Effect of sleep on overnight cerebrospinal fluid amyloid ß kinetics.

Sleep disturbances are associated with future risk of Alzheimer disease. Disrupted sleep increases soluble amyloid ß, suggesting a mechanism for sleep disturbances to increase Alzheimer disease risk. We tested this response in humans using indwelling lumbar catheters to serially sample cerebrospinal fluid while participants were sleep-deprived, treated with sodium oxybate, or allowed to sleep normally. All participants were infused with 13 C6 -leucine to measure amyloid ß kinetics. We found that sleep deprivation increased overnight amyloid ß38, amyloid ß40, and amyloid ß42 levels by 25 to 30% via increased overnight amyloid ß production relative to sleeping controls. These findings suggest that disrupted sleep increases Alzheimer disease risk via increased amyloid ß production. Ann Neurol 2018;83:197-204.

Clopidogrel bisulfate (Plavix) does not increase bleeding complications in patients undergoing rubber band ligation for symptomatic hemorrhoids.

BACKGROUND: The incidence of postprocedural bleeding in patients undergoing rubber band ligation (RBL) for symptomatic internal hemorrhoids while taking clopidogrel bisulfate is unknown. To determine the postprocedural bleeding risk of RBL for patients taking clopidogrel compared with age- and sex-matched controls. MATERIALS AND METHODS: This is a retrospective case-controlled cohort study analyzing data from 2005 to 2013 conducted at a single tertiary care academic center. The study included a total of 80 rubber bands placed on 41 patients taking clopidogrel bisulfate and 72 bands placed on 41 control patients not taking clopidogrel matched for age and sex. The 30-d rates of significant and insignificant bleeding events after RBL were recorded. A bleeding event was considered significant if the patient required admission to the hospital, transfusion of blood products, or additional procedures to stop the bleeding. Insignificant bleeding was defined as passage of blood or clots per rectum with spontaneous cessation and no need for additional intervention. RESULTS: There was no significant difference in the number of bleeding events per band placed in the clopidogrel group when compared with the control group (3.75% versus 2.78%, P = 0.7387). The rate of significant (2.5% versus 1.39%, P = 0.6244) and insignificant bleeding events (1.25% versus 1.39%, P = 0.9399) was also similar between the two groups. Two significant bleeding events occurred in the clopidogrel group requiring intervention: cauterization in one patient and colonoscopy and transfusion in the other. CONCLUSIONS: The risk of a bleeding complication after RBL for hemorrhoids does not appear to be increased in patients taking clopidogrel. Our results support the practice of continuing clopidogrel bisulfate in the periprocedural period as the associated risk of thrombosis is greater than the risk of bleeding.

Amyloid ß concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis.

INTRODUCTION: Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid-binding positron emission tomography studies, are limited by cost and availability. There is a need for a more practical amyloid ß (Aß) biomarker for central nervous system amyloid deposition. METHODS: We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover kinetics and concentrations of Aß38, Aß40, and Aß42 in human plasma. RESULTS: Aß isoforms have a half-life of approximately 3 hours in plasma. Aß38 demonstrated faster turnover kinetics compared with Aß40 and Aß42. Faster fractional turnover of Aß42 relative to Aß40 and lower Aß42 and Aß42/Aß40 concentrations in amyloid-positive participants were observed. DISCUSSION: Blood plasma Aß42 shows similar amyloid-associated alterations as we have previously reported in cerebrospinal fluid, suggesting a blood-brain transportation mechanism of Aß. The stability and sensitivity of plasma Aß measurements suggest this may be a useful screening test for central nervous system amyloidosis.

Variations in perioperative steroid management among surgical subspecialists.

