Depressive symptoms and daily living dependence in older adults with type 2 diabetes mellitus: the mediating role of positive and negative perceived stress.

BACKGROUND: Higher stress is associated with higher levels of depression and instrumental-activities-of-daily-living (IADL) dependence, and depression is strongly associated with specific IADL disabilities. Accordingly, the aim of this study was to investigate the mediating effect of perceived stress on the association between depression and IADL dependence among older adults with diabetes mellitus (DM). METHODS: We examined baseline data collected from a longitudinal study that recruited 110 patients with DM aged ≥ 65 years from the endocrinology outpatient clinic of a district hospital. The instruments used for our measurement processes comprised a demographic data sheet and Chinese versions of the Perceived Stress Scale (PSS), the short form of the Geriatric Depression Scale (GDS-S), and the Lawton IADL Scale. We assessed the mediating effects of positive perceived stress (PPS) and negative perceived stress (NPS) after controlling for five covariates by using a regression-based model run through the SPSS macro PROCESS. RESULTS: We observed negative correlations between GDS-S scores and PPS and between PPS and IADL dependence; we noted positive correlations between GDS-S scores and NPS and between NPS and IADL dependence (all P < 0.01). The indirect effect is coefficient = 0.12, [95% confidence interval = (0.0, 0.33)], suggesting that PPS achieves a mediating effect between depressive symptoms and IADL dependence. However, the NPS does not achieve a mediating effect in the relationship between depressive symptoms and IADL dependence (coefficient = 0.06, 95% CI = - 0.03, 0.15). CONCLUSIONS: Personal PPS mediates the association between depression and IADL dependence in older adults with DM. This finding suggests that providing patients with psychological education to promote their PPS may help prevent their functional decline.

Sodium-Glucose Cotransporter 2 Inhibitors Reduce the Risk of Hospitalization for Heart Failure and Amputation Rate Compared With Incretin-Based Therapy in Patients With Diabetic Foot Disease: A Nationwide Population-Based Study.

OBJECTIVE: Major adverse cardiovascular event (MACE) outcomes associated with sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies remain unclear in patients with type 2 diabetes and newly diagnosed diabetic foot complications (DFCs). This study examined the impact of SGLT2i and GLP-1 RA use on the rates of MACEs and amputations in patients with type 2 diabetes and without cardiovascular disease. METHODS: Data from the Taiwan National Health Insurance Research Database (2004-2017) were analyzed, focusing on patients with type 2 diabetes without previous MACE and newly diagnosed DFCs. The primary outcome was the first MACE occurrence, and the secondary outcomes included MACE components, all-cause mortality, and lower extremity amputation (LEA) rates. RESULTS: SGLT2i users showed a significant decrease in the MACE (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46-0.88) and hospitalization for heart failure (HR, 0.54; 95% CI, 0.35-0.83) rates compared with dipeptidyl peptidase-4 inhibitor users. The amputation rates were also lower in SGLT2i users without LEA at the first DFC diagnosis (HR, 0.28; 95% CI, 0.10-0.75) and did not increase in those with a history of peripheral artery disease or LEA. No significant differences were observed between dipeptidyl peptidase-4 inhibitor and GLP-1 RA users in terms of the primary or secondary outcomes. CONCLUSION: In patients with type 2 diabetes initially diagnosed with DFC, SGLT2i are effective in significantly reducing the hospitalization for heart failure and MACE rates. SGLT2i lower the amputation rates, especially in patients who have not previously had a LEA, than the dipeptidyl peptidase-4 inhibitor therapy.

Understanding Healthcare Providers' Care for Patients with Medications Treating Opioid Use Disorder in the Emergency Department: A Scoping Review.

BACKGROUND: There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder (MOUD). METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory. RESULTS: The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices. CONCLUSIONS: Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.

Advanced maternal age-related clustering of metabolic abnormalities is associated with risks of adverse pregnancy outcomes.

