Marvin P. Fried

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis

BACKGROUND As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. CONCLUSIONS Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.).

Image-guided endoscopic surgery: Results of accuracy and performance in a multicenter clinical study using an electromagnetic tracking system

Image‐guided surgery has recently been described in the literature as a useful technology for improved functional endoscopic sinus surgery localization. Image‐guided surgery yields accurate knowledge of the surgical field boundaries, allowing safer and more thorough sinus surgery. We have previously reviewed our initial experience with The InstaTrak System. This article presents a multicenter clinical study (n=55) that assesses the systems capability for localizing structures in critical surgical sites. The purpose of this paper is to present quantitative data on accuracy and performance. We describe several new advances including an automated registration technique that eliminates the redundant computed tomography scan, compensation for head movement, and the ability to use interchangeable instruments.

The Accuracy of Computed Tomography in the Diagnosis of Chronic Rhinosinusitis

Objective To determine the sensitivity, specificity, and diagnostic accuracy of paranasal sinus computed tomography (CT) in the diagnosis of chronic rhinosinusitis (CRS).

Simultaneous carcinomas of the esophagus and upper aerodigestive tract.

A review of 150 consecutive head and neck cancer patients over a 22-month period revealed a multiple primary cancer rate of 19%, 9% in the head and neck region. Nine patients (6%) had simultaneous esophageal and head and neck cancers. Complete systematic esophagoscopic examinations, in addition to barium swallow radiographic studies, are recommended for all patients with head and neck cancers.

Identifying and reducing errors with surgical simulation

The major determinant of a patient’s safety and outcome is the skill and judgment of the surgeon. While knowledge base and decision processing are evaluated during residency, technical skills—which are at the core of the profession—are not evaluated. Innovative state of the art simulation devices that train both surgical tasks and skills, without risk to patients, should allow for the detection and analysis of errors and “near misses”. Studies have validated the use of a sophisticated endoscopic sinus surgery simulator (ES3) for training residents on a procedural basis. Assessments are proceeding as to whether the integration of a comprehensive ES3 training programme into the residency curriculum will have long term effects on surgical performance and patient outcomes. Using various otolaryngology residencies, subjects are exposed to mentored training on the ES3 as well as to minimally invasive trainers such as the MIST-VR. Technical errors are identified and quantified on the simulator and intraoperatively. Through a web based database, individual performance can be compared against a national standard. An upgraded version of the ES3 will be developed which will support patient specific anatomical models. This advance will allow study of the effects of simulated rehearsal of patient specific procedures (mission rehearsal) on patient outcomes and surgical errors during the actual procedure. The information gained from these studies will help usher in the next generation of surgical simulators that are anticipated to have significant impact on patient safety.

Comparison of endoscopic sinus surgery with and without image guidance

Background Image guidance based on preacquired computed tomography scans of the patient is a technique used to assist the physician during endoscopic sinus surgery (ESS). This study seeks to compare ESS with and without image guidance, analyzing a number of parameters that can impact on efficacy. Methods Retrospective chart review took place at a tertiary care referral center. The study group consisted of 97 consecutive patients confirmed to have undergone ESS using an electromagnetic intraoperative image guidance system (IGS). The control group consisted of 61 consecutive patients who underwent ESS, before the IGS was available at the study hospital. The main outcomes measured were analysis of patient profile, including coexisting conditions such as asthma and polyposis, assessment of which specific sinuses underwent surgical treatment; major and minor complications; estimated blood loss (EBL); operative time; and the need for repeat surgery. Results The IGS group had 74% of patients with polyposis; more sinuses, on average, which underwent surgical revision; one major and three minor complications; an average EBL of 134 cc, an average procedure time of 154 minutes; and one patient who needed repeat surgery in a 3-month follow-up period. The non-IGS group had 40% of patients with polyposis; seven major complications and one minor complication; an average EBL of 94 cc; and three patients who needed repeat surgery within 3 months. Conclusions The use of an IGS for endoscopic sinus surgery may reduce the complications associated with the procedure and allow for a more thorough operation. However, operative time and EBL may be increased.

