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Purpose Emergency endotracheal intubations outside the operating room (OR) are associated with high complications. We compare the outcome of emergency endotracheal intubation in the general ward, the intensive care unit (ICU) and the emergency department (ED). Materials and methods We retrospectively analyzed adult patients requiring emergency endotracheal intubation that called for anesthesiologists at our tertiary care institution from January 1, 2015 to December 31, 2016. We evaluated the outcomes, including aspiration, hemodynamic collapse, pneumothorax, emergency tracheostomy, and survival to hospital discharge in the general ward, ICU, and ED. Results There were 416 non-OR emergency endotracheal intubation calls for the anesthesiologist. Among these areas, the ED had the highest proportion of difficult endotracheal (DET) intubation (n = 144 [80.4%]), followed by the general ward (n = 85 [66.4%]), and then the ICU (n = 65 [59.6%]). The incidence of hemodynamic collapse was higher in the general ward (n = 44 [34.4%]) than the ICU (n = 18 [16.5%]) or the ED (n = 16 [9.0%]). We reported the survival rate of the general ward (55.5%), which was lower than the ICU (63.3%) and the ED (80.4%). Among these locations, the ED had the highest rate of neurologically intact (91%) to hospital discharge, compared to the ICU (56.6%) and the general ward (55%). As for the ED, although there was no difference in survival between non-preventive and preventive intubations, preventive intubations was associated with high neurological intact with hospital discharge. Conclusion Emergency and DET intubation in the general ward and ICU resulted in a higher incidence of hemodynamic collapse and mortality than those performed in the ED. Early calls for the anesthesiologist for DET intubation without medications in the ED resulted in a higher rate of neurologically intact survival to hospital discharge.

BACKGROUND: Obesity, common condition among patients with coronavirus disease 2019 (COVID-19), contributes to illness severity during hospitalization. To date, knowledge on the prevalence, risk of hospital and intensive care units (ICU) admissions and mortality is limited. Therefore, systematic review and meta-analysis were conducted using a preferred reporting items for systematic reviews and meta-analyses guideline. AIM: The study aimed to address the prevalence, risk of hospital and ICU admissions and mortality among patients with COVID-19 and obesity. METHODS: The Newcastle–Ottawa scale was used to assess the quality of a study. Primary outcomes were the prevalence and risk of hospitalization, and secondary outcomes were the risk of ICU admissions and mortality risk. Mantel–Haenszel with random effects was applied, and the effect measure was odds ratio (OR) with 95% confidence interval (CI). RESULTS: Nine studies were included in the systematic review, and only four studies for meta-analysis. Among 29,776 patients with COVID-19, obesity was identified as the second-highest comorbidity. The prevalence rates of obesity and severe obesity among patients with COVID-19 were 26.1% and 15.5%, respectively. Obesity resulted in significantly increased risk of hospital admission (OR = 1.99, 95% CI = 1.12–3.53, p = 0.02) and ICU admission (OR = 1.77, 95% = CI 1.52–2.06, p < 0.00001). Severe obesity had a significantly increased risk of ICU admission (OR = 1.79, 95% CI = 1.42–2.25, p < 0.00001). The mortality rate of patients with COVID-19 and obesity was about 30.5% (438/1,434), and 19.7% (2,777/14,095) of them recovered from COVID-19. CONCLUSION: Obesity poses as nearly twice the risk of hospital and ICU admissions, and severe obesity contributes to almost twice the risk of ICU admissions.

The population pharmacokinetics (popPK) of ribociclib and population pharmacokinetic/pharmacodynamic (PK/PD) relationship between ribociclib and absolute neutrophil count (ANC) were characterized in patients with cancer. PopPK and ANC PK/PD modeling were both conducted in 2 rounds per data availability. Initial models were developed based on data sets from early-phase trials and qualified using external data from the phase III MONALEESA-2 trial. The second round of analyses was performed using updated data sets that included 2 more phase III trials (MONALEESA-3 and -7). The popPK and ANC PK/PD models adequately described the data and demonstrated reasonable predictive ability. Covariate analysis showed that ribociclib PK were not affected by age, sex, race, baseline Eastern Cooperative Oncology Group (ECOG) status (grade 1), mild/moderate renal impairment, mild hepatic impairment, or concomitant use of combination partners, including aromatase inhibitors (letrozole, anastrozole) or fulvestrant, proton-pump inhibitors, or weak cytochrome P450 3A4/5 inhibitors. Body weight had no impact on ribociclib clearance to warrant dose adjustment. The ANC PK/PD relationship was not affected by age, weight, sex, race, baseline ECOG status (grade 1), or concomitant use of letrozole, anastrozole, or fulvestrant. The PK/PD analysis confirmed reversibility of ribociclib's effect on ANC; it also suggested that lowering the dose of ribociclib would mitigate ANC decrease and neutropenia risk. The popPK and ANC PK/PD analyses support the use of ribociclib in combination with an aromatase inhibitor or fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced or metastatic breast cancer without dose adjustment in subpopulations, and the use of dose interruption/reduction to mitigate potential treatment-emergent neutropenia.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan had established a management consensus guideline in 2016. The current recommendations focus on updating critical issues regarding the management of HCC, including surveillance, diagnosis, and systemic treatment. For surveillance, the updated guideline suggests the role of dynamic computed tomography or magnetic resonance imaging and contrast-enhanced ultrasound (CEUS) in selected patients. For diagnosis, this update incorporates CEUS and recognizes the role of gadoxetic acid-enhanced magnetic resonance imaging. For systemic therapy, the updated guideline summarizes the multiple choices of targeted therapy, immune checkpoint inhibitors, and the combination of both. Through this update of the management consensus guideline, patients with HCC can benefit from receiving optimal diagnostic and therapeutic modalities.

Background Many systemic therapies for advanced hepatocellular carcinoma (HCC) may cause hypothyroidism; however, in these patients, hypothyroidism prevalence before therapy and its prognostic impact remain unclear. Materials and Methods We previously established a prospective cohort of patients who received sorafenib as first-line therapy for advanced HCC. No patients had been clinically diagnosed with hypothyroidism before or during sorafenib treatment. We retrospectively determined the levels of thyrotropin and free thyroxine before initiation of systemic therapy. Hypothyroidism was defined as thyrotropin level higher than the upper limit of the normal range. Among patients with hypothyroidism, free thyroxine level less than the lower normal range was defined as overt hypothyroidism, and free thyroxine level within the normal range was defined as subclinical hypothyroidism. Results In total, 79 patients were enrolled; of them, 16 (20%) had hypothyroidism (overt hypothyroidism, 10; subclinical hypothyroidism, 6). Patients with hypothyroidism, compared with those without hypothyroidism, were more likely to be older than 65 years (56% vs. 29%, p = .037), have a serum α-fetoprotein level of >400 ng/mL (81% vs. 52%, p = .037), and have a significantly poorer overall survival (OS; median, 5.5 vs. 11.6 months, p = .043). After adjusting for other potential prognostic factors, hypothyroidism remained an independent predictor for poorer OS (hazard ratio, 2.53, p = .018). Patients with overt hypothyroidism and subclinical hypothyroidism exhibited similarly poor OS (p = .768). Conclusion Underdiagnosis of hypothyroidism in patients with advanced HCC was common. Hypothyroidism, whether overt or subclinical, is associated with poor prognosis of advanced HCC. Implications for Practice The results of this study showed the underdiagnosis of hypothyroidism in patients with advanced hepatocellular carcinoma (HCC) and its influence on prognosis. These findings implied the importance of thyroid function check before initiation of systemic therapy for patients with advanced HCC.

Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is characterized by recurrent mucocutaneous blistering with non-healing ulcers which are often complicated by squamous cell carcinoma (SCC). Despite having as high as 80% death rate from SCC, RDEB still does not have an effective treatment. We report on the efficacy of single follicular unit extract (FUE) grafting to heal chronic ulcers of intermediate RDEB in a 54-year-old woman with extensive chronic wounds covering around 30% of the body surface area. On Day 17 post first graft session, the area of treated ulcers on her right upper back was reduced by 80%. Immunofluorescence study revealed positive type VII collagen expression along the epidermal and follicular basement membrane zone in the donor and recipient sites. A few grafted follicles continued to grow hair on the recipient sites. A total of 360 FUEs were grafted in nine sessions over five years, resulting in healing of most treated ulcers and reduced significantly her time for daily wound dressing. Importantly, FUE grafting using patient's own scalp follicles does not require any laboratory manipulation. It is safe and easy to perform. Autologous follicular grafting appears efficacious for healing of recalcitrant wounds and provides an innovative solution for RDEB patients with such wounds.

As a natural compound isolated from Paeoniae radix, Paeoniflorin (PF) has been shown the antitumor effects in various types of human cancers including glioma, which is one of the serious tumors in central nervous system. Translocator protein 18 KDa (TSPO) has been shown to be relevant to the glioma aetiology. However, the regulation of PF in TSPO and neurosteriods biosynthesis on glioma is still unclear. In the present study, the glioma cell (U87 and U251) were cultured and used to quantify the bindings of PF on TSPO. Results indicated that there was not significant different between IC50 of PF and TSPO ligand PK11195. Moreover, PF exerted the anti-proliferative effects in glioma cell with a dose dependent inhibition from 12.5 to 100 μM in vitro. Consistent with the effects of PK11195, lowered levels on progesterone, allopregnanolone, as well as TSPO mRNA were induced by PF (25 and 50 μM). Furthermore, a xenograft mouse model with U87 cell-derived was significant inhibited by PF treatment, as well as the PK11195 administration. These results demonstrate that PF exerts its antitumor effects associated with the TSPO and neurosteroids biosynthesis in glioma cells could be a promising therapeutic agent for glioma therapy.

Eosinophilic pustular folliculitis (EPF) is classified into Ofuji disease, immunosuppression-associated EPF, and infancy-associated EPF. The association of EPF with Demodex infestation is rarely reported. We report five cases of EPF with Demodex overgrowth. All patients were young females presenting with recurrent, itchy papulopustules on the face for 2 months to 2 years. Laboratory tests revealed eosinophilia (n = 2) and iron deficiency anemia (n = 1). Skin biopsy of papulopustular lesions was performed in each patient, and all revealed folliculocentric infiltration with eosinophils. Infundibular pustules containing Demodex mites were found in two patients. All patients had high Demodex densities examined by superficial needle-scraping method (7–18 mites/5 pustules) and/or thumbnail-squeezing method (37–255 mites/cm2). Based on the clinical and laboratory findings, the patients were either first treated as having demodicosis or as having EPF. According to the treatment responses, the cases might represent Demodex-induced EPF or EPF-like reaction (Cases 1–3) or demodicosis superimposed on EPF (Cases 4 and 5). In sum, we report five cases of EPF with Demodex overgrowth (demodicosis). These cases illustrate that the possibility of Demodex overgrowth should be considered in cases of EPF with incomplete treatment response to indomethacin and/or oral corticosteroids. Conversely, EPF should be considered in cases of demodicosis with incomplete responses to antiparasitic treatment.

In the current study, a novel mixed-ligand coordination polymer, {[Co(L)(dpe)]·(ClO4)} (1) (H2LCl = 3-carboxy-1-(3-carboxybenzyl)pyridin-1-ium, dpe = (E)-1,2-di(pyridin-4-yl)ethene), was synthesize...

Purpose Marin-Amat syndrome is an acquired facial synkinesis manifesting as involuntary eyelid closure on jaw movement. The authors investigate the clinical features, especially the quantitative changes in eyelid parameters of patients with Marin-Amat syndrome. Methods Patients with Marin-Amat syndrome between 2015 and 2017 in a medical center were collected. Clinical features and the change of eyelid parameters, including margin reflex distance 1 (MRD-1), margin reflex distance 2 (MRD-2), and palpebral fissure height, were evaluated. Results There were 5 men and 3 women with a mean age of 76 years. All had a history of facial palsy. The mean time to onset of Marin-Amat syndrome was 4.4 years after facial palsy. Seven patients (87.5%) developed subsequent ipsilateral facial spasm after facial palsy. Most patient complaints were ptosis (62.5%) and ptosis on eating (37.5%). The mean palpebral fissure height of involved eyes decreased from 5.88 to 2 mm on jaw opening (p = 0.011), which resulted from decrease in MRD-1 (from 2.06 to 0.06 mm, p = 0.012) and MRD-2 (from 3.81 to 1.94 mm; p = 0.012). Botulinum toxin A (Botox) injection into the periorbital orbicularis muscle in 6 patients significantly relieved the change of palpebral fissure height on jaw opening compared with that before injection (9.9% vs. 68.6 %, p = 0.027). Conclusions Most patients with Marin-Amat syndrome present with ptosis and might be overlooked or underestimated. The reduction in palpebral fissure height in our patients with Marin-Amat syndrome was due to involuntary orbicularis oculi muscle contraction, resulting in decrease of both the MRD-1 and MRD-2 on jaw opening.

