Comparisons on the intraoperative desaturation and postoperative outcomes in non-intubated video-assisted thoracic surgery with supraglottic airway devices or high-flow nasal oxygen: A retrospective study.

BACKGROUND: Few studies have compared intraoperative oxygenation and perioperative outcomes between non-intubated video-assisted thoracic surgery (NIVATS) with supraglottic airway devices (SADs) and NIVATS with high flow nasal oxygenation (HFNO). The aim of this retrospective study was to compare the intraoperative desaturation rate and postoperative outcomes between NIVATS with SADs and NIVATS with HFNO. METHODS: Data regarding NIVATS performed for lung cancer from January 2020 to December 2021 were collected. Intraoperative anesthetic results, post-anesthetic adverse effects, and surgical outcomes for patients who received SAD or HFNO were analyzed using propensity score-matched and unmatched analysis. RESULTS: In total, 199 patients with i-gel™ and 95 patients with HFNO were included. Significantly more female patients (91.6 vs. 82.4%, p = 0.0378) and fewer wedge resections (78.9 vs. 85.4%, p = 0.0258) were observed in the HFNO group. Among 250 patients who underwent NIVATS wedge resections under total intravenous anesthesia, those who received HFNO had a significantly higher desaturation event rate (19.8% vs. 7.9% in i-gel™ group; p = 0.0063), lower nadir SPO2 (94.0% vs. 96.1% in i-gel™ group; p = 0.0012), and longer hospitalization (4.0 ± 0.8 vs. 3.6 ± 0.6 in i-gel™ group; p < 0.0001). However, propensity score matching analysis revealed no significant between-group difference in the desaturation rate. A log-rank test revealed that smoking (p = 0.0005) and HFNO (p = 0.0074) were associated with intraoperative desaturation. CONCLUSION: The rate of SAD use in NIVATS was twice the rate of HFNO use, especially for wedge resections. There is uncertain airway patency and limited flow through HFNO during one-lung ventilation, whereas SADs like i-gel™ presented a significantly less intraoperative desaturation rate over time and similar postoperative outcomes.

Solving the deficit of cancer pain management skills by education programs.

BACKGROUND: Suboptimal cancer pain management is a worldwide problem. We examined whether an educational program on cancer pain management implemented during training could benefit primary care physicians. METHODS: We enrolled all the primary care physicians who visited the oncology ward at a medical center for the first time. Educational classes on cancer pain management were conducted. The participants' abilities in cancer pain management were measured in a pretest before the classes and approximately 2 weeks later in the first posttest. The second posttest was conducted on participants who visited the oncology ward again. All 3 tests had the same set of questions and were scored on a scale of 0 to 100. RESULTS: In total, 247 participants were enrolled. Less than 10% of them considered their previous education on cancer pain management adequate. The test scores increased significantly from the pretest to the first posttest (mean 65.6 vs. 89.7, p < 0.001). The participants' self-reported cancer pain management abilities, on a scale of 0 to 100, also improved significantly (mean 57.8 vs. 75.5, p < 0.001). The pretest scores were not associated with the participants' self-reported abilities or their perceptions about the adequacy of previous training on cancer pain management. The mean score on the second posttest, conducted 234.5 days after the program, on an average, remained similar to that of the first posttest (p = 0.254). CONCLUSION: A specific educational program on cancer pain management provided to primary care physicians improved their pain management skills substantially, with persistent effects.

New Era of Immunotherapy in Pediatric Brain Tumors: Chimeric Antigen Receptor T-Cell Therapy.

Immunotherapy, including chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, cancer vaccines, and dendritic cell therapy, has been incorporated as a fifth modality of modern cancer care, along with surgery, radiation, chemotherapy, and target therapy. Among them, CAR T-cell therapy emerges as one of the most promising treatments. In 2017, the first two CAR T-cell drugs, tisagenlecleucel and axicabtagene ciloleucel for B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), respectively, were approved by the Food and Drug Administration (FDA). In addition to the successful applications to hematological malignancies, CAR T-cell therapy has been investigated to potentially treat solid tumors, including pediatric brain tumor, which serves as the leading cause of cancer-associated death for children and adolescents. However, the employment of CAR T-cell therapy in pediatric brain tumors still faces multiple challenges, such as CAR T-cell transportation and expansion through the blood-brain barrier, and identification of the specific target antigen on the tumor surface and immunosuppressive tumor microenvironment. Nevertheless, encouraging outcomes in both clinical and preclinical trials are coming to light. In this article, we outline the current propitious progress and discuss the obstacles needed to be overcome in order to unveil a new era of treatment in pediatric brain tumors.

