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.

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.

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.

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.

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.

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.

Washed microbiota transplantation improves patients with metabolic syndrome in South China.

Background: Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China. Methods: The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation. Results: A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients. Conclusion: WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.

Washed microbiota transplantation improves patients with high blood glucose in South China.

Background and Aims: Although fecal microbiota transplantation (FMT) from healthy donors has been shown to have hypoglycemic effects in animal models of diabetes, its clinical impact in patients with abnormal blood glucose metabolism is unclear, especially in southern Chinese populations. The aim of this study was to investigate the feasibility and efficacy of washed microbiota transplantation (WMT) in the treatment of abnormal blood glucose metabolism in a population in southern China. Methods: The clinical data of patients with different indications who received 1-3 treatments of WMT were retrospectively collected. The changes of blood glucose, blood lipids, blood pressure, liver function and blood routine before and after WMT were compared, such as fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), systolic blood pressure (SBP), white blood cells (WBC), lymphocytes (LY) and platelets (PLT), etc. Results: A total of 195 patients were included in the First Affiliated Hospital of Guangdong Pharmaceutical University, including 20 patients with high blood glucose and 175 patients with normal blood glucose. WMT has a significant effect in reducing short term blood glucose level (FBG) in patients with high blood glucose (p < 0.05). The fasting blood glucose (FBG) of 72.22% of patients with high blood glucose decreased to normal in a short term (about 1 month) (p < 0.001); In the medium term (about 2 months), there was a significant hypolipidemic (TG) (p = 0.043) effect, long term (about 6 months) significant blood pressure lowering (SBP, p = 0.048) effect. Overall, WMT significantly reduced the risk of high risk classes of Atherosclerotic Cardiovascular Disease (ASCVD) in the short term (p = 0.029) and medium term (p = 0.050). Conclusion: WMT can significantly improve blood glucose in patients with high blood glucose, and there is no long-term elevated risk of blood glucose and ASCVD. FBG levels were significantly reduced in both the short and medium term in patients with high blood glucose treated with WMT. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of abnormal blood glucose metabolism.

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).

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.

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.

The molecular etiology and treatment of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, accounting for 20% of osteoporosis diagnoses. Using glucocorticoids for >6 months leads to osteoporosis in 50% of patients, resulting in an increased risk of fracture and death. Osteoblasts, osteocytes, and osteoclasts work together to maintain bone homeostasis. When bone formation and resorption are out of balance, abnormalities in bone structure or function may occur. Excess glucocorticoids disrupt the bone homeostasis by promoting osteoclast formation and prolonging osteoclasts' lifespan, leading to an increase in bone resorption. On the other hand, glucocorticoids inhibit osteoblasts' formation and facilitate apoptosis of osteoblasts and osteocytes, resulting in a reduction of bone formation. Several signaling pathways, signaling modulators, endocrines, and cytokines are involved in the molecular etiology of GIOP. Clinically, adults ≥40 years of age using glucocorticoids chronically with a high fracture risk are considered to have medical intervention. In addition to vitamin D and calcium tablet supplementations, the major therapeutic options approved for GIOP treatment include antiresorption drug bisphosphonates, parathyroid hormone N-terminal fragment teriparatide, and the monoclonal antibody denosumab. The selective estrogen receptor modulator can only be used under specific condition for postmenopausal women who have GIOP but fail to the regular GIOP treatment or have specific therapeutic contraindications. In this review, we focus on the molecular etiology of GIOP and the molecular pharmacology of the therapeutic drugs used for GIOP treatment.

Opportunistic gill infection is associated with TiO2 nanoparticle-induced mortality in zebrafish.