Background We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. Methods The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA Results A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. Conclusions In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

This study aimed to evaluate the prognostic value of combining pretreatment Epstein‐Barr virus (EBV) DNA level and cervical node necrosis (CNN) for patients with nasopharyngeal carcinoma (NPC) receiving intensity‐modulated radiotherapy (IMRT). A total of 607 incident nonmetastatic NPC patients treated with IMRT ± chemotherapy were reviewed. Patients were divided into four groups based on EBV DNA level and CNN status. The primary endpoint was progression‐free survival (PFS). Kaplan‐Meier curves with log‐rank test were applied to compare survival outcomes and the Cox proportional model was used to identify independent prognostic factors. Pretreatment EBV DNA level and CNN status were independent prognostic factors. Patients in the low‐level EBV DNA group or non‐CNN group had significantly better 5‐year PFS. Multivariate analyses demonstrated that CNN was an independent prognostic factor for overall survival (OS) (HR = 1.927, 95% CI: 1.129‐3.290, P = .016), PFS (HR = 1.492, 95% CI: 1.005‐2.214, P = .047), distant metastasis‐free survival (DMFS) (HR = 1.661, 95% CI: 1.044‐2.644, P = .032), but not locoregional relapse‐free survival. EBV DNA levels correlated significantly with CNN with a correlation coefficient of .324 (P, It is the first retrospective study that combined pretreatment plasma EBV DNA level and cervical node necrosis (CNN) status to assess the prognosis of nasopharyngeal carcinoma patients. We observed a significant association between plasma EBV DNA level and CNN status in the IMRT era. Compared with the low‐level EBV DNA and non‐CNN group, the high‐level EBV DNA and CNN group had poorer OS, progression‐free survival, and distant metastasis‐free survival. The Kaplan–Meier survival curves showed a significant difference in survival between the different risk groups according to the optimal cut‐off.

Purpose Intraarticular hyaluronic acid injection (IAHA) is a popular treatment for knee osteoarthritis (OA). This study investigates whether depression, anxiety, and pain affect self-reported knee function in geriatric OA people who have received IAHA. Methods Through convenience sampling, 102 geriatric patients (mean age = 70.91 ± 7.19; 28 males) with knee OA who had undergone IAHA participated in this study. All participants self-reported depression using the Geriatric Depression Scale (GDS), anxiety using the State-Trait Anxiety Inventory (STAI), knee function using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the International Knee Documentation Committee subjective knee evaluation form (IKDC), and pain severity using the Visual Analogue Scale (VAS). They completed the aforementioned questionnaires at baseline before injection and then again at 2-, 4-, and 6-month follow-ups. Results Depression was significantly associated with IKDC, WOMAC physical function subscale, and total WOMAC scores. Anxiety was only significantly associated with the WOMAC pain subscale score. Pain severity was significantly associated with IKDC, WOMAC stiffness subscale, WOMAC physical function subscale, and total WOMAC scores. Conclusion Given that depression negatively affected patient-reported knee function among geriatric OA patients who had undergone IAHA, further attention should be paid to the depressive status of this population.

Simple Summary Although uncommonly encountered, ocular melanoma may threaten the vision and even the life of a patient. The clinical feature and long-term results of ocular melanoma have rarely been described in the Asian population, as it has a low incidence for non-Caucasians. Therefore, we investigated the epidemiology, clinical manifestation, treatment strategy, and long-term outcome of ocular melanoma in a tertiary referral center in Taiwan. Abstract Malignant melanoma can arise from melanocytes in various structures of the eye, orbit, and ocular adnexa. We reviewed the clinical features and long-term results of all subjects with histologically proved melanoma originating from any of the ocular and periocular structures in a tertiary referral center. Overall, 88 patients including 47 men were recruited. The tumor was primarily located in the uvea, followed by the conjunctiva, orbit, eyelid, and lacrimal sac. Patients with uveal melanoma were diagnosed at a relatively younger age (47.0 years), while those with orbital and eyelid melanomas were older at presentation (79.5 years and 78.5 years, respectively). The overall local recurrence rate was 9% at a median follow-up of 41.0 months, among which orbital and eyelid melanomas recurred most commonly. The overall mortality rate was 41% in a median duration of 27.2 months (IQR, 13–58 months) from diagnosis, with the highest for lacrimal sac melanoma, followed by melanoma of the orbit, uveal, conjunctiva, and eyelid. Despite prompt local control, the risk for metastasis and mortality was high. Therefore, efficient modalities for early diagnosis and treatment of ocular melanoma are necessary.

Sarcopenic obesity is closely associated with knee osteoarthritis (KOA) and has high risk of total knee replacement (TKR). In addition, poor nutrition status may lead to sarcopenia and physical frailty in KOA and is negatively associated with surgery outcome after TKR. This study investigated the effects of sarcopenic obesity and its confounding factors on recovery in range of motion (ROM) after total knee replacement (TKR) in older adults with KOA. A total of 587 older adults, aged ≥60 years, who had a diagnosis of KOA and underwent TKR, were enrolled in this retrospective cohort study. Sarcopenia and obesity were defined based on cutoff values of appendicular mass index and body mass index for Asian people. Based on the sarcopenia and obesity definitions, patients were classified into three body-composition groups before TKR: sarcopenic-obese, obese, and non-obese. All patients were asked to attend postoperative outpatient follow-up admissions. Knee flexion ROM was measured before and after surgery. A ROM cutoff of 125 degrees was used to identify poor recovery post-surgery. Kaplan-Meier curve analysis was performed to measure the probability of poor ROM recovery among study groups. Cox multivariate regression models were established to calculate the hazard ratios (HRs) of postoperative poor ROM recovery, using potential confounding factors including age, sex, comorbidity, risk of malnutrition, preoperative ROM, and outpatient follow-up duration as covariates. Analyses results showed that patients in the obese and sarcopenic-obese groups had a higher probability of poor ROM recovery compared to the non-obese group (all p &lt, 0.001). Among all body-composition groups, the sarcopenic-obese group yielded the highest risk of postoperative physical difficulty (adjusted HR = 1.63, p = 0.03), independent to the potential confounding factors. Sarcopenic obesity is likely at the high risk of poor ROM outcome following TKR in older individuals with KOA.

Purpose: Tumor-infiltrating tissue-resident memory CD8 T cells (CD8 TRM, CD103+ CD8+) are considered tumor-specific and may correlate better with the tumor response to immune checkpoint blockade (ICB). This study evaluated the association of tumor-infiltrating CD8 TRM and their subsets with the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC). Experimental Design: Consecutive HCC patients who received ICB in prospective trials were analyzed. Formalin-fixed paraffin-embedded tumor sections were stained for DAPI, CD8, CD103, CD39, programmed cell death-1 (PD-1), and programmed cell death ligand 1 (PD-L1) using a multiplex immunohistochemical method. The densities of CD8 T cells, CD8 TRM, and CD39+ or PD-L1+ subsets of CD8 TRM were correlated with tumor response and overall survival (OS). Results: A total of 73 patients were identified, and 48 patients with adequate pretreatment tumor specimens and complete follow-up were analyzed. A median of 32.7% (range: 0–92.6%) of tumor-infiltrating CD8 T cells were TRM. In subset analyses, 66.6% ± 34.2%, 69.8% ± 33.4%, and 0% of CD8 TRM cells coexpressed CD39, PD-L1, and PD-1, respectively. The objective response rates for CD8 T cell-high, CD8 TRM-high, CD39+ CD8 TRM-high, and PD-L1+ CD8 TRM-high groups were 41.7%, 37.5%, 37.5%, and 29.2%, respectively. Patients with CD8 T cell-high, but not those with CD8 TRM-high, CD39+ CD8 TRM-high, or PD-L1+ CD8 TRM-high, tumors, had significantly prolonged OS (p = 0.0429). Conclusions: Compared with total tumor-infiltrating CD8 T cells, tumor-infiltrating CD8 TRM or their subsets failed to provide additional advantages in predicting the efficacy of immunotherapy for HCC.