Previously we demonstrated consistency in perioperative steroid dosing among colon and rectal surgeons. To determine whether patterns have changed and if dosing schedules differ across surgical specialties, we evaluated multiple specialties. Questionnaires were mailed to members of the American Society of Colon and Rectal Surgeons (CRS) (n = 1523), American Society of Transplant Surgeons (TS) (n = 988), American Society of General Surgeons (GS) (n = 2750), and American Association of Endocrine Surgeons (ES) (n = 278). Surveys addressed demographic factors and factors in dosing, whether steroids are managed by surgeon alone or in collaboration with colleagues, and the most common taper regimens used. Four hundred fifty surveys were returned. Sixty-four respondents had retired or answered less than 50 per cent; 386 (211CRS, 116GS, 45TS, and 14ES) were available for analysis. The majority managed both perioperative (85.5%) and tapers (77%) themselves; TS and ES were significantly less likely to use other physicians (P < 0.001). The preoperative dose used most frequently was 100 mg hydrocortisone intravenously (76% CRS, 64% GS, 22% TS, and 93% ES). Most CRS (44.5%) and GS (24.1%) taper intravenous steroids over 3 days, whereas TS (33.3%) and ES (50%) return patients to prednisone within 1 to 2 days. Discharge steroid use was inconsistent with CRS (46.4%) tapering prednisone over greater than 21 days, GS (19%) over less than 21 days, and TS (20%) and ES (21.4%) taper over 21 days to preoperative prednisone doses (P < 0.001). In the absence of standard guidelines for perioperative corticosteroid administration, significant variations exist in the regimens used by surgeons in multiple specialties.

Increased Cerebrospinal Fluid Amyloid-ß During Sleep Deprivation in Healthy Middle-Aged Adults Is Not Due to Stress or Circadian Disruption.

BACKGROUND: Concentrations of soluble amyloid-ß (Aß) oscillate with the sleep-wake cycle in the interstitial fluid of mice and cerebrospinal fluid (CSF) of humans. Further, the concentration of Aß in CSF increases during sleep deprivation. Stress and disruption of the circadian clock are additional mechanisms hypothesized to increase CSF Aß levels. Cortisol is a marker for stress and has an endogenous circadian rhythm. Other factors such as glucose and lactate have been associated with changes in sleep-wake activity and/or Aß. OBJECTIVE: In this exploratory study, we used samples collected in a previous study to examine how sleep deprivation affects Aß, cortisol, lactate, and glucose in plasma and CSF from healthy middle-aged adults (N = 11). METHODS: Eleven cognitively normal participants without evidence of sleep disturbance were randomized to sleep deprivation or normal sleep control. All participants were invited to repeat the study. Cortisol, lactate, glucose, and Aß were measured in 2-h intervals over a 36-h period in both plasma and CSF. All concentrations were normalized to the mean prior to calculating mesor, amplitude, acrophase, and other parameters. RESULTS: One night of sleep deprivation increases the overnight concentration of Aß in CSF approximately 10%, but does not significantly affect cortisol, lactate, or glucose concentrations in plasma or CSF between the sleep-deprived and control conditions. CONCLUSION: These data suggest that sleep deprivation-related changes in CSF Aß are not mediated by stress or circadian disruption as measured by cortisol.

Use of Sodium Hyaluronate/Carboxymethylcellulose Bioresorbable Membrane in Loop Ileostomy Construction Facilitates Stoma Closure.

BACKGROUND: Loop ileostomy is a common adjunct to surgical procedures for low rectal cancers and inflammatory bowel disease. Ileostomy closure through a limited incision can be technically challenging. We hypothesized that placing a sodium hyaluronate/carboxymethylcellulose (SH/CMC) bioresorbable membrane at loop ileostomy creation would decrease stoma closure time without increasing morbidity. METHODS: In a retrospective review at a single institution with 6 board-certified colorectal surgeons, patients with loop ileostomy creation and closure between September 1999 and December 2011 were grouped based on SH/CMC placement at ileostomy creation. Data were abstracted for age, sex, body mass index (BMI), primary diagnosis, length of surgery, staff surgeon, interval between surgeries, and postoperative morbidity. The primary endpoint was the length of the surgery for ileostomy closure. Secondary outcome measures were length of stay, wound infection rate, and other complications. RESULTS: A total of 293 patients were identified. Group 1 (with SH/CMC) included 146 patients, and Group 2 (without SH/CMC) included 147 patients. The groups were matched according to age, sex, BMI, interval between creation and closure, and indication for surgery. The average surgical time for closure was significantly shorter in Group 1 (46.4 minutes ± 2.7) compared to Group 2 (60 minutes ± 2.3) (P=0.0001). We found no difference between the groups in length of stay, wound infection rate, or complication rate. CONCLUSION: The use of SH/CMC in loop ileostomy creation significantly decreases the operative time required for stoma closure with no increase in the complication rate.

