A field test of functional status as performance of activities of daily living in COPD patients

Patients with chronic obstructive pulmonary disease (COPD) frequently experience activity restrictions and discomfort during activities of daily living (ADL). Functional status refers to the capacity to perform ADL. Available tests only partly measure this domain. Our aim was therefore to establish an assessment tool for functional status in COPD, the Glittre ADL-test. This field test includes a standardised set of ADL-like activities: Walking stairs, carrying, lifting objects, bending down and rising from a seated position. The primary variable was time to complete the test (ADL-time). Validity was investigated in 57 COPD patients by correlating ADL-time to pulmonary function, 6-min walking distance (6MWD) and questionnaires addressing health-related quality of life. Responsiveness was investigated in another 40 patients comparing ADL-time before and after rehabilitation. Median ADL-time was 4.16 min (range 2.57-14.47). Spearman rho=0.93 for test-retest reliability. ADL-time correlated with forced expiratory volume in 1s (rho=-0.61), St. George's Respiratory Questionnaire activity subscore (rho=0.43), dyspnoea during ADL (rho=0.35) and hospitalisation rate (rho=0.35). Despite a close overall correlation with 6MWD (rho=-0.82), variability was substantial, particularly for the more disabled patients. ADL-time improved significantly after rehabilitation. Glittre ADL-test yields information complementary to 6MWD. It is a valid and reliable measure of functional status, useful for assessment of individual patients and rehabilitation programs.     

Increased TFF1 trefoil protein expression in Opisthorchis viverrini-associated cholangiocarcinoma is important for invasive promotion

Aims: Cholangiocarcinoma (CCA) is a poor prognosis cancer that presents with metastatic disease. This cancer expresses MUC5AC, a mucin which normally co-expresses with trefoil factor family 1 (TFF1) protein. TFF1 is a signalling protein that can activate epithelial cell invasion and has been considered as a metastasis stimulating agent. The aim of this study was to determine the co-expression of TFF1 and MUC5AC in CCA tissues and examine the activity of TFF1 for stimulating the invasive property of CCA cell lines. Methods: In this study, TFF1 and MUC5AC were detected in CCA tissues by using immunohistochemistry. The correlations of both proteins expression with clinical data were analyzed. The activity of TFF1 was investigated using an in vitro invasion assay with established CCA cell lines KKU-100 and KKU-M213. Results: We demonstrated a high level of expression of TFF1 in 91.80% of CCA that is associated with a high level of co-expression with MUC5AC in 80.33% of cases. In vitro invasion assay showed that both cell lines have similar responses to TFF1 that could act as both a chemokinetic and chemotactic agent. The dose-response curves were bell-shaped. Conclusion: TFF1 showed co-expression with MUC5AC in CCA tissues and invasive stimulating activity in vitro. These results may indicate a role for TFF1 in promoting tumor invasion in CCA.     

Environmental factors underlying spatial patterns of sand flies (Diptera: Psychodidae) associated with leishmaniasis in southern Sinai, Egypt

Although Leishmania major is endemic in parts of the Sinai of Egypt, the ecology and distribution of Leishmania sand fly vectors in southern Sinai has not been well characterized. Accordingly, additional sand fly samples were obtained at 41 sites in the southern Sinai region during 1996-1997, and analyzed to improve the characterization of risk of sand fly-borne pathogens. Using a Geographic Information System (GIS), species-specific spatial distributions that might suggest zoonotic cutaneous leishmaniasis (ZCL) risk areas were determined in relation to contextual environmental factors, including geology, hydrogeology, climate variables and elevation. Southern Sinai was characterized by a diverse sand fly fauna (eight Phlebotomus species), probably attributable to highly variable landscape and environmental factors. Phlebotomus alexandri, Phlebotomus kazeruni and Phlebotomus sergenti were widespread and abundant, Phlebotomus papatasi and Phlebotomus bergeroti were less frequent, and Phlebotomus arabicus, Phlebotomus major and Phlebotomus orientalis had highly restricted distributions. Logistic regression models indicated that elevation and climatic conditions were limiting determinants for the distributions of sand flies in southern Sinai. Based on the predicted distribution of P. papatasi, a recognized vector of L. major, about one-quarter of southern Sinai may be at high risk of ZCL. Risk areas for the suspected ZCL vector P. bergeroti had a more patchy distribution. Results suggest that future studies should include other factors related to vector abundance, vector competence, human population, and parasite and reservoir host(s) to produce more comprehensive ZCL transmission risk maps, thus helping in planning effective prevention and control strategies.     

Performance of Matrix‐Based Risk Models for Rapid Radiographic Progression in a Cohort of Patients With Established Rheumatoid Arthritis

Objective

Matrix‐based risk models have been proposed as a tool to predict rapid radiographic progression (RRP) in rheumatoid arthritis (RA), but the experience with such models is limited. We tested the performance of 3 risk models for RRP in an observational cohort.

Methods

Subjects from an observational RA cohort with hand radiographs and necessary predictor variables to be classified by the risk models were identified (n = 478). RRP was defined as a yearly change in the Sharp/van der Heijde score of ≥5 units. Patients were placed in the appropriate matrix categories, with a corresponding predicted risk of RRP. The mean predicted probability for cases and noncases, integrated discrimination improvement, Hosmer‐Lemeshow statistics, and C statistics were calculated.

