Dropout from Interim Methadone and Subsequent Comprehensive Methadone Maintenance

Background: Methadone maintenance in the United States is delivered primarily through specialized clinics that provide psychosocial services together with medication. Interim methadone (IM) is an evidence-based approach to increase access by providing methadone without counseling for individuals waiting for admission to comprehensive treatment. Little is known about the role of patient characteristics in predicting outcomes in the IM service pathway (IM with comprehensive methadone treatment following IM). Methods: This study examined the relationship between patient motivation and dropout among patients in the IM service pathway (n = 183). Participants were assessed with the Addiction Severity Index, the Texas Christian University Motivation Scales, and study-specific instruments at baseline, 4-month follow-up or admission to comprehensive treatment (whichever occurred first), and 6 months thereafter. Multinomial logistic regression was used for the analysis, controlling for demographics, route of administration, cocaine use, criminal justice history, and treatment history. Results: Of the total sample, 62% were retained throughout the IM service pathway, 20% left IM, and 18% left subsequent comprehensive treatment. Motivation did not predict dropout from either IM or comprehensive treatment following IM. Unexpectedly, neither did any of the other explanatory variables included in the model. Conclusions: Most patients remained in the IM service pathway. The patient characteristics examined are not associated with discontinuation of IM or subsequent comprehensive methadone treatment. Scientific Significance: The findings that most patients were retained in the IM service pathway, and that no subgroup experienced higher probability of dropout, bolster the public health potential of IM as a service strategy.     

Population screening for coeliac disease in a low prevalence area in Italy

Objective. A screening program was proposed for the village of Carcare (population 5700), located in a region of Italy with an apparently low prevalence of coeliac disease (CD): only 1 patient diagnosed out of 2557 inhabitants. The study group comprised 1002 individuals (568?F, 434?M, age range 13–90 years) recruited from blood donors, secondary school pupils and people referred to the local outpatient facilities for routine blood chemistry. Material and methods. Total IgA, IgA anti-tissue transglutaminase (tTG) (ELISA, recombinant human antigen) and IgA antiendomysium (EMA) (IFI, umbilical cord substrate) antibodies were measured in the serum of all participants. All patients with IgA deficiency were investigated for IgG tTG antibodies, and in the case of disagreement between tTG and EMA, they were typed for HLA DQ2-DQ8 haplotypes. Results. Thirteen subjects were positive and 988 negative for autoantibodies (3/988 had IgA deficiency). One serum sample was positive for tTG antibodies but negative for EMA. Ten out of 13 positive subjects consented to undergo duodenal biopsy, which invariably produced evidence of CD despite the absence of clinical signs/symptoms. A post-diagnostic clinical investigation provided evidence showing mild iron deficiency (4 subjects) and osteoporosis (2 subjects). After counselling, all subjects accepted a gluten-free diet. Conclusions. The prevalence of CD in the study group was 1:100 (1.0%; 95% CI: 0.5–1.8%): this indicates that CD is largely underdiagnosed in Carcare. Our results suggest that the low prevalence of CD observed in some regions is likely to be due to underdiagnosis.     

Intestinal metaplasia at the gastroesophageal junction is associated with gastroesophageal reflux but not with Helicobacter pylori infection

Abstract

Objective: Studies of the etiology of intestinal metaplasia (IM) at a normal appearing gastroesophageal junction (GEJ) are conflicting as associations with both H. Pylori (HP) infection and gastroesophageal reflux has been reported. The aim of this study was to investigate whether IM at the GEJ is associated with gastroesophageal reflux or HP infection.

Material and methods: Fifty asymptomatic volunteers and 149 patients with reflux symptoms underwent endoscopy with biopsies obtained from the gastric antrum and the squamocolumnar junction (SCJ). All subjects underwent wireless 48?h pH monitoring with the electrode placed immediately above the SCJ and a fecal antigen test for HP infection. Clinical characteristics and the pattern of reflux were compared in subjects with and without IM.

