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This study aimed to provide preliminary evidence on feasibility of the inaugural use of teleconsultation between acute hospitals and primary care for acute wound management in Singapore. Post-surgical patients with carbuncle wounds, perianal abscess wounds or surgical abdominal dehiscence wounds were recruited from an acute hospital. Instead of receiving their follow up care at the acute care tertiary hospital, patients were given the option to receive their care at primary care facilities instead, supported by teleconsultation wound services provided by wound care nurses from the hospital. The following outcome measures were collected: number of care sessions required (until wound healed), readmissions or referrals back to hospital, cost (patient's and healthcare provider's perspective), patients' and nurses' satisfaction. In total, 18 patients were recruited and completed the study (teleconsult group = 5; tertiary care clinic group = 13). The mean age (SD) of patients were 63.2 (SD 11.5) years old in the teleconsult group and 47.9 years old (SD 11.5) in the tertiary care clinic group. There were 7 female (54%), and 6 male (46%) in the tertiary care clinic group whereas teleconsult group consisted of male only (n = 5). Most had carbuncle wounds (teleconsult group: n = 4; 80%); tertiary care clinic group: (n = 10; 77%). For patients with carbuncle wounds, the average number of care sessions required were 21 and 33 for the tertiary care clinic and teleconsult respectively. None of the patients in the teleconsult group were referred back to the tertiary care hospital. All 16 nurses (n = 6 from acute care hospital, n = 10 from polyclinics) who participated in the feedback survey cited convenience, ease of tracking wound sizes, and closer collaboration between the acute care and primary care nurses as advantages of the service. Wound teleconsultation is feasible and potentially cost savings for patients with acute complex wounds.

Objectives Increasing evidence supports a bidirectional relationship between major depressive disorder (MDD) and obesity, but the role of visceral adipose tissue (VAT) as a measure of obesity in relation to MDD is not well understood. Here we review literature investigating the link between MDD and VAT in terms of biomarkers, sex differences, and aging. Methods PubMed, EMBASE, PsycINFO, and CINAHL searches were conducted on December 11, 2020. No date or language limits were imposed. Major concepts searched were Depressive Disorder linked with Adipose Tissue, White, Hypothalmo-Hypophyseal System, and Pituitary-Adrenal System in addition to keywords. A final set of 32 items meeting criteria for inclusion. Results Converging biological evidence suggests a significant bidirectional relationship between VAT and MDD across the lifespan. In adulthood, greater VAT was associated with increased risk for depression, especially in vulnerable groups such as individuals who are overweight/obese, postmenopausal women, and individuals with comorbid medical or psychiatric illness. In older adults, sarcopenia had an impact on the relationship between abnormal VAT and risk of depression. Additionally, sex differences emerged as a potential factor affecting the strength of the association between VAT and depression. Conclusions Elucidating the pathophysiological mechanisms associated with increased rates of depression in obese individuals will be crucial for developing specific treatment strategies that seek to improve outcomes in individuals with comorbid depression and obesity. Moreover, identifying age- and sex-specific risk factors may contribute to a more personalized medicine approach, thereby improving the quality of clinical care.

The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME. Methods: Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs in vitro and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics. In vivo patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs. Results: The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity in vitro and in vivo, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs. Conclusions: The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.

The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) still remains controversial. We aimed to investigate whether HCV really affects renal function, and to analyze the association between clinical effects of CHC and decreased kidney function (assessed by glomerular filtration rate (eGFR) level).An estimated 3360 patients with HCV infection and 3360 age- and sex-matched community-based control individuals without HCV were enrolled (1:1, case and control ratio) in this study between 2004 and 2016. We used the modification of diet in renal diseases to calculate eGFR. Demographic and laboratory parameters were assessed, and appropriate statistical methods were performed for the analysis.Multivariate logistic regression analysis revealed that serum alanine aminotransferase level (odds ratio [OR] 0.998; 95% confidence interval [CI] 0.997-0.999; P = 0.001), platelet count (OR 0.997; 95% CI 0.995-0.999; p = 0.002), and hypertension (OR 1.31; 95% CI 1.03-1.66; P = 0.027) were significantly associated with HCV infection and serum triglyceride levels (OR 1.001; 95% CI 1.00-1.002; p = 0.005), platelet count (OR 0.996; 95% CI 0.995-0.997; p0.001), body mass index (BMI)25 (OR 1.43; 95% CI 1.23-1.67; p0.001), hypertension (OR 1.69; 95% CI 1.42-1.99; p0.001), hyperlipidemia (OR 1.32; 95% CI 1.02-1.71; p = 0.035), and diabetes (OR 1.33; 95% CI 1.03-1.71; p = 0.032) were significantly associated with a low eGFR (90 mL/min/m3) in control subjects. The BMI25 kg/m2, hypertension, and diabetes were found to be associated with low eGFR interaction with the HCV infection, via a multivariate analysis.Our study found that the patients with HCV infection are associated with a low eGFR compared with non-HCV-infected patients. This association is consistent in obese, diabetic, and hypertensive patients.

Pyuria is common in chronic kidney disease (CKD), which could be due to either urinary tract infection (UTI) or renal parenchymal inflammation. Only little is known regarding the association of pyuria or UTI with renal outcomes. We investigated 3226 patients with stage 3–5 CKD. Pyuria was defined as ≥ 50 WBC per high-power field (hpf) and was correlated to old age, female, diabetes, hypoalbuminemia, lower eGFR, and higher inflammation status. In Cox regression, patients with more than one episode of pyuria in the first year (11.8%) had increased risks for end-stage renal disease (ESRD) [hazard ratio (95% CI): 1.90 (1.58–2.28); p 0.001], rapid renal function progression [odds ratio (95% CI): 1.49 (1.13–1.95); p = 0.001], and all-cause mortality [hazard ratio: 1.63 (1.29–2.05); p 0.001], compared to those without pyuria. In a subgroup analysis, the risk of pyuria for ESRD was modified by CKD stages. We investigated the effects of UTI (urinary symptoms and treated by antibiotics) and pyuria without UTI (urine WBC

