Genome-wide CRISPR screening identifies tyrosylprotein sulfotransferase-2 as a target for augmenting anti-PD1 efficacy.

BACKGROUND: Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored. METHODS: To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells. The responsiveness of cancer cells to interferon-γ (IFNγ) was estimated by evaluating IFNγ-mediated induction of target genes, STAT1 phosphorylation, HLA expression, and cell growth suppression. The sulfotyrosine-modified target gene of TPST2 was identified by co-immunoprecipitation and mass spectrometry. The in vivo effects of TPST2 inhibition were evaluated using mouse syngeneic tumor models and corroborated by bulk and single-cell RNA sequencing analyses. RESULTS: Through in vivo genome-wide CRISPR screening, TPST2 loss-of-function emerged as a potential enhancer of anti-PD1 treatment efficacy. TPST2 suppressed IFNγ signaling by sulfating IFNγ receptor 1 at Y397 residue, while its downregulation boosted IFNγ-mediated signaling and antigen presentation. Depletion of TPST2 in cancer cells augmented anti-PD1 antibody efficacy in syngeneic mouse tumor models by enhancing tumor-infiltrating lymphocytes. RNA sequencing data revealed TPST2's inverse correlation with antigen presentation, and increased TPST2 expression is associated with poor prognosis and altered cancer immunity across cancer types. CONCLUSIONS: We propose TPST2's novel role as a suppressor of cancer immunity and advocate for its consideration as a therapeutic target in ICT-based treatments.

Protective Effect of Memantine on Cisplatin-Induced Ototoxicity: An in Vitro Study.

HYPOTHESIS: Memantine, an N-methyl-d-aspartate receptor antagonist, is widely used to treat Alzheimer's disease and has been found to have potential neuroprotective effects. In this study, we evaluated the protective effects of memantine against cisplatin-induced ototoxicity. BACKGROUND: Cisplatin is a widely used anticancer drug for various cancers; however, its use is limited by its side effects, including ototoxicity. Several drugs have been developed to reduce cisplatin toxicity. In this study, we treated cisplatin-damaged cochlear hair cells with memantine and evaluated its protective effects. METHOD: House Ear Institute Organ of Corti 1 (HEI-OC1) cells and cochlear explants were treated with cisplatin or memantine. Cell viability, apoptotic patterns, reactive oxygen species (ROS) production, Bcl-2/caspase-3 activity, and cell numbers were measured to evaluate the anti-apoptotic and antioxidative effects of memantine. RESULT: Memantine treatment significantly improved cell viability and reduced cisplatin-induced apoptosis in auditory cells. Bcl-2/caspase-3 activity was also significantly increased, suggesting anti-apoptotic effects against cisplatin-induced ototoxicity. CONCLUSION: Our results suggest that memantine protects against cisplatin-induced ototoxicity in vitro, providing a potential new strategy for preventing hearing loss in patients undergoing cisplatin chemotherapy.

Prognosis of Poorly Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Background: Poorly differentiated thyroid carcinoma (PDTC) accounts for a small portion of thyroid carcinomas but contributes to a significant proportion of thyroid carcinoma-associated deaths. The clinicopathological prognostic factors and clinical outcomes of PDTC remain unclear. We aimed to evaluate the clinical outcomes of patients with PDTC after curative treatment. Methods: A comprehensive search was performed up to September 2023. We included studies investigating treatment outcomes in patients with PDTC who underwent initial surgery. The 5-year disease-free survival (DFS) and overall survival (OS) were extracted. In this meta-analysis, the enrolled PDTC histological criteria included 3rd, 4th, and 5th World Health Organization (WHO) and Memorial Sloan Kettering Cancer Center (MSKCC) classification. A random-effects model was used for the pooled proportion analysis. Meta-regression analysis was conducted to evaluate the prognostic factors. Results: Twenty retrospective studies published between 2007 and 2023, including 1,294 patients, met all inclusion criteria. Studies that diagnosed PDTC based on various histological criteria including 3rd WHO (n=5), 4th WHO (n=12), 5th WHO (n=2), and MSKCC (n=1) were included. Overall, 5-year DFS and 5-year OS were 49.4% (95% confidence interval [CI], 42.3 to 56.4) and 73.8% (95% CI, 66.5 to 79.9), with moderate heterogeneity of 58% and 55%, respectively. In meta-regression analysis, extrathyroidal extension (ETE) was a prognostic factor for OS. Conclusion: The meta-analysis of DFS and OS in patients with PDTC show the moderate heterogeneity with a variety of histological criteria. ETE appears to have a significant impact on OS, regardless of histological criteria.

Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. METHODS: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. RESULTS: A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3 years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3 years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. CONCLUSIONS: Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3 years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.

Predicting postoperative lung function using ventilation SPECT/CT in patients with lung cancer.

Background: Single-photon emission computed tomography/computed tomography (SPECT/CT) has the advantage of assessing regional lung function. We aimed to investigate the potential of ventilation (SPECT/CT) for predicting postoperative lung function in patients with lung cancer. Methods: This retrospective study included consecutive patients with lung cancer who underwent lobectomy, preoperative ventilation, and perfusion SPECT/CT between January 2020 and December 2021. The percentage of predicted postoperative forced expiratory volume in 1 s (ppoFEV1%) and the percentage of predicted postoperative diffusion capacity of the lung for carbon monoxide (ppoDLCO%) were calculated from the % counts of each scan based on anatomical segments for lobar function. Correlation tests were performed between the predicted lung function values and actual ppoFEV1% and ppoDLCO%. Results: Among the 47 patients, 29 men and 18 women aged 67.5±9.6 years were included. Moreover, 46 ventilation and 41 perfusion SPECT/CT scans were obtained. The pulmonary function on ventilation SPECT/CT strongly correlated with perfusion SPECT/CT (correlation coefficient r=0.939 for ppoFEV1%, P<0.001; r=0.938 for ppoDLCO%, P<0.001). Both ppoFEV1% and ppoDLCO% values obtained from the ventilation and perfusion scans strongly correlated with postoperative FEV1% and DLCO% (correlation coefficient, r=0.774 and r=0.768 for ventilation; r=0.795 and r=0.751 for perfusion, each P<0.001). Conclusions: Ventilation SPECT/CT was comparable to perfusion SPECT/CT in predicting postoperative lung function.

Pulsed-dye laser as an effective treatment for recalcitrant granulomatous rosacea and a potential regulator of CXCL9 expression.

Granulomatous rosacea (GR) is a rare and distinct variant of rosacea. We report three cases of recalcitrant GR successfully treated with pulsed-dye laser (PDL) and provide experimental evidence supporting its potential as a treatment option. PDL treatment demonstrated remarkable efficacy in the three clinical cases, despite their resistance to conventional therapies. Chemokine ligand 9 (CXCL9), a key chemokine involved in inflammation and granuloma formation, was found to be increased in skin sections from all three patients. In vitro experiments using human monocytes and dermal fibroblasts demonstrated that PDL treatment significantly reduced CXCL9 expression in fibroblasts. These findings suggest that PDL may modulate CXCL9 secretion in fibroblasts, potentially limiting the recruitment of immune cells to the lesion. Although further research is needed to fully understand the precise mechanisms underlying the role of CXCL9 in GR, PDL may be a promising therapeutic approach for refractory GR.

Evaluation of a New Monofocal Intraocular Lens in Patients Undergoing Cataract and Vitrectomy Surgery for Idiopathic Macular Hole.

