A Nomogram for Predicting Cancer-Specific Survival in Young Patients With Advanced Lung Cancer Based on Competing Risk Model.

BACKGROUND: Young lung cancer is a rare subgroup accounting for 5% of lung cancer. The aim of this study was to compare the causes of death (COD) among lung cancer patients of different age groups and construct a nomogram to predict cancer-specific survival (CSS) in young patients with advanced stage. METHODS: Lung cancer patients diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and stratified into the young (18-45 years) and old (> 45 years) groups to compare their COD. Young patients diagnosed with advanced stage (IVa and IVb) from 2010 to 2015 were reselected and divided into training and validation cohorts (7:3). Independent prognostic factors were identified through the Fine-Gray's test and further integrated to the competing risk model. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), and calibration curve were applied for validation. RESULTS: The proportion of cancer-specific death (CSD) in young patients was higher than that in old patients with early-stage lung cancer (p < 0.001), while there was no difference in the advanced stage (p = 0.999). Through univariate and multivariate analysis, 10 variables were identified as independent prognostic factors for CSS. The AUC of the 1-, 3-, and 5-year prediction of CSS was 0.688, 0.706, and 0.791 in the training cohort and 0.747, 0.752, and 0.719 in the validation cohort. The calibration curves demonstrated great accuracy. The C-index of the competing risk model was 0.692 (95% CI: 0.636-0.747) in the young patient cohort. CONCLUSION: Young lung cancer is a distinct entity with a different spectrum of competing risk events. The construction of our nomogram can provide new insights into the management of young patients with lung cancer.

Association between exposure to organophosphate flame retardants and epidermal growth factor receptor expression in lung cancer patients.

BACKGROUND: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. METHODS: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. RESULTS: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression. CONCLUSIONS: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population.

Kinetic model-informed deep learning for multiplexed PET image separation.

BACKGROUND: Multiplexed positron emission tomography (mPET) imaging can measure physiological and pathological information from different tracers simultaneously in a single scan. Separation of the multiplexed PET signals within a single PET scan is challenging due to the fact that each tracer gives rise to indistinguishable 511 keV photon pairs, and thus no unique energy information for differentiating the source of each photon pair. METHODS: Recently, many applications of deep learning for mPET image separation have been concentrated on pure data-driven methods, e.g., training a neural network to separate mPET images into single-tracer dynamic/static images. These methods use over-parameterized networks with only a very weak inductive prior. In this work, we improve the inductive prior of the deep network by incorporating a general kinetic model based on spectral analysis. The model is incorporated, along with deep networks, into an unrolled image-space version of an iterative fully 4D PET reconstruction algorithm. RESULTS: The performance of the proposed method was evaluated on a simulated brain image dataset for dual-tracer [ 18 F]FDG+[ 11 C]MET PET image separation. The results demonstrate that the proposed method can achieve separation performance comparable to that obtained with single-tracer imaging. In addition, the proposed method outperformed the model-based separation methods (the conventional voxel-wise multi-tracer compartment modeling method (v-MTCM) and the image-space dual-tracer version of the fully 4D PET image reconstruction algorithm (IS-F4D)), as well as a pure data-driven separation [using a convolutional encoder-decoder (CED)], with fewer training examples. CONCLUSIONS: This work proposes a kinetic model-informed unrolled deep learning method for mPET image separation. In simulation studies, the method proved able to outperform both the conventional v-MTCM method and a pure data-driven CED with less training data.

Association of Decreased Bone Density and Hyperlipidemia in a Taiwanese Older Adult Population.

Objective: This study aimed to determine if a combination of 2 abnormal lipid profiles revealed a stronger association with low bone mass than a single blood lipid abnormality alone. Methods: This study enrolled 1373 participants who had received a dual-energy x-ray absorptiometry scan from January 2016 to December 2016 in a medical center in southern Taiwan. Logistic regression was used to examine association between lipid profiles and osteopenia or osteoporosis after adjusting for covariates. Results: Compared to people with total cholesterol (TC) < 200 mg/dL, those with TC ≥ 240 mg/dL tended to have osteopenia or osteoporosis (OR 2.61; 95% CI, 1.44-4.71). Compared to people with low-density lipoprotein cholesterol (LDL-C) < 130 mg/dL, those with LDL-C ≥ 160 mg/dL tended to develop osteopenia or osteoporosis (OR 2.13; 95% CI, 1.21-3.74). The association of increased triglyceride and decreased bone mass was similar, although not statistically significant. Those with the combination of TG ≥ 200 mg/dL and TC ≥ 240 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 3.51; 95% CI, 1.11-11.13) than people with only one blood lipid abnormality. Similarly, people with TG ≥ 200 mg/dL and LDL-C ≥ 160 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 9.31; 95% CI, 1.15-75.42) than people with only one blood lipid abnormality, after adjustment for the same covariates. Conclusion: Blood levels of TC, LDL-C, and TG were associated with osteopenia or osteoporosis. Results indicate that individuals aged older than 50 years with abnormal lipid profiles should be urged to participate in a bone density survey to exclude osteopenia or osteoporosis.

