Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients.

BACKGROUND: Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients. METHODS: We conducted a retrospective analysis of 308 patients with stage 0-III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes. RESULTS: The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1-2 skin reactions (91.6%). The most common late toxicity was grade 0-1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1-2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes. CONCLUSIONS: SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Effectiveness of WeChat-assisted preoperative education to reduce perioperative anxiety in breast cancer patients: a prospective randomized controlled study protocol.

BACKGROUND: Breast cancer is the most prevalent cancer among women globally, and surgical procedures continue to be the primary treatment. However, over 50% of patients experience preoperative anxiety due to the unknown and fear associated with surgery. Although drug therapy is commonly used to address this anxiety, its side effects have led to a heated debate regarding its effectiveness. Consequently, non-pharmacological therapies, such as preoperative education, have emerged as an alternative approach to alleviate anxiety. WeChat, a widely popular social media platform, offers a public platform that can potentially be utilized for effective preoperative education. This study aims to evaluate the use of WeChat public platform as a tool for preoperative education in patients undergoing breast surgery. METHODS: This is a prospective, randomized, and controlled trial will involve 392 adult women scheduled for breast cancer resection. Participants will be randomly assigned to either the WeChat education group or the regular group. In addition to regular preoperative visits, the WeChat education group will also watch science videos through the WeChat public platform. The regular group will only receive education from ward nurses during preoperative visits. The primary outcome measure will be the incidence of preoperative anxiety, defined by scores of the State Anxiety Inventory (SAI) exceeding 40 points. Secondary outcome measures include the incidence of severe anxiety (SAI > 44) on the day before surgery, incidence of anxiety 72 h after surgery, incidence of severe anxiety 72 h after surgery, NRS scores for pain at rest and during activity 24, 48, and 72 h after surgery, incidence of nausea and vomiting within 24 h after surgery, subjective sleep score at 1 week postoperatively, quality of life QoR-15 scores at 1 and 3 months postoperatively, incidence of chronic pain at 3 months postoperatively, bowel function recovery, length of hospital stay, and hospitalization expenses. DISCUSSION: This is the first clinical trial to investigate the use of WeChat public platform for delivering preoperative education on perioperative anxiety in breast cancer patients. By utilizing the renowned WeChat public platform, our study aims to improve patient outcomes by providing video education that explains the disease, surgery, and anesthesia in a more accessible manner, thereby reducing the incidence of perioperative anxiety. If our hypothesis is confirmed, this non-pharmacological approach can be universally acknowledged as a cost-effective and practical method in clinical care. Its application can also be extended to other medical fields beyond breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05291494. Registered on 29 December 2021.

[Effect of Pp2cm Gene Silencing on Mouse Macrophage Resistance Against Staphylococcus aureus Infection via TLR Pathway].

Objective: To investigate the effect of silencing protein phosphatase 2cm ( Pp2cm) gene on the expression of inflammatory factors in macrophages infected with Staphylococcus aureus ( S. aureus) and the mechanisms involved. Methods: The effects of Pp2cm knockdown on inflammatory factors, proliferation, apoptosis, and Toll-like receptor (TLR) signaling were analyzed in RAW 264.7 cells, a murine macrophage cell line, transfected with adenovirus (Ad). The cells were divided into four groups, including Ad-Ctrl group, Ad- Pp2cm group, Ad-Ctrl+ S. aureus group and Ad- Pp2cm+ S. aureus group. Cell transfection was achieved by separately introducing control adenovirus (Ad-Ctrl) or adenovirus targeting the Pp2cm gene (Ad- Pp2cm) and inflammation or the absence of inflammation was induced by applying or not applying S. aureus. The expression of tumor necrosis factor-alpha ( TNF-α), interleukin-1ß ( IL-1 ß), TLR2, TLR4, Toll-like receptor adaptor protein ( Tirap) and myeloid differentiation factor 88 ( Myd88) was determined by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). PP2Cm protein expression was determined by Western blot. Cell proliferation was determined by cell counting kit-8 (CCK-8) assay and cell apoptosis was measured by flow cytometry. Results: The expression of Pp2cmgene and PP2Cm protein was downregulated in the Ad- Pp2cm group when compared to the Ad-Ctrl group, with the diference showing statistical significance ( P<0.05). When compared to those of the Ad-Ctrl+ S. aureus group, macrophages in the Ad- Pp2cm+ S. aureus group showed significantly increase in the TNF- α and IL-1 ß gene levels ( P<0.01). Furthermore, the Ad- Pp2cm group demonstrated elevated gene expression levels of TLR2, TLR4, Tirap and Myd88 in macrophages when compared to the Ad-Ctrl group, with the difference showing statistical significance ( P<0.05). There were no statistically significant differences in cell apoptosis and proliferation between the Ad-Ctrl and Ad- Pp2cm groups. Conclusions: Silencing Pp2cm gene promotes the inflammatory response of macrophages to S. aureus infection. Moreover, the TLR pathway plays an important role in the inflammatory activation of macrophages.

