The relationship between dietary inflammatory potential and cancer outcomes among cancer survivors: A systematic review and meta-analysis of cohort studies.

Cancer remains the second leading cause of death globally. Chronic inflammatory environments promote the growth of tumors, and the intake of certain food items can increase systemic inflammation. This study examined the relationship between the inflammatory potential of diet, measured by the Dietary Inflammatory Index (DII), and recurrence, all-cause, and cancer-specific mortality among cancer survivors. Web of Science, Medline, CINHAL, and PsycINFO databases were searched in April 2022. Two independent reviewers screened all searches. Of the 1,443 studies, 13 studies involving 14,920 cancer survivors passed all the screening stages. Three studies reported cancer recurrence, 12 reported all-cause mortality, and six reported cancer-specific mortality. Seven studies calculated DII from pre-diagnosis diets, five from post-diagnosis diets, and one from both pre-and post-diagnosis diets. A random-effects model meta-analysis showed that high DII was not associated with an increased risk of recurrence (HR = 1.09, 95 % CI = 0.77, 1.54, n = 4) and all-cause (HR = 1.08, 95 % CI = 0.99, 1.19, n = 14) and cancer-specific mortality (H = 1.07, 95 % CI = 0.92, 1.25, n = 6). Analysis by the timing of dietary assessment showed that only post-diagnosis DII was associated with an increased risk of all-cause mortality (HR = 1.34, 95 % CI = 1.05, 1.72, n = 6) by 34 %; however, cancer type did not modify these associations. The quality of the study assessed using the Newcastle Ottawa Scale indicated all but one studies were good. The risk of all-cause mortality among cancer survivors could be reduced by consuming more anti-inflammatory diets after cancer diagnosis.

Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.

BACKGROUND/AIMS: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung. METHODS: For this purpose, Y733F-AAV8-PEDF (1010 viral genome) was administered intratracheally to C57BL/6 mice. Lung mechanics, morphometry, and inflammation were evaluated 7, 14, 21, and 28 days after injection. RESULTS: The tyrosine-mutant AAV8 vector was efficient at penetrating mucus in ex vivo assays and at transferring the gene to lung cells after in vivo instillation. Increased levels of transgene mRNA were observed 28 days after vector administration. Overexpression of PEDF did not affect in vivo lung parameters. CONCLUSION: These findings provide a basis for further development of Y733F-AAV8-based gene therapies for safe and effective delivery of PEDF, which has anti-angiogenic, anti-inflammatory and anti-fibrotic activities and might be a promising therapy for lung inflammatory disorders.

Oocyte Cryopreservation for Medical and Planned Indications: A Practical Guide and Overview.

Oocyte cryopreservation (OC) is the process in which ovarian follicles are stimulated, the follicular fluid is retrieved, and mature oocytes are isolated and vitrified. Since the first successful pregnancy utilizing previously cryopreserved oocytes in 1986, OC has become increasingly utilized as an option for future biologic children in patients facing gonadotoxic therapies, such as for the treatment of cancer. Planned OC, also termed elective OC, is growing in popularity as a means to circumvent age-related fertility decline. In this narrative review, we describe both medically indicated and planned OC, focusing on the physiology of ovarian follicular loss, OC technique and risks, timing of when OC should be performed, associated financial considerations, and outcomes.

Healthy Eating and Mortality among Breast Cancer Survivors: A Systematic Review and Meta-Analysis of Cohort Studies.

This systematic review examined the effect of diet quality, defined as adherence to healthy dietary recommendations, on all-cause and breast cancer-specific mortality. Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by May 2021. We used a random-effects model meta-analysis in two different approaches to estimate pooled hazard ratio (HR) and 95% confidence interval (CI) for highest and lowest categories of diet quality: (1) each dietary quality index as the unit of analysis and (2) cohort as the unit of analysis. Heterogeneity was examined using Cochran's Q test and inconsistency I2 statistics. The risk of bias was assessed by the Newcastle-Ottawa Scale for cohort studies, and the quality of evidence was investigated by the GRADE tool. The analysis included 11 publications from eight cohorts, including data from 27,346 survivors and seven dietary indices. Both approaches yielded a similar effect size, but cohort-based analysis had a wider CI. Pre-diagnosis diet quality was not associated with both outcomes. However, better post-diagnosis diet quality significantly reduced all-cause mortality by 21% (HR = 0.79, 95% CI = 0.70, 0.89, I2 = 16.83%, n = 7) and marginally reduced breast cancer-specific mortality by 15% (HR = 0.85, 95% CI = 0.62, 1.18, I2 = 57.4%, n = 7). Subgroup analysis showed that adhering to the Diet Approaches to Stop Hypertension and Chinese Food Pagoda guidelines could reduce breast cancer-specific mortality. Such reduction could be larger for older people, physically fit individuals, and women with estrogen receptor-positive, progesterone receptor-negative, or human epidermal growth factor receptor 2-positive tumors. The risk of bias in the selected studies was low, and the quality of evidence for the identified associations was low or very low due to imprecision of effect estimation, inconsistent results, and publication bias. More research is needed to precisely estimate the effect of diet quality on mortality. Healthcare providers can encourage breast cancer survivors to comply with healthy dietary recommendations to improve overall health. (Funding: University of Central Florida Office of Undergraduate Research, Registration: PROSPERO-CRD42021260135).