AI for PET image reconstruction.

Image reconstruction for positron emission tomography (PET) has been developed over many decades, with advances coming from improved modelling of the data statistics and improved modelling of the imaging physics. However, high noise and limited spatial resolution have remained issues in PET imaging, and state-of-the-art PET reconstruction has started to exploit other medical imaging modalities (such as MRI) to assist in noise reduction and enhancement of PET's spatial resolution. Nonetheless, there is an ongoing drive towards not only improving image quality, but also reducing the injected radiation dose and reducing scanning times. While the arrival of new PET scanners (such as total body PET) is helping, there is always a need to improve reconstructed image quality due to the time and count limited imaging conditions. Artificial intelligence (AI) methods are now at the frontier of research for PET image reconstruction. While AI can learn the imaging physics as well as the noise in the data (when given sufficient examples), one of the most common uses of AI arises from exploiting databases of high-quality reference examples, to provide advanced noise compensation and resolution recovery. There are three main AI reconstruction approaches: (i) direct data-driven AI methods which rely on supervised learning from reference data, (ii) iterative (unrolled) methods which combine our physics and statistical models with AI learning from data, and (iii) methods which exploit AI with our known models, but crucially can offer benefits even in the absence of any example training data whatsoever. This article reviews these methods, considering opportunities and challenges of AI for PET reconstruction.

Liver-specific metastases as an independent prognostic factor in cancer patients receiving hospice care in hospital.

BACKGROUND: Survival prediction is important in cancer patients receiving hospice care. Palliative prognostic index (PPI) and palliative prognostic (PaP) scores have been used to predict survival in cancer patients. However, cancer primary site with metastatic status, enteral feeding tubes, Foley catheter, tracheostomy, and treatment interventions are not considered in aforementioned tools. The study aimed to investigate the cancer features and potential clinical factors other than PPI and PaP to predict patient survival. METHODS: We conducted a retrospective study for cancer patients admitted to a hospice ward between January 2021 and December 2021. We examined the correlation of PPI and PaP scores with survival time since hospice ward admission. Multiple linear regression was used to test the potential clinical factors other than PPI and PaP for predicting survival. RESULTS: A total of 160 patients were enrolled. The correlation coefficients for PPI and PaP scores with survival time were -0.305 and -0.352 (both p < 0.001), but the predictabilities were only marginal at 0.087 and 0.118, respectively. In multiple regression, liver metastasis was an independent poor prognostic factor as adjusted by PPI (ß = -8.495, p = 0.013) or PaP score (ß = -7.139, p = 0.034), while feeding gastrostomy or jejunostomy were found to prolong survival as adjusted by PPI (ß = 24.461, p < 0.001) or PaP score (ß = 27.419, p < 0.001). CONCLUSIONS: Association between PPI and PaP with patient survival in cancer patients at their terminal stages is low. The presence of liver metastases is a poor survival factor independent of PPI and PaP score.

The Pattern of Hemoglobin A1C Trajectories and Risk of Herpes Zoster Infection: A Follow-Up Study.

