Real-World Setting Cost-Effectiveness Analysis Comparing Three Therapeutic Schemes of One-Year Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer from the Cyprus NHS Payer Perspective.

INTRODUCTION: This study is one of the first real-world cost-effectiveness analyses of one-year adjuvant trastuzumab used in HER2-positive early female breast cancer in comparison to chemotherapy alone. It is just the second one in Europe, the first one in Cyprus, and the fourth one worldwide ever carried out using real-world data. METHODS: Using a Markov model (four health states), a cost-effectiveness analysis was carried out both over 20 years and for a lifetime horizon. The sampling method used in this study was the randomized sampling of 900 women. RESULTS: The findings for the 20-year horizon showed that all trastuzumab arms were more cost-effective, with a willingness-to-pay threshold of only €60,000 per quality-adjusted life year (QALY) [incremental cost-effectiveness ratios (ICER): €40,436.10/QALY]. For the lifetime horizon, with thresholds of €20,000, €40,000, and €60,000/QALY, all trastuzumab arms were found to be more cost-effective (ICER: €17,753.85/QALY). Moreover, for the 20-year and the lifetime horizons, with thresholds of €20,000/QALY, €40,000/QALY, and €60,000/QALY, the most cost-effective of the three subgroups (anthracyclines and then trastuzumab, no anthracyclines and then trastuzumab, and anthracyclines, taxanes, and trastuzumab) was that of anthracyclines and then trastuzumab (ICER: €18,301.55/QALY and €8954.97/QALY, respectively). CONCLUSIONS: The study revealed that adjuvant trastuzumab for one year in female HER2-positive early breast cancer can be considered cost-effective.

Cytomegalovirus meningoencephalitis after rituximab treatment for primary central nervous system lymphoma.

The efficacy and safety of rituximab against B-cell lymphomas is well established. However, there has been an increased incidence of infectious complications after rituximab treatment, mostly hepatitis B reactivation and progressive multifocal leukoencephalopathy. This is the case of a 67-year-old patient with primary central nervous system lymphoma, who developed cytomegalovirus meningoencephalitis after receiving high-dose chemotherapy and rituximab. As there was no evidence of lymphoma relapse or additional immunosuppression, besides his previous treatment, an association between rituximab and cytomegalovirus meningoencephalitis cannot be ruled out.

Systemic mastocytosis accompanied by a non-secretory plasma cell dyscrasia and nephrotic syndrome-level proteinuria in a 76-year-old patient.

We report here the interesting case of a 76-year-old man with severe proteinuria who was diagnosed with systemic mastocytosis accompanied by a clonal non-mast-cell lineage haematological disorder (a non-secretory plasma cell dyscrasia). This is a unique report of systemic mastocytosis with a non-secretory plasma cell dyscrasia and nephrotic syndrome. The pathophysiological relevance between these entities along with the probability of occult amyloidosis is discussed.

Fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan contributes to the diagnosis and management of brucellar spondylodiskitis.

