[18F]FDG PET/CT imaging disproves renal allograft acute rejection in kidney transplant recipients with acute kidney dysfunction: a validation cohort.

PURPOSE: [18F]FDG PET/CT may predict the absence of acute allograft rejection (AR) in kidney transplant recipients (KTRs) with acute kidney injury (AKI). Still, the proposed threshold of 1.6 of the mean of mean standardized uptake values (mSUVmean) in the renal parenchyma needs validation. METHODS: We prospectively performed 86 [18F]FDG PET/CT in 79 adult KTRs who underwent per-cause transplant biopsy for suspected AR. Biopsy-proven polyoma BK nephropathies (n = 7) were excluded. PET/CT was performed 192 ± 18 min after administration of 254.4 ± 30.4 MBq of [18F]FDG. The SUVmean was measured in both upper and lower poles of the renal allograft. One-way analysis of variance (ANOVA) and Tukey's studentized range test were sequentially performed. The receiver operating characteristic (ROC) curve was drawn to discriminate "AR" from non-pathological ("normal" + "borderline") conditions. RESULTS: The median age of the cohort was 55 [43; 63] years, with M/F gender ratio of 47/39. The mean eGFR was 31.9 ± 14.6 ml/min/1.73m2. Biopsies were categorized in 4 groups: "normal" (n = 54), "borderline" (n = 9), "AR" (n = 14), or "others" (n = 2). The median [min; max] mSUVmean reached 1.72 [1.02; 2.07], 1.97 [1.55; 2.11], 2.13 [1.65, 3.12], and 1.84 [1.57; 2.12] in "normal," "borderline," "AR," and "others" groups, respectively. ANOVA demonstrated a significant difference of mSUVmean among groups (F = 13.25, p < 0.0001). The ROC area under the curve was 0.86. Test sensitivity and specificity corresponding to the threshold value of 1.6 were 100% and 30%, respectively. CONCLUSION: [18F]FDG PET/CT may help noninvasively prevent inessential transplant biopsies in KTR with AKI.

A Multicenter Study to Evaluate Harmonization of Assays for C-Terminal Telopeptides of Type I Collagen (ß-CTX): A Report from the IFCC-IOF Committee for Bone Metabolism (C-BM).

BACKGROUND: Biochemical bone turnover markers are useful tools to assess bone remodeling. C-terminal telopeptide of type I collagen (ß-CTX) has been recommended as a reference marker for bone resorption in research studies. METHODS: We describe the results of a multicenter study for routine clinical laboratory assays for ß-CTX in serum and plasma. Four centers (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers' instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method, and Concordance correlation coefficient for ß-CTX values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Two pools of serum were finally prepared and sent to the four centers to be measured in 5-plicates on 5 consecutive days with the different methods. RESULTS: We identified significant variations between methods and between centers although comparison results were generally more consistent in plasma compared to serum. We developed univariate linear regression equations to predict Roche Elecsys®, IDS-iSYS, or IDS ELISA ß-CTX results from any other assay and a multivariable model including the site of analysis, the age, and weight of the patient. The coefficients of determination (R2) increased from approximately 0.80 in the univariate model to approximately 0.90 in the multivariable one, with the site of analysis being the major contributing factor. Results observed on the pools also suggest that long-term storage could explain the difference observed with the different methods on serum. CONCLUSION: Our results show large within- and between-assay variation for ß-CTX measurement, particularly in serum. Stability of the analyte could be one of the explanations. More studies should be undertaken to overcome this problem. Until harmonization is achieved, we recommend measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed.

Outcomes of completion total mesorectal excision are not compromised by prior transanal minimally invasive surgery.