To investigate the risks of herpes zoster (HZ) infection among heterogeneous HbA1C trajectories of patients with newly diagnosed type 2 diabetes, this cohort study used data from the Chang Gung Research Database (CGRD), from the 10-year period of 1 January 2007 to 31 December 2017. We applied group-based trajectory modeling (GBTM) to identify the patterns of HbA1C trajectories, and multiple Cox proportional hazards regressions were used to estimate the hazard ratio (HR) for the risk of HZ infection with adjustment of age, sex, and comorbidities. This study enrolled 121,999 subjects to perform the analysis. The GBTM identified four HbA1C trajectories: 'good control' (58.4%), 'high decreasing' (8.9%), 'moderate control' (25.1%), and 'poor control' (7.6%) with the mean HbA1C of 6.7% (50 mmol/mol), 7.9% (63 mmol/mol), 8.4% (68 mmol/mol), and 10.7% (93 mmol/mol) respectively. The risk of HZ was significantly higher in the poor control with an HR = 1.44 (95% CI 1.26-1.64) after adjustment for confounders and comorbidities. The risk of HZ infection for the high decreasing group (initially poor then rapidly reaching optimal control) was nonsignificant compared to the good control group. In conclusion, the patients with poor glycemic control (mean HbA1C = 10.7%) had the highest risk of HZ infection. The patients with initial hyperglycemia then reaching optimal control could have a lower risk of HZ infection.

Could prokinetic agents protect long-term nasogastric tube-dependent patients from being hospitalized for pneumonia? A nationwide population-based case-crossover study.

BACKGROUND: Some studies have indicated that the use of prokinetic agents may reduce pneumonia risk in some populations. Nasogastric tube insertion is known to increase the risk of pneumonia because it disrupts lower esophageal sphincter function. The aim of this study was to evaluate whether prokinetic agents could protect long-term nasogastric tube-dependent patients in Taiwan from being hospitalized for pneumonia. METHODS: A case-crossover study design was applied in this study. Long-term nasogastric tube-dependent patients who had a first-time admission to a hospital due to pneumonia from 1996 to 2013 that was recorded in the Taiwan National Health Insurance Research Database were included. The case period was set to be 30 days before admission, and two control periods were selected for analysis. Prokinetic agent use during those three periods was then assessed for the included patients. Conditional logistic regression was used to calculate the odds ratio (OR) for pneumonia admission with the use of prokinetic agents. RESULTS: A total of 639 first-time hospitalizations for pneumonia among patients with long-term nasogastric tube dependence were included. After adjusting the confounding factors for pneumonia, no negative association between prokinetic agent use and pneumonia hospitalization was found, and the adjusted OR was 1.342 (95% CI 0.967-1.86). In subgroup analysis, the adjusted ORs were 1.401 (0.982-1.997), 1.256 (0.87-1.814), 0.937 (0.607-1.447) and 2.222 (1.196-4.129) for elderly, stroke, diabetic and parkinsonism patients, respectively. CONCLUSION: Prokinetic agent use had no negative association with pneumonia admission among long-term nasogastric tube-dependent patients in Taiwan.

Effects of Hospice Care for Terminal Head and Neck Cancer Patients: A Nationwide Population-Based Matched Cohort Study.

Background: Head and neck cancer was the fourth-most common cause of cancer death among Taiwanese men in 2018. Hospice care has been proven to reduce the use of invasive medical interventions and expenditures in caring for cancer patients. Aim: This study examined the effects of hospice care for terminal head and neck cancer patients. Design: A matched cohort study was used to compare the use of invasive interventions and expenditures among hospice care and nonhospice care patients. Setting/Participants: The investigated patients consisted of patients who died of head and neck cancer in Taiwan from 2004 to 2013 and were included in the Registry for Catastrophic Illness Patients in Taiwan and the Taiwan National Health Research Insurance Database. Results: A total of 45,948 terminal head and neck cancer patients were identified, and 9883 patients remained in each group after matching for comorbidities. After that matching, the rates of intensive care unit admission (23.9% vs. 38.94%, p < 0.0001), endotracheal intubation (10.05% vs. 31.32%, p < 0.0001), cardiopulmonary resuscitation (2.93% vs. 20.18%, p < 0.0001), defibrillation (0.51% vs. 4.36%. p < 0.0001), ventilator use (21.92% vs. 46.47%, p < 0.0001), blood transfusion (71.25% vs. 73.45%, p = 0.006), and hemodialysis (1.06% vs. 3.26%. p < 0.0001) were significantly lower in the hospice group than the nonhospice group, although the rates of parenteral nutrition for the two groups were similar (7.74% vs. 7.97%, p = 0.5432). The mean medical expenditure per person in the six months before death was 460,531 New Taiwan Dollar (NTD) for the nonhospice group and 389,079 NTD for those provided hospice care for more than three months, which was the lowest amount among various hospice enrollment durations. Conclusions: Hospice care can effectively reduce the use of invasive medical interventions in caring for terminal head and neck cancer patients and may improve their quality of death. Moreover, hospice care enrollment for more than three months can save on unnecessary medical expenditures for terminal head and neck cancer patients.

