The FIB-4 scores in the emergency department to predict the outcomes of COVID-19 patients in taiwan.

Objective: We aimed to determine the reliability of using the Fibrosis-4 (FIB-4) index in COVID-19 patients without underlying liver illness. Method: We employed multivariate logistic regression to identify variables that exhibited statistically significant influence on the ultimate outcome. Multilayer perceptron analysis was employed to develop a prediction model for the FIB-4 index concerning ICU admission and intubation rates. However, the scarcity of cases rendered the assessment of the mortality rate unfeasible. We plotted ROC curves to analyze the predictive strength of the FIB-4 index across various age groups. Result: In univariate logistic regression, only the FIB-4 index and respiratory rate demonstrated statistical significance on all poor outcomes. The FIB-4 index for mortality prediction had an ROC and AUC of 0.863 (95% CI: 0.781-0.9444). It demonstrates predictive power across age groups, particularly for age ≥65 (AUC: 0.812, 95% CI: 0.6571-0.9673) and age <65 (AUC: 0.878, 95% CI: 0.8012-0.9558). Its sensitivity for intubation and ICU admission prediction is suboptimal. Conclusion: FIB-4 index had promising power in prediction of mortality rate in all age groups.

Preclinical Animal Study and Pilot Clinical Trial of Using Enriched Peripheral Blood-Derived Mononuclear Cells for Intervertebral Disc Degeneration.

Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro. Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients.

Predictive factors for severe outcomes in substance abuse-related emergency visits: A 5-year retrospective analysis at a medical center in Taiwan.

BACKGROUND: Substance abuse is a considerable medical issue worldwide, yet current surveillance systems in Taiwan offer limited insights into the clinical characteristics and outcomes of substance abuse patients. This study aimed to delineate the epidemiology of emergency department visits related to substance abuse at a hospital in Taiwan and to identify factors predictive of severe complications or mortality. METHODS: A retrospective analysis was conducted on substance abuse-related emergency department visits at a medical center in Taiwan between 2009 and 2013. Eligible participants were individuals aged 20 or older who had confirmed substance abuse through urinalysis. Variables such as patient demographics, substances abused, clinical characteristics, and outcomes were collected. Severe outcomes were defined as admission to the intensive care unit, requirement for endotracheal intubation, or in-hospital death. Logistic regression models were employed to identify factors contributing to severe outcomes. RESULTS: The cohort consisted of 623 patients, of whom 64.0% were female and 67.1% were aged between 20 and 49 years. Benzodiazepines were detected in 75.3% of patients, while z-drugs (specifically zopiclone, zolpidem, or zaleplon) were found in 27.8%. Depressants, stimulants, and hallucinogens were present in 14.9%, 10.6%, and 0.6% of the cases, respectively. Of the patient, 121 (19.4%) experienced severe outcomes, including 116 (18.6%) intensive care unit admissions, 73 (11.7%) intubations, and 11 (1.8%) in-hospital deaths. Multivariable logistic regression analysis revealed multiple predictors of severe outcomes, such as emergency department triage level, aspiration pneumonia, leukocytosis, abnormal hepatic function, abnormal renal function, hypernatremia, and hypocalcemia. CONCLUSION: In Taiwan, benzodiazepines emerged as the most prevalent substance of abuse among emergency department visitors, and a significant proportion of these patients experienced severe outcomes. Continuous monitoring of severe outcome predictors is essential for enhanced understanding and management.

Enriched Peripheral Blood-Derived Mononuclear Cells for Treating Knee Osteoarthritis.

Osteoarthritis (OA) is a common chronic skeletal disease in the elderly. There is no effective therapy to reverse disease severity and knee OA (KOA) progression, particularly at the late stage. This study aims to examine the effect of peripheral blood-derived mononuclear cells (PBMNCs) on pain and motor function rescue in patients with Kellgren-Lawrence (KL) grade II to IV KOA. Participants received one intra-articular (IA) injection of autologous PBMNCs. The mononuclear cells were isolated from peripheral blood, enriched by a specialized medium (MoFi medium), and separated by Ficoll-Paque solution. The isolated and enriched PBMNCs could differentiate into M1 and M2 macrophages in vitro. The in vivo anti-inflammatory effect of the PBMNCs was similar to that of bone marrow mesenchymal stem cells, evaluated by complete Freund's adjuvant-induced arthritis in rodents. A single-arm and open-label pilot study showed that patients' knee pain and motor dysfunction were significantly attenuated after the cell transplantation, assessed by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months post-treatment. Notably, the therapeutic effect of the PBMNCs treatment can be stably maintained for 24 months, as revealed by the KOOS scores. These preclinical and pilot clinical data suggest that IA injection of MoFi-PBMNCs might serve as a novel medical technology to control the pain and the progress of KOA.

Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells.

The human type II collagen (Col II), specifically expressed in chondrocytes, is a crucial component of the adult hyaline cartilage. We examine the potential of artificial induction of Col II in human peripheral blood mononuclear cells (PBMNCs) as a novel Col II provider. Human PBMNCs were purified and were treated with high doses of macrophage-colony stimulating factor (M-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), or granulocyte-colony stimulating factor (G-CSF) and examined the Col II expression at indicated days. Quantitative Col II expression was validated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and flow cytometry. We demonstrate that monocytes in PBMNCs can be artificially induced to express both Col II proteins and M2 macrophage markers by the high concentration of colony-stimulating factors, especially M-CSF and GM-CSF. The Col II proteins were detected on the cell membrane and in the cytoplasm by flow cytometry and immunocytostaining. Combination with IL-4 provided a synergistic effect with M-CSF/GM-CSF to trigger Col II expression in M2 macrophages. These CD206 and Col II double-expressing cells, named modified macrophages, share M2 macrophages' anti-inflammatory potency. We demonstrated that the modified macrophages could significantly attenuate the inflammatory progress of Complete Freund's adjuvant (CFA)-induced arthritis and collagen-induced arthritis in rodents. Here, we provide the first evidence that a modified macrophage population could ectopically express Col II and control the progress of arthritis in animals.

Fabrication of Stromal Cell-Derived Factor-1 Contained in Gelatin/Hyaluronate Copolymer Mixed with Hydroxyapatite for Use in Traumatic Bone Defects

Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal stem cells (MSCs) in certain circumstances, which may also play an important role in bone regeneration. In this study, we fabricated a gelatin/hyaluronate (Gel/HA) copolymer mixed with hydroxyapatite (HAP) and SDF-1 to try and enhance bone regeneration in a bone defect model. After material characterization, these Gel/HA-HAP and Gel/HA-HAP-SDF-1 composites were tested for their biocompatibility and ability to recruit MSCs in vitro. A femoral condyle bone defect model of rats was used for in vivo studies. For the assessment of bone healing, micro-CT analysis, second harmonic generation (SHG) imaging, and histology studies were performed. As a result, the Gel/HA-HAP composites showed no systemic toxicity to rats. Gel/HA-HAP composite groups both showed better bone generation compared with the control group in an animal study, and the composite with the SDF-1 group even showed a trend of faster bone growth compared with the composite without SDF-1 group. In conclusion, in the management of traumatic bone defects, Gel/HA-HAP-SDF-1 composites can be a feasible material for use as bone void fillers.

Fabrication of Nanoarchitectonic AgOx/BiPO4 Electrochemical Sensor for Detection of Resveratrol.

In the present study, a novel AgOx/BiPO4 sensor was successfully prepared and used for detecting trans-resveratrol. Prepared samples were characterized using methods including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy. The results demonstrate that the AgOx/BiPO4 is composed of AgO, Ag2O, and BiPO4. In addition, a cyclic voltammetry method was used to measure resveratrol concentration using the electrochemical sensor based on AgOx/BiPO4. AgOx/BiPO4 presents a well-defined voltammetric peak at approximately +460 mV versus Ag/AgCl in phosphate-buffered saline solution. In addition, the sensor exhibits a detection limit of 1.0×10-7 M, and the wide dynamic concentration ranges from 2.0×10-7 to 12.5×10-6 M. Stability and interference tests were performed for 20 days. A possible mechanism for AgOx/BiPO4 detection of trans-resveratrol detection is proposed.

A Novel Co3O4-BiPO4 Nanoarchitectonics Material Preparation for the Electrocatalytic Detection of Epinephrine.

A novel sensing material of cobalt oxide-bismuth phosphate (Co3O4-BiPO4) was prepared by the hydrothermal method. Thus prepared sensing material was characterized by X-ray diffraction analysis (XRD) and transmission electron microscopy (TEM). The sensor was used for the determination of epinephrine by using modified Co3O4-BiPO4 on glassy carbon electrode (GCE). The cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods showed a wide linear response to a concentration range, from 1.71 to 55.00 µM, and the epinephrine detection limit for this sensing system was found to be 1.334 µM. The Co3O4-BiPO4 electrode has very high selectivity towards the detection of epinephrine supported by an interference test. The epinephrine sensor seems very advantageous for future clinical health and medical sectors.