Inhaled gene therapy of preclinical muco-obstructive lung diseases by nanoparticles capable of breaching the airway mucus barrier.

INTRODUCTION: Inhaled gene therapy of muco-obstructive lung diseases requires a strategy to achieve therapeutically relevant gene transfer to airway epithelium covered by particularly dehydrated and condensed mucus gel layer. Here, we introduce a synthetic DNA-loaded mucus-penetrating particle (DNA-MPP) capable of providing safe, widespread and robust transgene expression in in vivo and in vitro models of muco-obstructive lung diseases. METHODS: We investigated the ability of DNA-MPP to mediate reporter and/or therapeutic transgene expression in lung airways of a transgenic mouse model of muco-obstructive lung diseases (ie, Scnn1b-Tg) and in air-liquid interface cultures of primary human bronchial epithelial cells harvested from an individual with cystic fibrosis. A plasmid designed to silence epithelial sodium channel (ENaC) hyperactivity, which causes airway surface dehydration and mucus stasis, was intratracheally administered via DNA-MPP to evaluate therapeutic effects in vivo with or without pretreatment with hypertonic saline, a clinically used mucus-rehydrating agent. RESULTS: DNA-MPP exhibited marked greater reporter transgene expression compared with a mucus-impermeable formulation in in vivo and in vitro models of muco-obstructive lung diseases. DNA-MPP carrying ENaC-silencing plasmids provided efficient downregulation of ENaC and reduction of mucus burden in the lungs of Scnn1b-Tg mice, and synergistic impacts on both gene transfer efficacy and therapeutic effects were achieved when DNA-MPP was adjuvanted with hypertonic saline. DISCUSSION: DNA-MPP constitutes one of the rare gene delivery systems providing therapeutically meaningful gene transfer efficacy in highly relevant in vivo and in vitro models of muco-obstructive lung diseases due to its unique ability to efficiently penetrate airway mucus.

Bilateral Myelomatous Pleural Effusion in a Patient with IgA Kappa Multiple Myeloma.

Multiple myelomas is a neoplastic plasma cell disorder that accounts for one percent of all cancers and 13% of hematologic malignancies. Although primarily known to be a bone marrow disorder, it can metastasize to extramedullary sites or it can present as a solitary extramedullary plasmacytoma. Primary pleural effusion from myeloma is rare, occurring in less than one percent of the patients. The following case report highlights a case of bilateral pleural effusion, directly attributable to multiple myeloma after other causes were ruled out. The diagnosis was made using cytology and immunohistochemical (IHC) staining of the pleural fluid. Myelomatous pleural effusion (MPE) is a poor prognostic feature heralding an aggressive underlying disease state, as represented in this case.

Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) relies mainly on histopathological imaging examinations after surgical removal of the tumor. However, the rate of tumor recurrence is still high. Defining molecular signatures comprised of a number of distinct peptide ions specific for various tumor regions may improve the classification and prognosis of HCC patients. METHODS: MALDI imaging technology, cluster analysis and classification software were applied to investigate patients with hepatitis B virus (HBV)-related HCC to obtain differences in protein abundance and distribution from non-tumor to tumor regions. RESULTS: A number of mass spectra obtained from non-tumor and HCC tumor sections were readily distinguishable. Progressive change was found in a distance-dependent manner from non-tumor to tumor regions within the junction section of HCC. Fourteen of the peaks were determined from non-tumor and tumor sections as classifiers to classify various non-tumor and tumor regions of the junction section of HCC. The performance of the classification test for the tumor region with a coefficient of variation (CV) of 0.16 was better than the non-tumor region, which reached a CV of 0.53. CONCLUSIONS: Our findings provide peptide information pertaining to the classification of various tumor regions to supplement current histopathological analysis in tumor margins.