AIMS: Advanced maternal age (AMA) is correlated with higher risk of adverse pregnancy outcomes while the pathophysiology remains unclear. Our study aimed to investigate whether AMA is linked to the clustering of metabolic abnormalities, which in turn is associated with an increased risk of adverse pregnancy outcomes. METHOD: A total of 857 pregnant woman were recruited in a prospective cohort at National Taiwan University Hospital, from November 2013 to April 2018. Metabolic abnormalities during pregnancy were defined as following: fasting plasma glucose ≥92 mg/dl, body mass index (BMI) ≥24 kg/m2, plasma high-density lipoprotein cholesterol <50 mg/dl, hyper-triglyceridemia (≥140 mg/dl in the first trimester or ≥220 mg/dl in the second trimester), and blood pressure ≥130/85 mmHg. RESULT: Incidence of large for gestational age (LGA), primary caesarean section (CS), and the presence of any adverse pregnancy outcome increased with age. The advanced-age group tended to have more metabolic abnormalities in both the first and the second trimesters. There was a significant association between the number of metabolic abnormalities in the first and the second trimesters and the incidence of LGA, gestational hypertension or preeclampsia, primary CS, preterm birth, and the presence of any adverse pregnancy outcome, adjusted for maternal age. CONCLUSION: AMA is associated with clustering of metabolic abnormalities during pregnancy, and clustering of metabolic abnormalities is correlated with increased risk of adverse pregnancy outcomes.

Aldosterone-to-renin ratio (ARR) as a screening tool for primary aldosteronism (PA).

The aldosterone-to-renin ratio (ARR) is the standard screening test for primary aldosteronism (PA). Because of the poor reproducibility of the ARR, repeat testing is recommended if the result is not compatible with the clinical condition. Various methods to measure renin are used in different hospitals in Taiwan, and the ARR cutoff values also differ among laboratories. The Task Force of Taiwan PA recommend using plasma renin activity (PRA) to calculate ARR instead of direct renin concentration (DRC) unless PRA is unavailable, because PRA is widely used in international guidelines and most studies.

Evaluations of secondary hypertension and laboratory data in the elderly population.

Secondary hypertension in the elderly poses many challenges and requires a comprehensive diagnostic and management approach. This review explores the prevalence, diagnostic strategies, and treatment modalities for secondary hypertension in elderly patients, focusing on etiologies including primary aldosteronism, renal vascular disease, renal parenchymal disease, obstructive sleep apnea, thyroid disorders, Cushing's syndrome, pheochromocytomas and paragangliomas, and drug-induced hypertension. Key considerations include age-related changes in physiology and atypical presentations of underlying conditions necessitating thorough screening with a combination of clinical evaluation, laboratory tests, and imaging studies. Collaboration among healthcare providers is essential to ensure a timely diagnosis and personalized management tailored to the unique needs of elderly patients. Further research is needed to address knowledge gaps and optimize clinical strategies for managing secondary hypertension in this population.

Cognitive appraisals and coping strategies of registered nurses in the emergency department combating COVID-19: A scoping review.

OBJECTIVE: Explore the relevant evidence about stress-related cognitive appraisal and coping strategies among registered nurses in the emergency department (EDRNs) coping with the COVID-19 pandemic. METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus electronic databases for related studies from inception through February 2, 2022. This review further conducted study selection based on the PRISMA flow diagram and applied Lazarus and Folkman's Psychological Stress and Coping Theory to systematically organize, summarize, and report the findings. FINDINGS: Sixteen studies were included for synthesis. Most of the studies showed that the majority of EDRNs were overwhelmed by the COVID-19 pandemic. Depression, triaging distress, physical exhaustion, and intention to leave ED nursing were cited as major threats to their wellness. Additionally, comprehensive training, a modified triage system, a safe workplace, psychological support, promotion of resilience, and accepting responsibility may help EDRNs cope with pandemic-related challenges effectively. CONCLUSION: The long-lasting pandemic has affected the physical and mental health of EDRNs because they have increased their effort to respond to the outbreak with dynamically adjusted strategies. Future research should address a modified triage system, prolonged psychological issues, emergency healthcare quality, and solutions facing EDRNs during the COVID-19 or related future pandemics. CLINICAL RELEVANCE: EDRNs have experienced physical and psychological challenges during the pandemic. The ED administrators need to take action to ensure EDRNs' safety in the workplace, an up-to-date triage system, and mental health of frontline nurses to provide high-quality emergency care for combating COVID-19.

Taiwan's National Health Insurance at the Emergency Department following the COVID-19 outbreak.

Taiwan's National Health Insurance (NHI) is a widely acclaimed universal healthcare system. In the past few years, particularly following the COVID-19 outbreak, challenges related to maintaining the NHI system have surfaced. Since 2020, NHI has faced a series of challenges, including excessive patient visits to the hospital emergency department, a lack of an effective primary care and referral system, and a high turnover rate of healthcare workers. We review major problems related to Taiwan's NHI, emphasizing input from frontline healthcare workers. We provide recommendations for potential policies addressing the concerns around NHI, for example, strengthening the role of primary care services under the NHI administration, reducing the high turnover rate of healthcare workers, and increase the premium and copayments. We hope that this policy analysis may allow policymakers and scholars to understand both the merits and critical problems related to NHI from the clinical perspective.

