Strontium-89 (89Sr) is currently used for the treatment of painful bone metastases. This study reports the use of low-dose carboplatin as a radiosensitizer in 89Sr radioisotope therapy. The study ...design comprised two groups: 15 patients treated with 89Sr (148 MBq) followed by carboplatin (100 mg m-2 at 7 and 21 days) and 15 patients treated with 89Sr alone. Their pain response was assessed 8 weeks post-injection. Follow-up was continued for up to 1 year in the survivors. Twenty-seven patients were evaluable. A pain response was observed in 20 of 27 (74%) patients. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). No clinically significant adverse effects or myelosuppression by carboplatin were observed. Low-dose carboplatin enhances the effects of 89Sr radioisotope therapy on pain from bone metastases.
Radioiodine has been in use for over
60
years
as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects ...and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic
I
131
administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate,
T
eff
and target mass. The dose was converted to normalized total dose delivered at
2
Gy
per fraction
(
NTD
2
)
. Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The
TD
50
and
m
parameters of the NTCP model approach were then estimated using the likelihood method. The
TD
50
, expressed as
NTD
2
, resulted in
60
Gy
(95% C.I.:
45
-
75
Gy
) and
96
Gy
(95% C.I.:
86
-
109
Gy
) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The
m
parameter for all patients was 0.27 (95% C.I.: 0.22-0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.
This work presents a Raman based approach for the rapid identification of the molecular conformation in a series of new 2,3-thienoimide capped quaterthiophenes, whose crystal structures were ...determined by synchrotron radiation X-ray powder diffraction. These systems display two conformational polymorphs, known as forms A and B, as a result of the anti-anti-anti and syn-anti-syn arrangements of the quaterthiophene cores. In a micro-Raman and computational study, the spectroscopic differences between the conformers were detected and proved to be suitable markers for polymorph identification. Thus, the synergic employment of diffraction and Raman spectroscopy techniques yields a full and reliable characterization of 2,3-thienoimide capped quaterthiophene compounds in their solid state.
This study evaluates the addition of octreotide and L-thyroxine to shorten the period of exposure to unduly elevated TSH levels in patients with differentiated thyroid carcinoma undergoing total body ...scan with 131I.
Fourteen thyroidectomized patients were studied after total body scan and the restarting of different doses of thyroxine. After one year a second total body scan and a schedule of the same dose of thyroxine combined with octreotide were performed in each subject.
Patients were divided into four groups according to the treatment: seven patients received initially 100 micrograms of L-thyroxine (Group 1) and after 1 year 100 micrograms of L-thyroxine plus 300 micrograms of octreotide/day (Group 3); the other seven received initially 150 micrograms of L-thyroxine (Group 2) and then 150 micrograms of L-thyroxine plus 300 micrograms of octreotide/day (Group 4).
Serum TSH, T3 and T4 were measured on the day of radioiodine administration (day 0) and after 14, 21, 30, 45, 60 and 90 days.
Mean basal TSH levels were elevated in all four groups ranging from 104 to 91 mU/I without significant differences. The patterns of TSH inhibition were however different in the four groups studied. TSH remained very elevated for a long time in Group 1 patients: at day 90 the TSH value was still 2.1 +/- 1.2 mU/I (mean +/- SEM). Patients in Groups 2 and 3 showed a similar pattern: TSH was suppressed in 45 days. The most rapid TSH inhibition was observed in Group 4 patients with a mean decrease of 88% in 14 days and complete suppression in 30 days.
TSH suppression by L-thyroxine is very slow and it can be significantly enhanced by combined octreotide administration. Combined therapy is safe and offers an alternative choice when high dosages of L-thyroxine are inappropriate or in conditions of advanced illness.
Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients.
To assess ...dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort.
Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI).
A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect.
Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background. Cardiotoxicity is the major limiting factor in anthracycline chemotherapy of advanced neoplastic disease. Epirubicin shows a more favorable therapeutic index than does doxorubicin, but it ...is still cardiotoxic. Limited data regarding epirubicin cardiotoxicity are available, and suggested guidelines for doxorubicin with left ventricular ejection fraction (LVEF) measurement may not be empirically useful for epirubicin therapy. This study evaluates the diagnostic role of antimyosin immunoscintigraphy for early identification of patients at risk for late pump dysfunction from cardiotoxicity induced by high-dose administration of epirubicin up to high cumulative dosages.
