network (AKIN) criteria are widely used in nephrology, but information on cirrhosis is limited. We aimed at evaluating the AKIN criteria and their relationship with the cause of kidney impairment and survival. METHODS: We performed a prospective study of 375 consecutive patients hospitalized for complications of cirrhosis. One-hundred and seventy-seven (47%) patients fulfilled the criteria of Acute Kidney Injury (AKI) during hospitalization, the causes being hypovolemia, infections, hepatorenal syndrome (HRS), nephrotoxicity, and miscellaneous (62, 54, 32, 8, and 21 cases, respectively). RESULTS: At diagnosis, most patients had AKI stage 1 (77%). Both the occurrence of AKI and its stage were associated with 3-month survival. However, survival difference between stages 2 and 3 was not statistically significant. Moreover, if stage 1 patients were categorized into 2 groups according to the level of serum creatinine used in the classical definition of kidney impairment (1.5mg/dl), the two groups had a significantly different outcome. Combining AKIN criteria and maximum serum creatinine, 3 risk groups were identified: (A) patients with AKI stage 1 with peak creatinine ≤ 1.5mg/dl; (B) patients with stage 1 with peak creatinine >1.5mg/dl; and (C) patients with stages 2-3 (survival 84%, 68%, and 36%, respectively; p<0.001). Survival was independently related to the cause of kidney impairment, patients with HRS or infection-related having the worst prognosis. CONCLUSIONS: A classification that combines the AKIN criteria and classical criteria of kidney failure in cirrhosis provides a better risk stratification than AKIN criteria alone. The cause of impairment in kidney function is key in assessing prognosis in cirrhosis.

Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.

Ovarian cancer (OC) is one of the most lethal gynecological malignancies. The use of biological compounds such as non-coding RNAs (ncRNAs) is being considered as a therapeutic option to improve or complement current treatments since the deregulation of ncRNAs has been implicated in the pathogenesis and progression of OC. Old drugs with antitumoral properties have also been studied in the context of cancer, although their antitumor mechanisms are not fully clear. For instance, the antidiabetic drug metformin has shown pleiotropic effects in several in vitro models of cancer, including OC. Interestingly, metformin has been reported to regulate ncRNAs, which could explain its diverse effects on tumor cells. In this review, we discuss the mechanism of epigenetic regulation described for metformin, with a focus on the evidence of metformin-dependent microRNA (miRNAs) and long non-coding RNA (lncRNAs) regulation in OC.

Risk of Intraocular Lens Opacification After Endothelial Keratoplasty for Different Intraocular Lens Models: A Retrospective Single-Center Cohort Study.

PURPOSE: The aims of this study were to calculate the specific risk of opacification for different intraocular lens (IOL) models and to determine whether differences exist, even between lenses made of similar acrylic materials. METHODS: This is a retrospective cohort study of all patients who underwent endothelial keratoplasty (EK), either after or in conjunction with cataract surgery, from June 2009 to October 2020 at Fundación Jiménez Díaz Hospital. RESULTS: Three hundred seventy-two eyes of 308 patients with a median follow-up of 856 days [interquartile range (IQR): 384-1570] were included, of which 128 IOLs were hydrophobic, 120 hydrophilic, and 124 unknown. 12.9% of IOLs opacified after a median of 466 days (IQR: 255-743). Visual acuity (VA) was significantly lower in the opacified IOL group [0.51 (IQR: 0.36-1.13)] compared with the nonopacified group [0.22 (IQR: 0.11-0.65)] ( P < 0.001). IOL explantation and exchange was performed in 10 eyes, in which VA improved markedly, from 1.75 (IQR: 0.99-3.00) to 0.60 (IQR: 0.36-0.86) ( P = 0.004). IOL material and opacification events were not independent ( P < 0.001). Significant differences were found between the Akreos ADAPT AO and MI60P models and the Asphina 409M model ( P = 0.022). No significant differences were found in the opacification ratio for hydrophilic IOLs in the clinical diagnosis ( P = 0.11), the type of EK ( P = 0.25), the rebubbling rate ( P = 0.44), or the tamponade used ( P = 0.36). CONCLUSIONS: Hydrophilic lenses should be avoided in patients at risk of requiring EK. It is important to know the probability of opacification of each IOL model to balance risk and benefits when planning an EK procedure because not all lenses opacify equally. Opacification is an unwanted event with a negative impact on VA, making IOL explantation and exchange the only viable treatment, although one that is not without risks.

Ultra-High Resolution Optical Aberrometry in Patients with Keratoconus: A Cross-Sectional Study.

