Elipse™, a Procedureless Gastric Balloon for Weight Loss: a Proof-of-Concept Pilot Study

Background

Endoscopic gastric balloons have been used effectively as weight loss devices for decades, but the requirement for endoscopy and sedation poses several limitations. The goal of this pilot study was to evaluate the safety and performance of a prototype version of Elipse?, a procedureless gastric balloon.

Methods

Eight patients (mean BMI?=?31.0 kg/m²) participated in this study. Each patient swallowed one Elipse? balloon intended to remain in the stomach for 6 weeks, self-empty, and then pass. Each balloon was filled with 450 mL of filling fluid. Patients returned every 2 weeks for abdominal ultrasound. No specific diet or exercise plan was prescribed.

Results

All eight patients successfully swallowed the device. The most common adverse events were nausea and vomiting. There were no serious adverse events, and all balloons were excreted safely. Despite not being prescribed a diet or exercise plan, all eight patients lost weight. In 6/8 patients, the balloon remained full through 6 weeks, self-emptied, and passed. In one patient, the balloon appeared partially collapsed on ultrasound after 11 days and was endoscopically punctured. One asymptomatic patient elected to have the balloon endoscopically punctured after 19 days. Both balloons passed in the stool after 4 days. In both cases, endoscopic examination of the upper GI tract showed no abnormalities.

Conclusions

This pilot study demonstrates the safety and performance of Elipse?, a procedureless gastric balloon for weight loss. Future studies will test a commercial design filled to 550 mL intended to last in the stomach for at least 12 weeks.

     

Biodistribution and radiation dosimetry in healthy volunteers of a novel tumour-specific probe for PET/CT imaging: BAY 85-8050

Purpose

Novel tracers for the diagnosis of malignant disease with PET and PET/CT are being developed as the most commonly used ¹⁸F deoxyglucose (FDG) tracer shows certain limitations. Employing radioactively labelled glutamate derivatives for specific imaging of the truncated citrate cycle potentially allows more specific tumour imaging. Radiation dosimetry of the novel tracer BAY 85-8050, a glutamate derivative, was calculated and the effective dose (ED) was compared with that of FDG.

Methods

Five healthy volunteers were included in the study. Attenuation-corrected whole-body PET/CT scans were performed from 0 to 90 min, at 120 and at 240 min after injection of 305.0?±?17.6 MBq of BAY 85-8050. Organs with moderate to high uptake at any of the imaging time points were used as source organs. Total activity in each organ at each time point was measured. Time–activity curves (TAC) were determined for the whole body and all source organs. The resulting TACs were fitted to exponential equations and accumulated activities were determined. OLINDA/EXM software was used to calculate individual organ doses and the whole-body ED from the acquired data.

Results

Uptake of the tracer was highest in the kidneys due to renal excretion of the tracer, followed by the pancreas, heart wall and osteogenic cells. The mean organ doses were: kidneys 38.4?±?11.2 μSv/MBq, pancreas 23.2?±?3.8 μSv/MBq, heart wall 17.4?±?4.1 μSv/MBq, and osteogenic cells 13.6?±?3.5 μSv/MBq. The calculated ED was 8.9?±?1.5 μSv/MBq.

Conclusion

Based on the distribution and dose estimates, the calculated radiation dose of BAY 85-8050 is 2.67?±?0.45 mSv at a patient dose of 300 MBq, which compares favourably with the radiation dose of FDG (5.7 mSv).     

Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction

OBJECTIVE: To assess benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both considered to be associated with urogenital ageing, in ageing men in a cross-sectional population study, comparing them with healthy controls by using symptom scores and contrast-enhanced colour Doppler ultrasonography (CDUS). PATIENTS, SUBJECTS AND METHODS: Transrectal CDUS and quantitative measurement of colour pixel intensity (CPI) are excellent minimally invasive techniques for assessing normal and pathological blood flow. CDUS was performed using the microbubble-based ultrasound enhancer for evaluating prostate, bladder neck and corpus cavernosum vascularity in young healthy men, men with BPH, and men with severe vascular damage (diabetes mellitus type 2). Resistive index measurements and computer-assisted quantification of CPI were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF) were applied to quantify the symptoms. RESULTS: In patients with BPH, perfusion of the transition zone (TZ) of the prostate was significantly lower and the resistive index of the TZ significantly higher (both P < 0.001) than in healthy controls. The perfusion patterns of men with BPH and those who also had severe vascular damage (diabetes mellitus type 2) showed that vascularity in the latter group was lower in the prostatic TZ and the corpora cavernosa. In patients with BPH the IPSS, quality-of-life and IIEF scores were significantly worse than in the control group. Men with concomitant atherosclerosis had even worse symptom scores. CONCLUSION: These results strongly support the hypothesis that age-related impairment of blood supply to the lower urinary tract is important in the development of BPH and ED. Vascular damage may cause chronic ischaemia and thus be a contributing factor in the pathogenesis of BPH and ED.     