In this paper, our main objective was to predict survival outcomes using DCE-MRI biomarkers in patients with advanced hepatocellular carcinoma (HCC) after progression from 1st-line sorafenib treatment in two prospective phase II trials. This study included 74 participants (men/women = 64/10, mean age 60 ± 11.8 years) with advanced HCC who received 2nd-line targeted therapy (n = 41 with lenalidomide in one clinical trial, n = 33 with axitinib in another clinical trial) after sorafenib failure from two prospective phase II studies. Among them, all patients underwent DCE-MRI at baseline, and on days 3 and 14 of treatment. The relative changes (Δ) in the DCE-MRI parameters, including ΔPeak, ΔAUC, and ΔKtrans, were derived from the largest hepatic tumor. The treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The Cox model was used to investigate the associations of the clinical variables and DCE-MRI biomarkers with progression-free survival (PFS) and overall survival (OS). The objective response rate (ORR) was 10.8% (8/74) and the disease control rate (DCR) was 58.1% (43/74). The median PFS and OS values were 1.9 and 7.8 months, respectively. On day 3 (D3), participants with high reductions in ΔPeak_D3 (hazard ratio (HR) 0.4, 95% confidence interval (CI) 0.17–0.93, p = 0.017) or ΔAUC_D3 (HR 0.51, 95% CI 0.25–1.04, p = 0.043) were associated with better PFS. On day 14, participants with high reductions in ΔPeak_D14 (HR 0.51, 95% CI 0.26–1.01, p = 0.032), ΔAUC_D14 (HR 0.54, 95% CI 0.33–0.9, p = 0.009), or ΔKtrans_D14 (HR 0.26, 95% CI 0.12–0.56, p &lt, 0.001) had a higher PFS than those with lower reduction values. In addition, high reductions in ΔAUC_D14 (HR 0.53, 95% CI 0.32–0.9, p = 0.016) or ΔKtrans_D14 (HR 0.47, 95% CI 0.23–0.98, p = 0.038) were associated with a better OS. Among the clinical variables, ORR was associated with both PFS (p = 0.001) and OS (p = 0.005). DCR was associated with PFS (p = 0.002), but not OS (p = 0.089). Cox multivariable analysis revealed that ΔKtrans_D14 (p = 0.002) remained an independent predictor of PFS after controlling for ORR and DCR. An early reduction in tumor perfusion detected by DCE-MRI biomarkers, especially on day 14, may predict favorable survival outcomes in participants with HCC receiving 2nd-line targeted therapy after sorafenib failure.

Background: The kinesin Eg5, a mitosis-associated protein, is overexpressed in many cancers. Here we explored the clinical significance of Eg5 in hepatocellular carcinoma (HCC). Methods: HCC tissues from surgical resection were collected. Total RNA was prepared from tumorous and nontumorous parts. Eg5 expression levels were correlated with overall survival (OS) and disease-free survival (DFS). In vitro efficacy of LGI-147, a specific Eg5 inhibitor, was tested in HCC cell lines. In vivo efficacy of Eg5 inhibition was investigated in a xenograft model. Results: A total of 108 HCC samples were included. The patients were divided into three tertile groups with high, medium, and low Eg5 expression levels. OS of patients with low Eg5 expression was better than that of patients with medium and high Eg5 expression (median, 155.6 vs. 75.3 vs. 57.7 months, p = 0.002). DFS of patients with low Eg5 expression was also better than that of patients with medium and high Eg5 expression (median, 126.3 vs. 46.2 vs. 39.4 months, p = 0.001). In multivariate analyses, the associations between Eg5 expression and OS (p < 0.001) or DFS remained (p < 0.001). LGI-147 reduced cell growth via cell cycle arrest and apoptosis and induced accumulation of abnormal mitotic cells. In the xenograft model, the tumor growth rate under LGI-147 treatment was significantly slower than under the control. Conclusion: High Eg5 expression was associated with poor HCC prognosis. In vitro and in vivo evidence suggests that Eg5 may be a reasonable therapeutic target for HCC.

Purposes This study aimed to understand the influence of health beliefs, demographic factors, and health characteristics on the intention to undergo Pap smear testing among women in rural areas of Indonesia. Methods A descriptive cross-sectional study was conducted and 687 married women participated in the study. A convenience sampling was applied to recruit the participants from community health centres in a rural region in Indonesia. Self-reported data using the Health Beliefs Model Scale for Cervical Cancer and Pap Smear Test was collected to assess the health beliefs. Independent t-tests, simple logistic regressions, and a hierarchical logistic regression with 3 steps were run. Statistical significance for analysis was set at p, Plain language summary Cervical cancer is a leading cancer among women and a significant cause of mortality for females around the world, including Indonesia. Globally, the screening rate for cervical cancer among women in rural areas remains low. In Indonesia, the incidence and the mortality from cervical cancer remain high compared to other female cancers. The Indonesian government has offered a free Pap smear screening to women since 2014, but the screening rate is still low, around 28%. A total of 687 married women were included in the study. Approximately 80% of Indonesian women living in rural areas have never undergone a Pap smear test, and 60% of women reported a high intention of receiving a Pap smear test. Education, income, previous experience of Pap smear testing, a friend with a history of cervical cancer, perceived severity, perceived benefits, perceived barriers, and health motivations were significantly associated with the intention of Pap smear testing. Low screening rates of cervical cancer and high intentions toward the cervical cancer screening exist among rural Indonesian women. Health beliefs significantly affect the women’s intention of Pap smear testing.

