c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator-induced acute lung injury

Background As one of the basic treatments performed in the intensive care unit, mechanical ventilation can cause ventilator-induced acute lung injury (VILI). The typical features of VILI are an uncontrolled inflammatory response and impaired lung barrier function; however, its pathogenesis is not fully understood, and c-Fos protein is activated under mechanical stress. c-Fos/activating protein-1 (AP-1) plays a role by binding to AP-1 within the promoter region, which promotes inflammation and apoptosis. T-5224 is a specific inhibitor of c-Fos/AP-1, that controls the gene expression of many proinflammatory cytokines. This study investigated whether T-5224 attenuates VILI in rats by inhibiting inflammation and apoptosis. Methods The SD rats were divided into six groups: a control group, low tidal volume group, high tidal volume group, DMSO group, T-5224 group (low concentration), and T-5224 group (high concentration). After 3 h, the pathological damage, c-Fos protein expression, inflammatory reaction and apoptosis degree of lung tissue in each group were detected. Results c-Fos protein expression was increased within the lung tissue of VILI rats, and the pathological damage degree, inflammatory reaction and apoptosis in the lung tissue of VILI rats were significantly increased; T-5224 inhibited c-Fos protein expression in lung tissues, and T-5224 inhibit the inflammatory reaction and apoptosis of lung tissue by regulating the Fas/Fasl pathway. Conclusions c-Fos is a regulatory factor during ventilator-induced acute lung injury, and the inhibition of its expression has a protective effect. Which is associated with the antiinflammatory and antiapoptotic effects of T-5224.

Effect of Exercise Volume on Plantar Microcirculation and Tissue Hardness in People With Type 2 Diabetes

Objective: Exercise has been reported to be beneficial for people with type 2 diabetes (T2DM), but exercise, especially weight-bearing exercise, may increase the risk of diabetic foot ulcers (DFUs). This study aimed to explore the associations between different volumes of weight-bearing physical activities and plantar microcirculation and tissue hardness in people with T2DM.Methods: 130 elderly people with T2DM were enrolled for this cross-sectional study. They were classified into the high exercise volume group and the low exercise volume group based on their weekly energy expenditure (metabolic equivalents per week) in the past year. Weekly energy expenditure was calculated using the International Physical Activity Questionnaire and the Compendium of Physical Activities. The plantar oxygen saturation (SO2) and soft tissue hardness of each participant’s right foot were measured.Results: A total of 80 participants completed the trial. The average exercise energy expenditure of the high exercise volume group and the low exercise volume group were significantly different (p < 0.05). The results showed that the SO2 of the high exercise volume group (67.25 ± 6.12%) was significantly higher than the low exercise volume group (63.75 ± 8.02%, p < 0.05). The plantar tissue hardness of the high exercise volume group was lower than the low exercise volume group in the big toe, midfoot and hindfoot regions (p < 0.05).Conclusion: This study demonstrates that higher volumes of exercise are associated with better plantar microcirculation and lower plantar tissue hardness in people with T2DM. The findings of this study indicate that weight-bearing exercise may not increase risk of developing diabetic foot ulcers.

Potential factors in postoperative dislocation of Oxford phase III mobile bearing UKA in Chinese patients: a single-center retrospective study

Background Bearing dislocation is the main complication after mobile bearing unicompartmental knee arthroplasty. The purpose of this study was to analyze the potential risk factors of bearing dislocation after Oxford phase III mobile bearing unicompartmental knee arthroplasty in Chinese patients. Methods We retrospectively investigated 492 patients (578 knees) who underwent Oxford phase III mobile bearing unicompartmental knee arthroplasty in our institution between February 2009 and June 2019. The patients were divided into two groups based on surgeons’ annual surgical volume. Those with/ without bearing dislocation were compared based on patient, surgeon and implant factors. Results Among the 492 patients, 21 (4.3%, 4 men and 17 women) experienced bearing dislocation. Of these, 14 (4.0%) were in the high surgical volume group and 7 (5.1%) were in the low surgical volume group. Multivariate analysis revealed that trauma to the operated leg and daily life involving high knee flexion cumulatively predicted bearing dislocation (p < 0.05). Conclusions Trauma to the operated leg and daily life involving high knee flexion were risk factors for bearing dislocation after Oxford phase III mobile bearing unicompartmental knee arthroplasty.