Patient-controlled epidural analgesia reduces analgesic requirements compared to continuous epidural infusion after major abdominal surgery

PURPOSE: To compare the quality of pain relief and incidence of side effects between 24-hr postoperative continuous epidural infusion (CEI) and subsequent patient-controlled epidural analgesia (PCEA) with different analgesics after major abdominal surgery. METHODS: Twenty-eight women undergoing extended gynecological tumour surgery received postoperative CEI with 0.15 mL x kg(-1) x hr(-1) 0.2% ropivacaine (R: n = 14) or 0.125% bupivacaine plus 0.5 micro g x mL(-1) sufentanil (BS: n = 14) during 24 postoperative hours. Twenty-four hours later, postoperative pain management was switched to PCEA without background infusion and 5 mL single bolus application of R or BS every 20 min at most. Visual analogue scales (VAS; 1-100 mm) were assessed by patients at rest and on coughing after 24 hr of CEI and PCEA. Side effects, doses of local anesthetics and opioids were recorded and plasma concentrations of total and unbound ropivacaine and bupivacaine were measured. RESULTS: Patients required lower doses of each respective analgesic medication with PCEA (R: 108 +/- 30 mL; BS: 110 +/- 28 mL) than with CEI (R: 234 +/- 40; BS: 260 +/- 45; P < 0.01). Ropivacaine plasma concentrations were lower 24 hr after PCEA when compared with CEI (P < 0.01). No patient after PCEA but two after CEI (n = 4; NS) presented motor block. PCEA with R provided better postoperative pain relief than CEI (37 +/- 32 vs 59+/-27, P < 0.05). No difference in parenteral opioid rescue medication between CEI and PCEA was seen. CONCLUSION: PCEA in comparison to preceding CEI provides equivalent analgesia with lower local anesthetic doses and plasma levels, and without motor blocking side effects, irrespective of the applied drug regimen.     

Sex-related differences in patients with severe head injury: greater susceptibility to brain swelling in female patients 50 years of age and younger

OBJECT: The goal of this study was to study the influence of sex and age on factors affecting patient outcome in severe head injury. METHODS: Data from the prospectively conducted international trial of tirilazad mesylate in patients with head injury were analyzed retrospectively. Included were 957 patients, 23% of whom were female and all of whom were between the ages of 15 and 79 years. All patients presented with Glasgow Coma Scale (GCS) scores between 3 and 8 and evidence of structural brain damage and/or subarachnoid hemorrhage (SAH) on the initial CT scan. Frequencies of recognized risk factors, including brain swelling, intracranial hypertension, systemic hypotension, advanced age, SAH, and injury severity (based on GCS scores), as well as dichotomized Glasgow Outcome Scale (GOS) scores (good recovery or moderate disability compared with severe disability, persistent vegetative state, or death) obtained 6 months postinjury were compared between male and female patients. CONCLUSIONS: Overall significantly greater frequencies of brain swelling and intracranial hypertension were found in female compared with male patients (35% compared with 24% [p < 0.0008] and 39 compared with 31% [p < 0.03], respectively). The highest rates were found in female patients younger than 51 years old (38% compared with 24% [p < 0.002] and 40% compared with 30% [p < 0.02], respectively, in male patients younger than 51 years of age). This effect was independent of injury severity (GCS) scores, which were not different in male and female patients. Female patients younger than 50 years tended to have worse outcomes, but the difference was not statistically significant. Thus, female patients who sustain severe head injury, especially (presumably) premenopausal ones aged 50 years and younger, are significantly more likely to experience brain swelling and intracranial hypertension than male patients with a comparable injury severity, suggesting that younger women may benefit from more aggressive monitoring and treatment of intracranial hypertension.     

Zenker’s Diverticula: Feasibility of a Tailored Approach Based on Diverticulum Size