Results: Three asymptomatic volunteers and 35 patients who had clearly irregular SCJs with short extensions of columnar mucosa were excluded from the study. In the remaining 47 asymptomatic volunteers and 114 patients, variables that reached a significance level of 0.1 or less on univariate analyses were used in a binomial regression analysis to assess their relative importance for the finding of IM. IM at the GEJ was significantly associated with abnormal distal esophageal acid exposure (5.5 (1.2–24.6), p?=?.026), the frequency of reflux episodes/hour (1.5 (1.1–2.2), p?=?.031), and an endoscopic appearance of the SCJ corresponding to ZAP grade I (4.6 (1.4–15.6), p?=?.013). There was no association with HP infection.

Conclusion: The finding of IM at an endoscopically normal-appearing GEJ is associated with gastroesophageal reflux but not with HP infection.     

Correction of Bcl-x splicing improves responses to imatinib in chronic myeloid leukaemia cells and mouse models

Imatinib mesylate (IM) resistance has become a major clinical problem for chronic myeloid leukaemia (CML). It is known that Bcl-x splicing is deregulated and is involved in multiple malignant cancer initiation and chemotherapy resistance, including CML. The aim of the present study was to correct the abnormal splicing of Bcl-x in CML and investigate the subsequent malignant phenotype changes, especially response to IM. The aberrant Bcl-x splicing in CML cells was effectively restored using vivo-Morpholino Antisense Oligomer (vMO). CCK-8 cell viability assay and flow cytometry showed that restoring of Bcl-x splicing increases IM-induced growth inhibition and apoptosis of K562 cells. Moreover, a more significant similar phenomenon was observed in imatinib-resistant CML cell lines K562/G01. Finally, establishment of CML xenograft model had also proved that correcting Bcl-x splicing in vivo can also enhance the anti-tumor effect of IM. Our findings suggest that vMO co-operating with IM can effectively increase the sensitivity of CML cells to IM both in vitro and in vivo, and Bcl-x splicing could become good candidates for chemotherapy-sensitized target in IM-resistant CML.     

Adrenocorticotropic hormone and dehydroepiandrosterone sulfate levels of rheumatoid arthritis patients treated with glucocorticoids

Abstract

To assess adrenal function with respect to the presence or absence of steroid therapy, we investigated differences in the blood levels of adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) in relation to steroid (prednisolone) administration in 123 patients with rheumatoid arthritis (RA). Levels of ACTH and DHEAS were significantly lower in the steroid-treated group than in the non-treated group (ACTH: 11.79?pg/ml vs 27.92?pg/ml) (DHEAS: 418.12?ng/ml vs 883.91?ng/ml) (P < 0.0001). We observed no steroid dose-related differences in ACTH levels. However, DHEAS levels showed a slight decrease at a prednisolone dose of 2.5?mg/day, with a significant decrease being observed at a dose of 5?mg/day when statistical adjustments were made for age and sex (P < 0.0001). At doses of 7.5?mg/day or greater, DHEAS levels were significantly lower than those for 5?mg/day (P < 0.0006). These results suggest that low-dose prednisolone reduces adrenal function in patients with RA. We recommend that doses of prednisolone should be limited to 5?mg/day or less in consideration of adrenal function when treating RA patients. The measurement of ACTH and DHEAS may be useful for evaluating adrenal function in patients with RA.     

Relevance of high virulence Helicobacter pylori strains and futility of CDX2 expression for predicting intestinal metaplasia after eradication of infection

Abstract

Objective. Different Helicobacter pylori genotypes are associated with distinct inflammatory responses and consequent development of pre-neoplastic lesions, namely intestinal metaplasia (IM), which is dependent on the expression of CDX2. We aimed to evaluate IM progression/regression in the context of H. pylori eradication, bringing into play the effect of the virulence of infecting H. pylori strains and the hypothesis that CDX2 expression might be a marker for later development of IM. Material and methods. Sixty-five male volunteers were evaluated by endoscopy before H. pylori eradication and after a median six-year follow-up. Histological diagnosis was performed at baseline and follow-up, and baseline H. pylori genotypes and CDX2 expression in non-metaplastic foci were also assessed. Results. Fifty-one individuals remained free from infection at follow-up. Six out of 27 who had no metaplastic lesions at baseline developed IM. CDX2 nuclear expression was observed in 15 of the 21 cases (71.4%) showing no progression to IM, and in three out of six cases (50%) with progression to IM (p = 0.367). Six of the 24 cases with IM at baseline showed regression to less severe outcomes, which was less frequent in those infected with high-virulence strains (7.7% vs. 50%, p = 0.047). In the latter there is a significant persistence of lymphoid follicles. Conclusions. Our results support that under infection with high virulence H. pylori strains, IM is a point of difficult return in the gastric carcinogenic pathway. The appearance of CDX-expressing cells in non-metaplastic foci was not associated with the development of IM during the six-year follow-up.     

Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma after radical hepatectomy: a real world study

Abstract

Objective: To investigate the clinical value of the adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) after radical resection, and identify the potential beneficiaries.

Methods: Patients were identified through the primary liver cancer big data (PLCBD) between 2012 and 2015. Overall survival (OS) between adjuvant TACE group and non-TACE was evaluated by Kaplan-Meier before and after propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors.

Results: A total of 2066 HCC patients receiving radical resection were identified. Patients with multiple tumors, tumor diameter >5?cm, satellite, and advanced stage were more likely to accept adjuvant TACE. Before PSM, the 1-, 3-, and 5-year OS rates in the TACE group and non-TACE group were 89%, 58%, 17%, and 88%, 53%, 13% (p?=?.43), respectively. While, the corresponding rates were 89%, 58%, 17%, and 86%, 49%, 11%, (p?=?.038), respectively after 1:1 PSM. In addition, patients were found to significantly benefit from adjuvant TACE if they had age ≥50?years, no cirrhosis, AFP ≤ 200?ng/ml, surgical margin <1?cm, tumor diameter >5?cm, no capsule, no satellite, or CN stage Ib/IIa (all p?<?.05), but patients with age < 50?years, tumor size ≤5?cm, or CN stage Ia were found to significantly benefit from radical resection in DFS (all p?<?.05).

Conclusion: Currently, we concluded that not all of patients with HCC would benefit from adjuvant TACE. Patients with age ≥50?years, tumor size >5?cm, or CN stage Ib/IIa were strongly recommended to receive adjuvant TACE.     

Mad2 overexpression is associated with high cell proliferation and reduced disease-free survival in primary gastrointestinal diffuse large B-cell lymphoma

Objectives: Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is a rare hematological malignancy with limited results on carcinogenesis and clinical characteristics. The aims of the current study were to examine mitotic arrest deficiency protein 2 (Mad2) expressions in PGI-DLBCL, and assess its association with Ki-67 expression, Helicobacter pylori (H. pylori) infection, BCL-6 gene rearrangement, and clinicopathological variables.

Methods: Cancer tissues from 38 PGI-DLBCL patients were examined for Mad2, Ki-67, and H. pylori expression by immunohistochemistry, using normal gastrointestinal tissues and nodal DLBCL as controls. BCL-6 gene translocation was analyzed by fluorescence in situ hybridization (FISH), and Mad2 expression status was evaluated along with clinicopathological characteristics.

Results: Mad2 expression was increased in PGI-DLBCL patients when compared with controls. The expression of Mad2 was 51.55?±?22.88% in PGI-DLBCL, which was higher than reactive lymph node (28.77?±?10.89%) and lymphoid nodule in normal gastrointestinal tissue (26.41?±?11.30%) (P?=?0.002), while it was comparable to nodal DLBCL (57.23?±?20.79%) (P?=?0.358). Mad2 overexpression had a positive correlation with Ki-67 proliferation index (r?=?0.55, P?=?0.01) in PGI-DLBCL, and patients with BCL-6 gene rearrangement had lower Mad2 expression (P?=?0.032) than patients with intact BCL-6, while no relation was found between Mad2 expression and H. pylori infection. PGI-DLBCL patients with higher Mad2 expression had lower estimated disease-free survival (DFS) (17.10% vs. 53.00%) (P?=?0.049). However, no correlation was found between Mad2 expression levels and overall survival (OS) (P?=?0.443).

