Does Preoperative Pharmacogenomic Testing of Patients Undergoing TKA Improve Postoperative Pain? A Randomized Trial.

BACKGROUND: Pharmacogenomics is an emerging and affordable tool that may improve postoperative pain control. One challenge to successful pain control is the large interindividual variability among analgesics in their efficacy and adverse drug events. Whether preoperative pharmacogenomic testing is worthwhile for patients undergoing TKA is unclear. QUESTIONS/PURPOSES: (1) Are the results of preoperative pharmacogenetic testing associated with lower postoperative pain scores as measured by the Overall Benefit of Analgesic Score (OBAS)? (2) Do the results of preoperative pharmacogenomic testing lead to less total opioids given? (3) Do the results of preoperative pharmacogenomic testing lead to changes in opioid prescribing patterns? METHODS: Participants of this randomized trial were enrolled from September 2018 through December 2021 if they were aged 18 to 80 years and were undergoing primary TKA under general anesthesia. Patients were excluded if they had chronic kidney disease, a history of chronic pain or narcotic use before surgery, or if they were undergoing robotic surgery. Preoperatively, patients completed pharmacogenomic testing (RightMed, OneOME) and a questionnaire and were randomly assigned to the experimental group or control group. Of 99 patients screened, 23 were excluded, one before randomization; 11 allocated patients in each group did not receive their allocated interventions for reasons such as surgery canceled, patients ultimately undergoing spinal anesthesia, and change in surgery plan. Another four patients in each group were excluded from the analysis because they were missing an OBAS report. This left 30 patients for analysis in the control group and 38 patients in the experimental group. The control and experimental groups were similar in age, gender, and race. Pharmacogenomic test results for patients in the experimental group were reviewed before surgery by a pharmacist, who recommended perioperative medications to the clinical team. A pharmacist also assessed for clinically relevant drug-gene interactions and recommended drug and dose selection according to guidelines from the Clinical Pharmacogenomics Implementation Consortium for each patient enrolled in the study. Patients were unaware of their pharmacogenomic results. Pharmacogenomic test results for patients in the control group were not reviewed before surgery; instead, standard perioperative medications were administered in adherence to our institutional care pathways. The OBAS (maximum 28 points) was the primary outcome measure, recorded 24 hours postoperatively. A two-sample t-test was used to compare the mean OBAS between groups. Secondary measures were the mean 24-hour pain score, total morphine milligram equivalent, and frequency of opioid use. Postoperatively, patients were assessed for pain with a VAS (range 0 to 10). Opioid use was recorded preoperatively, intraoperatively, in the postanesthesia care unit, and 24 hours after discharge from the postanesthesia care unit. Changes in perioperative opioid use based on pharmacogenomic testing were recorded, as were changes in prescription patterns for postoperative pain control. Preoperative characteristics were also compared between patients with and without various phenotypes ascertained from pharmacogenomic test results. RESULTS: The mean OBAS did not differ between groups (mean ± SD 4.7 ± 3.7 in the control group versus 4.2 ± 2.8 in the experimental group, mean difference 0.5 [95% CI -1.1 to 2.1]; p = 0.55). Total opioids given did not differ between groups or at any single perioperative timepoint (preoperative, intraoperative, or postoperative). We found no difference in opioid prescribing pattern. After adjusting for multiple comparisons, no difference was observed between the treatment and control groups in tramadol use (41% versus 71%, proportion difference 0.29 [95% CI 0.05 to 0.53]; nominal p = 0.02; adjusted p > 0.99). CONCLUSION: Routine use of pharmacogenomic testing for patients undergoing TKA did not lead to better pain control or decreased opioid consumption. Future studies might focus on at-risk populations, such as patients with chronic pain or those undergoing complex, painful surgical procedures, to test whether pharmacogenomic results might be beneficial in certain circumstances. LEVEL OF EVIDENCE: Level I, therapeutic study.

A resilience intervention involving mindfulness training for transplant patients and their caregivers.

Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness-based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness-based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6-week mindfulness-based resilience training (MBRT) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty-one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health-related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant (P<.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality-of-life mental component (P=.006) and positive affect (P=.02) also improved at follow-up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well-being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.

Muscle Tension Dysphagia: Symptomology and Theoretical Framework.