PURPOSE: To evaluate the usefulness of a newly generated monofocal intraocular lens (IOL) in patients who underwent combined cataract and pars plana vitrectomy (PPV) surgery for idiopathic macular hole (MH). METHODS: A prospective study was conducted on 89 eyes of 89 patients who underwent combined cataract and PPV surgery for MH. The patients were divided into two groups: Eyhance ICB00 and Tecnis ZCB00. Pre-operative characteristics, post-operative visual outcomes, contrast sensitivity, and complications were compared between the two groups. A univariate regression analysis was performed to identify the factors that may affect the postoperative visual outcomes. RESULTS: Both groups showed significant improvement in mean corrected distance visual acuity (CDVA) six months post-operation (p < 0.001). There was no significant difference in pre-operative characteristics or complications between the two groups. However, the Eyhance ICB00 group showed a significantly higher uncorrected intermediate visual acuity (UCIVA) value at 6 months after surgery than the Tecnis ZCB00 group (p = 0.014). Contrast sensitivity values were not significantly different between the two groups. The univariate regression analysis revealed a significant correlation between preoperative CDVA and minimum linear diameter of MH with postoperative UCIVA in the Eyhance ICB00 group. CONCLUSIONS: The newly generated Eyhance ICB00 IOL showed promising results in terms of post-operative UCIVA, with no significant difference in complications or contrast sensitivity values compared to the Tecnis ZCB00 IOL. These findings suggest that the Eyhance ICB00 IOL may be a useful option for patients who undergo combined cataract and PPV surgery for idiopathic MH, particularly for those who require intermediate visual acuity.

Sarcopenia assessed with DXA and CT increases the risk of perioperative complications in patients with gastrectomy.

OBJECTIVES: We investigated sarcopenia prevalence using various diagnostic criteria based on dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) in gastric cancer patients who underwent gastrectomy, and evaluated the association between sarcopenia and perioperative complications. METHODS: This retrospective study included consecutive patients with gastric cancer who underwent gastrectomy, and preoperative DXA and CT from January 2013 to November 2020. Body composition was measured using DXA and CT. Height-adjusted DXA-based Appendicular Skeletal Muscle Mass Index (ASMI) and CT-based skeletal muscle cross-sectional area at the L3 level (SMI) were measured. Sarcopenia and sarcopenic obesity were defined using reported cutoff values. The chi-square test and univariate analysis were performed to determine risk factors for significant and severe perioperative complications (Clavien-Dindo Grades ≥ 2 and ≥ 3, respectively). RESULTS: In total, 77 males and 43 females aged 61.4 ± 11.0 years were included. ASMI and SMI were correlated (r = 0.819), but sarcopenia prevalence varied (20.0-63.3%), depending on the criteria applied. Univariate analysis revealed sarcopenia defined using the Asian Working Group on Sarcopenia (AWGS) criteria and sarcopenic obesity as risk factors for significant (odds ratio [OR] 2.76, p = 0.030 vs. OR 4.31, p = 0.002) and severe perioperative complications (OR 3.77, p = 0.036 vs. OR 4.78, p = 0.010). In subgroup analyses, sarcopenia and sarcopenic obesity were significantly associated with perioperative complications only in males. CONCLUSION: Perioperative complication risk can be predicted from sarcopenia defined using the AWGS criteria and sarcopenic obesity measured using DXA and CT, particularly in males. KEY POINTS: • The prevalence of sarcopenia varies due to definition differences. • Sarcopenia and sarcopenic obesity are risk factors for significant and severe perioperative complications, particularly in males. • Our results suggest that physicians need to pay attention to perioperative complications after surgical treatment of male patients with sarcopenia and sarcopenic obesity.

Colonoscopic Screening and Risk of All-Cause and Colorectal Cancer Mortality in Young and Older Individuals.

PURPOSE: The incidence of early-onset colorectal cancer (CRC) and associated mortality have been increasing. However, the potential benefits of CRC screening are largely unknown in young individuals. We aimed to evaluate the effect of CRC screening with colonoscopy on all-cause and CRC mortality among young (aged < 45 years) and older (aged ≥ 45 years) individuals. Materials and Methods: This cohort study included 528,046 Korean adults free of cancer at baseline who underwent a comprehensive health examination. The colonoscopic screening group was defined as those who reported undergoing colonoscopy for CRC screening. Mortality follow-up until December 31, 2019 was ascertained based on nationwide death certificate data from the Korea National Statistical Office. RESULTS: Colonoscopic screening was associated with a lower risk of all-cause mortality in both young and older individuals. Multivariable-adjusted time-dependent hazard ratios (95% confidence intervals) for all-cause mortality comparing ever- to never-screening were 0.86 (0.75-0.99) for young individuals and 0.71 (0.65-0.78) for older individuals. Colonoscopic screenings were also associated with a reduced risk of CRC mortality without significant interaction by age, although this association was significant only among participants aged ≥ 45 years, with corresponding time-dependent hazard ratios of 0.47 (0.15-1.44) for young individuals and 0.52 (0.31-0.87) for those aged ≥ 45 years. CONCLUSION: Colonoscopic CRC screening decreased all-cause mortality among both young and older individuals, while significantly decreased CRC mortality was observed only in those aged ≥ 45 years. Screening initiation at an earlier age warrants more rigorous confirmatory studies.