Cutis verticis gyrata (CVG) is a rare skin disorder characterised by thick skin folds and grooves, resembling the gyri and sulci of the cerebral cortex. It can be classified as primary essential, primary non-essential and secondary CVG. The rarity of the condition poses a challenge in the diagnosis and ultimately requires good communication between the clinician and the dermatopathologist for diagnosis. Many names have been given to the condition, including Robert-Unna syndrome, cutis verticis plicata, paquidemia verticis gyrata, cutis sulcata, cutis striata or “bulldog” scalp syndrome. To date, the treatment is still limited to plastic surgeons with excision of the folds, scalp reduction and reconstruction. In this article, we are sharing a rare case and the surgical management of a middle age gentleman with cutis verticis gyrata secondary to cerebral intradermal nevus (CIN) over his occipital scalp., {"references":["Larsen F, Birchall N. Cutis verticis gyrata: three cases with different aetiologies that demonstrate the classification system. Australas J Dermatol. 2007;48(2):91-4. doi: 10.1111/j.1440-0960.2007.00343.x.","Tucci A, Pezzani L, Scuvera G, Ronzoni L, Scola E, Esposito S, et al. Is cutis verticis Gyrata-Intellectual Disability syndrome an underdiagnosed condition? A case report and review of 62 cases. Am J Med Genet A. 2017;173(3):638-46. doi: 10.1002/ajmg.a.38054.","El-Husseiny M, Yarrow J, Moiemen N. Primary cutis gyrata: Review of literature and a successful new surgical approach. Eur J Plast Surg. 2010;33(3):153-7. doi: 10.1007/s00238-009-0383-y.","Beier JP, Kneser U, Horch RE. Surgical treatment of facial cutis verticis gyrata with direct excision. J Cutan Med Surg. 2007;11(1):4-8. doi: 10.2310/7750.2007.00003.","Taha HM, Orlando A. Butterfly-shape scalp excision: a single stage surgical technique for cutis verticis gyrata. J Plast Reconstr Aesthet Surg. 2014;67(12):1747-9. doi: 10.1016/j.bjps.2014.07.039.","Zhang MJ, Sun ZY, Liu Y, Wu SM, Lu KH. Rare giant secondary cutis verticis gyrata. J Plast Surg Hand Surg. 2011;45(4-5):212-4. doi: 10.3109/02844311.2010.488883.","Mutlu OO, Colak O, Canli M, Akcay A. Scalp Reconstruction With Free Latissimus Dorsi Flap in a Patient With Giant Cutis Verticis Gyrata. J Craniofac Surg. 2016;27(6):e553-e554. doi: 10.1097/SCS.0000000000002862.","Orkin M, Frichot BC 3rd, Zelickson AS. Cerebriform intradermal nevus. A cause of cutis verticis gyrata. Arch Dermatol. 1974;110(4):575-82. doi: 10.1001/archderm.110.4.575.","Desai SC, Sand JP, Sharon JD, Branham G, Nussenbaum B. Scalp reconstruction: an algorithmic approach and systematic review. JAMA Facial Plast Surg. 2015;17(1):56-66. doi: 10.1001/jamafacial.2014.889.","Moehrle M, Lischner S, Dunsche A, Breuninger H, Hauschild A. Cerebriform giant melanocytic nevus of the scalp: report of two cases with different surgical approaches. Dermatol Surg. 2002;28(1):75-9. doi: 10.1046/j.1524-4725.2002.01105.x."]}

Hidradenitis suppurativa (HS) is a chronic debilitating inflammatory disease of the apocrine gland-bearing body areas, characterized by painful recurrent abscess, sinus tract formation, and scarring. The treatment for HS consists of medical and surgical treatments in a multidisciplinary approach. Wide excision and reconstruction over the axillary hidradenitis suppurativa can be challenging due to possible morbidities; for example, scarring can lead to contracture over the axilla. In this report, we present 10 patients who underwent wide excision and reconstruction for the axilla hidradenitis suppurativa in our center from the year 2007 until the year 2017 with a mean follow-up of 3.17 years. All relevant operative information and data were collected from past medical records. Seventeen sites of affected axilla were reconstructed post-wide excision using various methods; from primary closure (n = 5), split thickness skin grafting (n = 5), and local fasciocutaneous flap (n = 2) to pedicle partial latissimus dorsi myocutaneous flap (n = 5). Primary closure is only achievable in smaller axillary defects with mean size of 65.2 cm2. Larger defects with averages 2 to 3 times the size are not amenable for primary closure and require skin grafting or flap coverage. Complications include wound dehiscence (n = 1), poor graft take (n = 3), and marginal flap edge necrosis (n = 1). Local fasciocutaneous flap is versatile and easily designed with the shortest mean operative time of 95 min. Hospital stay is shorter for primary closure and local fasciocutaneous flap with an average of 6 days for each as compared to using skin grafting (20 days) and pedicle partial latissimus dorsi myocutaneous flap (9 days). Only one recurrence (5.8%) was noted in a patient with primary closure post excision. All patients are satisfied with the surgical outcome and have no restriction of movement over their shoulders. Esthetically, reconstruction using primary closure and flap coverage methods is superior to skin grafting. Axillary HS requires complete excision to prevent future recurrence. Reconstructive method with soft tissue coverage presented a better outcome compared to split thickness skin grafting in terms of surgical time, recovery rate, morbidity, as well as functional and esthetic outcomes. Level of evidence: Level IV, therapeutic study.

We aimed to examine the association between metabolic syndrome and the risk of kidney stone development in a large-scale community-based cohort. A total of 121,579 participants enrolled in the Taiwan Biobank were analyzed. They were divided into two groups on the basis of presence of metabolic syndrome. The presence of kidney stone disease was defined by self-reported history of kidney stones. The mean age of participants was 50 years old, and self-reported kidney stones were observed in 3446 (10%) and 4292 (5%) participants with metabolic syndrome and without metabolic syndrome, respectively. Higher prevalence of kidney stone disease was found in participants with metabolic syndrome compared to those without metabolic syndrome (odds ratio (OR), 1.32, 95% confidence interval (95% CI), 1.25 to 1.39). In addition, the risk of incident kidney stone development was analyzed in a longitudinal cohort of 25,263 participants without kidney stones at baseline during a mean follow-up of 47 months. Multivariable Cox regression analysis revealed that the risk for incident kidney stone disease was higher in participants with metabolic syndrome than those without metabolic syndrome (hazard ratio, 1.24, 95% CI, 1.04 to 1.49). Our study suggests that metabolic syndrome does increase the risk of kidney stones.