Conclusions: Aberrant Mad2 expression was associated with cell proliferation and genetic instability, which may contribute to the carcinogenesis of PGI-DLBCL. Mad2 overexpression indicated a poor DFS and may be a potential biomarker for estimating prognosis for PGI-DLBCL patients.     

ABBV-105, a selective and irreversible inhibitor of Bruton’s tyrosine kinase,is efficacious in multiple preclinical models of inflammation

Abstract

Objectives: Bruton’s tyrosine kinase (BTK) is a non-receptor tyrosine kinase required for intracellular signaling downstream of multiple immunoreceptors. We evaluated ABBV-105, a covalent BTK inhibitor, using in vitro and in vivo assays to determine potency, selectivity, and efficacy to validate the therapeutic potential of ABBV-105 in inflammatory disease.

Methods: ABBV-105 potency and selectivity were evaluated in enzymatic and cellular assays. The impact of ABBV-105 on B cell function in vivo was assessed using mechanistic models of antibody production. Efficacy of ABBV-105 in chronic inflammatory disease was evaluated in animal models of arthritis and lupus. Measurement of BTK occupancy was employed as a target engagement biomarker.

Results: ABBV-105 irreversibly inhibits BTK, demonstrating superior kinome selectivity and is potent in B cell receptor, Fc receptor, and TLR-9-dependent cellular assays. Oral administration resulted in rapid clearance in plasma, but maintenance of BTK splenic occupancy. ABBV-105 inhibited antibody responses to thymus-independent and thymus-dependent antigens, paw swelling and bone destruction in rat collagen induced arthritis, and reduced disease in an IFNα-accelerated lupus nephritis model. BTK occupancy in disease models correlated with in vivo efficacy.

Conclusion: ABBV-105, a selective BTK inhibitor, demonstrates compelling efficacy in pre-clinical mechanistic models of antibody production and in models of rheumatoid arthritis and lupus.     

Successful Outcome of Hyperhemolysis in Sickle Cell Disease following Multiple Lines of Treatment: The Role of Complement Inhibition

Abstract

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication in patients with sickle cell disease, characterized by difficulties in diagnosis and management. Certain reports have suggested successful salvage treatment with the terminal complement inhibitor, eculizumab. We here report evidence of complement activation and successful complement inhibition with one dose of eculizumab in an adult sickle cell disease patient presenting DHTR with hyperhemolysis. A 21-year old female sickle cell disease patient [Hb S (HBB: c.20A>T)/β-thalassemia (β-thal)] presented at our Adult Thalassaemia Unit, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece, with headaches, perioral numbness and pain in both antibrachia. The patient was admitted with the diagnosis of vaso-occlussive crisis (VOC) and treated symptomatically. On her third day of admission, due to hemoglobin (Hb) value of 6.9?g/dL with increase in reticulocytes, the patient was transfused with one unit of compatible leukodepleted red blood cells (RBC). The following day, hemolytic parameters increased, although Coombs, panel antibodies and screening tests were negative. Five days later, she again received a unit of RBCs, resulting in another increase of hemolytic parameters. During the following 2 days, there was a dramatic decrease of Hb levels to 5.4?g/dL with reticulocytes at 6.0%, negative Coombs testing and negative alloantibodies. Based on these findings, we recognized the syndrome of DHTR with hyperhemolysis. Given the lack of immediate access to other treatment, we administered intravenous rituximab, immunoglobulins and corticosteroids. As there was no response, one dose of eculizumab (900?mg) was then administered with ciprofloxacin as prophylaxis. The patient remains well 6 months post treatment.     