Inpatients with shoulder osteoarthritis who received integrative Korean medicine treatment: Long-term follow-up of an observation study.

This study aimed to investigate the long-term clinical efficacy of and satisfaction with integrative Korean medicine (KM) treatment in patients with shoulder osteoarthritis (SOA). We conducted a prospective observational study of patients with SOA. Patients aged 19 years and older who underwent inpatient treatment for more than 1 week were eligible for enrollment in the study. The primary evaluation index was the numeric rating scale for shoulder pain. Sub-evaluation indices included the Shoulder Pain and Disability Index for shoulder function, EuroQol-5-dimension score for overall quality of life, and Patient Global Impression of Change. Outcome measures were assessed at admission, discharge, and follow-up. For the follow-up questionnaire survey, the following information was collected: current status, surgery after discharge, reasons for finding integrative KM treatment satisfactory/unsatisfactory, and quality of life after discharge. In total, 186 patients were enrolled in the primary analysis, and 103 patients completed the follow-up survey. The mean number of days of follow-up was 1019 ±â€…439. Compared with the baseline, the mean differences in the numeric rating scale and Shoulder Pain and Disability Index were 3.05 ±â€…0.34 and 36.06 ±â€…5.53, respectively. Regarding the Patient Global Impression of Change, 89 out of 103 (86.4%) patients chose "minimally improved" or better. Furthermore, the EuroQol-5-dimension score also increased, showing an improvement of health-related quality of life after treatment. Integrative KM treatment is a potential option for reducing pain severity and improving function and health-related quality of life in patients with SOA. Prospective randomized studies would support this finding for the next step.

Current therapeutic insights regarding problematic fingernails and toenails in the Republic of Korea.

BACKGROUND: Problematic nails and toenails are infected by germs and increasingly have many causes. AIMS: To investigate the types and treatment of problematic nails and toenails, we focused on bacteria that may appear in problematic nail toenail symptoms. METHODS: We have searched for PubMed and Google Scholar and correlated the words Onychomycosis, Tinea ungium, Melanonychia, and ingrown toenail related to symptoms. RESULTS: To measure onychomycosis, KOH tests and fungal culture tests will be used. Treatment can be treated with full-body treatment using anti-fungal agents and local treatment (laser therapy) that can minimize the side effects. A biopsy should be performed when Melanonychia is diagnosed with brown or black pigments on the patient's fingernail plate. Moreover, ingrown toenail surgical treatment can be improved by acquired lifestyle. CONCLUSIONS: There are many different types of treatments, but many studies show that problematic nail and toenail improvement periods are long and treatment success rates are low.

Factors Affecting Postoperative Lung Functions in Patients Undergoing Lobectomy for Non-Small Cell Lung Cancer.