INTRODUCTION: This study performs optical aberration assessment in patients using a novel ultra-high-resolution device. The objective of this study is to analyze optical aberrations, especially the very high order wavefront (more than 10th order of Zernike coefficients), and compare between keratoconus and healthy patients. METHODS: In this cross-sectional study, we analyzed 43 eyes from 25 healthy patients and 43 eyes from 27 patients with keratoconus using corneal tomography and a very high-resolution (8.55 µm) aberrometer prototype (T-eyede) outfitted with a sensor originally developed for use in the field of astrophysics. Corneal aberration values were assessed using an optical model built with Zemax optical software, while ocular aberrations were assessed using T-eyede. In addition, image-processing analysis was performed of the wavefront phase, creating a high-pass filter map. RESULTS: We found lower values for ocular aberrations than corneal aberrations in both groups (p < 0.001). Specifically, we found a reduction in primary astigmatism (0.145 µm) and primary coma (0.017 µm). Also, the keratoconus group showed significantly higher wavefront aberration values compared with controls (p < 0.001). An analysis of the high-pass filter map revealed 2 contrasting results: one smooth or clear, while the other presented a banding pattern. Almost all in the control group (95%) showed the first pattern, while 77% of the keratoconus group showed a banding pattern on the filtered map (chi-squared test, p < 0.001). CONCLUSION: This device provides reliable, precise measurements of ocular aberrations that correlate well with corneal aberrations. Furthermore, the extraordinary high-resolution measurements revealed unprecedented micro changes in the wavefront phase of patients with keratoconus that varied with disease stage. These findings could lead to new screening or follow-up methods.

Optical Evaluation of Intracorneal Ring Segment Surgery in Keratoconus.

Purpose: The purpose of this study was to assess the impact of different intracorneal ring segments (ICRS) combinations on corneal morphology and visual performance on patients with keratoconus. Methods: A total of 124 eyes from 96 patients who underwent ICRS surgery were analyzed and classified into 7 groups based on ICRS disposition and the diameter of the surgical zone (5- and 6-mm). Pre- and postoperative complete ophthalmological examinations were conducted. Corneal geometry, volume, and symmetry were studied. Zernike polynomials were used to build a virtual ray-tracing model to evaluate optical aberrations and the Visual Strehl (VS). Results: ICRS induced significant flattening across the cornea, being more pronounced on the anterior (+0.38 mm, P < 0.001) than on the posterior (+0.15 mm, P < 0.001) corneal radius. Asphericity experienced a larger change for a 6-mm surgical zone diameter (from -1.23 ± 1.1 to -1.86 ± 1.2, P < 0.001) than for a 5-mm zone (from -1.99 ± 1.1 to -2.10 ± 1.5, P = 0.536). Mean astigmatism was reduced by 2.05 D (P < 0.001). Combination four was the most effective in reducing astigmatism. Coma decreased by 30% on average and combination one produced an average reduction by 51% (P < 0.05). Patients experienced significant improvement in visual performance, best corrected visual acuity increased from 0.57 ± 0.21 to 0.69 ± 0.21 and VS changed from 0.049 ± 0.02 to 0.065 ± 0.041. Conclusions: ICRS combinations implanted within 5 mm diameter zone are more effective in flattening the cornea, whereas those implanted on 6 mm diameter are as effective in reducing astigmatism and are a good choice if the asymmetry and the intended flattening are smaller. Combinations with asymmetrical implants are the best option to regularize corneal surface. Translational Relevance: This study uses methods and metrics of optical research applied to daily clinical practice.

Correction: Assesment of the QuickSee wavefront autorefractor for characterizing refractive errors in school-age children.

[This corrects the article DOI: 10.1371/journal.pone.0240933.].

"Ophthalmia Venerea": A dreadful complication of fluoroquinolone-resistant Neisseria gonorrhoeae.

Infections caused by quinolone-resistant Neisseria gonorrhoeae are increasing worldwide. Although mostly mild and uncomplicated, serious infections causing severe morbidity are occasionally observed. We report 2 cases of sexually transmitted keratoconjunctivitis in adults resulting in severe visual disturbance.

[Characteristics of patients with familial adenomatous polyposis in Spain. First results of the Spanish Registry of Familial Adenomatous Polyposis]. / Características de los pacientes con poliposis adenomatosa familiar en España. Resultados iniciales del Registro Español de Poliposis Adenomatosa Familiar.