OBJECTIVE: To identify symptoms, common diagnostic findings, pattern of treatments and referrals offered, and their efficacy in a group of patients with idiopathic functional dysphagia in an otolaryngology setting with multiple providers. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Following Mayo Clinic Institutional Review Board approval, a retrospective chart review was conducted of patients with dysphagia who had a videofluoroscopic swallow study between January 1, 2013, and April 30, 2015. Each patient's dysphagia symptomology, videofluoroscopic swallow study, flexible laryngoscopy, and medical chart were reviewed to identify the treatment paradigms that were utilized. RESULTS: Sixty-seven adult patients met the inclusion criteria. Abnormal laryngeal muscle tension was present in 97% of patients. Eighty-two percent of patients also demonstrated signs of laryngeal hyperresponsiveness. Nonspecific laryngeal inflammation was evident in 52% of patients. Twenty-seven patients were referred to speech-language pathology for evaluation. Thirteen patients completed a course of voice therapy directed toward unloading muscle tension. All 13 patients self-reported resolution of dysphagia symptoms. CONCLUSION: The study results suggest that laryngeal muscle tension may be a factor in the underlying etiology in patients with idiopathic functional dysphagia. We propose the diagnostic term muscle tension dysphagia to describe a subset of patients with functional dysphagia. Further prospective studies are needed to better evaluate potential gastroesophageal confounders in this group of patients and to identify an effective paradigm for treatment. In our limited series, speech-language pathology intervention directed toward unloading muscle tension appears effective.

Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings.

INTRODUCTION: Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha-synucleinopathy in early PD. METHODS: Twenty-five early PD (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive. RESULTS: Mean (standard deviation) age was 69.5 (8.3) for the PD group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six PD and 1 control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 (74%) PD and 2 of 9 (22%) control subjects. PD-positive and -negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient. CONCLUSIONS: Submandibular gland needle biopsies identified phosphorylated alpha-synuclein staining in 74% of early PD subjects. False positives may be true false positives or may represent prodromal PD. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early PD may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation.

Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program.

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0-hour median post-mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant-funded projects.

The Chitranjan Ranawat Award: Periarticular injections and femoral & sciatic blocks provide similar pain relief after TKA: a randomized clinical trial.

BACKGROUND: Two of the more common methods of pain management after TKA are peripheral nerve blocks and intraarticular/periarticular injections. However, we are not aware of any study directly comparing the commonly used combination of a continuous femoral block given with a single-shot sciatic block with that of a periarticular injection after TKA. QUESTIONS/PURPOSES: This randomized clinical trial compared a combined femoral and sciatic nerve block with periarticular injection as part of a multimodal pain protocol after total knee arthroplasty with respect to (1) pain; (2) narcotic use; (3) quadriceps function and length of stay; and (4) peripheral nerve complications. METHODS: One hundred sixty patients completed randomization into two treatment arms: (1) peripheral nerve blocks (PNB; n=79) with an indwelling femoral nerve catheter and a single shot sciatic block; or (2) periarticular injection (PAI; n=81) using ropivacaine, epinephrine, ketorolac, and morphine. All patients received standardized general anesthesia and oral medications. The primary outcome was postoperative pain, on a 0 to 10 scale, measured on the afternoon of postoperative day 1 (POD 1). Secondary outcomes were narcotic use, quadriceps function, length of stay, and peripheral nerve complications. RESULTS: Mean pain scores on the afternoon of POD 1 were not different between groups (PNB group: 2.9 [SD 2.4]; PAI group: 3.0 [SD 2.2]; 95% confidence interval, -0.8 to 0.6; p=0.76). Mean pain scores taken at three times points on POD 1 were also similar between groups. Hospital length of stay was shorter for the PAI group (2.44 days [SD 0.65] versus 2.84 days [SD 1.34] for the PNB group; p=0.02). Narcotic consumption was higher the day of surgery for the PAI group (PAI group: 11.7 mg morphine equivalents [SD 13.1]; PNB group: 4.6 mg [SD 9.1]; p<0.001), but thereafter, there was no difference. More patients in the PNB group had sequelae of peripheral nerve injury (mainly dysesthesia) at 6-week followup (nine [12%] versus one [1%]; p=0.009). CONCLUSIONS: Patients receiving periarticular injections had similar pain scores, shorter lengths of stay, less likelihood of peripheral nerve dysesthesia, but greater narcotic use on the day of surgery compared with patients receiving peripheral nerve blocks. Periarticular injections provide adequate pain relief, are simple to use, and avoid the potential complications associated with nerve blocks. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Polyp and adenoma detection rates in the proximal and distal colon.