Background: The safety profile of medications for COVID-19 remains unknown in Malaysia. Our study aims to establish the incidence of adverse drug reaction (ADR) for drugs used in COVID-19 management in a Malaysian tertiary hospital. Methods: This retrospective observational study enrolled patients started on drugs for COVID-19 in Sungai Buloh Hospital from 1 March 2020 to 31 May 2020. Suspected ADRs were evaluated with a trigger tool of pre-defined laboratory values or the adverse events listed in the registered product insert. Causality assessment was conducted when an ADR was suspected using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system, and only cases classified as certain, probable and possible ADR were analysed. Data analysis was completed with descriptive, univariate and multivariate analysis. Results: The study (N = 1,080) identified 217 patients (20.1%) who experienced ADR, with 246 adverse events detected. Most events were related to the gastrointestinal (43.5%), hepatobiliary (36.2%) and cardiac (16.3%) systems. The most commonly suspected drugs were atazanavir (52.7%), chloroquine (36.8%) and lopinavir/ritonavir (34.6%). The independent risk factors of ADR were female (adjusted odds ratio (OR): 1.53; 95% CI 1.06-2.20; p = 0.024), diagnosis of COVID-19 stage 3 (adjusted OR: 2.58; 95% 1.20-5.55; p = 0.015) and stage 4 (adjusted OR: 4.17; 95% CI 1.79-9.73; p = 0.001), and the number of COVID-19 drugs (adjusted OR: 3.34; 95% CI 2.51-4.44; p < 0.001). Conclusion: Medications used in COVID-19 management had resulted in one in five patients experiencing ADR. Our study suggests a similar safety profile when used for FDA-approved indications. Disclaimer: Abstract text might vary slightly from what is displayed in the e-poster., This poster was submitted to the 14th National Conference for Clinical Research (NCCR) in August 18-20, 2021. https://nccrconference.com.my/

The epidermal growth factor receptor (EGFR) is an essential driver of oncogenic signalling, and EGFR inhibitors are some of the earliest examples of successful targeted therapies in multiple types of cancer. The tractability of EGFR as a therapeutic target is overshadowed by the inevitable drug resistance that develops. Overcoming resistance mechanisms requires a deeper understanding of EGFR regulation in cancer cells. In this review, we discuss our recent discovery that the palmitoyltransferase DHHC20 palmitoylates EGFR on the C-terminal domain and plays a critical role in signal regulation during oncogenesis. Inhibiting DHHC20 expression or mutating the palmitoylation site on EGFR alters the EGF-induced signalling kinetics from a transient signal to a sustained signal. The change in signalling is accompanied by a decrease in cell proliferation in multiple human cancer cell lines. Our in vivo studies demonstrate that ablating the gene Zdhhc20 by CRISPR/Cas9-mediated inhibition in a mouse model of oncogenic Kras-driven lung adenocarcinoma potently inhibits tumorigenesis. The negative effect on tumorigenesis is mediated by EGFR since the expression of a palmitoylation-resistant mutant form of EGFR also inhibits Kras-driven lung adenocarcinoma. Finally, reducing EGFR palmitoylation increases the sensitivity of multiple cancer cell lines to existing inhibitors of EGFR and downstream signalling effector pathways. We will discuss the implications of these effects and strategies for targeting these new vulnerabilities.

Bowel perforation as the first presentation of inflammatory bowel disease is rare and unusual in young patients. A previously asymptomatic 21-year-old Asian male presented with perforated small bowel secondary to previously undiagnosed Crohn’s disease. He underwent an exploratory laparotomy and subsequent small bowel resection and was commenced on mesalazine post-operation. He recovered well with subsequent regular follow-up with gastroenterology. The main management of Crohn’s disease is multidisciplinary in nature, and collaboration between different disciplines is inherent with the aim of reducing symptoms and maximizing patient quality of life.

Research indicates smoking increases the risk of various kidney diseases, although the risk of developing kidney stone disease in non-smokers exposed to secondhand smoke is unknown. This study analyzed a total of 19,430 never-smokers with no history of kidney stone disease who participated in the Taiwan Biobank from 2008 to 2019. They were divided into two groups by secondhand smoke exposure; no exposure and exposure groups; the mean age of participants was 51 years, and 81% were women. Incident kidney stone development was observed in 352 (2.0%) and 50 (3.3%) participants in the no exposure and exposure groups during a mean follow-up of 47 months. The odds ratio (OR) of incident kidney stone was significantly higher in the exposure group than the no exposure group [OR, 1.64; 95% confidence interval (95% CI) 1.21 to 2.23]. Participants with > 1.2 h per week exposure were associated with almost twofold risk of developing kidney stones compared with no exposure (OR, 1.92; 95% CI 1.29 to 2.86). Our study suggests that secondhand smoke is a risk factor for development of kidney stones and supports the need for a prospective evaluation of this finding.

Cast immobilization is a noninvasive and effective option in the treatment of fractures in children. However, its use can be associated with complications, such as pressure sores, skin infections, thermal injuries, and joint stiffness. In clinical practice, retained foreign objects in casts are not uncommon. This study aims to ascertain reasons for foreign objects being retained in casts and their effects on the skin. Eighteen children with retained foreign objects in their casts were identified and interviewed. Patient demographics, type of fracture and cast applied, nature of foreign body, and medical complications caused directly by the foreign object were also recorded for analysis. The foreign objects retained included coins, stationery, toy parts, cutlery, and hygiene items. The most common reason for their retention was to relieve itch, followed by accidental insertion and deliberate play. More than half of the children did not suffer complications, and the rest were all skin complications, with the most severe one being an infected skin ulcer that required oral antibiotics. Although the complications of retained foreign bodies are limited to the skin, they can worsen with delayed treatment. Cast care and itch reduction advice must be clearly communicated to patients and their caregivers. Foreign objects in casts must be emergently removed. Level of Evidence: Level 4 Evidence.

The aim of this study was to investigate whether the timing of surgery and surgical technique affect the rate of osteonecrosis in unstable slipped capital femoral epiphysis (SCFE). This is a retrospective review of all unstable slips that were treated at our institution over 8.5 years with a minimum follow-up period of 12 months. Patients with stable slips were excluded from this analysis. Demographic data, time to surgery, and surgical technique were analyzed. Twenty-three unstable slips were included for study after excluding 40 stable slips. There were 17 males and six females, with an average age of 11.9 years; 13 patients had right SCFEs. The average time from diagnosis to surgery was 57.7 h. Nine (39.1%) surgeries were performed within 24 h of admission, whereas 14 (60.9%) surgeries were performed after 24 h. Minimum follow-up was 23 months. Two patients developed osteonecrosis: one underwent surgery within 24 h of admission and the other after 24 h. Both underwent in-situ screw fixation. In the group that did not develop osteonecrosis, 76.2% underwent in-situ screw fixation and 23.8% underwent manipulative reduction. The rate of developing osteonecrosis following screw fixation in unstable SCFE was unrelated to whether surgery was performed before or after 24 h of admission (P = 1.0), or whether in-situ screw fixation or manipulative reduction pre-fixation was performed (P = 0.605). The results of this small series challenge the practice of stabilizing unstable SCFEs emergently and the belief that gentle manipulative reduction pre-fixation is not recommended because it may increase the rate of osteonecrosis. Level of Evidence: Level IV Evidence.

