Fulvenallenyl Radical (C7H5·)-Mediated Gas-Phase Synthesis of Bicyclic Aromatic C10H8 Isomers: Can Fulvenallenyl Efficiently React with Closed-Shell Hydrocarbons?

To understand the reactivity of resonantly stabilized radicals, often found in relevant concentrations in gaseous environments, it is important to determine their main reaction pathways. Here, it is investigated whether the fulvenallenyl radical (C7H5·) reacts preferentially with closed-shell molecules or radicals. Electronic structure calculations on the C10H9 potential energy surface accessed by the reactions of C7H5· with methylacetylene (CH3CCH) and allene (H2CCCH2) were combined with RRKM-ME calculations of temperature- and pressure-dependent rate constants using the automated EStokTP software suite and kinetic modeling to assess the reactivity of C7H5· with closed-shell unsaturated hydrocarbons. Experimentally, the reactions were attempted in a chemical microreactor heated to 998 ± 10 K by preparing fulvenallenyl radicals via pyrolysis of trichloromethylbenzene (C7H5Cl3) and seeding the radicals in methylacetylene or allene carrier gas, with product identification by means of photoionization mass spectrometry. The measured photoionization efficiency curve of m/z = 128 was assigned to a linear combination of the reference curves of two C10H8 isomers, azulene (minor) and naphthalene (major), presumably resulting from the C7H5· plus C3H4 reactions. However, the calculations demonstrated that these reactions are too slow, and kinetic modeling of processes in the reactor allowed us to conclude that the observation of naphthalene and azulene is due to the C7H5· plus C3H3· reaction, where propargyl is produced by direct hydrogen atom abstraction by chlorine (Cl) atoms from allene or methylacetylene and Cl stem from the pyrolysis of C7H5Cl3. Modeling results under the copyrolysis conditions of toluene and methylacetylene in high-temperature shock tube experiments confirmed the prevalence of the fulvenallenyl reaction with propargyl over its reactions with C3H4 even when the concentrations of allene and methylacetylene largely exceed that of propargyl. Overall, the reactions of fulvenallenyl with both allene and methylacetylene were found to be noncompetitive in the formation of naphthalene and azulene thus attesting the inefficiency of the fulvenallenyl radical reactions with the prototype closed-shell hydrocarbon species. In the meantime, the new reaction pathways revealed, including H-assisted isomerizations between C10H8 isomers and decomposition reactions of various C10H9 isomers, emerge as relevant and are recommended for inclusion in combustion kinetic models for naphthalene formation.

Gas-Phase Preparation of the 14π Hückel Polycyclic Aromatic Anthracene and Phenanthrene Isomers (C14H10) via the Propargyl Addition-BenzAnnulation (PABA) Mechanism.

Polycyclic aromatic hydrocarbons (PAHs) imply the missing link between resonantly stabilized free radicals and carbonaceous nanoparticles, commonly referred to as soot particles in combustion systems and interstellar grains in deep space. Whereas gas phase formation pathways to the simplest PAH - naphthalene (C10H8) - are beginning to emerge, reaction pathways leading to the synthesis of the 14π Hückel aromatic PAHs anthracene and phenanthrene (C14H10) are still incomplete. Here, by utilizing a chemical microreactor in conjunction with vacuum ultraviolet (VUV) photoionization (PI) of the products followed by detection of the ions in a reflectron time-of-flight mass spectrometer (ReTOF-MS), the reaction between the 1'- and 2'-methylnaphthyl radicals (C11H9⋅) with the propargyl radical (C3H3⋅) accesses anthracene (C14H10) and phenanthrene (C14H10) via the Propargyl Addition-BenzAnnulation (PABA) mechanism in conjunction with a hydrogen assisted isomerization. The preferential formation of the thermodynamically less stable anthracene isomer compared to phenanthrene suggests a kinetic, rather than a thermodynamics control of the reaction.

Association of prognostic nutritional index with prognostic outcomes in patients with glioma: a meta-analysis and systematic review.

