Mutations of the Imprinted CDKN1C Gene as a Cause of the Overgrowth Beckwith–Wiedemann Syndrome: Clinical Spectrum and Functional Characterization

Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder associating macroglossia, abdominal wall defects, visceromegaly, and a high risk of childhood tumor. Molecular anomalies are mostly epigenetic; however, mutations of CDKN1C are implicated in 8% of cases, including both sporadic and familial forms. We aimed to describe the phenotype of BWS patients with CDKN1C mutations and develop a functional test for CDKN1C mutations. For each propositus, we sequenced the three exons and intron–exon boundaries of CDKN1C in patients presenting a BWS phenotype, including abdominal wall defects, without 11p15 methylation defects. We developed a functional test based on flow cytometry. We identified 37 mutations in 38 pedigrees (50 patients and seven fetuses). Analysis of parental samples when available showed that all mutations tested but one was inherited from the mother. The four missense mutations led to a less severe phenotype (lower frequency of exomphalos) than the other 33 mutations. The following four tumors occurred: one neuroblastoma, one ganglioneuroblastoma, one melanoma, and one acute lymphoid leukemia. Cases of BWS caused by CDKN1C mutations are not rare. CDKN1C sequencing should be performed for BWS patients presenting with abdominal wall defects or cleft palate without 11p15 methylation defects or body asymmetry, or in familial cases of BWS.     

Cardiac CT: Technological Advances in Hardware,Software, and Machine Learning Applications

Purpose of Review

Multidetector row computed tomography (CT) allows noninvasive imaging of the heart and coronary arteries. The purpose of this review is to briefly summarize recent advances in CT hardware and software technology, and machine learning applications for cardiovascular imaging.

Recent Findings

In the last decades, there have been significant improvements in CT hardware focusing on faster gantry rotation resulting in improved temporal resolution. Concurrent hardware improvements include improved spatial resolution and higher coverage of the patient, enabling faster acquisition. Advances in cardiac CT software include methods for measurement of noninvasive FFR, coronary plaque characterization, and adipose tissue characteristics around the heart. Machine learning approaches using cardiac CT have been shown to improve both risk of prognosis and lesion-specific ischemia.

Summary

Recent advances in CT hardware and software have expanded the clinical utility of CT for cardiovascular imaging. In the next decades, continued advances can be anticipated in these areas, and in machine learning applications in cardiac CT, as they are incorporated into clinical routine for image acquisition, image analysis, and prediction of patient outcomes.

     

In-stent fractional flow reserve variations and related optical coherence tomography findings: the FFR–OCT co-registration study

We sought to assess in-stent variations in fractional flow reserve (FFR) in patients with previous percutaneous coronary intervention (PCI) and to associate any drop in FFR with findings by optical coherence tomography (OCT) imaging. Suboptimal post-PCI FFR values were previously associated with poor outcomes. It is not known to which extent in-stent pressure loss contributes to reduced FFR. In this single-arm observational study, 26 patients who previously underwent PCI with drug-eluting stent or scaffold implantation were enrolled. Motorized FFR pullback during continuous intravenous adenosine infusion and OCT assessments was performed. Post-PCI FFR?<?0.94 was defined as suboptimal. At a median of 63 days after PCI (interquartile range: 59–64 days), 18 out of 26 patients (72%) had suboptimal FFR. The in-stent drop in FFR was significantly higher in patients with suboptimal FFR vs. patients with optimal FFR (0.08?±?0.07 vs. 0.01?±?0.02, p?<?0.001). Receiver operating characteristic curve analysis showed that an in-stent FFR variation of >?0.03 was associated with suboptimal FFR. In patients with suboptimal FFR, the OCT analyses revealed higher mean neointimal area (respectively: 1.06?±?0.80 vs. 0.51?±?0.23 mm²; p?=?0.018) and higher neointimal thickness of covered struts (respectively 0.11?±?0.07 vs. 0.06?±?0.01 mm; p?=?0.021). Suboptimal FFR values following stent-implantation are mainly caused by significant in-stent pressure loss during hyperemia. This finding is associated to a larger neointimal proliferation.     

