Feasibility to Measure Tissue Oxygen Saturation Using Textile-Integrated Polymer Optical Fibers.

Tissue oxygen saturation (StO2) is a crucial factor in the aetiology of pressure injury (PI), since hypoxia leads to necrotization. Pressure on the tissue occludes blood circulation and reduces the StO2, resulting in hypoxia. PI causes severe suffering, heals slowly and is expensive to treat. Hence it is important to prevent PI by detecting hypoxia, e.g., by near-infrared spectroscopy (NIRS) monitoring of StO2. For this, the NIRS device has to be wearable for a long time and it is crucial that it provokes no pressure itself. An integration of optical fibres into a textile achieves this. The aim was to investigate the feasibility of such a textile NIRS device.Knots and loops were tested as textile light emitters (LEs) or detectors (LDs) on a phantom. The light coupling efficiency of the LEs and LDs was investigated.Results show that knots perform similarly to loops. More loops per fibre increase efficiency both in LEs and in LDs. The best trade-off is at 3 loops. LEs are slightly more efficient than LDs, with an average attenuation from baseline of about -2 dB for loops of 0.5 mm diameter. Adding fibres multiplies the signal by the number of fibres. Inclusions mimicking hypoxia in phantoms were successfully identified. In-vivo arm occlusion tests showed the expected decrease in StO2. This shows feasibility of optical fibres in a textile to prevent PI.

Numerical Optimisation of a NIRS Device for Monitoring Tissue Oxygen Saturation.

The present work aims to develop a wearable, textile-integrated NIRS-based tissue oxygen saturation (StO2) monitor for alerting mobility-restricted individuals - such as paraplegics - of critical tissue oxygen de-saturation in the regions such as the sacrum and the ischial tuberosity; these regions are proven to be extremely susceptible to the development of pressure injuries (PI).Using a combination of numerical methods including finite element analysis, image reconstruction, stochastic gradient descent with momentum (SGDm) and genetic algorithms, a methodology was developed to define the optimal combination of wavelengths and source-detector geometry needed for measuring the StO2 in tissue up to depths of 3 cm. The sensor design was optimised to account for physiologically relevant adipose tissue thicknesses (ATT) between 1 mm and 5 mm. The approach assumes only a priori knowledge of the optical properties of each of the three tissue layers used in the model (skin, fat, muscle) based on the absorption and scattering coefficients of four chromophores (O2Hb, HHb, H2O and lipid).The results show that the selected wavelengths as well as the source-detector geometries and number of sources and detectors depend on ATT and the degree and volume of the hypoxic regions. As a result of a genetic algorithm used to combine the various optimised designs into a single sensor layout, a group of four wavelengths was chosen, coinciding with the four chromophores and agreeing very well with literature. The optimised number of source points and detector points and their geometry resulted in good reconstruction of the StO2 across a wide range of layer geometries.

Point shear wave elastography and vibration controlled transient elastography for estimating liver fibrosis in a cohort of liver transplant patients.

OBJECTIVE: Liver transplant (LT) patients need regular follow-up both by ultrasonography and elastography. Shear wave elastography is now available in high-end ultrasound systems that, however, may yield different values for any given liver, reflecting technological differences. The aim of this study was to establish whether the point shear wave elastography QElaXto® (QEpSWE), available on Esaote (Genoa, Italy) systems, is comparable to the standard Fibroscan® (vibration-controlled transient elastography, VCTE) in the real-life setting of liver transplant (LT) patients. PATIENTS AND METHODS: We prospectively examined with QEpSWE 196 consecutive LT patients referred for VCTE and ultrasound examination. The agreement between QEpSWE and VCTE was assessed with Lin concordance correlation coefficient (CCC) and Bland-Altman analysis. The performance of QEpSWE was assessed with the ROC curves using the VCTE cut-offs of 7 and 12 kPa for F2-F3 and F4, respectively. RESULTS: The two methods showed 100% of successful and reliable liver stiffness measurements (LSM), similar median LSM in the whole group and in the two subgroups F2-F3 and F4 of fibrosis, with a disagreement in categorization of liver fibrosis in only 2% of cases, and never more than 1 stage of fibrosis. Further, they presented the same degree of higher LSMs in clinically unstable LT patients and an excellent overall agreement (CCC=0.91, accuracy=0.95, precision=0.96), even if agreement was less satisfactory in the range of severe fibrosis. The optimal cutoffs of QEpSWE were 6.7 and 11.6 kPa for F2-F3 and F4, respectively. CONCLUSIONS: The values of VCTE and QEpSWE showed a very high correlation in the staging of liver fibrosis. QEpSWE seems a promising method for staging liver fibrosis in LT patients.