AIM: Transanal minimally invasive surgery (TAMIS) is used increasingly often as an organ-preserving treatment for early rectal cancer. If final pathology reveals unfavourable histological prognostic features, completion total mesorectal excision (cTME) is recommended. This study is the first to investigate the results of cTME after TAMIS. METHOD: Data were retrieved from the prospective database of the Elisabeth-TweeSteden Hospital. Completion TME patients were case matched with a control group of patients undergoing primary TME (pTME). Primary and secondary outcomes were surgical outcomes and oncological outcomes, respectively. RESULTS: From 2011 to 2017, 20 patients underwent cTME and were compared with 40 patients undergoing pTME. There were no significant differences in operating time (238 min vs 226 min, P = 0.53), blood loss (137 ml vs. 158 ml, P = 0.88) or complications (45% vs 55%, P = 0.07) between both groups. There was no 90-day mortality in the cTME group. The mesorectal fascia was incomplete in three patients (15%) in the cTME group compared with no breaches in the pTME group (P = 0.083). There were no local recurrences in either group. In three patients (15%), distant metastases were detected after cTME compared with one patient (2.5%) in the pTME group (P = 0.069). After cTME patients had a 1- and 5-year disease-free survival of 85% compared with 97.5% for the pTME group (P = 0.062). CONCLUSION: Completion TME surgery after TAMIS is not associated with increased peri- or postoperative morbidity or mortality compared with pTME surgery. After cTME surgery patients have a similar disease-free and overall survival when compared with patients undergoing pTME.

The effect of proctoring on the learning curve of transanal minimally invasive surgery for local excision of rectal neoplasms.

BACKGROUND: The current method of choice for local resection of benign and selected malignant rectal tumors is transanal endoscopic microsurgery. Transanal minimally invasive surgery (TAMIS) yields similar oncological results and better patient reported outcomes when compared to transanal endoscopic micro surgery. However, due to the technical complexity of TAMIS, a significant learning curve has been suggested. Data on the surgical learning curve are limited. The aim of our study was to investigate surgeon specific learning curves for TAMIS procedures for the local excision of selected rectal tumors, and analyze the effects of proctoring on operating time and outcome. METHODS: The current study was prospective of all TAMIS procedures performed by two surgeons from October 2010 to November 2017. Margin positivity, specimen fragmentation, adverse events and operative time were evaluated with a cumulative sum analysis to determine the number of procedures required to reach proficiency. Cumulative sum (CUSUM) analysis was used to determine trends in changes over time. RESULTS: The earliest adopter, surgeon A, performed 103 procedures, was not proctored and developed the standardized institutional program. Surgeon B, performed 26 cases, had the benefit of a proctorship and availability of a standardized program. The CUSUM curve for operative time showed a change after 36 cases for surgeon A and after 10 cases for surgeon B. For margin positivity proficiency was reached after 31 and 6 cases for surgeon A and B, respectively. The complications curve for surgeon A showed a three-phase learning curve with a decrease after the 26th case whereas surgeon B only had one (3.8%) complication in the learning phase with no change point in the CUSUM curve. Comparing pre- and post-proficiency periods there was a decrease in operating time for both surgeon A (84.4 ± 47.3 to 55.9 ± 30.1 min) and surgeon B (90.6 ± 64.to 53 ± 26.5 min; p < 0.001). Overall margin positivity rates decreased non significantly from 21.7 to 4.8% (p = 0.23). Complications were higher in the pre-proficiency period (21.7% vs. 13.0%; p = 0.02). Surgeon A had significantly more postoperative complications in pre-proficiency phase when compared to surgeon B (25% vs. none, p < 0.001), in the post-proficiency phase there was no statistically significant difference between both surgeons (p = 0.08). CONCLUSIONS: Our results suggest that to reach satisfactory results for TAMIS, 18-31 procedures are required. Standardized institutional operative protocols together with proficient proctorship may contribute to a shorter learning curve with fewer cases (6-10) required to reach proficiency.

Persistent aggregates in apheresis platelet concentrates are commonly collected from donors with a history of aggregate donation.