OBJECTIVES: Little is known about the correlation between the polyp detection rate (PDR) and the adenoma detection rate (ADR) in individual colonic segments. The adenoma-to-polyp detection rate quotient (APDRQ) has been utilized in retrospective study as a constant to estimate ADR from PDR. It has been previously stated that diminutive polyps in the rectum are more likely to be non-adenomatous, compared with more proximal segments, yet the APDRQ uses data from the entire colon. We sought to characterize and compare ADR and PDR in each colonic segment, estimate ADR using the conversion factor, APDRQ, and assess the correlation between estimated and actual ADR for each colonic segment. METHODS: As part of a quality improvement program, a retrospective chart review was conducted of all outpatient colonoscopies performed by 20 gastroenterologists between 1 October 2010 and 31 March 2011 at a single academic tertiary-care referral center. PDR, ADR, and the APDRQ were calculated for each gastroenterologist, using data from the entire colon and then for each colonic segment separately. Actual ADR was compared with estimated ADR based on the measured APDRQ. RESULTS: During 1,921 colonoscopies, 2,285 polyps were removed; 1,122 (49%) were adenomas. The mean (s.d.) PDR for the group was 49% (12.4%) (range, 16-64%). The mean (s.d.) ADR was 31% (7.4%) (range, 13-42%). PDR and ADR correlated well in segments proximal to the splenic flexure, but diverged in distal segments. ADR was significantly higher in the right colon (17.1%) than in the left (13.5%) (P=0.001). The correlation between estimated and actual ADR using the APDRQ was significantly higher in the right colon (r=0.95 (95% confidence interval (CI), 0.87-0.98)) than in the left (r=0.59 (95% CI, 0.17-0.83)) (P<0.05). CONCLUSIONS: Although PDR and ADR correlate well in segments proximal to the splenic flexure, they do not correlate well in the left colon. Caution should be exercised when using PDR as a surrogate for ADR if data from the rectum and sigmoid are included.

Bladder wall fat on computed tomography with pathologic correlation.

OBJECTIVES: To determine the prevalence and significance of fat in the urinary bladder wall detectable by computed tomography (CT). METHODS: Retrospective review of 200 consecutive patients with noncontrast CT. Cystectomy specimen CT/pathologic correlation. RESULTS: CT-detectable fat in 30 (15%) patients was significantly more predominant in men (P=.003) and in patients with past renal stones (P<.001). Urinary tract infections were significantly less common in patients with bladder wall fat (P=.05). Pathologically, CT-detectable fat was submucosal. CONCLUSION: CT-detectable bladder wall fat is more common in men than women and in patients with a history of renal stones and urinary tract infections.

A double-blind randomized controlled trial of continuous intravenous Ketorolac vs placebo for adjuvant pain control after renal surgery.

OBJECTIVE: To evaluate the efficacy and safety of a novel, continuous intravenous infusion of ketorolac, a powerful nonopioid analgesic, for postoperative pain control. PATIENTS AND METHODS: A prospective, double-blind, randomized, placebo-controlled trial of a continuous infusion of ketorolac tromethamine in 1 L of normal saline vs placebo was performed in 135 patients aged 18 to 75 years after laparoscopic donor nephrectomy or percutaneous nephrolithotomy completed from October 7, 2008, through July 21, 2010. Primary study end points were the 24-hour differences in visual analog pain scores and total narcotic consumption, whereas secondary end points were differences in urine output, serum creatinine level, and hemoglobin level. RESULTS: The study was stopped after randomization of 135 patients (68 in the ketorolac group and 67 in the placebo group) when interim analysis indicated that the difference in mean pain scores between the 2 groups (difference, 0.6) was smaller than the 1-point threshold set forth in the power calculations. No statistically significant change was noted in hemoglobin levels from preoperative to postoperative values (P=.13) or in postoperative serum creatinine levels (P=.13). CONCLUSION: Although continuous infusion of ketorolac produced only a modest decrease in the use of narcotics, it appears to offer a safe therapeutic option for nonnarcotic pain control. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00765128 and NCT00765232.

Patient preference and acceptance with sodium phosphate tablet preparation for colonoscopy.