Clinical relevance Conjunctivitis, chalazion and blepharitis are routinely managed by optometrists. However, it is especially important to consider the diagnosis of canaliculitis in patients with chronic or recurrent conditions. Background This study aimed to report the clinical features, radiological findings and treatment outcomes in patients with plug-related canaliculitis. Methods This retrospective study included patients with canaliculitis secondary to plug insertion between 2007 and 2020. All data regarding epidemiological characteristics, clinical presentation, isolated microorganisms, computed tomography imaging findings, treatment, and outcomes were analysed. Results A total of 20 plug-related canaliculitis from 19 patients (18.3%) among all 109 cases of canaliculitis were identified. All patients with plug-related canaliculitis were females with a past history of lacrimal plug insertion for dry eye (mean age: 58.2 years). Most patients were initially treated as conjunctivitis with the mean time lapse to a diagnosis of 5.2 months. The average time from plug insertion to onset of symptoms was 5.1 years. Eighteen patients underwent canaliculotomy, and one patient received lacrimal irrigation. Plugs were identified in 18 cases, with SmartPlug in 13 cases (72%), followed by EaglePlugTM (two cases), Herrick Lacrimal Plug (two cases), and migrated FCI Painless Plug (1 case). Cultures of discharge, concretions, and/or infected plugs mostly revealed Pseudomonas aeruginosa (42%). Orbital computed tomography in four cases with SmartPlug revealed central radiolucency with surrounding soft-tissue enhancement. No recurrent canaliculitis was observed throughout a mean follow-up period of 13.7 months. No patient needed re-plugging after canaliculotomy and plug removal, with only one required additional lubricants for recurrent dry eye. Conclusion Plug-related canaliculitis is often underdiagnosed due to late onset and similar symptoms to common ocular diseases. Awareness of plug insertion history as well as meticulous removal of the plug, concretion and/or granulation tissue is important for early diagnosis and to ensure a good outcome.

High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2-related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Here, we showed that hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. We further found that hTERT increases NRF2 expression at both the mRNA and protein levels. Our data also revealed that hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability. Using DNA pull-down/MS analysis, we found that hTERT can recruit YBX1 to upregulate NRF2 promoter activity. We also found that hTERT/YBX1 may localize to the P2 region of the NRF2 promoter. Taken together, our results demonstrate that hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter. These results provide a new theoretical basis for CRC treatment.

POEMS syndrome, a paraneoplastic disorder, caused by plasma cell dyscrasia, is characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. Calciphylaxis is a vasculopathy of subcutaneous arteries with calcification and skin ulceration, most commonly associated with end-stage renal disease. Calciphylaxis occurring in patients with POEMS syndrome is very rare; only 8 cases have been reported to date. We report the 9th case. A middle-aged woman with chronic inflammatory demyelinating polyneuropathy and monoclonal plasma cell proliferative disorder with IgA gammopathy presented with a 3-month history of multiple painful violaceous plaques with gangrenous necrosis and ulceration on the abdomen and extremities. The skin lesions worsened after surgical debridement and fasciotomy but improved with weekly intravenous bortezomib combined with thalidomide and dexamethasone for POEMS syndrome. The present case illustrates that effective control of the disease activity of POEMS syndrome may improve the surgical outcome of extensive skin necrosis in POEMS syndrome-associated calciphylaxis.

BACKGROUND Post-treatment decline in serum alpha-foetoprotein (AFP) levels has been shown to predict the treatment efficacy of antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). We explored whether a decline in AFP levels was also associated with treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with advanced HCC. METHODS We reviewed all patients who received ICI therapy for advanced HCC. AFP response was evaluated in patients with the pretreatment AFP level of >20 ng/mL. We defined early AFP response as a >20% decline in serum AFP levels within the first 4 weeks of treatment initiation relative to pretreatment levels. We then studied whether early AFP response was associated with treatment outcomes. RESULTS Sixty patients were enrolled in this study; 43 of them were evaluable for early AFP response. The objective response rate of early AFP responders was significantly higher than that of early AFP nonresponders (73% vs. 14%, P

BackgroundDiabetes self-care reminders are widely applied to improve self-care among diabetes patients. Unfortunately, there is a lack of self-care reminders for diabetes patients who live in rural areas of developing countries with limited resources.AimsThe study evaluated the feasibility of the Diabetes Self-Care Calendar as a reminder tool for self-care.MethodsThe study was conducted in a community health centre in Pekalongan Regency, Indonesia. The Diabetes Self-Care Calendar was developed as a reminder tool following the American Association of Diabetes Educator self-care guidelines. The feasibility of the calendar was evaluated using the quality assessment questionnaire that assessed accessibility, acceptability, effectiveness, efficiency and appropriateness. The participants’ qualitative feedback was organised into themes.ResultsA total of 10 patients with type 2 diabetes mellitus participated in the study. The quality of the calendar was evaluated in terms of accessibility (m = 9.5; range = 0 – 10), acceptability (m = 9.7; range = 0 – 10), effectiveness (m = 9.3; range = 0 – 10), efficiency (m = 9; range = 0 – 10) and appropriateness (m = 9; range = 0 – 10). The feasibility of the calendar was m = 9.3 (range = 9 to 9.7). Three themes emerged based on the participants' qualitative feedback included family involvement, calendar portability and calendar design.ConclusionsThe findings suggest the Diabetes Self-Care Calendar is feasible as a reminder tool for type 2 diabetes mellitus patients who live in rural areas.

Introduction: Clinical trials in hepatocellular carcinoma (HCC) exhibit a high degree of heterogeneity. These heterogeneities may lead to unexpected results among clinical trials. Area covered: In this review, we address the heterogeneity noted in early phase HCC trials, trials involving transarterial chemoembolization, and advanced HCC trials. Furthermore, we discuss possible methods to attenuate the detrimental effects of heterogeneity when conducting clinical trials. Expert opinion: Clinical trials in HCC exhibit an inherently high degree of heterogeneity because of various reasons: tumor heterogeneity, different cirrhotic backgrounds, various etiologies of cirrhosis, and geographical differences in practice and expertise. Such heterogeneity may cause imbalance among the enrolled patient population, premature withdrawal from the clinical trial, and variable response to the treatment. In addition, methodological heterogeneity also exists in designing trial protocol and response evaluation. All these factors may eventually lead to conflicting results among clinical trials. Accounting for these heterogeneities is important to foster the success of future trials. In recent years, significant progress with molecular targeted agents and immune checkpoint inhibitors was made in advanced HCC. These new agents are also being tested in clinical trials involving earlier stage HCC and will also face the challenge of these issues.

Objective To investigate difference in bilateral diaphragm movement of patients with tracheal aspiration according to post stroke residue severity and determine correlations of Penetration-Aspiration Scale (PAS), residue scale, and bilateral diaphragm movement. Methods A total of 47 patients diagnosed with hemiplegic stroke were enrolled in this study. PAS, severity of valleculae, and pyriform sinus retention during videofluoroscopic swallowing study (VFSS) were assessed. Bilateral fluoroscopic diaphragm movements during spontaneous breathing and forced breathing were measured. Results Patients with tracheal aspiration (PAS≥6) had significantly (p=0.035) lower ipsilateral diaphragm movement during spontaneous breathing. Post-swallow residue severity showed statistically significant (p=0.028) difference in patients with ipsilateral diaphragm movement during forced breathing. In linear regression analysis, PAS showed weak correlations with ipsilateral spontaneous diaphragm movement (r=0.397, p=0.006), ipsilateral forced diaphragm movement (r=0.384, p=0.008), and contralateral forced diaphragm movement (r=0.323, p=0.027). Weak correlation was also observed between post swallow residue severity and ipsilateral diaphragm movement during spontaneous breathing (r=0.331, p=0.023) and forced breathing (r=0.343, p=0.018). Conclusion We confirmed the relationship between swallowing function and bilateral diaphragm movement in this study. The severity of dysphagia after hemiplegic stroke was correlated with bilateral diaphragm movement. Further longitudinal studies are needed to assess the effect of breathing exercise on post-stroke dysphagia.