Background and Objectives: The estimation of lung function impairment after pulmonary lobectomy for primary non-small cell lung cancer (NSCLC) has been of great interest since the reduction of respiratory function might severely affect a patient's quality of life. The perioperative factors that may have an influence on widening the gap between the postoperative measured lung function and predicted postoperative lung function were our greatest concern. We aimed to analyze the perioperative patient factors that may influence postoperative lung function in patients undergoing pulmonary lobectomy. Materials and Methods: A retrospective study was conducted using the medical records of 199 patients who underwent lobectomy for lung cancer between July 2017 and May 2020. After comparing the achieved postoperative forced expiratory volume in 1 s (FEV1) and predicted postoperative (ppo) FEV1, patients were divided into two groups: group A (n = 127), who had preserved pulmonary lung function; and group B (n = 72), who had decreased pulmonary lung function. Primary endpoints included location of pulmonary resection, preoperative performance status, body mass index (BMI) on admission, total muscle area, and muscle index. Results In group A, the proportion of normal weighted patients was significantly higher than that in group B (67.7% vs. 47.2%, p = 0.003). Conversely, the proportion of overweight patients was significantly higher in group B than in group A (47.2% vs. 28.3%, p = 0.003). Group B had a significantly high incidence of upper lobe resection (p = 0.012). The mean total muscle area in group A was higher than that in group B, but the difference was not statistically significant. Conclusions: A greater decrease in postoperative lung function than in ppo FEV1 was associated with BMI and the location of pulmonary resection in patients who underwent lobectomy. Postoperative physiologic changes due to high BMI and the resection of upper lobes need to be discussed to prevent postoperative morbidities.

Feasibility of anomaly score detected with deep learning in irradiated breast cancer patients with reconstruction.

The aim of this study is to evaluate cosmetic outcomes of the reconstructed breast in breast cancer patients, using anomaly score (AS) detected by generative adversarial network (GAN) deep learning algorithm. A total of 251 normal breast images from patients who underwent breast-conserving surgery were used for training anomaly GAN network. GAN-based anomaly detection was used to calculate abnormalities as an AS, followed by standardization by using z-score. Then, we reviewed 61 breast cancer patients who underwent mastectomy followed by reconstruction with autologous tissue or tissue expander. All patients were treated with adjuvant radiation therapy (RT) after reconstruction and computed tomography (CT) was performed at three-time points with a regular follow-up; before RT (Pre-RT), one year after RT (Post-1Y), and two years after RT (Post-2Y). Compared to Pre-RT, Post-1Y and Post-2Y demonstrated higher AS, indicating more abnormal cosmetic outcomes (Pre-RT vs. Post-1Y, P = 0.015 and Pre-RT vs. Post-2Y, P = 0.011). Pre-RT AS was higher in patients having major breast complications (P = 0.016). Patients with autologous reconstruction showed lower AS than those with tissue expander both at Pre-RT (2.00 vs. 4.19, P = 0.008) and Post-2Y (2.89 vs. 5.00, P = 0.010). Linear mixed effect model revealed that days after baseline were associated with increased AS (P = 0.007). Also, tissue expander was associated with steeper rise of AS, compared to autologous tissue (P = 0.015). Fractionation regimen was not associated with the change of AS (P = 0.389). AS detected by deep learning might be feasible in predicting cosmetic outcomes of RT-treated patients with breast reconstruction. AS should be validated in prospective studies.

Augmentation of the RNA m6A reader signature is associated with poor survival by enhancing cell proliferation and EMT across cancer types.

N6-Methyladenosine (m6A) RNA modification plays a critical role in the posttranscriptional regulation of gene expression. Alterations in cellular m6A levels and m6A-related genes have been reported in many cancers, but whether they play oncogenic or tumor-suppressive roles is inconsistent across cancer types. We investigated common features of alterations in m6A modification and m6A-related genes during carcinogenesis by analyzing transcriptome data of 11 solid tumors from The Cancer Genome Atlas database and our in-house gastric cancer cohort. We calculated m6A writer (W), eraser (E), and reader (R) signatures based on corresponding gene expression. Alterations in the W and E signatures varied according to the cancer type, with a strong positive correlation between the W and E signatures in all types. When the patients were divided according to m6A levels estimated by the ratio of the W and E signatures, the prognostic effect of m6A was inconsistent according to the cancer type. The R and especially the R2 signatures (based on the expression of IGF2BPs) were upregulated in all cancers. Patients with a high R2 signature exhibited poor prognosis across types, which was attributed to enrichment of cell cycle- and epithelial-mesenchymal transition-related pathways. Our study demonstrates common features of m6A alterations across cancer types and suggests that targeting m6A R proteins is a promising strategy for cancer treatment.

Prognostic factors in fluid-gas exchange after primary idiopathic macular hole surgery.

