Serum proteome signatures associated with ileal and colonic ulcers in Crohn's disease.

At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (n = 23), isolated ileal ulcers (n = 17), or isolated colonic ulcers (n = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (p-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location. SIGNIFICANCE: Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (n = 23); 2) isolated ileal ulcers (n = 17); 3) isolated colonic ulcers (n = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location.

Influence of hyperbaric oxygen therapy on thrombus formation ability in humans.

Background: Hyperbaric oxygen (HBO2) therapy was introduced nearly 300 years ago. However, its effect on thrombus formation is unclear. This may be because platelet and coagulation functions are unstable, yielding variable results; hence, accurate measurement is difficult. Our study aimed to analyze changes in thrombus formation before and after HBO2 therapy by using a total thrombus formation analysis system (TTAS). Methods: Six patients were prescribed HBO2 therapy for skin and soft tissue ulcers, and necrotic fasciitis. Blood samples were collected immediately before and after treatment. Then samples were put into a reservoir that connected to AR-chip to assess changes in the thrombus formation ability of both platelets and coagulation factors. We examined the differences in the thrombus formation ability using T-TAS. Time until the onset of white thrombus formation (T10) and complete occlusion of the capillary (T80) were analyzed by a two-way repeated measure analysis of variance (ANOVA). Results: The duration to pressure increase of samples after HBO2 therapy was longer than the duration before HBO2 therapy (p<0.05). This suggests decreased clot adhesiveness to the inner surface of the simulated blood vessel and reduced clot formation ability. Conclusions: The results for T10 and T80 suggest that HBO2 therapy reduced thrombus formation ability in the enrolled patients. We believe that T-TAS is a promising method to predict the efficacy of HBO2 therapy.

Characterization of a partial-body irradiation model with oral cavity shielding in nonhuman primates.

Purpose: Characterization of a novel partial-body irradiation (PBI) shielding strategy in nonhuman primates (NHP; rhesus macaques), aimed at protecting the oral cavity, with respect to various gastrointestinal acute radiation syndrome (GI-ARS) syndrome parameters as well as buccal ulceration development.Materials and methods: NHPs were irradiated using a Cobalt-60 gamma source, in a single uniform dose, ranging from 9-13 Gy and delivered at 0.60-0.80 Gy min-1. Animals were either partially shielded via oral cavity shielding (PBIOS) or underwent total-body irradiation (TBI).Results: Clinical manifestations of GI-ARS, and also radiation-induced hematology and clinical chemistry changes, following PBIOS were comparable to the PBI NHP GI-ARS model utilizing shielding of the distal pelvic limbs and were significantly milder than TBI at similar radiation doses. Nadir citrulline levels were comparable between PBIOS and TBI but signs of recovery appeared earlier in PBIOS-treated animals. The PBIOS model prevented oral mucositis, whereas the TBI model presented buccal ulcerations at all tested radiation dose levels.Conclusions: Taken together, these results suggest that the PBIOS model is a suitable alternative to traditional PBI. For GI-ARS investigations requiring orally administered medical countermeasures, PBIOS confers added value due to the prevention of oral mucositis over traditional PBI.

Faecal but not serum calprotectin levels look promising in predicting active disease in Behçet's syndrome patients with gastrointestinal involvement.

OBJECTIVES: The faecal calprotectin (FC) test is widely used as a non-invasive method for identifying intestinal inflammation. A recent study suggested FC may help to diagnose gastrointestinal involvement of Behçet's syndrome (GIBS). We aimed to determine whether FC helps to distinguish active from inactive intestinal involvement in GIBS. METHODS: We tried to contact 70 GIBS patients registered in our tertiary multidisciplinary clinic. We prospectively collected faecal specimens and serum from 39 GIBS patients who gave informed consent assessing calprotectin and CRP levels followed by a colonoscopy. We included 47 Crohn's disease (CD) patients as controls. Active disease was defined as having ulcer/s on colonoscopy. We filled the Disease Activity Index for Intestinal Behçet's Disease (DAIBD) and Crohn's Disease Activity Index (CDAI). The cut-off for positive FC was defined as ≥150 µg/g. RESULTS: Ulcers were detected in 12/39 GIBS patients. Sensitivity and specificity of the FC test for active disease was 91.7 (95%CI:61.5-99.8) and 74.1% (95%CI:53.7-88.9). Median FC and CRP levels and DAIBD scores were higher among patients with ulcers, whereas serum calprotectin and CDAI scores were not. A negative FC test was the only significant predictor of remission (OR:37.04, 95%CI:2.4-561.6; p=0.009) on multivariate analysis. Among CD patients, 16/25 active patients and 3/22 patients in endoscopic remission had a positive FC test (OR:11, 95%CI:11-49). CONCLUSIONS: FC, but not serum calprotectin seems to be a useful non-invasive tool for assessing disease activity in GIBS. Whether the presence of oral ulcers can cause false positive results remains to be studied.

Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn's disease.

BACKGROUND: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations in the SLCO2A1 gene and characterized by multiple small intestinal ulcers of nonspecific histology. SLCO2A1 is also a causal gene of primary hypertrophic osteoarthropathy (PHO). However, little is known about the clinical features of CEAS or PHO. METHODS: Sixty-five Japanese patients recruited by a nationwide survey of CEAS during 2012-2016 were enrolled in this present study. We reviewed the clinical information of the genetically confirmed CEAS patients. RESULTS: We identified recessive SLCO2A1 mutations at 11 sites in 46 patients. Among the 46 patients genetically confirmed as CEAS, 13 were men and 33 were women. The median age at disease onset was 16.5 years, and parental consanguinity was present in 13 patients (28%). Anemia was present in 45 patients (98%), while a single patient experienced gross hematochezia. All patients showed relatively low inflammatory markers in blood tests (median CRP 0.20 mg/dl). The most frequently involved gastrointestinal site was the ileum (98%), although no patient had mucosal injuries in the terminal ileum. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO. CONCLUSIONS: The clinical features of CEAS are distinct from those of Crohn's disease. Genetic analysis of the SLCO2A1 gene is therefore recommended in patients clinically suspected of having CEAS.

Microbial Diversity of Genital Ulcers of HSV-2 Seropositive Women.

We measured the microbial community structure of genital ulcers in women. Swabs from clinically detected ulcers were tested for HSV-2 and Treponema pallidum by polymerase chain reaction (PCR). HSV-2 and T. pallidum were detected by serum antibody testing. Microbial community structure was characterized by high-throughput 16 s rRNA gene amplicon sequencing. Multiple group testing and Elastic net and Lasso regressions identified taxa associated with differences in factors of interest. Among 49 ulcer specimens from 49 HSV-2 seropositive women, by PCR HSV-2 was recovered from 28 (57%) specimens and T. pallidum from none; one woman showed serologic evidence of syphilis. Overall, 63% of women were HIV-positive and 49% had an uncircumcised male sex partner. By both multiple group testing and regression, Porphyromonas (FDR p-value = 0.02), Prevotella (FDR p-value = 0.03), Anaerococcus (FDR p-value = 0.07), and Dialister (FDR p-value = 0.09) were detected at higher relative abundance in HSV-2 PCR-positive than negative ulcers. The presence of HSV-2 in a lesion was associated with presumed bacterial agents of Bacterial vaginosis. Differences in bacterial communities may contribute to HSV-2 ulcer pathogenesis, severity, or prolonged healing. If these results are confirmed, future studies may consider the influence of BV treatment on women's GUD and HSV-2 incidence and recurrence.

Acute hemorrhagic rectal ulcer syndrome: Comparison with non-hemorrhagic rectal ulcer lower gastrointestinal bleeding.

OBJECTIVE: The aim of this study was to describe the clinical characteristics of acute hemorrhagic rectal ulcer (AHRU) and to elucidate its predictive factors. METHODS: The medical records of patients with AHRU were retrospectively reviewed. Their baseline clinical characteristics were compared with those of patients with non-AHRU lower gastrointestinal bleeding to identify predictive factors for AHRU. RESULTS: Among the 118 patients who underwent emergency endoscopy due to acute massive hematochezia from 2013 to 2015, 25 (21.2%) were diagnosed as having AHRU. Of them, 22 (88.0%) were successfully managed endoscopically and 3 (12.0%) underwent surgery. Six (24.0%) patients developed rebleeding within 1-9 days after the initial bleeding, which was controlled by a repeat endoscopy. Five (20.0%) died during follow-up. A multivariate-adjusted logistic regression analysis revealed that a lower serum albumin level, worse Eastern Cooperative Oncology Group (ECOG) performance status and history of constipation were significant factors for predicting AHRU. Hypoalbuminemia (<30 g/L) had a sensitivity, specificity and positive and negative predictive values of 84.0%, 78.5%, 51.2% and 94.8% for predicting AHRU, respectively. CONCLUSIONS: Approximately 20% of patients with massive hematochezia had AHRU. Most patients with AHRU can be managed endoscopically. Low serum albumin level, poor ECOG performance status and prior constipation could be used in distinguishing patients with and without AHRU, facilitating the selection of optimal bowel preparation method for massive hematochezia.