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies.

With advances in the understanding of characteristics of molecules, specific antigens on the surface of hematological malignant cells were identified and multiple therapies targeting these antigens as neoplasm treatments were developed. Among them, chimeric antigen receptor (CAR) T-cell therapy, which got United States Food and Drug Administration (FDA) approval for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) as well as for recurrent acute lymphoblastic leukemia (ALL) within the past five years, and for r/r mantle cell lymphoma (MCL) this year, represents one of the most rapidly evolving immunotherapies. Nevertheless, its applicability to other hematological malignancies, as well as its efficacy and persistence are fraught with clinical challenges. Currently, more than one thousand clinical trials in CAR T-cell therapy are ongoing and its development is changing rapidly. This review introduces the current status of CAR T-cell therapy in terms of the basic molecular aspects of CAR T-cell therapy, its application in hematological malignancies, adverse reactions during clinical use, remaining challenges, and future utilization.

Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia.

Morphine is the most commonly used drug for treating physical and psychological suffering caused by advanced cancer. Although morphine is known to elicit multiple supraspinal analgesic effects, its behavioral correlates with respect to the whole-brain metabolic activity during cancer-induced bone pain have not been elucidated. We injected 4T1 mouse breast cancer cells into the left femur bone marrow cavity of BALB/c mice. All mice developed limb use deficits, mechanical allodynia, and hypersensitivity to cold, which were effectively suppressed with morphine. Serial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed for each mouse before cancer induction (0 day), after cancer-induced bone pain was established (14 days), and during effective morphine treatment (16 days). The longitudinal FDG-PET imaging analysis demonstrated that cancer-induced bone pain increased glucose uptake in the insular cortex and hypothalamus and decreased the activity of the retrosplenial cortex. Morphine reversed the activation of the insular cortex and hypothalamus. Furthermore, morphine activated the amygdala and rostral ventromedial medulla and suppressed the activity of anterior cingulate cortex. Our findings of hypothalamic and insular cortical activation support the hypothesis that cancer-induced bone pain has strong inflammatory and affective components in freely moving animals. Morphine may provide descending inhibitory and facilitatory actions in the treatment of cancer-induced bone pain in a clinical setting.

Right or left? Side selection for a totally implantable vascular access device: a randomised observational study.

BACKGROUND: Totally implantable vascular access device (TIVAD)-related complications interfere in the anticancer treatment and increase medical expenses. We examined whether the implantation side of central line TIVADs is associated with the occurrence of thrombotic or occlusion events. METHODS: We enrolled patients with cancer who required central line TIVADs and randomised them to receive the TIVAD implantation on either the left or right side. The primary endpoint was the occurrence of catheter-related thrombotic or occlusion events. RESULTS: We randomised 240 patients, of which 235 received TIVAD implantation according to the protocol. In the per-protocol cohort, 117 and 118 patients received implantation on the left and right sides, respectively. Catheter-related thrombotic or occlusion events occurred in 9 (4%) patients, accounting for 0.065 events per 1000 catheter-days. Between the patients with left- and right-sided implantations, the occurrence rates (P=0.333) and the time from catheter implantation to the occurrence of thrombotic or occlusion events (P=0.328) were both similar. In the multivariate analysis, the side of implantation remained unassociated with the occurrence of thrombotic or occlusion events. CONCLUSIONS: The side of central line TIVAD implantation was not associated with the occurrence of catheter-related thrombotic or occlusion events in patients with cancer.

Synergistic Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Gating by Two Chemically Distinct Potentiators, Ivacaftor (VX-770) and 5-Nitro-2-(3-Phenylpropylamino) Benzoate.