Methods and Results. Chemotherapy with epirubicin was administered to 36 patients with cancer at a dosing rate of 160 mg/m
2 as a bolus injection every 21 days to a cumulative dosage of 960 mg/m
2. Radionuclide angiography (LVEF) and antimyosin immunoscintigraphy with heart-lung ratio (HLR) measurements were performed before chemotherapy, at intermediate cumulative epirubicin dosages, at the end of treatment, and during the follow-up. LVEF decreased significantly at the end of the treatment and after therapy discontinuation. HLR values were significantly increased at intermediate epirubicin dosage levels and continued to increase to the end of the treatment but thereafter remained substantially unmodified for 3 to 6 months after therapy discontinuation. A value of HLR >1.85 at intermediate epirubicin dosage level showed a sensitivity of 95% and a specificity of 57% as a predictor of late LVEF impairment.
Conclusions. LVEF appears more useful at high cumulative dosages and during follow-up to monitor late pump dysfunction, whereas HLR may be effective during the early phase of the therapy in determining which patients are at risk for development of late cardiac dysfunction.
Objective
To compare the impact of immediate and delayed introduction of anti–tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)–treated patients with early ...rheumatoid arthritis (RA).
Methods
Twenty‐four patients with erosive early RA (duration <3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high‐frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system.
Results
From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between‐group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076).
Conclusion
The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.
Background: The pathology of neuromyelitis optica (NMO), in contrast to multiple sclerosis, comprises granulocyte infiltrates along extensive lengths of spinal cord, as well as optic nerve. ...Furthermore, IFN-β treatment worsens NMO. We recently found that experimental autoimmune encephalomyelitis (EAE) induced with Th17 cells is exacerbated by IFN-β, in contrast to disease induced with Th1 where treatment attenuated symptoms.
Objective: This study demonstrates the similarities between NMO and Th17 EAE and how neutrophils mediate pathology in Th17 disease.
Methods: Levels of blood biomarkers in NMO were assessed by Luminex and ELISA. Effects of IFN-β on neutrophils were assessed by culture assays and immunofluorescence. EAE was induced by transfer of myelin-specific Th1 or Th17 cells and treated with Sivelestat sodium hydrate, a neutrophil elastase inhibitor.
Results: We show Th17 cytokines, granulocyte chemokines, type 1 interferon and neutrophil elastase are elevated in patients with definitive NMO. In culture, we find that IFN-β stimulates neutrophils to release neutrophil elastase. In Th17 EAE, we demonstrate neutrophilic infiltration in the optic nerve and spinal cord which was not present in Th1 EAE. Blockade of neutrophil elastase with Sivelestat had efficacy in Th17 EAE but not Th1 EAE.
Conclusions: The similarities between Th17 EAE and NMO indicate that this model represents several aspects of NMO. Neutrophils are critical in the pathologies of both Th17-EAE and NMO, and therefore blockade of neutrophil elastase is a promising target in treating NMO.
Superselective transcatheter arterial radioembolization with radioiodinated lipiodol and gelatin sponges was evaluated in 11 patients with nodular hepatocellular carcinoma. Thirteen tumor nodules ...were treated using 3-5 ml of lipiodol labeled with 259 to 2220 MBq of I-131 followed by gelatin sponge with the following results1) there was elevated uptake in 12 tumor nodules with high tumor-to-background ratios; 2) there was excellent clinical tolerance to the treatment (stable cirrhosis in 5 patients and cirrhosis progression in 2 cases); 3) there was good disease control with size reduction in five tumor lesions (41%) and no increase in seven lesions (59%) followed for 2 years; 4) there was a 2-year survival rate of 70%; and 5) three deaths due to hepatic failure at 2, 3, and 20 months after therapy. Superselective arterial radioembolization with I-131 lipiodol is a useful palliative approach to inoperable hepatocarcinoma, providing long-term local control without severe complications in the progression of cirrhosis.
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