Treatment of chronic non-healing ulcers using autologous platelet rich plasma: a case series.

BACKGROUND: Non-healing ulcers are a major health problem worldwide and have great impact at personal, professional and social levels, with high cost in terms of human and material resources. Recalcitrant non-healing ulcers are inevitable and detrimental to the lower limb and are a major cause of non-traumatic lower limb amputations. Application of autologous Platelet Rich Plasma (PRP) has been a major breakthrough for the treatment of non-healing and diabetic foot ulcers, as it is an easy and cost-effective method, and provides the necessary growth factors that enhance tissue healing. PRP is a conglomeration of thrombocytes, cytokines and various growth factors which are secreted by α-granules of platelets that augment the rate of natural healing process with decrease in time. The purpose of this case series was to evaluate the safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers on the lower extremity. METHODS: Autologous PRP was prepared from whole blood utilizing a rapid, intraoperative point-of-care system that works on the principle of density gradient centrifugation. Twenty Four (24) patients with non-healing ulcers of different etiologies, who met the inclusion criteria, were treated with single dose of subcutaneous PRP injections along with topical application of PRP gel under compassionate use. RESULTS: The mean age of the treated patients was 62.5 ± 13.53 years and they were followed-up for a period of 24 weeks. All the patients showed signs of wound healing with reduction in wound size, and the mean time duration to ulcer healing was 8.2 weeks. Also, an average five fold increase in the platelet concentrate was observed in the final PRP product obtained using the rapid point-of-care device, and the average platelet dose administered to the patients was 70.10 × 108. CONCLUSION: This case series has demonstrated the potential safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers. TRIAL REGISTRATION: NCT03026855 , Registered 4 January 2017 'Retrospectively'.

Thoracic Endovascular Repair of Complicated Penetrating Aortic Ulcer: An 11-Year Single-Center Experience.

PURPOSE: To analyze an 11-year single-center experience of treating complicated penetrating aortic ulcer (PAU) using thoracic endovascular aortic repair (TEVAR). METHODS: This study included 63 consecutive patients (mean age 69.1±11.5 years; 40 men) with complicated PAU (42 symptomatic, 22 with rupture) who underwent TEVAR between 2002 and 2013. The PAUs were located in the aortic arch (n=11), the descending thoracic aorta (n=43), and the thoracoabdominal aorta (n=9). RESULTS: TEVAR was performed within 14 days of diagnosis in 33 (52.3%) cases (19 ruptures treated immediately); the other 30 (47.6%) patients had an average interval between diagnosis and intervention of 40±39 days. Technical success was 98.4% (62/63). One patient had a type I endoleak after stent-graft repair of a PAU in the aortic arch without great vessel transposition; another procedure was required for carotid-subclavian bypass and proximal stent-graft extension. No patient experienced spinal cord ischemia after TEVAR. Five (7.9%) patients died in-hospital; 3 had severe cardiac complications, 1 died from complications of aortic rupture, and the other succumbed to septic shock. Mean follow-up was 45.6±47.2 months, during which 12 (19.0%) patients needed a secondary intervention because of late endoleaks (n=4, 6.3%) or new complications due to disease progression. Multivariate analysis indicated that a PAU depth >15 mm was an independent predictor of mortality (hazard ratio 6.92, p=0.03). In the biomarker analysis, symptomatic patients had significantly higher D-dimer and troponin levels compared to asymptomatic patients [559.5±460.7 vs 283.2±85.2 µg/L (p=0.016) and 0.22±0.61 vs 0.02±0.03 ng/mL (p=0.04), respectively]. CONCLUSION: Patients with PAU suffer from underlying severe atherosclerotic disease and have a significant number of cardiovascular comorbidities that lead to relevant mortality and morbidity after TEVAR. As a PAU diameter >15 mm represented high risk for disease progression, these patients may be candidates for early intervention. D-dimer levels may help identify patients at risk and with progression of PAU.

Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study.