Cystic fibrosis (CF) is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding a phosphorylation-activated but ATP-gated chloride channel. Previous studies suggested that VX-770 [ivacaftor, N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide], a CFTR potentiator now used in clinics, increases the open probability of CFTR by shifting the gating conformational changes to favor the open channel configuration. Recently the chloride channel blocker and CFTR potentiator 5-nitro-2-(3-phenylpropylamino) benzoate (NPPB) has been reported to enhance CFTR activity by a mechanism that exploits the ATP hydrolysis-driven, nonequilibrium gating mechanism unique to CFTR. Surprisingly however, NPPB increased the activity of nonhydrolytic G551D-CFTR, the third most common disease-associated mutation. Here, we further investigated the mechanism of NPPB's effects on CFTR gating by assessing its interaction with well-studied VX-770. Interestingly, once G551D-CFTR was maximally potentiated by VX-770, NPPB further increased its activity. However, quantitative analysis of this drug-drug interaction suggests that this pharmacologic synergism is not due to independent actions of NPPB and VX-770 on CFTR gating; instead, our data support a dependent mechanism involving two distinct binding sites. This latter idea is further supported by the observation that the locked-open time of a hydrolysis-deficient mutant K1250A was shortened by NPPB but prolonged by VX-770. In addition, the effectiveness of NPPB, but not of VX-770, was greatly diminished in a mutant whose second nucleotide-binding domain was completely removed. Interpreting these results under the framework of current understanding of CFTR gating not only reveals insights into the mechanism of action for different CFTR potentiators but also brings us one step forward to a more complete schematic for CFTR gating.

Fast Track ultrasound protocol to detect acute complications after totally implantable venous access device placement.

BACKGROUND: The role of ultrasound examination in detection of postprocedure complications from totally implantable venous access devices (TIVAD) placement is still uncertain. In a cohort of 665 cancer outpatients, we assessed a quick ultrasound examination protocol in early detection of mechanical complications of catheterization. METHODS: Immediately after TIVAD placement, an ultrasound examination and chest radiography were performed to detect hemothorax, pneumothorax, and catheter malposition. The two methods were compared. RESULTS: Of the 668 catheters inserted, 628 were placed into axillary veins and 40 into internal jugular veins. The ultrasound examination took 2.5 ± 1.1 min. No hemothorax was detected, and neither pneumothorax nor catheter malposition was evident among the 40 internal jugular vein cannulations. Ultrasound and chest radiography examinations of the 628 axillary vein cannulations detected five and four instances of pneumothorax, respectively. Ultrasound detected all six catheter malpositions into the internal jugular vein. However, ultrasound failed to detect two out of three malpositions in the contralateral brachiocephalic vein and one kinking inside the superior vena cava. Without revision surgery, the operating time was 34.1 ± 15.6 min. With revision surgery, the operating time was shorter when ultrasound detected catheter malposition than when chest radiography was used (96.8 ± 12.9 vs. 188.8 ± 10.3 min, p < 0.001). CONCLUSIONS: Postprocedure ultrasound examination is a quick and sensitive method to detect TIVAD-related pneumothorax. It also precisely detects catheter malposition to internal jugular vein thus reduces time needed for revision surgery while chest radiography remains necessary to confirm catheter final position.

Gabapentin reverses central hypersensitivity and suppresses medial prefrontal cortical glucose metabolism in rats with neuropathic pain.

BACKGROUND: Gabapentin (GBP) is known to suppress neuropathic hypersensitivity of primary afferents and the spinal cord dorsal horn. However, its supra-spinal action sites are unclear. We identify the brain regions where GBP changes the brain glucose metabolic rate at the effective dose that alleviates mechanical allodynia using 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning. RESULTS: Comparing the PET imaging data before and after the GBP treatment, the spared nerve injury-induced increases of glucose metabolism in the thalamus and cerebellar vermis were reversed, and a significant decrease occurred in glucose metabolism in the medial prefrontal cortex (mPFC), including the anterior cingulate cortex. GBP treatment also reversed post-SNI connectivity increases between limbic cortices and thalamus. CONCLUSIONS: Our results indicate that GBP analgesic effect may be mediated by reversing central hypersensitivity, and suppressing mPFC, a crucial part of the cortical representation of pain, in the brain.

Clinical outcomes and safety of remdesivir in hospitalized individuals with COVID-19, with or without severe renal impairment.

BACKGROUND: The use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment. METHODS: Hospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m2) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis. RESULTS: A total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment. CONCLUSIONS: Remdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment.

Discontinuity third harmonic generation microscopy for label-free imaging and quantification of intraepidermal nerve fibers.

Label-free imaging methodologies for nerve fibers rely on spatial signal continuity to identify fibers and fail to image free intraepidermal nerve endings (FINEs). Here, we present an imaging methodology-called discontinuity third harmonic generation (THG) microscopy (dTHGM)-that detects three-dimensional discontinuities in THG signals as the contrast. We describe the mechanism and design of dTHGM and apply it to reveal the bead-string characteristics of unmyelinated FINEs. We confirmed the label-free capability of dTHGM through a comparison study with the PGP9.5 immunohistochemical staining slides and a longitudinal spared nerve injury study. An intraepidermal nerve fiber (IENF) index based on a discontinuous-dot-connecting algorithm was developed to facilitate clinical applications of dTHGM. A preliminary clinical study confirmed that the IENF index was highly correlated with skin-biopsy-based IENF density (Pearson's correlation coefficient R = 0.98) and could achieve differential identification of small-fiber neuropathy (p = 0.0102) in patients with diabetic peripheral neuropathy.

