Prospective cohort study of effects of infliximab on rheumatoid factor,anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis

BackgroundAntibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFα antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy.MethodsThirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3 mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined.ResultsAt baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly (p < 0.001), whereas anti-CCP showed little change (p = 0.053). ANA titres increased significantly (p < 0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16–3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16–4.13]).ConclusionsDuring infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.     

Readmission Following Gastric Cancer Resection: Risk Factors and Survival

Background

This study utilized a multi-institutional database to evaluate risk factors for readmission in patients undergoing curative gastrectomy for gastric adenocarcinoma with the intent of describing both perioperative risk factors and the relationship of readmission to survival.

Methods

Patients who underwent curative resection of gastric adenocarcinoma from 2000 to 2012 from seven academic institutions of the US Gastric Cancer Collaborative were analyzed. In-hospital deaths and palliative surgeries were excluded, and readmission was defined as within 30 days of discharge. Univariate and multivariable logistic regression analyses were employed and survival analysis conducted.

Results

Of the 855 patients, 121 patients (14.2 %) were readmitted. Univariate analysis identified advanced age (p?<?0.0128), American Society of Anesthesiology status ≥3 (p?=?0.0045), preexisting cardiac disease (p?<?0.0001), hypertension (p?=?0.0142), history of smoking (p?=?0.0254), increased preoperative blood urea nitrogen (BUN; p?=?0.0426), concomitant pancreatectomy (p?=?0.0056), increased operation time (p?=?0.0384), estimated blood loss (p?=?0.0196), 25th percentile length of stay (<7 days, p?=?0.0166), 75th percentile length of stay (>12 days, p?=?0.0256), postoperative complication (p?<?0.0001), and total gastrectomy (p?=?0.0167) as risk factors for readmission. Multivariable analysis identified cardiac disease (odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.6–3.3, p?<?0.0001), postoperative complication (OR 2.3, 95 % CI 1.6–5.4, p?<?0.0001), and pancreatectomy (OR 2.2, 95 % CI 1.1–4.1, p?=?0.0202) as independent risk factors for readmission. There was an association of decreased overall median survival in readmitted patients (39 months for readmitted vs. 103 months for non-readmitted). This was due to decreased survival in readmitted stage 1 (p?=?0.0039), while there was no difference in survival for other stages. Stage I readmitted patients had a higher incidence of cardiac disease than stage I non-readmitted patients (58 vs. 24 %, respectively, p?=?0.0002).

Conclusions

Within this multi-institutional study investigating readmission in patients undergoing curative resection for gastric cancer, cardiac disease, postoperative complication, and concomitant pancreatectomy were identified as significant risk factors for readmission. Readmission was associated with decreased overall median survival, but on further analysis, this was driven by differences in survival for stage I disease only.

     

Repeat Low‐Trauma Fractures Occur Frequently Among Men and Women Who Have Osteopenic BMD

Fracture risk assessment based solely on BMD has limitations. Additional risk factors include the presence of a previous low‐trauma fracture. We sought to quantify the fracture burden attributable to first versus repeat fracture. We studied 2179 men and 5269 women, 50–90 yr of age, participating in the Canadian Multicentre Osteoporosis Study (CaMos). We included all low‐trauma fractures that occurred over 8 yr of follow‐up and classified these as either first or repeat clinical low‐trauma fracture based on lifetime fracture history. Analyses were further stratified by sex, age, BMD risk categories (normal, osteopenia, osteoporosis), and vertebral deformity status. There were 128 fractures in men and 577 fractures in women. About 25% of fractures in men and 40% in women were repeat fractures. Just over one half of first fractures occurred in those with osteopenic BMD (58% in men, 54% in women). Just under one half of repeat fractures also occurred in those with osteopenic BMD (42% in men, 47% in women). The incidence of repeat fracture was, in most cases, nearly double, but sometimes nearly quadruple, the incidence of first fracture within a given BMD risk category in both men and women. Repeat fractures contribute substantially to overall fracture burden, and the contribution is independent of BMD. Furthermore, those with a combination of prior low‐trauma fracture and another risk factor were at especially high risk of future fracture.     

The frontal pelvic plane provides a valid reference system for implantation of the acetabular cup: spatial orientation of the pelvis in different positions

Background The frontal pelvic plane has traditionally served as the reference plane for implantation of the acetabular cup during total hip arthroplasty, with referencing performed with the patient supine on the operating table. During daily activities in an upright position, the frontal pelvic plane changes from a horizontal to a vertical orientation. If this change in orientation is accompanied by a substantial change in pelvic inclination angle, it would mean that the use of the frontal pelvic plane as a reference plane for implantation of the acetabular cup would not be valid for proper alignment of the cup. To evaluate this possibility, we measured the change of inclination of the pelvis from the supine to the standing position.

