Clinical diagnosis of Larsen syndrome, Stickler syndrome and Loeys-Dietz syndrome in a 19-year old male: a case report.

BACKGROUND: Larsen syndrome is a hereditary disorder characterized by osteochondrodysplasia, congenital large-joint dislocations, and craniofacial abnormalities. The autosomal dominant type is caused by mutations in the gene that encodes the connective tissue protein, filamin B (FLNB). Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by arterial aneurysms, dissections and tortuosity, and skeletal, including craniofacial, manifestations. Mutations in five genes involved in the transforming growth factor beta (TGF-ß) signaling pathway cause five types of LDS. Stickler syndrome is a genetically heterogeneous arthro-ophthalmopathy caused by defects in collagen, exhibiting a wide specter of manifestations in connective tissue. A rare case is reported that was diagnosed with all these three hereditary connective tissue disorders. CASE PRESENTATION: A 19 year-old, Norwegian male with a clinical diagnosis of Larsen syndrome and with healthy, non-consanguineous parents attended a reference center for rare connective tissue disorders. Findings at birth were hypotonia, joint hypermobility, hyperextended knees, adductovarus of the feet, cervical kyphosis, craniofacial abnormalities, and an umbilical hernia. From toddlerhood, he required a hearing aid due to combined conductive and sensorineural hearing loss. Eye examination revealed hyperopia, astigmatism, and exotropia. At 10 years of age, he underwent emergency surgery for rupture of an ascending aortic aneurysm. At 19 years of age, a diagnostic re-evaluation was prompted by the findings of more distal aortic dilation, tortuosity of precerebral arteries, and skeletal findings. High throughput sequencing of 34 genes for hereditary connective tissue disorders did not identify any mutation in FLNB, but did identify a de novo missense mutation in TGFBR2 and a nonsense mutation in COL2A1 that was also present in his unaffected father. The diagnosis was revised to LDS Type 2. The patient also fulfills the proposed criteria for Stickler syndrome with bifid uvula, hearing loss, and a known mutation in COL2A1. CONCLUSION: LDS should be considered in patients with a clinical diagnosis of Larsen syndrome, in particular in the presence of arterial aneurysms or tortuosity. Due to genetic heterogeneity and extensive overlap of clinical manifestations, genetic high throughput sequencing analysis is particularly useful for the differential diagnosis of hereditary connective tissue disorders.

Editor's Choice - The National Norwegian Carotid Study: Time from Symptom Onset to Surgery is too Long, Resulting in Additional Neurological Events.

OBJECTIVE/BACKGROUND: The objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery. METHODS: This was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated. RESULTS: Three hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%. CONCLUSION: This national study with almost complete inclusion and follow-up shows that the delays occur mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

Trends in Abdominal Aortic and Iliac Aneurysm Repairs in Norway from 2001 to 2013.

OBJECTIVE/BACKGROUND: The objective was to examine trends in abdominal aortic and iliac aneurysm repairs in Norway from 2001 to 2013, and study regional variations and organizational developments in this type of vascular surgery. METHODS: This was a retrospective study on aortic and iliac aneurysm repairs using data from the Norwegian Patient Register. The vascular centers were categorized by yearly volume of repairs into small (<18), medium (18-49) and large (≥50). Incidence rates were assessed per 100,000 ≥ 60 years. The percentage of endovascular aneurysm repairs (EVAR) was calculated among the conducted repairs at the three categories of centers and the South-Eastern, Western, Central, and Northern Norway Regional Health Authority (NRHA). RESULTS: The national incidence rates of intact repairs per 100,000 ≥ 60 years increased from 57.4 to 65.7 (p < .01). Ruptured repairs decreased from 19.7 to 9.2 (p < .01). The rate of EVAR increased from 6.0 to 29.9 (p < .01) in intact and from 0.4 to 2.5 (p < .01) in ruptured repairs. The vascular centers were reduced from 25 to 16. The rate of EVAR was 27.1% (p < .01) higher at large centers and 7.9% (p < .03) higher at medium centers compared with small centers, and from 11.1% to 15.7% higher (p < .01) at the Central, Western, and Northern NRHA compared with the South-Eastern NRHA, which had the most centers (also in the large category). The national increase in intact EVAR from 10.6% to 43.3% was less compared with many other Western countries. CONCLUSION: During the study period the rates of intact repairs increased while the ruptured repairs decreased. EVAR was associated with centers performing high volumes of abdominal aortic and iliac aneurysm repairs and regional authorities organized with few centers.

Periprosthetic leak and rupture after endovascular repair of abdominal aortic aneurysm: the significance of device design for long-term results.