Results

The median age was 59 years (interquartile range [IQR] 50–66 years), the median disease duration was 12 years (IQR 4–23 years), the median swollen joint count was 6 (IQR 2–13), 84% were women, and 86% had erosions at baseline. Twelve percent of patients (32 of 271) treated with synthetic disease‐modifying antirheumatic drugs (DMARDs) at baseline and 10% of patients (21 of 207) treated with biologic DMARDs experienced RRP. Most of the predictor variables had a skewed distribution in the population. All models had a suboptimal performance when applied to this cohort, with C statistics of 0.59 (model A), 0.65 (model B), and 0.57 (model C), and Hosmer‐Lemeshow chi‐square P values of 0.06 (model A), 0.005 (model B), and 0.05 (model C).

Conclusion

Matrix risk models developed in clinical trials of patients with early RA had limited ability to predict RRP in this observational cohort of RA patients.     

Kringle glycosylation in a modified human tissue plasminogen activator improves functional properties

Native tissue plasminogen activator (ntPA) has a variable glycosylation site on its kringle-2 domain. We have examined the effects of kringle glycosylation on functional properties by studying the simplified tPA molecule, tPA-6. tPA-6 is composed of kringle-2 and the serine protease domains and, like ntPA, cells expressing tPA-6 process it into two glycoforms: the monoglycosylated tPA-6-primary (tPA-6P, type II) with N- linked glycosylation at Asn-448 in the serine protease domain and diglycosylated tPA-6-variant (tPA-6V, type I) with glycosylation at Asn- 448 and at Asn-184 in kringle-2. When the two glycoforms were separated, we found that purified tPA-6V had reduced fibrin-stimulated plasminogenolytic activity toward Glu-plasminogen when compared to purified tPA-6P. However, in the presence of fibrin, tPA-6V unexpectedly exhibited a sixfold increase in selectivity toward Lys- plasminogen. In addition, tPA-6V was less susceptible than tPA-6P to plasmin-mediated conversion to the two-chain form. By site-directed mutagenesis of tPA-6, we eliminated variable glycosylation at Asn-184 and engineered a new glycosylation signal at a remnant site in the kringle. This derivative, designated tPA-6D, was secreted with complete kringle glycosylation. Like the naturally occurring tPA-6V, tPA-6D had lower rates of fibrin-stimulated Glu-plasminogen activation, increased specificity toward Lys-plasminogen, and greater resistance to plasmin digestion. Although the activity of tPA-6D could be stimulated by fibrin, its activity was not stimulated significantly by fibrinogen, and in human plasma the rate of fibrinogen depletion was reduced threefold. Although fibrin binding to kringle-2 of tPA-6D was slightly improved, there was a substantial increase in the dissociation constant (kd) for lysine binding, demonstrating a lack of correlation between these ligand-binding sites. Overall, our data demonstrate the marked effect of kringle glycosylation on functional properties. In addition, we have generated a derivative with properties that potentially improve clot specificity and single-chain half-life and reduce the potential for plasminogen activation in the plasma.     

Combined Lumbar Spinal and Thoracic High-Epidural Regional Anesthesia as an Alternative to General Anesthesia for High-Risk Patients Undergoing Gastrointestinal and Colorectal Surgery

Objective  A prospective study was undertaken to review the use of combined lumbar spinal and thoracic high-epidural regional anesthesia in high-risk patients who underwent gastrointestinal/colorectal surgery from 2004 to 2006. Methods  Twelve high-risk patients underwent 13 gastrointestinal/colorectal surgical procedures, using a regional anesthetic technique, which consisted of a thoracic epidural and lumbar subarachnoid block. All patients were classified as high risk based on anesthetic assessment (American Society of Anesthesiologists (ASA) score 3 or 4). Results  Six (46.2%) of the patients were men, and the overall median age was 86 years. Ten (76.9%) patients presented as emergencies, whereas only three (23.1%) patients underwent elective procedures. All patients subjectively rated their postoperative pain relief as effective. The 30-day mortality was 2 (15.4%); however, both of these patients refused initial treatment. Only one (7.7%) patient required delayed ITU admission for respiratory support (CPAP). None of the patients required intubation at any stage. There were two (15.4%) minor and two (15.4%) major early complications and only one (7.7%) delayed complication to date. Median length of stay was 7 days. Two (15.4%) patients had delayed discharge dates, for social reasons. Discussion  These patients demonstrated early postoperative recovery, with effective analgesia, no requirements for intubation, and lower morbidity and mortality rates than similar studies of high-risk patients who underwent procedures using general anesthesia. Using this technique, patients were managed appropriately in HDU and the surgical ward, without affecting their overall length of hospital stay. Conclusions  This study supports the role of regional anesthetic techniques, combined with targeted, minimally invasive surgery—particularly for the management of high-risk patients presenting in the emergency setting.     

Are survival predictions reliable? Hospital volume versus standardisation of histopathologic reporting for accuracy of survival estimates after pancreatoduodenectomy for adenocarcinoma

Histopathologic reporting after pancreatoduodenectomy is often non-standardised. Inappropriate reporting may bias survival estimates and make comparison between institutions difficult. Using population-based nationwide data from the Cancer Registry of Norway, we examined the influence on survival estimates of standardised histopathologic reporting versus non-standardised histopathologic reporting after pancreatoduodenectomy for adenocarcinomas in the pancreas, distal bile duct, ampulla and duodenum (n = 506). Standardised histopathologic reports from a study hospital (n = 113) were compared with reports from all other institutions (24 hospitals; n = 393) discriminating between high/medium-volume and low-volume institutions. In the study hospital, more tissue blocks were sampled, more nodes were evaluated, and more details about resection margins, size, origin and vascular and perineural infiltration were reported (p < 0.001). Multivariable survival analysis identified lymph node involvement as the factor that is most dependent on standardised reporting to discriminate between favourable and poor prognostic subgroups (p = 0.018). Standardised evaluation was more important than hospital volume for completeness of histopathologic reporting and for accuracy of survival estimates.