How to Improve Compliance With Dermatologic Screening in Liver Transplant Recipients: Experience in a (Spoke) Peripheral Center for Follow-up.

Annual dermatologic examination is required in all transplant recipients because of the high risk of skin cancers. Nevertheless, if the transplant recipient is merely advised to have a dermatologic consultation, the adherence usually appears to be poor. We analyzed our population of liver transplant recipients in 2 periods: in 2014 (group 1) and in 2016 (group 2), when we had organized the presence of a dermatologist at scheduled intervals to annually examine the entire liver transplant population we actively follow-up. The adherence to dermatologic screening during period 1 was significantly lower (50/179; 28% of patients) than during period 2 (198/200; 99% of patients) (P < .0001). In group 1 and 2, respectively, we found cutaneous lesions in 3 of 50 (6%) and in 13 of 198 (7%) examined patients and in 3 of 179 (1.7%) and in 13 of 200 (6.5%) of the whole groups of patients in follow-up (P = .02). The type of neoplastic lesions found at dermatologic visits were similar in group 1 (1 squamous cell carcinoma, 1 basal cell carcinoma) and group 2 (2 squamous cell carcinoma, 3 basal cell carcinoma) (P = .45), but with this intensive protocol of surveillance we discovered more preneoplastic lesions (1 leukoplakia in group 1 vs 7 actinic keratosis and 1 dysplastic nevus in group 2; P = .03). These results suggest that the planned presence of a dermatologist is mandatory among the many aspects of a well-organized transplant follow-up team.

Eradication of Hepatitis C After Liver Transplantion: Consequences for the Organization of the Transplant Patient's Follow-up.

The recurrence of the hepatitis C virus (HCV) in the liver graft has been so far the main cause of morbidity and mortality in post-transplantation patients. The treatment has significantly committed the resources of transplant hepatologists despite the poor results obtained with the past standard treatment with the use of interferon plus ribavirin. The new direct-acting antivirals (DAAs) are safe and effective even in the transplant setting, and our purpose was to check whether the eradication of HCV can make predominant other clinical problems that require different skills from those classic to hepatology. Prevalence of different items, such as metabolic syndrome, chronic renal insufficiency, and post-transplantation neoplasms, analyzed in the pre-DAA and post-DAA periods within a homogeneous population of all-cause and HCV transplant patients referred to our local hepatology service resulted in an increase in the post-DAA period after the substantial eradication of HCV. The suggestion that the main active issue has become extrahepatic sets the stage for the diversification of resources to be committed in the follow-up of liver transplantation.

Conversion from twice-daily to once-daily tacrolimus in stable liver transplant patients: effectiveness in a real-world setting.

BACKGROUND: The prolonged-release once-daily (QD) tacrolimus is a formulation developed to improve adherence to immunosuppressant (IS) regimen, reducing the frequency of dosing, and to increase safety, avoiding toxic peak concentrations. We evaluated efficiency and quality of conversion from twice-daily (BID) to QD tacrolimus formulation in stable liver transplant (LT) recipients in the real-setting of a gastrohepatology team peripheral to LT centers. PATIENTS AND METHODS: Thirty-four LT recipients (median age 60 years, range 33-69) were switched from BID tacrolimus to QD tacrolimus (1:1 dose) at a median of 38 months (range 8-211) after transplantation. Tacrolimus levels and laboratory analyses were recorded before and postconversion. Adherence to IS treatment was measured by a modified "Basel Assessment of Adherence Scale to Immunosuppressives." RESULTS: Median postconversion follow-up was 21 months (range 6-35, at least 12 months in 30 patients). Mean total tacrolimus daily dose and mean tacrolimus trough level were not significantly different before and after the switch (3.1 ± 2.3 preconversion versus 3.1 ± 2.5 and 3.0 ± 2.5 mg at 6 and 12 months postconversion, respectively; and 5.3 ± 1.8 preconversion versus 4.6 ± 1.4 and 4.5 ± 1.8 ng/mL at 6 and 12 months postconversion, respectively). All patients maintained stable liver and metabolic parameters. Renal function by glomerular filtration rate increased (67 ± 17 preconversion versus 73 ± 19 and 73 ± 20 mL/min at 6 and 12 months postconversion, respectively; P = .003). No acute rejection episode or major severe adverse events occurred postconversion. Patient-reported outcome showed a reduction of missed IS doses. CONCLUSION: We observed that in a real-world setting far from LT centers, the switch from BID tacrolimus to QD tacrolimus in stable LT recipients is efficient (safe and effective) to improve quality of medical care, with possibly better IS adherence and improvement of renal function.

Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial.

BACKGROUND: In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment. METHODS: The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death. RESULTS: 496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis. CONCLUSIONS: the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.

Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study.

The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.

Combined ranitidine and pirenzepine in the treatment of duodenal ulcer: a multicentre double-blind study using endoscopy.

The efficacy of a combination of ranitidine and pirenzepine in the short-term treatment of duodenal ulcer was evaluated in a double-blind trial. In a multicentre study, 352 patients with active duodenal ulcers were randomly allocated to be treated with 300 mg/day ranitidine plus placebo (group I), 300 mg/day ranitidine plus 50 mg/day pirenzepine (group II), or 300 mg/day ranitidine plus 100 mg/day pirenzepine (group III) for 4 weeks. The respective healing rates assessed using endoscopic examination after 2 and 4 weeks' treatment were 40% and 70% in group 1, 44% and 82% in group II, and 37% and 77% in group III. The differences between the treatment groups were not significant, although 300 mg/day ranitidine plus 50 mg/day pirenzepine tended to be superior to the other treatments. Analgesic activity was the same in the three groups with 33%, 34% and 33% reductions, respectively, in the numbers of patients experiencing pain after 2 weeks. Side-effects (mainly dry mouth and blurred vision) were significantly more frequent in group III patients.

The influence of severe bulb deformity on duodenal ulcer relapse.

In order to evaluate the prognostic role of duodenal bulb deformation in the recurrence of peptic ulcer, duodenal bulb morphology and the complete healing of duodenal ulcer were endoscopically evaluated in sixty patients, who were subsequently allocated at random to either maintenance therapy with ranitidine or no treatment. Endoscopic checkups were done at regular intervals, up to the first ulcer recurrence. As expected, long-term ranitidine treatment significantly reduced the relapse rate (12 month cumulative relapse rate was 32% versus 86% in the untreated). A set of prognostic factors which might interfere with this result (sex, age, alcohol consumption, history of ulcerous relatives, duration of the disease, previous H2-blocking treatment, previous complications, smoking and morphology of the duodenal bulb) were evaluated by multivariate analysis using the Cox regression model. Only duodenal bulb morphology appeared to have any independent prognostic value. In the untreated group ulcer recurrence seemed to occur earlier (median relapse time = 2 months) in the patients with severe non-stenosing bulb deformity, and later in those with normal or mildly deformed bulb (median relapse time = 8 months); ranitidine treatment delayed relapse in deformed bulb patients (median relapse time = 14 months) and almost eliminated it in those with normal duodenal bulb morphology. No association was found between the presence of duodenal bulb deformity and the above-mentioned covariates. Our study confirms the primary importance of anti-H2 treatment and suggests that anatomical characteristics of the duodenal bulb also influence the occurrence of ulcer relapse.

Comparative study of mifentidine and ranitidine in the short-term treatment of duodenal ulcer.

The efficacy and safety of mifentidine 20 mg at night, a new, potent, long-acting H2-receptor antagonist, has been compared with ranitidine 300 mg at night in 60 patients with acute duodenal ulcer, in a randomized double-blind study. Antacid tablets were allowed as additional treatment for pain relief. The treatment lasted for 4 weeks. After 4 weeks of treatment the healing rate was similar; amongst the patients who completed the treatment, healing was 68% for mifentidine, 63% for ranitidine, and on intention-to-treat analysis, healing in both groups was 63%. Pain relief and antacid consumption were similar in both groups. Clinically significant adverse effects were not detected and any changes in laboratory values were minimal, clinically insignificant and reversible. Mifentidine appears to be an effective and safe once-a-day treatment for acute duodenal ulcer disease.

Prophylactic sclerotherapy of high-risk esophageal varices: results of a multicentric prospective controlled trial.