Platelet apheresis sometimes causes persistent aggregates (PA). This study (n = 211) shows that changing the apheresis settings to reach fixed product volumes instead of yields does not influence PA incidence, even though PA products on average contain more platelets than controls. Furthermore, logistic regression was used to model if PA can be predicted on the basis of certain predonation parameters. PA donation history was the only parameter retained, proving a strong determinant of predictability [AUC = 0.735 (SE = 0.022)]. Consequently, donations from a donor with previous PA history are 7.8 times more likely to contain PA than from a donor without preceding history.

The influence of propofol and sevoflurane on intestinal motility during laparoscopic surgery.

BACKGROUND: Volatile anaesthetics have an influence on small bowel peristalsis during laparoscopic surgery. A recent study concluded that desflurane increased intestinal motility compared to sevoflurane. Hence, a desflurane-based anaesthesia protocol may reduce surgical exposure during intestinal suturing or stapling due to small bowel hyperperistalsis. The effect of propofol on intestinal motility is not well studied. We tested the hypothesis that a propofol-remifentanil anaesthesia increases intestinal contractions in comparison with a sevoflurane-remifentanil anaesthesia. METHODS: Patients scheduled for laparoscopic gastric bypass surgery were randomized in this single blind randomized controlled trial to receive remifentanil combined with sevoflurane or propofol (ISRCTN 12921661). Bispectral index monitoring was used to guide depth of anaesthesia. Visual observation of peristaltic waves was performed during 1 min at the planned site of the jejunostomy. Statistical analysis was performed using Wilcoxon two-sample test. RESULTS: After obtaining written informed consent 50 patients were included. Groups were similar for demographic variables, and depth of anaesthesia during the observations. The median number of peristaltic waves was lower in the sevoflurane-remifentanil group compared to the propofol-remifentanil group (0 vs. 6, P < 0.001). CONCLUSION: Propofol-remifentanil increases intestinal motility compared with sevoflurane-remifentanil during laparoscopic gastric bypass surgery. A sevoflurane-based protocol can help to avoid disturbing peristalsis.

Persistent aggregates in apheresis platelet concentrates.

BACKGROUND: Aggregates often appear during apheresis. Sometimes, these persist throughout storage, causing product wastage. This study assessed product quality of apheresis concentrates containing persistent aggregates (PA) and aimed to identify the factors that contribute to their formation. METHODS: Donation (n = 180) and platelet indices (n ≥ 10) from apheresis concentrates with PA were compared with aggregate-free products. RESULTS: The proportion of donors with at least one previous PA donation was twofold higher in the PA group (P < 0·0001) indicating a donor dependence. Significantly higher donor whole blood platelet counts (286 ± 50 vs. 266 ± 49 × 10(3) /µl, P < 0·0001) and higher apheresis yields (6·0 ± 1·6 vs. 5·4 ± 1·5 × 10(11) , P < 0·0001) were noted in the PA group. Haematocrit was also slightly higher, but age, gender and body mass were similar. The pH of PA products on day six postdonation was significantly lower (P < 0·001), in line with higher lactic acid concentrations. Flow cytometry showed no differences in GPIbα levels or phosphatidylserine exposure. However, there was slightly more integrin activation as well as increased degranulation measured by P-selectin expression. Cytokine concentrations were also significantly higher in PA concentrates. Aggregation was normal in response to SFLLRN peptide and collagen stimulation, but agglutination at low-dose ristocetin was significantly higher (P = 0.01) in PA products. Finally, PA were disintegrated by plasmin-mediated thrombolysis but not by integrin αIIb ß3 inhibition. CONCLUSION: Products with PA have acceptable quality parameters, but additional functional studies are warranted. Furthermore, PA are more likely to recur in certain donors who have higher platelet counts.

A randomised controlled trial of intravenous dexamethasone combined with interscalene brachial plexus blockade for shoulder surgery.