Background  Zenker’s diverticula (ZD) can be treated by transoral diverticulostomy or open surgery (upper esophageal sphincter myotomy and diverticulectomy or diverticulopexy). The aim of this study was to compare the effectiveness of a minimally invasive (group A) versus a traditional open surgical approach (group B) in the treatment of ZD. Material and Methods  Between 1993 and September 2007, 128 ZD patients underwent transoral diverticulostomy (n = 51) or cricopharyngeal myotomy and diverticulectomy or diverticulopexy (n = 77). All patients were evaluated for symptoms using a detailed questionnaire. Manometry recorded upper esophageal sphincter (UES) pressure, relaxations, and intrabolus pharyngeal pressure. The size of the pouch was measured on the barium swallow. The choice of treatment was based on the size of the diverticulum and the patients’ preference. Long-term follow-up data were available for 121/128 (94.5%) patients with a median follow-up of 40 months (interquartile range, 17–83). Results  Mortality was nil. Three patients in group A (5.8%) and ten in group B (13%) had postoperative complications (p = n.s.). Hospital stays were markedly shorter for patients after diverticulostomy (p < 0.01). Postoperative manometry showed a reduction in UES pressure, improved UES relaxation, and lower intrabolus pressure in both groups (p < 0.05). Four patients in the open surgery group (5.2%) complained of severe dysphagia after surgery (three of them required endoscopic dilations). In the transoral diverticulostomy group, 11 patients (21.5%) required additional septal reduction (n = 8) or a surgical myotomy (n = 3) for persistent symptoms (p < 0.01); nine of these 11 patients had a ZD ≤ 3 cm in size. After primary and complementary treatments, symptoms disappeared or improved significantly at long-term follow-up in 93.5% of patients in group A and 96% of those in group B. Conclusion  Diverticulostomy is safe, quick, and effective for most patients with medium-sized ZD, but open surgery offers better long-term results as a primary treatment and should be recommended for younger, healthy patients, especially those with small diverticula. Small ZD may represent a formal contraindication to the transoral approach because an excessively short septum prevents a complete division of the sphincter fibers.     

Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy

Background

The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy.

Objective

This study evaluated the clinical utility of the PROGENSA PCA3 assay.

Design, setting, and participants

This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy.

Measurements

After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA).

Results and limitations

In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score ≥7 versus <7, and “significant” versus “indolent” (clinical stage T1c, PSA density [PSAD] <0.15 ng/ml, Gleason score in biopsy ≤6, and percent positive cores ≤33%) pCA.

Conclusions

The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.     

Febrile urinary tract infection in children: ampicillin and trimethoprim insufficient as empirical mono-therapy

The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in defined groups of children (total number 694) with urinary tract infection (UTI) regarding age, first UTI (FUTI) or recurrent UTI (RUTI), renal abnormalities or vesico-ureteric reflux (VUR) in order to optimize empirical antibiotic therapy and prophylaxis. In patients aged between 1 month and 24 months with a first febrile UTI (FUTI; n = 205) the leading pathogen was Escherichia coli (E. coli) (83.4%). In comparison with patients with FUTI, those with RUTI (n = 24) had more Enterococcus and Enterobacter infections and higher resistance rates of E. coli against trimethoprim (TMP), trimethoprim/sulfamethoxazole (SXT) or ampicillin (AMP). Boys with ultrasound-detected renal abnormalities (n = 71) showed 14.2% Pseudomonas and 59.1% E. coli infections versus girls (n = 48) (2.1% Pseudomonas and 93.7% E. coli). Of 390 patients who underwent voiding cysto-urethrography, 31.5% had VUR. Of them, 45.5% received antimicrobial prophylaxis with SXT (n = 30) or cefazolin (n = 26). There was no difference between girls (n = 242) and boys (n = 148) regarding the frequency of VUR and pathogens. There were more TMP- and SXT-resistant E. coli cultures from patients with VUR (37.8%) than from those without VUR (25.8%). Treatment with TMP, SXT and AMP alone appeared to be insufficient in many cases because of high resistance rates of E. coli and other uropathogens.     

Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.     

Dominance of virus-specific CD8 T cells in human primary cytomegalovirus infection

Cellular immune responses are of high importance in initiating and maintaining immunity against virus infections. Whereas the cellular immune response during persistent cytomegalovirus (CMV) infection is well assessable, the individual contribution of CD4 and CD8 T cell responses during primary infection has not been described. A novel whole-blood assay, which relies on the flow-cytometric detection of antigen-induced cytokine expression, was used to characterize CMV-specific CD4 and CD8 T cell responses during primary infection of CMV seronegative recipients of a renal allograft from a CMV seropositive donor. These T cell responses were compared with long-term CMV-positive patients with known history of transplantation-related seroconversion. Results were further correlated to CMV load and serum IgG and IgM. The long-term seroconverted patients consistently showed a dominant CMV-specific CD4 T cell response (median frequencies: CD4, 1.12% [range, 0.35 to 8.10%] versus CD8 0.13% [range, <0.05 to 0.55%]). In contrast, during primary infection, the cellular immune response is strongly dominated by CMV-specific CD8 T cells (median peak frequencies: CD4, 1.24% [range, 0.21 to 1.60%] versus CD8, 2.47% [range, 1.34 to 6.67%]). Upon receipt of ganciclovir, viral load as well as CMV-specific CD8 responses decreased. The frequency of the respective CD4 T cells fluctuated during decrease of CMV load and became dominant over CMV-specific CD8 T cell responses. These results are consistent with the view of an effective direct antiviral activity of CD8 T cells, which is most critical during periods of high viremia. Later on during persistent infection, CD4 T cells dominate the immune response to support the state of antiviral immunity.