Sri Naveen Surapaneni

A noninvasive clinical scoring model predicts risk of nonalcoholic steatohepatitis in morbidly obese patients

BackgroundA simple model to predict nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease is desirable to optimize the selection of patients for liver biopsy. We investigated a large group of morbidly obese patients to derive a scoring system based on simple clinical and laboratory variables.MethodsConsecutive subjects undergoing bariatric surgery and without evidence of other liver disease or significant alcohol use underwent intraoperative liver biopsy. Demographic, clinical, and biochemical variables were collected. A scoring model was derived using variables found to be independent predictors of NASH. The scores were divided into four risk categories (low, intermediate, high, and very high). Positive and negative predictive values (PPV/NPV) were derived for each category and the area under the receiver operator curve (AUROC) was calculated.ResultsA total of 253 subjects were included: 52 (20.6%) had NASH, 116 (45.8%) had simple steatosis, and 85 (33.6%) had normal liver histology. Only ten subjects (19% of NASH group) had significant (≥ stage 2) fibrosis. Multivariate analysis identified diabetes, abnormal ALT, and hypertriglyceridemia as independent predictors of NASH. Sleep apnea showed a strong trend toward significance and was also included in the model. This model showed a NPV of 89.7% in the low risk category and a PPV of 75% in the very high risk category, with AUROC of 0.76.ConclusionsA simple scoring system performs well in predicting NASH and can be used in the clinic to optimize the selection of morbidly obese patients for liver biopsy.

Pharyngeal airway protective reflexes are triggered before the maximum volume of fluid that the hypopharynx can safely hold is exceeded

Aerodigestive reflexes triggered by pharyngeal stimulation can protect the airways by clearing fluid from the pharynx. The objective of this study was to determine the relationship between the maximum capacity of fluid that can safely dwell in the hypopharynx [hypopharyngeal safe volume (HPSV)] before spilling into the larynx and the threshold volumes required to trigger pharyngoglottal closure reflex (PGCR), pharyngo-upper esophageal sphincter contractile reflex (PUCR), and reflexive pharyngeal swallow (RPS). Twenty-five healthy volunteers (mean age 24 yr, 8 males) were studied in the semi-inclined supine position. PGCR, PUCR, and RPS were elicited using techniques of concurrent upper esophageal sphincter manometry and pharyngo-laryngoscopy. The hypopharynx was then anesthetized to abolish RPS. HPSV was determined by infusing water in the pharynx, and perfusion was stopped when the infusate reached the superior margin of the interarytenoid fold. The threshold volumes for triggering PGCR, PUCR, and RPS by slow and rapid injections before pharyngeal anesthesia were 0.18 ± 0.02 and 0.09 ± 0.02 ml; 0.20 ± 0.020 and 0.13 ± 0.04 ml; and 0.61 ± 0.04 and 0.4 ± 0.06 ml, respectively. All of the above volumes were significantly smaller than the HPSV (0.70 ± 0.06 ml, P < 0.01) except for the threshold volume to elicit RPS during slow perfusion, which was not significantly different (P = 0.23). We conclude that pharyngeal aerodigestive reflexes are triggered by both slow and rapid pharyngeal perfusion of water at significantly smaller volumes than the maximum capacity of the hypopharynx to safely hold contents without spilling into the airway. These reflexes thereby aid in prevention of aspiration.

Protective Role of Aerodigestive Reflexes Against Aspiration: Study on Subjects With Impaired and Preserved Reflexes

BACKGROUND & AIMS Direct evidence to support the airway protective function of aerodigestive reflexes triggered by pharyngeal stimulation was previously demonstrated by abolishing these reflexes by topical pharyngeal anesthesia in normal subjects. Studies have also shown that these reflexes deteriorate in cigarette smokers. Aim of this study was to determine the influence of defective pharyngeal aerodigestive reflexes on airway protection in cigarette smokers. METHODS Pharyngoglottal Closure reflex; PGCR, Pharyngo-UES Contractile reflex; PUCR, and Reflexive Pharyngeal Swallow; RPS were studied in 15 healthy non-smokers (24.2±3.3 SD y, 7 males) and 15 healthy chronic smokers (27.3±8.1, 7 males). To elicit these reflexes and to evaluate aspiration, colored water was perfused into the hypopharynx at the rate of 1 mL/min. Maximum volume of water that can safely dwell in the hypopharynx before spilling into the larynx (Hypopharyngeal Safe Volume; HPSV) and the threshold volume to elicit PGCR, PUCR, and RPS were determined in smokers and results compared with non-smokers. RESULTS At baseline, RPS was elicited in all non-smokers (100%) and in only 3 of 15 smokers (20%; P<.001). None of the non-smokers showed evidence of laryngeal spillage of water, whereas 12 of 15 smokers with absent RPS had laryngeal spillage. Pharyngeal anesthesia abolished RPS reflex in all non-smokers resulting in laryngeal spillage. The HPSV was 0.61±0.06 mL and 0.76±0.06 mL in non-smokers and smokers respectively (P=.1). CONCLUSIONS Deteriorated reflexive pharyngeal swallow in chronic cigarette smokers predispose them to risks of aspiration and similarly, abolishing this reflex in non-smokers also results in laryngeal spillage. These observations directly demonstrate the airway protective function of RPS.

