[Prevalence of anti-CCP antibodies in systemic sclerosis]. / Prevalenza degli anticorpi anti-peptide ciclico citrullinato (anti-CCP) nella sclerosi sistemica.

Joint involvement in systemic sclerosis (SSc) commonly occurs as arthralgias, while a true arthritis is less frequent. The most common arthritis developing in SSc is rheumatoid arthritis (RA) and its diagnosis may be misled by concomitant joint contracture or tendon sheath involvement due to SSc. Anti-citrullinated cyclic peptide (CCP) antibodies are an emerging tool to diagnose RA and have shown to be more specific than rheumatoid factor. We assessed the prevalence of anti-CCP antibodies in SSc patients and evaluated their sensitivity and specificity for associated RA. Searching for RF and anti-CCP antibodies and joint examination were carried out in sixty consecutive SSc patients. Hands and feet standard x-rays were performed in patients complaining with arthralgia and/or arthritis. Six out of sixty (10%) SSc patients had RA according to 1987 ARA revised criteria. Anti-CCP were detected in 5 patients (sensitivity 83%) and RF was present in all RA patients (sensitivity 100%). However, anti-CCP antibodies had a much higher specificity (94%) than RF (41%) for RA. Our study suggests that anti-CCP antibodies are a useful test to identify patients with SSc having also RA. This is crucial in the management of SSc because may allow an adequate therapy of RA and prevent further joint damage in patients who already have a poor quality of life.

Proteomic: new advances in the diagnosis of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting the joints. A number of novel treatment modalities have been introduced over the past years, and rheumatologists are now attempting to institute optimal treatment in recent-onset arthritis. To facilitate diagnosis during the early stages of disease, when often not all clinical symptoms are manifest, a good serological marker is needed. METHODS: Antibodies directed to citrullinated proteins provide this ability. The most sensitive assay for detecting these antibodies is the so-called anti-cyclic citrullinated peptide, second generation (CCP II) enzyme-linked immunosorbent assay (ELISA). RESULTS: The diagnostic and prognostic potential of anti-CCP antibodies and the availability of a fully automated assay method lead us to conclude that the test is satisfactory for routine use as a serological marker of RA. In addition, we consider the potential of multiplex autoantibody assays, including miniaturized, high-throughput microarray technology, to improve diagnosis and prognostication in early onset arthritis patients.

Non-enveloped HCV core protein as constitutive antigen of cold-precipitable immune complexes in type II mixed cryoglobulinaemia.

Hepatitis C virus (HCV) infection has been detected in a large proportion of patients with mixed cryoglobulinaemia (MC). Circulating 'free' non-enveloped HCV core protein has been demonstrated in HCV-infected patients, and this suggests its possible involvement in the formation of cryoprecipitable immune complexes (ICs). Thirty-two anti-HCV, HCV RNA-positive patients with type II MC were evaluated. Non-enveloped HCV core protein, HCV RNA sequences, total IgM, rheumatoid factor (RF) activity, IgG and IgG subclasses, C3 and C4 fractions, C1q protein and C1q binding activity were assessed in both cryoprecipitates and supernatants. Non-enveloped HCV core protein was demonstrated in 30 of 32 (93.7%) type II MC patients. After separation of cold-precipitable material, the protein was removed completely from supernatant in 12 patients (40%), whereas it was enriched in the cryoprecipitates of the remaining 18. In addition, HCV RNA and IgM molecules with RF activity were concentrated selectively in the cryoprecipitates. Differential precipitation was found for both total IgG and IgG subclasses, as they were less represented in the cryoglobulins and no selective enrichment was noted. Immunological characterization of HCV core protein-containing cryoprecipitating ICs after chromatographic fractionation showed that the IgM monoclonal component had RF activity, whereas anti-HCV core reactivity was confined to the IgG fraction. C1q enrichment in addition to high avidity of ICs for C1q binding in the cryoprecipitates suggest that complement activation may occur through the C1q protein pathway. The present data demonstrate that non-enveloped HCV core protein is a constitutive component of cryoprecipitable ICs in type II MC patients.

Total testing process: appropriateness in laboratory medicine.