Image-Guided Surgery in a New Magnetic Resonance Suite: Preclinical Considerations†‡

Surgical procedures require correct identification of exposed anatomy with concomitant localization amidst contiguous structures. In endoscopic procedures the surgeon is provided a real‐time endoscopic view and is prepared with radiologic images. Here we present an overview of a methodology of localization using intraoperatively acquired magnetic resonance(MR) images in preparation for magnetic resonance imaging‐guided endoscopic sinus surgery. The methodology centers around a unique prototype imaging device and operating environment. An “open” 0.5 Tesla MR unit has been created that allows complete access to the patients head and neck while concomitant images are obtained. Illustrative examples of the localization technique from cadaver experiments are presented, as well as insights into the host of concerns for anesthesia, equipment, surgical instrumentation, communications, and documentation.

Speech and Survival

Abstract In Stage T3 carcinoma of the larynx (carcinoma restricted to the vocal cords, causing complete immobility of the cords but not extending to adjacent structures), laryngectomy leads to a three-year survival rate of approximately 60 per cent and the loss of normal speech. Radiation therapy, on the other hand, leads to a lower survival (30 to 40 per cent at three years) but preserves normal or nearly normal speech. We investigated attitudes toward the quantity and quality of life in 37 healthy volunteers, interviewing 12 firefighters and 25 middle and upper management executives to determine their preferences for longevity and voice preservation. We used the principles of expected utility theory to develop a method for sharpening decisions involving tradeoffs between quantity and quality of life. Our analysis indicates that to maintain their voices, approximately 20 per cent of volunteers would choose radiation instead of surgery. These results suggest that treatment choices should be made on the ba...

Assessment of the Airway in Obstructive Sleep Apnea Syndrome with 3-Dimensional Airway Computed Tomography:

OBJECTIVE: The goal was to evaluate 3-dimensional airway CT for upper airway assessment in obstructive sleep apnea syndrome (OSAS). DESIGN: Airway CT was obtained and 3-dimensional airway models were constructed prospectively for 40 patients with OSAS and 10 controls. Airway dimensions were correlated with polysomnography, and comparison was made between patients with and without OSAS. RESULTS: OSAS patients had a mean respiratory distress index of 51.9 events per hour. The mean minimum cross-sectional area (XSA) in the neutral position was 67.1 mm 2 . Minimum XSA decreased in both the inspiratory and expiratory phases to 16.3 mm 2 and 15.0 mm 2 , respectively (P < 0.001). Complete airway obstruction occurred in 1 or more phases of respiration in 28 patients. Neither airway XSA nor length of obstruction correlated with sleep apnea parameters. No statistically significant differences in airway dimensions were found between OSAS and control patients. CONCLUSIONS: Airway CT demonstrates dynamic airway obstruction in OSAS but does not correlate well with clinically important disease parameters. (Otolaryngol Head Neck Surg 2000;123:444-9.)

Anatomic location of the tongue base neurovascular bundle

Knowledge of the location of the hypoglossal/lingual artery neurovascular bundle (HLNVB) is essential in performing tongue base resections for neoplasm and for obstructive sleep apnea. Transoral and transcervical resections of the tongue base may be performed with greater exposure and certainty when the relationship of the HLNVB to local landmarks is understood; knowledge of the HLNVB allows resection of a larger amount of contralateral tongue base during partial glossectomy without violating the contralateral remnant tongues blood supply. Ten cadaver heads were dissected to determine the position of the HLNVB with respect to soft tissue and bony landmarks at the tongue base. Our results indicate the position of the tongue base HLNVB is significantly inferior and lateral, that is, 2.7 cm inferior and 1.6 cm lateral to the foramen cecum, 0.9 cm superior to the hyoid bone, and 2.2 cm medial to the mandible. This inferolateral location allows the potential for aggressive tongue base resection without neurovascular compromise.