BACKGROUND: Limited data suggest that fluorine-18 fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography combined with computed tomography (PET/CT) scan may be useful for diagnosing infections of the spine. Brucellar spondylodiskitis might be devastating and current imaging techniques lack sensitivity and specificity. The aim of this prospective study was to determine the role of F-18 FDG PET/CT scan in the diagnosis of brucellar spondylodiskitis and in monitoring the efficacy of its treatment. METHODS: Ten consecutive patients with brucellar spondylitis were prospectively evaluated with PET/CT. Baseline evaluation included also magnetic resonance imaging (MRI) of the affected spine, indices of inflammation, the slide agglutination test (SAT), and the standard hematology and biochemistry. All cases were treated with suitable antibiotics until resolution or significant improvement of clinical and radiological (MRI) findings. Upon completion of treatment, they were re-evaluated with follow-up PET/CT scan. The maximum standardized uptake values (SUV) were measured and compared with SAT. RESULTS: In all patients there was an increased F-18 FDG activity in the infected spine region detected by the initial MRI. F-18 FDG PET/CT provided additional information, compared to MRI, in 4 (40%) patients. More specifically it revealed additional spine lesions (in 3 patients), lymphadenitis, arthritis, organomegaly, as well as new paravertebral soft tissue involvement and epidural masses. This additional information had an impact on the duration of treatment in these patients. At the end of treatment all patients had a complete clinical response; 5 patients had positive serology, 6 patients had residual MRI findings, while 9 had a positive PET/CT but with significantly decreased FDG uptake compared to baseline (median 2.6, range 1.4 - 4.4 vs. median 5.5, range 2.8 - 9.4, p = 0.005). During the follow up period (median 12.5 months) no relapses have been observed. No significant association was observed between the SUV and SAT. CONCLUSIONS: Our study suggests that in patients with brucellar spondylodiskitis F-18 FDG PET/CT scan can provide additional information on the spread of the infection, compared to MRI. Successful treatment is associated with a significant decrease in SUVmax values; thus, PET/CT scan may be a complementary method for determining the efficacy of treatment.

Tri-cyclo-[3.3.1.0(3,7)]nonane-3,7-diyl bis-(4-methyl-benzene-sulfonate).

The title compound, C23H26O6S2 was synthesized by esterification of tri-cyclo-[3.3.1.0(3,7)]nonane-3,7-diol with p-toluene-sulfonyl chloride. The mol-ecule has symmetry 2 and is situated on site 4e. The C-C bond length between the quartenary C atoms is 1.598 (2) Å, which is considerably longer than other C-C bonds in the mol-ecule. There are C-H⋯O inter-actions present in the structure. As a consequence, the packing of the molecule (viewed along [100]) appears as chains where the molecules run parallel, but each chain has the opposite direction to the neighboring ones.

2,9-Diiodo-hexa-cyclo-[9.3.1.1(2,6).1(4,8).1(9,13).0(1,8)]octa-deca-ne.

The title compound, C(18)H(24)I(2), has an adamantanoid structure with tetra-hedral cages having four C atoms lying on the same plane [(I-)C-C-C-C(-I) torsion angle = 0°]. The plane is extended by the two I atoms, each having a deviation of 1.0 (6) Š[C-C-C-I torsion angle = 178.9 (4)°]. The central C-C bond connecting the two quaternary carbons seems enlarged [1.593 (9) Å] in comparison to the corresponding bond in [2]diadamantane [1.554 (3) Å]. This is attributed to the presence of the electronegative I atoms, which affect inductively the C atoms of the four-C-atom plane, making the central C-C bond weaker.

Penta-cyclo-[9.3.1.1(2,6).1(4,8).1(9,13)]octa-deca-1(2),8(9)-diene.

The title compound, C(18)H(24), was the main product of thermolysis of noradamantene dimer (hepta-cyclo-[9.3.1.1(2,6).1(4,8).1(9,13).0(1,9).0(2,8)]octa-deca-ne). The crystal structure was determined to prove that the thermolysis product of noradamantene dimer is favored by stretch release due to ring opening of the four-membered ring. The bond length of the quaternary C atoms of the starting material was calculated as 1.6 Å, enlarged in comparison to other single bonds. After the rearrangement, the stretch release of the above carbons leads to an increase of the distance between them (2.824 Å) with respect to the crystallographic data.

2,4-Dioxa-λ(6)-thia-tetra-cyclo-[5.3.1.1(5,9).0(1,5)]dodecane-3,3-dione.

The crystal structure of the title compound, C(9)H(12)O(4)S, was determined in order to investigate the effect of the eclipsed O atoms on the bond length of the vicinal quaternary C atoms. The two quaternary C atoms of the noradamantane skeleton and the two O atoms to which they are connected all located essentially in the same plane (maximum deviation = 0.01 Å), resulting in an eclipsed conformation of the C-O bonds. The C-C bond of the quaternary C atoms is 1.581 (3) Å, considerably longer than the other C-C bonds of the mol-ecule due to the stretch of the cage structure.