Effect of systemic alcohol and nicotine on airway protective reflexes.

OBJECTIVES:Injection of water into the pharynx induces contraction of the upper esophageal sphincter (UES), triggers the pharyngo-UES contractile reflex (PUCR), and at a higher volume, triggers an irrepressible swallow, the reflexive pharyngeal swallow (RPS). These aerodigestive reflexes have been proposed to reduce the risks of aspiration. Alcohol ingestion can predispose to aspiration and previous studies have shown that cigarette smoking can adversely affect these reflexes. It is not known whether this is a local effect of smoking on the pharynx or a systemic effect of nicotine. The aim of this study was to elucidate the effect of systemic alcohol and nicotine on PUCR and RPS.METHODS:Ten healthy non-smoking subjects (8 men, 2 women; mean age: 32±3 s.d. years) and 10 healthy chronic smokers (7 men, 3 women; 34±8 years) with no history of alcohol abuse were studied. Using previously described techniques, the above reflexes were elicited by rapid and slow water injections into the pharynx, before and after an intravenous injection of 5% alcohol (breath alcohol level of 0.1%), before and after smoking, and before and after a nicotine patch was applied. Blood nicotine levels were measured.RESULTS:During rapid and slow water injections, alcohol significantly increased the threshold volume (ml) to trigger PUCR and RPS (rapid: PUCR: baseline 0.2±0.05, alcohol 0.4±0.09; P=0.022; RPS: baseline 0.5±0.17, alcohol 0.8±0.19; P=0.01, slow: PUCR: baseline 0.2±0.03, alcohol 0.4±0.08; P=0.012; RPS: baseline 3.0±0.3, alcohol 4.6±0.5; P=0.028). During rapid water injections, acute smoking increased the threshold volume to trigger PUCR and RPS (PUCR: baseline 0.4±0.06, smoking 0.67±0.09; P=0.03; RPS: baseline 0.7±0.03, smoking 1.1±0.1; P=0.001). No similar increases were noted after a nicotine patch was applied.CONCLUSIONS:Acute systemic alcohol exposure inhibits the elicitation PUCR and RPS. Unlike cigarette smoking, systemic nicotine does not alter the elicitation of these reflexes.

Suppressive anti-HCV therapy for prevention of donor to recipient transmission in stem cell transplantation

A 48-yr-old man with acute myeloid leukemia (AML) required urgent allogeneic hematopoietic stem cell transplantation because of failed attempts to induce remission via chemotherapy. He had an HLA identical donor sister who was hepatitis C virus (HCV) RNA positive. In order to prevent HCV transmission to her brother, the donor was treated with weekly injections of pegylated interferon alfa-2b (150 μg subcutaneously every week) and daily ribavirin (1 g/day) for 5 wk at which time her qualitative polymerase chain reaction (PCR) was negative. Her stem cells were successfully grafted into the recipient. The recipient remained HCV PCR negative after transplant until death from relapsed AML.

Anatomic-manometric correlation of the upper esophageal sphincter: a concurrent US and manometry study.

