Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = −0.62, P = 5.30 × 10−5) but not between CCT and primary open-angle glaucoma (r = −0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Preoperative chemoradiotherapy affects postoperative outcomes and functional results in patients treated with transanal endoscopic microsurgery for rectal neoplasms

Background: The aim of this study was to quantify the incidence of short-term postoperative complications and functional disorders at 1 year from transanal endoscopic microsurgery (TEM) for rectal neoplasms, to compare patients treated with TEM alone and with TEM after preoperative chemoradiotherapy (CRT) and to analyse factors influencing postoperative morbidity and functional outcomes. Methods: A retrospective study was conducted on all patients treated with TEM for rectal neoplasms at our institution in January 2000–December 2017. Data from a prospectively maintained database were retrospectively analysed. Patients were divided into two groups: adenoma or early rectal cancer (no CRT group) and locally advanced extraperitoneal rectal cancer with major or complete clinical response after preoperative CRT (CRT group). Short-term postoperative mortality and morbidity and the functional results at 1 year were recorded. The two groups were compared, and a statistical analysis of factors influencing postoperative morbidity and functional outcomes was performed. Functional outcome was also evaluated with the low anterior resection syndrome (LARS) score (0–20 no LARS, 21–29 minor LARS and 30–42 major LARS). Results: One hundred and thirteen patients (71 males, 42 females, median age 64 years [range 41–80 years]) were included in the study (46 in the CRT group). The overall postoperative complication rate was 23.0%, lower in the noCRT group (p < 0.001), but only 2.7% were grade ≥ 3. The most frequent complication was suture dehiscence (17.6%), which occurred less frequently in the noCRT group (p < 0.001). At 1 year from TEM, the most frequent symptoms was urgency (11.9%, without significant differences between the CRT group and the noCRT group); the noCRT group experienced a lower rate of soiling than the CRT group (0% vs. 7.7%; p: 0.027). The incidence of LARS was evaluated in 47 patients from May 2012 on and was 21.3% occurring less frequently in the noCRT group (10% vs. 41.2%; p: 0.012). Only 6.4% of the patients evaluated experienced major LARS. In multivariate analysis, preoperative CRT significantly worsened postoperative morbidity and functional outcomes. Conclusions: TEM is a safe procedure associated with only low risk of severe postoperative complications and major LARS. Preoperative CRT seems to increase the rate of postoperative morbidity after TEM and led to worse functional outcomes at 1 year after surgery

Neck complaints before and after uncomplicated thyroidectomy: prevalence, postoperative outcome and relationships with thyroid weight and reflux like symptoms

Purpose: The surgical thyroid disease includes upper aerodigestive complaints with not homogenous prevalence and specific features. The purpose was to analyze before and after total thyroidectomy (TT) the prevalence and severity of voice, swallowing, respiratory, and reflux airway symptoms in relation with thyroid weight. Methods: A total of 98 consenting patients undergoing TT were enrolled. Preoperatively, 1 and 3 months after TT, patients underwent videolaryngoscopy, subjective evaluation of voice (VIS), swallowing (SIS and EAT-10), respiratory (mMRC), and reflux symptoms (RSI, Gerd-Q). The scores were analyzed based on thyroid weight (<25 gr, 26\u201350 gr, 51\u201375 gr, >75 gr) and post-operative score gain was calculated from the score before TT and the follow-up examination. Results: In total, 40/98 selected cases of uncomplicated TT completed the postoperative evaluation. Endoscopic signs suggestive of reflux disease were observed in 1/40 (2.5%) and 0/19 cases before and after TT respectively. The prevalence of cases with abnormal reflux symptom index decreased significantly after surgery (8/40 vs 1/40) (p < 0.05), similarly occurred for the Gerd-Q (4/40 vs 1/40) (p < 0.05). Three months after TT the voice, swallowing and respiratory scores were significantly lower than the preoperative ones (p < 0.05). The SIS correlated positively with EAT-10 and RSI. After 3 months the postoperative score gain of voice, swallowing, respiratory, and reflux symptoms (Gerd-Q) was statistically higher (p < 0.05) in the cases with heaviest gland. Conclusions: The surgical thyroid disease is associated to mild aerodigestive preoperative compressive symptoms, that include respiratory abnormalities and reflux like symptoms, regardless of the gland weight. In absence of endoscopic signs of airway reflux the presence of reflux symptoms suggests an overlapping with thyroid neck complaints. The patients undergoing uncomplicated TT had improvement in compressive symptoms and the greatest improvement is seen in larger goiters

Anastomosis configuration and technique following ileocaecal resection for Crohn\u2019s disease: a multicentre study

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade 65 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade 65 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade 65 3, a penetrating phenotype of disease and ileo-colonic distribution of CD

Surgical treatment of colonic Crohn’s disease: a national snapshot study

Aim: The different surgical options for patients with colonic Crohn’s disease (CD) include segmental colectomy, subtotal colectomy or proctocolectomy with end ileostomy. We present a national, multicentre study, promoted by the Italian Society of Colorectal Surgery with the aim to collect benchmark data and national variations on multidisciplinary management and postoperative outcomes of patients undergoing surgery for colonic CD. Methods: All adult patients having elective surgery for colonic CD from June 2018 to May 2019 were eligible for participation in this retrospective study. The primary outcome measure was postoperative morbidity within 30 days of surgery. Results: One hundred twenty-two patients were included: 55 subtotal colectomy, 30 segmental colectomy, 25 proctectomy and 12 proctocolectomy. Eighty-six patients (70.4%) were discussed at the inflammatory bowel disease (IBD) multidisciplinary team meeting (MDT) prior to surgery. This ranged from 76.6% for segmental colectomy to 60% for subtotal colectomy, 66.6% for proctocolectomy and 48% for proctectomy. The proportion of patients counselled by a stoma nurse preoperatively was 50%. Laparoscopy was associated with reduced postoperative morbidity (p = 0.017) and shorter length of hospital stay (p < 0.001), whilst pre-operative anti-TNF was associated with Dindo-Clavien ≥ 3 complications (p = 0.023) and longer in-hospital stay (p = 0.007). The main procedure performed (segmental colectomy, subtotal colectomy, proctocolectomy or proctectomy) was not associated with postoperative morbidity (p = 0.626). Conclusions: Surgery for colonic CD has a high rate of postoperative complications. Almost a third of the patients were not preoperatively discussed at the IBD MDT, whilst the use of minimally invasive surgery for surgical treatment of colonic CD ranges from 40 to 66%