We present a case of abdominal aortic aneurysm treated with an endovascular bifurcated aortic graft in which a periprosthetic leak caused by a tear in the polyester prosthesis appeared between 9 and 12 months after surgery. The tear appeared adjacent to a suture breakage that caused separation of two struts of the nitinol wire framework in the body of the stent graft. The leak was sealed with insertion of a new endovascular tube graft into the body of the bifurcation. Eight months later, the patient had a nonfatal rupture of the abdominal aortic aneurysm because detachment of the second limb from the bifurcation caused a new major periprosthetic leak. According to the manufacturer of this device, suture breakage with separation of metal components is commonly seen, but perforation of the polyester prosthesis caused by movement of the metal stent against the fabric has not been reported. It is likely that this occurred in our patient. Detachment of the second limb from the bifurcated stent, causing a rupture, has been described before. Increasing angulation and tortuosity of the stent graft, as a result of either remodeling of the sac or elongation of the stent, and reduced compliance to angulation after the stent-in-stent procedure might have contributed to the detachment in this case.

[Surgery for abdominal aortic aneurysm. What is an acceptable complications rate?]. / Kirurgi for abdominale aortaaneurismer. Hva er akseptabel komplikasjonsfrekvens?

At the annual meeting of the Vascular Section of the Scandinavian Surgical Society in 1993 it was decided to discuss standards for quality in vascular surgery. This article is discussing operations for abdominal aortic aneurysms with special reference to early mortality and complications like graft infection and aortoenteric fistula. The discussion is based on national vascular registers and investigations on vascular surgical activity in the Scandinavian countries. In addition, a survey of the literature is given. Although these data should be regarded as a guide-line only, we feel that one should try to keep the 30 day mortality following elective resection for asymptomatic abdominal aortic aneurysm below 5-7 per cent. A mortality less than 50-60 per cent following operation for ruptured aneurysm may be regarded as reasonable. Patient-selection regarding age, concomitant disease etc. could significantly influence these results, and should be taken into consideration when comparison between different series is made. Graft infection is a serious complication and if the frequency is higher than 2 per cent, or there is an accumulation of graft infections in a vascular centre, the hospital routines should be reviewed carefully. The occurrence of infection is higher following operations for ruptured aneurysms than following elective operations. Early operations for haemorrhage and early occlusion should be below 5-6 per cent. Some authors have shown a correlation between the volume of operation, postoperative mortality and the frequency of complications. We therefore think that it might be reasonable to suggest that at least patients who have concomitant diseases like serious coronary heart disease or renal insufficiency should be operated on in vascular centres.(ABSTRACT TRUNCATED AT 250 WORDS)

The significance of probe design in evaluation of colonic perfusion with laser Doppler flowmetry.

The significance of probe design for laser Doppler flowmetry measurement depth and variation was investigated by determining flux versus pressure relations and spatial variability with various probes placed on the serosal surface of porcine sigmoid colon. For two large probes (three optical fibers with diameter and center separation > or = 500 microns) the flux versus pressure relations showed autoregulation, indicating that the mucosal perfusion contributed to the flux signal. The curves were reproducible between individuals. With two smaller probes linear flux versus pressure relations were obtained, indicating a shallow measurement not influenced by the autoregulated mucosal perfusion. The spatial variation expressed as coefficients of variation of repeated recordings at each pressure level was significantly greater with the smaller probes (p < 0.001). For clinical use the larger probes should be preferred. These include all wall layers, and only 3 repeated recordings are needed to obtain a reproducible mean flux value within +/- 10%, as opposed to 10 with the smaller probes.

Laser Doppler flux and tissue oxygen tension as indicators of colonic perfusion in pigs.

OBJECTIVE: To evaluate laser Doppler flowmetry (LDF) and tissue oximetry (TpO2) for intraoperative assessment of colonic perfusion in pigs. MATERIAL: Eight pigs weighing from 19-22 kg. INTERVENTIONS: Relationships of laser Doppler flux and TpO2 to mean arterial pressure (MAP) were measured in porcine sigmoid colon. The influence of different fractional inspired oxygen concentrations (FiO2) and the variability of the laser Doppler flux were evaluated. RESULTS: Highly significant reproducible non-linear perfusion compared with pressure relations were found with both methods (r > or = 0.9, p < 0.0001). There was a rapid decrease when MAP fell below 90 mmHg. The dependency of TpO2 on FiO2 was omitted by using the ratio TpO2:PaO2. The coefficient of variation of repeated LDF recordings of 30 second duration with the hand held probe was 0.11 (0.07-0.16) (median and 95% confidence interval). Three recordings gave a reproducible mean flux with an estimated precision of 10% either way. Simultaneous recordings with sutured and hand-held probes correlated well (r > or = 0.9, p < or = 0.01). CONCLUSION: Both methods yielded quantitative and reproducible intraoperative assessments of colonic perfusion, and are applicable for clinical use.

