Ogilvie's syndrome

We reviewed the clinical presentation, management, and outcome of 25 patients with Ogilvie's syndrome (acute colonic pseudoobstruction) at Memorial Sloan-Kettering Cancer Center from 1982 through 1985. All patients had cancer and severe associated medical problems. Abdominal x-rays uniformly showed cecal distension ranging between 9 and 18 cm. Twenty-four of the 25 patients were treated with conservative nonendoscopic management. One patient had an exploratory laparotomy for prophylactic cecostomy after only one day of conservative therapy. Of the 24 patients treated conservatively, 23 (96%) improved by both clinical and radiologic criteria in a mean of 3.0 days. The remaining patient died of multisystem failure not related to the acute colonic pseudoobstruction. Colonoscopic decompression was not attempted in any of the 25 patients. There were no colonic perforations, and there were no pseudoobstruction-related deaths. This study questions the need for early endoscopic or surgical treatment in cancer patients with acute colonic pseudoobstruction.     

Carcinoma associated with achalasia

Carcinoma developed in a 67-year-old woman with achalasia of the esophagus 23 years after esophagomyotomy. Postoperative manometric and radiologic studies showed satisfactory relief of esophageal obstruction. The development of carcinoma after an unusually long interval after adequate surgical treatment emphasizes the need for lifelong surveillance for this complication.     

Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing

Currently, the methods available for preimplantation genetic diagnosis (PGD) of in vitro fertilized (IVF) embryos do not detect de novo single-nucleotide and short indel mutations, which have been shown to cause a large fraction of genetic diseases. Detection of all these types of mutations requires whole-genome sequencing (WGS). In this study, advanced massively parallel WGS was performed on three 5- to 10-cell biopsies from two blastocyst-stage embryos. Both parents and paternal grandparents were also analyzed to allow for accurate measurements of false-positive and false-negative error rates. Overall, >95% of each genome was called. In the embryos, experimentally derived haplotypes and barcoded read data were used to detect and phase up to 82% of de novo single base mutations with a false-positive rate of about one error per Gb, resulting in fewer than 10 such errors per embryo. This represents a ∼100-fold lower error rate than previously published from 10 cells, and it is the first demonstration that advanced WGS can be used to accurately identify these de novo mutations in spite of the thousands of false-positive errors introduced by the extensive DNA amplification required for deep sequencing. Using haplotype information, we also demonstrate how small de novo deletions could be detected. These results suggest that phased WGS using barcoded DNA could be used in the future as part of the PGD process to maximize comprehensiveness in detecting disease-causing mutations and to reduce the incidence of genetic diseases.Worldwide, more than 5 million babies (Ferraretti et al. 2013) have been born through in vitro fertilization (IVF) since the birth of the first in 1978 (Steptoe and Edwards 1978). Exact numbers are difficult to determine, but it has been estimated that currently 350,000 babies are born yearly through IVF (de Mouzon et al. 2009, 2012; Centers for Disease Control and Prevention 2011; Ferraretti et al. 2013). That number is expected to rise, as advanced maternal age is associated with decreased fertility rates and women in developed countries continue to delay childbirth to later ages. In 95% of IVF procedures, no diagnostic testing of the embryos is performed (https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0). Couples with prior difficulties conceiving or those wishing to avoid the transmission of highly penetrant heritable diseases often choose to perform preimplantation genetic diagnosis (PGD). PGD involves the biopsy of one cell from a 3-d embryo or the recently more preferred method, due to improved implantation success rates (Scott et al. 2013b), of up to 10 cells from a 5- to 6-d blastocyst-stage embryo. Following biopsy, genetic analysis is performed on the isolated cell(s). Currently this is an assay for translocations and the correct chromosome copy number (Hodes-Wertz et al. 2012; Munne 2012; Yang et al. 2012; Scott et al. 2013a; Yin et al. 2013), a unique test designed and validated for each specific heritable disease (Gutierrez-Mateo et al. 2009), or a combination of both (Treff et al. 2013). Importantly, none of these approaches can detect de novo mutations.Advanced maternal age has long been associated with an increased risk of producing aneuploid embryos (Munne et al. 1995; Crow 2000; Hassold and Hunt 2009) and giving birth to a child afflicted with Down syndrome or other diseases resulting from chromosomal copy number alterations. Conversely, children of older fathers have been shown to have an increase in single base and short multibase insertion/deletion (indels) de novo mutations (Kong et al. 2012). Many recent large-scale sequencing studies have found that de novo variations spread across many different genes are likely to be the cause of a large fraction of autism cases (Michaelson et al. 2012; O’Roak et al. 2012; Sanders et al. 2012; De Rubeis et al. 2014; Iossifov et al. 2014), severe intellectual disability (Gilissen et al. 2014), epileptic encephalopathies (Epi4K Consortium and Epilepsy Phenome/Genome Project 2013), and many other congenital disorders (de Ligt et al. 2012; Veltman and Brunner 2012; Yang et al. 2013; Al Turki et al. 2014). Additionally rare and de novo variations have been suggested to be prevalent in patients with schizophrenia (Fromer et al. 2014; Purcell et al. 2014), and Michaelson et al. (2012) found that single base de novo mutations affect conserved regions of the genome and essential genes more often than regions of unknown function. Current targeted approaches to PGD would miss many of these important functional changes within the embryonic DNA sequence, and even a whole-genome sequencing (WGS)–based carrier screen of both parents would not enable comprehensive preimplantation or prenatal diagnoses due to de novo mutations. As more parents delay childbirth into their mid-30s and later, these studies suggest we should try to provide better diagnostic tests for improving the health of newborns. In this study, we demonstrate the use of an advanced WGS process that provides an accurate and phased genome sequence from about 10 cells, allowing highly sensitive and specific detection of single base de novo mutations from IVF blastocyst biopsies.     