We recruited patients scheduled for shoulder rotator cuff repair or subacromial decompression under general anaesthesia and interscalene brachial plexus blockade (30 ml ropivacaine 0.5%). We allocated 240 participants into four groups of 60 that were given pre-operative saline 0.9% or dexamethasone 1.25 mg, 2.5 mg or 10 mg, intravenously. We recorded outcomes for 48 h. The median (IQR [range]) time to first postoperative analgesic request after saline was 12.2 (11.0-14.1 [1.8-48]) h, which was extended by intravenous dexamethasone 2.5 mg and 10 mg to 17.4 (14.9-21.5 [7.2-48]) h, p < 0.0001, and 20.1 (17.2-24.3 [1.3-48]) h, p < 0.0001, respectively, but not by dexamethasone 1.25 mg, 14.0 (12.1-17.7 [2.1-48]) h, p = 0.05. Postoperative analgesia was given sooner after rotator cuff repair than subacromial decompression, hazard ratio (95% CI) 2.2 (1.6-3.0), p < 0.0001, but later in older participants, hazard ratio (95% CI) 0.98 (0.97-0.99) per year, p < 0.0001.

Serial comprehensive geriatric assessment in elderly head and neck cancer patients undergoing curative radiotherapy identifies evolution of multidimensional health problems and is indicative of quality of life.

Head and neck (H&N) cancer is mainly a cancer of the elderly; however, the implementation of comprehensive geriatric assessment (CGA) to quantify functional age in these patients has not yet been studied. We evaluated the diagnostic performance of screening tools [Vulnerable Elders Survey-13 (VES-13), G8 and the Combined Screening Tool 'VES-13 + (17-G8)' or CST], the feasibility of serial CGA, and correlations with health-related quality of life evolution [HRQOL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ)-C30 and -HN35] during therapy in hundred patients, aged ≥65 years, with primary H&N cancer undergoing curative radio(chemo)therapy. Respectively 36.8%, 69.0%, 62.1% and 71.3% were defined vulnerable according to VES-13, G8, CST and CGA at week 0, mostly due to presence of severe grade co-morbidities, difficulties in community functioning and nutritional problems. At week 4, significantly more patients were identified vulnerable due to nutritional, functional and emotional deterioration. The CST did not achieve the predefined proportion necessary for validation. Vulnerable patients reported lower function and higher symptom HRQOL scores as compared with fit patients. A comparable deterioration in HRQOL was observed in both groups through therapy. In conclusion, G8 remains the screening tool of choice. Serial CGA identifies the evolution of multidimensional health problems and HRQOL conditions during therapy with potential to guide individualised supportive care.

I.V. and perineural dexamethasone are equivalent in increasing the analgesic duration of a single-shot interscalene block with ropivacaine for shoulder surgery: a prospective, randomized, placebo-controlled study.

BACKGROUND: Interscalene brachial plexus block (ISB) provides excellent, but time-limited analgesia. Dexamethasone added to local anaesthetics prolongs the duration of a single-shot ISB. However, systemic glucocorticoids also improve postoperative analgesia. The hypothesis was tested that perineural and i.v. dexamethasone would have an equivalent effect on prolonging analgesic duration of an ISB. METHODS: We performed a prospective, double blind, randomized, placebo-controlled study. Patients presenting for arthroscopic shoulder surgery with an ISB were randomized into three groups: ropivacaine 0.5% (R); ropivacaine 0.5% and dexamethasone 10 mg (RD); and ropivacaine 0.5% with i.v. dexamethasone 10 mg (RDiv). The primary outcome was the duration of analgesia, defined as the time between performance of the block and the first analgesic request. Standard hypothesis tests (t-test, Mann-Whitney U-test) were used to compare treatment groups. The primary outcome was analysed by Kaplan-Meier survival analysis with a log-rank test and Cox's proportional hazards regression. RESULTS: One hundred and fifty patients were included after obtaining ethical committee approval and patient informed consent. The median time of a sensory block was equivalent for perineural and i.v. dexamethasone: 1405 min (IQR 1015-1710) and 1275 min (IQR 1095-2035) for RD and RDiv, respectively. There was a significant difference between the ropivacaine group: 757 min (IQR 635-910) and the dexamethasone groups (P<0.0001). CONCLUSIONS: I.V. dexamethasone is equivalent to perineural dexamethasone in prolonging the analgesic duration of a single-shot ISB with ropivacaine. As dexamethasone is not licensed for perineural use, clinicians should consider i.v. administration of dexamethasone to achieve an increased duration of ISB.