BACKGROUND The pharyngoesophageal segment commonly referred to as the upper esophageal sphincter (UES) generates a high-pressure zone (HPZ) between the pharynx and the esophagus. However, the exact anatomical components of the UES-HPZ remain incompletely determined. OBJECTIVE To systematically define the US signature of various components of the pharyngoesophageal junction and to determine how these structures contribute to the development of the UES-HPZ. DESIGN Prospective, experimental study. SETTING Tertiary Academic Medical Center. PATIENTS This study involved 18 healthy volunteers. INTERVENTION We studied 5 participants by using a high-frequency US miniprobe (US-MP) and concurrent fluoroscopy and another 13 participants by using the US-MP and concurrent manometry. MAIN OUTCOME MEASUREMENTS Relative contribution of various muscles in the UES-HPZ. RESULTS Manometrically, the UES-HPZ had a median length of 4.0 cm (range 3.0-4.5 cm). A C-shaped muscle, believed to represent the cricopharyngeus muscle, was observed for a median length of 3.5 cm (range 2.0-4.0 cm). The oval configuration representing the esophageal contribution to the UES was seen in 10 of 13 participants (77%) at the distal HPZ (esophagus to UES transition zone). The flat configuration of the inferior constrictor muscle was noted in 7 of 13 participants (54%) at the proximal HPZ (UES to pharynx transition zone). There were 4 to 5 wall layers versus 3 layers in the distal and proximal HPZ, respectively. The mean (+/- SD) muscle thickness was relatively constant along the length of the UES-HPZ. LIMITATIONS Air artifacts in the UES-HPZ. CONCLUSION The configuration and layers of the UES-HPZ vary along its length. The upper esophagus is a significant contributor to the distal UES-HPZ.

Effect of aging on hypopharyngeal safe volume and the aerodigestive reflexes protecting the airways.

Studies on young volunteers have shown that aerodigestive reflexes are triggered before the maximum volume of fluid that can safely collect in the hypopharynx before spilling into the larynx is exceeded (hypopharyngeal safe volume [HPSV]). The objective of this study was to determine the influence of aging on HPSV and pharyngo‐glottal closure reflex (PGCR), pharyngo‐UES contractile reflex (PUCR), and reflexive pharyngeal swallow (RPS).

Unsedated transnasal endoscopy with ultrathin endoscope as a screening tool for research studies

Asymptomatic subjects volunteering for research studies are generally stratified as healthy based on a questionnaire, medical interviewing, and physical examination. The aim of this study was to evaluate the prevalence of upper gastrointestinal (GI) abnormalities in healthy asymptomatic volunteers using unsedated transnasal esophagogastroduodenoscopy (T‐EGD) with an ultrathin endoscope as an additional screening tool.

63 Aerodigestive Protective Reflexes are Triggered Before the Safe Capacity of Pharynx is Exceeded

Introduction: Although achalasia is the best defined esophageal motor disorder, no standardized patient reported outcome measure currently exists for intervention trials. Furthermore, treatment outcome from a patients perspective can be quite different from the goals and assessment of the treating physician. This may reflect different levels of expectation and also a lack of a threshold definition of success. Our goal was to compare patient reported outcomes assessed with the Hospital Odynophagia Dysphagia Questionnaire (HODQ) to the clinical impression of the treating physician. Methods: 40 non-spastic achalasia patients (15F, ages 24-82) undergoing either pneumatic dilation (PD) or Heller myotomy (HM) were contacted by phone to assess clinical outcome using the HODQ. The HODQ is comprised of 10 questions related to post-procedure frequency of symptoms, severity of symptoms, and food impaction events (scores ranging 0-5 per question, max score of 50). A HODQ score ≤6 is the upper limit of normal. Post-treatment HODQ scores between HM and PD were compared. In addition, we compared the HODQ score with the clinical impression of the treating physician. A good outcome was defined as the physicians impression that the patient had a symptomatic improvement, no weight loss, and no need for further treatment. A poor response was defined as minimal to no improvement requiring further intervention. Results: Of the 40 patients, 15 had HM (3F, ages 24-65) and 25 had PD (12F, ages 22-82). The meanHODQ score after follow-up of 3-30monthswas 7.85 (SD, 8.2). Patients that underwent HM had a lower mean HODQ score compared with PD (HM, 5.7 SD (5.9); PD, 9.2, SD (9.2)), but this was not statistically significant (p=0.15). Thirty-two patients (80%) had a good clinical outcome based on the treating physician assessment, while 5 had a poor outcome and another 3 had insufficient documentation to define physician assessed outcome. Fourteen (44%) of the 32 patients deemed to have a good outcome by their physician had an abnormal HODQ score (mean 12.4, range, 7-25). Conclusion: There is substantial discepancy in physician-reported versus patient-reported outcome in achalasia treatment. Although 80% of the patients were assessed as treatment successes by their physician, 44% had a HODQ score suggesting significant persistent dysphagia. Future studies of achalasia teatment should recognize the distinction between the expectations of the patients in terms of symptom relief and the goals of reducing complications such asmalnutrition and aspiration. In addition, achalasia patients shoiuld be counseled that some dysphagia will likely persist despite successful therapy.