[Potential implications of ketone body metabolism changes and ketogenic therapy in the treatment of heart failure].

Heart failure (HF) has become a major challenge in the treatment of global cardiovascular diseases. Great progress has been made in the drug treatment of HF, however, rehospitalization rate and mortality of patients with HF are still high. Hence, there is an urgent need to explore new treatment strategy and new underlying pathogenic mechanisms. In recent years, some researchers have suggested that regulation of ketone body metabolism may become a potentially promising therapeutic approach for HF. Some studies showed that the oxidative utilization of fatty acids and glucose was decreased in the failing heart, accompanied by the increase of ketone body oxidative metabolism. The enhancement of ketone body metabolism in HF is a compensatory change during HF. The failing heart preferentially uses ketone body oxidation to provide energy, which helps to improve the body's cardiac function. This review will discuss the potential significance of ketone body metabolism in the treatment of HF from three aspects: normal myocardial ketone body metabolism, the change of ketone body metabolism in HF, the effect of ketogenic therapy on HF and its treatment.

Efficacy of prolonged intravenous lidocaine infusion for postoperative movement-evoked pain following hepatectomy: a double-blinded, randomised, placebo-controlled trial.

BACKGROUND: The analgesic effect of intravenous lidocaine varies with the duration of lidocaine infusion and surgery type. We tested the hypothesis that prolonged lidocaine infusion alleviates postoperative pain in patients recovering from hepatectomy over the first 3 postoperative days. METHODS: Patients undergoing elective hepatectomy were randomly assigned to receive prolonged i.v. lidocaine treatment or placebo. The primary outcome was incidence of moderate-to-severe movement-evoked pain at 24 h postoperatively. The secondary outcomes included incidence of moderate-to-severe pain during movement and at rest throughout the first 3 postoperative days, postoperative opioid consumption, and pulmonary complications. Plasma lidocaine concentration was also monitored. RESULTS: We enrolled 260 subjects. Intravenous lidocaine lowered the incidence of moderate-to-severe movement-evoked pain at 24 h and 48 h postoperatively (47.7% vs 67.7%, P=0.001; 38.5% vs 58.5%, P=0.001) and reduced movement-evoked pain scores (3.7 [1.7] vs 4.2 [1.6]; mean difference 0.5 [95% confidence interval {CI}: 0.1-0.9]; P=0.018) and morphine equivalent consumption (47.2 [16.7] mg vs 52.6 [19.2] mg; mean difference 5.4 mg [95% CI: 1.0-9.8]; P=0.016) at 24 h postoperatively. Lidocaine also lowered the incidence of postoperative pulmonary complications (23.1% vs 38.5%; P=0.007). Median plasma lidocaine concentrations were 1.5, 1.9, and 1.1 µg ml-1 (inter-quartile ranges: 1.1-2.1, 1.4-2.6, and 0.8-1.6, respectively) after bolus injection, at the end of the surgery, and 24 h postoperatively. CONCLUSIONS: Prolonged intravenous lidocaine infusion reduced the incidence of moderate-to-severe movement-evoked pain for 48 h after hepatectomy. However, the reduction in pain scores and opioid consumption by lidocaine was below the minimal clinically important difference. CLINICAL TRIAL REGISTRATION: NCT04295330.

Effect of low temperature on the resistance of Listeria monocytogenes and Escherichia coli O157:H7 to acid electrolyzed water.