Restorative proctocolectomy: the current ochsner experience.

BACKGROUND: Restorative proctocolectomy with an ileal pouch-anal anastomosis is a technically demanding procedure to treat ulcerative colitis and familial adenomatous polyposis. Since its initial description almost 30 years ago, the operation has undergone technical and perioperative modifications to improve the patient's experience. METHODS: We performed a retrospective review of the records of patients undergoing restorative proctocolectomy at the Ochsner Clinic Foundation Hospital from 2008 to 2012 and compared data from that period to data from 1989-1995 (prior to laparoscopic pouch surgery) to determine factors associated with patient outcome. RESULTS: Ileal pouch-anal procedures were performed in 77 patients. The 30 male and 47 female patients ranged in age from 13 to 63 years (mean, 34.5 years). The indications for the procedure were ulcerative colitis in 62 patients, polyposis coli in 12 patients, and Crohn disease in 3 patients. Forty patients (52%) had laparoscopic-assisted procedures. The overall hospital length of stay for pouch creation averaged 6.9 days (range 3-29) and for ileostomy closure averaged 4.3 days (range 1-15). No perioperative deaths occurred within 30 days. Complications occurred in 37.7% of patients. Compared to a previous report of 72 patients from 1989 to 1995, the recent group had more laparoscopic procedures, shorter hospital stays, a smaller percentage of 3-stage procedures, and fewer general and pouch-related complications. Pouch failures were similar for both groups. CONCLUSION: Advances in operative techniques and perioperative management have improved the outcome of restorative proctocolectomies.

Rectal prolapse: a 10-year experience.

PURPOSE: To compare perineal to abdominal procedures for rectal prolapse over a 10-year period at a single tertiary care institution. METHODS: Between May 1, 1995, and January 1, 2005, 75 patients underwent surgical intervention for primary rectal prolapse at a tertiary referral center. Surgical techniques included perineal-based repairs (Altemeier and Delorme procedures) and abdominal procedures (open and laparoscopic resection and/or rectopexy). Medical records were abstracted for data pertaining to patient characteristics, signs and symptoms at presentation, surgical procedure, postoperative length of hospitalization, morbidity and mortality, and recurrence of rectal prolapse. RESULTS: Seventy-five patients underwent surgical intervention for rectal prolapse during the study period. The average patient age was 60.8 years. Sixty-two patients (82.7%) underwent perineal-based repair (Altemeier n = 48, Delorme n = 14); eight patients (10.7%) underwent open abdominal procedures (resection and rectopexy n = 4, rectopexy only n = 4); and five patients (6.7%) underwent laparoscopic repair (laparoscopic LAR n = 3, laparoscopic resection and rectopexy n = 2). Average hospitalization was shorter with perineal procedures (2.6 days) than with abdominal procedures (4.8 days) (p < 0.0031). Postoperative complications were observed in 13.3% of cases. With a median follow-up of 39 months (range 6-123 months), there was no mortality for primary repair, a postoperative morbidity occurred in 13% of patients, and the overall rate of recurrent prolapse was 16% (16.1% for perineal-based repairs, 15.4% for abdominal procedures). CONCLUSION: Perineal resections were more common, performed in significantly older patients, and resulted in a shorter hospital stay. Their minimal morbidity and similar recurrence rates make perineal procedures the preferred option.

Local recurrence, distant recurrence and survival of rectal cancer.

