Patient-Reported Outcome and Clinical Scores Are Equally Accurate in Predicting Mucosal Healing in Ulcerative Colitis: A Prospective Study

Digestive Diseases and Sciences - Optimal management of patients with ulcerative colitis (UC) requires the accurate, objective assessment of disease activity. We aimed to determine how strong...     

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center:Access,resource utilization and outcomes

BACKGROUND Emergency situations in inflammatory bowel diseases(IBD)put significant burden on both the patient and the healthcare system.AIM To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service(RAC)at a tertiary IBD center.METHODS Patient access,resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study.For comparing resource utilization and healthcare costs,emergency department(ED)visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019.Time to appointment,diagnostic methods,change in medical therapy,unplanned ED visits,hospitalizations and surgical admissions were calculated and compared.RESULTS 488 patients(Crohn’s disease:68.4%/ulcerative colitis:31.6%)contacted the RAC with a valid medical reason.Median time to visit with an IBD specialist following the index contact was 2 d.Patients had objective clinical and laboratory assessment(C-reactive protein and fecal calprotectin in 91%and 73%).Fast-track colonoscopy/sigmoidoscopy was performed in 24.6%of the patients,while computed tomography/magnetic resonance imaging in only 8.1%.Medical therapy was changed in 54.4%.ED visits within 30 d following the RAC visit occurred in 8.8%(unplanned ED visit rate:5.9%).Diagnostic procedures and resource utilization at the ED(n=135 patients)were substantially different compared to RAC users:Abdominal computed tomography was more frequent(65.7%,P<0.001),coupled with multiple specialist consults,more frequent hospital admission(P<0.001),higher steroid initiation(P<0.001).Average medical cost estimates of diagnostic procedures and services per patient was$403 CAD vs$1885 CAD comparing all RAC and ED visits.CONCLUSION Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care,optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.     

YKL-40 is elevated in patients with peripheral arterial disease and diabetes or pre-diabetes

ObjectiveYKL-40 is secreted by macrophages in atherosclerotic lesions and involved in plaque rupture. YKL-40 is elevated in coronary artery disease, and predicts cardiovascular mortality. Experimental in vivo and in vitro data suggest a role of YKL-40 in tissue remodeling. A disease modulating potency of YKL-40 was not investigated in peripheral arterial disease (PAD).MethodsWe measured YKL-40 in 460 subjects: 316 PAD: 71 normal glucose metabolism (PAD-NGM), 90 pre-diabetes (PAD-PREDM) and 155 diabetes (PAD-DM); 20 diabetes with atherosclerosis but without PAD (AS-DM); 85 diabetes without macro-vascular complications (DM) and 39 healthy controls (CO).ResultsYKL-40 is higher in PAD vs. CO (median [25–75 percentile]: 103 [69–159] vs. 43 [30–80] ng/ml; p < 0.001). In addition, YKL-40 is elevated in DM (p < 0.001), PAD-NGM (p = 0.001), PAD-PREDM (p < 0.001), PAD-DM (p < 0.001) and AS-DM (p = 0.002) compared to CO. Among PAD, YKL-40 is increased in PAD-PREDM (p = 0.001) and PAD-DM (p = 0.01) vs. PAD-NGM. By multivariate regression YKL-40 is significantly associated with age (beta = 0.272), triglycerides (beta = 0.216), aspartate-amino-transferase (beta = 0.177) and c-reactive-protein (beta = 0.178). Underpinning its role YKL-40 was found to be associated with micro-/macroalbuminuria (p = 0.014/p = 008) – a strong remodeling inducer. In addition, YKL-40 was elevated in existence of mediasclerosis (p = 0.008), a remodeling process.ConclusionWe are first to show that YKL-40 is higher in subjects with peripheral arterial disease. YKL-40 was higher in PAD patients with pre-/diabetes. In addition, YKL-40 was associated with the “severity” of generalized atherosclerosis estimated by affected vascular beds. All our findings point towards a role of YKL-40 in the progression/prognosis of patients with PAD and concomitant diabetes.     