Low temperature can affect the resistance of pathogenic bacteria to other external stress. The present study was envisaged to assess the tolerance of L. monocytogenes and E. coli O157:H7 to acidic electrolyzed water (AEW) under low temperature stress. AEW treatment caused a damage to cell membrane of the pathogenic bacteria, which led to protein leakage and DNA damage. Compared with the pathogenic bacteria cultured at 37 °C (pure culture), the L. monocytogenes and E. coli O157:H7 cells cultivated at low temperature presented a less damage and had a higher survival rate when exposed to AEW. Therefore, 4 °C or 10 °C grown bacteria were less susceptible to AEW than those cultured at 37 °C. And this phenomenon was verified when AEW was used to treat the pathogenic bacteria inoculated in salmon. In addition, transcriptomic sequencing technology (RNA-seq) was used to reveal the mechanism of AEW tolerance of L. monocytogenes under low temperature stress. Transcriptomic analysis showed the expression of the cold shock protein, regulation of DNA-templated transcription, ribosome pathway, phosphotransferase system (PTS), bacteria chemotaxis, SOS response and DNA repair were involved in the resistance of L. monocytogenes to AEW. We speculated that the direct modulation of the expression of cold shock protein CspD, the indirect effect on the expression of cspD by inhibiting the expression of Crp/Fnr family transcriptional regulator or enhancing the level of cAMP by regulating PTS could reduce the resistance of L. monocytogenes cultivated at 4 °C to AEW. Our study contributes to solving the problem of the reduced bacteriostatic effect in cold storage environment.

Appropriate Duration of Perioperative Intravenous Administration of Lidocaine to Provide Satisfactory Analgesia for Adult Patients Undergoing Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Perioperative lidocaine infusion has been reported to alleviate pain intensity after colorectal surgery. However, there is no consensus on whether prolonged lidocaine infusion is more effective than short lidocaine infusion. This meta-analysis aimed to determine an appropriate duration of lidocaine infusion in patients undergoing colorectal surgery. METHODS: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases to identify articles published before December 17, 2021. Randomized controlled trials comparing intravenous lidocaine with placebo for pain relief in patients undergoing colorectal surgery were included. The primary outcome was pain scores (visual analog scale [VAS], 0-10 cm) at 24 hours postoperatively at rest and on movement. Secondary outcomes included pain scores at 12, 48, and 72 hours postoperatively, analgesic consumption (mg), gastrointestinal function return (hour), length of hospital stay (days), and incidence of complications. According to the duration of lidocaine infusion, studies were grouped into infusion for at least 24 hours (prolonged lidocaine infusion) and less than 24 hours (short lidocaine infusion) to assess the impact of lidocaine infusion duration on the outcomes of interests. Quantitative analyses were performed using a random effects model. RESULTS: Eleven studies with 548 patients were included. Five studies used prolonged lidocaine infusion, while 6 studies used short lidocaine infusion. Prolonged lidocaine infusion reduced postoperative pain scores versus placebo at 24 hours at rest (mean difference [MD], -0.91 cm; 95% confidence interval [CI], -1.54 to -0.28; P = .02) and on movement (MD, -1.69 cm; 95% CI, -2.15 to -1.22; P < .001), while short lidocaine infusion showed no benefit. Compared with placebo, prolonged lidocaine infusion reduced pain scores at 12 hours at rest and at 12 and 48 hours on movement, but short lidocaine infusion did not. However, there was no significant difference in pain scores between the prolonged and short lidocaine infusion groups at these time points. Compared with placebo, prolonged lidocaine infusion shortened the length of hospital stay (MD, -1.30 days; 95% CI, -1.72 to -0.88; P < .001) and time to first postoperative defecation (MD, -12.51 hours; 95% CI, -22.67 to -2.34; P = .02). There were no differences between groups regarding the other outcomes. CONCLUSIONS: The analgesic effect of intravenous lidocaine may depend on the duration of infusion, and our results suggest that lidocaine infusion should be administered for at least 24 hours after colorectal surgery. Since overall evidence quality was low, further high-quality, large-sample trials are needed to explore an optimal lidocaine infusion strategy in patients undergoing colorectal surgery.