BACKGROUND: The need to reduce costs in Laboratory Medicine is often related to the possibility of reducing test requests without taking into account patients' outcomes. Therefore, the term "appropriateness" in Laboratory Medicine as referred to the specific steps (pre-analytical, analytical, post-analytical) and related to the clinical process could allow the improvement of clinical effectiveness and economic efficiency. METHODS: Our experience has shown an improvement in analytical appropriateness (reorganization and re-engineering by Laboratory automation) and pre-analytical appropriateness (critical revision of the panel for cardiac markers) by evaluating the workload and errors rate in the pre-analytical phase. RESULTS: We obtained an economic saving (119,580 euro/year) in cardiac markers request (analytical appropriateness: 60%, pre-analytical appropriateness: 40%) and also an improvement in clinical appropriateness (diagnosis and therapy). CONCLUSIONS: Our data confirm the need to improve communications between physicians and Laboratory Medicine as regards the pre-analytical step and to implement educational programs for defining criteria and procedures. Appropriateness in analytical and post-analytical steps contribute to achieve economic saving (Core lab, POCT) and improvement of the turn-around time (TAT).

Application of a diagnostic algorithm in autoantibody testing: assessment of clinical effectiveness and economic efficiency.

BACKGROUND: Guidelines aim to assist physicians about appropriate health care for specific clinical circumstances. Therefore, they must be continuously updated, integrated and tailored to local situations. METHODS: We applied recently developed guidelines for autoantibody testing by assessing their economic (efficiency) and clinical (effectiveness) impact. Since June 2002, a test order algorithm has been adopted for autoantibody testing requests (3258). In particular, the guidelines were modified taking into account the needs of different departments and the results were compared to those (2762) of the previous period (January-May 2002) that had not been integrated with any diagnostic algorithm. RESULTS: A significant reduction in the number of anti-double stranded DNA (anti-dsDNA) (21.4%) and anti-Extractable Nuclear Antigens (anti-ENA) (19%) was found (p<0.0001), while the number of anti-nuclear antibody (ANA) test was unchanged (p=n.s.); further reduction in clinically inappropriate test request rates (23%) was observed. CONCLUSIONS: The application of guidelines allowed the improvement of diagnostic tests' efficiency and clinical effectiveness (patient's outcomes), thus confirming the need to apply eventual modifications to the diagnostic process taking into consideration different clinical needs.

Endometrial biopsies using small-diameter hysteroscopes and 5F instruments: how can we obtain enough material for a correct histologic diagnosis?

STUDY OBJECTIVE: To evaluate the quantity of biopsy tissue obtained by hysteroscopic grasp technique compared with classic punch technique. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: One thousand two hundred seventy-six women. INTERVENTION: Targeted biopsies performed in an office setting using two biopsy forceps, classic spoon and crocodile, and two methods, classic punch and grasp technique. MEASUREMENTS AND MAIN RESULTS: With either biopsy forceps, the mean increase in amount of tissue obtained by grasp technique compared with punch technique was statistically significant (p <0.005). With grasp technique, the mean amount of tissue obtained was even larger with crocodile than with spoon forceps. CONCLUSION: Targeted biopsy, when performed with the appropriate instrument and applying correct technique, can provide the pathologist with a large amount of tissue (mean 5.7 mm2) that is invariably adequate for histologic examination.

Paracervical anesthesia for hysteroscopy and endometrial biopsy in postmenopausal women. A randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficiency of paracervical anesthesia in reducing pain and the incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women. STUDY DESIGN: A randomized, placebo-controlled, double-blind study. Seventy-two postmenopausal women underwent diagnostic hysteroscopy and endometrial biopsy. Hysteroscopies were performed by using a lens-based endoscope with a diameter of < 4 mm and endometrial biopsies by using a 3-mm Novak's curette. Ten milliliters of 1.5 mepivacaine or saline solution was injected at the junction of the cervix and vagina (at the 4 and 8 o'clock positions) by means of an appropriate needle before performing the intrauterine procedures. Referred pain was evaluated by means of a visual analogue scale; continuous monitoring of heart rate and blood pressure was also performed. RESULTS: Paracervical anesthesia significantly reduced pain at hysteroscopy and biopsy. The incidence of vasovagal reactions was also significantly lower in the anesthetized group. CONCLUSION: Paracervical anesthesia is effective for hysteroscopy and endometrial biopsy in postmenopausal women and may be indicated particularly for patients with cervical stenosis, for very anxious subjects and in all situations where pain stimulation could trigger threatening side effects due to systemic pathologies.

Diagnostic accuracy of hysteroscopy in endometrial hyperplasia.