BACKGROUND: Colonoscopy is considered the primary procedure for colorectal cancer screening and prevention. However patient acceptance of this procedure has been poor. A major deterrent for patients is the need for a large-volume (4-l) preprocedure colonic preparation (polyethylene glycol [PEG] solution) that can be associated with a bad taste. AIM: To determine patient preference and acceptance of the NaP tablet preparation in patients who have previously used PEG solutions for their prior colonoscopy exams. METHODS: Patients who had used a standard 4-l PEG solution preparation for a colonoscopy within the past 12 months and who were scheduled for a repeat colonoscopy were invited to participate in this study. A preprocedural questionnaire was administered to the patients. The primary outcome measure was whether the patient indicated a preference for the NaP tablet preparation over the previous PEG solution. RESULTS: Thirty-five of 53 participants (66%) who completed the study preferred the NaP tablet preparation over 4-l PEG. A majority of patients also indicated that they would use the NaP tablet preparation again and would like to have a choice of preparation for their next colonoscopy. CONCLUSIONS: Among patients who previously used a 4-l PEG preparation for colon cleansing and participated in this study, 66% of patients preferred the NaP tablet preparation over the PEG preparation for their colonoscopy.

Vasovagal reactions and other complications of cervical vs. lumbar translaminar epidural steroid injections.

OBJECTIVE: To document the per patient rate of vasovagal reactions and other complications of cervical vs. lumbar translaminar epidural steroid injections. BACKGROUND: Anecdotal observations at our institution suggested that vasovagal reactions are much more common during cervical epidural steroid injections than lumbar injections, and more frequent than previously reported. METHODS: Records of 249 patients undergoing their first cervical epidural steroid injection were reviewed for vasovagal reactions and other adverse events. For comparison, a first lumbar epidural steroid injection performed by the same staff physician was matched to each cervical procedure and reviewed for complications. RESULTS: The incidence of vasovagal reaction was 7 points more common (P < 0.001, 95% confidence interval 0.04-0.12) in the cervical group (8%) than in the lumbar group (1%). This correlates to an additional vasovagal reaction for every 14 patients who were treated with cervical injection in comparison with those treated with lumbar injection. DISCUSSION: The risk of vasovagal reaction is significantly higher for cervical translaminar epidural steroid injections than for lumbar injections. The risk of vasovagal reaction remained higher for cervical injection even when adjusting for differences between the two populations. The higher rate of cervical vasovagal reactions may result from a combination of anxiety, the prone position with neck flexed, head drapes, and stimulus from a neck procedure. CONCLUSION: Increased vigilance for patients undergoing translaminar cervical epidural steroid injections may be warranted. Clinicians may choose to consider these results when counseling patients regarding risk and the need for conscious sedation during the procedure.

Randomized trial of preemptive local analgesia in vaginal surgery.

Preemptive analgesia in vaginal surgery has had conflicting efficacy reported in the existing literature. This study was designed to clarify the usefulness of preemptive local analgesia (PLA) in patients undergoing vaginal hysterectomy. A prospective, randomized, double-blinded trial of PLA in 90 women undergoing vaginal hysterectomy was conducted. PLA consisted of 20 ml of 0.5% bupivacaine with 1:200,000 epinephrine injected in a paracervical-type fashion. Total narcotic use and pain (using a visual analog scale (VAS)) was recorded at 30 min, 3, 12, and 24 h postoperatively. The mean total dose of narcotic was significantly less in the PLA group versus the placebo group (P = 0.009) at every time point postoperatively. Additionally, the mean pain VAS 30 min and 3 h postoperatively was 43% (P = 0.003) and 33% (P = 0.02) lower, respectively, in the PLA group. PLA with bupivacaine prior to vaginal hysterectomy is associated with significantly lower pain scores and a reduction in narcotic use postoperatively.

Using CT enterography to monitor Crohn's disease activity: a preliminary study.