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe

AIM: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI).METHODS: A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed.RESULTS: Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ.CONCLUSION: CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI.     

Trends in health expectancy indicators in the older adult population in Belgium between 1997 and 2004

The objective is to assess if longer life in Belgium is associated with more healthy years through the evaluation of trends (1997–2004) in health expectancy indicators at ages 65 and 80 covering different health domains: self-perceived health, chronic morbidity, disease clusters, and disability. Information was obtained from Belgian Health Interview Surveys. Health expectancies were calculated using the Sullivan method. Among males at age 65, the increase in years expected to live without chronic morbidity, without a disease cluster or without disability exceeded the increase of the life expectancy (LE). The rise in LE in good self-perceived health was equal to the gain in LE. Among women at age 65 and among men and women at age 80, none of the changes in the expected years of life in good health in any health domain were statistically significant. At age 65 among women, the increase in LE was smaller than the increase in years without chronic disease or without disability. The increase in years without disease clusters was less that the LE increase. At age 80 among men, the years without disability increased as the LE, with a shift toward years with moderate limitations. In any other health domains for men (except co-morbidity) and in all domains for women the years in good health either decreased or increased less than the LE. The recent rise in life expectancy in Belgium is, among the youngest old and especially among males, accompanied by an improved health status. At age 80 and particularly among women expansion of unhealthy years prevails.

Modifying the vessel walls in porcine kidneys during machine perfusion

Background

Endothelial glycocalyx regulates the endothelial function and plays an active role in maintaining vascular homeostasis. During ischema and reperfusion, the glycocalyx is rapidly shed into the blood stream. A Corline heparin conjugate (CHC; Corline systems AB, Uppsala, Sweden) consists of 70 heparin molecules that have the capacity to adhere strongly to biological tissues expressing heparin affinity. We hypothesized that CHC could be used to restore disrupted glycocalyx in vivo in kidneys from brain-dead pigs.

Materials and methods

Brain death was induced in male landrace pigs (n = 6) by inflating a balloon catheter in the epidural space until obtaining negative cerebral perfusion. The recovered kidneys (n = 5 + 5) were perfused by hypothermic machine perfusion using two Lifeport kidney transporters (Organ Recovery Systems, Chicago, IL). CHC (50 mg) (including 25 mg biotinylated CHC) or 50 mg unfractionated heparin (control) was added to the perfusion fluid in the respective machines. In one case, the kidneys were used only for dose escalation of CHC with the same procedure.

Results

CHC was detected by immunofluorescence and confocal microscopy in the inner surface of the vessel walls. The binding of CHC in the kidney was confirmed indirectly by consumption of CHC from the perfusion fluid.

Conclusions

In this first attempt, we show that CHC maybe used to coat the vessel walls of perfused kidneys during hypothermic machine perfusion, an approach that could become useful in restoring endothelial glycocalyx of kidneys recovered from deceased donors to protect vascular endothelium and possibly ameliorate ischemia and reperfusion injuries.     

The use of a remote-controlled minivalve, carried by freely moving animals on their head, to achieve instant pharmacological effects in intracerebral drug-perfusion studies