Perfusion of the human distal colon and rectum evaluated with endoscopic laser Doppler flowmetry. Methodologic aspects.

The aim of this study was to evaluate methodologic aspects of colonoscopic laser Doppler flowmetry. A Periflux PF1d flowmeter, set to 4 kHz/0.2 sec, with an endoscopic probe (PF 109) was used. In 20 patients, with a median age of 70 years and without colonic disease, flux was recorded at 10, 40, 30, 20, and again at 10 cm from the anal verge. A median of three repeated recordings were made at each level, to calculate average flux and spatial variation. Median flux was 158 (150-167) perfusion units, and the coefficient of variation of repeated recordings 0.14 (0.12-0.17). There was no regional variation, and no increase in flux at 10 cm from the start until the end of the procedure. Pressure of the probe against the bowel wall and severe distention significantly reduced the flux. The interference of light from the endoscopic light source on the flux could not be predicted. It differed with different light sources, and also with the length of probe coming out of the colonoscope--that is, the distance from the light to the measurement point. To avoid the problem, the light source should be turned off while recording.

Intraoperative prediction of ischaemic injury of the bowel: a comparison of laser Doppler flowmetry and tissue oximetry to histological analysis.

Intraoperative diagnosis of inadequate colonic perfusion would contribute to prevention of ischaemic colitis after abdominal aortic reconstructions. The aim of this study was to evaluate laser Doppler flowmetry (LDF) and tissue oximetry (TpO2) as predictors of the development of bowel necrosis. Devascularised loops of colon and ileum in anaesthetised pigs were divided into 10-20 mm segments and measurements of laser Doppler flux and TpO2 were performed in each segment. After 7 h of ischaemia the segments were resected for histological and biochemical analysis. In 65 colonic and 58 ileal segments a significantly lower flux was found in segments with necrosis of greater than or equal to 30% of the mucosal thickness compared to segments with necrosis of less than or equal to 10% (p less than 0.01). The discriminant flux value was 50 perfusion units, confirming a previous clinical study. The specificity was 0.96 and the sensitivity 0.94. Flux was inversely correlated to tissue lactate concentration. Significantly lower TpO2 was found in 19 colonic segments with necrosis of greater than or equal to 30% of mucosa compared to 19 colonic segments with necrosis of less than or equal to 10% (p less than 0.01). Using a discriminant value of 5kPa, a specificity of 0.79, and a sensitivity of 0.95 were calculated. In 27 ileum segments no significant difference in TpO2 between different histological groups was found (p greater than 0.30). The results show that LDF and TpO2 can predict ischaemic injury of the colon, and LDF also of the small bowel.

Laser Doppler flowmetry in evaluation of colonic blood flow during aortic reconstruction.

Intraoperative laser Doppler flowmetry (LDF) was used to measure blood perfusion in terminal ileum and sigmoid colon in eight patients operated on for aorto-iliac occlusive disease (AIO) and eight patients for abdominal aortic aneurysm (AAA). The aim of the study was to evaluate the influence of clamping the inferior mesenteric artery (IMA) on intestinal perfusion. LDF-measured sigmoid colon flow was also compared with the postoperative clinical course, to define a limit below which risk of ischaemic colitis is high and revascularisation should be considered. Neither clamping of the IMA nor aortic reconstruction affected perfusion in the terminal ileum in any group. Sigmoid colon perfusion in the AAA-group showed a slight, not significant reduction after reconstruction (P = 0.09). AIO patients showed significant flow reduction in the sigmoid colon when the IMA was clamped (P less than 0.05), returning to the initial value after aortic reconstruction with end-to-side proximal anastomosis and preservation of IMA. AAA patients, operated with end-to-end proximal anastomosis and ligation of IMA, had significantly lower sigmoid colon perfusion after aortic reconstruction than AIO patients (P less than 0.05). Thirteen patients had sigmoid colon flux values greater than 5 RFU (Relative Flux Units) after reconstruction, and had no complications. Three aneurysm patients had flux values less than 3.3 RFU, and developed symptoms of ischaemic colitis. We conclude that LDF can be easily applied to the evaluation of colonic blood flow during aortic surgery. Flux values less than 4 RFU may indicate a risk of ischaemic colitis, and justify revascularisation of the colon.