Zika virus (ZIKV) is a mosquito-borne virus that has garnered a lot of attention in recent years, due to the explosive epidemic from 2014 to 2016. Since its introduction in the Americas in late 2014, ZIKV has spread at an unprecedented rate and scale throughout the world and infected millions of people. Its infection has also been associated with severe neurological disorders like Guillain-Barre syndrome and microcephaly in fetuses. Despite these, there is currently no approved antiviral against ZIKV. In this study, an immunofluorescence-based high throughput screen was conducted on a library of 483 flavonoid derivatives to identify potential anti-ZIKV compounds. Flavonoids, which are natural polyphenolic compounds found in plants, represent an attractive source of antivirals due to their abundance in food and expected low toxicity. From the primary screen, three hits were selected for validation by cell viability and viral plaque reduction assays. Pinocembrin, a flavanone found in honey, tea and red wine, was chosen for downstream studies as it exhibited the strongest inhibition of ZIKV infection in human placental JEG-3 cells (IC50 = 17.4 μM). Time-course studies revealed that pinocembrin acts on post-entry process(es) of the ZIKV replication cycle. Furthermore, pinocembrin inhibits viral RNA production and envelope protein synthesis based on quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses. This study has demonstrated for the first time the in vitro anti-ZIKV activity of pinocembrin.

Congenital bifid tongue with cleft palate is a very rare malformation with different variations. We are reporting 2 cases of rare congenital bifid tongue with cleft palate in our hospital setting and their surgical management. A multidisciplinary approach, well-planned staged operations, rehabilitation, and follow-up are needed to achieve favorable outcomes.

Background Mutations in PKD1 or PKD2 gene lead to autosomal dominant polycystic kidney disease (ADPKD). The mechanism of ADPKD progression and its link to increased cardiovascular mortality is still elusive. Methods We differentiated ADPKD patient induced pluripotent stem cells (iPSCs) to cardiomyocytes (CMs). The electrophysiological properties at the cellular level were analyzed by calcium imaging and whole cell patch clamping. Findings The ADPKD patient iPSC-CMs had decreased sarcoplasmic reticulum calcium content compared with Control-CMs. Spontaneous action potential of the PKD2 mutation line-derived CMs demonstrated slower beating rate and longer action potential duration. The PKD1 mutation line-derived CMs showed a comparable dose-dependent shortening of phase II repolarization with the Control-CMs, but a significant increase in beating frequency in response to L-type calcium channel blocker. The PKD1-mutant iPSC-CMs also showed a relatively unstable baseline as a greater percentage of cells exhibited delayed afterdepolarizations (DADs). Both the ADPKD patient iPSC-CMs showed more β-adrenergic agonist-elicited DADs compared with Control-CMs. Interpretation Characterization of ADPKD patient iPSC-CMs provides new insights into the increased clinical risk of arrhythmias, and the results enable disease modeling and drug screening for cardiac manifestations of ADPKD. Fund Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Technology Supporting Platform Axis Scheme, Thematic Research Program and Summit Research Program, and Kaohsiung Medical University Hospital, Taiwan.

Low transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1–4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (

BACKGROUND This study aimed to (1) investigate the association of prognostic awareness with psychological (distress level and emotional well-being) and spiritual well-being among patients with heart failure, and (2) assess the main and moderating effects of illness acceptance on the relationship between prognostic awareness and psychological and spiritual well-being. METHODS AND RESULTS This study used baseline data of a Singapore cohort of patients with heart failure (N = 245) who had New York Heart Association class 3 or 4 symptoms. Patients reported their awareness of prognosis and extent of illness acceptance. Multivariable linear regressions were used to investigate the associations. Prognostic awareness was not significantly associated with psychological and spiritual well-being. Illness acceptance was associated with lower levels of distress (β [SE] = -0.9 [0.2], P < .001), higher emotional well-being (β [SE] = 2.2 [0.4], P < .001), and higher spiritual well-being (β [SE] = 5.4 [0.7], P < .001). Illness acceptance did not moderate the associations of prognostic awareness with psychological and spiritual well-being. CONCLUSIONS This study suggests that illness acceptance could be a key factor in improving patient well-being. Illness acceptance should be regularly assessed and interventions to enhance illness acceptance should be considered for those with poor acceptance.

BACKGROUND AND AIM Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P

CASE We report a rare case of polymetatarsia without polydactyly. Our patient presented with pain and difficulty with shoewear. Radiographs showed an accessory metatarsal arising from the lateral aspect of the fourth metatarsal proximal metaphysis, fusing distally with the medial aspect of the fifth metatarsal head to form a single metatarsophalangeal joint. He was treated with a chevron osteotomy of the conjoined complex and an Akins osteotomy of the fifth proximal phalanx. Our patient recovered functionally, and his pain improved postoperatively. CONCLUSION The chevron osteotomy is an option for treating polymetatarsia without polydactyly with the aim of reducing the forefoot width. LEVEL OF EVIDENCE Case study, level 5.

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P

Background The rising prevalence of childhood obesity in developing and developed countries poses a major public health challenge to policy makers and an effective strategy to promote physical activity among adolescents is warranted. This study aimed to evaluate the effectiveness of providing descriptive norms messages with personal identification in promoting physical activity among adolescents by measuring step counts via a randomized controlled trial (NCT03081013). Methods A total of 311 participants aged 13–16 were randomized into two study arms (Onymous and Anonymous Arms). Each arm consisted of 13 groups of 12 participants. During the trial, participants received weekly short message service (SMS) about their past week’s physical activity performance. Participants in the Anonymous Arm received information about step counts of group members ranked from highest to lowest. Participants in the Onymous Arm received the same information with the group members’ full names. Participants’ quality of life, depression, physical activity social support, self-efficacy and enjoyment before and after the intervention were also evaluated. This study adheres to the CONSORT guidelines. Results The number of steps was not higher when descriptive norm message was onymous compared to when it was anonymous. Scores in quality of life, depression, social support, self-efficacy, and enjoyment of physical activity were not significantly different between both arms (p > 0.05). Conclusions Our findings indicated that the effect of providing descriptive norms messages containing personal identification on physical activity promotion was not evident in the main analysis. Future studies may consider using a more relevant reference group to use social norms as a tool to increase physical activity among adolescents. Trial registration ClinicalTrials.gov - NCT03081013. Registered 15 Mar 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03081013