Fiducial-based fusion of 3D dental models with magnetic resonance imaging

Purpose

Magnetic resonance imaging (MRI) is widely used in study of maxillofacial structures. While MRI is the modality of choice for soft tissues, it fails to capture hard tissues such as bone and teeth. Virtual dental models, acquired by optical 3D scanners, are becoming more accessible for dental practice and are starting to replace the conventional dental impressions. The goal of this research is to fuse the high-resolution 3D dental models with MRI to enhance the value of imaging for applications where detailed analysis of maxillofacial structures are needed such as patient examination, surgical planning, and modeling.

Methods

A subject-specific dental attachment was digitally designed and 3D printed based on the subject’s face width and dental anatomy. The attachment contained 19 semi-ellipsoidal concavities in predetermined positions where oil-based ellipsoidal fiducial markers were later placed. The MRI was acquired while the subject bit on the dental attachment. The spatial position of the center of mass of each fiducial in the resultant MR Image was calculated by averaging its voxels’ spatial coordinates. The rigid transformation to fuse dental models to MRI was calculated based on the least squares mapping of corresponding fiducials and solved via singular-value decomposition.

Results

The target registration error (TRE) of the proposed fusion process, calculated in a leave-one-fiducial-out fashion, was estimated at 0.49 mm. The results suggest that 6–9 fiducials suffice to achieve a TRE of equal to half the MRI voxel size.

Conclusion

Ellipsoidal oil-based fiducials produce distinguishable intensities in MRI and can be used as registration fiducials. The achieved accuracy of the proposed approach is sufficient to leverage the merged 3D dental models with the MRI data for a finer analysis of the maxillofacial structures where complete geometry models are needed.

     

Metachronous solitary mediastinal lymph node metastases of hepatocellular carcinoma treated by video‐assisted thoracic surgery twice: Report of a case

Solitary mediastinal lymph node metastasis of hepatocellular carcinoma (HCC) is rare. We report a case of metachronically solitary mediastinal metastases of HCC treated by video‐assisted thoracic surgery (VATS) twice. A 66‐year‐old man underwent repeated laparoscopic radiofrequency ablation or trans‐arterial catheter chemo‐embolization against HCC for more than 10 years. The level of alpha fetoprotein protein was elevated, and radiological modalities including FDG‐PET revealed solitary mediastinal tumor metachronically. VATS was performed bilaterally twice. The postoperative course was uneventful and there had no recurrence of extra‐hepatic metastases and tumor markers are within normal limits at 18 months after second VATS. VATS is a minimally invasive and useful procedure for solitary mediastinal lymph node metastasis of HCC. If primary HCC was controlled and lymph node metastasis was solitary, mediastinum lymphadenectomy using VATS might give good short and long term results.     

Coronary CTA for Surveillance of Cardiac Allograft Vasculopathy

Purpose of Review

The purpose of this review is to highlight recent hardware and software advances in coronary computed tomography angiography (CTA) that make it a potentially viable alternative to invasive coronary angiography for surveillance of cardiac allograft vasculopathy (CAV) in heart transplant recipients.