Stability of estrogen receptor status in breast carcinoma: a comparison between primary and metastatic tumors with regard to disease course and intervening systemic therapy.

BACKGROUND: The purposes of this study were to address a persistent controversy as to whether the ER status of a primary tumor remains stable during progression to metastasis and to evaluate the influence of disease course and prior systemic therapy on ER status. METHODS: Breast carcinomas from 227 women with known ER status in both primary tumor and paired metastasis were retrospectively reviewed. ER status was compared between primary and metastatic tumors with respect to metastatic site, interval between two ER assays, and intervening chemotherapy and endocrine therapy. Semiquantitative comparison of ER values was performed for 92 tumor pairs. RESULTS: ER status agreed in 210 (92.5%) patients, including 147 positive and 63 negative. Of the 17 patients (7.5%) with discordant ER status, both negative to positive conversion (n = 7) and positive to negative conversion (n = 10) were observed. ER discordance was not significantly associated with metastatic site (locoregional vs distant), time interval between assays (< 5 years vs. ≥ 5 years), or intervening chemotherapy and endocrine therapy. Semiquantitative levels of ER expression were similar between primary and metastatic tumors. In discordant cases, variations in testing methods and marginal scores were common. CONCLUSIONS: ER status in breast carcinoma is generally stable during progression to metastasis. Preanalytical and analytical variability may contribute to discordance in some cases. Given the importance of ER status for clinical management, ER testing in metastatic breast carcinoma should be repeated, especially for patients whose clinical courses are not compatible with stated ER status.

3D sensitivity encoded ellipsoidal MR spectroscopic imaging of gliomas at 3T.

PURPOSE: The goal of this study was to implement time efficient data acquisition and reconstruction methods for 3D magnetic resonance spectroscopic imaging (MRSI) of gliomas at a field strength of 3T using parallel imaging techniques. METHODS: The point spread functions, signal to noise ratio (SNR), spatial resolution, metabolite intensity distributions and Cho:NAA ratio of 3D ellipsoidal, 3D sensitivity encoding (SENSE) and 3D combined ellipsoidal and SENSE (e-SENSE) k-space sampling schemes were compared with conventional k-space data acquisition methods. RESULTS: The 3D SENSE and e-SENSE methods resulted in similar spectral patterns as the conventional MRSI methods. The Cho:NAA ratios were highly correlated (P<.05 for SENSE and P<.001 for e-SENSE) with the ellipsoidal method and all methods exhibited significantly different spectral patterns in tumor regions compared to normal appearing white matter. The geometry factors ranged between 1.2 and 1.3 for both the SENSE and e-SENSE spectra. When corrected for these factors and for differences in data acquisition times, the empirical SNRs were similar to values expected based upon theoretical grounds. The effective spatial resolution of the SENSE spectra was estimated to be same as the corresponding fully sampled k-space data, while the spectra acquired with ellipsoidal and e-SENSE k-space samplings were estimated to have a 2.36-2.47-fold loss in spatial resolution due to the differences in their point spread functions. CONCLUSION: The 3D SENSE method retained the same spatial resolution as full k-space sampling but with a 4-fold reduction in scan time and an acquisition time of 9.28 min. The 3D e-SENSE method had a similar spatial resolution as the corresponding ellipsoidal sampling with a scan time of 4:36 min. Both parallel imaging methods provided clinically interpretable spectra with volumetric coverage and adequate SNR for evaluating Cho, Cr and NAA.

Feasibility of dynamic susceptibility contrast perfusion MR imaging at 3T using a standard quadrature head coil and eight-channel phased-array coil with and without SENSE reconstruction.