PURPOSE: This retrospective study aimed to evaluate the prognostic factors associated with the success of fluid-gas exchange in patients who had undergone failed primary idiopathic macular hole (IMH) surgery. METHODS: In total, 19 eyes of 19 patients with failed IMH surgery who then underwent fluid-gas exchange were included. Of those, 18 eyes had macular hole (MH) closure (successful, 15 eyes; unsuccessful, 3 eyes). Demographics, pre-operative characteristics, and pre-procedural characteristics were assessed. The patients were divided into successful (U or V-type closure) and unsuccessful groups (W-type or unclosed), following fluid-gas exchange. One eye was unclosed after fluid-gas exchange; therefore, this patient underwent additional vitrectomy for MH closure (unsuccessful). RESULTS: The outcomes of the fluid-gas exchange were categorized as unclosed or as U-type, V-type, or W-type closure. None of the patients experienced complications after the procedure. The successful group showed a significantly lower pre-operative and pre-procedural minimum diameter, base diameter, and macular hole volume, and higher pre-operative and pre-procedural macular hole index, hole form factor, and tractional hole index values. Moreover, a better visual prognosis was observed in the successful group. CONCLUSION: These findings suggest that indices predicting favorable results of primary surgery for IMH are useful for predicting the success of fluid-gas exchange in patients with failed primary MH surgery.

Meta-Analysis on the Neutrophil-Lymphocyte Ratio in Rectal Cancer Treated With Preoperative Chemoradiotherapy: Prognostic Value of Pre- and Post-Chemoradiotherapy Neutrophil-Lymphocyte Ratio.

BACKGROUND: To evaluate the prognostic value of neutrophil-lymphocyte ratio (NLR) in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative surgery. METHODS: A comprehensive search of the EMBASE and PubMed databases was performed to screen studies that compared treatment outcomes according to the pre-CRT and/or post-CRT NLR in patients receiving preoperative CRT and curative surgery for locally advanced rectal cancer. Hazard ratios (HRs) for disease-free survival (DFS) and/or overall survival (OS) were extracted, and a random-effects model was used for pooled analysis. RESULTS: Totally, 22 retrospective studies comprising 6316 patients were included. Preoperative CRT was administered with concurrent chemotherapy (mostly fluoropyrimidine-based regimens). The elevated pre-CRT NLR was significantly associated with an increased risk of recurrence (HR, 1.54; 95% confidence interval [CI], 1.31-1.81) and death (HR, 2.14; 95% CI, 1.61-2.84). Post-CRT NLR was reported in only 3 of 22 studies, and the correlation was not statistically significant for recurrence (HR, 1.44; 95% CI, 0.86-2.41) or death (HR, 2.38; 95% CI, 0.94-6.07). CONCLUSIONS: Elevated pre-CRT NRL, but not post-CRT NRL, is associated with inferior DFS and OS. Further studies are needed to confirm the prognostic value of NLR in rectal cancer patients receiving preoperative CRT.

Physicochemical Characteristics and Occupational Exposure of Silica Particles as Byproducts in a Semiconductor Sub Fab.

This study aimed to elucidate the physicochemical characteristics and occupational exposure of silica powder and airborne particles as byproducts generated from the first scrubbers of chemical vapor deposition and diffusion processes during maintenance in a semiconductor facility sub fab to reduce unknown risk factors. The chemical composition, size, morphology, and crystal structure of powder and airborne particles as byproducts were investigated using a scanning electron microscopy and transmission electron microscopy equipped with an energy dispersive X-ray spectroscopy, and an X-ray diffraction. The number and mass concentration measurements of airborne particles were performed by using an optical particle sizer of a direct-reading aerosol monitor. All powder and airborne particle samples were mainly composed of oxygen (O) and silicon (Si), which means silica. The byproduct particles were spherical and/or nearly spherical and the particle size ranged from 10 to 90 nm, based on primary particles. Most of the particles were usually agglomerated within a particle size range from approximately 100 nm to 35 µm. In addition, most of the powder samples exhibited diffraction patterns with a broad and relatively low intensity at 2θ degrees 21.6-26.7°, which is similar to that of pure amorphous silica. The above results show the byproduct particles are amorphous silica, which are considered a less toxic foam compared to crystalline silica. The number and mass concentrations of PM10 (particles less than 10 µm in diameter) ranged from 4.250-78.466 particles/cm3 and 0.939-735.531 µg/m3, respectively. In addition, 0.3-1.0 and 2.5-10 µm particles occupied the highest portion of the number and mass concentrations, respectively. Meanwhile, several peak exposure patterns were observed at a specific step, which is the process of removing powder particles on the inner chamber and cleaning the chamber by using a vacuum cleaner and a clean wiper, during the maintenance task.