The Effect of Laparoscopic Radical Hysterectomy Surgical Volume on Oncology Outcomes in Early-Stage Cervical Cancer

Purpose: To examine the association between surgical volume and surgical and oncological outcomes of women with stage IB1 cervical cancer who underwent laparoscopic radical hysterectomy (LRH).Methods: We retrospectively analyzed the oncological outcomes of 1,137 patients with stage IB1 cervical cancer receiving LRH from 2004 to 2016. The surgical volume for each surgeon was defined as low [fewer than 50 surgeries, n = 392(34.5%)], mid [51-100 surgeries, n = 315(27.7%)], and high [100 surgeries or more, n = 430(37.8%)]. Surgical volume-specific survival was examined with Kaplan–Meier analysis, multivariable analysis, and propensity score matching.Results: The operative times of the high-volume group (227.35 ± 7.796 min) were significantly shorter than that of the low- (272.77 ± 4.887 min, p &lt; 0.001) and mid-volume (255.86 ± 4.981 min, p &lt; 0.001) groups. Blood loss in the high-volume group (169.42 ± 8.714 ml) was significantly less than that in the low-volume group (219.24 ± 11.299 ml, p = 0.003). The 5-year disease-free survival (DFS) and overall survival (OS) in the low-volume, mid-volume, and high-volume groups were similar (DFS: 91.9, 86.7, and 89.2%, p = 0.102; OS: 96.4, 93.5, and 94.2%, p = 0.192). Multivariable analysis revealed surgical volume was not an independent risk factor for OS or DFS. The rate of intraoperative and postoperative complications was similar among the three groups (p = 0.210).Conclusions: Surgical volume of LRH may not be a prognostic factor for patients with stage IB1 cervical cancer. Surgery at high-volume surgeon is associated with decreased operative time and blood loss.

Patients with undetectable PSA 2 years after docetaxel for metastatic castration sensitive prostate cancer (mCSPC).

e17044 Background: Patients with mCPSC have multiple treatment options to combine with androgen deprivation therapy (ADT) including docetaxel, abiraterone, enzalutamide and apalutamide, all of which have demonstrated a survival advantage. While oral anti-androgens are administered daily until progression but are less toxic, docetaxel has more upfront side effects. One of the advantages of using docetaxel is that the 6-cycle regimen (over approximately 4 months) potentially affords patients a respite from daily therapies thereafter. Furthermore, docetaxel may be more cost-effective. In this prospective study, mCSPC patients were treated with docetaxel and Prostvac, a therapeutic cancer vaccine. Since this study was initiated, Prostvac did not demonstrate independent clinical activity in a phase 3 trial in metastatic castration resistant prostate cancer. Nonetheless, this study provides an opportunity to evaluate responses to docetaxel-based therapy in mCSPC. Methods: Eligible patients included those with mCSPC and ECOG of ≤ 2. All patients were treated with docetaxel and were planned to receive 75mg/m2 for 6 cycles within 4 months of starting ADT, as per the CHAARTED regimen. Patients were randomized to receive Prostvac prior to, concurrent with or after docetaxel. Patients were restaged annually with CT and Tc99 bone scan. The study was powered to evaluate immunologic responses, which is ongoing. For the purposes of this analysis, all patients were analyzed as one group and long-term PSA responses were evaluated. Results: The study enrolled 73 patients. Age range was 41-86 with a median of 63 years. Race distribution was 71.6% White, 20.3% Black, 4.1% other, and 4.1% unknown. Gleason scores were 6 (4.1%), 7 (21.6%), and 8-10 (68.9%), with 5.4% being unknown. Median pre-ADT PSA was 34.75 ng/mL. Low-volume disease represented 41.1% of patients and high-volume was 58.9%. After 2 years from the start of ADT, 22% of all patients had PSA values of ≤ 0.2 ng/mL. This included 37% of the low-volume group and 12% of the high-volume group. Three years from the start of ADT, 14% of all patients had PSA values ≤ 0.2 ng/mL (20% of the low-volume group, 9% of the high-volume group). Conclusions: These data highlight long-term outcomes of 6 cycles of docetaxel for men with mCSPC. Although there are concerns about the short-term toxicity of docetaxel, there is potential for prolonged stable disease after ̃4 months of chemotherapy that allows these patients to defer additional oral anti-androgen therapy for years in some patients. The proportions of patients presented here are an underestimate of those who could continue to be monitored for slowly rising, but low PSAs, before starting the next line of therapy. Additional research is required to determine the optimal therapeutic sequence for men diagnosed with mCSPC and long-term implications for quality of life and cost-effectiveness. Clinical trial information: NCT02649855.