PURPOSE: To investigate changes in image and dynamic signal-to-noise ratios (SNRs) of the DeltaR2* curve, as well as magnetic susceptibility-induced artifacts between a standard quadrature head coil and an eight-channel phased-array coil with and without sensitivity-encoding (SENSE) at 3T, compared to the current clinical standard head coil acquisition at 1.5T. MATERIALS AND METHODS: Dynamic susceptibility contrast (DSC) perfusion MRI was performed on 80 brain tumor patients using a gradient-echo, echo-planar imaging (EPI) sequence. Image and dynamic SNR were compared between 1.5T and 3T field strengths, a quadrature and eight-channel phased-array coil, and a conventional vs. partially parallel EPI acquisition with SENSE reconstruction. The amount of geometric distortion and signal dropout was quantified and compared between conventional and SENSE EPI acquisitions within the same exam at 3T. RESULTS: An initial 2.6-fold elevation in dynamic SNR was observed in normal-appearing white matter when doubling the field strength (P < 0.001), with an additional 1.7-fold increase found when employing an eight-channel phased-array coil (P < 0.002). Compared to the standard 3T eight-channel coil acquisition, the implementation of SENSE reduced the number of voxels experiencing large anterior shifts in the phase-encode direction, lowered the volume of signal dropout by 2.0-11.5%, and allowed a 1.4-fold increase in slice coverage, while only decreasing the dynamic SNR by 22%. CONCLUSION: SENSE EPI at 3T yielded a significant improvement in dynamic SNR over the 1.5T acquisitions. A significant reduction in magnetic susceptibility-induced artifacts was achieved with SENSE EPI compared to the standard EPI eight-channel coil acquisition at 3T.

Quantitative apparent diffusion coefficients and T2 relaxation times in characterizing contrast enhancing brain tumors and regions of peritumoral edema.

PURPOSE: To investigate the potential value and relationship of in vivo quantification of apparent diffusion coefficients (ADCs) and T2 relaxation times for characterizing brain tumor cellularity and tumor-related edema. MATERIALS AND METHODS: A total of 26 patients with newly diagnosed gliomas, meningiomas, or metastases underwent diffusion-weighted and six-echo multisection T2-preparation imaging. Regions of interest (ROIs) were drawn on conventional MR images to include tumor (as defined by contrast agent enhancement) and immediate and peripheral edema. Areas of necrosis were excluded. Median values of ADCs and T2 in the ROIs were calculated. RESULTS: ADCs for gliomas were similar to those for meningiomas or metastases in all regions. Tumor T2 values for gliomas (159.5+/-30.6 msec) were significantly higher than those for meningiomas or metastases (125.0+/-31.1 msec; P=0.005). Immediate-edema T2 values for meningiomas or metastases (226.0+/-44.1 msec) were significantly higher than those for gliomas (203.5+/-32.8 msec; P=0.033). Peripheral-edema T2 values for gliomas (219.5+/-41.9 msec) were similar to those for meningiomas or metastases (202.5+/-26.5 msec; P=0.377). Both immediate- and peritumoral-edema ADCs and T2 values were significantly higher than those in tumor for both tumor types. ADCs and T2 values from all regions correlated significantly for gliomas (r=0.95; P<0.0001) and for meningiomas or metastases (r=0.81; P<0.0001). CONCLUSION: The higher immediate-edema T2 values for nonglial tumors than for gliomas suggest tumor-related edema (vasogenic vs. infiltrated) can be further characterized by using T2 values. There were significant correlations between ADC and T2 values.

Musculoskeletal MRI at 3.0 T: relaxation times and image contrast.

OBJECTIVE: The purpose of our study was to measure relaxation times in musculoskeletal tissues at 1.5 and 3.0 T to optimize musculoskeletal MRI methods at 3.0 T. MATERIALS AND METHODS: In the knees of five healthy volunteers, we measured the T1 and T2 relaxation times of cartilage, synovial fluid, muscle, marrow, and fat at 1.5 and 3.0 T. The T1 relaxation times were measured using a spiral Look-Locker sequence with eight samples along the T1 recovery curve. The T2 relaxation times were measured using a spiral T2 preparation sequence with six echoes. Accuracy and repeatability of the T1 and T2 measurement sequences were verified in phantoms. RESULTS: T1 relaxation times in cartilage, muscle, synovial fluid, marrow, and subcutaneous fat at 3.0 T were consistently higher than those measured at 1.5 T. Measured T2 relaxation times were reduced at 3.0 T compared with 1.5 T. Relaxation time measurements in vivo were verified using calculated and measured signal-to-noise results. Relaxation times were used to develop a high-resolution protocol for T2-weighted imaging of the knee at 3.0 T. CONCLUSION: MRI at 3.0 T can improve resolution and speed in musculoskeletal imaging; however, interactions between field strength and relaxation times need to be considered for optimal image contrast and signal-to-noise ratio. Scanning can be performed in shorter times at 3.0 T using single-average acquisitions. Efficient higher-resolution imaging at 3.0 T can be done by increasing the TR to account for increased T1 relaxation times and acquiring thinner slices than at 1.5 T.