Value of preoperative esophagogastroduodenoscopy in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass hinders post-operative endoscopic evaluation of the upper gastrointestinal tract. Our aims were to determine the prevalence of preoperative endoscopic findings in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) and to determine the proportion of patients in which these findings changed surgical management. METHODS: We retrospectively evaluated electronic medical records of patients undergoing esophagogastroduodenoscopy (EGD) with routine antral biopsy for Helicobacter pylori (HP) detection, prior to LRYGB between January 2003 and January 2010 at our institution. The prevalence of all endoscopic findings was determined. RESULTS: 652 underwent preoperative endoscopy prior to LRYGB. The mean age was 39.5 +/- 11.3 years and mean body mass index was 42.8 +/- 5.0 kg/m2. Abnormalities were found in 444 patients (68.1%). Findings at EGD were hiatal hernia 24.3% (n = 159), esophagitis 30.8% (n = 201), Barrett's esophagus 0.8% (n = 5), gastritis 36.2% (n = 236), gastric or duodenal ulcers 7.5% (n = 69) and 2 cases of gastric cancer. The prevalence of HP infection was 17.6% (n = 115). In 51 patients (7.8%), endoscopic findings led to postponement of surgery: in 49 patients, gastric or duodenal ulcer had to be treated prior to surgery, in 2 patients, gastric cancer led to changement in surgical approach. CONCLUSIONS: Routine preoperative EGD detects different abnormalities which need a specific approach prior to bariatric surgery. EGD with routine biopsies for HP detection should be included in the preoperative workup prior to LRYGB. Positive EGD findings led to a change in medical treatment in a quarter (24.3%) of patients. Postponement of surgery due to the EGD findings was less frequent (7.8%).

Transition from laparoscopic to robotic liver surgery: clinical outcomes, learning curve effect, and cost-effectiveness.

The reproducibility of the implementation of robotic liver surgery (RLS) is still debated. The aim of the present study is to evaluate short-term outcomes and cost differences during the implementation of RLS, performed by an early adopter in laparoscopic liver surgery (LLS). Patients undergoing RLS between February 2020 and May 2021 were included. Short-term outcomes of the robotic group (RG) were compared to the "Initial Phase" group (IP) of 120 LLS cases and the 120 most recent laparoscopic cases or "Mastery Phase" group (MP). A cost analysis per procedure for the three groups was performed. Seventy-one patients underwent RLS during the study period. Median operative time in the RG was comparable to the IP, but significantly shorter in the MP (140 vs 138 vs 120 min, p < 0.001). Median intraoperative blood loss in the RG was lower than in both laparoscopic groups (40 ml [20-90 ml] vs 150 ml [50-250 ml] vs 80 ml [30-150 ml], p < 0.001). Median hospital stay in the RG was significantly shorter than the IP group (p < 0.001). There were no significant differences in postoperative complication, conversion, or readmission rates. Procedural cost analysis was in favor of robotic surgery (€5008) compared to the IP (€ 6913) and the MP (€6099). Surgeons with sufficient experience in LLS can rapidly overcome the learning curve for RLS. In our experience, the short-term outcomes of the implementation phase of RLS are similar to the mastery phase of LLS. The total average cost per procedure is lower for RLS compared to LLS.

Randomized clinical trial on the influence of anaesthesia protocol on intestinal motility during laparoscopic surgery requiring small bowel anastomosis.

