The Effect of Age on Corneal Topographic Indices, Keratometry and Visual Acuity After Combined Intrastromal Corneal Ring Segment (ICRS) Implantation and Corneal Crosslinking

We aimed to assess age-related changes in corneal topographic indices, keratometry and visual acuity after sequential intracorneal ring segment implantation (ICRS) and crosslinking (CXL). This was a retrospective matched case-control series including 26 eyes of patients ≤18 years as the cases and 26 eyes of adult patients as control. All eyes received ICRS+CXL for progressive keratoconus. Eyes were matched regarding the keratoconus parameters and the treatment (type, number and thickness of ICRS). Data was analyzed for refractive and topographic values [uncorrected and corrected distance visual acuity (UDVA; CDVA) sphere; cylinder; spherical equivalent; maximum keratometry (Kmax); flat keratometry (Kflat); steep keratometry (Ksteep); all 7 pentacam topographic indices] preoperatively and one year postoperatively. Preoperatively, there was no significant difference for any refractive, clinical or topographic parameters between the groups except for vertical asymmetry. After one year, children had a significantly higher improvement in Ksteep (3.05D) than adults (2.10D; P=0.036) and a trend to significance for Kflat (2.7D compared to 1.78D, respectively; P=0.081). UDVA improved by 4.3 ETDRS lines in children compared to 3.3 ETDRS lines in adults and CDVA improved by 1.7 ETDRS lines in children compared to 1.2 ETDRS lines in adults, but with no statistical significance. The effects on keratometry indicated that corneal response after ICRS and CXL for keratoconus is more pronounced in young patients than adults. This assumption is also supported by functional improvement and by the fact that a few eyes (5) of some very young patients (<13years) showed highly remarkable improvements after surgery (higher than any adult eye)

Portal Vein Thrombosis and Thrombocytopenia in Eosinophilic Granulomatosis with Polyangiitis: A Paradox?

A 36-year-old woman with eosinophilic granulomatosis with polyangiitis (EGPA) presented with necrotic skin lesions and pulmonary infiltrates. There was eosinophilic vasculitis on skin biopsy, and substantial tissue eosinophilia in her bone marrow. She had unexplained worsening thrombocytopenia, which prompted a thrombophilia work-up. However, abnormalities in liver enzymes led to the extraordinary finding of portal vein thrombosis. Thrombocytopenia resolved with treatment with low molecular weight heparin. This case highlights the risk of hypercoagulability in eosinophilia specifically, and in EGPA. We suggest that thrombosis should be ruled out in all cases of EGPA

Chronic ocular GVHD: limbal and conjunctival stem cell allografts from the same hematopoietic stem cell donor

Letter to the edito

Culprit-Vessel Percutaneous Coronary Intervention Followed by Contralateral Angiography Versus Complete Angiography in Patients With St-Elevation Myocardial Infarction

In patients with ST-elevation myocardial infarction, delay in door-to-balloon time strongly increases mortality rates. To our knowledge, no randomized studies to date have focused on reducing delays within the catheterization laboratory. We performed a retrospective analysis of all patients who presented with ST-elevation myocardial infarction at our institution from July 2006 through June 2010, looking primarily at time differences between percutaneous coronary intervention in the culprit vessel on the basis of ECG criteria, followed by contralateral angiography (Group 1), versus complete coronary angiography followed by culprit-vessel percutaneous intervention (Group 2). There were 49 patients in Group 1 and 57 patients in Group 2. No major differences in baseline characteristics were observed between the groups, except a higher prevalence of diabetes mellitus in Group 2. There was a statistically significant difference between Groups 1 and 2 in door-to-balloon time (median and interquartile range, 75 min [61–89] vs 87 min [70–115], P=0.03, respectively) and access-to-balloon time (12 min [9–18] vs 21 min [11–33], P=0.0006, respectively). Five Group 1 patients (10%) with inferior myocardial infarction had a contralateral culprit vessel. There were no differences in mortality rate or ejection fraction at the median 1-year follow-up. Four patients in Group 1 and 3 patients in Group 2 were referred for coronary artery bypass grafting after percutaneous intervention. This study suggests that performing culprit-vessel percutaneous intervention on the basis of electrocardiographic criteria, followed by angiography in patients with anterior ST-elevation myocardial infarction, might be the preferred approach, given the door-to-balloon time that is saved