Background: The potential link between Prognostic Nutritional Index (PNI) and prognosis in patients with glioma remains uncertain. This meta-analysis was conducted to assess the clinical value of PNI in glioma patients by integrating all available evidence to enhance statistical power. Method: A systematic search of databases including Medline, EMBASE, Google Scholar, and Cochrane Library was conducted from inception to January 8, 2023 to retrieve all pertinent peer-reviewed articles. The primary outcome of the study was to examine the association between a high PNI value and overall survival, while secondary outcome included the relationship between a high PNI and progression-free survival. Results: In this meta-analysis, we included 13 retrospective studies published from 2016 to 2022, which analyzed a total of 2,712 patients. Across all studies, surgery was the primary treatment modality, with or without chemotherapy and radiotherapy as adjunct therapies. A high PNI was linked to improved overall survival (Hazard Ratio (HR) = 0.61, 95% CI: 0.52 to 0.72, p < 0.00001, I2 = 25%), and this finding remained consistent even after conducting sensitivity analysis. Subgroup analyses based on ethnicity (Asian vs. non-Asian), sample size (<200 vs. >200), and source of hazard ratio (univariate vs. multivariate) yielded consistent outcomes. Furthermore, patients with a high PNI had better progression-free survival than those with a low PNI (HR=0.71, 95% CI: 0.58 to 0.88, p=0.001, I2 = 0%). Conclusion: Our meta-analysis suggested that a high PNI was associated with better overall survival and progression-free survival in patients with glioma. These findings may have important implications in the treatment of patients with glioma. Additional studies on a larger scale are necessary to investigate if integrating the index into the treatment protocol leads to improved clinical outcomes in individuals with glioma. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42023389951].

Correction: Alkhaleefah et al. Connected-SegNets: A Deep Learning Model for Breast Tumor Segmentation from X-ray Images. Cancers 2022, 14, 4030.

In the original publication [...].

Fibula Jaw-during-Admission.

BACKGROUND: Fibula Jaw-in-a-Day (JIAD) is considered the most advanced approach for segmental mandibular defect reconstruction and dental rehabilitation. However, it has limitations and challenges for further pursuit. We propose Fibula Jaw-during-Admission (JDA) as a solution. MATERIALS AND METHODS: From 2019 to 2021, six patients received fibula "Jaw-during-Admission." Segmental mandibulectomy, fibula transfer, and immediate dental implantation were performed simultaneously during a single surgery. Intraoral scans were used to fabricate temporary light occlusion contact dental prostheses while on the ward prior to discharge during the first and second week post operation. The prostheses were installed before discharge and changed to permanent ones with normal occlusal contact in the clinic at about six months after X-ray confirmation of bone healing. RESULTS: All six surgeries succeeded. Four patients received palatal muco-periosteal graft after debridement of peri-implant overgrown granulation tissue. Follow-up ranged from 12 to 34 months (average 21.2 months) and revealed good function and appearance in all patients. CONCLUSION: Fibula JDA is superior to the Fibula JIAD approach for simultaneous mandibular reconstruction with fibula and dental rehabilitation. There is no need for postoperative intermaxillary fixation. The surgery can be performed more reliably with less stress. It provides an additional opportunity for dental rehabilitation if initial dental prosthesis installation during JIAD fails. Postreconstruction intraoral scans provide greater precision and more flexibility in milling dental prosthesis which are mapped to the reconstructed mandible during the postoperative period.

Evaluation of Blepharoptosis in Patients With Refractory Blepharospasm by VISA-Video Recordings, Idiosyncratic Expressions, Sensory Tricks, and Ancillary Procedures.