INTRODUCTION: Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselected cohorts of SSc and MCTD. METHODS: Sera of SSc patients (N = 298) and MCTD patients (N = 162) from two longitudinal Norwegian cohorts were included. Blood donors were included as controls (N = 100). Circulating VEGF and endostatin were analyzed by enzyme immunoassay. RESULTS: Mean endostatin levels were increased in SSc patients 93.7 (37) ng/ml (P < .001) and MCTD patients 83.2 (25) ng/ml (P < .001) compared to controls 65.1 (12) ng/ml. Median VEGF levels were elevated in SSc patients 209.0 (202) pg/ml compared to MCTD patients 181.3 (175) pg/ml (P = .017) and controls 150.0 (145) pg/ml (P < .001). Multivariable analysis of SSc subsets showed that pulmonary arterial hypertension (coefficient 15.7, 95 % CI: 2.2-29.2, P = .023) and scleroderma renal crisis (coefficient 77.6, 95 % CI: 59.3-100.0, P < .001) were associated with elevated endostatin levels. Multivariable analyses of MCTD subsets showed that digital ulcers were associated with elevated endostatin levels (coefficient 10.5, 95 % CI: 3.2-17.8, P = .005). The risk of death increased by 1.6 per SD endostatin increase (95 % CI: 1.2-2.1, P = .001) in the SSc cohort and by 1.6 per SD endostatin increase (95 % CI: 1.0-2.4, P = .041) in the MCTD cohort after adjustments to known risk factors. CONCLUSIONS: Endostatin levels were elevated in patients with SSc and MCTD, particularly SSc patients with pulmonary arterial hypertension and scleroderma renal crisis, and MCTD patients with digital ulcers. Elevated endostatin levels were also associated with increased all-cause mortality during follow-up in both groups of patients. We propose that endostatin might indicate the degree of vascular injury in SSc and MCTD patients.

25-Hydroxyvitamin D2 /D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort.

Lower 25-hydroxyvitamin D2 /D3 levels at melanoma diagnosis are associated with thicker primaries and poorer survival. We postulated that this might relate to the deleterious effect of systemic inflammation as 25-hydroxyvitamin D2 /D3 levels are inversely associated with levels of C-reactive protein. 2,182 participants in the Leeds Melanoma Cohort (median follow-up 7.98 years) provided data on drug exposure, comorbidities and a serum 25-hydroxyvitamin D2 /D3 level at recruitment. Factors reported to modify systemic inflammation (low vitamin D levels, high body mass index, use of aspirin or nonsteroidal anti-inflammatory drugs or smoking were tested as predictors of microscopic ulceration (in which primary tumors are inflamed) and melanoma-specific survival (MSS). Ulceration was independently associated with lower 25-hydroxyvitamin D2 /D3 levels (odds ratio (OR) = 0.94 per 10 nmol/L, 95% CI 0.88-1.00, p = 0.05) and smoking at diagnosis (OR = 1.47, 95% CI 1.00-2.15, p = 0.04). In analyses adjusted for age and sex, a protective effect was seen of 25-hydroxyvitamin D2 /D3 levels at diagnosis on melanoma death (OR = 0.89 per 10 nmol/L, 95% CI 0.83-0.95, p < 0.001) and smoking increased the risk of death (OR = 1.13 per 10 years, 95% CI 1.05-1.22, p = 0.001). In multivariable analyses (adjusted for tumor thickness) the associations with death from melanoma were low 25-hydroxyvitamin D2 /D3 level at recruitment (<20 nmol/L vs. 20-60 nmol/L, hazard ratio (HR) = 1.52, 95% CI 0.97-2.40, p = 0.07) and smoking duration at diagnosis (HR = 1.11, 95% CI 1.03-1.20, p = 0.009). The study shows evidence that lower vitamin D levels and smoking are associated with ulceration of primary melanomas and poorer MSS. Further analyses are necessary to understand any biological mechanisms that underlie these findings.

Evaluation of the HerpeSelect Express rapid test in the detection of herpes simplex virus type 2 antibodies in patients with genital ulcer disease.