Five Years of Deferasirox Therapy for Cardiac Iron in β-Thalassemia Major

Abstract

Myocardial siderosis in β-thalassemia major (β-TM) remains the leading cause of death. Deferasirox (DFX), a new iron chelation treatment, has proved to be effective in reducing or preventing cardiac iron burden in thalassemic patients according to clinical trials with maximum duration of up to 3 years except one that was recently published and lasted 5 years. The aim of this study was to evaluate the efficacy of DFX in reducing or preventing cardiac iron burden in 23 patients with β-TM after 5 years of therapy. All patients had a magnetic resonance imaging (MRI) T2* evaluation of their cardiac iron load before starting DFX therapy and after a period of 5 years. Ferritin levels and left ventricular ejection fraction (LVEF) were also evaluated at the same time. Deferasirox was administered in a starting dose of 30?mg/kg/day and never increased to more than 40?mg/kg/day. The MRI T2* cardiac iron load mean values before DFX was 32.82?±?10.86?ms, and after 32.13?±?7.74?ms, showing a stability in MRI T2* myocardial value but a significant improvement in two patients with an intermediate iron load (12 vs. 23?ms). The mean LVEF value was 68.43?±?7.08% before treatment with DFX and 67.95?±?5.94% after DFX therapy without significant change. Our results confirm previous studies that DFX is considered an effective chelating agent used as monotherapy for at least 5 years and is more efficacious in moderate to severe cardiac iron loaded thalassemic patients.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

Abstract

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score ?1 to ?2.5) and 23 patients (27.7%) had osteoporosis (T < ?2.5). The body mass index of patients with normal BMD (T score ≥ ?1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

The correlation between histological gastritis staging- ‘OLGA/OLGIM’ and serum pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China

Background: Serum pepsinogen (PG) test, as an indicator of gastric mucosal atrophy, reflects the functional and morphologic status of gastric mucosal and it is suggested to serve as a useful predictive marker for patients with gastric cancer (GC). The available classifications of gastritis, known as the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia (OLGIM), integrating the severity and topography of atrophy/intestinal metaplasia (IM), have been gradually accepted and used in screening for GC in recent years.

Goals: To assess whether serum pepsinogen test, including PGI, PGII, PGI/PGII and gastrin-17 (G-17) could reflect the extent and topography of gastric mucosal atrophy/IM. Furthermore, to discuss the relationship between OLGA/OLGIM staging system and serum pepsinogen test in assessment of gastric atrophy/IM.

Methods: The OLGA/OLGIM ranks the gastric staging according to both the topography and the severity of gastric atrophy/IM. A retrospective study was conducted with 331 patients who underwent endoscopy with consecutive biopsy sampling and reassessed according to OLGA/OLGIM staging system. Serum pepsinogen test, including PGI, PGII, PGI/PGII and G-17, as well as serological Helicobacter pylori (Hp) antibody were also measured. Results were presented as gastritis stage, serum pepsinogen level and Hp status. Baseline characteristics were compared using analysis of variance (ANOVA) test for continuous data and Pearson’s χ² test for categorical data. A logistic regression model was used for the correlation analysis between OLGA/OLGIM and serological pepsinogen test.

Results: A total of 177 non-atrophic gastritis and 154 atrophic gastritis were analyzed, among which 40 were antrum atrophy, 32 were corpus atrophy and 82 were pan-atrophy. All patients were assessed applying the OLGA/OLGIM criteria with a mean age of 54.7?±?10.8 years. Patients among OLGA/OLGIM Stage III–IV were presented with a lower level of serum PGI and PGI/PGII (p?<?.05), especially for Stage IV (p?=?.01). For both Hp-positive patients and Hp-negative patients according to OLGA system, PGI/PGII level correlated inversely with the rising stage (p?=?.022; p?=?.028). As for OLGIM system, similar difference can be seen in PGI/PGII level in either Hp-positive patients, or Hp-negative patients (p?=?.036; p?=?.013). In addition, the percentage of G-17 <1?pmol/L combined with PG-negative in antrum atrophy group was much higher than that of non-atrophy group and corpus atrophy group (25 versus 15.8 versus 6.3%) (p?=?.029). The proportion of G-17?>?15?pmol/L combined with PG-positive was apparently higher in corpus atrophy group, compared with other two groups (25 versus 11.3 versus 8.1%) (p?=?.023). Logistic regression modeling showed there exist significant connections between OLGA/OLGIM stages and serum pepsinogen test in patient stratification for gastric mucosal atrophy assessment (p?<?.001, p?<?.001).

Conclusions: Serum pepsinogen test has a strong correlation with OLGA/OLGIM gastritis stage and could provide important information in assessment of atrophy/intestinal metaplasia.     

