Comprehensive management of post-LASIK ectasia: From prevention to treatment.

Post-laser in situ keratomileusis (post-LASIK) ectasia (PLE) is one of the most serious complications after refractive surgery, mainly manifested as progressive thinning and trembling thinning of the cornea, accompanied by increased myopia and astigmatism. The mechanisms behind mainly include genetic risk factors and external environmental factors such as eye rubbing and cornea surgery. In order to achieve the goal of reducing the incidence of ectasia, preoperative screening strategies need to be continuously improved, through the collection and assessment of genetic and environmental risk factors. Although previous preoperative screening methods did not have a uniform standard, the emergence of artificial intelligence (AI) can help us process a large amount of information and make rational use of the data. By using high-fidelity finite element modelling, differences in preoperative and postoperative strain distributions can be observed, which can predict the risk of postoperative ectasia. In this review, we describe the incidence, aetiology, prevention and treatment of PLE for the purpose of comprehensive management. In terms of treatment, corneal collagen cross-linking has been widely used to treat progressive keratoconus and other ectasia disease, either as a preventive measure during surgery or as a therapeutic modality after surgery to prevent progression of corneal dilation. Although the standard Dresden protocol has been identified as the gold standard treatment for corneal dilatation, a series of refinements, investigations and long-term studies have been conducted in recent years. Thus, understanding the factors involved in delaying the onset and slowing progression of cornea ectasia will be key to reducing the incidence worldwide.

A contemporary approach to a young female patient with Loeys-Dietz syndrome and an uncomplicated type B aortic dissection: a case report.

BACKGROUND: Aortic dissection is a relatively uncommon, but often catastrophic disease that requires early and accurate diagnosis. It often presents in patients with congenital connective tissue disorders. The current aortic surgical techniques are related with serious early and late complications. This case report emphasizes the importance of early diagnosis of aortic root dilatation and the risk of dissection, especially in patients with congenital connective tissue disorders. We present an alternative, contemporary and multidisciplinary approach based on the present state of knowledge. CASE PRESENTATION: We present a rare case of a young female patient with Loeys-Dietz syndrome who was admitted with an uncomplicated aortic dissection (Stanford type B / DeBakey type III) and a dilated aortic root. After a period of close surveillance and extensive vascular imaging, thoracic endovascular aortic repair was deemed to be technically not possible. Medical treatment was optimized and our patient successfully underwent a personalised external aortic root support procedure (PEARS) as a contemporary alternative to existing aortic root surgical techniques. CONCLUSIONS: This case highlights the importance of interdisciplinary approach, close follow-up and multimodality imaging. The decision to intervene in a chronic type B aortic dissection is still challenging and should be made in experienced centers by an interdisciplinary team. However, if an acute complication occurs, thoracic endovascular aortic repair TEVAR is the method of choice. In all cases optimal medical treatment is important. There is increasing evidence that personalized external aortic root support procedure PEARS is effective in stabilizing the aortic root and preventing its dilatation and dissection not only in patients with Marfan syndrome, but also in other cases of aortic root dilation of other etiologies. Moreover, many publications have reported the additional benefit of reduction or even eradication of aortic regurgitation by improving coaptation of the aortic valve leaflets in dilated aortas.

Meta-analysis Examining the Usefulness of Angiotensin Receptor blockers for the Prevention of Aortic Root Dilation in Patients With the Marfan Syndrome.

The Marfan syndrome (MFS) patients are highly predisposed to thoracic aortic aneurysm and/or dissection, with virtually every patient having evidence of aortic disease at some point during their lifetime. We conducted a meta-analysis to investigate the efficacy of angiotensin receptor blockers (ARBs) in slowing down the progression of aortic dilatation in MFS patients. PUBMED, EMBASE, and COCHRANE databases were searched for relevant articles published from inception to February 1, 2020. We included randomized clinical trials evaluating the effect of ARBs on aortic root size in patients with MFS with a follow-up period of at least 2.5 years. Seven studies were included with a total of 1,510 patients. Our analysis demonstrated a significantly smaller change in aortic root and ascending aorta dilation in the ARBs treated group when compared with placebo (mean difference 0.68; 95% confidence interval [CI] -1.31 to -0.04; p = 0.04, I2 = 94%, and mean difference -0.13, 95% CI -0.17 to -0.09; p < 0.00001, I2 = 0%, respectively). ARBs as an add-on therapy to beta-blockers resulted in a significantly smaller change in aortic root dilation when compared with the arm without ARBs (mean difference -2.06, 95% CI -2.54 to -1.58; p < 0.00001, I2 = 91%). However, there was no statistically significant difference in the number of clinical events (aortic complications/surgery) observed in the ARBs arm when compared with placebo (Risk ratio of 1.01, 95% CI 0.74 to 1.38; p = 0.94, I2 = 0%). In conclusion, ARBs therapy is associated with a slower progression of aortic root dilation when compared with placebo and as an addition to beta-blocker therapy.

Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome.

BACKGROUND: Beta-blockers are the standard treatment in Marfan syndrome (MFS). Recent clinical trials with limited follow-up yielded conflicting results on losartan's effectiveness in MFS. OBJECTIVES: The present study aimed to evaluate the benefit of losartan compared with atenolol for the prevention of aortic dilation and complications in Marfan patients over a longer observation period (>5 years). METHODS: A total of 128 patients included in the previous LOAT (LOsartan vs ATenolol) clinical trial (64 in the atenolol and 64 in the losartan group) were followed up for an open-label extension of the study, with the initial treatment maintained. RESULTS: Mean clinical follow-up was 6.7 ± 1.5 years. A total of 9 events (14.1%) occurred in the losartan group and 12 (18.8%) in the atenolol group. Survival analysis showed no differences in the combined endpoint of need for aortic surgery, aortic dissection, or death (p = 0.462). Aortic root diameter increased with no differences between groups: 0.4 mm/year (95% confidence interval: 0.2 to 0.5) in the losartan and 0.4 mm/year (95% confidence interval: 0.3 to 0.6) in the atenolol group. In the subgroup analyses, no significant differences were observed considering age, baseline aortic root diameter, or type of dominant negative versus haploinsufficient FBN1 mutation. CONCLUSIONS: Long-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups. Therefore, losartan might be a useful, low-risk alternative to beta-blockers in the long-term management of these patients.

Inducing fibrogenesis and new interfibrillary bonds in post-laser in situ keratomileusis keratectasia.

Flap creation weakens the cornea and is a risk factor for keratectasia after laser in situ keratomileusis (LASIK). We describe a new technique to halt the progression of keratectasia by mechanically reintegrating the flap into the residual stroma. Deep stromal vertical puncturing is performed in the 4.0 to 9.0 mm paracentral corneal zone at a depth of 350 to 420 µm. The puncturing is applied in circumferential rows using a 25-gauge needle or a diamond blade, with denser puncturing at the level of the cone. In 5 eyes with worsening post-LASIK keratectasia, improved uncorrected and corrected visual acuities, corneal flattening, and a hyperopic shift were observed. There was no progression of keratectasia on serial topographies. New collagen fibrogenesis was documented by optical coherence tomography. The technique seems to be promising to halt the progression of post-LASIK keratectasia. More clinical data and longer follow-up are needed for validation.

Bracy procedure with ductal mucosal pancreaticogastrostomy and an internal stent for pancreatic complex deep injury: how to do it.

Pancreatic complex deep injury extending to the main pancreatic duct (MPD), caused by strong external forces such as traffic accidents, is lethal without emergency surgery. However, the best surgical procedure for this serious injury has not been established. The Bracey procedure is a relatively simple reconstructive technique involving pancreaticogastrostomy, but it is often followed by postoperative complications, such as dilatation of the MPD caused by anastomotic stenosis, as well as subsequent serious sequela such as repetitive pancreatitis and new-onset pancreatic diabetes. It is possible that the combination of ductal mucosal pancreaticogastrostomy (DMPG) and an internal stent might prevent anastomotic stenosis of the MPD. We found that the Bracey procedure was a safe and effective reconstructive procedure for five patients who suffered a pancreatic complex deep injury with MPD involvement. In three of these patients, postoperative dilatation of the MPD was prevented by combining the Bracey procedure with DMPG including an internal stent. Our experience suggests that this procedure is one of the best techniques for treating pancreatic complex deep injury extending to the MPD.