The Development of Gelatin/Hyaluronate Copolymer Mixed with Calcium Sulfate, Hydroxyapatite, and Stromal-Cell-Derived Factor-1 for Bone Regeneration Enhancement.

In clinical practice, bone defects still remain a challenge. In recent years, apart from the osteoconductivity that most bone void fillers already provide, osteoinductivity has also been emphasized to promote bone healing. Stromal-cell-derived factor-1 (SDF-1) has been shown to have the ability to recruit mesenchymal stem cells (MSCs), which play an important role in the bone regeneration process. In this study, we developed a gelatin-hyaluronate (Gel-HA) copolymer mixed with calcium sulfate (CS), hydroxyapatite (HAP), and SDF-1 in order to enhance bone regeneration in a bone defect model. The composites were tested in vitro for biocompatibility and their ability to recruit MSCs after material characterization. For the in vivo test, a rat femoral condyle bone defect model was used. Micro computed tomography (Micro-CT), two-photon excitation microscopy, and histology analysis were performed to assess bone regeneration. As expected, enhanced bone regeneration was well observed in the group filled with Gel-HA/CS/HAP/SDF-1 composites compared with the control group in our animal model. Furthermore, detailed blood analysis of rats showed no obvious systemic toxicity or side effects after material implantation. In conclusion, the Gel-HA/CS/HAP/SDF-1 composite may be a safe and applicable material to enhance bone regeneration in bone defects.

The role of enhanced velocity shears in rapid ocean cooling during Super Typhoon Nepartak 2016.

Typhoon is a major cause of multiple disasters in coastal regions of East Asia. To advance our understanding of typhoon-ocean interactions and thus to improve the typhoon forecast for the disaster mitigation, two data buoys were deployed in the western North Pacific, which captured Super Typhoon Nepartak (equivalent to Category 5) in July 2016 at distances <20 km from the typhoon's eye center. Here we demonstrate that the unprecedented dataset combined with the modeling results provide new insights into the rapid temperature drop (~1.5 °C in 4 h) and the dramatic strengthening of velocity shear in the mixed layer and below as the driving mechanism for this rapid cooling during the direct influence period of extremely strong winds. The shear instability and associated strong turbulence mixing further deepened the mixed layer to ~120 m. Our buoys also observed that inertial oscillations appeared before the direct wind influence period.

Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains.

Nijmegen breakage syndrome (NBS) is a chromosomal-instability syndrome. The NBS gene product, NBS1 (p95 or nibrin), is a part of the Mre11-Rad50-NBS1 complex. SIN1 is a component of the mTOR/Rictor/SIN1 complex mediating the activation of Akt. Here we show that NBS1 interacted with mTOR, Rictor, and SIN1. The specific domains of mTOR, Rictor, or SIN1 interacted with the internal domain (a.a. 221-402) of NBS1. Sucrose density gradient showed that NBS1 was located in the same fractions as the mTOR/Rictor/SIN1 complex. Knockdown of NBS1 decreased the levels of phosphorylated Akt and its downstream targets. Ionizing radiation (IR) increased the NBS1 levels and activated Akt activity. These results demonstrate that NBS1 interacts with the mTOR/Rictor/SIN1 complex through the a.a. 221-402 domain and contributes to the activation of Akt activity.

Impact of vaccination with seven-valent pneumococcal conjugate vaccine on virologic and immunologic outcomes among HIV-infected adult patients in the era of highly active antiretroviral therapy.

