Itolizumab,a novel anti-CD6 monoclonal antibody: a safe and efficacious biologic agent for management of psoriasis

Introduction: Psoriasis, a chronic immune-mediated skin disorder is associated with significant physical, psychological, and quality of life impairments. Along with well-documented genetic and environmental factors, immunological factors also contribute to the pathogenesis of psoriasis. Among the immunological factors, CD6 – dependent T-cell proliferation to form Th1 and Th17 cells play a major role in the pathogenesis of psoriasis. Itolizumab is the first humanized IgG1 monoclonal antibody, which selectively targets CD6.

Areas covered: The current article presents the pharmacology of itolizumab and provides a review of the currently available data on the efficacy and safety of itolizumab for management of moderate to severe plaque psoriasis.

Expert opinion: The use of biologics to attenuate the immune-mediated pathological events in psoriasis is a relatively well-established clinical practice. However, the safety and efficacy of biologics continues to be an unsettled topic of ongoing research. While available data seems to suggest that itolizumab may be a safer option, additional studies with higher sample sizes and active comparators are needed before definitive conclusions can be drawn on the place of itolizumab in the management of psoriasis.     

尿幽门螺杆菌抗体测定在幽门螺杆菌感染诊断中的价值

目的：探讨幽门螺杆菌（Hp)抗体阴性用于排除近期Hp感染的临床价值。方法：Hp感染诊断采用^13C尿素呼气试验、快速尿素酶试验和W－S银染色，Hp抗体测定采用Hp抗体测定层析板。结果：31例Hp感染患10分钟阳性率87．1％（27／31），30分钟阳性率96．7％（30／31），56例无Hp感染患假阳性率19．7％（11／56）。对Hp感染诊断敏感性96．78％，特异性80．3％。对Hp感染阳性组以Hp抗体，^13C尿素呼气试验阳性率最高，Hp感染阴性组以Hp抗体阳性率最高。46例阳性病例中仅1例^13C尿素呼气试验阳性，W－S银染色、快速尿素酶试验均阴性。结论：Hp抗体阴性基本可排除近期有Hp感染，可避免病人作进一步的无益检查。     

Escherichia coli O157 infection mimicking acute appendicitis: usefulness of computed tomography for differential diagnosis

A 19-year-old man was admitted to our hospital with acute abdominal pain in the right lower quadrant. He had had mild diarrhea, of 1 days duration, 2 days before admission. Although physical findings were consistent with a diagnosis of acute appendicitis, computed tomography findings showed marked wall thickening from the ascending colon to the cecum, findings which were similar to those in patients with hemorrhagic colitis due to Escherichia coli O157. Instead of emergency laparotomy, the patient was treated with antimicrobial agents, which led to rapid recovery. Diagnosis of intestinal infection due to E. coli O157 was established later, as serum antibody against lipopolysaccharide of E. coli O157 was positive. E. coli O157 infection should be included in the differential diagnosis of diseases that exhibit marked wall thickening of the right colon on CT in patients with acute abdominal pain in the right lower quadrant who have mild transient diarrhea.     

Anticardiolipin antibodies and vascular access thrombosis in Taiwanese haemodialysis patients with chronic hepatitis C: a retrospective study

Hepatitis C virus causes various extrahepatic immunologic abnormalities. Vascular access thrombosis (VAT) is a major cause of morbidity in chronic haemodialysis (HD) patients. Immunoglobulin-G anticardiolipin antibody (IgG-ACA) is strongly associated with venous and arterial thrombosis in patients with normal renal function. Previous investigations have reported the association of raised IgG-ACA titre recurrent with VAT in HD patient, and also few equivalent studies were reported the same in Taiwan. This study attempted to determine whether raised IgG-ACA titres are associated with increased risk of recurrent VAT in HD patients with chronic hepatitis C. This study enrolled 98 chronic hepatitis C patients undergoing HD. IgG-ACA titre and hepatitis C marker were measured for all subjects. Raised IgG-ACA titres were present in 29.6% (29/98) of patients. In both groups (raised and normal IgG-ACA), the type of shunt did not differ (p = 0.416). There was strong association between raised IgG-ACA titre and recurrent VAT (p = 0.0004). In predicting for more or one episodes of VAT using multiple logistic regression, synthetic graft (p < 0.0001), raised IgG-ACA titre (p = 0.039), presence of hepatitis B (p = 0.004) and haemodialysis duration (p = 0.039) were significant factors. The prevalence of raised IgG-ACA titres was 39.6% among chronic hepatitis C with HD patients. There was strong association between raised IgG-ACA titre and recurrent VAT, and this finding may be the consequence of pathogenetic role of raised IgG-ACA titres on the development of VAT status in HD patients with chronic hepatitis C.     