The large amounts of engineered titanium dioxide nanoparticles (TiO2NPs) that have been manufactured have inevitably been released into the ecosystem. Reports have suggested that TiO2 is a relatively inert material that has low toxicity to animals. However, as various types of NPs increasingly accumulate in the ocean, their effects on aquatic life-forms remain unclear. In this study, a zebrafish model was used to investigate TiO2NP-induced injury and mortality. We found that the treatment dosages of TiO2NP are positively associated with increased motility of zebrafish and the bacterial counts in the water. Notably, gill but not dorsal fin and caudal fin of the zebrafish displayed considerably increased bacterial load. Metagenomic analysis further revealed that gut microflora, such as phyla Proteobacteria, Bacteroidetes, and Actinobacteria, involving more than 95% of total bacteria counts in the NP-injured zebrafish gill samples. These results collectively suggest that opportunistic bacterial infections are associated with TiO2NP-induced mortality in zebrafish. Infections secondary to TiO2NP-induced injury could be a neglected factor determining the detrimental effects of TiO2NPs on wild fish.

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.

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.

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.

Emerging trends in gene-modified-based chimeric antigen receptor-engineered T-cellular therapy for malignant tumors: The lesson from leukemia to pediatric brain tumors.

In 2017 and 2018, Food and Drug Administration has approved YESCARTA (axicabtagene ciloleucel) and KYMRIAH (tisagenlecleucel), two chimeric antigen receptor (CAR)-engineered T-cell products, for B-cell malignancies. It also marked a watershed moment in the development of immunotherapies for cancer. Despite the successes in adults, it remains clinically applicable only in B-cell acute lymphoblastic leukemia in pediatrics. Notably, multiple clinical trials and recent case reports about childhood central nervous system (CNS) tumors, the leading cause of deaths in children, have emerged and granted promising results. With the growing consideration of the biological responses in the interaction of human immunity, the major technical obstacles such as on-target off-tumor toxicity in widespread solid tumors, antigenic heterogeneity, adaptive resistance, difficult T-cell (CD4/CD8) trafficking, and immunosuppressive environments in CNS are gradually approached and ameliorated. The new spotlights of this review are focusing on current development, and emerging treatments for pediatric CNS tumors integrating molecular research with the mainstream of CAR-T therapeutic strategies to sketch a main axis and pathway forward in the improvement of novel gene-modified-based cellular platform.

Suction Ventilation for Uniportal Video-Assisted Thoracic Surgery Without Endotracheal Intubation.

The aim of this study is to describe the technique of pulmonary expansion by suction control from a surgical wound during nonintubated uniportal video-assisted thoracic surgery. Five patients developed oxygen desaturation intraoperatively even with facial mask ventilation. Oxygenation was completed after 3 minutes with the suction technique through the uniportal wound. All the patients underwent the operation under spontaneous ventilation, without conversion to endotracheal intubation. The suction ventilation technique can provide an alternative solution during deoxygenation conditions of nonintubated video-assisted thoracic surgery.

Synergistic symptom-specific effects of ketorolac-tramadol and ketorolac-pregabalin in a rat model of peripheral neuropathy.

BACKGROUND: Although current neuropathic pain treatment guidelines do not recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), whether NSAIDs can serve as a useful adjuvant to conventional multimodal therapy remains unclear. METHODS: The spared nerve injury (SNI) rats rapidly developed profound and long-lasting spontaneous and evoked pain behaviors, including mechanical and cold allodynia of the ipsilateral hind paw. At day 5, we first characterized the nociceptive responses to ketorolac, tramadol, pregabalin, and their combinations. RESULTS: We found that tramadol and pregabalin exerted dose-dependent analgesic effects on both spontaneous and evoked behaviors. However, ketorolac alone did not suppress any behaviors regardless of the dose. Ketorolac-tramadol and ketorolac-pregabalin produced variable degrees of additive suppression of spontaneous and evoked behavioral responses. Cold allodynia was profoundly diminished after ketorolac was added to ineffective pregabalin or tramadol. Mechanical allodynia was markedly attenuated by ketorolac-pregabalin but less so by ketorolac-tramadol mixtures. CONCLUSION: Our data demonstrated that an NSAID alone failed to relieve spontaneous or evoked pain behaviors in the rat SNI model, but when combined with a weak opioid and α-2-δ-ligand produced a profound synergistic analgesic effect on cold allodynia and discrepant efficacy for mechanical allodynia and spontaneous pain.