BACKGROUND: How to evaluate blepharoptosis concomitantly presented with refractory and uncontrollable blepharospasm? To date, there is a paucity of publications on the ideal evaluation methods. An innovative method-video recordings, idiosyncratic facial expressions, sensory tricks, and ancillary procedures (VISA)-is developed for preoperative evaluation, and the surgical outcomes are demonstrated. METHODS: A retrospective study using VISA for blepharoptosis evaluation was conducted on 51 patients with refractory blepharospasm. Based on the evaluation, patients underwent blepharoptosis correction simultaneously besides the selective myectomy and myotomy in situ of the eyelid protractors for blepharospasm. Preoperative and postoperative palpebral fissure height, margin reflex distance 1, ptosis severity, and levator function were assessed to identify the effectiveness of VISA. All the procedures were performed by the senior author C.-S.L. RESULTS: There were 42 patients diagnosed with essential blepharospasm and 9 patients with Meige syndrome. Forty-one patients (82/102 eyelids [80.4%]) had concomitant blepharoptosis and blepharospasm. Ptosis severity was mild in 21 eyelids (25.6%), moderate in 12 eyelids (14.6%), and severe in 49 eyelids (59.8%). Preoperative/postoperative (6 months) values of palpebral fissure height, margin reflex distance 1, and levator function were 4.70 ± 2.45 mm/8.35 ± 1.33 mm (P < 0.05), -0.30 ± 3.19 mm/3.73 ± 1.05 mm (P < 0.05), and 13.07 ± 2.56 mm/13.68 ± 2.34 mm (P < 0.05), respectively. Undercorrection and revision rate reported 9.8% and 3.7%, individually. CONCLUSIONS: VISA approach overcomes the difficulty of blepharoptosis assessment in patients with refractory blepharospasm. It provides useful preoperative information required for adequate blepharoptosis correction in blepharospasm surgery and yielded desirable outcomes.

An efficient cellular image-based platform for high-content screening of neuroprotective agents against chemotherapy-induced neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect, with no approved therapy for prevention or treatment. Here, we aimed to establish a high-content image platform based on the neurite outgrowth of dorsal root ganglia (DRG)-derived neuron cells for the discovery of neuroprotective agents against paclitaxel-induced CIPN. ND7/23 cells, an immortalized hybrid DRG cell line, were maturely differentiated by induction with nerve growth factor and upregulation of intracellular cAMP levels. High-content image analyses of the neurofilament-stained neurite network showed that paclitaxel disrupted the neurite outgrowth of well-differentiated ND7/23 DRG neuron cells, recapitulating characteristic effects of paclitaxel on primary cultured DRG neurons. This process coincided with the upregulated activity of store-operated Ca2+ entry, similar to those found in rodent models of paclitaxel-induced CIPN. The previously identified neuroprotective agents, minoxidil and 8-Br-cyclic adenosine monophosphate ribose (8-Br-cADPR), attenuated the reduction in total neurite outgrowth in paclitaxel-damaged ND7/23 cells. Additionally, the total neurite outgrowth of well-differentiated ND7/23 cells was concentration-dependently reduced by the neurotoxic chemotherapeutic agents, oxaliplatin and bortezomib, but not the less neurotoxic 5-fluorouracil. We demonstrated that high-content analyses of neurite morphology in well-differentiated DRG neuron-derived cells provide an effective, reproducible, and high-throughput strategy for developing therapeutics against CIPN.

Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity.

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4+ T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4+ T cell responses and autoantibody production in autoimmune diseases.

Selective Myectomy and Myotomy In Situ for the Management of Refractory Blepharospasm in Meige Syndrome.

BACKGROUND: Meige syndrome is characterized by involuntary blepharospasm and varied subphenotypes of oromandibular tonic-clonic muscle contraction. Despite botulinum toxin (BTx) being the mainstay of treatment for Meige syndrome, a small subset of patients remain refractory to its effects because the disease is a form of functional blindness. An integrative surgical procedure combining selective myectomy and myotomy in situ of eyelid protractors, blepharoptosis correction, and tightening of the lower eyelid laxity was first applied to treat refractory blepharospasm in patients with Meige syndrome. MATERIALS AND METHODS: This study is a retrospective review conducted on 24 patients with refractory Meige syndrome between 2013 and 2020. Besides selective myectomy and myotomy in situ of eyelid protractors, levator plication and lateral tarsoplasty or canthopexy was performed for blepharoptosis correction and lower eyelid tightening, respectively. Patient demographics, associated diseases, medical treatment history, associated surgical procedures, final aesthetic outcomes, and therapeutic effects as reflected by changes in function disability score and Botox (BTx) treatment were thoroughly recorded and analyzed. RESULTS: The mean age of the patients was 65.2 ± 8.9 years. Twenty-one patients (87.5%) received blepharoptosis correction by levator plication with an average of 11.2 ± 2.9 mm in length. Lateral tarsoplasty was performed in 16 patients (66.7%) by pentagonal tarsal resection with an average of 3.9 ± 0.8 mm in width. Five patients (20.8%) received lateral canthopexy. Among the total of 96 operated eyelids, scar revision with fat graft was performed in 3 eyelids (3.1%). The average amount of BTx treatment decreased from 49.2 ± 12.8 U once every 2.7 ± 0.8 months before surgery to 35.4 ± 7.8 U once every 3.8 ± 0.7 months after surgery. Function disability score improved from 76.7 ± 17.5% preoperatively to 15.6 ± 9.9% postoperatively ( P < 0.001). Only 3 upper eyelids (3.1%) received scar revision and fat grafting due to minor postoperative contour depression. All patients expressed high satisfaction with both functional and aesthetic outcomes (Likert scale 4.5 ± 0.5). CONCLUSIONS: Selective myectomy and myotomy in situ of eyelid protractors combining blepharoplasty correction and lower eyelid tightening can produce long-lasting functional and aesthetic results with minimal complication in patients with refractory Meige syndrome.

Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species.

The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1-/- mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/- mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1-/- cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Establishment of a Bama miniature pig burn model with different burn depths.

Background: The skin morphological characteristics of the Bama miniature pig are very similar to those of humans; thus, the Bama miniature pig is an ideal choice for establishing a skin burn model. Methods: In this study, 6 ordinary, male, Bama miniature pigs (weight: 23-28 kg and length: 71-75 cm) were used to establish burn models. A mixture of 1 mg of Ketamine and Sumianxin II was used for Bama miniature pigs anesthetizing, and 1 mg of Pentobarbital sodium was added as necessary. The different burn depths were made using a continuous pressure of 1 kg and contact times of 0 s, 10 s, 15 s, 20 s, 25 s, 30 s, 35 s, 40 s, and 45 s by the newly invented electronic burn instrument. The burned tissues were collected and examined with hematoxylin and eosin (H&E) and Masson staining. Results: Burning for 10-15 s caused a first-degree burn; the blood vessels in the superficial dermis were dilated and congested, and necrosis occurred above the basal layer of the epidermis. Burning for 20-25 s caused a superficial partial-thickness burn; the whole epidermal layer was necrotic, and the collagen fibers were slightly deformed. Burning for 30-35 s caused a deep partial-thickness burn; the whole epidermal layer and dermal layers were necrotic with leukocyte infiltration zones, and the collagen fibers were disordered, degenerated, and necrotized. Burning for 40-45 s caused a third-degree burn; the skin layers and adipose tissues were necrotic, and the thick blood vessels in the skin adipose tissues were full of disintegrated and agglutinated red blood cells. Conclusions: Stable burn depth models of Bama miniature pigs were constructed using a new and innovative electronic burn instrument. Our findings provide a basis for further research on the burn mechanism and evaluations of therapeutic drugs.

Connected-SegNets: A Deep Learning Model for Breast Tumor Segmentation from X-ray Images.

Inspired by Connected-UNets, this study proposes a deep learning model, called Connected-SegNets, for breast tumor segmentation from X-ray images. In the proposed model, two SegNet architectures are connected with skip connections between their layers. Moreover, the cross-entropy loss function of the original SegNet has been replaced by the intersection over union (IoU) loss function in order to make the proposed model more robust against noise during the training process. As part of data preprocessing, a histogram equalization technique, called contrast limit adapt histogram equalization (CLAHE), is applied to all datasets to enhance the compressed regions and smooth the distribution of the pixels. Additionally, two image augmentation methods, namely rotation and flipping, are used to increase the amount of training data and to prevent overfitting. The proposed model has been evaluated on two publicly available datasets, specifically INbreast and the curated breast imaging subset of digital database for screening mammography (CBIS-DDSM). The proposed model has also been evaluated using a private dataset obtained from Cheng Hsin General Hospital in Taiwan. The experimental results show that the proposed Connected-SegNets model outperforms the state-of-the-art methods in terms of Dice score and IoU score. The proposed Connected-SegNets produces a maximum Dice score of 96.34% on the INbreast dataset, 92.86% on the CBIS-DDSM dataset, and 92.25% on the private dataset. Furthermore, the experimental results show that the proposed model achieves the highest IoU score of 91.21%, 87.34%, and 83.71% on INbreast, CBIS-DDSM, and the private dataset, respectively.

