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In our quest to develop new drug delivery systems, we designed and synthesized PEG-conjugates and PEG-hydrogels with a degradable linkage to the drug. Specifically, methoxyPEG-doxorubicin (MPEG-CH=N-Doxo) and doxorubicin-PEG aldehyde (OHC-PEG-CH=N-Doxo) conjugates, plus poly (vinyl amine)-PEG-doxorubicin (PVAm-PEG-Doxo) hydrogels were prepared. The hydrogels were crosslinked by PEG-Schiff base linkages, and the Doxo was conjugated to the gel by pendant Schiff base bonds (PVAm-N=CH-PEG-CH=N-Doxo). The release profile of Doxo from the hydrogels was dependent on pH and on the ratio of PVAm to the PEG-dialdehyde crosslinker. These degradable PEG hydrogels could be good candidates for slow release of Doxo from subcutaneous or IM implants.

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Object:This study aimed to clarify the outcomes of stereotactic body radiotherapy for spinal metastases with a uniform dose fractionation schedule in our institution.Materials and Methods:Patients treated with spine stereotactic body radiotherapy were retrospectively reviewed. The prescribed dose was 24 Gy in 2 fractions. End points were local control, pain control, and adverse events. Local control was defined as elimination, shrinkage, or stable disease in the tumor on imaging evaluations. Pain status was measured on a scale of 0 to 10 by patients’ self-reports, and pain response was defined as the time at which pain scale score decreased by 2 or more from the baseline score without increase in analgesics. In addition, various treatment- and tumor-specific factors were evaluated to determine predictive values for local and pain control.Results:This study included 134 lesions in 131 patients, with: lesion histopathology, lung/colorectal/thyroid/renal/breast/prostate/sarcoma/other cancer, 24/22/18/14/12/10/6/25; reirradiation stereotactic body radiotherapy, 82 (61.2%) cases; and postoperative stereotactic body radiotherapy for epidural spinal cord compression, 45 (33.6%) cases. Median follow-up after stereotactic body radiotherapy was 9 months. The 1-year local control rate was 72.3%. Seventy (79.5%) of the 88 cases with pain from spinal metastases achieved pain response. The 1-year pain progression-free rate was 61.7%. Regarding metastases from colorectal cancer, local and pain control rates at 1 year were significantly lower compared with other cancer types (local control rate, 34.1% vs 81.8%; P < .01; pain progression-free rate, 36.9% vs 69.9%; P = .02). On multivariate analysis, colorectal cancer metastases and radiation history were identified as independent predictors of lower local and pain control rates. Radiation-induced myelopathy, radiculopathy, and vertebral compression fractures were observed in 0, 2 (1.5%), and 16 (11.9%) cases, respectively.Conclusions:This study showed that spine stereotactic body radiotherapy achieved good local and pain control, with a clinically acceptable safety profile. However, stereotactic body radiotherapy may be less effective against spinal metastases from colorectal cancer.

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Background The clinical role of sputum Gram stain (SGS) in community-acquired pneumonia (CAP) diagnosis remains controversial. A 1996 meta-analysis of the diagnostic accuracy of SGS reported heterogeneous results. To update the available evidence, we performed a systematic review and a Bayesian standard and latent-class model meta-analysis. Methods We searched Medline, Embase, and Cochrane Central by 23 August 2018 to identify studies reporting on the diagnostic accuracy, yield (percentage of patients with any pathogen[s] correctly identified by SGS), and clinical outcomes of SGS in adult patients with CAP. Two reviewers extracted the data. We quantitatively synthesized the diagnostic accuracy and yield, and descriptively analyzed other outcomes. Results Twenty-four studies with 4533 patients were included. The methodological and reporting quality of the included studies was limited. When good-quality sputum specimens were selected, SGS had a summary sensitivity of 0.69 (95% credible interval [CrI], .56–.80) and specificity of 0.91 (CrI, .83–.96) for detecting Streptococcus pneumoniae, and a sensitivity of 0.76 (CrI, .60–.87) and specificity of 0.97 (CrI, .91–.99) for Haemophilus influenzae. Adjusted analyses accounting for imperfect reference standards provided higher-specificity estimates than the unadjusted analyses. Bacterial pathogens were identified in 73% (CrI, 26%–96%) of good-quality specimens, and 36% (CrI, 22%–53%) of all specimens regardless of quality. Evidence on other bacteria was sparse. Conclusions SGS was highly specific to diagnose S. pneumoniae and H. influenzae infections in patients with CAP. With good-quality specimens, SGS can provide clinically actionable information for pathogen-directed antibiotic therapies.

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