Changes in three tumor markers in patients with advanced lung adenocarcinoma after combination therapy with pemetrexed and platinum: Short-term treatment efficacy

Purpose: To study changes in three tumor markers before and after combination treatment with pemetrexed and platinum, and evaluate the short-term therapeutic effectiveness of the treatment in advanced lung adenocarcinoma (ALA) subjects. Method: Patients with ALA (n =120) admitted to JinHua Municipal Central Hospital from January 2017 to May 2018 were selected as the research subjects. According to the results of chemotherapy, they were divided into two groups: significantly-reduced tumor volume group (90 cases), and nonsignificantly-reduced tumor volume group (21 cases). The two groups were treated with chemotherapy using a combination of pemetrexed and cisplatin. The levels of CEA, CA125 and CYFRA21-1 before and after chemotherapy were assayed to determine their relationship with short-term therapy effectiveness. Result: Overall analysis of tumor markers in the 120 patients with ALA showed statistically significant reduction in overall tumor marker levels before and after chemotherapy (p < 0.05). At the end of chemotherapy, the tumor markers were markedly reduced in subjects with significant tumor volume, and there was statistical difference between the two groups before chemotherapy (p < 0.05). Changes in CEA, CA125 and CYFRA21-1 were positively correlated with the chemotherapeutic effects on patients with ALA. Conclusion: In ALA patients treated with pemetrexed and platinum, changes in serum CEA, CA125 and CYFRA21-1 profiles before and after treatment depend on the effect of chemotherapy, and they are reliable for prediction of short-term therapeutic efficacy.

Feasibility of Ultrasound-Guided Peritoneal Perfusion with Ozone in the Treatment of Chronic Pelvic Pain: A Bicenter Retrospective Analysis

Background: Numerous therapies have been developed for the treatment of chronic pelvic pain (CPP). Oxygen-ozone therapy is a new method for the treatment of CPP. Objectives: This article evaluated the feasibility of ultrasound-guided peritoneal perfusion with ozone in patients with CPP. Study Design: This is a bicenter retrospective study. Setting: The study was conducted at 2 pain centers of a university hospital. Methods: The medical records of patients with CPP (n = 60) from March 2016 until October 2018 were collected and reviewed. Group A contained 19 patients who were treated with a 1500 mcg dose of ozonated water (10 mcg/mL concentration and 150 mL volume), group B contained 23 patients using the same dose of ozonated water but a 15 mcg/mL concentration and 100 mL volume. Group C included 18 patients using a similar ozone dose but delivered in an oxygen-ozone mixture (15 mcg/mL concentration and 100 mL volume oxygen-ozone mixture). Visual Analog Scale (VAS) scores for pain of the 3 groups were compared at pretreatment, posttreatment, 1, 3, and 6 months posttreatment. The injection pain was evaluated using a 4-point verbal rating scale. Quality of life (QoL), anxiety, and depression were assessed at pretreatment and at 6 months posttreatment. Results: The VAS scores of the 3 groups decreased over time following treatment. Group A showed much higher pain scores compared with groups B and C at 1, 3, and 6 months posttreatment. However, the injection pain for groups B and C was higher than group A, but there was no difference seen between group B and C. At 6 months posttreatment, the QoL for all patients improved compared with pretreatment, whereas the anxiety and depression did not demonstrate differences. Limitations: The main limitations of this study are the retrospective study design, limited case number, and short follow-up period. Conclusions: Ultrasound-guided peritoneal perfusion with ozone is a feasible therapy for patients with CPP. Key words: Chronic pelvic pain, ozone, peritoneal perfusion

Lung-protective ventilation increases cerebral metabolism and non-inflammatory brain injury in porcine experimental sepsis

Background Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg−1 and nine animals were ventilated with a tidal volume of 10 mL × kg−1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg−1 × h−1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour. Results No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium–high tidal volume ventilation. Conclusions Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium–high tidal volume ventilation.