BACKGROUND AND OBJECTIVES: Familial adenomatous polyposis is an inherited disorder characterized by the presence of multiple colorectal adenomas (more than 100 in the classic form and between 10 and 100 in the attenuated one), with a high risk of colorectal cancer development. To improve the diagnostic and therapeutic management of these patients, the Spanish Registry of Familial Adenomatous Polyposis was created in 2007.We aimed to evaluate the clinicopathological characteristics of patients with familial adenomatous polyposis in Spain. PATIENTS AND METHODS: All patients included in the Registry during one year were evaluated with respect to their demographic, clinical, pathological, and genetic characteristics. RESULTS: 243 patients of 156 unrelated families from 15 Spanish centers were included. One hundred thirty patients were male, and the mean age at diagnosis was 40 years. According to the clinical presentation, 127 corresponded to the classic form and 116 to the attenuated one. Colorectal adenoma with high-grade dysplasia was identified in 67 (28%) patients, and colorectal cancer in 42 (17%). Extracolonic manifestations were: duodenal involvement (n=46), gastric involvement (n=44), desmoid tumors (n=24), thyroid cancer (n=8), osteomas (n=6) and brain tumor (n=1). APC and/or MYH gene testing was performed in 140 (90%) families, detecting the causative mutation in 75 (54%) of them (70 in the APC gene and 5 in the MYH gene). CONCLUSIONS: During its first year of operability, a large number of patients and families were included in the Registry. The reduced prevalence of colorectal cancer as well as the large proportion of families submitted to gene testing demonstrated a high-quality clinical practice in Spain.

Pre-treatment magnetic resonance enterography findings predict the response to TNF-alpha inhibitors in Crohn's disease.

BACKGROUND: Identifying predictors of therapeutic response is the cornerstone of personalised medicine. AIM: To identify predictors of long-term healing of severe inflammatory lesions based on magnetic resonance enterography (MRE) findings in patients with Crohn's disease (CD) treated with tumour necrosis factor alpha (TNF-α) inhibitors. METHODS: This prospective longitudinal single-centre study included patients with clinically active CD requiring treatment with TNF-α inhibitors with at least one intestinal segment with a severe inflammatory lesion detected by MRE (segmental MaRIA ≥11). MRE data were obtained at baseline, and at weeks 14 and 46. The primary endpoint was healing of severe inflammatory lesions (MaRIA <11) in each segment. The secondary endpoint was healing of all severe inflammatory lesions on a per-patient analysis. RESULTS: We included 58 patients with 86 intestinal segments with severe inflammatory lesions. At week 46, healing of severe lesions was found in 51/86 (59.3%) segments, and complete healing of inflammatory lesions in all segments was found in 28/58 (48.6%) patients. Multivariable analysis found baseline-negative predictors of long-term healing of severe inflammation were ileal (as opposed to colonic) location (OR 0.00, [0.00-0.56] P = 0.002) and presence of creeping fat on MRE (OR 0.00 [0.00-0.57]; P = 0.001). Persistence of segmental MaRIA score >10.6 at week 14 was a negative predictor of healing at week 46 (OR 0.3 [0.04--0.38]; P < 0.001). CONCLUSION: In patients with CD, the absence of creeping fat detected at baseline MRE and location of severe inflammatory lesions are clinically relevant predictors of long-term healing of severe inflammation under treatment with TNF-α inhibitors.

Validation of the Simplified Magnetic Resonance Index of Activity [sMARIA] Without Gadolinium-enhanced Sequences for Crohn's Disease.

BACKGROUND: Gadolinium-enhanced sequences are not included in the simplified Magnetic Resonance Index of Activity [sMARIA], but in the derivation of this index readers had access to these sequences. The current study aimed to validate the sMARIA without gadolinium-enhanced sequences for assessing disease activity, severity, and response to treatment in patients with Crohn's disease. METHODS: We prospectively included patients with active Crohn's disease and at least one segment with severe inflammation [ulcers] at ileocolonoscopy, who required treatment with biologic drugs. Patients were evaluated by both magnetic resonance enterography [MRE] and ileocolonoscopy at baseline and 46 weeks after initiation of medical treatment. We compared the quantification of disease activity and response to treatment with sMARIA versus with ileocolonoscopy Crohn's Disease Index of Severity [CDEIS], considered the gold standard. RESULTS: Data from both MRE and ileocolonoscopy 46 weeks after treatment initiation were available for 39 of the 50 patients. As in the derivation study, the optimal cutoffs were sMARIA ≥1 for predicting active disease (area under the curve [AUC] 0.92) and sMARIA ≥2 for predicting the presence of ulcers at ileocolonoscopy [AUC 0.93]. In evaluating the response to treatment, the sMARIA detected endoscopic ulcer healing at the segment level [sMARIA <2] with 89.5% sensitivity and 87.5% specificity. The sMARIA decreased significantly [p <0.001] in segments achieving endoscopic ulcer healing, but did not change [p = 0.222] in segments with persistent ulceration. CONCLUSIONS: The sMARIA is accurate and reliable in quantifying disease activity and response to treatment in luminal Crohn's disease, without the need for gadolinium-enhanced sequences.