Background The accurate assessment of liver fibrosis among hemodialysis patients with chronic hepatitis C (CHC) is important for both treatment and for follow up strategies. Applying the non-invasive methods in general population with viral hepatitis have been successful but the applicability of the aminotransferase/platelet ratio index (APRI) or the fibrosis-4 index (FIB-4) in hemodialysis patients need further evaluation. Materials and methods We conducted a prospective, multi-center, uremic cohort to verify the applicability of APRI and FIB-4 in identifying liver fibrosis by reference with the standard transient elastography (TE) measures. Results There were 116 CHC cases with valid TE were enrolled in our analysis. 46 cases (39.6%) were classified as F1, 35 cases (30.2%) as F2, 11 cases (9.5%) as F3, and 24 cases (20.7%) as F4, respectively. The traditional APRI and FIB-4 criteria did not correctly identify liver fibrosis. The optimal cut-off value of APRI was 0.28 and of FIB-4 was 1.91 to best excluding liver cirrhosis with AUC of 76% and 77%, respectively. The subgroup analysis showed that female CHC hemodialysis patients had better diagnostic accuracy with 74.1% by APRI. And CHC hemodialysis patients without hypertension had better diagnostic accuracy with 78.6% by FIB-4. Conclusions This study confirmed the traditional category level of APRI and FIB-4 were unable to identify liver fibrosis of CHC hemodialysis patients. With the adjusted cut-off value, APRI and FIB-4 still showed suboptimal diagnostic accuracy. Our results suggest the necessary of TE measures for liver fibrosis in the CHC uremic population.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is used in managing and staging prostate cancer, but can identify other non-prostate pathology. We present the first reported case where small bowel gastrointestinal stromal tumour (GIST) has been incidentally identified on PSMA-PET scan and highlight the need for awareness of other pathology being identified on PSMA-PET/CT.

Epithelial–mesenchymal transition (EMT)/mesenchymal–epithelial transition (MET) processes are proposed to be a driving force of cancer metastasis. By studying metastasis in bone marrow-derived mesenchymal stem cell (BM-MSC)-driven lung cancer models, microarray time-series data analysis by systems biology approaches revealed BM-MSC-induced signaling triggers early dissemination of CD133+/CD83+ cancer stem cells (CSCs) from primary sites shortly after STAT3 activation but promotes proliferation towards secondary sites. The switch from migration to proliferation was regulated by BM-MSC-secreted LIF and activated LIFR/p-ERK/pS727-STAT3 signaling to promote early disseminated cancer cells MET and premetastatic niche formation. Then, tumor-tropic BM-MSCs circulated to primary sites and triggered CD151+/CD38+ cells acquiring EMT-associated CSC properties through IL6R/pY705-STAT3 signaling to promote tumor initiation and were also attracted by and migrated towards the premetastatic niche. In summary, STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates the EMT–MET switch within the distinct molecular subtypes of CSCs to complete the metastatic process.

This study aimed to investigate the risk of dementia among subgroups of patients receiving concurrent antidepressant and hypnotic treatment, antidepressants alone, and hypnotics alone.Multivariate Cox proportional hazards regression models were used to determine the effects of antidepressants and hypnotics on dementia risk after adjusting for potential confounders.Compared with the reference group, patients receiving concurrent antidepressant and hypnotic treatment had the highest adjusted hazard ratio (aHR: 2.390, 95% CI: 2.224-2.536; P0.001) for all-cause dementia, followed by those receiving antidepressants alone (aHR: 1.919, 95% CI: 1.811-2.012; P0.001) and hypnotics alone (aHR: 1.458, 95% CI: 1.397-1.527; P0.001). With regard to dementia subtypes, trends similar to those for all-cause dementia were observed for Alzheimer's dementia, vascular dementia and other types of dementia. The sensitivity analysis conducted also found the robustness of findings. Notably, inconsistent findings were observed in subgroup with depression, revealing a null association between concurrent antidepressant and hypnotic treatment (aHR: 0.496; 95% CI: 0.183-1.343; P = 0.175) or hypnotics alone (aHR: 2.750; 95% CI: 0.797-9.482; P = 0.102) and the risk of dementia, and a negative association between antidepressants alone (aHR: 0.351; 95% CI: 0.130-0.942; P = 0.032) and the risk of dementia.A null or negative association was observed between concurrent antidepressant and hypnotic treatment, antidepressants alone, hypnotics alone, and the dementia risk in the subgroup of patients with depression, suggesting the absence of an association between dementia risk and antidepressants alone or hypnotics alone.

We report the engendering an isogenic iPSC line from the IBMS-iPSC-014-05 with homozygous correction of the R803X, Chr4: 88989098C > T in PKD2, using CRISPR/Cas9 technology. The results from the isogenic control, IBMS-iPSC-014-05C, showed that mutation had been corrected, while maintaining normal morphology, pluripotency, and differentiation capacity into three germ layers.

The surgical treatment of moderate-advanced hallux rigidus is controversial. Cheilectomy is widely used but has recurrence rates of up to 30%. Dorsal oblique metatarsal osteotomy (DOO) has also shown good results, however, there is no study comparing outcomes of the DOO against cheilectomy.This was a retrospective propensity score matched study based on registry data from a single tertiary institution. Between 2007 and 2017, all patients who had undergone dorsal cheilectomy or DOO for hallux rigidus were included. Patients with previous foot surgery, revision surgeries, and concomitant surgical procedures were excluded. Clinical outcomes, complication rates, revision rates and patient satisfaction were assessed at 2 years postoperatively.There were 44 patients (34 cheilectomy, 10 DOO). After propensity score matching, 17 cheilectomy and all 10 DOO cases were selected for comparison. Patients in both groups had a significant improvement in visual analogue pain scores (VAS) and AOFAS 1st toe scores 2-years post-operatively (P0.001) with high levels of post-operative satisfaction (85.1%). Overall there were no statistically significant differences in post-operative scores, improvement in scores, complication rates, revision rates, and levels of patient satisfaction between groups.Both the DOO and cheilectomy give similarly good outcomes for moderate-advanced hallux rigidus. Further studies are needed to elucidate differences in indications for each procedure.

Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. The expression of CAD180 and CAD112 was elevated in human umbilical vein endothelial cells transduced with scAAV2-CAD180 or scAAV2-CAD112, respectively, and both inhibited angiogenic activity in vitro. Intravitreal gene delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly inhibited ischemia-induced retinal neovascularization in rat eyes (CAD180: 52.7% reduction; CAD112: 49.2% reduction) compared to scAAV2-mCherry, as measured in retinal flatmounts stained with isolectin B4. Moreover, the retinal structure and function were unaffected by scAAV2-CAD180 or scAAV2-CAD112, as measured by optical coherence tomography and electroretinography. Moreover, subretinal delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly attenuated laser-induced choroidal neovascularization in mouse eyes compared to scAAV2-mCherry, as measured by fundus fluorescein angiography (CAD180: 62.4% reduction; CAD112: 57.5% reduction) and choroidal flatmounts (CAD180: 40.21% reduction; CAD112: 43.03% reduction). Gene delivery using scAAV2-CAD180 or scAAV2-CAD112 has significant potential as a therapeutic option for the management of ocular neovascularization.

Nicotine is a major toxic and hazardous component of cigarette smoke, and it has been widely used in nicotine replacement therapy (NRT). This study was aimed to investigate the effects of chronic low-dose nicotine on sperm characteristics and reproductive organ integrity in adolescent male Sprague-Dawley rats.Twelve rats were equally divided into two groups. Group I received normal saline, and group II received 0.6 mg/kg body weight nicotine intraperitoneally for 28 consecutive days. At the end of the experimental period, sperm was collected for sperm characteristic evaluation, and the testes and prostate were isolated for biochemical and morphological analysis. The effects of nicotine on the body and reproductive organ weights of the animals were evaluated.Chronic nicotine treatment significantly (A low-dose nicotine exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and induced oxidative stress in the testes and prostate.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited forms of polycystic kidney disease, and is characterized by the growth of numerous cysts in both kidneys. Here we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 63-year-old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the Sendai-virus delivery system. Downstream characterization of these iPSCs showed that they possessed normal karyotyping, were free of genomic integration, retained the disease-causing PKD2 mutation, expressed pluripotency markers and could differentiate into three germ layers.

Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment. We reported the generation and characterization of an iPS cell line, IBMS-iPSC-063-06, from a patient carrying the BBS2 homologous c534 + 1G > T mutation. The generated iPS cell line retains the mutation and exhibits pluripotency and differentiation ability both in vivo and in vitro condition.

Autosomal dominant polycystic kidney disease is one of the most prevalent forms of inherited cystic kidney disease, and can be characterized by kidney cyst formation and enlargement. Here we report the generation of a Type 1 ADPKD disease iPS cell line, IBMS-iPSC-012-12, which retains the conserved deletion of PKD1, normal karyotype and exhibits the properties of pluripotent stem cells such as ES-like morphology, expression of pluripotent markers and capacity to differentiate into all three germ layers. Our results show that we have successfully generated a patient-specific iPS cell line with a mutation in PKD1 for study of renal disease pathophysiology.

// Po-Chih Chen 1, 2 , Jiun-Chi Huang 3, 4, 5, 6, * , Szu-Chia Chen 3, 4, 5, 6 , Pei-Yu Wu 4, 5 , Jia-Jung Lee 4, 6 , Yi-Wen Chiu 4, 7 , Jer-Ming Chang 4, 6, 8 , Hung-Chun Chen 4, 7 and Yeou-Lih Huang 1, 2, 9, * 1 Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Department of Internal Medicine, Kaohsiung Municipal Cijin Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Department of Chemistry, National Sun Yat-sen University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Jiun-Chi Huang, email: karajan77@gmail.com Yeou-Lih Huang, email: yelihu@kmu.edu.tw Keywords: diabetes mellitus, transmitral E wave velocity, early diastole mitral velocity, chronic kidney disease, cardiovascular event Received: June 16, 2017 Accepted: September 21, 2017 Published: October 10, 2017 ABSTRACT The association between DM and left ventricular diastolic dysfunction, assessed using the ratio of peak early transmitral filling wave velocity (E) to early diastolic velocity of mitral annulus (Ea), with cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) remains uncertain. This study included 356 CKD stage 3–5 patients underwent echocardiography. All patients were classified into four groups based on the presence of DM and E/Ea ≤ or > 9. CV events included CV death, hospitalization for heart failure, unstable angina or nonfatal myocardial infarction, sustained ventricular arrhythmia, transient ischemic attack, and stroke. There were 58 CV events during the mean observation period of 25.0 months. A combination of the presence of DM and E/Ea > 9 (vs . a combination of non-DM and E/Ea ≤ 9) was associated with CV events in unadjusted model (hazard ratio [HR], 6.990; 95% confidence interval [CI], 2.753–17.744; p < 0.001), and in a multivariate adjusted model (HR, 3.037; 95% CI, 2.088–7.177; p = 0.025). In the patients without DM, the E/Ea ratio ( p = 0.033) improved the prediction of CV events, compared to the E/Ea ratio ( p = 0.018), left atrial diameter ( p = 0.016) and left ventricular mass index ( p = 0.001) in the patients with DM. The combination of DM and left ventricular diastolic dysfunction was associated with CV events in patients with CKD stage 3–5. Assessments of DM status and E/Ea ratio may facilitate identifying high-risk patient population of unfavorable CV outcomes.

// Chiao-Yin Sun 1, 2, 3 , Mei-Ling Cheng 3, 4, 5, 6 , Heng-Chih Pan 1, 2 , Jia-Hung Lee 1, 7 and Chin-Chan Lee 1, 3 1 Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan 2 Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 3 School of Medicine, Chang Gung University, Taoyuan, Taiwan 4 Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan 5 Clinical Phenome Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 6 Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 7 Medical Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan Correspondence to: Chiao-Yin Sun, email: fish3970@gmail.com Keywords: uremic toxins, metabolic stress, mitochondrial fusion, mitochondrial mass, mitophagy Received: May 02, 2017 Accepted: July 29, 2017 Published: September 08, 2017 ABSTRACT Protein-bound uremic toxins, indoxyl sulfate and p -cresol sulfate, increase oxidative stress and adversely affect chronic kidney disease progression and cardiovascular complications. In this study, we examined whether mitochondria are the target of indoxyl sulfate and p -cresol sulfate intoxication in vivo and in vitro . The kidneys of 10-week-old male B-6 mice with ½-nephrectomy treated with indoxyl sulfate and p -cresol sulfate were used for the animal study. Cultured human renal tubular cells were used for the in vitro study. Our results indicated that indoxyl sulfate and p -cresol sulfate impaired aerobic and anaerobic metabolism in vivo and in vitro . Indoxyl sulfate and p -cresol sulfate caused mitochondrial fission by modulating the expression of mitochondrial fission–fusion proteins. Mitochondrial dysfunction and impaired biogenesis could be protected by treatment with antioxidants. The in vitro study also demonstrated that indoxyl sulfate and p -cresol sulfate reduced mitochondrial mass by activating autophagic machinery. In summary, our study suggests that mitochondrial injury is one of the major pathological mechanisms for uremic intoxication, which is related to chronic kidney disease and its complications.

Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non-invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub-challenges: Sub-Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state-of-the-art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state-of-the-art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub-acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles-challenge.org).

Background and aims Uremic patients are characterized by an increased risk of atherosclerotic cardiovascular diseases. Vascular smooth muscle cell (VSMC) proliferation contributes to neointimal formation, a main pathological feature in atherosclerosis. Activation of CREB/ATF3 signaling is pivotal in VSMC proliferation, yet its role in uremic atherosclerosis is unknown. This study aimed to explore whether CREB/ATF3 signaling is involved in the molecular mechanism underlying neointimal formation in uremia. Methods and results Treatment of VSMCs with uremic toxin (indoxyl sulfate [IS]) activated cAMP/CREB/ATF3/cyclin D signaling, which was reflected by increased VSMC proliferation. Blocking cAMP/PKA/CREB/ATF3 signaling attenuated the promoting effect of IS on cyclin D1 expression and VSMC proliferation. Loss-of-function and time-dependent experiments showed that ATF3 lies downstream of the CREB signaling. Mutational analysis of cyclin D1 promoter along with chromatin immunoprecipitation assays showed that CREB/ATF3 signaling participated in IS-induced cyclin D transcription. In vivo, phosphorylated CREB (an active form of CREB) and ATF3 were prominently upregulated in the neointima of experimental uremic rats, the atherosclerotic plaques of uremic ApoE−/− mice, and the iliac arteries of uremic patients. Notably, the use of lentivirus to knock down ATF3 in the neointima of balloon-injured arteries could suppress the effect of uremia in vivo, including neointimal formation and cyclin D expression. Conclusions In this study, we demonstrated that CREB/ATF3-related signaling may be involved in IS-induced VSMC proliferation and the pathogenesis of neointimal formation during uremia.

Mental well-being among community-dwelling individuals with type 2 diabetes has not been well established. The primary objective was to evaluate the change in the mental well-being of individuals with diabetes. The secondary objective was to evaluate the association between changes in mental well-being and perceived health over 6 months, and any interacting factors in this association. This was a prospective, multicenter study. Community-dwelling individuals aged ≥ 21 years with type 2 diabetes were invited to meet with community pharmacists monthly for 6 months. Individuals who were unable to converse independently were excluded. A 12-item General Health Questionnaire (GHQ), measuring mental well-being was administered at baseline, and after 3 and 6 months. Perception of health was measured using the visual analog scale (VAS) of the EuroQoL 5-Dimension tool. Linear mixed model was used to analyze the change in mean GHQ and VAS scores. Association between the changes in GHQ and VAS scores was determined, and moderation analysis was conducted to elucidate the interacting variables of this association. Ninety-six individuals (82.4%) were included for analysis. The mean age was 60.3 years with a baseline mean HbA1c of 7.6%. A mean GHQ score reduction of 1.36 (p = 0.022) was observed. This reduction of mean GHQ score was associated with the change in mean VAS score. Having a duration of diabetes diagnosis of

Atrial fibrillation (AF) is associated with oxidative stress and Ca2+-handling abnormalities in atrial myocytes. Our prior study has demonstrated the involvement of CD44, a membrane receptor for hyaluronan (HA), in the pathogenesis of AF. This study further evaluated whether CD44 and its related signaling mediate atrial tachycardia-induced oxidative stress and Ca2+-handling abnormalities. Tachypacing in atrium-derived myocytes (HL-1 cell line) induced the activation of CD44-related signaling, including HA and HA synthase (HAS) expression. Blocking HAS/HA/CD44 signaling attenuated tachypacing-induced oxidative stress (NADPH oxidase [NOX] 2/4 expression) and Ca2+-handling abnormalities (oxidized Ca2+/calmodulin-dependent protein kinase II [ox-CaMKII] and phospho-ryanodine receptor type 2 [p-RyR2] expression) in HL-1 myocytes. Furthermore, a direct association between CD44 and NOX4 was documented in tachy-paced HL-1 myocytes and atrial tissues from AF patients. In vitro, Ca2+ spark frequencies in atrial myocytes isolated from CD44-/- mice were lower than those from wild-type mice. Furthermore, administration of an anti-CD44 blocking antibody in atrial myocytes isolated from wild-type mice diminished the frequency of Ca2+ spark. Ex vivo tachypacing models of CD44-/- mice exhibited a lower degree of oxidative stress and expression of ox-CaMKII/p-RyR2 in their atria than those of wild-type mice. In vivo, burst atrial pacing stimulated a less inducibility of AF in CD44-/-mice than in wild-type mice. In conclusion, atrial tachypacing-induced Ca2+-handling abnormalities are mediated via CD44/NOX4 signaling, which provides a possible explanation for the development of AF.

The American College of Emergency Physicians has identified early palliative care referral for patients with advanced cancer as a key competent of the Choosing Wisely campaign.To study the feasibility of a new 3-way model of care between emergency department (ED), hospital palliative care department, and inpatient/home hospice.This was a prospective, descriptive study that included oncology patients who attended the hospital ED over a 3-year period from January 2015 to December 2017. The inclusion criteria were as follows: (1) presence of metastatic cancer with either; (2) any 1 of the following symptoms: pain, dyspnea, nausea and vomiting, delirium, or swelling; or (3) potential care difficulties (requiring home hospice care or inpatient hospice).A total of 340 patients were referred from the ED. Mean age was 72 years, 59% were males and 41% females, and the majority (88%) were Chinese. The most common cancers were lung 89 (26%), colorectal 71 (21%), and hepatobiliary cancer 49 (14%). The most common symptoms on Edmonton Symptom Assessment Scale scoring were pain (34%), poor appetite (31%), and dyspnea (26%).This tripartite model of palliative care, hospice, and ED collaboration allows earlier access to palliative care in the ED and direct admissions to the palliative care unit and comfort care rooms. The ED patients who did not need admission were also attended to in the palliative care "Hot Clinics" within a week with home hospice help. Patients who required inpatient hospice care were directly admitted there from the ED.