Dental Implant Outcomes in Fibula Mandible Reconstruction with or without Vertical Distraction for Symphysis Cross-Arch Segmental Defects.

SUMMARY: Dental implant complications in patients with a symphysis cross-arch defect occur following fibula mandible reconstruction due to mechanical stress. The authors compared implant outcomes after single-barrel fibula mandible reconstruction with immediate implant placement or after completion of vertical distraction osteogenesis.

External validity of four risk scores predicting 30-day mortality after surgery.

Background: Surgical risk prediction tools can facilitate shared decision-making and efficient allocation of perioperative resources. Such tools should be externally validated in target populations before implementation. Methods: Predicted risk of 30-day mortality was retrospectively derived for surgical patients at Royal Perth Hospital from 2014 to 2021 using the Surgical Outcome Risk Tool (SORT) and the related NZRISK (n=44 031, 53 395 operations). In a sub-population (n=31 153), the Physiology and Operative Severity Score for the enumeration of Mortality (POSSUM) and the Portsmouth variant of this (P-POSSUM) were matched from the Copeland Risk Adjusted Barometer (C2-Ai, Cambridge, UK). The primary outcome was risk score discrimination of 30-day mortality as evaluated by area-under-receiver operator characteristic curve (AUROC) statistics. Calibration plots and outcomes according to risk decile and time were also explored. Results: All four risk scores showed high discrimination (AUROC) for 30-day mortality (SORT=0.922, NZRISK=0.909, P-POSSUM=0.893; POSSUM=0.881) but consistently over-predicted risk. SORT exhibited the best discrimination and calibration. Thresholds to denote the highest and second-highest deciles of SORT risk (>3.92% and 1.52-3.92%) captured the majority of deaths (76% and 13%, respectively) and hospital-acquired complications. Year-on-year SORT calibration performance drifted towards over-prediction, reflecting a decrease in 30-day mortality over time despite an increase in the surgical population risk. Conclusions: SORT was the best performing risk score in predicting 30-day mortality after surgery. Categorising patients based on SORT into low, medium (80-90th percentile), and high risk (90-100th percentile) might guide future allocation of perioperative resources. No tools were sufficiently calibrated to support shared decision-making based on absolute predictions of risk.

Outpatient autologous stem cell transplantation in Royal Hobart Hospital, Tasmania: a single-centre, retrospective review in the Australian setting.

BACKGROUND: Several international centres have published their experiences with outpatient autologous stem cell transplantation (ASCT) as treatment of haematological malignancies. AIM: In this single-centre retrospective review, we aim to examine the outcomes of outpatient autograft and review healthcare resource utilisation in the pre-cytopenic period. METHODS: Patients undergoing ASCT in Royal Hobart Hospital, Tasmania between 2008 and 2018 had their records reviewed and key outcomes data collected based on whether they received inpatient/outpatient ASCT. An outpatient ASCT was defined as conditioning as an outpatient; patients could then be managed with an elective admission during the cytopenic period or admission only when clinically indicated. RESULTS: Of 231 ASCT performed, 135 (58%) were as outpatients: 59 used carmustine-etoposide-cytarabine-melphalan conditioning for lymphoma (BEAM-ASCT) and 76 used high-dose melphalan for myeloma and amyloidosis (MEL-ASCT). Approximately one-third of patients undergoing outpatient ASCT were admitted electively during nadir period; the majority of patients required minimal interventions prior to this time. The most common causes for unplanned hospitalisation (which occurred in 71 (80%) of the 89 planned outpatient transplants) were febrile neutropenia (39%) and mucositis (35%). Age was the only risk factor identified to increase risk of requiring unplanned hospitalisation. Use of oral antibiotic prophylaxis reduced febrile neutropenia rates among melphalan outpatient ASCT. Outpatient ASCT led to significantly reduced inpatient bed-days and overall cost (approximately A$13 000-A$16 000) compared with inpatient autografts, with no significant differences in engraftment, rates of febrile neutropenia, intensive care admissions or mortality. CONCLUSION: Outpatient autografts may save healthcare resources without compromising patient outcomes.