OBJECTIVE: The purpose of our study was to determine whether imaging changes of Crohn's disease at sequential CT enterography examinations correlate with disease progression or regression. MATERIALS AND METHODS: Forty CT enterography examinations in 20 patients (12 women, eight men; mean age, 55.5 years) with known Crohn's disease were retrospectively evaluated by a radiologist who was blinded to the clinical history. One radiologist determined whether imaging findings of Crohn's disease were present and, if so, whether the findings progressed, regressed, or remained stable between examinations. CT enterography findings were then compared with disease progression or regression based on symptoms and clinical follow-up. Direct comparison of CT enterography and endoscopy was also performed when available. RESULTS: Disease progression or regression by CT enterography correlated with symptoms in 16 of 20 (80%) patients. Specifically, CT enterography and symptoms agreed in 12 patients with clinical disease progression, two patients with clinical regression, and two with clinically stable disease. In four of 20 (20%) patients, symptoms progressed although CT enterography findings were negative (n = 2) or improved (n = 2). No treatment change was initiated; and at follow-up, three of four patients were improved and the remaining patient was stable symptomatically. Sixteen ileoscopies were attempted in 12 patients; however, four examinations did not reach the ileum. In the remaining examinations, endoscopy correlated with CT enterography in all cases (12/12, 100%) and with symptoms in nine of 12 (75%) cases. The weighted kappa statistic, which measures the chance-adjusted agreement between CT enterography and symptoms, was 0.57 (95% CI, 0.20-0.94). CONCLUSION: This preliminary study indicates that imaging changes between CT enterography examinations have excellent potential for reliably monitoring Crohn's disease progression or regression.

Preoperative dobutamine stress echocardiographic findings and subsequent short-term adverse cardiac events after orthotopic liver transplantation.

Cardiovascular (CV) complications are the leading cause of non-graft-related death in orthotopic liver transplant (OLT) patients. Pretransplant cardiac evaluation using dobutamine stress echocardiography (DSE) is commonly utilized for risk stratification of OLT candidates. To determine if clinical and echocardiographic variables identify patients with increased CV risk, we performed a retrospective chart review of all 284 patients that underwent OLT at our institution between June 1999 and August 2005. Of these patients, 157 had a DSE prior to their OLT. Serious adverse CV events occurring during surgery and up to 4 months post-transplantation were defined as cardiac-related death, myocardial infarction (MI), new heart failure, or asystole or unstable ventricular arrhythmia requiring acute treatment. Sixteen of 157 patients (10%) had an adverse CV event with 2 deaths. These included ventricular tachycardia (n = 8), asystole (n = 2), MI (n = 5), and new heart failure (n = 1). Nine of the 16 CV events occurred at the time of surgery (including both deaths), 5 occurred postoperatively, and 3 occurred after hospital discharge. Variables that correlated with increased CV events were inability during DSE to achieve >82% of the maximum predicted heart rate (22% versus 6%, P = 0.01), a peak rate pressure product during DSE of <16,333 (17% versus 5%, P = 0.02), and a Model for End-Stage Liver Disease (MELD) score of >24 at the time of OLT. A multivariate model calculated from the DSE maximum achieved heart rate (MAHR) and MELD score (result = 3.78 + 0.07 MELD - 0.05 MAHR) identified a 47% risk for a value > 0 versus a 6% risk for a value < 0 (P < 0.001). In conclusion, the maximum heart rate achieved during DSE together with the MELD score may be a predictor of adverse CV events up to 4 months post-OLT. A large prospective study is needed to more decisively support this conclusion.

The MUC1 Cytoplasmic Tail and Tandem Repeat Domains Contribute to Mammary Oncogenesis in FVB Mice.

BACKGROUND: Though the importance of the transmembrane mucin MUC1 in mammary oncogenesis has long been recognized, the relative contributions of the cytoplasmic tail and tandem repeat domains are poorly understood. METHODS: To address this, mouse models of mammary carcinogenesis were created expressing full-length, cytoplasmic tail-deleted, or tandem repeat-deleted MUC1 constructs. RESULTS: Overexpression of full-length MUC1 resulted in tumor formation in young mice (≤12 months); however, loss of either the cytoplasmic tail or the tandem repeat domain abrogated this oncogenic capacity. Aged mice in all strains developed late-onset mammary tumors similar to those previously described for the FVB background. CONCLUSIONS: This study is the first spontaneous cancer model to address the relative importance of the cytoplasmic tail and tandem repeat domains to MUC1-driven mammary oncogenesis, and suggests that both of these domains are essential for tumor formation.

Distinctive heavy metal composition of pancreatic juice in patients with pancreatic carcinoma.