Surgical strategies protecting against right ventricular dilatation following tetralogy of Fallot repair.

BACKGROUND: Right ventricular (RV) volume overload increases morbidity and mortality after tetralogy of Fallot (TOF) repair. Surgical strategies like pulmonary leaflets sparing and tricuspid valve repair at time of primary repair may decrease RV overload. Our objective is to evaluate early and midterm results of pulmonary leaflets sparing with infundibular preservation and tricuspid valve repair in selected TOF patients with moderate pulmonary annular hypoplasia. METHODS: From 2011 to 2016; 46 patients with TOF and moderate pulmonary annular hypoplasia had surgical repair with sparing of the pulmonary valve leaflets. Concomitant tricuspid valve repair was performed in 33 patients (71.8%). Mean age was 13.1 ± 4.8 months, 68% were males (n = 31) and mean weight was 9.5 ± 2.3 kg. Preoperative McGoon ratio was 1.9 ± 0.4 and pulmonary valve z-score ranges from - 2 to - 3. Preoperative pressure gradient of RVOT was 80.9 ± 7.7 mmHg and 10.9% had minor coronary anomalies (n = 5). RESULTS: All repairs were performed through trans-atrial trans-pulmonary approach. 87% had pulmonary valve commissurotomy (n = 40). Mean cardiopulmonary bypass time was 71 ± 6.3 min and ischemic time 42.4 ± 4.9 min. Hospital mortality occurred in 4.3% (n = 2). Mean RVOT pressure gradient decreased significantly postoperatively (28.8 ± 7.2 mmHg, p-value< .001) and at the last follow up (23.6 ± 1.8 mmHg, p-value< .001). Pulmonary regurgitation progressed by one grade in 2 patients compared to the postoperative grade. 1 patient (2.5%) had late mortality and reintervention was required in 5 patients (12.5%). CONCLUSION: Pulmonary leaflets sparing, and tricuspid valve repair are safe for TOF repair with no added morbidity or mortality. These procedures could contribute to reducing right ventricular volume overload over time after TOF repair.

Biomechanics of Failed Pulmonary Autografts Compared With Normal Pulmonary Roots.

BACKGROUND: Progressive dilatation of pulmonary autografts after the Ross operation may reflect inadequate remodeling of the native pulmonary root to adapt to systemic circulation. Understanding the biomechanics of autograft root dilatation may aid designing strategies to prevent dilatation. We have previously characterized normal human pulmonary root material properties; however, the mechanical properties of failed autografts are unknown. In this study, failed autograft roots explanted during reoperation were acquired, and their material properties were determined. METHODS: Failed pulmonary autograft specimens were obtained from patients undergoing reoperation after the Ross operation. Fresh human native pulmonary roots were obtained from the transplant donor network as controls. Biaxial stretch testing was performed to determine tissue mechanical properties. Tissue stiffness was determined at patient-specific physiologic stresses at pulmonary pressures. RESULTS: Nonlinear stress-strain response was present in both failed autografts and normal pulmonary roots. Explanted pulmonary autografts were less stiff than were their native pulmonary root counterparts at 8 mm Hg (134 ± 42 vs 175 ± 49 kPa, respectively) (p = 0.086) and 25 mm Hg (369 ± 105 vs 919 ± 353 kPa, respectively) (p = 0.006). Autograft wall stiffness at both 8 and 25 mm Hg was not correlated with age at the Ross procedure (p = 0.898 and p = 0.813, respectively) or with time in the systemic circulation (p = 0.609 and p = 0.702, respectively). CONCLUSIONS: Failed pulmonary autografts retained nonlinear response to mechanical loading typical of healthy human arterial tissue. Remodeling increased wall thickness but decreased wall stiffness in failed autografts. Increased compliance may explain progressive autograft root dilatation in autograft failures.

Combined laser in-situ keratomileusis and accelerated corneal cross-linking: an update.