Novel Z Scores to Correct Biases Due to Ventricular Volume Indexing to Body Surface Area in Adolescents and Young Adults

BackgroundReference values for cardiac magnetic resonance imaging (cMRI) in children and young adults are scarce. This leads to risk stratification of patients with congenital heart diseases being based on volumes indexed to body surface area (BSA). We aimed to produce cMRI Z score equations for ventricular volumes in children and young adults and to test whether indexing to BSA resulted in an incorrect assessment of ventricular dilation according to sex, body composition, and growth.MethodsWe retrospectively included 372 subjects aged < 26 years with either normal hearts or conditions with no impact on ventricular volumes (reference group), and 205 subjects with repaired tetralogy of Fallot (TOF) aged < 26 years. We generated Z score equations by means of multivariable regression modelling. Right ventricular dilation was assessed with the use of Z scores and compared with indexing to BSA in TOF subjects.ResultsVentricular volume Z scores were independent from age, sex, and anthropometric measurements, although volumes indexed to BSA showed significant residual association with sex and body size. In TOF subjects, indexing overestimated dilation in growing children and underestimated dilation in female compared with male subjects, and in overweight compared with lean subjects.ConclusionsIndexed ventricular volumes measured with cMRI did not completely adjust for body size and resulted in a differential error in the assessment of ventricular dilation according to sex and body size. Our proposed Z score equations solved this problem. Future studies should evaluate if ventricular volumes expressed as Z scores have a better prognostic value than volumes indexed to BSA.     

Electromechanical time course in frog ventricle: Manipulation of calcium level during voltage clamp

Extracellular calcium concentration was rapidly altered in the “diastolic” interval between two contractions, and also during the time course of a single 10 s clamp pulse. The results strongly suggest that contraction of frog ventricular muscle is largely determined by a continuous, voltage-dependent influx of calcium into the cell, with little or no contribution from mechanisms involving release of calcium from intracellular stores. In addition, contraction can be graded, as a rapid response to alterations in extracellular calcium concentration.     

Portomesenteric Venous Thrombectomy Using Inari Triever Aspiration Catheter (FlowTriever)

CardioVascular and Interventional Radiology -     

Diagnostic dilemmas in patients with cystic neoplasms of the pancreas

Summary Cystic neoplasms of the pancreas (CNP) are rare lesions that can be difficult to diagnose preoperatively. Twenty patients with cystic neoplasms of the pancreas including five microcystic adenomas, six benign mucinous cystic neoplasms, three malignant mucinous cystic neoplasms, two solid and papillary epithelial neoplasms, and four cystic neuroendocrine tumors were treated at a single institution between 1962 and 1987. The average duration of symptoms prior to diagnosis was 10 months. Five patients were asymptomatic. Forty percent of patients presented with an abdominal mass. Plain abdominal x-rays and UGI barium contrast studies were never diagnostic. Ultrasonography, computerized tomography (CT) and visceral angiography aided in the correct diagnosis in 28%, 36%, and 75% of patients studied, respectively. Overall a correct diagnosis was made preoperatively in only 35% of patients. Twelve of 13 patients were correctly diagnosed at laparotomy with intraoperative biopsy. Without biopsy the mass was misdiagnosed at laparotomy in five of six cases. CNP must be suspected inany patients who present with an upper abdominal mass with or without abdominal pain and no history of pancreatitis. CT may be diagnostic in up to one third of cases and should be obtained routinely to demonstrate the proximity of the lesion to other structures. Visceral angiography should also be obtained prior to operation. A generous incisional biopsy should be obtained of all pancreatic cysts that are not to be resected.     

Results of ileal J-pouch-anal anastomosis in familial adenomatous polyposis complicated by rectal carcinoma

PURPOSE: Rectal cancer frequently occurs in patients with familial adenomatous polyposis (FAP) and, in some cases, proctocolectomy and ileal pouch-anal anastomosis (IPAA) can be proposed as an alternative to end ileostomy. This study aimed to assess the results of IPAA for familial adenomatous polyposis complicated by rectal carcinoma. PATIENTS AND METHODS: Postoperative morbidity and bowel function following IPAA were assessed in six patients who had a mesorectal excision for rectal cancer. The functional results were compared with those obtained after IPAA in 134 FAP patients without bowel cancer. RESULTS: Carcinomas were located at a mean of 11 cm from the dentate line. There were no postoperative complications. One patient with synchronous hepatic metastases died 6 months after operation and the 5 others were alive without recurrence after a mean follow-up of 29 months. Mean frequency of defecation was 6.5/day (vs. 4.2/day in patients without carcinoma), 86 percent of patients had nocturnal defecation (vs. 50 percent), day and night continence were normal in 66 percent and 33 percent of patients, respectively, compared with 90 percent and 85 percent for IPAA without cancer. Pouch excision was required in one patient for unsatisfactory functional result. CONCLUSION: IPAA can be safely performed for cancer of the upper rectum complicating FAP, but a poor functional outcome related to mesorectal excision has to be expected.