Quality of life outcomes after surgical intervention in patients with multiple rib fractures: A prospective cohort study.

BACKGROUND: Optimized conservative treatment of rib fractures has long been practiced, but surgical fixation has not been promising until recently. We aimed to examine and analyze immediate postoperative outcomes and 6-month quality of life after injury in patients with moderately severe traumatic rib fractures. METHODS: We conducted a prospective cohort study between July 2017 and June 2019 at the National Taiwan University Hospital. Seventy-two patients with moderately severe thoracic trauma were enrolled; 38 received conservative treatment and 34 underwent surgical fixation. Quality of life was measured using the 36-item Short Form Survey at; the first 3 days of hospitalization; before discharge; and at 1-, 2-, and 6-month follow-ups (visits 1-5). Baseline characteristics and clinical outcomes were recorded, and linear regression analysis was conducted using the generalized estimating equation. RESULTS: Among patients with moderately severe thoracic injury (chest Abbreviated Injury Scale score≥ 2), the operative group had more severe injuries and longer intensive care unit and in-hospital stays. However, they had a comparable quality of life 6 months after injury and higher physical component scores in the early postoperative period. Linear regression analysis obtained an equation with several factors positively affecting prediction of the mean physical component score, such as body mass index ≤25, age ≤36 years, fewer ribs requiring fixation, and diabetes mellitus. Mental component score did not show an upward trend, but the Work Quality Index largely determined the predicted mean value of the mental component score. CONCLUSION: Surgical rib fixations hasten recovery in patients with severe thoracic injury (chest Abbreviated Injury Scale ≥3) to achieve 6-month quality of life comparable to patients injured less severely (chest Abbreviated Injury Scale ≥2). The ability to resume previous work positively influenced the mental component score; thus, surgical intervention should also aim to help patients regain their social function.

Washed Microbiota Transplantation Improves Patients with Overweight by the Gut Microbiota and Sphingolipid Metabolism.

BACKGROUND: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients. METHODS: The changes in body mass index (BMI = weight (kg)/height (m)2), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics. RESULTS: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism. CONCLUSION: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism.

Herpes zoster prophylaxis: Essential for treating newly diagnosed multiple myeloma patients.

BACKGROUND: Multiple myeloma (MM) is known for its immune disturbance and patients suffering from MM are thus vulnerable to opportunistic infections, including herpes zoster (HZ). As HZ infection remarkably affects patients' quality of life and poses huge economic burdens on the health system, we aim to identify the risk factors of HZ infection and evaluate the effects of different dosages, types, and durations of anti-HZ prophylaxis drugs to prevent HZ infection. METHODS: 551 MM patients at Taipei Veterans General Hospital in Taiwan between January 1, 2009 and August 31, 2021 were restrospectively analyzed. The patients' baseline characteristics were recorded. The primary endpoint of the study was the incidence of HZ infection among the studied patient population. Due to the lack of cost coverage from Taiwanese public health insurance on HZ prophylaxis drugs, the use of anti-HZ drugs mainly depends on physicians' preferences and patients' choices. RESULTS: In our study, prophylaxis was given to 283 of the patients. In the multivariate analysis, we included non-prophylaxis, age ≥ 60, corrected serum calcium ≥12 mg/dl, serum creatinine ≥2 mg/dl, serum ß2-microglobulin ≥5500 mg/L, autologous stem cell transplant (SCT), and allogeneic SCT for analysis. Our results demonstrated that the non-prophylaxis group (HR: 2.37, 95% CI 1.57-3.57) and patients receiving autologous SCT (HR: 2.22, 95% CI 1.28-3.86) and allogeneic SCT (HR: 5.12, 95% CI 1.13-23.22) had higher risk of HZ infection. The difference in dosage and types of anti-HZ drugs showed similar protective effects. In patients who stopped anti-HZ prophylaxis before active cancer-related treatment, a higher risk of getting HZ infection compared to the corresponding group was also observed (adjusted HR 3.09, 95% CI 1.35-7.07, p = 0.008). CONCLUSIONS: We concluded that MM patients should receive HZ prophylaxis drugs while receiving active cancer-related treatment. Patients receiving SCT are also at high risk of getting HZ infection, even under prophylaxis.

