Correction to: An in vitro and in vivo study of the combination of the heat shock protein inhibitor 17-allylamino-17-demethoxygeldanamycin and carboplatin in human ovarian cancer models

The corresponding author of this article has informed us of concerns about the immunoblots in Fig. 2 which were carried out in the collaborating laboratory of Professor Ann Jackman.

https://ift.tt/2otm1d9

The relationship between quality of life, cognition, and thyroid status in Graves’ disease

Summary

Purpose

To assess quality of life (QoL) and cognitive function among Graves' disease (GD) patients with different thyroid status, with and without ophthalmopathy.

Methods

This is a cross-sectional clinic-based study involving 154 patients with GD (81.27% were female, mean age 45.6 ± SD 11.2 years) and 54 (35.06%) had ophthalmopathy. Data were collected after an informed consent from all patients was obtained. All patients completed the 36-Item Short Form Health Survey and Mini-Mental State Examination. Patients with ophthalmopathy also completed the Graves' Orbitopathy Quality of Life Questionnaire.

Results

Patients with hyperthyroidism presented a greater impairment in QoL when compared to euthyroidism group. A lower score in physical role functioning was found in both subgroups with active disease (hyperthyroidism and euthyroidism using thionamides). A lower score was also seen in visual function, only in patients with hyperthyroidism, without difference in appearance. No difference was found in cognition between patients. Younger ages at diagnosis, male sex, euthyroidism and absence of ophthalmopathy were factors associated with better QoL, as well as a shorter disease duration was associated with better recall, attention and calculation.

Conclusions

An impairment in QoL among patients with active GD was evidenced, even in those receiving thionamides and in euthyroidism. Ophthalmopathy was a factor associated with a poor QoL and no clear evidence of cognitive impairment was demonstrated.

https://ift.tt/2PoQPqO

The relationship between quality of life, cognition, and thyroid status in Graves’ disease

Summary

Purpose

To assess quality of life (QoL) and cognitive function among Graves' disease (GD) patients with different thyroid status, with and without ophthalmopathy.

Methods

This is a cross-sectional clinic-based study involving 154 patients with GD (81.27% were female, mean age 45.6 ± SD 11.2 years) and 54 (35.06%) had ophthalmopathy. Data were collected after an informed consent from all patients was obtained. All patients completed the 36-Item Short Form Health Survey and Mini-Mental State Examination. Patients with ophthalmopathy also completed the Graves' Orbitopathy Quality of Life Questionnaire.

Results

Patients with hyperthyroidism presented a greater impairment in QoL when compared to euthyroidism group. A lower score in physical role functioning was found in both subgroups with active disease (hyperthyroidism and euthyroidism using thionamides). A lower score was also seen in visual function, only in patients with hyperthyroidism, without difference in appearance. No difference was found in cognition between patients. Younger ages at diagnosis, male sex, euthyroidism and absence of ophthalmopathy were factors associated with better QoL, as well as a shorter disease duration was associated with better recall, attention and calculation.

Conclusions

An impairment in QoL among patients with active GD was evidenced, even in those receiving thionamides and in euthyroidism. Ophthalmopathy was a factor associated with a poor QoL and no clear evidence of cognitive impairment was demonstrated.

https://ift.tt/2PoQPqO

Rhoton's Atlas of Head, Neck, and Brain

No abstract available

https://ift.tt/2LLNNef

Prospective comparison of 68 Ga-PSMA PET/CT, 18 F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer

Abstract

Purpose

To prospectively compare diagnostic accuracies for detection of bone metastases by ⁶⁸Ga-PSMA PET/CT, ¹⁸F-NaF PET/CT and diffusion-weighted MRI (DW₆₀₀-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR).

Methods

Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent ⁶⁸Ga-PSMA PET/CT, a ¹⁸F-NaF PET/CT and a DW₆₀₀-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm²). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic.

Results

Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98–1.00 and 0.89–0.90 for ⁶⁸Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90–0.98 and 0.90–0.94 for ¹⁸NaF PET/CT (n = 67 patients); and 0.25–0.38, 0.87–0.92 and 0.59–0.62 for DW₆₀₀-MRI (n = 60 patients). The diagnostic performance of DW₆₀₀-MRI was significantly lower than that of ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT (p = 0.65).

Conclusion

⁶⁸Ga-PSMA PET/CT and ¹⁸F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW₆₀₀-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

https://ift.tt/2LK1zOs

Trifunctional PSMA-targeting constructs for prostate cancer with unprecedented localization to LNCaP tumors

Abstract

Purpose

Treatment of late-stage prostate cancer by targeted radiotherapeutics such as ¹³¹I-MIP-1095 and ¹⁷⁷Lu-PSMA-617 has shown encouraging early results. Lu-177 is preferred to I-131 in clinical settings, but targeted radioligand therapy (RLT) with ¹⁷⁷Lu-PSMA-617 has not reached its full potential due to insufficient dose delivery to the tumor. We recently developed a dual-targeting radioiodinated ligand, RPS-027, that targets PSMA and uses albumin binding to enable good tumor uptake and significantly reduced kidney uptake in a preclinical model. Further development of this ligand is limited by the inability to independently modify PSMA and albumin binding and the requirement of I-131 for therapeutic application. We therefore sought to devise a new class of trifunctional ligands for RLT with (1) a high-affinity PSMA-binding domain, (2) an albumin-binding group (ABG), and (3) a chelator for radiometals such as ⁶⁸Ga³⁺, ¹⁷⁷Lu³⁺ and ²²⁵Ac³⁺.

Methods

Ligands incorporating a triazolylphenylurea-containing PSMA-targeting group, an N^ε-(2-(4-iodophenyl)acetyl)lysine ABG and the bifunctional chelator p-SCN-Bn-DOTA linked by a PEG-containing polymer containing 0,3,4,6,8 or 12 repeats were prepared. PSMA affinity was determined in LNCaP cells and uptake and tissue distribution was studied in mice bearing LNCaP tumor xenografts and compared to ¹⁷⁷Lu-PSMA-617. Imaging studies were performed up to 24 h post-injection (p.i.) using ⁶⁶Ga³⁺ and biodistribution studies at 4 h, 24 h and 96 h p.i. with ¹⁷⁷Lu³⁺.

Results

PSMA affinity was high (IC₅₀ = 1–10 nM) and inversely proportional to the linker length. Tumor uptake correlated with binding affinity and was significantly greater than for ¹⁷⁷Lu-PSMA-617 over 96 h. The highest uptake was achieved with ¹⁷⁷Lu-RPS-063 (30.0 ± 6.9 %ID/g; 4 h p.i.). Kidney uptake was generally high, with the exception of the lowest affinity ligand ¹⁷⁷Lu-RPS-067. Each of the compounds showed slower blood clearance than ¹⁷⁷Lu-PSMA-617, with clearance proportional to linker length.

Conclusions

The high tumor uptake achieved with these trifunctional ligands predicts larger (up to 4×) doses delivered to the tumor than can be achieved with ¹⁷⁷Lu-PSMA-617. Although PSMA-mediated kidney uptake was also observed, the exceptional area under the curve (AUC) in the tumor warrants further investigation of these novel ligands as candidates for RLT.

https://ift.tt/2wEAsjl

A rare presentation of skull-base osteomyelitis with neurovascular sheath extension following external otitis resolved by PET/MRI

https://ift.tt/2LOKJxQ