Anaesthetic considerations in Shrinking Man syndrome: two case reports.

BACKGROUND: Shrinking Man syndrome (SMS) is a rare but often serious complication of dialysis-dependent end-stage renal disease, characterized by significant loss of height, bone pain, bone deformity, and skin itching. Patients with SMS always have abnormal facial changes and cardiovascular system damage (manifested by hypertension, hypotension, cardiovascular calcification, and valvular heart disease), which pose a great challenge to anaesthesiologists. The purpose of this report is to describe our anaesthetic experience regarding two patients with SMS combined with alterations of the airway and cardiovascular system. CASE PRESENTATION: We describe two cases of SMS treated at West China Hospital, a tertiary care centre in Chengdu, China. All cases met the diagnostic criteria, which comprised 1) dialysis-dependent end-stage renal disease, 2) loss of height, and 3) bone pain and bone deformity. One patient had an anticipated difficult airway and moderate-to-severe mitral stenosis. The other patient presented with significant hypotension. Anaesthetic considerations included awake fibreoptic bronchoscopy-assisted tracheal intubation, real-time transoesophageal echocardiogram monitoring and individualized blood pressure management strategies. CONCLUSION: This case series highlights the importance of adequate preoperative assessment and preparation, as well as individualized anaesthetic management, in patients with SMS.

Antibacterial activity of essential oils extracted from the unique Chinese spices cassia bark, bay fruits and cloves.

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three spices with unique Chinese characteristics widely used were selected: cassia bark (bark of Cinnamomum camphora Presl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%) and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria ivanovii, Listeria grayi and Vibrio parahaemolyticus. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.

Outcomes of peritoneal dialysis in elderly vs non-elderly patients: A systemic review and meta-analysis.

OBJECTIVES: Several studies have compared outcomes of peritoneal dialysis (PD) between elderly and non-elderly patients but with variable results. We hereby designed this review to compare mortality, peritonitis, and technique survival between elderly and non-elderly patients on PD. METHODS: PubMed, Embase, and Google Scholar were searched for studies comparing outcomes of PD between elderly and non-elderly patients. The last search date was 14th July 2021. RESULTS: Fourteen studies were included. 12 studies defined the elderly as ≥65 years of age and these were included in the meta-analysis. Pooled analysis of crude (RR: 2.45 95% CI: 1.36, 4.40 I2 = 97% p = 0.003) and adjusted data (HR: 2.80 95% CI: 2.45, 3.09 I2 = 0% p<0.00001) indicated a statistically significant increased risk of mortality amongst elderly patients as compared to non-elderly patients. Meta-analysis of four studies demonstrated a statistically significant increased risk of peritonitis in the elderly (RR: 1.56 95% CI: 1.18, 2.07 I2 = 76% p = 0.002). Pooled analysis demonstrated no statistically significant difference in technique survival between the two groups (RR: 0.95 95% CI: 0.86, 1.05 I2 = 86% p = 0.32). CONCLUSION: Elderly patients on PD have a significantly increased risk of mortality as compared to non-elderly patients. The risk of peritonitis is also significantly increased in older adults but the increased age has no impact on technique survival. Further studies are needed to strengthen our conclusions.

Mitochondrial protein hyperacetylation underpins heart failure with preserved ejection fraction in mice.

Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction (HFrEF). The prevalence of HFpEF continues to increase, while the pathogenic mechanisms underlying HFpEF remain largely elusive and evidence-based therapies are still lacking. This study was designed to investigate the metabolic signature of HFpEF and test the potential therapeutic intervention in a mouse model. By utilizing a "3-Hit" HFpEF mouse model, we observed a global protein hyperacetylation in the HFpEF hearts as compared to the pressure overload-induced HFrEF and adult/aged non-heart failure (NHF) hearts. Acetylome analysis identified that a large proportion of the hyperacetylated proteins (74%) specific to the HFpEF hearts are in mitochondria, and enriched in tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and fatty acid oxidation. Further study showed that the elevated protein acetylation in the HFpEF hearts was correlated with reduced NAD+/NADH ratio, impaired mitochondrial function, and depleted TCA cycle metabolites. Normalization of NAD+/NADH ratio by supplementation of nicotinamide riboside (NR) for 30 days downregulated the acetylation level, improved mitochondrial function and ameliorated HFpEF phenotypes. Therefore, our study identified a distinct protein acetylation pattern in the HFpEF hearts, and proposed NR as a promising agent in lowering acetylation and mitigating HFpEF phenotypes in mice.