BACKGROUND: Hyperperistalsis of the small bowel during laparoscopic surgery may cause mucosal prolapse and reduce exposure, making laparoscopic suturing or stapling more demanding for the surgeon. Although it is commonly accepted that both opioids and volatile anaesthetics induce intestinal paralysis, intestinal hyperactivity during anaesthesia is not uncommon. This randomized trial investigated the effect of different volatile anaesthetics on intestinal motility and the impact on surgeon satisfaction. METHODS: Patients scheduled for laparoscopic gastric bypass surgery were randomized to receive sevoflurane or desflurane in a balanced anaesthetic regimen. After surgical exposure peristaltic waves were counted over 1 min in a segment of the jejunum. Following evaluation of intestinal motility, N-butylhyoscine, an antimuscarinic anticholinergic agent that relaxes bowel smooth muscle cells, could be administered if the surgeon judged the intestinal motility as disturbing. The endpoints were number of peristaltic waves and incidence of N-butylhyoscine administration, a surrogate for surgeon satisfaction. RESULTS: Twenty-two patients were randomized to each group. The groups were similar in age, sex and body mass index. There was a statistically significant difference in intestinal motility between the desflurane and sevoflurane groups: median (range) 7 (0-12) versus 1 (0-10) waves counted over 1 min respectively (P < 0·001). A higher proportion of patients in the desflurane group received N-butylhyoscine (10 of 22 versus 1 of 22 in the sevoflurane group; P = 0·004). CONCLUSION: Desflurane increased intestinal motility and decreased surgeon satisfaction compared with sevoflurane during laparoscopic gastric bypass surgery. A sevoflurane-based anaesthetic protocol can help to avoid disturbing hyperperistalsis. REGISTRATION NUMBER: B39620097060 (http://www.clinicaltrials.be).

Impact of FDG PET on the management of TBC treatment. A pilot study.

UNLABELLED: The aim of this study is to assess the potential impact of double-phase FDG PET versus routine staging in HIV-negative patients suffering from tuberculosis. PATIENTS, METHODS: 16 consecutive patients suffering from tuberculosis underwent contrast-enhanced CT and double-phase FDG PET imaging (45 min, 120 min). Early (E) and delayed (D) SUVmax values were determined for all identified lesions and % change in SUV calculated (DeltaSUV). RESULTS: Seven patients presented with lung lesions on PET as well as CT (mean SUVmaxE 8.2, mean SUVmaxD 11.1, (p = 0.002), DeltaSUV 35%. In two patients, lesions were judged as non-active on CT. In nine patients, 18 sites of LN involvement were identified on both early and delayed FDG PET images (mean SUVmaxE 6.3, mean SUVmaxD 7.9, (p = 0.0001), DeltaSUV: 25%). 9 out of 18 sites of LN involvement, occurring in five patients, were missed on CT. In four of these five patients, sites of LN involvement were the only sites of extra-pulmonary involvement identified. In 6 out of 16 patients, pleural involvement was identified, respectively in 5 on FDG PET and in 6 on CT imaging (mean SUVmaxE 1.3, mean SUVmaxD 1.7, (p = 0.06), DeltaSUV 21%). In 4 patients, osseous involvement was identified by both FDG PET and CT (mean SUVmaxE 7.2, mean SUVmaxD 10.7, (p = 0,06), DeltaSUV 45%). Finally, in 3 patients, joint involvement was identified on both FDG PET as well as on CT imaging (mean SUVmaxE 4.7, mean SUVmaxD 5.2, DeltaSUV 23%). FDG PET did not identify CT-additional sites of involvement that would have resulted in a prolonged treatment. CONCLUSION: In HIV-negative patients suffering from tuberculosis, FDG PET images suggested a more extensive involvement by Mycobacterium tuberculosis when compared to contrast enhanced CT.

Stroke coach: a pilot study of a personal digital coaching program for patients after ischemic stroke.