Impact of intravenous and topical lidocaine on clinical outcomes in patients receiving propofol for gastrointestinal endoscopic procedures: a meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of i.v. or topical lidocaine as an anaesthesia adjunct in improving clinical outcomes in patients receiving gastrointestinal endoscopic procedures under propofol sedation remains unclear. METHODS: Electronic databases (MEDLINE, EMBASE, and Cochrane Library) were searched for RCTs comparing the clinical outcomes with or without lidocaine application (i.v. or topical) in patients receiving propofol for gastrointestinal endoscopic procedures from inception to 29 March 2021. The primary outcome was propofol dosage, while secondary outcomes included procedure time, recovery time, adverse events (e.g. oxygen desaturation), post-procedural pain, and levels of endoscopist and patient satisfaction. RESULTS: Twelve trials (1707 patients) published between 2011 and 2020 demonstrated that addition of i.v. (n=7) or topical (n=5) lidocaine to propofol sedation decreased the level of post-procedural pain (standardised mean difference [SMD]=-0.47, 95% confidence interval [CI]: -0.8 to -0.14), risks of gag events (risk ratio [RR]=0.51, 95% CI: 0.35-0.75), and involuntary movement (RR=0.4, 95% CI: 0.16-0.96). Subgroup analysis demonstrated that only i.v. lidocaine reduced propofol dosage required for gastrointestinal endoscopic procedures (SMD=-0.83, 95% CI: -1.19 to -0.47), increased endoscopist satisfaction (SMD=0.75, 95% CI: 0.21-1.29), and shortened the recovery time (SMD=-0.83, 95% CI: -1.45 to -0.21). Intravenous or topical lidocaine did not affect the incidence of oxygen desaturation (RR=0.72, 95% CI: 0.41-1.24) or arterial hypotension (RR=0.6, 95% CI: 0.22-1.65) and procedure time (SMD=0.21, 95% CI: -0.09 to 0.51). CONCLUSION: This meta-analysis demonstrated that i.v. or topical lidocaine appears safe to use and may be of benefit for improving propofol sedation in patients undergoing gastrointestinal endoscopic procedures. Further large-scale trials are warranted to support our findings.

Efficacy of intraoperative intravenous lidocaine for postoperative analgesia following bariatric surgery: a meta-analysis of randomized controlled studies.

BACKGROUND: The impact of intravenous lidocaine in adults undergoing laparoscopic bariatric surgeries (LBS) remains unclear. OBJECTIVES: This study aimed at investigating the effect of intravenous lidocaine on postoperative opioid consumption and recovery following LBS. SETTING: Meta-analysis. METHODS: We searched databases including MEDLINE, Embase, Google Scholar, and the Cochrane Library for randomized controlled trials that evaluated the use of intravenous lidocaine compared to placebo only prior to May 2021. The primary outcome was 24-hour postoperative opioid consumption, while secondary outcomes included pain score, quality of recovery (QOR)-40 score, length of hospital stay (LOS), and postoperative nausea/vomiting (PONV). RESULTS: Seven trials (496 participants) were included. Intraoperative intravenous lidocaine significantly reduced 24-hour equivalent morphine consumption (mean difference [MD]: -11.97 mg; 95% confidence interval [CI]: -23.12 to -.83), pain score at 1 to 3 hours (MD: -.77; 95% CI: -1.5 to -.04), and LOS (MD: -8.93 hr; 95% CI: -13.41 to -4.44) without positive impact on 24-hour pain score and PONV. There was also an increase in time to first opioid requirement (MD: 20.23 min; 95% CI: 11.76-28.7) and QOR-40 score (MD: 24.38; 95% CI: 5.57-43.18). However, sensitivity analysis demonstrated evidence supporting the beneficial effect of lidocaine only for time to first opioid requirement and QOR-40. The associations of intraoperative intravenous lidocaine with reductions in morphine consumption, pain score at 1 to 3 hours, and LOS after LBS were also weak. CONCLUSION: Intraoperative intravenous lidocaine during LBS prolonged time to first opioid requirement and improved quality of recovery postoperatively without 24-hour pain or nausea/vomiting benefits. Due to the small number of trials, larger studies are warranted to verify our findings.