Comparison of an in-house hybrid DIR method to NiftyReg on CBCT and CT images for head and neck cancer.

An in-house hybrid deformable image registration (DIR) method, which combines free-form deformation (FFD) and the viscous fluid registration method, is proposed. Its results on the planning computed tomography (CT) and the day 1 treatment cone-beam CT (CBCT) image from 68 head and neck cancer patients are compared with the results of NiftyReg, which uses B-spline FFD alone. Several similarity metrics, the target registration error (TRE) of annotated points, as well as the Dice similarity coefficient (DSC) and Hausdorff distance (HD) of the propagated organs at risk are employed to analyze their registration accuracy. According to quantitative analysis on mutual information, normalized cross-correlation, and the absolute pixel value differences, the results of the proposed DIR are more similar to the CBCT images than the NiftyReg results. Smaller TRE of the annotated points is observed in the proposed method, and the overall mean TRE for the proposed method and NiftyReg was 2.34 and 2.98 mm, respectively (p < 0.001). The mean DSC in the larynx, spinal cord, oral cavity, mandible, and parotid given by the proposed method ranged from 0.78 to 0.91, significantly higher than the NiftyReg results (ranging from 0.77 to 0.90), and the HD was significantly lower compared to NiftyReg. Furthermore, the proposed method did not suffer from unrealistic deformations as the NiftyReg did in the visual evaluation. Meanwhile, the execution time of the proposed method was much higher than NiftyReg (96.98 ± 11.88 s vs. 4.60 ± 0.49 s). In conclusion, the in-house hybrid method gave better accuracy and more stable performance than NiftyReg.

Expressing MLH1 in HCT116 cells increases cellular resistance to radiation by activating the PRKAC.

Mut L homolog-1 (MLH1) is a key DNA mismatch repair protein which participates in the sensitivity to DNA damaging agents. However, its role in the radiosensitivity of tumor cells is less well characterized. In this study, we investigated the role of MLH1 in cellular responses to ionizing radiation (IR) and explored the signaling molecules involved. The isogenic pair of MLH1 proficient (MLH1+) and deficient (MLH1-) human colorectal cancer HCT116 cells was exposed to IR for 24 h at the dose of 3 cGy. The clonogenic survival was examined by the colony formation assay. Cell cycle distribution was analyzed with flow cytometry. Changes in the protein level of MLH1, DNA damage marker γH2AX, and protein kinase A catalytic subunit (PRKAC), a common target for anti-tumor drugs, were examined with Western blotting. The results showed that the HCT116 (MLH1+) cells demonstrated increased radio-resistance with increased S population, decreased G2 population, a low level of γH2AX, a reduced ratio of phosphorylated PRKACαß to total PRKAC, and an elevated level of total PRKAC and phosphorylated PRKACßII following IR compared with the HCT116 (MLH1-) cells. Importantly, silencing PRKAC in HCT116 (MLH1+) cells increased the cellular radiosensitivity. In conclusion, MLH1 may increase cellular resistance to IR by activating PRKAC. Our finding is the first to demonstrate the important role of PRKAC in MLH1-mediated radiosensitivity, suggesting that PRKAC has potential as a biomarker and a therapeutic target for increasing radio-sensitization.

A clinical trial to compare a 3D-printed bolus with a conventional bolus with the aim of reducing cardiopulmonary exposure in postmastectomy patients with volumetric modulated arc therapy.