Toll-like receptors, tissue injury, and tumourigenesis.

Toll-like receptors (TLRs) belong to a class of molecules known as pattern recognition receptors, and they are part of the innate immune system, although they modulate mechanisms that impact the development of adaptive immune responses. Several studies have shown that TLRs, and their intracellular signalling components, constitute an important cellular pathway mediating the inflammatory process. Moreover, their critical role in the regulation of tissue injury and wound healing process as well as in the regulation of apoptosis is well established. However, interest in the role of these receptors in cancer development and progression has been increasing over the last years. TLRs are likely candidates to mediate effects of the innate immune system within the tumour microenvironment. A rapidly expanding area of research regarding the expression and function of TLRs in cancer cells and its association with chemoresistance and tumourigenesis, and TLR-based therapy as potential immunotherapy in cancer treatment is taking place over the last years.

Aplastic anemia associated with interferon alpha 2a in a patient with chronic hepatitis C virus infection: a case report.

INTRODUCTION: Hepatitis-associated aplastic anemia is a common syndrome in patients with bone marrow failure. However, hepatitis-associated aplastic anemia is an immune-mediated disease that does not appear to be caused by any of the known hepatitis viruses including hepatitis C virus. In addition, to the best of our knowledge there are no reported cases of patients with chronic hepatitis C virus infection developing aplastic anemia associated with pegylated interferon alpha 2a treatment. CASE PRESENTATION: We report the case of a 46-year-old Greek man who developed severe aplastic anemia during treatment with pegylated interferon alpha 2a for chronic hepatitis C virus infection. He presented with generalized purpura and bruising, as well as pallor of the skin and mucous membranes. His blood tests showed pancytopenia. He underwent allogeneic bone marrow transplantation after completing two courses of immunosuppressive therapy with antithymocyte globulin and cyclosporin A. CONCLUSIONS: The combination of a specific environmental precipitant represented by the hepatitis C virus infection, an altered metabolic detoxification pathway due to treatment with pegylated interferon alpha 2a and a facilitating genetic background such as polymorphism in metabolic detoxification pathways and specific human leukocyte antigen genes possibly conspired synergistically in the development of aplastic anemia in this patient. Our case clearly shows that the causative role of pegylated interferon alpha 2a in the development of aplastic anemia must not be ignored.

Tricyclo-[3.3.1.0]nonane-3,7-diyl bis-(methane-sulfonate).

The crystal structure of the title compound, C(11)H(18)O(6)S(2), was determined to investigate the effect of the eclipsed mesyl groups on the bond length of the vicinal quaternary C atoms. The two quaternary C atoms of the noradamantane skeleton and the two O atoms to which they are connected all located essentially in the same plane [maximum deviation 0.01 Å], resulting in an eclipsing conformation of the C-O bonds. The C-C bond of the quaternary C atoms is 1.597 (3) Šis considerably longer than the other C-C bonds of the mol-ecule.

Cryptogenic organizing pneumonia associated with primary Sjogren's syndrome.

The association of cryptogenic organizing pneumonia (COP) with primary Sjogren's syndrome (PSS) is extremely rare. We report a case of simultaneous diagnosis of PSS and COP. A 70-year-old female presented with fever, non-productive cough and dyspnea of 2 months' duration. She had experienced sicca symptoms for the past 2 years. The chest radiograph revealed a right lower lobe infiltrate, which was unresponsive to antibiotics. Bronchoscopy, bronchoalveolar lavage and an open lung biopsy established the diagnosis of COP, while a lip biopsy was consistent with PSS. The patient improved on steroids. Organizing pneumonia may be one of the early manifestations of PSS. Exclusion of PSS should be part of a thorough evaluation of the patient with COP.