Intravenous electrocardiography helps inexperienced operators to place totally implantable venous access device more accurately.

BACKGROUND: Proper tip position is a major determinant of totally implantable venous access device (TIVAD) outcome. The aim of this study is to analyze the potential utilization of intravenous electrocardiography (IV-ECG) to help inexperienced operators for TIVAD placement. PATIENTS AND METHODS: This is a retrospective, observational, uni-institutional study. 331 patients receiving TIVAD implantation from July 2008 to December 2008 were recruited. In IV-ECG group, IV-ECG was used to help decide catheter tip location and catheter length. In Landmark group, catheter length was decided by surface landmarks. Catheter tip position was confirmed by post-operative supine chest X-ray. RESULTS: There were 153 patients in IV-ECG group, and 178 patients in Landmark group. No immediate reoperation due to catheter mal-position was noted in IV-ECG group, but it happened in eight patients in Landmark group. In IV-ECG group, 97.3% of the catheter tip located at proper position (within 2 cm from junction of right atrium and superior vena cava, as compared to 88.8% of the tip position in Landmark group was proper. The difference was statistically significant (P < 0.05). There was no complication associated with the use of IV-ECG. CONCLUSION: IV-ECG is a safe and convenient method to help inexperienced operators placing TIVAD.

Efficacy of intrathecal drug delivery system for refractory cancer pain patients: a single tertiary medical center experience.

BACKGROUND/PURPOSE: Between 10% and 20% of cancer pain patients fail to obtain adequate pain relief despite comprehensive medical management. The totally implantable programmable intrathecal drug delivery system (IDDS) is an attractive option for managing refractory cancer pain. In suitable patients, IDDS can provide reliable long-term analgesia without any permanent nerve or plexus destruction. IDDS can also allow patient care on an outpatient basis. In Taiwan, however, the experience of using IDDS in terminally ill cancer patients is very limited. METHODS: This retrospective study, describes experience of managing totally implantable programmable IDDS in 6 refractory cancer pain patients including patient selection, intraspinal morphine trial, surgical techniques, complications, and drug adjustment. Pain scores and functional status were compared before and after IDDS. RESULTS: By delivering liberal dose of intrathecal morphine, patients' pain scores decreased from 10 to 3.5. Due to much better pain control and improved quality of life, Eastern Cooperative Oncology Group performance status also improved in 4/6 patients. During the mean 5 ± 4.1 months of follow-up, two patients experienced pocket seroma, and resolved spontaneously after short-term abdominal binder compression. Otherwise, no serious complication was noted. CONCLUSION: Intrathecal morphine delivery by using totally implantable programmable IDDS is an effective method to relieve refractory cancer pain.

Altered metabolic connectivity between the amygdala and default mode network is related to pain perception in patients with cancer.

We investigated the neural correlates for chronic cancer pain conditions by retrospectively analyzing whole brain regions on 18F-fluoro-2-deoxyglucose-positron emission tomography images acquired from 80 patients with head and neck squamous cell carcinoma and esophageal cancer. The patients were divided into three groups according to perceived pain severity and type of analgesic treatment, namely patients not under analgesic treatment because of no or minor pain, patients with good pain control under analgesic treatment, and patients with poor pain control despite analgesic treatment. Uncontrollable cancer pain enhanced the activity of the hippocampus, amygdala, inferior temporal gyrus, and temporal pole. Metabolic connectivity analysis further showed that amygdala co-activation with the hippocampus was reduced in the group with poor pain control and preserved in the groups with no or minor pain and good pain control. The increased although imbalanced activity of the medial temporal regions may represent poor pain control in patients with cancer. The number of patients who used anxiolytics was higher in the group with poor pain control, whereas the usage rates were comparable between the other two groups. Therefore, further studies should investigate the relationship between psychological conditions and pain in patients with cancer and analyze the resultant brain activity.Trial registration: This study was registered at clinicaltrials.gov on 9/3/20 (NCT04537845).