Transdermal buprenorphine (TDB) has demonstrated effectiveness in treating a range of chronic pain conditions, including cancer pain, nociceptive pain, and neuropathic pain and has a favorable safety profile. Worldwide, clinical experience of its use is relatively limited. There is considerable misunderstanding about the pharmacology, mechanism of action, and safety of buprenorphine. There is also limited guidance on the appropriate use of TDB for chronic pain management. This article presents an overview of TDB and also provides practical recommendations for its use as part of a multifaceted strategy in chronic cancer and non-cancer pain.

Purpose We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. Materials and Methods From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. Results For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05). Conclusion Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.

The main aim of the present study was to investigate the biological function of uric acid. The level of uric acid in different organs in normal male rats was determined with uric acid assay kits, and the expression level of genes in the organs was determined by RNA quantitative sequencing. The correlation analysis between uric acid in the organs and gene expression (measured by FPKM value) was made. Serum uric acid (SUA) in patients with breast cancer or with breast benign tumor was assayed when the diagnosis was made, and SUA in patients with breast cancer was also assayed just after chemotherapy. There were 1937 mRNAs whose expression level significantly correlated with the level of uric acid, and most of which were associated with purine or nucleoside metabolism, cellular metabolism, cell cycles, and cell death pathways. Further analysis showed that the level of uric acid was highly correlated with cell death rather than cell viability. The level of SUA in patients with breast cancer was higher than that in patients with breast benign tumor, and the SUA increased after chemotherapy. All the results suggested that uric acid was mainly synthesized from local nucleosides degraded from dead cells, and uric acid could be an important biomarker for cell death rather than an antioxidant for neural protection.

Background and Aims: Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs. Methods: We reviewed the data of patients with advanced HCC who had received ICIs. Patients with measurable diseases were enrolled. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used to evaluate the objective response to ICIs in tumors located in the liver, lung, lymph node, and other intra-abdominal sites. Results: Of the 75 enrolled patients with advanced HCC, 51 and 11 patients had chronic hepatitis B virus and chronic hepatitis C virus infection, respectively. Regarding ICI treatment, 58, 1, and 16 patients had undergone anti-PD-1/anti-PD-L1 monoclonal antibody (mAb) alone, anti-CTLA4 mAb alone, and anti-PD-1 mAb plus anti-CTLA4 mAb, respectively; 20 and 55 patients had received ICIs as first-line or ≥second-line therapy. The overall objective response rate (ORR) was 28.0%. In total, 58, 34, 19, and 18 patients had measurable hepatic tumors and lung, lymph node, and other intra-abdominal metastases, and the corresponding organ-specific ORRs were 22.4, 41.2, 26.3, and 38.9%, respectively. Of the 39 patients who had both hepatic and extrahepatic tumors, 12 had disease control in extrahepatic tumors while progressive disease (PD) in hepatic tumors, whereas only 4 exhibited disease control in hepatic tumors while PD in extrahepatic tumors (p = 0.046, McNemar test). Of the 16 patients with only evaluable tumors in the liver and lungs at baseline, 8 had disease control in the lungs while PD in the liver, and none experienced disease control in the liver while PD in the lungs (p = 0.005). Conclusions: The hepatic tumors of HCC may be less responsive to ICIs than extrahepatic lesions. Lung metastases responded most favorably to ICIs. The mechanisms underlying this differential response to ICIs warrant further investigation.

Objective Thoracic endovascular aortic repair (TEVAR) can be complicated by a type Ia endoleak. However, its natural history remains unclear. This report describes the natural history and midterm outcome of conservatively treated type Ia endoleaks in the proximal aorta. Methods Between 2007 and 2015, 395 patients underwent TEVAR at our institution. Only TEVARs landing proximally at landing zones 0, 1, and 2 were included (221/395). Type Ia endoleak’s flow was classified as “fast” or “slow” based on the time needed to visualize the aneurysmal sac during arteriogram. Results The median follow-up was 4.1 years. Aortic dissection, thoracic aortic aneurysm, and traumatic aortic injury were the most common indications for TEVAR, the incidence of type Ia endoleak was not statistically different. Forty-seven patients (21.3%) had a type Ia endoleak. TEVAR landing proximally at zone 1 increased the odds of developing a type Ia endoleak (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3–5.9; p=0.0072). The thirty-day mortality and the overall survival rates were not influenced by the development of immediate-type Ia endoleak. In thirty-four (72.3%) patients, the endoleak resolved spontaneously. Ninety-four percent of these patients had a SlowE (n = 32/34). All of the spontaneous resolutions occurred before the end of the first postoperative year. Conclusions SlowE tends to resolve within one year after TEVAR. Initial conservative treatment seems to be a reasonable approach in patients with SlowE.

Poor adherence to analgesic drugs is one of the most common barriers to adequate pain management. This prospective, cross-sectional, patient-oriented observational study aimed to explore the adherence rate, clinical factors, and impact of adherence to analgesic drugs on the quality of life (QoL) among cancer outpatients in Taiwan. Eight hundred ninety-seven consecutive adult outpatients with cancer who had reported tumor pain and received regular analgesic drug treatment were enrolled from 16 medical centers across Taiwan. The Brief Pain Inventory was used to assess pain intensity and QoL. Morisky’s four-item medication adherence scale was used to assess adherence to analgesic drugs. Clinical factors possibly associated with good adherence to analgesic drugs were analyzed using multivariate logistic regression analyses. Of the 897 patients, 26.9% met criteria for the good, 35.5% for the moderate, and 37.6% for the poor adherence groups. The good adherence group had significantly better QoL outcomes than the moderate and poor adherence groups (all p

Context Little is known about cancer-related symptoms in terms of prevalence, severity, and distress among patients with cancer in Indonesia because of a lack of a valid and reliable scale. Objectives To translate and validate the Memorial Symptom Assessment Scale (MSAS) among cancer patients in Indonesia. Methods Two procedures consisting of forward-backward translation and validation were conducted. The validation process including pretesting involved 34 cancer patients, and the psychometric testing of the Indonesian version of MSAS (MSAS-I) involved 207 cancer patients. Internal consistency, test-retest reliability, construct, and concurrent validity of the MSAS-I were established. Results Cronbach's alpha coefficients for the total scale and subscales of the MSAS-I ranged from 0.75 to 0.87. The interclass correlations for test-retest reliability ranged from 0.80 to 0.89. A two-factor structure in the MSAS-I was produced by exploratory factor analysis, and the two factors accounted for 28.34% of the cumulative variance. In addition, the concurrent validity was demonstrated by the significant associations between the subscales of the MSAS-I and their corresponding subscales in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, with r = −0.25 to −0.65 (all P Conclusion The MSAS-I presents a valid and reliable scale for assessing symptom frequency, severity, and distress among patients with cancer in Indonesia. Implication for Nursing The MSAS-I can assess physical and psychological symptoms during cancer treatment. In addition, the MSAS-I may facilitate in measuring the effectiveness of symptom management strategies.

Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to migraine. This systematic review and meta-analysis aimed to evaluate the impact of Vitamin B2 supplementation on the days, duration, frequency, and pain score of the migraine attack.: The PRISMA guideline was used for the studying process. Five electronic databases, PubMed, Embase, Cochrane, CINAHL, and CEPS were searched from 1990 to March 2019. The search terms were Vitamin B2, migraine, and prophylactic. A meta-analysis was performed using Comprehensive Meta-Analysis (CMA) version.: Nine articles were included in systemic review and finally meta-analysis. Eight randomized controlled trials and one controlled clinical trial with 673 subjects were analyzed using meta-analysis. Vitamin B2 supplementation significantly decreased migraine days (A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.

Topical ivermectin is effective in treating papulopustular rosacea, but its effect on persistent facial erythema of rosacea with high Demodex densities has not been well documented. We retrospectively reviewed 39 rosacea patients with persistent facial erythema and high Demodex densities. Clinician's erythema assessment (CEA) and Demodex density were evaluated before and after topical ivermectin alone or combined with oral carvedilol. Three patients (all with papulopustular rosacea, in ivermectin group) dropped out due to early ivermectin-induced local flare of rosacea. In the remaining patients (ivermectin group n = 14; ivermectin-carvedilol group n = 22), the CEA grade and Demodex density were significantly reduced, both P < .01. There was no statistically significant difference between the two groups in CEA before and after treatment (P = .07 and P = .23, respectively), and in Demodex density (P = .82 and .10, respectively). Both regimens markedly improved the persistent facial erythema with response being excellent in 26 of 36 patients (72%), good in 2, fair in 4 and none in 4. There was a correlation between the reduction of CEA and Demodex density after treatment (rho = 0.50, P = .002). The results showed that topical ivermectin was effective in reducing persistent facial erythema of rosacea with Demodex overgrowth.

Background Remarkable progress has been made in immunotherapy, specifically antibodies for programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1), for treating advanced cancers. In this study, we explored whether circulating immune cells can be used as biomarkers of the efficacy of such therapy. Methods We enrolled patients who received nivolumab, an anti-PD-1 antibody, for advanced hepatocellular carcinoma (HCC) in clinical trials and who consented to the collection of their peripheral blood. Using flow cytometry, we analyzed lymphocyte subclasses and the PD-1 or PD-L1 positivity of immune cells. These results were compared between patients with disease control (complete response, partial response, or stable disease) and those with disease progression. Results This study included 16 patients. The objective response rate was 19%, and the disease control rate was 75%. The hemogram results and the percentage of total αβ T cells or CD4 T cells did not significantly change after nivolumab treatment; moreover, they were not associated with treatment outcomes. The number of CD8 T cells significantly increased after 4 weeks (p = .016); however, this change was not associated with treatment outcomes. Patients with disease control exhibited peripheral B cells with significantly lower pretreatment PD-1 positivity than did patients with disease progression (p = .042). Patients with disease progression were more likely to exhibit monocytes with increased PD-L1 positivity after 28 (p = .020) or 42 (p = .008) days of treatment. Conclusion The low pretreatment PD-1 positivity of peripheral B cells and the constant posttreatment PD-L1 positivity of monocytes were associated with disease control after nivolumab treatment for advanced HCC.

Background Patients with knee osteoarthritis (KOA) often complain about clinical symptoms affected by weather-related factors. The purpose of the present study was to use cross-sectional analysis to determine whether weather sensitivity was associated with clinical symptoms, as well as structure abnormalities, in KOA patients.Methods Data from 80 participants were obtained from the Feng Hans Shi Effects on OA (FHS) study, an OA cohort study initiated in China in 2015. The weather sensitivity of each participant was determined by a self-reported questionnaire. The following measurements were used to assess clinical and biological outcomes: a visual analog scale (VAS) for pain; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); and blood levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1(IL-1). Structural changes identified via magnetic resonance imaging (MRI) were also evaluated. Independent sample t-tests, chi-square tests, Fisher’s exact tests, Cochran-Armitage tests for linear trends, and binary linear regression were used to evaluate the clinical characteristics, biomarkers, WOMAC, and Whole-Organ Magnetic Resonance Imaging Score (WORMS) of weather-sensitive KOA patients and non-weather-sensitive KOA patients.Results Most of the KOA participants (57.5%) perceived the weather as affecting their knee-joint clinical symptoms. Through logistic regression analysis, the presence of weather sensitivity was found to increase the risk of KOA participants reporting higher levels of WOMAC pain scores [OR = 3.3 (95% CI: 1.1, 9.9), P > 0.032], functional scores [OR = 5.5 (95% CI: 1.8,16.8), P > 0.003], total scores [OR = 3.3 (95% CI: 1.1, 10.2), P = 0.034], WORMS cartilage scores [OR = 3.1 (95% CI: 1.1, 8.5), P < 0.027], and marrow abnormality scores [OR = 3.0 (95% CI: 1.1, 8.1), P > 0.029].Conclusions Weather-sensitive KOA patients were prone to show more serious clinical symptoms and structural abnormalities in their knee joints. Therefore, the existence of weather sensitivity may accelerate the progress of KOA.

The relationship between intestinal bacteria and hyperuricemia is a hot research topic. To better understand this relationship, uricase-deficient Sprague–Dawley rats (Kunming-DY rats) were used. The wild-type rats and Kunming-DY rats were used as controls. Kunming-DY rats were treated with ampicillin (90 mg/kg) and ciprofloxacin (150 mg/kg) for 5 days. Bacterial 16S rDNA in the fresh stool was sequenced, and the abundance was calculated. The rats’ serum uric acid (SUA) level was assayed, and the rats’ intake and output in 24 h were recorded. The bacterial diversity in three groups’ fresh stool was analyzed. The gut bacterial diversity and abundance changed in the Kunming-DY rats. More than 99% of bacteria were inhibited or killed by the combination of antibiotics. In contrast to each of the antibiotics alone, the combination of antibiotics lowered the Kunming-DY rats’ SUA level; it also caused mild diarrhea, which increased uric acid excretion through stool. These results suggested that the aboriginal gut bacteria in uricase-deficient rats play a minor role in determining the SUA levels. It is too early to conclude that aboriginal gut bacteria are a tempting target for lowering SUA levels.