Changes in Trimethylamine-N-oxide Levels in Obese Patients following Laparoscopic Roux-en-Y Gastric Bypass or Sleeve Gastrectomy in a Korean Obesity Surgical Treatment Study (KOBESS).

Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite, has been implicated as a novel risk factor for cardiovascular events related to obesity and type 2 diabetes mellitus (T2DM). The aim of the study was to test the hypothesis if TMAO is associated with the reduction of cardiovascular disease in the Korean obese patients who underwent bariatric surgery. From a subgroup of a multicenter, nonrandomized, controlled trial, titled KOBESS, 38 obese patients, 18 with and 20 without T2DM, who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were investigated. Bariatric surgery is indicated for Korean patients with a body mass index (BMI) ≥ 35 kg/m2 or for Korean patients with a BMI ≥ 30 kg/m2 who have comorbidities. Serum levels of TMAO and its precursors, betaine, carnitine, and choline were measured before and six months after bariatric surgery. The levels of TMAO and its precursors did not differ between obese patients with T2DM and non-T2DM at baseline. However, TMAO increased more than twofold in patients with T2DM after RYGB surgery, but not in patients without T2DM. Choline levels were decreased by half in all patients after RYGB. In patients with T2DM who underwent SG, TMAO, betaine, and carnitine levels did not change after the surgery. Furthermore, in obese patients who underwent bariatric surgery, increased TMAO levels were associated with both T2DM and RYGB, while reduced choline levels were associated with RYGB. These associations need to be further elucidated in follow-up studies to gain further insights into the relationship between TMAO levels and bariatric surgery outcomes.

Changes in treatment intent and target definition for preoperative radiotherapy after 18F-Fluorodeoxyglucose positron emission tomography in rectal cancer: A Meta-analysis.

PURPOSE: To evaluate the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on changes in treatment plan and target definition for preoperative radiotherapy in patients with rectal cancer. METHODS: Embase, PubMed, and Cochrane Library were searched up to November 2020 for all studies investigating the role of preoperative FDG PET in patients who underwent neoadjuvant radiotherapy before curative-intent surgery. The proportion of patients whose treatment plan (curative vs. palliative intent) or target definition was changed after FDG PET was analyzed. A random-effects model was used for pooled analysis. The change in target definition was compared between conventional radiological imaging-based target volume [gross tumor volume (GTV) or planning target volume (PTV)] and PET-based target volume (GTV or PTV) using the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 336 patients from twelve studies were included. In eight studies, PET changed either the treatment intent or target definition in 24.8% of patients (95% CI 15.1% to 37.9%, I2 = 69%). In ten studies, the PET-based GTV was lower than the conventional imaging-based target volume (SMD -7.0, 95% CI -1.39 to -0.01). However, there was no significant difference between conventional imaging-based and PET-based PTV (SMD -0.07, 95% CI -0.75 to 0.62). In six studies evaluating the initial staging based on PET, the initial staging (nodal or metastasis status) was changed in 53 of 229 patients (23.1%). Newly detected or additional distant metastases were identified in 22 patients (9.6%) after FDG PET. CONCLUSION: The use of FDG PET influences radiotherapy planning in a fourth of patients with rectal cancer. FDG PET can provide additive information for accurate tumor delineation, although PET-based PTV did not significantly change. These findings suggest that FDG PET may be beneficial to patients with rectal cancer before establishing a radiotherapy plan.