Intracerebral drug-perfusion studies in animals can be very efficiently performed with the 'reverse-dialysis' procedure. In this procedure, drugs are delivered into the brain via an intracerebrally implanted microdialysis probe. Traditionally, in reverse-dialysis studies the flow of control and drug solutions in the microdialysis site is alternated by large and heavy valves placed far from the experimental animal. In this arrangement, the drugs travel from the fluid-alternating device for a long (20--60 min) period before reaching the brain. This can obscure the onset of drug action, makes it difficult to deliver drugs into the extracellular space during short-lasting behavioral episodes, and considerably limits the number of drug solutions that can be perfused within an experimental session. This report describes the use of a miniature (15 mm long and 8 mm diameter), lightweight (1.4 g) minivalve (patent pending) for combined neuronal recording--intracerebral microdialysis studies in freely moving rats. The device is activated remotely and carried by the animals on their head. This allows the experimenter to alternate the control and drug solutions in the intracerebral recording/dialysis site rapidly and to detect the drug-induced neuronal firing pattern changes instantly, without interfering with the animal's behavior. It is demonstrated that with this novel device the onset of drug actions on hippocampal neurons can be clearly defined and that these actions occur within 2 min after minivalve activation. Furthermore, it is demonstrated that the minivalve allows one to test a large number of drug solutions, successively, within the same experimental session. The described protocol offers a high-throughput method for testing the neuron-specific pharmacological effects of intracerebrally perfused drugs during various behaviors.     

Putative regulatory T cells are impaired in cord blood from neonates with hereditary allergy risk

The hygiene hypothesis implies that the increasing prevalence of allergy in 'westernized' countries is explained by reduced bacterial exposure in early life, but the underlying mechanism remains elusive. We therefore wanted to study the effect of bacterial lipopolysaccharide (LPS) on the generation of regulatory T (T(R)) cells in neonates, and to analyze differences between neonates with allergy risk because of a family history of atopy (FH+) and controls without such hereditary risk (FH-). Cord blood mononuclear cells from the FH+ and FH- groups were stimulated with beta-lactoglobulin in the presence of LPS. T-cell phenotypes suggestive of T(R) cells [CD25+, CD25high and integrin (CD103+)], and the intracellular proliferation antigen Ki-67 were quantified by flow cytometry. Release of the immunosuppressive cytokine transforming growth factor beta1 (TGF-beta1) from its inactive complex was determined by enzyme-linked immunosorbent assay. The analyses revealed the generation of T-cell phenotypes suggestive of T(R) cells including a CD25high T-cell subset which was inversely related to T-cell proliferation (r=-0.54, p<0.05) and to activation-induced release of TGF-beta1 (r=-0.80, p<0.001). The CD25high T-cell subset tended to be impaired in the FH+ group (% of CD3+ T cells: FH+, 5.1% vs. FH-, 12.6%), and notably, the FH+ group showed a significantly reduced capacity for generation of both CD25+ (FH+, 16.2% vs. FH-, 34.9%; p<0.01) and T cells (FH+, 2.1% vs. FH-, 3.9%; p<0.05). Our findings suggested that early-life exposure to a dietary antigen in the presence of LPS might modulate the immune system by generating T(R) cells. This capacity was impaired in neonates with hereditary allergy risk, but clinical follow-up will be required to determine a possible effect on allergy emergence.     

Extended indications for functional limb-sparing surgery in extremity sarcoma using complex reconstruction.

From 1980 to 1991, 29 patients underwent complex reconstruction following extremity sarcoma resection. Soft tissue was the site of origin in 15 patients (52%) and bone was the site of origin in 14 patients (48%), with 20 sarcomas (69%) in the lower extremity. Resection consisted of the following procedures: extended anatomical soft-tissue resections (21 patients [72%]), bone resections (18 patients [62%]), and joint resections (14 patients [48%]). Reconstruction involved the following: myocutaneous flaps (20 patients [69%]), joint prosthesis (eight patients [28%]), and bone reconstruction (15 patients [52%]). There was no surgical mortality; one patient required an amputation owing to surgical complications. The site of the first failure was local (four [31%] of 13 patients), lung (five patients [38%]), others (four patients [31%]). At a median follow-up of 23 months, 18 patients (62%) had no evidence of disease, 27 (93%) had no local disease, 21 (72%) had good extremity function, three (10%) had major disabilities, and five (17%) underwent amputations. Local control improved when the margin of resection was larger than 10 mm. Disease-free survival was 67% at 3 years. Overall survival was 51% at 5 years. Tumor size was an independent predictor of overall survival. Local recurrence did not affect overall survival.