Despite recent advances in acute stroke care, the risk of recurrent stroke remains high. On behalf of the Belgian Stroke Council (BSC), a nurse-led self-management program was developed, using a personal coach and digital platform with the aim of improving cardiovascular risk factor control in patients after ischemic stroke. The program was implemented in four Belgian hospitals. The stroke coach provided one educational session during hospitalization. After discharge, the patient received tips and tricks concerning a healthy lifestyle through the customized platform. The stroke coach set up video appointments through the platform at regular intervals. Primary endpoint of our study was the change in SCORE (Systematic COronary Risk Evaluation: High and Low cardiovascular Risk Charts) risk at baseline and 6 months compared with a historical control group who received standard care. A total of 147 patients were included for a follow-up period of 6 months. The mean SCORE in the intervention group showed a statistically significant reduction of 3.2 (p < 0.001) at 6 months. However, comparison between control and intervention groups was non-significant (p = 0.55). Secondary endpoints are promising with a medication adherence of 96%. Reported quality of life also improved (p < 0.001). No significant improvement in the modified Rankin scale (mRS) was observed (p = 0.720). Five percent of patients suffered a recurrent stroke. Our project consisting of a coached lifestyle intervention and digital platform shows promise in improving stroke recurrence rates, therapeutic adherence and quality of life in a Belgian healthcare setting.

PEGylated cholecystokinin is more potent in inducing anorexia than conditioned taste aversion in rats.

BACKGROUND AND PURPOSE: The physiological involvement of endogenous cholecystokinin (CCK) in the termination of feeding has been challenged by evidence of aversive effects of exogenous CCK8. We previously prolonged the anorectic effect of CCK by conjugation to polyethylene glycol (PEGylation) to produce PEG-CCK9. In this study, we investigated the ability of different doses of PEG-CCK9 to induce conditioned taste aversion (CTA) and satiety and identified the receptors involved in CTA induction. EXPERIMENTAL APPROACH: Induction of CTA, measured by the saccharin preference ratio determined in a two-bottle CTA procedure, and of satiety in adult male Wistar rats after intraperitoneal (i.p.) injection of different doses of PEG-CCK9 (1, 2, 4, 8, 16 or 32 microg kg(-1)) was compared. Devazepide (100 microg kg(-1)) and 2-NAP (3 mg kg(-1)), two selective CCK1-receptor antagonists, were co-administered i.p. with PEG-CCK9 (8 microg kg(-1)) and the CTA effects monitored. KEY RESULTS: PEG-CCK9 dose-dependently induced CTA, with a minimal effective dose of 8 microg kg(-1), whereas the minimal effective dose to induce satiety was 1 microg kg(-1). The CTA effects of PEG-CCK9 were completely abolished by i.p. administration of devazepide prior to PEG-CCK9 treatment and only partially abolished by administration of 2-NAP. CONCLUSIONS AND IMPLICATIONS: Although PEG-CCK9-induced satiety and PEG-CCK9-induced CTA both increased with dose, the conjugate was more potent in inducing satiety, suggesting that the anorexia could not be completely attributed to the aversiveness of the drug. As observed with induction of satiety, PEG-CCK9-induced CTA was mediated by CCK1-receptors.

Chronic pain after Kugel inguinal hernia repair.