Efficacy of combination therapy with transcatheter arterial chemoembolization and radiofrequency ablation for intermediate-stage hepatocellular carcinoma

Abstract

Objectives: Transcatheter arterial chemoembolization (TACE) is the standard therapy for patients with intermediate-stage hepatocellular carcinoma (HCC). This study aimed to determine whether combination therapy with radiofrequency ablation (RFA) and TACE was superior to TACE monotherapy for intermediate-stage HCC and identify cases in which this technique was the most effective.

Materials and methods: We selected patients with intermediate HCC who met the following eligibility criteria: (1) ≥ 20 years of age, (2) receiving initial therapy, (3) ≤7 tumors, and (4) maximum tumor diameter <5?cm. We performed propensity score matching (PSM) using potential confounding factors. We retrospectively compared the cumulative overall survival rate and recurrence-free survival rate between the TACE?+?RFA and TACE groups. Additionally, a sub-group analysis was performed for preoperative factors.

Results: Among the 103 patients, 92 were selected using PSM. The cumulative overall survival rates at 1, 3, and 5 years for the TACE?+?RFA group were 97.4%, 70.4%, and 60.4%, respectively, which were significantly higher than those for the TACE group (92.7%, 55.7%, and 22.8%, respectively, p?=?.045). The recurrence-free survival rates at 0.5, 1, and 2 years for the TACE?+?RFA group were 80.0%, 58.6%, and 33.3%, respectively, which were significantly higher than those for the TACE group (34.5%, 8.8%, and 2.9%, respectively, p?p?=?.036).

Conclusions: The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP <100.     

Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg capsule of methotrexate three times per week

Abstract

Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA); however, the pharmacodynamics of MTX in Japanese patients with RA treated legitimately according to the government recommended dosage, 6?mg per week, are unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured in sera of 16 outpatients with active RA in the first week of MTX treatment and 4–12 weeks after the introduction at 0, 1, 2, 4, and 8?h after administration of the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168?h. The mean maximal serum drug concentration (mean C_max) of MTX attained at 1–2?h after ingestion of the first capsule was 0.215 and 0.252?µM, respectively, in the first and the follow-up week. The mean C_max after ingestion of the third capsule was 0.223?µM and 0.357?µM. The mean C_max of 7-OH MTX was 0.0334 and 0.0289?µM for the first capsule, and 0.0495 and 0.0672?µM for the third capsule. The results indicate that MTX does not accumulate or deposit in the body of Japanese patients with RA when treated with 6?mg per week, and pharmacodynamics of MTX are comparable to those in overseas patients treated with 7.5?mg per week.     

Detection of Helicobacter pylori in Faeces with a New Enzyme Immunoassay Method: Preliminary Results

Objective. The epidemiology of Barrett's oesophagus (BO) is characterized by divergent results. The aim of this study was to estimate the prevalence of BO and intestinal metaplasia (IM) at the gastro-oesophageal junction (GOJ) in a population-based series of patients referred for first-time gastroscopy. Material and methods. Consecutive patients who underwent endoscopy for the first time at endoscopy units exclusively serving defined catchment areas were invited to take part in the study. Biopsies were taken immediately below the GOJ and from the distal oesophagus, and clinical data were recorded. Results. A total of 769 patients (mean age 53 years, 43% M) were examined. Overall IM prevalence was 14%. BO was noted in 4%. Overall, the prevalence of IM increased by 8% (95% CI 6–10%) per year of age. BO patients were predominately women (69%). Presence of cardia-type mucosa in the cardia increased with age from 25% among the youngest to 59% among the oldest patients. Pancreatic acinar metaplasia (PAM) was found in 18%. Conclusions. While BO is not common among Swedish gastroscopy patients, IM and PAM are found in every 7th and 6th patient, respectively. Age-dependent increments in prevalence suggest that not only BO and IM, but also cardia-type mucosa are acquired and/or progressive lesions.     