PURPOSE: To assess our institution's ability to minimize local and distant recurrence with a preference for sphincter preserving surgery in the management of rectal cancer. METHODS: A retrospective analysis of all patients treated between 1982 and 1998. Patients with Stage 0 (AJCC) disease and those treated for palliation were not included. Clinical and pathologic stage, operation type, adjuvant therapy, recurrence, and survival were compared. Kaplan-Meier analysis was also performed. RESULTS: Rectal cancer was identified in 332 patients (mean follow-up: 5.5 years). One hundred and seventy-three patients (52.1%) underwent low anterior resection, while 107 patients (32.2%) required abdominoperineal resection, 6 patients (1.8%) required exenteration to control disease, and 46 (13.9%) patients were treated with local excision. Of the 332 patients, 63 (19.0%) received adjuvant radiotherapy alone, 85 (25.6%) received combination chemoradiotherapy, and 4 (1.2%) received chemotherapy. Sphincter preserving procedures were used more frequently in the later half of the experience. Local/regional recurrences occurred in 5 patients (3.3%) treated with adjuvant therapy, and in 16 patients (8.9% of total) who did not receive adjuvant therapy (p=0.02, Chi-square test) although the total risk of recurrence (local and/or distant) was not different (30.2% vs. 27.7%, p=0.54). The actuarial rate of local recurrence (regardless of adjuvant therapy) for all stages was 7% at 5 years, and the risk of any recurrence (local or distant) was 21.1% at 5 years. Cancer specific 5-year survival was 77% overall. CONCLUSIONS: In rectal cancer, the therapeutic objectives are to control disease, limit recurrence, and preserve sphincter function; these goals were met for many patients at this institution. These data compare favorably with the current literature. Careful surgical technique and adjuvant therapy can allow successful treatment, even of advanced rectal cancers.

The importance of colonoscopy in colorectal surgeons' practices: results of a survey.

PURPOSE: The role of colonoscopy in the prevention of colorectal cancer has been accepted, not only by the medical community but by the federal government as well. This study sought to document the current role of colonoscopy in the practices of colorectal surgeons. METHODS: A survey was mailed to members of The American Society of Colon and Rectal Surgeons detailing the scope of colonoscopy in their practices. RESULTS: Surveys were mailed to 1,800 members of The American Society of Colon and Rectal Surgeons; responses were received from 778 (43.2 percent). The mean age was 48 +/- 10 (range, 27-79) years; the mean number of years in practice was 14 +/- 10 (range, 0.2-48). The majority of respondents (91 percent) were male. Responses were received from 47 U.S. states and 30 foreign countries. Seventy-four respondents (9.5 percent) reported not performing colonoscopy; the most common reason cited was "referring physicians' preference" (45 percent). Seven-hundred four respondents (90.5 percent) reported performing colonoscopy as part of their clinical practice and reported an average of 41 +/- 41 colonoscopies in the last month (range, 0-635) and 457 +/- 486 in the last year (range, 2-7,000). Colonoscopy accounted for 23 +/- 16 percent of responding physicians' clinical time (range, 1-100 percent) and 27 +/- 19 percent of total charges (range, 0-100 percent). Nearly all respondents (97 percent) anticipated maintaining or increasing their volume of colonoscopy in the coming year. Eighty-four percent of respondents reported receiving some or all of their training in colonoscopy during a colon and rectal surgery fellowship. More than one-half of respondents (55 percent) believed that there should be more of an emphasis on colonoscopy on the American Board of Colon and Rectal Surgery board examination, and 81 percent believed that the annual meeting of The American Society of Colon and Rectal Surgeons should include lectures and/or courses covering colonoscopy. CONCLUSIONS: Colonoscopy plays a major role in the practices of colorectal surgeons across the world, accounting for approximately one-quarter of clinical time and total charges. Based on the expectation that this trend will continue, The American Society of Colon and Rectal Surgeons needs to aggressively support its members not only in the technical aspects of colonoscopy but also in the practice management issues.