Different cutoffs of hypertension, risk of incident diabetes and progression of insulin resistance: A prospective cohort study.

BACKGROUND/PURPOSE: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance. METHODS: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used. RESULTS: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p < 0.001) and ΔHOMA2-IR/5 yr, compared with subjects with normal blood pressure. However, the associations of hypertension, HR of incident diabetes and ΔHOMA2-IR/5 yr were attenuated by the 2017 ACC/AHA criteria, as compared with that by the JNC7 and 2018 ESC/ESH criteria. CONCLUSION: Hypertension by both criteria is associated with incident diabetes and accelerated progression of insulin resistance, and the associations are attenuated by the 2017 ACC/AHA criteria.

Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell.

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: -0.91 ± 0.023, atropine: -0.3 ± 0.08, and diacerein: -0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) ß1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-ß1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

The Gaps of Healthcare Service Quality in Nurse Practitioner Practice and Its Associated Factors From the Patients' Perspective.

PURPOSE: This study investigates the expectations, perceptions, and gaps of the healthcare service quality (HSQ) from the patients' perspective, and explores the significant demographic and clinical factors associated with the HSQ in nurse practitioner practice (NPP). DESIGN: A cross-sectional design was carried out, with convenience sampling performed under the NPP in Taiwan, from June to November 2016. METHODS: The Nurse Practitioner Healthcare Service Quality Scale was used to assess the expectations, perceptions, and gaps of the HSQ. The demographics, clinical characteristics, and symptom severity of patients were collected, and the Importance-Performance Analysis was applied to identify the priority of ranking items for the improvement of nurse practitioners (NPs). The Generalized Estimating Equation was used to explore the factors associated with the HSQ in NPP. FINDINGS: A total of 200 patients completed the questionnaires. The results revealed that the patients had overall high expectations (M = 6.35, SD = 0.46), moderate perceptions (M = 4.21, SD = 0.95), and a mild HSQ gap (M = -2.14, SD = 0.69), with statistically significant differences (p < .001). In NPP, the largest gap in the HSQ dimensions was reliable responsiveness, followed by empathy, assurance, and tangibility. Patients with greater symptom severity and a longer in-hospital stay were associated with larger HSQ gaps; however, patients who were transferred from the emergency department had smaller gaps than those in the outpatient department. CONCLUSIONS: The patients' expectations were not fully satisfied in the NPP, especially for the dimensions of reliable responsiveness and empathy. The patients' symptom severity was a significant factor related to the gaps in the HSQ. The awareness of unmet needs, from the patients' perspective, could guide the convergence of a rational policy to promote healthcare delivery in the NPP. CLINICAL RELEVANCE: The managers of NPP need to pay attention to increasing NPs' reliable responsiveness and empathy, by setting the appropriate scope of practice, regulating the NP-to-patient ratio, applying for certification programs in prescribing training, and cultivating patient-centered care with shared decision making. In addition, building up the knowledge and competency of symptom management is also suggested for NP training.

Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis.

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

Transition of Living Arrangement and Cognitive Impairment Status among Chinese Older Adults: Are They Associated?

Background and Objectives: Living arrangement is a crucial factor for older adults' health. It is even more critical for Chinese older adults due to the tradition of filial piety. With the aging of China's population, the prevalence of cognitive impairment among older adults has increased. This study examines the association between living arrangement transition and cognitive function among Chinese older adults. Materials and Methods: Using three waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS; 2008-2009, 2011-2012, and 2014), we analyzed data for older adults (age ≥ 65) who lived with other household members and reported good cognitive function or mild cognitive impairment when they participated in the survey. Multistate Cox regression was employed to study changes in cognitive function. Results: Older adults who transitioned to living alone had lower risk of cognitive impairment (hazard ratio (HR) = 0.66, 95% CI: 0.52, 0.83; p < 0.01), compared with those who continued to live with other household members. Moving into an institution was also not associated with cognitive impairment. Conclusions: With older adults' transition to living alone, public health practitioners or social workers might educate them on the benefits of such a living arrangement for cognitive function.

Deep learning for fully automated tumor segmentation and extraction of magnetic resonance radiomics features in cervical cancer.