Subjects and methods We evaluated 120 patients, first positioned in a standing position and then supine on a table. Three pelvic landmarks were digitized percutaneously, and the spatial coordinates were calculated with regard to pelvic orientation in the horizontal and the vertical plane.

Results We found a mean inclination of 6.7° in the standing position and 5.6° in the supine position. Patients who were more than 60 years of age who did not have coxarthrosis had a greater inclination angle (8.7°) while standing. Pelvic orientation was stable with regard to the supine and standing positions. These results were independent of sex, level of arthrosis, or status after implantation of a total hip replacement.

Interpretation The frontal pelvic plane is a valid reference plane for implantation of the acetabular cup.

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Refractory monosymptomatic nocturnal enuresis: a combined stepwise approach in childhood and follow-up into adolescence, with attention to the clinical value of normalizing bladder capacity

OBJECTIVE: To assess the importance of normalizing bladder capacity to the age-expected capacity in children with refractory monosymptomatic nocturnal enuresis (MNE), and to evaluate the long-term results when these children grow into adolescence. PATIENTS AND METHODS: The study included 34 children with refractory MNE; all were treated > 5 years earlier for their MNE using a combined stepwise approach, consisting of retention control training, oxybutynin and an enuresis alarm. Data were obtained on their enuretic state, night-time voiding behaviour and bladder capacity, from a questionnaire and a voiding chart. RESULTS: Before starting treatment, all patients had a bladder capacity that was too small for their age. After the combined stepwise approach, MNE improved in all patients and 24 (71%) were cured. Although the bladder capacity was increased to the age-expected capacity in 26 (76%), most woke at night to void. Currently, at a mean of 7.7 years after the primary treatment, 28 (82%) of the patients are completely dry at night, of whom 15 (54%) arouse to void for 35% of the nights. Six patients (18%) still have some enuretic episodes. Only those who were dry after primary treatment and remained dry had a normal age-expected increase in bladder capacity. For all others there was a decrease in age-related bladder capacity. CONCLUSIONS: In patients with refractory MNE, a combined stepwise approach improves and may even eliminate enuresis, but normal night-time bladder behaviour in adolescence and adulthood is only achieved in some. Furthermore, about a fifth still have some enuretic episodes.     

Quality-of-life outcome following hemiarthroplasty or total shoulder arthroplasty in patients with osteoarthritis. A prospective, randomized trial

BACKGROUND: Both total shoulder arthroplasty and hemiarthroplasty have been used commonly to treat severe osteoarthritis of the shoulder; however, their effect on disease-specific quality-of-life outcome is unknown. The purpose of this study was to compare the quality-of-life outcome following hemiarthroplasty with that following total shoulder arthroplasty in patients with osteoarthritis of the shoulder. METHODS: Forty-two patients with a diagnosis of osteoarthritis of the shoulder were randomized to receive a hemiarthroplasty or a total shoulder arthroplasty. One patient died, and all others were evaluated preoperatively and at six weeks and three, six, twelve, eighteen, and twenty-four months postoperatively with use of a standardized format including a disease-specific quality-of-life measurement tool (Western Ontario Osteoarthritis of the Shoulder [WOOS] index), general shoulder rating scales (University of California at Los Angeles [UCLA] shoulder scale, Constant score, and American Shoulder and Elbow Surgeons [ASES] evaluation form), general pain scales (McGill pain score and visual analogue scale), and a global health measure (Short Form-36 [SF-36]). When a patient required revision of a hemiarthroplasty to a total shoulder arthroplasty, the last score before he or she "crossed over" was used for the analysis. RESULTS: Significant improvements in disease-specific quality of life were seen two years after both the total shoulder arthroplasties and the hemiarthroplasties. There were no significant differences in quality of life (WOOS score) between the group treated with total shoulder arthroplasty and that treated with hemiarthroplasty (90.6 +/- 13.2 and 81.5 +/- 24.1 points, respectively; p = 0.18). The other outcome measures demonstrated similar findings. Two patients in the hemiarthroplasty group crossed over to the other group by undergoing a revision to a total shoulder arthroplasty because of glenoid arthrosis. CONCLUSIONS: Both total shoulder arthroplasty and hemiarthroplasty improve disease-specific and general quality-of-life measurements. With the small number of patients in our study, we found no significant differences in these measurements between the two treatment groups. LEVEL OF EVIDENCE: Therapeutic Level I.     