BACKGROUND: The incidence of chronic pain after Kugel herniorrhaphy is not well documented, since it was not used as a primary outcome measure in studies reporting on the Kugel technique. The aim of the present study was to report on the incidence and severity of chronic pain 1 year after Kugel herniorrhaphy and to identify the risk factors associated with the development of chronic pain. METHODS: The study population comprised all patients in our teaching hospital who underwent a Kugel inguinal hernia repair between January 2002 and June 2005. Postoperative complications, analgesia consumption and postoperative functional impairment were recorded during an outpatient clinic after 4-6 weeks. Chronic pain and cutaneous sensory changes were followed-up by means of a telephone questionnaire 1 year after surgery. RESULTS: After 1 year, 57 (15.1%) of 377 patients complained of mild to moderate pain. The incidence of mild and moderate chronic pain was 14.3 and 0.8%, respectively. None of the patients had severe chronic pain. Only one patient reported numbness in the groin area. Age and immediate postoperative pain were significant risk factors associated with chronic pain after Kugel inguinal herniorrhaphy. Although the difference was not significant, female patients seemed to be more prone to develop chronic pain. CONCLUSIONS: The Kugel inguinal hernia repair is associated with a low rate of postoperative chronic pain. The minimally invasive preperitoneal approach of the Kugel technique probably causes less nerve damage and subsequent neuropathic pain. Chronic pain seems to be more common in young female patients with immediate postoperative pain.

Sonographic Development of the Pericallosal Vascularization in the First and Early Second Trimester of Pregnancy.

BACKGROUND AND PURPOSE: Anomalies of the corpus callosum are rare. Routine scanning in midtrimester of the pregnancy often fails to identify defective development. The purpose of the study was to identify the pericallosal artery and all its main branching arteries during early gestation from the first trimester onward, to measure the length of the pericallosal artery during its development, and to establish a normal vascular map for each week of development. MATERIALS AND METHODS: We performed a single-center prospective, longitudinal clinical study in 15 patients between 11 and 22 weeks of gestation. The origin and course of the different blood vessels were identified. RESULTS: There was a linear association among gestational age, the biparietal diameter, and the length of the pericallosal artery. The curvature of the developing pericallosal artery increases linearly with the gestational age and biparietal diameter, and 4 variations of branching of the callosomarginal artery were observed. CONCLUSIONS: The pericallosal artery and its branches can be identified and measured from 11 weeks on, and the pericallosal artery takes its characteristic course. A defective course or an abnormal biometry of the pericallosal artery could be an early sonographic marker of abnormal development of the corpus callosum.

PEGylated cholecystokinin prolongs satiation in rats: dose dependency and receptor involvement.

BACKGROUND AND PURPOSE: Acute intraperitoneal (i.p.) administration of cholecystokinin (CCK) is known to induce a significant, but short-lasting, reduction in food intake, followed by recovery within hours. Therefore, we had covalently coupled CCK to a 10 kDa polyethylene glycol and showed that this conjugate, PEG-CCK(9), produced a significantly longer anorectic effect than unmodified CCK(9). The present study assessed the dose-dependency of this response and the effect of two selective CCK(1) receptor antagonists, with different abilities to cross the blood-brain barrier (BBB), on PEG-CCK(9)-induced anorexia. EXPERIMENTAL APPROACH: Food intake was measured, for up to 23 h, after i.p. administration of different doses (2, 4, 8, 16 and 32 microg kg(-1)) of CCK(9) or PEG-CCK(9) in male Wistar rats. Devazepide (100 microg kg(-1)), which penetrates the BBB or 2-NAP (3 mg kg(-1)), which does not cross the BBB, were coadministered i.p. with PEG-CCK(9) (6 microg kg(-1)) and food intake was monitored. KEY RESULTS: In PEG-CCK(9)-treated rats, a clear dose-dependency was seen for both the duration and initial intensity of the anorexia whereas, for CCK(9), only the initial intensity was dose-dependent. Intraperitoneal administration of devazepide or 2-NAP, injected immediately prior to PEG-CCK(9), completely abolished the anorectic effect of PEG-CCK(9). CONCLUSIONS AND IMPLICATIONS: The duration of the anorexia for PEG-CCK(9) was dose-dependent, suggesting that PEGylation of CCK(9) increases its circulation time. Both devazepide and 2-NAP completely abolished the anorectic effect of i.p. PEG-CCK(9) indicating that its anorectic effect was solely due to stimulation of peripheral CCK(1) receptors.