OBJECTIVE: To develop and evaluate the performance of U-Net for fully automated localization and segmentation of cervical tumors in magnetic resonance (MR) images and the robustness of extracting apparent diffusion coefficient (ADC) radiomics features. METHODS: This retrospective study involved analysis of MR images from 169 patients with cervical cancer stage IB-IVA captured; among them, diffusion-weighted (DW) images from 144 patients were used for training, and another 25 patients were recruited for testing. A U-Net convolutional network was developed to perform automated tumor segmentation. The manually delineated tumor region was used as the ground truth for comparison. Segmentation performance was assessed for various combinations of input sources for training. ADC radiomics were extracted and assessed using Pearson correlation. The reproducibility of the training was also assessed. RESULTS: Combining b0, b1000, and ADC images as a triple-channel input exhibited the highest learning efficacy in the training phase and had the highest accuracy in the testing dataset, with a dice coefficient of 0.82, sensitivity 0.89, and a positive predicted value 0.92. The first-order ADC radiomics parameters were significantly correlated between the manually contoured and fully automated segmentation methods (p < 0.05). Reproducibility between the first and second training iterations was high for the first-order radiomics parameters (intraclass correlation coefficient = 0.70-0.99). CONCLUSION: U-Net-based deep learning can perform accurate localization and segmentation of cervical cancer in DW MR images. First-order radiomics features extracted from whole tumor volume demonstrate the potential robustness for longitudinal monitoring of tumor responses in broad clinical settings. U-Net-based deep learning can perform accurate localization and segmentation of cervical cancer in DW MR images. KEY POINTS: • U-Net-based deep learning can perform accurate fully automated localization and segmentation of cervical cancer in diffusion-weighted MR images. • Combining b0, b1000, and apparent diffusion coefficient (ADC) images exhibited the highest accuracy in fully automated localization. • First-order radiomics feature extraction from whole tumor volume was robust and could thus potentially be used for longitudinal monitoring of treatment responses.

Comparative effects of combined physical therapy with Kinesio taping and physical therapy in patients with knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To compare therapeutic effects between physical therapy (PT) combined with Kinesio taping (KT) and PT alone in knee osteoarthritis treatment. DATA SOURCES: PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, CNKI, WangFang Data, and Google Scholar were searched until 16 April 2020. REVIEW METHODS: Randomized controlled trials comparing pain reduction (visual analogue scale and numeric pain rating scale) and functional improvement (Western Ontario and McMaster Universities Osteoarthritis Index) between PT + KT and PT in knee osteoarthritis treatment were included. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: A total of 15 studies with 546 patients were included, and their outcomes for one to six weeks after initial treatments were compared. An overall trend favoring PT + KT over PT alone was indicated by greater pain score reduction (mean difference (MD) = -0.70, 95% confidence interval (CI) = -1.14 to -0.26; P = 0.002) and functional improvement (MD = -5.45, 95% CI = -10.23 to -0.66; P = 0.03) with the former. Significant pain reduction (MD = -0.72, 95% CI = -1.18 to -0.26; P = 0.002) and functional improvement (MD = -6.05, 95% CI = -11.18 to -0.93; P = 0.02) were reported within six weeks after initial treatments. CONCLUSION: Compared with PT alone, PT combined with KT provided better therapeutic effect regarding pain reduction and functional improvement in patients with knee osteoarthritis. The additional pain reduction and functional improvement could last at least six weeks after initial treatments.

Label-Free Impedimetric Immunosensors Modulated by Protein A/Bovine Serum Albumin Layer for Ultrasensitive Detection of Salbutamol.

The sensing properties of immunosensors are determined not only by the amount of immobilized antibodies but also by the number of effective antigen-binding sites of the immobilized antibody. Protein A (PA) exhibits a high degree of affinity with the Fc part of IgG antibody to feasibly produce oriented antibody immobilization. This work proposes a simple method to control the PA surface density on gold nanostructure (AuNS)-deposited screen-printed carbon electrodes (SPCEs) by mixing concentration-varied PA and bovine serum albumin (BSA), and to explore the effect of PA density on the affinity attachment of anti-salbutamol (SAL) antibodies by electrochemical impedance spectroscopy. A concentration of 100 µg/mL PA and 100 µg/mL BSA can obtain a saturated coverage on the 3-mercaptoproponic acid (MPA)/AuNS/SPCEs and exhibit a 50% PA density to adsorb the amount of anti-SAL, more than other concentration-varied PA/BSA-modified electrodes. Compared with the randomly immobilized anti-SAL/MPA/AuNS/SPCEs and the anti-SAL/PA(100 µg/mL):BSA(0 µg/mL)/MPA/AuNS/SPCE, the anti-SAL/PA(100 µg/mL): BSA(100 µg/mL)/MPA/AuNS/SPCE-based immunosensors have better sensing properties for SAL detection, with an extremely low detection limit of 0.2 fg/mL and high reproducibility (<2.5% relative standard deviation). The mixture of PA(100 µg/mL):BSA(100 µg/mL) for the modification of AuNS/SPCEs has great promise for forming an optimal protein layer for the oriented adsorption of IgG antibodies to construct ultrasensitive SAL immunosensors.