Mechanisms of desflurane-induced preconditioning in isolated human right atria in vitro

BACKGROUND: The authors examined the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels, adenosine A1 receptor, and alpha and beta adrenoceptors in desflurane-induced preconditioning in human myocardium, in vitro. METHODS: The authors recorded isometric contraction of human right atrial trabeculae suspended in oxygenated Tyrode's solution (34 degrees C; stimulation frequency, 1 Hz). Before a 30-min anoxic period, 3, 6, and 9% desflurane was administered during 15 min. Desflurane, 6%, was also administered in the presence of 10 microm glibenclamide, a K(ATP) channels antagonist; 10 microm HMR 1098, a sarcolemmal K(ATP) channel antagonist; 800 microm 5-hydroxy-decanoate (5-HD), a mitochondrial K(ATP) channel antagonist; 1 microm phentolamine, an alpha-adrenoceptor antagonist; 1 microm propranolol, a beta-adrenoceptor antagonist; and 100 nm 8-cyclopentyl-1,3-dipropylxanthine (DPX), the adenosine A1 receptor antagonist. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- SD). RESULTS: Desflurane at 3% (95 +/- 13% of baseline), 6% (86 +/- 6% of baseline), and 9% (82 +/- 6% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (50 +/- 11% of baseline). Glibenclamide (60 +/- 12% of baseline), 5-HD (57 +/- 21% of baseline), DPX (63 +/- 19% of baseline), phentolamine (56 +/- 20% of baseline), and propranolol (63 +/- 13% of baseline) abolished desflurane-induced preconditioning. In contrast, HMR 1098 (85 +/- 12% of baseline) did not modify desflurane-induced preconditioning. CONCLUSIONS: In vitro, desflurane preconditions human myocardium against simulated ischemia through activation of mitochondrial K(ATP) channels, adenosine A1 receptor, and alpha and beta adrenoceptors.     

Ovarian metastases of appendiceal tumors with goblet cell carcinoidlike and signet ring cell patterns: a report of 30 cases

Synchronous and metachronous ovarian and appendiceal mucinous tumors are often the subject of diagnostic consultations in gynecologic pathology practices to address whether the tumors are independent neoplasms or related as primary and metastasis. Those with goblet cell carcinoidlike patterns have not been extensively evaluated in a large series. Clinicopathologic features of 30 cases were examined. All patients presented with signs or symptoms related to a pelvic/adnexal or abdominal mass. The ovarian tumors were bilateral in 25 of 28 cases with data on both ovaries and were typically large (mean/median: 14 cm, range: 4.5 to 24.0 cm). The appendices were often firm or thickened but usually did not have a discrete measurable tumor and were not notably enlarged; microscopically, transmural invasion was present in all of them. The ovarian and appendiceal tumors exhibited a variety of patterns of differentiation, including signet ring cell and glandular, with all displaying some goblet cell carcinoidlike patterns (nests, islands, cords, or cryptlike tubules with goblet cells); teratomatous elements were not identified in any ovarian tumors. Chromogranin was expressed in 7 of 19 ovarian tumors (mean/median: 6.3%/0%; range: 0% to 20%) and synaptophysin was expressed in 4 of 18 of these (mean/median: 7.8%/0%; range: 0% to 90%). Chromogranin was expressed in 6 of 16 appendiceal tumors (mean/median: 11.9%/0%; range: 0% to 70%) and synaptophysin was expressed in 6 of 15 of these (mean/median: 16.7%/0%; range: 0% to 90%). Follow-up was available for 25 patients: 17 died of disease at intervals ranging from 4 to 47 months (mean/median: 18/16) and 8 were alive with disease at 1 to 25 months (mean/median: 11/10); median survival was 19 months and the 1-year and 2-year survival rates were 63% and 34%, respectively. The clinicopathologic features of these ovarian tumors indicate they should be labeled as metastatic appendiceal adenocarcinomas rather than as goblet cell carcinoid tumors both to reflect their behavior and help distinguish them from the rare true primary ovarian goblet cell carcinoid tumors. As the ovarian tumors have appreciable components of signet ring cells they qualify as Krukenberg tumors. In cases in which the primary tumor is not already evident, their "goblet cell carcinoidlike" patterns should direct attention to the appendix as a possible source.     

Male overactive bladder: The role of urodynamics and anticholinergics

Millions of men suffer from overactive bladder and lower urinary tract symptoms. The adverse effects on quality of life and costs associated with the condition have been well described. In men, the pathophysiology of lower urinary tract symptoms may be from a number of causes including bladder outlet obstruction, detrusor overactivity, or both. Increasing data and clinical experience support the efficacy and safety of anticholinergics in men; the rate of urinary retention has been equal to that of placebo in short-term studies. Urodynamics play a vital role in defining the bladder and/or outlet dysfunction and help direct one’s therapy.