Efficient inhibition of Cronobacter biofilms by chitooligosaccharides of specific molecular weight.

Biofilms enable Cronobacter spp. to contaminate food, infect infants and resist different environmental stresses, especially desiccation, which is the main reason why Cronobacter can survive in powdered infant formula (PIF) for a long time. Considering the high lethality of Cronobacter infection in infants, it is important to find efficient and safe inhibitors of Cronobacter biofilms. In this study, we found that chitooligosaccharides (COS) with a molecular weight of 2000 Da efficiently inhibited Cronobacter biofilms, especially in skim milk broth. The minimum biofilm inhibitory concentration (MBIC77) of COS was as low as 20 µg/mL, which is lower than that reported in most previous studies. Besides, the elimination rate of COS for Cronobacter mature biofilms was 50% when the concentration was 10 mg/mL. COS could significantly inhibit soluble polysaccharide secretion and biofilm cell growth, as well as change the cell membrane permeability of Cronobacter. These might be the possible reasons for COS's efficient inhibition of Cronobacter biofilms. However, during the inhibition, five important genes-related to biofilm formation-flhD, flgJ, luxR, ompA, and wcaJ-were all up-regulated after COS treatment, except the gene bcsA. In summary, our findings showed that COS could be used as an efficient and safe inhibitor against Cronobacter biofilms for better control of Cronobacter contamination and infection.

Relationship between Helicobacter pylori infection and bone mineral density: a retrospective cross-sectional study.

BACKGROUND: Helicobacter pylori (H. pylori) infection can induce individual inflammatory and immune reactions which associated with extra-digestive disorders. Our aim is to investigate the association between H. pylori infection and bone mineral density. METHODS: This retrospective cross-sectional study was performed by using the data from the health examination database in a medical center of southern Taiwan in 2013. We investigated the relationship between sex, age, body mass index (BMI), waist circumstance, lipid profile, H. pylori infection, the findings of upper gastrointestinal endoscopy and bone mineral density (BMD). Because of nonrandomized assignment and strong confounding effect of age on BMD, the 1:1 propensity score match was applied for age adjustment. The simple and multiple stepwise logistic regression analysis were performed to assess the risk factors of decreased BMD in these well-balanced pairs of participants. RESULTS: Of the 867 subjects in final analysis with the mean age of 55.9 ± 11.3 years, 381 (43.9%) subjects had H. pylori infection, and 556 (64.1%) subjects had decreased BMD. In decreased BMD group, the portion of woman was higher than a normal BMD group (37.2% versus 29.6%, P = 0.023), the age was significantly older (59.4 ± 9.8 versus 49.8 ± 11.3, p < 0.001) and BMI was significantly lower (24.7 ± 3.5 versus 25.4 ± 3.7, p = 0.006) than the normal BMD group. The prevalence of H. pylori infection was 39.9% and 46.2% in the normal BMD group and the decreased BMD group respectively (P = 0.071). The multivariate analysis which was used for these possible risk factors showed that only advanced age (OR 1.09, 95% CI 1.08-1.11, P < 0.001), and low BMI (OR 0.91, 95% CI 0.87-0.95, P < 0.001) were independently significantly associated with decreased BMD in this nonrandomized study. In the propensity score-matched participants, the multiple stepwise logistic regression analysis revealed H. pylori infection (OR 1.62, 95% CI 1.12-2.35, P = 0.011) and low BMI (OR 0.92, 95% CI 0.87-0.97, P = 0.001) were independently significantly associated with decreased BMD. CONCLUSIONS: H. pylori infection and low BMI were independently significantly associated with decreased BMD in selected propensity score-matched populations after age adjustment.

Basic and Clinical Evidence of an Alternative Method to Produce Vivo Nanofat.