BACKGROUND: A rapid point-of-care test with high sensitivity and specificity is required in order to fulfill the need for early detection and screening of Herpes simplex virus type 2 (HSV-2) infection among patients with genital ulcer disease (GUD), for better management and control of virus transmission. METHODS: The goal of this study is to evaluate the performance of the commercially available HerpeSelect Express rapid test in comparison with three ELISA assays: HerpeSelect ELISA, Kalon HSV-2 glycoprotein G2 assay, and monoclonal antibody blocking enzyme immunoassay, which was used as the gold standard for the detection of HSV-2 antibodies. RESULTS: This study showed high sensitivity (ranging from 82.6 to 100%) and specificity (100%) of the HerpeSelect Express rapid test when compared to the three ELISA assays. The agreement between the HerpeSelect Express rapid test with the three ELISAs ranged from 93.3 to 100%. CONCLUSION: The HerpeSelect Express rapid test has adequate sensitivity and specificity for confirming HSV-2 infection in patients with GUD, indicating its suitability for epidemiological studies.

Endoscopic findings of gastrointestinal involvement in Chinese patients with Behcet's disease.

AIM: To report the incidence, clinical features and outcomes of gastrointestinal (GI) involvement in Behcet's disease (BD). METHODS: A total of 168 consecutive patients with BD were screened and upper and lower GI endoscopies were performed in 148 patients. Four hundred age- and sex-matched controls were enrolled for comparison. RESULTS: Fifty-two (35.1%) patients had GI lesions. After a mean follow-up of 10 mo, ileocecal ulcers had been confirmed in 20 patients, including active ulcer(s) in 18 patients, but no ileocecal ulceration was found in controls. GI symptoms were present in 14 patients with active ulcer(s), while 4 patients with smaller ulcer were asymptomatic. Endoscopic features of ileocecal ulcer were: a single ulcer (50%), larger than 1 cm in diameter (72.2%), and round/oval or volcano-type in shape (83.3%). Compared with patients without GI involvement, less ocular lesions, lower levels of albumin, erythrocyte count and hemoglobin, and higher levels of C-reactive protein and erythrocyte sedimentation rate were confirmed in the intestinal BD group. Four patients had esophageal ulcers in the BD group but no case in controls. The other endoscopic findings were similar between the two groups. The prevalence of Helicobacter pylori infection was similar in both groups. Most patients received an immunomodulator and responded well. CONCLUSION: GI lesions commonly occur in Chinese BD patients. The most frequently involved area is the ileocecal region. Esophageal ulcer might be a rare but unique lesion.

Prognostic value of sustained elevated C-reactive protein levels in patients with acute aortic intramural hematoma.

OBJECTIVES: The appropriate management of aortic intramural hematoma is still controversial, because a variety of aortic events can arise during follow-up in some patients. However, simplified identification of these patients remains challenging. The present study aimed to determine the prognostic significance of serial C-reactive protein measurements for the prediction of adverse events in patients with acute aortic intramural hematoma. METHODS: A total of 180 patients with aortic intramural hematoma were retrospectively reviewed. The C-reactive protein data were obtained at admission and 2 days, 1 week, and 2 weeks from the onset, and the maximum value was obtained during the acute phase. Adverse aorta-related events were defined by a composite of aortic rupture, aortic aneurysm, and surgical or endovascular aortic repair. RESULTS: The C-reactive protein value was 3.0 ± 4.6, 8.7 ± 5.9, 9.0 ± 5.5, and 5.7 ± 4.5 mg/dL on admission and 2 days, 1 week, and 2 weeks from the onset, respectively. The maximal value of C-reactive protein was 12.4 ± 6.3 mg/dL at a mean of 4 days from the onset. Patients with elevated C-reactive protein levels (≥7.2 mg/dL) at 2 weeks had significantly greater rates of aorta-related events (P < .001). On multivariate analysis, an elevated C-reactive protein level at 2 weeks (hazard ratio, 3.16; P < .001) and the development of an ulcer-like projection (hazard ratio, 2.68; P = .002) were independent predictors of adverse aorta-related events. In addition, an elevated C-reactive protein level at 2 weeks had incremental value compared with the development of an ulcer-like projection (chi-square, 16.94 for ulcer-like projection only vs 34.32 with the addition of C-reactive protein at 2 weeks, P < .001). CONCLUSIONS: C-reactive protein was a simple and useful marker providing incremental prognostic information compared with the development of an ulcer-like projection in patients with aortic intramural hematoma.

Serum gastrin concentrations in dogs with liver disorders.