OBJECTIVES: To determine the diagnostic accuracy of hysteroscopy in the diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding. METHODS: From 1993 through 1995, 980 women referred to our institution for abnormal uterine bleeding underwent diagnostic hysteroscopy with eye direct biopsy of the endometrium in case of macroscopic abnormalities. Hysteroscopic features were compared with pathologic findings in order to detect the reliability of the endoscopic procedure. Statistical analysis was performed with the McNemar test. RESULTS: Positive predictive value of hysteroscopy in the diagnosis of endometrial hyperplasia accounted for 63%. In fact hysteroscopic diagnosis of endometrial hyperplasia was confirmed at pathologic examination in 81 out of 128 patients. Sensitivity and specificity of the endoscopic procedure accounted for 98% and 95%, respectively. Negative predictive value accounted for 99%, as only two cases of atypical hyperplasia were missed at hysteroscopy. Positive predictive value was higher in postmenopausal patients compared to women in the fertile age (72 vs. 58%). CONCLUSIONS: Overall, results appear encouraging, since no case of endometrial hyperplasia was missed by hysteroscopy. The high diagnostic accuracy, associated with a minimal trauma, renders hysteroscopy the ideal procedure for both diagnosis and follow-up of conservative management of endometrial hyperplasia.

Anatomic Impediments to the Performance of Hysteroscopy

Infertility and menorrhagia in menopausal women are the most frequent indications for hysteroscopy. Often, however, the procedure turns out to be difficult or impossible due to stenosis and reduction in the size of the cervical canal. With the availability of more and more atraumatic endoscopic instrumentations and improvements in the technique, hysteroscopy can be performed in all women, whatever the obstacle. In our 5-year experience of 1500 hysteroscopies, we often found anatomic conditions that, besides being obstacles to performing the examination, increased patient discomfort. With the office hysteroscope with a 5F operative sheath one can rapidly overcome the obstacles and complete the examination without discomfort to the patient.

Hyperplastic Human Endometrium

Endometrial hyperplasia is considered to be a frequent cause of menorrhagia. Traditionally, this pathology was diagnosed from specimens obtained by uterine curettage or after hysterectomy for benign disease. With hysteroscopy one can visualize the uterine cavity directly and perform guided biopsies of the endometrial mucosa. We assessed the reliability of hysteroscopic procedures in the diagnosis of endometrial hyperplasia. We performed 980 hysteroscopies in 3 years for menorrhagia and found endometrial hyperplasia in 128 women. We compared the results with histologic findings. Statistical analysis was performed according to McNemar test. On the basis of the results, hysteroscopy diagnoses and monitors endometrial hyperplasia.

Hysteroscopic Polypectomy in the Office without Anesthesia

Hysteroscopy is a reliable procedure not only for diagnosis, but also for office treatment of uterine pathologies that, until recently, required general or at least topical anesthesia. The vaginoscopic approach without a speculum and tenaculum avoids discomfort to patients and ensures complete compliance. We treated 253 endometrial and cervical polyps with 5F instruments and an office hysteroscope with operative sheath. All polyps were removed on diagnosis, and the women were able to resume their normal activity soon after the procedure. Pretreatment with danazol or gonadotropin-releasing hormone analogs was necessary only for polyps larger than 2 cm. Recurrence at follow-up was 5%.

The role of contact hysteroscopy.

Contact hysteroscopy has been replaced by a new technique based on the use of a special hysteroscope. The instrument was designed to study the squamocolumnar junction and the lesions of the portio. A new technique, endometrial dating, uses the Hamou hysteroscope to study endometrial physiology. We improved endometrial dating and discovered a new pattern, the pseudofunctional dysvascular endometrium (PFDE), that seemed to pertain to uterine bleeding. We also studied the PFDE syndrome in the presence of dysfunctional uterine bleeding. In this study we reviewed the three procedures and assessed their results. We conclude that contact microhysteroscopy is a reliable diagnostic procedure, and should be considered part of diagnostic hysteroscopy, not an independent technique.

Mitoxantrone and continuous infusion of cytosine arabinoside in refractory and relapsed acute lymphoblastic leukemia.

Twenty adult patients with relapsed or refractory acute lymphoblastic leukemias (ALL) received a regimen employing two courses of mitoxantrone 12 mg/m2 by rapid intravenous infusion on days 1, 2 and 3 and cytosine arabinoside (ARA-C) 200 mg/m2/day by continuous infusion on days 1-7. Complete remission (CR) was achieved in 10 of 20 (50%) patients (3 refractory and 7 relapsed). Median duration of CR was 5 months (range 2-9). The treatment was associated with minimal extrahematologic toxicity, with no cardiac toxicity. Our results are nearly in line with therapeutic responses obtained with regimens employing megadose therapy (HD ARA-C). Because of acceptable toxicity, mitoxantrone plus continuous infusion of a standard dose of ARA-C could be considered for relapsed of refractory ALL patients eligible for an intensive therapeutic approach (bone marrow transplantation) after a second CR.