Background: Diaphragmatic movement affects dyspnea in the COPD patient.Research Question: Which of the diaphragm-related factors are closely related to Pulmonary Function test in the COPD patients? Study design and Methods: We enrolled 60 patients with COPD who attend respiratory outpatients. The diaphragm evaluation was performed using ultrasound, and PFT, 6MWT was performed in a respiratory outpatient clinic. Dyspnea scare, BMI, PFT, 6MWT and diaphragmatic factors collected and statistically analyzed. Results:In total patients, the right forced-excursion at supine positon was 6.9 ±2.000, left forced-excursion at supine position was 7.6 ±1.649. Right forced-excursion at supine position (p=0.003, R 2 =0.137), left forced-excursion at supine position (p=0.048, R 2 =0.074) and thickness of right end-expiratory (p=0.016, R 2 =0.094) were significantly associated with FEV1. When the group with right diaphragmatic excursion ≥ 6.7 was further divided into groups according to FEV1 (< 50% or ≥ 50%) , FEV1/FVC, MIP , portable peak flow meter, 6-minute walk distance, SpO2 before and after the 6MWT, and right diaphragmatic thickness at end-expiration subgroups were significantly different between the two groups. Interpretation: Right diaphragmatic forced excursion was closely related to FEV1, and analysis according to cut-off value which based on Right diaphragmatic forced excursion showed a large difference between groups. W hen the diaphragm function was maintained, MIP , portable peak flow meter, 6-minute walk distance, SpO2 before and after the 6 MWT, and right diaphragmatic thickness at end-expiration were different between the two FEV1 groups. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The study procedures were reviewed and approved by our institutional review board [IRB No. 05-2020-217].

Purpose This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients.Materials and Methods Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS).Results Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05).Conclusion Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein–Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

Osteoarthritis (OA) causes oxidative stress. Coenzyme Q10 is an antioxidant that participates in energy production in the human body. The purpose of this study was to investigate the relationships among coenzyme Q10 status, oxidative stress, antioxidant capacity, and muscle function in patients with OA. This case-control study recruited 100 patients with OA and 100 without OA. The coenzyme Q10 status, oxidative stress, antioxidant capacity, muscle mass (by dual-energy X-ray absorptiometry), muscle strength (hand-grip and leg-back strength), and muscle endurance (dumbbell curls, gait speed, chair-stand test, and short physical performance battery) were measured. The results showed that both OA and elderly subjects had a low coenzyme Q10 status (&lt, 0.5 &mu, M). Oxidative stress was significantly negatively correlated with muscle function (protein carbonyl, p &lt, 0.05). Coenzyme Q10 level was positively associated with antioxidant capacity, muscle mass, muscle strength and muscle endurance in patients with OA (p &lt, 0.05). Since OA is an age-related disease, coenzyme Q10 may be consumed by oxidative stress and thereby affect muscle function. Raising coenzyme Q10 in patients with OA could be suggested, which may benefit their antioxidant capacity and muscle function.

Chronic leg ulcers effect millions of people around the world. It is imperative to search for effective treatments for such challenging ulcers. We report the success of aminolevulinic acid-mediated antimicrobial photodynamic therapy (A-PDT) to enhance wound healing of chronic ulcers for 3 patients who were refractory to conventional treatments. These ulcers healed after one to three sessions of A-PDT and there was no recurrence for more than 29 months. Interestingly, no bacteria were isolated from the ulcers after A-PDT treatment. In vitro, A-PDT also inactivated all bacteria isolated from the patients. A-PDT conditioned medium containing IL-6 enhanced keratinocyte migration. The results suggest in addition to bactericidal effects, A-PDT also alters the wound microenvironment. A-PDT may be an effective treatment for patients with recalcitrant infected ulcers.

Summary Lymphoma is a group of blood cancers that develop from the immune system, and one of the main risk factors is associated with exposure to environmental chemicals. Bisphenol A (BPA) is a common chemical used in the manufacture of materials in polycarbonate and epoxy plastic products and can interfere with the immune system. BPA is considered to possibly induce lymphoma development by affecting the immune system, but its potential mechanisms have not been well established. This study performed a gene-network analysis of microarray data sets in human lymphoma tissues as well as in human cells with BPA exposure to explore module genes and construct the potential pathway for lymphomagenesis in response to BPA. This study provided evidence that BPA exposure resulted in disrupted cell cycle and DNA damage by activating CTNNB1, the initiator of the aberrant constructed CTNNB1-NFKB1-AR-IGF1-TWIST1 pathway, which may potentially lead to lymphomagenesis., Graphical abstract, Highlights • CTNNB1 is an initiator of BPA-mediated lymphomagenesis by gene-network analysis • BPA exposure promotes clonogenic survival of damaged TK6 lymphoblastoid cells • BPA/CTNNB1 dysregulates DNA-repair-associated genes TP53 and CDKN1A • BPA-/CTNNB1-mediated lymphomagenesis is attributable to DNA breaks and G2/M arrest, Molecular biology; Cancer

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Antrodia camphorata is a unique mushroom of Taiwan and has been used as a folk medicine for protection against liver damage induced by alcohol intoxication. However, no report has been presented in this respect. In this rat study, we examined whether the mycelium and sporocarp of Antrodia camphorata protect against acute liver damage induced by ethanol (EtOH). Rats were orally administered with mycelium and sporocarp of Antrodia camphorata for 9 days before EtOH challenge (5.5 g/kg body wt., i.p.). Rats were divided into eight groups (A-H) and except for groups A and H, all rats were injected with alcohol. A: Control; B: EtOH control: C: Silymarin (250 mg/kg bw., p.o.); D: 0.5 g mycelium/kg; E: 1.0 g mycelium/kg; F: 0.5 g sporocarp/kg; G: 1.0 g sporocarp/kg; and H: 1.0 g mycelium/kg. The results showed that EtOH administration markedly increased the activities of glutamate-pyruvate aminotransferase (GPT) and glutamate-oxaloacetate aminotransferase (GOT). Both mycelium and sporocarp of Antrodia camphorata significantly decreased the activity of GOT and GPT, but the effects were not dose-dependent. Mycelium and sporocarp of Antrodia camphorata also significantly and dose-dependently decreased lipid peroxidation (measured as TBARS) induced by EtOH. EtOH treatment significantly increased the activities of hepatic superoxide dismutase (SOD) and catalase, but did not significantly affect the activity of glutathione peroxidase. Pre-treatment with either the mycelium or the sporocarp completely prevented the rise in the activity of SOD and catalase. The histopathological examination revealed that both mycelium and sporocarp markedly protected against lipid vacuole accumulation and hydropic degeneration of hepatocytes induced by EtOH. Thus, the present results demonstrated that both mycelium and sporocarp of Antrodia camphorata protect against acute liver damage induced by EtOH. In addition, rats fed 1.0 g mycelium without EtOH treatment produced no observable toxicity during the experimental period.