Level V in therapeutic neck dissections for papillary thyroid carcinoma

Neck dissection for papillary thyroid carcinoma (PTC) is the standard of care for patients with clinical evidence of regional metastases. However, the extent of neck dissection is debatable. The purpose of the current study was to develop evidence‐based recommendations for when to include level V, or 1 of its sublevels, among patients with PTC undergoing neck dissection. A literature review of all studies evaluating the occurrence of metastases in level V in patients with regional metastases from PTC undergoing neck dissection was performed. Occurrence of metastases at level V is low in most series (5% to 10%), although a wide range was noticed. In cases in which metastases were found at level V, they occurred almost exclusively at sublevel VB. Sublevel VA was rarely, if ever, involved with metastatic lymph nodes. However, only recently have investigators begun to specify which sublevels of level V are at risk. Therapeutic dissection of level V is indicated when there is clinical evidence of disease involving this zone. Elective dissection of sublevel VB is indicated when there is involvement of level IV, or possibly multiple nodes at levels II and III. Under these circumstances, dissection of sublevel VB is indicated but sublevel VA may be spared. © 2012 Wiley Periodicals, Inc. Head Neck, 2013     

Do medullary thyroid carcinoma patients with high calcitonin require bilateral neck lymph node clearance? A case report

BACKGROUNDIn clinical work, 85%-90% of malignant thyroid diseases are papillary thyroid cancer (PTC); thus, clinicians neglect other types of thyroid cancer, such as medullary thyroid carcinoma (MTC).CASE SUMMARYWe report a 53-year-old female patient with a preoperative calcitonin level of 345 pg/mL. There was no definitive diagnosis of MTC by preoperative fine-needle aspiration cytology or intraoperative frozen pathology, but the presence of PTC and MTC was confirmed by postoperative paraffin pathology. The patient underwent total thyroidectomy and bilateral central lymph node dissection. Close follow-up at 1.5 years after surgery revealed no signs of recurrence or metastasis.CONCLUSIONThe issue in clinical work-up regarding types of thyroid cancer provides a novel and challenging idea for the surgical treatment of MTC. In the absence of central lymph node metastasis, it is worth addressing whether patients with high calcitonin can undergo total thyroidectomy and bilateral central lymph node dissection without bilateral lateral neck lymph node dissection.     

Recurrent pericarditis in children: elevated cardiac autoantibodies

Summary Recurrent pericarditis is a rare disease in childhood. Nevertheless, it may represent a challenge to the clinician due to its resistance to anti-inflammatory treatment. The initial etiology often remains unclear; specific laboratory parameters predicting the frequency or severity of the recurrences are lacking. We report on four patients with recurrent pericarditis in whom antimyolemmal antibodies (AMLAs) were detected. A prolonged persistence of IgM-type AMLAs was found in three patients: two of them presented with acute inflammation as the initial event and one with 48 recurrences during 5.5 years. The fourth patient showed a fast conversion from IgM to IgG-type AMLAs after a less acute initial presentation and showed 4 mild recurrences during the 48-month follow-up. Conclusion We were able to detect AMLAs in four children with recurrent pericarditis. This finding may be attributed to an auto-immunological disease following a first, acute event. We propose the detection of AMLAs in all children with unexplained recurrent pericarditis. Pediatric patients with a persistence of IgM-type AMLAs may face frequent recurrences and should be monitored therefore more closely. In addition, medical treatment may be changed in these patients with a slower tapering of the dosage of steroidal and non-steroidal antiinflammatory drugs.     

