Emad Kandil

Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET)

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimers disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[18F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimers disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.

Hippocampal formation glucose metabolism and volume losses in MCI and AD

We used MRI volume sampling with coregistered and atrophy corrected FDG-PET scans to test three hypotheses: 1) hippocampal formation measures are superior to temporal neocortical measures in the discrimination of normal (NL) and mild cognitive impairment (MCI); 2) neocortical measures are most useful in the separation of Alzheimer disease (AD) from NL or MCI; 3) measures of PET glucose metabolism (MRglu) have greater diagnostic sensitivity than MRI volume. Three groups of age, education, and gender matched NL, MCI, and AD subjects were studied. The results supported the hypotheses: 1) entorhinal cortex MRglu and hippocampal volume were most accurate in classifying NL and MCI; 2) both imaging modalities identified the temporal neocortex as best separating MCI and AD, whereas widespread changes accurately classified NL and AD; 3) In most between group comparisons regional MRglu measures were diagnostically superior to volume measures. These cross-sectional data show that in MCI hippocampal formation changes exist without significant neocortical changes. Neocortical changes best characterize AD. In both MCI and AD, metabolism reductions exceed volume losses.

Volumetric analysis of the pre-frontal regions: findings in aging and schizophrenia

Frontal lobe dysfunction is thought to be involved in schizophrenia and age-associated cognitive decline. Frontal lobe volume changes have been investigated in these conditions using MRI, but results have been inconsistent. Few volumetric MRI protocols exist that divide the pre-frontal cortex into its sub-regions. In the present article, we describe a new method, which allows assessment of the superior, middle and inferior frontal gyrus, as well as the orbitofrontal and cingulate regions. The method uses multiple planes to help guide the anatomical decisions and combines this with a geometric approach utilizing readily apparent anatomical landmarks. Using this protocol, the frontal lobe volumes in young healthy subjects were contrasted with those of young schizophrenic patients and elderly healthy subjects (nine male subjects per group). The results showed that the method could be reproduced with high reliability (r(icc)> or =0.88-0.99). Schizophrenic as well as old subjects had specific significant reductions in the superior frontal gyrus and orbitofrontal regions compared with the young group. However, old and schizophrenic subjects did not differ from each another. No volume differences were observed in the other three regions assessed. Whether or not these volume reductions reflect a common pathological process remains to be investigated in future studies.

American Thyroid Association statement on outpatient thyroidectomy.

BACKGROUND The primary goals of this interdisciplinary consensus statement are to define the eligibility criteria for outpatient thyroidectomy and to explore preoperative, intraoperative, and postoperative factors that should be considered in order to optimize the safe and efficient performance of ambulatory surgery. SUMMARY A series of criteria was developed that may represent relative contraindications to outpatient thyroidectomy, and these fell into the following broad categories: clinical, social, and procedural issues. Intraoperative factors that bear consideration are enumerated, and include choice of anesthesia, use of nerve monitoring, hemostasis, management of the parathyroid glands, wound closure, and extubation. Importantly, postoperative factors are described at length, including suggested discharge criteria and recognition of complications, especially bleeding, airway distress, and hypocalcemia. CONCLUSIONS Outpatient thyroidectomy may be undertaken safely in a carefully selected patient population provided that certain precautionary measures are taken to maximize communication and minimize the likelihood of complications.

Robotic Transaxillary Thyroidectomy: An Examination of the First One Hundred Cases

BACKGROUND The influence of minimally invasive options has led to the application of new evolving techniques in thyroid surgery to eliminate visible neck scars. Here, we describe one authors experience with transaxillary robotic thyroidectomy and examine the effect of experience on determining the learning curve and improvements over time in operative performance. STUDY DESIGN With IRB approval, a prospective analysis of our surgical experience was performed. All patients underwent robotic transaxillary thyroidectomy by a single surgeon between September 2009 and June 2011. Principal outcomes measures included length of hospital stay, incidence of complications, and effect of obesity on outcomes. RESULTS One hundred consecutive operations were performed on 91 patients. Sixty-nine hemithyroidectomy, 22 total or near-total thyroidectomy, and 9 completion thyroidectomy procedures were performed. Of patients who underwent hemithyroidectomy, 21.7% were discharged within 4 hours; the remaining patients were discharged within 23 hours. Mean operative time for hemithyroidectomy was 108.1 ± 60.5 minutes, and for total or near-total thyroidectomy, mean operative time was 118.1 ± 51.3 minutes. Mean robot docking time was 9.1 ± 2.2 minutes for all cases. Obesity contributed to prolonged total operative time. Improvement in the length of time to perform components of the procedure was noted after 45 cases. Two cases required conversion to a cervical approach. There were no instances of permanent vocal cord palsy on postoperative laryngoscopy. CONCLUSIONS Here we report the largest experience of robotic gasless thyroid surgery in the United States. This novel technique provides excellent cosmetic results and can be performed as an outpatient procedure in selected group of patients. It is feasible and safe, however, has a lengthy learning curve.