Zebrafish models for glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis due to excessive or long-term glucocorticoid administration, disturbing the homeostasis between bone formation and bone resorption. The bone biology of zebrafish shares a high degree of similarities with mammals. In terms of molecular level, genes and signaling pathways related to skeletogenesis are also highly correlated between zebrafish and humans. Therefore, zebrafish have been utilized to develop multiple GIOP models. Taking advantage of the transparency of zebrafish larvae, their skeletal development and bone mineralization can be readily visualized through in vivo staining without invasive experimental handlings. Moreover, the feasibility of using scales or fin rays to study bone remodeling makes adult zebrafish an ideal model for GIOP research. Here, we reviewed current zebrafish models for GIOP research, focused on the tools and methods established for examining bone homeostasis. As an in vivo, convenient, and robust model, zebrafish have an advantage in performing high-throughput drug screening and could be used to investigate the action mechanisms of therapeutic drugs.

Nonintubated bronchoscopic interventions with high-flow nasal oxygen: A retrospective observational study.

ABSTRACT: To determine the feasibility on maintaining oxygenation of high-flow nasal oxygenation (HFNO) with bispectral index-guided intravenous anesthesia for nonintubated interventional bronchoscopy (NIIB). If desaturation happens, the factors influencing intraprocedural desaturation were also analyzed.This is a single-center retrospective study on patients receiving NIIB with HFNO and intravenous anesthesia guided by bispectral index levels to the depth of general anesthesia, which were between 40 and 60. Intraprocedural desaturation (SPO2 < 90%) and complications (bleeding, delayed discharge, unexpected admission) were collected. Factors affecting desaturation and complications were analyzed including patients' factors (age, American Society of Anesthesiologists classification, body mass index [BMI]), procedural factors (procedural time, with or without use of cryoprobe), and setting (outpatient or hospitalized).Records of 223 patients receiving NIIB were collected. The NIIB procedures time was 56.1 ±â€Š26.8 minute. Sixty patients (26.9%) presented desaturation events. Higher BMI, but not procedure time or setting, was significantly associated with desaturation. The desaturation were resolved after relieving upper airway obstruction but 1 patient required bag-valve-mask ventilation to restore oxygenation. Accidental massive bleeding and intraprocedural desaturation during tracheal and bronchial recannulation with cryoprobes happened in 2 patients and 1 of them was admitted to intensive care unit.HFNO is feasible to maintain oxygenation during NIIB only if there is effective upper airway management especially for patients with higher BMI. Longer procedural time and different setting did not affect the desaturation rate. Complications and unexpected admission were associated with the use of cryoprobes.

Gu Sui Bu (Drynaria fortunei J. Sm.) antagonizes glucocorticoid-induced mineralization reduction in zebrafish larvae by modulating the activity of osteoblasts and osteoclasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Gu Sui Bu (GSB), the dried rhizome of Drynaria fortunei J. Sm., is widely used in traditional Chinese medicine for treating fractures and osteoporosis. Although glucocorticoids are widely prescribed in modern medicine, the efficacy of GSB in treating glucocorticoid-induced osteoporosis (GIOP) remains unclear. AIM OF THE STUDY: GIOP is one of the most prevalent forms of osteoporosis and increases the risk of fracture, which can cause severe complications in elderly people. Safe, efficacious, and cost-effective treatment options for GIOP are thus warranted. The present study investigated the efficacy and mechanism of GSB for treating GIOP. MATERIALS AND METHODS: We established an efficient and robust in vivo GIOP model by optimizing zebrafish larvae rearing conditions and the dose and duration of dexamethasone treatment. Bone calcification was evaluated through calcein staining. To quantify the degree of vertebral mineralization in the larvae, we developed a scoring system based on the rate of vertebral calcification; this system reduced quantification errors among individual zebrafish caused by inconsistencies in staining or imaging parameters. Quantitative real-time polymerase chain reaction was used to access the expression levels of genes essential to the differentiation and function of bone cells. High-performance liquid chromatography was employed to identify naringin in the GSB extract. RESULTS: GSB significantly reversed the dexamethasone-induced calcification delay in zebrafish larvae. GSB enhanced osteoblast activity by increasing the expression of collagen I, osteopontin, and osteonectin and repressed bone resorption by decreasing the expression of matrix metalloproteinases (mmps), including mmp9 and mmp13a. We also identified naringin as one of the constituents of GSB responsible for the herbal extract's anti-GIOP activity. CONCLUSIONS: Using the in vivo zebrafish GIOP model that we established, the efficacy of traditional Chinese medicines in treating GIOP could be systematically investigated. GSB has an osteogenic effect and may thus be an efficacious and cost-effective treatment option for GIOP. Notably, bone resorption activity was found to be retained after GSB treatment, which would be beneficial for maintaining normal bone remodeling.