PURPOSE OF REVIEW: The purpose is to review the literature of combined laser in-situ keratomileusis (LASIK) and accelerated corneal collagen cross-linking (CXL) in context of its indications-contraindications, kerato-refractive, visual and safety outcomes, particularly with reference to preventing the development of post-LASIK ectasia. RECENT FINDINGS: LASIK + accelerated CXL has been developed with the rationale that the addition of CXL after LASIK may strengthen the LASIK compromised corneal biomechanics and minimize the complications such as post-LASIK ectasia. Different clinical studies have documented the safety and efficacy of LASIK + accelerated CXL for the correction of myopia or hyperopia and in the patients with low predicted residual bed thickness. SUMMARY: Available literature shows that refractive and keratometric outcomes of LASIK + accelerated CXL are comparable or better than LASIK alone. Less regression has been observed after LASIK + accelerated CXL compared with LASIK alone and no case of post-LASIK ectasia development has been reported among 673 eyes with the follow-up ranging from 3 months to 4.5 years. Future studies with large numbers of patients and longer postoperative follow-ups are needed to establish the efficacy of LASIK + accelerated CXL in preventing the development of post-LASIK ectasia.

[Aortic root dilatation rate in pediatric patients with Marfan syndrome treated with losartan]. / Progressione della dilatazione aortica nel paziente pediatrico con sindrome di Marfan in terapia medica con losartan.

BACKGROUND: Medical therapy with angiotensin II receptor blockers/angiotensin-converting enzyme inhibitors and/or beta-blockers was reported to reduce aortic root dilatation rates in pediatric patients with Marfan syndrome. No data are available in the literature on losartan effects after 3 years of therapy. The aim of our study was to establish whether losartan reduces aortic root dilatation rates in pediatric patients with Marfan syndrome in the mid and long term. METHODS: This is a retrospective analysis of 38 pediatric patients with Marfan syndrome followed at the Marfan Clinic of S. Orsola-Malpighi Hospital of the University of Bologna (Italy). Aortic diameters were measured at sinuses of Valsalva and proximal ascending aorta with transthoracic echocardiography. RESULTS: After a mean follow-up of 4.5 ± 2.5 years (range 2-9 years), aortic root z score at sinuses of Valsalva and proximal ascending aorta remained stable. The average annual rate of change in aortic root z score was -0.1 ± 0.4 and 0 ± 0.3 at sinuses of Valsalva and proximal ascending aorta, respectively. The mean dose of losartan was 0.7 ± 0.3 mg/kg/day. Three patients were non-responders, probably because of late beginning or low dose of therapy. Eight patients underwent cardiac surgery (aortic root surgery in 5 and mitral valve repair in 3), all of them started losartan later in life. CONCLUSIONS: Despite the retrospective design of the study and the small sample size, a beneficial effect of losartan therapy was observed in pediatric patients with Marfan syndrome in the mid and long term. Late beginning or low doses of losartan can turn off the effects of therapy.

A modification of the pulmonary autograft procedure to prevent late autograft dilatation.

Although the pulmonary autograft procedure for aortic valve replacement is a commonly utilized option for children, its use is diminishing in adult-aged patients. One commonly cited concern is the tendency for the pulmonary autograft to dilate in the aortic position. This article reviews a technique we have used in 36 patients since October, 2004 that stabilizes the autograft so that it cannot dilate. There have been no operative or late deaths and the autograft has continued to function in 34 patients. Two patients have undergone autograft replacement because of early failure, which we believe was likely related to technical considerations in our early technique (first reported in the 2005 STCVS Pediatric Cardiac Surgery Annual). The technical modifications described in this article have produced a more reliable and reproducible technique and have not resulted in any autograft failures in our experience. One patient with Marfan's syndrome and a bicuspid aortic valve is symptom- and dilation-free 8 years post op, with no autograft or pulmonary homograft insufficiency, normal activity and a stable aortic root by serial echocardiography. Our results suggest that this technique might be applicable for selected adult patients in whom autograft growth is not necessary and for whom the risk of autograft dilatation would provide a reason to avoid a pulmonary autograft procedure.

Aorta pathology and pregnancy.

In addition to the haemodynamic changes in pregnancy, hormones also induce changes in the aortic wall. Women with diseases like Marfan syndrome, Ehlers-Danlo syndrome, or other aortic abnormalities, have an increased risk of complications during pregnancy. Counselling and risk assessment before pregnancy is mandatory for all women with known aortic disease. Proper information should be provided about the risks of morbidity and mortality during pregnancy and information on the risks for the fetus, including the potential recurrence of disease in the offspring. Evaluation of past medical and family history, the aortic size before conception, and any increase in size before and during pregnancy, is essential to try and estimate the risk of aortic dissection. If the aorta is dilated, prophylactic repair before pregnancy may be indicated. In some cases, elective surgery during pregnancy may be warranted. In women with a severely dilated ascending aorta, caesarean section is, at present, the advised mode of delivery.