Epidemiologic studies have shown the health risks of exposure to cigarette smoke and air pollution, with heavy metal composition implicated as contributing to both. Environmental exposure to cigarette smoke has been epidemiologically associated with pancreatic cancer, but the pathophysiologic basis for this is not yet clear. In the current work, we have used inductively coupled plasma mass spectrometry to quantify the metal composition of pancreatic juice collected in response to secretin stimulation in successive patients evaluated for abdominal pain (35 with pancreatic cancer, 30 with chronic pancreatitis, and 35 with normal pancreas). Indeed, metal composition of pancreatic juice was distinctive in patients with pancreatic cancer relative to those without such a cancer. The metal concentrations that were found to have the strongest association with pancreatic cancer were chromium, selenium, and molybdenum, with 1 SD increases in the concentrations of each associated with substantial increases in the odds of having pancreatic cancer relative to those in patients with normal pancreas (210%, 160%, and 76%, respectively). Of note, elevations in concentrations of chromium and selenium did not correlate in individuals, whereas those having a 1 SD increase in the sum of the concentrations of these two metals in their pancreatic juice had a 480% increase in the odds of having pancreatic cancer. Elevations of nickel and zinc correlated with elevated chromium in individuals, with each of these metals known to be present in cigarette smoke, whereas other recognized metal components of cigarette smoke were not elevated. An understanding of why these metals are elevated in pancreatic juice and what effects they might have on pancreatic cells may have important implications for the diagnosis, treatment, and even prevention of pancreatic cancer.

Patient understanding of the importance of beta-blocker use in the perioperative period.

OBJECTIVE: Perioperative beta-adrenergic blockade has been shown to decrease morbidity and mortality after noncardiac surgery. The objective of this study was to determine patient knowledge of the importance of perioperative beta-blockade in a population already taking chronic therapy and to assess the effectiveness of medical and surgical providers in patient education regarding these benefits. DESIGN: Survey. SETTING: Teaching hospital. PARTICIPANTS: One hundred twenty-six patients taking daily beta-blockers presenting to a preoperative medical evaluation clinic completed a 12-question survey that assessed their understanding of the potential benefit of taking the medication in the perioperative period. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Mean coronary artery disease risk factors per individual were 3.2 (standard deviation, 1.5). Forty-nine percent indicated that beta-blockers are beneficial in the perioperative period. Of those identifying benefit, 8% recognized decrease in myocardial infarction or decrease in mortality as the reason. Sixty-nine percent of patients who identified perioperative benefit cited blood pressure control as the reason. This correlated to the 67% of the total sample who identified their indication for the medication as antihypertensive. Only 7% recalled their prescribing physician ever mentioning the beta-blocker in relation to surgery. The same percentage recalled their surgeon mentioning it in relation to the planned procedure. CONCLUSIONS: This study suggests low patient understanding of the potential importance and reasons for perioperative beta-blockade. Patients who recognized perioperative benefit identified antihypertensive versus cardioprotective effects. Clinicians can improve education of patients already taking daily beta-blockers regarding these potential benefits.

Outcomes, health status, and medical resource utilization after bariatric surgery.

Surgical results, economic consequences, and shortterm health of obese patients were evaluated before and after bariatric surgery. Of 35 patients in Mayo Health Plan Arizona eligible for bariatric surgery and scheduled for gastric restriction with Roux-en-Y gastrojejunostomy, 22 (7 men, 15 women) completed pre- and postoperative (6- and 12-mo) short form (SF)-12 Health Surveys. Nineteen patients had open bariatric procedures and 3 had laparoscopic procedures. Comorbid conditions, hospital course, weight loss, and complications were examined. Health care utilization (actual dollars paid by plan) for the preceding year and at 1- and 2-yr follow-up were compared. Major comorbid conditions included diabetes mellitus or impaired fasting glucose, hyperlipidemia, sleep apnea, and hypertension. Mean length of hospital stay was 4.8 d after open procedures and 2 d after laparoscopic procedures. No serious operative or postoperative complications occurred. From a baseline average body mass index (BMI) of 51.9, the 6- and 12-mo BMI averages were 39.6 (23.7% decrease) and 35.3 (32% decrease), respectively. Both physical and mental status improved. From baseline, physical health changed 18 and 21.2 points at 6 and 12 mo, respectively (p < 0.001), and mental health changed 9.3 points at each interval (p =0.003). Each postoperative year, resource utilization decreased (mean= $1300 per patient). Our findings of good surgical outcomes, significant weight loss, improved health status, and potential financial savings in this small sample may help patients, insurers, and self-funded employer groups evaluate the appropriateness of bariatric procedures.