The Important Role of Tumor Volume In Surgical Approach Choice, Surgical Complexity, and Post-Operative Complications In Renal Cell Carcinoma With Venous Tumor Thrombus From A Large Chinese Center Experience

Background: To evaluate the significance of interactions between tumor volume (TV) and surgical approach choice, surgical complexity, intra-operative blood loss, post-operative complications, as well as overall survival (OS) for patients with inferior vena cava tumor thrombus (IVCT-T) in locally advanced renal cell carcinoma (RCC). Method: From Jan 2014 to Jan 2020, we identified 132 patients who underwent radical nephrectomy with inferior vena cava thrombectomy (RN-IVCT) in Peking University Third Hospital (PKUTH) and had available imaging for review. TV for RCC, renal vein (RV) and IVCT were separately measured through the well-known and commonly used application by medical professions，3D slicer. The significance of differences between groups was evaluated using linear regression. Prognostic factors were identified by univariate and multivariate analyses using the Cox proportional hazards model, and hazard ratios (HRs) with 95% confidence intervals were calculated. Results: Patients were divided into three groups based on the inferior vena caval tumor thrombus volume (IVCT-TV); group 1 comprised of all patients with IVCT-TV between 0-15 cubic centimeter (cm3), group 2 comprised of all patients with IVCT-TV between 15-30 cm3, and group 3 comprised of all patients with IVCT-TV greater than 30 cm3. Using these criteria, there were 48 patients in group 1, 38 in group 2, and 46 in group 3, representing 36.6%, 28%, and 35% of the total number of patients, respectively. There were 24 patients with Mayo grade I, 74 patients with Mayo grade II, 19 patients with Mayo grade III, and 18 patients with Mayo grade IV. Fifty-nine patients (44.7%) underwent complete laparoscopic surgery, and 73 patients (55%) underwent open surgery. The median surgery time was 334 minutes for group 1, 341 minutes for group 2, and 374 minutes for group 3 (p <0.044). The median intra-operative blood loss was 650 ml for group 1, 600 ml for group 2, and 2350 ml for Group 3 (p <0.001). Post-operative complications occurred in 13 (27.1%) patients from group 1, 15 (39.5%) patients from group 2, and 35 (76.1%) patients from group 3 (p < 0.001). Open approach surgery was the more desirable choice for caval tumor group (p< 0.001) and total thrombi volume group (P<0.001). Overall surgery time was significantly longer, and operation was more difficult for renal venous thrombus volume group (P < 0.014), caval tumor volume group (P <0.033), and total thrombi volume group (P <0.005). Intra-operative blood loss was more and statistical difference was seen for caval tumor volume (p<0.001) and total tumor volume (p<0.001). No significant difference was noted for a demographic characteristic such as age, gender, side, size, BMI index, tumor type. Operative time, intra-operative blood loss, depth of IVC vascular wall invasion, surgical approach, and Mayo level were identified as the independent factors in this study. Conclusion: Results of this present study indicate that a larger TV necessitates open surgery approach, and is associated with a prolonged operative time, increased intra-operative blood loss, increased surgical complexity, and a higher incidence of post-operative complications. However, TV does not affect the overall patient survival and hospitalization time.

Robotic-Assisted Unicompartmental Knee Arthroplasty Reduces Components' Positioning Differences among High- and Low-Volume Surgeons

Robotic-assisted medial unicompartmental knee arthroplasty (mUKA) has been introduced to improve accuracy in implant positioning and limb alignment, overcoming the reported high failure rates of conventional UKA. Indeed, mUKA is a technically challenging procedure strongly related to surgeons' skills and expertise. The purpose of this study was to evaluate the likelihood of robotic-assisted surgery in reducing the variability of coronal and sagittal component positioning between high- and low-volume surgeons. We evaluated a prospective cohort of 161 robotic mUKA implanted between May 2018 and December 2019 at two high-volume robotic centers. Patients were divided into two groups: patients operated by “high-volume” (group A) or “low-volume” (group B) surgeons. We recorded intraoperative lower-limb alignment, component positioning, and surgical timing. Postoperatively, every patient underwent a radiographical protocol to assess coronal and sagittal femoral/tibial component alignment. Range of motion and other clinical outcomes were assessed pre- and 12 months postoperatively by using oxford knee score, forgotten joint score, and visual analog scale. Of 161 recruited knees, 149 (A: 101; B: 48) were available for radiographic analysis at 1 month, and clinical evaluation at 12 months. No clinical difference neither difference in mechanical alignment nor coronal/sagittal component positioning were found (p > 0.05). A significant difference was recorded in surgical timing (A: 57 minutes; B: 86 minutes; p < 0.05). No superficial or deep infections or other major complications have been developed during the follow-up. Robotics surgery in mUKA confirmed its value in improving the reproducibility of such technical procedure, with satisfactory clinical outcomes. Moreover, it almost eliminates any possible differences in component positioning, and lower limb alignment among low-and high- volume knee surgeons.