Autologous intestinal reconstructive surgery to reduce bowel dilatation improves intestinal adaptation in children with short bowel syndrome.

OBJECTIVES: Intestinal failure (IF) is a common consequence of neonatal small bowel pathology. In our experience, bowel dilatation is often responsible for the IF state in patients who fail to adapt despite adequate residual bowel length. The aim of the present study was to investigate the role of surgery to reduce bowel dilatation, and thus favour PN independence, for these children. METHODS: Data were collected prospectively for all of the patients referred to our unit for a 7-year period (2004-2011). Eight patients (2 congenital atresia, 2 gastroschisis with atresia, 1 simple gastroschisis, 3 necrotising enterocolitis) with gut dilatation who failed adaptation despite a bowel length >40 cm were identified. Preoperatively, all patients were totally dependent on parenteral nutrition (PN). Patients were managed by longitudinal intestinal lengthening and tailoring (n = 3), serial transverse enteroplasty (n = 2), or tapering enteroplasty (n = 3). RESULTS: Median age at time of surgery was 273 days (103-1059). Mean gut length increased from 51 (35-75) to 73 cm (45-120) following surgery (P = 0.02). Incidence of sepsis (P = 0.01) and peak serum bilirubin levels (P = 0.005) were reduced postoperatively. PN was discontinued after a median of 110 days (35-537) for 7 patients; 1 patient remains on PN 497 days after surgery. CONCLUSIONS: These data indicate that reconstructive surgery to reduce bowel diameter may be an effective technique for treating IF in patients with short bowel syndrome, without sacrificing intestinal length. We suggest that this technique may reduce the need for bowel transplantation in this group of patients.

Effect of novel limited-spectrum MMP inhibitor XL784 in abdominal aortic aneurysms.

BACKGROUND: Inhibiting the growth of small abdominal aortic aneurysms (AAAs) is a clinically valuable goal and fills an important therapeutic void. Based on studies in animals and humans, inhibition of the activity of elastolytic matrix metalloproteinases (MMPs) has the potential to slow AAA expansion and limit morbidity and the need for surgery. Previous attempts to make use of the synthetic MMP inhibitors in the treatment of chronic conditions have been limited by intolerable side effects. The limited-spectrum synthetic MMP inhibitor, XL784, was well tolerated and devoid of side-effects associated with other nonspecific MMP inhibitors in phase I studies. We hypothesized that clinically relevant doses of XL784 would be effective at inhibiting aneurysm development in a mouse model. METHODS: The 14-day elastase-perfusion model of AAA in mice was used. An initial screening study of XL784 (50 [n = 17], 125 [n = 17], and 250 mg/kg [n = 18]) administered via gavage daily until harvest. Controls received diluent alone (n = 18) or doxycycline in drinking water (n = 19). Aortic diameter was measured pre-perfusion (AD(pre)) and at harvest (AD(har)). A second study used XL784 (250 [n = 9]; 375 [n = 9], and 500 mg/kg [n = 14]) and diluent alone (n = 9) administered via gavage. The percentage dilatation [%ΔAD = [(AD(har) - AD(pre))/AD(pre)] ×100] was calculated and elastin and inflammatory content was scored. RESULTS: All mice tolerated the treatments similarly. Control mice all developed aneurysms with a mean %ΔAD of 158.5% ± 4.3%. Treatment with all doses of XL784 and doxycycline were effective in inhibiting aortic dilatation. There was a clear dose-response relationship between XL784 and reductions in aortic dilatation at harvest (50 mg/kg 140.4% ± 3.2%; 125 mg/kg 129.3% ± 5.1%; 250 mg/kg 119.2% ± 3.5%; all Ps < .01 compared to control). This continued with the higher doses (375 mg/kg 88.6% ± 4.4%; 500 mg/kg 76.0% ± 3.5%). The highest 2 doses of XL784 tested were more effective than doxycycline (112.2% ± 2.0%, P < .05) in inhibiting maximal dilatation of the aorta after elastase perfusion.