A Novel Role for CSRP1 in a Lebanese Family with Congenital Cardiac Defects

Despite an obvious role for consanguinity in congenital heart disease (CHD), most studies fail to document a monogenic model of inheritance except for few cases. We hereby describe a first-degree cousins consanguineous Lebanese family with 7 conceived children: 2 died in utero of unknown causes, 3 have CHD, and 4 have polydactyly. The aim of the study is to unveil the genetic variant(s) causing these phenotypes using next generation sequencing (NGS) technology. Targeted exome sequencing identified a heterozygous duplication in CSRP1 which leads to a potential frameshift mutation at position 154 of the protein. This mutation is inherited from the father, and segregates only with the CHD phenotype. The in vitro characterization demonstrates that the mutation dramatically abrogates its transcriptional activity over cardiac promoters like NPPA. In addition, it differentially inhibits the physical association of CSRP1 with SRF, GATA4, and with the newly described partner herein TBX5. Whole exome sequencing failed to show any potential variant linked to polydactyly, but revealed a novel missense mutation in TRPS1. This mutation is inherited from the healthy mother, and segregating only with the cardiac phenotype. Both TRPS1 and CSRP1 physically interact, and the mutations in each abrogate their partnership. Our findings add fundamental knowledge into the molecular basis of CHD, and propose the di-genic model of inheritance as responsible for such malformations

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Under-the-Flap Crosslinking and LASIK in Early Ectasia with Hyperopic Refractive Error

Purpose. To present safety, efficacy, and early results of a new combinational treatment for early corneal ectasia with hyperopic refractive error aimed to reinstate emmetropia and stabilize cornea. Method. This is a retrospective case series. All surgeries were performed at the Beirut Eye Specialist Hospital, Lebanon. Surgical procedure consisted of (1) lifting flap (post-LASIK ectasia)/creation of corneal flap (keratoconus), (2) application of excimer laser ablation to correct refractive error, (3) loose repositioning of flap, (4) under-the-flap irrigation with riboflavin 0.1% dextran solution, and (5) application of UVA light. Results. A total of 7 eyes (4 patients; mean age 24.25 years; all male) were included. 2 patients had early keratoconus, and 2 patients had early post-LASIK ectasia. Pretreatment vs. last postoperative follow-up visit (mean 11.25 months; range 6–15 months) UDVA (logMAR), spherical equivalent (SE) (D), astigmatism (D), and central pachymetry (µm) were 0.35 ± 0.18 vs. 0.05 ± 0.07, p=0.017; −0.81 ± 0.67 vs. −0.46 ± 0.57, p=0.078; 2.46 ± 0.53 vs. 0.68 ± 0.28, p=0.018; and 547 ± 58 vs. 536 ± 49, p=0.07, respectively. In all eyes, BCVA was 0.1 logMAR or better before and after treatment. No eye showed a decrease in BCVA. Two eyes of one patient had an epithelial ingrowth, which was removed in one case. Follow-up results showed no major complications and no progression of corneal ectasia. Conclusion. Early results showed that under-the-flap CXL with excimer laser correction is an effective treatment for early hyperopic keratectasia, with the advantage of rapid recovery, postoperative corneal stability, and no epithelial healing complications. The procedure seems to bear a risk for postoperative epithelial growth into the flap interface

Geology and palaeoenvironments of Quaternary Tawil deposits in Ma’an desert, Jordan

This article briefly outlines the geology of aquatic deposits in the Ma‘an desert, which consist of semi-consolidated gypsum layers intercalated by semi-consolidated sandstones, siltstones and mudstones with stromatolitic structures. They were deposited in a periodic river, called the Tawil River, and after that in a pond environment. The Tawil River is incised into the chalky limestone (Um Rijam Chert Limestone Formation, Eocene) and was filled later with cross-bedded sand. In the shallower parts, the river bed sediments dried out and mud cracks have been formed. Muddy deposits of the pond had been penetrated by plant roots, which traces are still quite clearly visible in some places. When the ponds dried out, salts started to precipitate forming crusts of gypsum and halides. Halides became washed away again by the next flood while gypsum remained in solid form. The outcrops are overlain by a recent soil covered by eroded chert fragments of the Um Rijam Chert Limestone Formation. The area has been influenced by tectonic events which can be made responsible for the preservation or disappearance of the river deposits. The Tawil River surrounding and the subsequent ponds had also served for ancient humans as a settlement ground and the hunting area