Dogs with liver disorders often display gastrointestinal signs that may be triggered by ulceration. The liver is important for inactivation of some forms of gastrin. Therefore, hypergastrinaemia has been implicated in the pathogenesis of gastrointestinal ulcerations related to liver dysfunction. The aim of this study was to determine serum gastrin concentrations in dogs with liver disease. Fasted blood samples were collected from 15 dogs with newly diagnosed liver disease and 18 healthy dogs. Gastrin concentrations were significantly lower in dogs with congenital portosystemic shunt compared with healthy dogs (P=0.003). No significant difference (P=0.6) in gastrin concentration was revealed between dogs with hepatocellular disease and healthy dogs. Serum gastrin concentrations were not significantly associated with the occurrence of vomiting, anorexia, diarrhoea, or melaena in dogs with liver disorders. These findings did not provide support for the role of hypergastrinaemia in the development of gastrointestinal signs associated with liver disease in dogs. Decreased serum concentrations of gastrin in a dog with liver disease may suggest the presence of portosystemic shunt. Further investigation is warranted to determine the importance of hyopogastrinaemia in congenital postosystemic shunts in dogs and to evaluate potential alterations in serum gastrin concentrations in specific hepatocellular diseases.

Serum levels of galectin-3: possible association with fibrosis, aberrant angiogenesis, and immune activation in patients with systemic sclerosis.

OBJECTIVE: Galectin-3 is a multifunctional protein implicated in a variety of biological processes including fibrosis, angiogenesis, and immune activation, all of which are associated with the development of systemic sclerosis (SSc). We investigated the clinical significance of serum galectin-3 levels in SSc. METHODS: Serum galectin-3 levels were determined by a specific ELISA in 58 patients with SSc and 19 healthy controls. RESULTS: Serum galectin-3 levels were significantly lower in patients with diffuse cutaneous SSc (dcSSc) than in controls (3.29 ± 3.27 ng/ml vs 4.91 ± 2.67 ng/ml, respectively; p < 0.05), while being comparable between limited cutaneous SSc (3.70 ± 2.39 ng/ml) and healthy controls. In dcSSc, serum galectin-3 levels significantly correlated with total skin score (r = 0.45, p < 0.05). Serum galectin-3 levels were significantly decreased in early dcSSc (disease duration < 1 year; 1.64 ± 1.74 ng/ml; p < 0.05), but not in mid-stage dcSSc (1 to 6 years; 3.22 ± 3.16 ng/ml) or late-stage dcSSc (> 6 years; 4.86 ± 4.10 ng/ml), compared with controls. Serum galectin-3 levels were higher in SSc patients with both digital ulcers (DU) and elevated right ventricular systolic pressure (RVSP) than in those without each symptom (DU: 5.44 ± 3.74 ng/ml vs 2.99 ± 2.36 ng/ml, p < 0.05; elevated RVSP: 4.44 ± 3.14 ng/ml vs 2.82 ± 2.64 ng/ml, p < 0.05). CONCLUSION: Galectin-3 may be related to the developmental process of skin sclerosis in dcSSc and of DU and pulmonary vascular involvements in total SSc.

Herpes simplex virus type 2, genital ulcers and HIV-1 disease progression in postpartum women.

BACKGROUND: Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear. METHODS: HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12-24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression. RESULTS: Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33-5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93-15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07). CONCLUSIONS: HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.

A critical role of surgery in the treatment for paraneoplastic pemphigus caused by localized Castleman's disease.

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with lymphoproliferative tumors, and sometimes with a very rare tumor, Castleman's disease (CD). PNP can present as a variety of dermatological diseases, and so far, only limited studies of PNP caused by CD have been reported, resulting in its higher possibility of misdiagnosis. Because of the variability of clinical presentation of PNP caused by CD, selection of the appropriate therapeutic approach remains unclear. To investigate the efficacy of surgery to patients with PNP caused by localized CD, the clinical, laboratory and pathological data of 5 patients with PNP caused by localized CD, 3 females and 2 males, aged 34 years (ranging from 29 to 42), with the tumor size from 6 x 4 x 4 cm(3) to 8 x 8 x 7 cm(3), located in the mediastinum (n = 3) and retroperitoneum (n = 2), were compared before and after surgery. All patients underwent surgery, and the diagnosis was confirmed by pathological examination. Surgery significantly improved mucosal lesions, cured skin lesions and decreased serum pemphigus autoantibody 6 months after surgery. Most patients were followed up for 6-48 months, and they all had no clinical or radiological recurrence and remain disease free. Therefore, surgery is an effective approach to cure patients with PNP caused by localized CD.