BACKGROUND: Fat grafting technologies are popularly used in plastic and reconstructive surgery. Due to its size limitation, it is hard to directly inject untreated fat tissue into the dermal layer. Nanofat, which was introduced by Tonnard, solves this problem by mechanically emulsifying fat tissue. However, the viability of the cells was greatly destroyed. In this study, we reported a new method by "gently" digesting the fat tissue to produce viable adipocytes, progenitors, and stromal stem cells using collagenase I digestion and centrifugation. This was named "Vivo nanofat". METHODS: Human liposuction aspirates were obtained from five healthy female donors with mean age of 28.7 ± 5.6 years. Colony-forming assay, flow cytometry analysis, and adipogenic and osteogenic induction of the adherent cells from the Vivo nanofat were used to characterize the adipose mesenchymal stem cells (MSCs). To investigate in vivo survival, we respectively injected Vivo nanofat and nanofat subcutaneously to the back of 8-week-old male BALB/c nude mice. Samples were harvested 2 days, 2 weeks, and 4 weeks postinjection for measurement, hematoxylin and eosin staining, and immunostaining. RESULTS: Our results showed that the Vivo nanofat contained a large number of colony-forming cells. These cells expressed MSC markers and had multi-differentiative potential. In vivo transplantation showed that the Vivo nanofat had lower resorption ratio than that of nanofat. The size of the transplanted nanofat was obviously smaller than that of Vivo nanofat 4 weeks postinjection (0.50 ± 0.17 cm vs. 0.81 ± 0.07 cm, t = -5783, P = 0.01). CONCLUSION: Vivo nanofat may serve as a cell fraction injectable through a fine needle; this could be used for cosmetic applications.

Chronic kidney disease associated with decreased bone mineral density, uric acid and metabolic syndrome.

OBJECTIVE: The relationship between decreased bone mineral density (BMD) and chronic kidney disease (CKD) is controversial. The associations among metabolic syndrome (MetS), serum uric acid and CKD are also unclear. We aimed to investigate the relationship between decreased BMD, MetS, serum uric acid and CKD in a general population. METHODS: A total of 802 subjects who visited a medical center in Southern Taiwan and underwent a BMD measured by dual-energy X-ray absorptiometry (DEXA) during a health examination were enrolled in this retrospective cross-sectional study. Either osteopenia or osteoporosis was defined as decreased BMD. CKD was defined as the estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2. Simple and multivariate logistic regression analyses were used to investigate the association between variables, decreased BMD and CKD. RESULTS: Of the 802 subjects with a mean age of 54.4±10.2 years, the prevalence of decreased BMD was 62.9%, and CKD was 3.7%. Simple logistic analysis showed that sex (OR 3.50, 95% CI 1.21-10.12, p = 0.021), age (OR 1.14, 95% CI 1.07-1.21, p<0.001), BMI (OR 1.11, 95% CI 1.01-1.22, p = 0.028), waist circumference (OR 1.06, 95% CI 1.02-1.10, p = 0.002), SBP (OR 1.03, 95% CI 1.01-1.04, p = 0.003), DBP (OR 1.03, 95% CI 1.00-1.06, p = 0.030), HDL-C (OR 0.97, 95% CI 0.94-1.00, p = 0.026), uric acid (OR 1.84, 95% CI 1.49-2.27, p<0.001), metabolic syndrome (OR 2.68, 95% CI 1.29-5.67, p = 0.009), and decreased BMD (OR 3.998, 95% CI 1.38-11.57, p = 0.011) were significantly associated with CKD. Multivariate analysis showed that age (OR 1.05, 95% CI 1.03-1.07, p<0.001), decreased BMD (OR 0.64, 95% CI 0.45-0.91, p = 0.013), and uric acid (OR 1.40, 95% CI 1.24-1.59, p<0.001) were significantly independently associated with CKD. CONCLUSIONS: Decreased BMD, uric acid and MetS were significantly associated with CKD.. Further large and prospective cohort studies are necessary to investigate whether management of osteoporosis, hyperuricemia, or MetS might prevent the progression of CKD.

Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin­1.

Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from keloid fibroblasts (KFs) promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and this effect may have been abrogated by the short hairpin RNA knockdown of periostin. Treatment with recombinant human periostin promoted the migration and tube formation of HUVECs by activating the extracellular signal­regulated kinase 1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased the secretion of vascular endothelial growth factor and angiopoietin­1 in the KFs. In conclusion, these data suggested that upregulation in the level of periostin may promote angiogenesis directly and indirectly in keloids and may be a key factor in keloid development. Periostin may, therefore, be a promising therapeutic target in the treatment of keloids and other angioproliferative diseases.