Relevance of autoantibody detection to the rapid diagnosis of brucellosis

The rose bengal test is often used for rapid diagnosis of human brucellosis in endemic areas. However, autoantibodies have never been investigated as a reason for false-positive or false-negative results. Therefore, the aim of this study was to show the effect of autoantibody detection on the rapid diagnosis of human brucellosis in an endemic area. The study included 2 groups: antinuclear antibody (ANA)-positive and ANA-negative groups. Diagnosis of brucellosis was established by isolation of Brucella spp. from blood culture. The overall sensitivity and specificity of the rose bengal test were 100% and 90.8%, respectively. The specificity (100% versus 89%) and positive predictive value of the test (100% versus 8%) fell markedly from the ANA-negative to the ANA-positive group. As a conclusion, this study verified our suspicion about the effect of autoantibodies on rose bengal test results to the diagnosis of human brucellosis. However, to have definite decisions, extensive studies with larger populations are needed.     

Rapid and simple detection of a mycobacterium circulating antigen in serum of pulmonary tuberculosis patients by using a monoclonal antibody and Fast-Dot-ELISA

OBJECTIVES: Several immunoassays have been established for detection of Mycobacterium tuberculosis (MTB) antigens in serum, sputum and cerebrospinal fluid of tuberculous patients using polyclonal or monoclonal antibodies raised against different mycobacterium antigens. Some of these assays display both high sensitivity and specificity for the detection of these antigens. However, these assays require special and highly expensive equipment and the procedures require long periods for their completion. Thus, the rationale of this study was to establish and evaluate Fast-Dot-Enzyme-Linked Immunosorbent Assay (FD-ELISA) as a fast, cheap and field applicable assay for detection of mycobacterium antigen in serum of patients with pulmonary TB. DESIGNS AND METHODS: This study included three groups: group I: 175 tuberculous patients with pulmonary TB proves with sputum Ziehl-Neelsen (ZN) for acid-fast bacilli and sputum culture (all cases were culture positive for MTB); Group II: 65 patients with diseases other than pulmonary TB as bronchial carcinoma (17 patients), bronchial asthma (29 patients) and chronic obstructive pulmonary disease (19 patients); group III: 50 healthy individuals. Groups II and III served as negative control groups. The target mycobacterium antigen was identified in both crude mycobacterium antigens extract and serum of patients with pulmonary TB, using western blotting technique and anti-TB monoclonal antibody (TB20-mAb) and then it was estimated in the serum samples of all studied groups as an index of tuberculosis, using a newly developed FD-ELISA. RESULTS: The target mycobacterium antigen was identified at 20 kDa molecular mass in crude mycobacterium antigens extract as well as in serum of patients with pulmonary TB. The developed FD-ELISA detected the mycobacterium antigen in the sera of 159 out of 175 pulmonary TB patients with a sensitivity of 90.8% and 93.0% positive predictive value (PPV). In addition, it identified 12 false weakly positive cases out of 115 samples of negative control groups (7 out of 65 non-TB patients and 5 out of 50 healthy individuals) with a specificity of 89.6% and 86.6% negative predictive value (NPV). Standardization of the FD-ELISA using a serial dilution of the purified mycobacterium antigen indicated that the assay was able to detect 1.8 microg/ml as a lowest detectable antigen concentration. CONCLUSIONS: The newly developed FD-ELISA is a simple, rapid and highly sensitive assay for detection of mycobacterium antigen in patients with pulmonary TB. Moreover, all steps were performed at room temperature and without the need to use expensive equipment, and this may enhance the application of this assay in tuberculosis screening programs. Further study is needed for confirmation of FD-ELISA reproducibility in light infected pulmonary TB patients and in a large population.