BACKGROUND/PURPOSE: Pneumococcal polysaccharide vaccination may be associated with adverse outcomes in HIV-infected individuals who did not receive highly active antiretroviral therapy (HAART). Our aim was to evaluate the impact of vaccination with seven-valent pneumococcal conjugate vaccine (PCV) on the short-term clinical, virologic, and immunologic outcomes among HIV-infected adult patients in the HAART era. METHODS: A total of 429 HIV-infected adult patients were enrolled from October 2008 to March 2010: 213 received two doses of seven-valent PCV given at a 4-week interval and 216 received one dose. All patients were given 1-week diary to record any discomfort after vaccination. Data of serial CD4 and plasma HIV RNA load measurements were recorded. RESULTS: Of the 429 patients with a mean CD4 count of 305 cells/µL, 289 (67.4%) were receiving HAART and 175 (40.8%) had plasma HIV RNA load <40 copies/mL at vaccination. Of the 396 patients (92.3%) who returned the diary, injection site soreness (24.0%) and pain (10.4%) were the most commonly reported adverse effects. After 3-4 months of vaccination, CD4 count increased by 40 cells/µL in 278 patients (68.2%) who continued HAART, compared with a decrease of 38 cells/µL in 131 patients (31.8%) who were not on HAART (p < 0.001), while the respective change in plasma HIV RNA load was 0.8 versus 0.2 log(10) copies/mL (p = 0.09). One patient died, two developed opportunistic infections, and one developed pneumococcal pneumonia following vaccination. CONCLUSION: Vaccination with seven-valent PCV among HIV-infected patients is generally safe, which has no detrimental effect on CD4 count and plasma HIV RNA load in patients receiving HAART. (ClinicalTrials.gov number, NCT00885628).

Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the hiv infection epidemic: incidence and risk factors.

The incidence of and risk factors for Jarisch-Herxheimer (JH) reaction were investigated prospectively among 240 human immunodeficiency virus (HIV)-infected and 115 HIV-uninfected patients with syphilis who received penicillin treatment. The overall rate of JH reaction was 31.5% (34.6% in HIV-infected patients and 25.2% in HIV-uninfected patients). In multivariate analysis, risk factors for JH reaction included high rapid plasma reagin (RPR) titers (per log(2) RPR increase, risk ratio [RR], 1.19; 95% confidence interval [CI], 1.04-1.37), early syphilis (RR, 8.59; 95% CI, 4.75-15.56), and prior penicillin treatment (RR, 0.39; 95% CI, 0.20-0.78).

Postirradiated neuroendocrine carcinoma of the sinonasal tract.

OBJECTIVES/HYPOTHESIS: Neuroendocrine carcinoma (NEC) of the sinonasal tract is rare. In this present study, we report our treatment experience with sinonasal NEC. STUDY DESIGN: Retrospective case series. METHODS: A retrospective review of the clinical outcomes and pathology of 18 patients with NEC arising from the sinonasal region. RESULTS: Ten tumors were primary NEC without previous radiation, and eight tumors were postirradiated NEC occurring within the radiation field for previous nasopharyngeal carcinoma in six patients and tonsillar lymphoma in one and neck metastasis of unknown primary origin in one, with an interval between previous radiotherapy and diagnosis of NEC from 82 to 385 months, with a mean of 197 months. Fifteen tumors were small cell carcinoma, two were atypical carcinoid, and one was typical carcinoid tumor. Fifteen patients underwent surgery with/without postoperative adjuvant chemoradiotherapy. Three patients received induction chemotherapy or primary radiotherapy with further definitive treatment. The 5-year disease-free and overall survival rates of all 18 patients were 56.1% and 62.2%, respectively. In comparing primary NEC with postirradiated NEC, they were similar in age, sex distribution, stage, pathology, and treatment, and the 5-year overall survival rates were 70% and 62.5%, respectively. CONCLUSIONS: In this series, postirradiated NEC is common, which may be the result of there being a large number of long-term nasopharyngeal carcinoma survivors. The prognoses of postirradiated NEC and primary NEC appear to be similar despite the relatively short follow-up period in the postirradiated NEC group.

Retropharyngeal schwannoma excised through a transoral approach: a case report.

The contents of the retropharyngeal space are limited to fat and retropharyngeal nodes. Primary tumors originating from the retropharyngeal space are rare. More than 25% of schwannomas are found in the head and neck region, and they are rarely found in the retropharyngeal space. Here, we report the case of a 44-year-old woman with a schwannoma confined to the left retropharyngeal space, who presented with snoring and a mild lump in the throat sensation. Physical examination revealed anterior bulging of the left oropharyngeal wall, with intact mucosa. Magnetic resonance imaging showed a well-defined, encapsulated tumor in the left retropharyngeal space with bright signal intensity on T2-weighted images and low signal intensity on T1-weighted images, which was strongly enhanced after gadolinium administration. The tumor was removed through a transoral approach, resulting in a short postoperative recovery time without complications. The pathologic diagnosis was schwannoma. The patient has been well and free of tumor recurrence for 2 years. From anatomic and physiologic viewpoints, excision through a transoral approach is a good choice for a confined retropharyngeal schwannoma.