Thyroid hormone autoantibodies: are they a better marker to detect early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments?

BACKGROUND: Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage that leads to dysfunction of the gland. To find a more reliable thyroid marker, we assessed the presence of antibodies binding thyroid hormones (thAbs) in a cancer population undergoing potentially thyrotoxic treatment. METHODS: From April 2010 to September 2013, 82 patients with hematologic malignancies treated with tyrosine kinase inhibitors or immunoregulatory drugs were recruited. Healthy volunteers (n = 104) served as control subjects. Thyroid function, autoimmunity tests, thAbs, and thyroid sonography were assessed once during treatment. RESULTS: Overall, thAb positivity was recorded in 13% of the entire cohort. In most cases, the thAbs were of a single type, with a predominance of T3 immunoglobulin G. More specifically, thAbs were detected in 11 cancer patients; and abnormal levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroperoxidase antibody were detected in 6 (p = 0.05), 0 (p = 0.0006), and 2 cancer patients (p = 0.001) respectively. Ultrasonographic alterations of the thyroid were observed in 12 cancer patients. In contrast, of the 104 healthy control subjects, only 1 was positive for thAbs (1%). CONCLUSIONS: We have demonstrated for the first time that thAbs are a reliable marker of early thyroid dysfunction when compared with the widely used standard thyroid tests. A confirmatory prospective trial aiming at evaluating thAbs at various time points during treatment could clarify the incidence and timing of antibody appearance.

A diachronic-comparative analysis for the identification of the most powerful prognostic index for localized diffuse large B-cell lymphoma.

BACKGROUND: In the rituximab era, the conventional International Prognostic index (IPI) lost at least in part its predictive power, while the National Comprehensive Cancer Network-IPI (NCCN-IPI) seems to be a new and valid prognosticator. However, it has not yet been evaluated in patients with localized disease and it has not been compared with the modified IPI (mIPI) of the pre-rituximab era. In order to evaluate the different prognosticators and to assess the importance of rituximab and radiotherapy (RT), we carried out the so far largest retrospective analysis of patients with localized diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We retrospectively assessed clinical and therapeutical data of 1405 patients treated in from 1987 to 2012 in 10 cancer centers in Italy and 1 in Austria. RESULTS: All patients underwent an anthracycline containing polychemotherapy and 254 additional rituximab. The median follow-up was 5.7 years (range 0.1-23 years). The 5-year overall survival (OS) was 75%, being significantly superior in those who underwent additional rituximab, while RT consolidation did not improve the outcome of those who received immunochemotherapy. Patients with extranodal disease benefited from the addition of rituximab, while RT did not improve OS of the immunochemotherapy subgroup. In the pre-rituximab era, the mIPI showed a better performance than the others. In rituximab-treated patients, the NCCN-IPI had the highest discriminant value and the 5-years OS varied significantly (P < 0.001) between the three risk groups and was 98% in low-risk patients, 82% in those with a low-intermediate risk and 57% among high-intermediate and high-risk cases. CONCLUSIONS: The NCCN-IPI is so far the best prognosticator for patients with localized DLBCL who underwent R-CHOP(-like). The addition of rituximab is indispensable regardless of the risk category and site of involvement, while the addition of RT should be reserved to those cases who are ineligible to rituximab.

R-CHOP versus R-COMP: are they really equally effective?

The first-line standard treatment for diffuse large B-cell lymphoma (DLBCL) is the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). It is associated with cardiotoxicity, which is why new treatment strategies are needed. Liposomial doxorubicin has been proven to reduce these side-effects, but until now a direct comparison regarding efficacy has not yet been published. We retrospectively assessed 364 consecutive DLBCL patients who underwent either R-CHOP (218; 60%) or R-COMP (doxorubicin replaced by non-pegylated liposomal doxorubicin; 146; 40%) in first line and compared outcome and survival. We provide evidence that both regimens induce a high and comparable number of complete remissions and that both are able to cure patients with DLBCL. Confirmatory data are needed.

Efficacy and tolerability of bendamustine, bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study.

Bendamustine demonstrated synergistic efficacy with bortezomib against multiple myeloma (MM) cells in vitro and seems an effective treatment for relapsed-refractory MM (rrMM). This phase II study evaluated bendamustine plus bortezomib and dexamethasone (BVD) administered over six 28-day cycles and then every 56 days for six further cycles in patients with rrMM treated with 4 prior therapies and not refractory to bortezomib. The primary study end point was the overall response rate after four cycles. In total, 75 patients were enrolled, of median age 68 years. All patients had received targeted agents, 83% had 1-2 prior therapies and 33% were refractory to the last treatment. The response ratepartial response (PR) was 71.5% (16% complete response, 18.5% very good PR, 37% partial remission). At 12 months of follow-up, median time-to-progression (TTP) was 16.5 months and 1-year overall survival was 78%. According to Cox regression analysis, only prior therapy with bortezomib plus lenalidomide significantly reduced TTP (9 vs 17 months; hazard ratio=4.5; P=0.005). The main severe side effects were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), neuropathy (8%) and gastrointestinal and cardiovascular events (both 6.5%). The BVD regimen is feasible, effective and well-tolerated in difficult-to-treat patients with rrMM.