BACKGROUND: We compared the dosimetry, application, and acute toxicity of a 3D-printed and a conventional bolus for postmastectomy radiotherapy (PMRT) with volumetric modulated arc therapy (VMAT). Materials and Methods Eligible patients (n = 75) with PMRT breast cancer were randomly selected to receive VMAT with a conventional bolus or a 3D-printed bolus. The primary endpoint was a 10% decrease in the mean heart dose to left-sided breast cancer patients. The secondary endpoint was a 5% decrease in the mean ipsilateral lung dose to all patients. A comparative analysis was carried out of the dosimetry, normal tissue complication probability (NTCP), acute skin toxicity, and radiation pneumonitis. RESULTS: Compared to a conventional bolus, the mean heart dose in left-sided breast cancer was reduced by an average of 0.8 Gy (5.5 ± 1.3 Gy vs. 4.7 ± 0.8 Gy, p = 0.035) and the mean dose to the ipsilateral lung was also reduced by an average of 0.8 Gy (12.4 ± 1.0 Gy vs. 11.6 ± 0.8 Gy, p < 0.001). The values for V50Gy of the PTV of the chest wall for the 3D-printed and conventional boluses were 95.4 ± 0.6% and 94.8 ± 0.8% (p = 0.026) and the values for the CI of the entire PTV were 0.83 ± 0.02 and 0.80 ± 0.03 (p < 0.001), respectively. The NTCP for the 3D-printed bolus was also reduced to an average of 0.14% (0.32 ± 0.19% vs. 0.18 ± 0.11%, p = 0.017) for the heart and 0.45% (3.70 ± 0.67% vs. 3.25 ± 0.18%, p < 0.001) for the ipsilateral lung. Grade 2 and Grade 1 radiation pneumonitis were 0.0% versus 7.5% and 14.3% versus 20.0%, respectively (p = 0.184). CONCLUSIONS: The 3D-printed bolus may reduce cardiopulmonary exposure in postmastectomy patients with volumetric modulated arc therapy.

Identifying an optimal machine learning model generated circulating biomarker to predict chronic postoperative pain in patients undergoing hepatectomy.

Chronic postsurgical pain (CPSP) after hepatectomy is highly prevalent and challenging to treat. Several risk factors have been unmasked for CPSP after hepatectomy, such as acute postoperative pain. The current secondary analysis of a clinical study sought to extend previous research by investigating more clinical variables and inflammatory biomarkers as risk factors for CPSP after hepatectomy and sifting those strongly related to CPSP to build a reliable machine learning model to predict CPSP occurring. Participants included 91 adults undergoing hepatectomy who was followed 3 months postoperatively. Twenty-four hours after surgery, participants completed numerical rating scale (NRS) grading and blood sample collecting. Three months after surgery, participants also reported whether CPSP occurred through follow-up. The Random Forest and Support Vector Machine models were conducted to predict pain outcomes 3 months after surgery. The results showed that the SVM model had better performance in predicting CPSP which consists of acute postoperative pain (evaluated by NRS) and matrix metalloprotease 3 (MMP3) level. What's more, besides traditional cytokines, several novel inflammatory biomarkers like C-X-C motif chemokine ligand 10 (CXCL10) and MMP2 levels were found to be closely related to CPSP and a novel spectrum of inflammatory biomarkers was created. These findings demonstrate that the SVM model consisting of acute postoperative pain and MMP3 level predicts greater chronic pain intensity 3 months after hepatectomy and with this model, intervention administration before CPSP occurs may prevent or minimize CPSP intensity successfully.

Efficacy of Perioperative Continuous Intravenous Lidocaine Infusion for 72 Hours on Postoperative Pain and Recovery in Patients Undergoing Hepatectomy: Study Protocol for a Prospective Randomized Controlled Trial.

PURPOSE: Many patients develop severe and persistent pain after hepatectomy delaying postoperative rehabilitation. Studies have suggested that intravenous lidocaine infusion relieved postoperative pain and improved overall postoperative outcomes. However, its efficacy on hepatectomy is still masked, due to the postoperative metabolic change of lidocaine by the liver. We hypothesized that intravenous lidocaine infusion in the perioperative period would lead to postoperative pain reduction and improve the overall patient experience. STUDY DESIGN AND METHODS: In this prospective double-blind, randomized controlled design trial, 260 adults scheduled for hepatectomy will be allocated to the lidocaine and the placebo groups. The lidocaine group will be administered lidocaine intravenously during intraoperative period and 72 postoperative hours; the placebo group will be administered normal saline at the same volume, infusion rate, and timing. The primary outcome is the incidence of moderate-severe pain (numeric rating scale ≥4) during movement at 24 hours after surgery. The secondary outcomes include the incidence of moderate-severe pain at 24 hours after surgery at rest, the incidence of moderate-severe pain at 48 and 72 hours after surgery at rest and during movement, the cumulative morphine consumption at 24, 48 and 72 hours postoperatively, bowel function recovery, the incidence of postoperative nausea and vomiting, the incidence of postoperative pulmonary complications, the length of hospital stay, levels of inflammatory factors and patient satisfaction scores. DISCUSSION: This is the first prospective trial to shed light on the efficacy of intraoperative period and 72 postoperative hours intravenous lidocaine on postoperative pain and recovery after hepatectomy. The findings will provide a new strategy of perioperative pain management for hepatectomy.