The mediating effects of leisure engagement on relationships between caregiving stress and subjective wellbeing among family caregivers of persons with cognitive impairment: A cross-sectional study.

Family caregivers of persons with cognitive impairment experience changes in reductions in leisure engagement, which can decrease their subjective wellbeing (leisure satisfaction, negative affect and positive affect). We recruited 100 dyads of patients with cognitive impairment and family caregivers by convenience sampling from outpatient memory clinics and daycare centers in northern Taiwan. Hierarchical regression analysis tested the mediating effects of leisure engagement on the relationship between caregiving stress and subjective wellbeing. Results indicated that the restorative experience of event/tourism activities (ß = 0.23, p < .05) significantly mediated between caregiving stress and leisure satisfaction. In addition, the only significant mediator between caregiving stress and negative affect was leisure barriers (ß = 0.21, p < .05). Both of the regression models explained 27% of the variance. Future development of leisure interventions should focus on reducing leisure barriers and providing event and tourism activities to the dyads. (146 words).

Immune checkpoint inhibitor therapy-induced hypophysitis ∼ a case series of Taiwanese patients.

Immune checkpoint blockade-based immunotherapy is a new modality of cancer treatment with a unique mechanism that has gained increased numbers of indication and is now used in several cancer types. However, immune-related adverse events (irAEs) emerge as a new entity of diseases involving one or multiple organ systems. irAEs could result in interruption of immunotherapy, morbidities or even death. Among various manifestations of irAEs, immune-mediated hypophysitis is rare but important, requiring prompt diagnosis and treatment to avoid life-threatening conditions. We report seven cases of immune-mediated hypophysitis in Taiwan. They suffered from various types of advanced cancer and received different regimens of immune checkpoint inhibitors. The time of onset after initiation of immunotherapy ranged from 5 to 36 weeks. All seven subjects were diagnosed of central adrenal insufficiency, while four of them had primary hypothyroidism. There was no typical finding of infiltrative hypophysitis on the pituitary MRI. There was no documented hormone recovery after diagnosis of hypophysitis, and the tumor responses to immunotherapy were variable in these seven patients. In conclusion, immune-mediated hypophysitis is often irreversible. Fortunately, it can be managed adequately with hormone replacements. Further investigations are warranted to unveil underlying mechanisms and ethnic differences to guide the solutions.

Application of two-dimensional fractional-order convolution and bounding box pixel analysis for rapid screening of pleural effusion.

Pleural effusion is a pathologic symptom in which there is accumulation of body fluids around the lungs. A chest radiograph is a rapid examination technique and does not require complex setup for making a preliminary diagnosis of lung and heart diseases. In radiographic visualization, the symptom patterns appear as light or dark areas in the lung cavity. Computer-aided diagnosis is an automatic manner that can rapidly highlight the object region by preanalyzing medical images. It can improve the problems of manual inspection and allow diagnosis in remote medical facilities. Based on the ratios of lung anatomy, the automatic screening manner based on pattern recognition can be viewed as pixel value detection in the bilateral lung cavities. In this study, a fractional-order convolution (FOC) process is used to enhance the original image for an accurate extrapolation of the desired object in an image. The specific object image feature can be improved, and an accurate quantification of the pleural effusion region can be obtained using the suitable ranges of fractional-order parameters. Based on the boundaries of homogeneous regions, the pixel ratios of the lung anatomy between normal and abnormal conditions can be computed. The pleural effusion sizes and volumes can be rapidly estimated through the number of pixel changes. The experimental results reveal that the feature maps are similar and stable on image enhancement and segmentation with two fractional-order enhancement masks, as fractional-order v = 0.05 to 0.20 for mask 1# and v = 0.80 to 0.95 for mask 2#, respectively. The results also demonstrate the feasibility of the study on combining two-dimensional image FOC-process and bounding box pixel analysis to estimate the moderate and large effusion sizes from 500-2,000 mL.