Association between perioperative intravenous lidocaine and subjective quality of recovery: A meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: To evaluate the impact of perioperative intravenous lidocaine on the quality of recovery (QoR) following surgery. DESIGN: Meta-analysis of randomized controlled trials (RCTs). SETTING: Postoperative care. INTERVENTION: Intravenous lidocaine during perioperative period. PATIENTS: Adults undergoing surgery under general anesthesia. MEASUREMENTS: The primary outcome was postoperative QoR measured with QoR-40 questionnaire, while the secondary outcomes included five individual dimensions (i.e., emotional, state, physical comfort, psychological support, physical independence, and pain) of QoR-40, intraoperative opioid consumption, and risk of chronic postsurgical pain (CPSP). MAIN RESULTS: Medline, Cochrane Library, Google scholar, and EMBASE databases were searched from inception to June 2021. Fourteen RCTs involving 1148 patients in total undergoing elective surgery published from 2012 to 2021 were included. QoR-40 scores were evaluated at postoperative 24 h (12 trials), 72 h (one trial), and Day 5 (one trial), respectively. Pooled results revealed significantly higher global [mean difference (MD) = 9.65, 95% confidence interval (CI): 6.33 to 12.97; I2 = 97%; 13 RCTs; n = 1085] and individual dimension QoR-40 scores in the lidocaine group than those in placebo group. Subgroup analysis demonstrated no significant impact of the type of surgery, age, gender, surgical time, anesthetic technique, lidocaine dosage, and time of assessment on global QoR-40 scores. The use of intravenous lidocaine was associated with a significant reduction in intraoperative remifentanil consumption compared with that in the placebo group (standardized MD = -0.91, 95%CI: -1.32 to -0.51; I2 = 86%; 10 RCTs; n = 799). There was no difference in risk of CPSP between the two groups [relative risk (RR) = 0.65, 95%CI: 0.33 to 1.25; I2 = 58%; 4 RCTs; n = 309]. CONCLUSION: Our results verified the efficacy of intravenous lidocaine for enhancing postoperative quality of recovery by using a validated subjective tool and reducing intraoperative remifentanil consumption in patients receiving elective surgery under general anesthesia. Further studies are warranted to verify its efficacy in the acute care setting.

Reconstruction of mandibular defects involving the central segment with fibula osteoseptocutaneous free flap following ameloblastoma resection: Patient-reported outcomes.

OBJECTIVES: Mandibular defects involving the central segment are challenging. This study analyzes the impact of defect extent and reconstruction method on quality of life (QOL) and obstructive sleep apnea (OSA). MATERIALS AND METHODS: Twenty-nine ameloblastoma patients received segmental mandibulectomy involving the C-segment and immediate fibula free flap reconstruction were recruited. Defects: (C: 2, LC: 11, LCL: 19). Mean defect length: 8.79 cm (± 2.34). Inset: Low-single-barrel (n: 19), with secondary distraction osteogenesis (n: 8/19), high-single-barrel (n: 7), double barrel (n: 3). Patients were surveyed using University of Washington Quality of Life (UW-QOL) and Berlin risk of postoperative sleep apnea questionnaires. RESULTS: Flap failure: None. Mean follow-up: 109.6 ±â€¯92.8 months. UW-QOL: Physical function 91.83 (± 14.92); social function 90.17 (± 17.19). No statistical difference between C, LC, and LCL was found, but C group which received low-single-barrel had the lowest score in appearance and chewing domains. In health-related QOL (HR-QOL) compared with 1 month before cancer, 69% reported best results. "Appearance" was the most important issue for the past 7 days, followed by "Chewing," prevailing in LC and C groups that predominately reconstructed by low-single-barrel. Berlin score: 7 patients (4 LCL, 3 LC≥8 cm) were at high risk for postoperative OSA. CONCLUSION: "Like-with-like" reconstruction with immediate endosteal dental implants yields the best results. Inset of fibula bone could affect outcomes, favoring double-barrel or single-high-barrel inset. Appearance and chewing remain the main concerns, largely, in those with low-single-barrel inset and no dental restoration. After long/extensive LCL and LC mandibulectomies, postoperative OSA warrants further investigation, and modification of resection/reconstruction techniques.

Nano-realgar suppresses lung cancer stem cell growth by repressing metabolic reprogramming.

BACKGROUND: Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. METHODS: The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. RESULTS: Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. CONCLUSIONS: These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.