Background. The ratio of early mitral inflow velocity to the global diastolic strain rate (E/E’sr) and global longitudinal systolic strain (GLS) of the left ventricle (LV) are emerging indices of diastolic and systolic functions, respectively, for the LV. Their prognostic significance in the prediction of mortality and cardiovascular (CV) outcomes remains underexplored in hemodialysis (HD) patients. Methods. This prospective study included 190 maintenance HD patients. The E/E’sr ratio and GLS were assessed using two-dimensional speckle tracking echocardiography. The clinical outcomes included overall mortality, CV mortality, and major adverse cardiovascular events (MACE). The associations between the E/E’sr ratio, GLS, and clinical outcomes were evaluated using multivariate Cox regression analysis. The incremental values of the E/E’sr ratio and GLS in outcome prediction were assessed by χ2 changes in Cox models. Results. Over a median follow-up period of 3.7 years, there were 35 overall deaths, 16 CV deaths, and 45 MACE. Impaired diastolic function with a higher E/E’sr ratio was associated with overall mortality (HR, 1.484; 95% CI, 1.201−1.834; p<0.001), CV mortality (HR, 1.584; 95% CI, 1.058–2.371; p=0.025), and MACE (HR, 1.205; 95% CI, 1.040−1.397; p=0.013) in multivariate adjusted Cox analysis. Worsening GLS was associated with overall mortality (HR, 1.276; 95% CI, 1.101−1.480; p=0.001), CV mortality (HR, 1.513; 95% CI, 1.088−2.104; p=0.014), and MACE (HR, 1.214; 95% CI, 1.103−1.337; p<0.001). The E/E’sr ratio and GLS had better outcome prediction than the E to early diastolic mitral annular velocity (E/E’) ratio and left ventricular ejection fraction (LVEF). Moreover, adding the E/E’sr ratio and GLS to Cox models containing relevant clinical and conventional echocardiographic parameters improved the prediction of overall mortality (p<0.001), CV mortality (p<0.001), and MACE (p<0.001). Conclusion. The E/E’sr ratio and GLS, as emerging indices of LV diastolic and systolic functions, significantly predict mortality and CV outcomes and outperform conventional echocardiographic parameters in outcome prediction in HD patients.

Given the complexity of foot and ankle deformities, 3-dimensional printing has a definite role in helping Orthopedic surgeons better appreciate patient specific anatomy and interactions between the bony articulations, offering solutions with customized implants and patient specific instrumentation. We report a case where three-dimensional (3D) printing technology was used in reconstruction of a complex malunited calcaneal fracture in foot and ankle surgery. To our knowledge, this is the first reported case utilizing 3D printing technology to aid deformity correction for chronic malunited calcaneal fractures. 3D printing is a promising aide to the Foot and Ankle surgeon in reconstructing complex deformities. Statement of informed consent: Informed consent was granted by the patient for data collection and submission of details for publication prior to the initiation of this report.

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aorta wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1mgR/mgR mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy (AFM) was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1mgR/mgR tissues, whereas the media layer of mutant aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, mutant mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

Ocular manifestation in immunocompromised hosts can stem from a wide range of possible diagnoses. Endophthalmitis means bacterial or fungal infection inside the eye involving the vitreous and/or aq...

ObjectiveTo outline the facilitators and barriers to patients’ self-management of predialysis chronic kidney disease (CKD).DesignQualitative.SettingThree polyclinics in a public primary care institution in Singapore.Participants20 patients entered and completed the study. Inclusion criteria were: (1) English speaking, (2) aged 40 years and above, (3) identified by clinical coding as ‘DM (diabetes mellitus) nephropathy-overt’ and ‘DM nephropathy-incipient’, by their physicians in the polyclinic, with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 (based on electronic health records) and (4) aware of their CKD illness. Exclusion criteria were: (1) receiving dialysis or had received a kidney transplant, (2) suffered from any visual, auditory or cognitive impairment which could hinder their ability to participate in the study or (3) pregnant.ResultsWe found that the major barriers to CKD management were a lack of knowledge and awareness of CKD, a passive attitude toward self-management and insufficient patient-physician communication. Major facilitators included patient trust and satisfaction with the physician and family support. Many patients reported that there was an overload of information and too little guidance on how to manage their condition, especially regarding dietary recommendations.ConclusionWe identified several barriers and facilitators to the management of predialysis CKD among patients. A multi-pronged approach for raising CKD awareness is required: improving patient-physician communication, implementing CKD workshops and home-visits and disseminating accurate online information about CKD. Strategies should also focus on increasing patient engagement and optimising family support by involving family members in patients’ care. Furthermore, clear dietary recommendations and patient-specific advice are needed to empower patients to manage their own condition.

Platypnea-orthodeoxia syndrome, characterized by dyspnoea and arterial desaturation while upright, is a rare complication of acute respiratory distress syndrome. We report here 2 patients with COVID-19 pneumonia, who were diagnosed with platypnea-orthodeoxia syndrome during commencement of rehabilitation, 18 and 9 days respectively after admission to the intensive care unit. Both patients presented with normocapnic hypoxaemia. One patient required mechanical ventilation with supplemental oxygen during intensive care, while the other required high-flow nasal oxygen therapy. The manifestations of platypnea-orthodeoxia syndrome were most prominent during physiotherapy, when verticalization was attempted, and hindered further mobilization out of bed, including ambulation. This report describes the clinical manifestations of platypnea-orthodeoxia syndrome and the rehabilitative strategies carried out for these 2 patients. The platypnea-orthodeoxia syndrome in these patients resolved after 65 and 22 days respectively from the day of detection. This report highlights this potentially under-recognized phenomenon, which may be unmasked during rehabilitation of patients with COVID-19 pneumonia. Good functional outcomes were achieved with a combination of verticalization training with supplemental oxygen support, respiratory techniques training and progressive endurance and resistance training, whilst awaiting resolution of the platypneaorthodeoxia syndrome. LAY ABSTRACT Platypnea-orthodeoxia syndrome can be a rare complication in severe pneumonia. Patients with platypnea-orthodeoxia syndrome experience decreasing oxygen levels when assuming upright positions. This can interfere with walking and other activities that require an upright posture. We report here 2 patients with platypnea-orthodeoxia syndrome in severe COVID-19 pneumonia and describe their journey to recovery whilst undergoing rehabilitation and physical therapy. The various strategies that were helpful included the use of additional oxygen, special breathing techniques, as well as reducing the pace of the exercises delivered. By the end of their rehabilitation programmes, the 2 patients were able to walk without the need for additional oxygen. The platypnea-orthodeoxia syndrome resolved after 22 and 65 days from the day of detection.