Recent Findings

Dual-source CT, multisegment reconstruction, and intracycle motion correction algorithms are all technologies applied during or after image acquisition that can improve image quality and diagnostic accuracy in patients with elevated heart rates, such as heart transplant recipients. CT fractional flow reserve may also add value in this clinical scenario.

Summary

Coronary CTA now has equivalent diagnostic accuracy, offers more nuanced anatomic information, is inherently safer, and could be less costly than invasive coronary angiography. For these reasons, coronary CTA may now be a viable alternative to ICA for CAV surveillance in heart transplant recipients.

     

What's Next for Acute Heart Failure Research?

Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either “inpatient” or “ED‐based.” Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high‐priority research areas.     

Immediate and short-term effects of mulligan concept positional sustained natural apophyseal glides on an athletic young-adult population classified with mechanical neck pain: an exploratory investigation

Objectives: Mechanical neck pain (MNP) is common in the athletic population. While symptoms may present at the cervical spine for patients complaining of MNP, thoracic spinal alignment or dysfunction may influence cervical positioning and overall cervical function. Clinicians often employ cervical high-velocity low-amplitude (HVLA) thrust manipulations to treat MNP, albeit with a small level of inherent risk. Mulligan Concept positional sustained natural apophyseal glides (SNAGs) directed at the cervicothoracic region are emerging to treat patients with cervical pain and dysfunction, as evidence supporting an interdependent relationship between the thoracic and cervical spine grows. The purpose of this a priori study was to evaluate outcome measures of patients classified with MNP treated with the Mulligan Concept Positional SNAGs. Methods: Ten consecutive young-adult patients, ages ranging from 15 to 18 years (mean = 16.5 ± 1.78), classified with MNP were treated utilizing Mulligan Concept Positional SNAGs. The Numeric Rating Scale (NRS), Patient-Specific Functional Scale (PSFS), Neck Disability Index (NDI), Disablement in the Physically Active (DPAS), and Fear-Avoidance Based Questionnaire-Physical Activity (FABQPA) were collected for inclusion criteria and to identify patient-reported pain and dysfunction. Results: Patients reported decreases in pain on the NRS [5.4 to .16, p = .001], increases in function on the PSFS [5.2 to 10, p = .001], and increases in cervical range of motion (CROM) [ext p = .003, flex p = .009, left rot p = .001, right rot p = .002] immediately post-treatment and between treatments. Discussion: Positional SNAGs directed at the cervicothoracic region may address a variety of patient reported symptoms for MNP, and the number of treatment sessions needed for symptom resolution may be closer to a single session rather than multiple treatments. Level of Evidence: 4.     

Outcomes of Patients With Syncope and Suspected Dementia

Objectives

Syncope and near‐syncope are common in patients with dementia and a leading cause of emergency department (ED) evaluation and subsequent hospitalization. The objective of this study was to describe the clinical trajectory and short‐term outcomes of patients who presented to the ED with syncope or near‐syncope and were assessed by their ED provider to have dementia.

Methods

This multisite prospective cohort study included patients 60 years of age or older who presented to the ED with syncope or near‐syncope between 2013 and 2016. We analyzed a subcohort of 279 patients who were identified by the treating ED provider to have baseline dementia. We collected comprehensive patient‐level, utilization, and outcomes data through interviews, provider surveys, and chart abstraction. Outcome measures included serious conditions related to syncope and death.

Results

Overall, 221 patients (79%) were hospitalized with a median length of stay of 2.1 days. A total of 46 patients (16%) were diagnosed with a serious condition in the ED. Of the 179 hospitalized patients who did not have a serious condition identified in the ED, 14 (7.8%) were subsequently diagnosed with a serious condition during the hospitalization, and an additional 12 patients (6.7%) were diagnosed postdischarge within 30 days of the index ED visit. There were seven deaths (2.5%) overall, none of which were cardiac‐related. No patients who were discharged from the ED died or had a serious condition in the subsequent 30 days.

Conclusions

Patients with perceived dementia who presented to the ED with syncope or near‐syncope were frequently hospitalized. The diagnosis of a serious condition was uncommon if not identified during the initial ED assessment. Given the known iatrogenic risks of hospitalization for patients with dementia, future investigation of the impact of goals of care discussions on reducing potentially preventable, futile, or unwanted hospitalizations while improving goal‐concordant care is warranted.