The effects of a growth hormone-releasing hormone antagonist and a gastrin-releasing peptide antagonist on intimal hyperplasia of the carotid artery after balloon injury in a diabetic rat model

IntroductionArterial restenosis after angioplasty/stenting has hindered coronary artery disease treatment, especially in diabetics. We theorized that gastrin-releasing peptide (GRP) antagonists and growth hormone-releasing hormone (GHRH) antagonists might decrease neointimal hyperplasia and restenosis in diabetic rats after common carotid arterial balloon injury.MethodsTwo separate experiments were conducted to test the effects of a GRP antagonist (RC-3095) and a GHRH antagonist (MZ-4-71) on vascular smooth muscle (VSM) growth. In a preliminary in vitro experiment non-injured human aortic vascular smooth muscle (VSM) proliferation was compared between growth media and control. In a second in vivo experiment, intimal and medial area, intima/media ratio (IM) and percent stenosis were compared between injured carotid arteries in twelve Zucker type II obese rats treated with subcutaneously injected RC-3095, MZ-4-71, or control media.ResultsIn the in vitro experiment, decreased VSM cell growth was observed in GRP antagonist (p < 0.05) and GHRH antagonist groups (p < 0.05) compared to the control group. In the in vivo experiment, the GRP antagonist group had a decreased IM ratio (1.63 ± 0.41, p < 0.05) and an increased area of stenosis (98.78% ± 1.48 p = NS) compared to control (2.38 ± 1.09) while the GHRH antagonist group had decreased IM ratio (1.33 ± 0.58 SD, p < 0.05) and percent area of stenosis (78.84% ± 24.97, p < 0.05) compared to control (2.38 ± 1.09).ConclusionsThe significant decrease in both IM ratio and percent area of stenosis in the GHRH antagonist group supports the hypothesis that this peptide may reduce neointimal hyperplasia and restenosis.     

Abnormal Hemoglobins in Gurkhas

Abstract

β-Thalassemia (β-thal) is an inherited blood disorder characterized by reduced or absent synthesis of the β chains of hemoglobin (Hb). Although a number of causative mutations have been reported, here we report two novel mutations detected in Chinese patients. Red blood cell (RBC) indices were indicative of β-thal, but no mutations were detected by routine methods. Sequencing of the β-globin gene uncovered one mutant with a 12?bp deletion (TCTGTGTGCTGG) from codon 111 to codon 115 (HBB: c.335-346del12bp) in exon 3. The other was found to be a nonsense mutation at codon 35 (HBB: c.108?C?>?G). The identification of these novel mutations will facilitate future diagnoses of β-thal caused by either of these mutations and will also be useful for genetic counseling and prenatal diagnosis.     

Announcements

Abstract

Objective: Transthyretin (ATTR) amyloidosis is an under-recognized, progressive disease manifesting as cardiomyopathy and/or polyneuropathy. Diflunisal, a nonsteroidal anti-inflammatory drug (NSAID), has demonstrated transthyretin stabilization in vitro and slowing of polyneuropathy progression in the hereditary ATTR subtype (ATTRm). However, the use of diflunisal has only been described in a small cohort of patients with ATTR cardiac amyloidosis (CA). We hypothesized that selected patients with ATTR-CA, both hereditary and wild-type (ATTRwt), would tolerate diflunisal with limited adverse events.

Materials and methods: This is a retrospective, longitudinal study of 23 patients with ATTR-CA (10 ATTRm and 13 ATTRwt) diagnosed at the Cleveland Clinic from May 2007 to August 2017 who were treated with diflunisal. Patients were prescribed diflunisal, fully informed of the risks of side effects. Patient characteristics and subsequent adverse events were recorded.

Results: The duration of diflunisal therapy ranged from 1–89 months (median 15?months). Average eGFR at diflunisal initiation was 61.9?±?15.4?mL/min/m². Only one patient had a transient rise in Cr of 0.31?mg/dL. There were no clinically significant bleeding events, despite most of the patients being on anticoagulants or antiplatelet agents. Three of 23 patients (13%) withdrew treatment due to drug side effects (erosive gastritis, epigastric pain and decreased appetite). No patients died or were hospitalized for heart failure.

Conclusion: Diflunisal was well-tolerated in both the ATTRm- and ATTRwt-CA populations. Withdrawal due to side effects was related to gastrointestinal complaints, but most patients had no adverse events. Diflunisal can be safely used in a selected group of ATTR-CA patients with appropriate clinical, renal and hematologic monitoring.