A survey of methicillin-resistant Staphylococcus aureus control strategies in Italy.

PURPOSE: Data regarding the implementation of state-of-the-art methicillin-resistant Staphylococcus aureus (MRSA) control procedures in Italy are lacking. There is a need to evaluate compliance with MRSA recommendations (CR) in Italian hospitals. METHODS: A 67-question closed-answer survey was sent to all Italian hospitals, in order to analyze and evaluate program consistency with CR [hand hygiene (HH), contact precautions, screening of high-risk patients, decolonization, feedback on surveillance data, and antimicrobial guidelines and education programs]. RESULTS: 205 hospitals, which account for 42 % of national admissions, returned questionnaires. 131 hospitals (64 %) did not have written MRSA control guidelines. Hospitals reported the following levels of compliance with CR: (1) HH: 67 hospitals (33 %); (2) contact precautions: 33 (16 %); (3) MRSA screening: 66 (32 %); (4) MRSA decolonization: 42 (20 %); (5) surveillance data feedback: 87 (43 %); and (6) antimicrobial guidelines and education programs: 41 (20 %). One hospital (0.5 % of responses) had implemented all recommendations and 28 hospitals (14 %) had implemented four or five recommendations. 31 % of hospitals surveyed had implemented none. Multivariate analysis showed that the only factor identified as being associated with the implementation of MRSA control recommendations was the number of meetings/year of the infection control team (ICT) (p = 0.004). CONCLUSIONS: Written MRSA control guidelines are available in only one-third of Italian facilities. An organized system, with ≥4 interventions, has been implemented in just 1 out of 7 hospitals. HH programs and ICT activity are related to better MRSA control. In Italy, there is significant opportunity for improvement in MRSA control.

[Prevalence of Staphylococcus aureus methicillin-resistant (MRSA) among health care workers]. / Prevalenza di Staphylococcus aureus meticillino-resistente (MRSA) tra gli operatori sanitari.

Methicillin-resistant Staphylococcus Aureus (MRSA) is a type of Staphylococcus that is resistant to certain antibiotics. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin and amoxicillin. Staphylococcus infections, including MRSA, occur most frequently among persons in hospitals and healthcare facilities. The present study was performed to investigate the in vitro activity of oxacillin and other antimicrobial agents against S. aureus strains obtained from nursing personnel. The study included 56 hospital personnel of Universitary Policlinic of Messina. S. aureus strain was isolated in 14 samples (25%); resistent patterns have been studied and results have demonstrated: none methicillin resistant, while 14% oxacillin and tetraciclin resistant. The incidence of methicillin sensitive was 100%, while 86% proved to be sensitive to oxacillin and tetraciclin. In conclusion, the usually hygienic methods (disposable gowns, hygienic hand disinfection after each patients contact, masks use when is a risk of aerosolization of MRSA) are indicate for significantly reducing of these strains. Continuing education programmes can help to increase awareness among hospital staff.

Unexpected cytological diagnosis of two cases of echinococcosis.

The Authors report two cases of hydatid cysts localized in the soft tissues of the thigh and in para-renal region respectively. In both cases the cystic nature of the lesion was revealed by echography while the common serologic and hematologic preoperative tests did not show pathologic values. The working diagnosis was traumatic or developmental lesion and the patients were undergone to fine needle aspiration (FNA) cytology which permitted to make the unexpected diagnosis of hydatid cysts. The enzyme linked immunosorbent assay for echinococcus, done at the time in monitoring the disease, was positive only in one case. Although the routine use of FNA cytology for the diagnosis of echinococcosis should be discouraged, this procedure may represent a real aid in the definitive diagnose of clinically unsuspected hydatid cysts.

Diphasic or prolonged course of viral hepatitis A in children.

A study on nine cases of diphasic viral hepatitis A was carried out in 130 children admitted to pediatric hospital from January to December 1982. One hundred and eight children (83.0%) showed IgM anti-HAV (one of them was a chronic HBsAg carrier), 19 (14.6%) were HBsAg positive at the admission and 3 (2.3%) became positive for anti-HBc IgM marker during the course of the illness. Nine anti-HAV IgM positive children showed an atypical course of their disease in that after a short period of progressive enzyme level normalization, a relapse occurred without signs of subsequent HBV, CMV or EBV infection. Probable although hypothetical interpretations of these cases are discussed.

Hepatitis B virus in diabetic patients.

The presence of HBV markers was determined in 149 serum samples obtained from diabetic patients and was compared with a normal population. Diabetics have the same incidence of HBsAg but significantly higher anti-HBc antibodies. These differences were seen in the group of diabetics on oral hypoglycemic therapy. These results cannot yet be explained.