The impact of surgical volume on patient outcomes following thyroid surgery

BACKGROUND This study aimed to evaluate the effects of indications for thyroidectomy on patient outcomes and to examine the impact of surgical volume on these outcomes. METHODS The nationwide inpatient sample was used to identify all patients who underwent total thyroidectomy (TT) between 2000 and 2009. We examined the effects of surgeon volume and hospital characteristics on predicting patient outcomes. Univariate and multivariate analyses were used to examine the effects of the indication for surgical care on postoperative outcomes. RESULTS Overall, 46,261 procedures were identified. Patients with Graves disease had the highest postoperative complications (17.5%) compared to patients undergoing TT for other benign (13.9%) and malignant (13.2%) thyroid disease (P < .001). After stratification by surgeon volume, Graves disease was found to be a significant predictor of postoperative complications in surgeries performed by low- and intermediate-volume surgeons (P < .05). However, Graves disease was not a significant predictor of postoperative complications when performed by high volume surgeons (P = .81). Hospital volume had an inconsistent and marginal protective effect on postoperative outcomes. CONCLUSION Surgery for Graves disease is associated with a higher risk for complications when performed by less experienced surgeons. This finding should prompt recommendations for increasing surgical specialization and referrals to high-volume surgeons in the management of Graves disease.

Safety of robotic thyroidectomy approaches: Meta‐analysis and systematic review

This study compared the efficacy of robotic thyroidectomy via a gasless, axillary approach with conventional cervical and endoscopic techniques by meta‐analysis.

Targeted inhibition of gene expression of pancreatitis‐associated proteins exacerbates the severity of acute pancreatitis in rats

Background: Pancreatitis‐associated protein (PAP) is a secretory protein not normally expressed in healthy pancreas but highly induced during acute pancreatitis. While PAP has been shown to be anti‐bacterial and anti‐apoptotic in vitro, its definitive biological function in vivo is not clear. Methods: To elucidate the function of PAP, antisense oligodeoxyribonucleotides (AS‐PAP) targeting all three isoforms of PAP were administered via intrapancreatic injections (5 mg kg −1 day −1 , 2 days) to rats prior to induction of pancreatitis. Results: Severity of pancreatitis and cytokine gene expression in peripheral blood mononuclear cells (PBMC) were evaluated. Administration of AS‐PAP, but not the scrambled oligodeoxyribonucleotide (SC‐PAP) control, reduced pancreatitis‐induced PAP expression by 55.2 ± 6.4%, 44.0 ± 8.9%, and 38.9 ± 10.7% for PAP isoforms I, II, and III, respectively, compared to saline‐treated controls (P < 0.05 for all). Inhibition of PAP expression significantly worsened pancreatitis: serum amylase activity, pancreas wet weight (reflecting edema), and serum C‐reactive protein levels all increased in AS‐PAP‐treated animals compared to SC‐PAP‐treated controls (by 3.5‐, 1.7‐, and 1.7‐fold, respectively; P < 0.05 for all). Histopathologic evaluation of pancreas revealed worsened edema, elevated leukocyte infiltration, and fat necrosis after AS‐PAP treatment. Gene expressions of IL‐1 μm and IL‐4 were significantly higher in PBMC isolated from AS‐PAP‐treated rats compared to SC‐PAP controls. Conclusion: This is the first in vivo evidence indicating that PAP mediates significant protection against pancreatic injury. Our data suggest that PAP may exert its protective function by suppressing local pancreatic as well as systemic inflammation during acute pancreatitis.

B-Type Natriuretic Peptide: A Biomarker for the Diagnosis and Risk Stratification of Patients With Septic Shock

BACKGROUND The importance of cardiomyocyte damage during sepsis has been a recent subject of interest. The progression of sepsis results in the upregulation of proinflammatory cytokines, which act in concert to damage cardiomyocytes and produce cardiac contractile dysfunction. B-type natriuretic peptide (BNP) is a neurohormone released from the ventricles of the heart in response to myocardial dysfunction. The goal of this study was to examine the relationship between BNP levels and the severity of sepsis independent of congestive heart failure. DESIGN Prospective, nonrandomized control study. SETTING University hospital. PATIENTS Forty-nine patients were divided into 3 groups: 13 patients with septic shock, 18 with early sepsis, and 18 age-matched healthy control subjects. We excluded patients with septic shock who had comorbid conditions (congestive heart failure or renal failure); sepsis severity was determined using the Sequential Organ Failure Assessment scoring system. Patients with sepsis were followed up for 21 days. MAIN OUTCOME MEASURES Serum BNP levels, determined at the time of diagnosis of sepsis and on patient improvement or deterioration. RESULTS Patients with septic shock had significantly higher BNP levels on admission compared with the other 2 groups (P < .05). The BNP levels were not significantly elevated in patients with early sepsis. Plasma BNP levels for patients with septic shock were positively correlated with Sequential Organ Failure Assessment scores (r(2) = 0.74, P < .05) and prognosticated survival. CONCLUSIONS This study confirms the relationship between BNP level elevation and severity of sepsis independent of congestive heart failure. It also supports the utility of BNP level as a marker for mortality in septic shock.

Nicotinamide Phosphoribosyltransferase in Malignancy A Review

Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of nicotinamide adenine dinucleotide (NAD) synthesis. Both intracellular and extracellular Nampt (iNampt and eNampt) levels are increased in several human malignancies and some studies demonstrate increased iNampt in more aggressive/invasive tumors and in tumor metastases. Several different molecular targets have been identified that promote carcinogenesis following iNampt overexpression, including SirT1, CtBP, and PARP-1. Additionally, eNampt is elevated in several human cancers and is often associated with a higher tumor stage and worse prognoses. Here we review the roles of Nampt in malignancy, some of the known mechanisms by which it promotes carcinogenesis, and discuss the possibility of employing Nampt inhibitors in cancer treatment.