[Advances in research on the relationship between changes in cellular metabolism and lung diseases].

As the place for gas exchange, the lungs are metabolically active, and their energy consumption are essential for regulating common cell functions and maintaining the unique function of lung tissues to synthesize pulmonary surfactants. The metabolic pathways of pulmonary cells mainly include glycolysis, pentose phosphate pathway, and tricarboxylic acid cycle. Recent studies have found that changes in pulmonary cells metabolism are closely related to a variety of lung diseases. Herein, we review the main pathways of pulmonary cells metabolism and the relationship between changes in cell metabolism and the four lung diseases of chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH), to find new ways to treat lung diseases.

Extubation in the operating room results in fewer composite mechanical ventilation-related adverse outcomes in patients after liver transplantation: a retrospective cohort study.

BACKGROUND: To investigate the effect of extubation in the operating room (OR) on mechanical ventilation-related adverse outcomes in patients who undergo liver transplantation. METHODS: Patients who underwent liver transplantation between January 2016 and December 2019 were included. According to the timing of extubation, patients were divided into OR extubation group and intensive care unit (ICU) extubation group. The propensity score was used to match OR extubation group and ICU extubation group at a 1:2 ratio by demographical and clinical covariates. The primary outcome was a composite of mechanical ventilation-related adverse outcomes, including 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), and in-hospital moderate to severe pulmonary complications. Secondary outcomes included in-hospital moderate to severe infectious complications, unplanned reintubation rates, ICU and postoperative hospital lengths of stay, and total hospital cost. RESULTS: A total of 438 patients were enrolled. After propensity score matching, 94 patients were in OR extubation group and 148 patients were in ICU extubation group. Incidence of the composite mechanical ventilation-related adverse outcomes was significantly lower in OR extubation group than ICU extubation group, even after adjusting for confounding factors (19.1% vs. 31.8%; Odds Ratio, 0.509; 95% Confidence Index [CI], 0.274-0.946; P=0.031). The duration of ICU stay was much shorter in OR extubation group than ICU extubation group (median 4, Interquartile range [IQR] (3 ~ 6) vs. median 6, IQR (4 ~ 8); P<0.001). Meanwhile, extubation in the OR led to a significant reduction of total hospital cost compared with extubation in the ICU (median 3.9, IQR (3.5 ~ 4.6) 10000 US dollars vs. median 4.1, IQR (3.8 ~ 5.1) 10000 US dollars; P=0.021). However, there were no statistically significant differences in moderate to severe infectious complications, unplanned reintubation rates, and the length of postoperative hospital stay between groups. CONCLUSIONS: Among patients who underwent liver transplantation, extubation in the OR compared with extubation in the ICU, significantly reduced the primary composite outcome of 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), or in-hospital moderate to severe pulmonary complications. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov with registration number NCT04261816. Retrospectively registered on 1st February 2020.

A dosimetric and radiobiological evaluation of VMAT following mastectomy for patients with left-sided breast cancer.