Progesterone induced mesenchymal differentiation and rescued cystic dilation of renal tubules of Pkd1(-/-) mice.

Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary disease affecting the kidneys, is caused in 85% of cases by mutations in the PKD1 gene. The protein encoded by this gene, polycystin-1, is a renal epithelial cell membrane mechanoreceptor, sensing morphogenetic cues in the extracellular environment, which regulate the tissue architecture and differentiation. However, how such mutations result in the formation of cysts is still unclear. We performed a precise characterization of mesenchymal differentiation using PAX2, WNT4 and WT1 as a marker, which revealed that impairment of the differentiation process preceded the development of cysts in Pkd1(-/-) mice. We performed an in vitro organ culture and found that progesterone and a derivative thereof facilitated mesenchymal differentiation, and partially prevented the formation of cysts in Pkd1(-/-) kidneys. An injection of progesterone or this derivative into the intraperitoneal space of pregnant females also improved the survival of Pkd1(-/-) embryos. Our findings suggest that compounds which enhance mesenchymal differentiation in the nephrogenesis might be useful for the therapeutic approach to prevent the formation of cysts in ADPKD patients.

Accelerated corneal crosslinking concurrent with laser in situ keratomileusis.

PURPOSE: To assess accelerated corneal collagen crosslinking (CXL) applied concurrently with laser in situ keratomileusis (LASIK) in a small group of patients. SETTING: Beyoglu Eye Research and Training Hospital, Istanbul, Turkey. DESIGN: Prospective pilot interventional case series. METHODS: In May 2010, patients had LASIK with concurrent accelerated CXL in 1 eye and LASIK only in the fellow eye to treat myopia or myopic astigmatism. The follow-up was 12 months. The attempted correction (spherical equivalent) ranged from -5.00 to -8.50 diopters (D) in the LASIK-CXL group and from -3.00 to -7.25 D in the LASIK-only group. Main outcome measures were manifest refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, and the endothelial cell count. RESULTS: Eight eyes of 3 women and 1 man (age 22 to 39 years old) were enrolled. At the 12-month follow-up, the LASIK-CXL group had a UDVA and manifest refraction equal to or better than those in the LASIK-only group. No eye lost 1 or more lines of CDVA at the final visit. The endothelial cell loss in the LASIK-CXL eye was not greater than in the fellow eye. No side effects were associated with either procedure. CONCLUSIONS: Laser in situ keratomileusis with accelerated CXL appears to be a promising modality for future applications to prevent corneal ectasia after LASIK treatment. The results in this pilot series suggest that evaluation of a larger study cohort is warranted. FINANCIAL DISCLOSURE: Drs. Yilmaz and Marshall are paid consultants to Avedro, Inc. No other author has a financial or proprietary interest in any material or method mentioned.

Carbon dioxide vs. air insufflation in ileo-colonoscopy and in gastroscopy plus ileo-colonoscopy: a comparative study.

INTRODUCTION: insufflation with carbon dioxide (CO2) during endoscopies compared to air is associated with a decrease in abdominal discomfort after the examination, because CO2 is readily absorbed through the small intestine and eliminated by the lungs. AIM: the objective of this randomized clinical trial was to assess the effect of CO2 insufflation on pain and abdominal distension after an ileo-colonoscopy (I) and after an ileo-colonoscopy plus gastroscopy (I+G). MATERIAL AND METHODS: we included a total of 309 patients in the study and all endoscopies were performed under sedation with propofol. Two hundred fourteen patients underwent an I (132 with CO2 / 82 with air) and 95 underwent an I+G (53 with CO2 / 42 with air). Abdominal pain was studied at 10, 30 and 120 minutes of exploration and abdominal perimeter difference before and after the procedure. RESULTS: both in group I and in group I+G, the use of CO2 translated into an average of abdominal pain significantly lower (p < 0.05). Similarly, a smaller increase in waist circumference was found among group I and group I+G, in patients where CO2 was used (p < 0.05). CONCLUSION: the insufflation of CO2 instead of air during the performance of endoscopy significantly reduces the discomfort and abdominal pain after an ileo-colonoscopy and after a gastroscopy + ileo-colonoscopy.