In this prospective, multicenter trial, 140 cirrhotic patients with no previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage were randomized to receive either sclerotherapy or conservative treatment for the prevention of first variceal bleeding. The end-points of the study were bleeding and death. Life table curves showed that prophylactic sclerotherapy significantly diminished the incidence of variceal hemorrhage (p less than 0.001) and overall mortality (p less than 0.01). Two-year cumulative bleeding rate was 18% in the sclerosis group (95% confidence interval = 10 and 31) and 57% (95% confidence interval = 40 and 72) in the control group. Two-year cumulative mortality rate was 30% (95% confidence interval = 19 and 45) in the sclerotherapy group and 56% (95% confidence interval = 39 and 72) in the controls. One patient died after hemorrhage from an ulcer secondary to sclerotherapy. Analysis by the Cox model of the factors potentially confounding or interacting with the effect of sclerotherapy suggested that sclerotherapy was more efficient in preventing first bleeding in patients with decompensated disease (Child B and C) than in those in good condition (Child A). However, the 2-year cumulative bleeding rate of untreated Child A patients was only 19%, showing how in this group the endoscopic findings were unreliable in selecting high-risk varices and explaining why after a 2-year follow-up prophylactic sclerosis did not show any benefit in such patients. We conclude that sclerotherapy can decrease the incidence of first variceal bleeding and death for a period of 2 years in cirrhotic patients with high-risk varices.

Comparison of pirenzepine and carbenoxolone in the treatment of chronic gastric ulcer. A double-blind endoscopic trial.

The purpose of the present study was to compare the effectiveness of pirenzepine and carbenoxolone in accelerating the healing of chronic gastric ulcer. Sixty-six out-patients with endoscopically proven gastric ulcer, without major systemic diseases, were admitted to the study. Patients were randomly allocated to either pirenzepine, 50 mg three times a day for 6 weeks, or carbenoxolone, 100 mg three times a day for one week followed by 50 mg three times a day for the remaining five weeks. At 6 weeks, the ulcers had healed in 20 out of 34 patients (59%) treated with pirenzepine, and in 15 out of 29 patients (52%) treated with carbenoxolone. Symptomatic improvement was similar with both drugs. Some major side effects (oedema, hypokalaemia and hypertension) occurred in approximately 30% of patients treated with carbenoxolone; of those receiving pirenzepine 25% complained of minor symptoms (e.g. dry mouth, headache, tachycardia). It is concluded that pirenzepine and carbenoxolone are of similar, but rather limited, efficacy in speeding the healing of chronic gastric ulcer, but show important differences with respect to tolerability.

Peritoneoscopy in chronic hepatitis. A retrospective evaluation of its role in the management of the asymptomatic patient.

The course of chronic hepatitis was retrospectively evaluated in 26 patients in whom both peritoneoscopy and liver biopsy were initially performed. At entry all patients were clinically asymptomatic and showed mild or moderate histological and chemical abnormalities, so that none of them needed steroid treatment. The duration of the follow-up ranged from 24-82 months. At the end of follow-up liver biopsy was obtained in all patients. In a few patients peritoneoscopy was also ultimately performed. In six patients in whom initially chronic persistent hepatitis (CPH) was diagnosed both by peritoneoscopy and liver biopsy, the subsequent course of the disease was benign. In all the nine patients in whom initially peritoneoscopy suggested CPH, in contrast to the histological diagnosis of chronic aggressive hepatitis (CAH), chemical and morphological parameters of liver disease activity did not worsen to require steroid treatment. In five of six patients in whom both liver biopsy and peritoneoscopy initially showed CAH, chemical and morphological abnormalities progressed so that steroids had to be initiated. Finally in four of five patients in whom initially peritoneoscopy showed CAH and liver biopsy CPH, steroid treatment was ultimately required because of chemical and morphological worsening. In conclusion peritoneoscopy may be a useful aid in the management of the asymptomatic patient with moderate chemical and histological features of chronic liver disease.

Prifinium bromide in the treatment of the irritable colon syndrome.

Eighteen patients with irritable colon syndrome were treated with a new anticholinergic drug (prifinium bromide) and with a placebo in a 6-wk, randomized, double-blind cross-over study. The drug was orally administered in a daily dose of 90 mg before meals. Three manifestations (pain, flatulence, constipation, and/or diarrhea), scored weekly, were used as assessment criteria. Mean over-all ratings showed a difference in favor of the drug, and were statistically significant. Side effects were rare and mild. We have come to the conclusion that this anticholinergic drug may be of benefit to patients with pain-predominant forms of irritable colon syndrome.