BACKGROUND: To compare the dosimetric, normal tissue complication probability (NTCP), secondary cancer complication probabilities (SCCP), and excess absolute risk (EAR) differences of volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for left-sided breast cancer after mastectomy. METHODS AND MATERIALS: Thirty patients with left-sided breast cancer treated with post-mastectomy radiation therapy (PMRT) were randomly enrolled in this study. Both IMRT and VMAT treatment plans were created for each patient. Planning target volume (PTV) doses for the chest wall and internal mammary nodes, PTV1, and PTV of the supraclavicular nodes, PTV2, of 50 Gy were prescribed in 25 fractions. The plans were evaluated based on PTV1 and PTV2 coverage, homogeneity index (HI), conformity index, conformity number (CN), dose to organs at risk, NTCP, SCCP, EAR, number of monitors units, and beam delivery time. RESULTS: VMAT resulted in more homogeneous chest wall coverage than did IMRT. The percent volume of PTV1 that received the prescribed dose of VMRT and IMRT was 95.9 ± 1.2% and 94.5 ± 1.6%, respectively (p < 0.001). The HI was 0.11 ± 0.01 for VMAT and 0.12 ± 0.02 for IMRT, respectively (p = 0.001). The VMAT plan had better conformity (CN: 0.84 ± 0.02 vs. 0.78 ± 0.04, p < 0.001) in PTV compared with IMRT. As opposed to IMRT plans, VMAT delivered a lower mean dose to the ipsilateral lung (11.5 Gy vs 12.6 Gy) and heart (5.2 Gy vs 6.0 Gy) and significantly reduced the V5, V10, V20, V30, and V40 of the ipsilateral lung and heart; only the differences in V5 of the ipsilateral lung did not reach statistical significance (p = 0.409). Although the volume of the ipsilateral lung and heart encompassed by the 2.5 Gy isodose line (V2.5) was increased by 6.7% and 7.7% (p < 0.001, p = 0.002), the NTCP was decreased by 0.8% and 0.6%, and SCCP and EAR were decreased by 1.9% and 0.1% for the ipsilateral lung. No significant differences were observed in the contralateral lung/breast V2.5, V5, V10, V20, mean dose, SCCP, and EAR. Finally, VMAT reduced the number of monitor units by 31.5% and the treatment time by 71.4%, as compared with IMRT. CONCLUSIONS: Compared with IMRT, VMAT is the optimal technique for PMRT patients with left-sided breast cancer due to better target coverage, a lower dose delivered, NTCP, SCCP, and EAR to the ipsilateral lung and heart, similar doses delivered to the contralateral lung and breast, fewer monitor units and a shorter delivery time.

TLR4 is required for macrophage efferocytosis during resolution of ventilator-induced lung injury.

Mechanical ventilation is a life-sustaining therapy for patients with respiratory failure but can cause further lung damage known as ventilator-induced lung injury (VILI). However, the intrinsic molecular mechanisms underlying recovery of VILI remain unknown. Phagocytosis of apoptotic cells (also known as efferocytosis) is a key mechanism orchestrating successful resolution of inflammation. Here we show the positive regulation of macrophage Toll-like receptor (TLR) 4 in efferocytosis and resolution of VILI. Mice were depleted of alveolar macrophages and then subjected to injurious ventilation (tidal volume, 20 mL/kg) for 4 h. On day 1 after mechanical ventilation, Tlr4+/+ or Tlr4-/- bone marrow-derived macrophages (BMDMs) were intratracheally administered to alveolar macrophage-depleted mice. We observed that mice depleted of alveolar macrophages exhibited defective resolution of neutrophilic inflammation, exuded protein, lung edema, and lung tissue injury after ventilation, whereas these delayed responses were reversed by administration of Tlr4+/+ BMDMs. Importantly, these proresolving effects by Tlr4+/+ BMDMs were abolished in mice receiving Tlr4-/- BMDMs. The number of macrophages containing apoptotic cells or bodies in bronchoalveolar lavage fluid was much less in mice receiving Tlr4-/- BMDMs than that in those receiving Tlr4+/+ BMDMs. Macrophage TLR4 deletion facilitated a disintegrin and metalloprotease 17 maturation and enhanced Mer cleavage in response to mechanical ventilation. Heat shock protein 70 dramatically increased Mer tyrosine kinase surface expression, phagocytosis of apoptotic neutrophils, and rescued the inflammatory phenotype in alveolar macrophage-depleted mice receiving Tlr4+/+ BMDMs, but not Tlr4-/- BMDMs. Our results suggest that macrophage TLR4 promotes resolution of VILI via modulation of Mer-mediated efferocytosis.