A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Compliance with rigid gas-permeable contact lens use in children younger than 6 years in China: a 6-year retrospective study.

PURPOSE: To explore the abandonment rate and factors influencing the use of rigid gas-permeable contact lenses (RGPCL) among children aged < 6 years. METHODS: This retrospective case series study included 70 children aged < 6 years who were fitted with RGPCL for visual rehabilitation between January 2016 and December 2021. We collected data on indications, discontinuation rates, and reasons for discontinuation from medical records and via telephone calls and investigated the factors influencing contact lens abandonment. RESULTS: The median age of the 70 participants was 5.0 (interquartile range: 4.0-5.9) years. Further, 36 (51.4%) children stopped wearing contact lenses; among them, 17 (47.2%) stopped within 3 months, and the median duration of lens wearing was 4.0 (interquartile range: 1.0-11.5) months. Additionally, there was a correlation between the duration of lens wearing and lens abandonment (r = -0.698, P < 0.001). A high parental education level (hazard ratio [HR] = 0.425; 95% confidence interval [CI] 0.198, 0.913; P = 0.028) was a protective factor against lens abandonment, while parental assessment indicating harder than expected practicality (HR = 4.062; 95% CI 1.204, 13.707; P = 0.024) was a risk factor for abandonment. CONCLUSION: Children aged < 6 years are susceptible to early discontinuation of RGPCL use. Since parents perform daily lens manipulation, they are crucial to the continuity of lens use in these children. To improve RGPCL use continuity, communication and supervision should be strengthened before and after RGPCL fittings.

A Prospective Study Using Propensity Score Matching to Compare Long-term Survival Outcomes After Robotic-assisted, Laparoscopic, or Open Liver Resection for Patients With BCLC Stage 0-A Hepatocellular Carcinoma.

OBJECTIVE: To compare the short- and long-term outcomes of robot-assisted (RALR), laparoscopic (LLR), or open liver resection (OLR) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Following the Balliol IDEAL classification, long-term oncological outcomes can be used to evaluate the value of minimally invasive techniques in the treatment of HCC, and to assess whether they should become a standard practice. METHODS: Data from prospective cohorts of patients with BCLC stage 0-A HCC who underwent curative liver resection using OLR, LLR, or RALR at Tongji Hospital were reviewed. The short-term and long-term oncological outcomes of these 3 different surgical approaches after adequate follow-up were compared using propensity score matching to reduce selection bias. RESULTS: Of 369 patients included in this study (71, RALR; 141, LLR; and 157, OLR), 56 patients in each of the 3 groups were chosen for further comparison, after propensity score matching. In the minimally invasive group (RALR+LLR), both the operative time and duration of Pringle's maneuver were significantly longer than those in the OLR group; however, the length of hospital stay was significantly shorter. There were no significant differences in the other intraoperative parameters and the incidence of postoperative complications among the 3 groups. HCC recurrence in the minimally invasive group when compared with the OLR group was characterized by a significantly higher proportion of single lesion or early-stage HCC. However, there were no significant differences in the 5-year disease-free survival (63.8%, 54.4%, and 50.6%) or overall survival rates (80.8%, 78.6%, and 75.7%, respectively) among the 3 groups. Clinically significant portal hypertension was the only risk factor that negatively affected the 5-year disease-free survival rate. Multivariate Cox regression analysis showed that clinically significant portal hypertension, serum alpha-fetoprotein level (≥400 ng/mL), and Edmondson-Steiner grading (III+IV) were independent risk factors for poor long-term survival. CONCLUSION: Both robotic and laparoscopic hepatectomies were safe and effective for patients with BCLC stage 0-A HCC when compared with open hepatectomy.

The OsNLP3/4-OsRFL module regulates nitrogen-promoted panicle architecture in rice.

Rice panicles, a major component of yield, are regulated by phytohormones and nutrients. How mineral nutrients promote panicle architecture remains largely unknown. Here, we report that NIN-LIKE PROTEIN3 and 4 (OsNLP3/4) are crucial positive regulators of rice panicle architecture in response to nitrogen (N). Loss-of-function mutants of either OsNLP3 or OsNLP4 produced smaller panicles with reduced primary and secondary branches and fewer grains than wild-type, whereas their overexpression plants showed the opposite phenotypes. The OsNLP3/4-regulated panicle architecture was positively correlated with N availability. OsNLP3/4 directly bind to the promoter of OsRFL and activate its expression to promote inflorescence meristem development. Furthermore, OsRFL activates OsMOC1 expression by binding to its promoter. Our findings reveal the novel N-responsive OsNLP3/4-OsRFL-OsMOC1 module that integrates N availability to regulate panicle architecture, shedding light on how N nutrient signals regulate panicle architecture and providing candidate targets for the improvement of crop yield.

Fabrication of a Magnetic Porous Organic Polymer for α-Glucosidase Immobilization and Its Application in Inhibitor Screening.

The technology based on immobilized enzymes was employed to screen the constituents inhibiting disease-related enzyme activity from traditional Chinese medicine, which is expected to become an important approach of innovative drug development. Herein, the Fe3O4@POP composite with a core-shell structure was constructed for the first time with Fe3O4 magnetic nanoparticles as the core, 1,3,5-tris (4-aminophenyl) benzene (TAPB) and 2,5-divinylterephthalaldehyde (DVA) as organic monomers, and used as the support for immobilizing α-glucosidase. Fe3O4@POP was characterized by transmission electron microscopy, energy-dispersive spectrometry, Fourier transform infrared, powder X-ray diffraction, X-ray photoelectron spectroscopy, and vibrating sample magnetometry. Fe3O4@POP exhibited a distinct core-shell structure and excellent magnetic response (45.2 emu g-1). α-Glucosidase was covalently immobilized on core-shell Fe3O4@POP magnetic nanoparticles using glutaraldehyde as the cross-linking agent. The immobilized α-glucosidase possessed improved pH stability and thermal stability as well as good storage stability and reusability. More importantly, the immobilized enzyme exhibited a lower Km value and enhanced affinity for the substrate than the free one. The immobilized α-glucosidase was subsequently used for inhibitor screening from 18 traditional Chinese medicines in combination with capillary electrophoresis analysis among which Rhodiola rosea exhibited the highest enzyme inhibitory activity. These positive results demonstrated that such magnetic POP-based core-shell nanoparticles were a promising carrier for enzyme immobilization and the screening strategy based on immobilized enzyme provided an effective way to rapidly explore the targeted active compounds from medicinal plants.

Peripherally Inserted Central Catheter-Related Skin Injury in Patients with a Chest Tumor: Characteristics and Risk Factors.

OBJECTIVE: To investigate the characteristics and risk factors of skin injury in patients with chest tumors who have peripherally inserted central catheters (PICCs). METHODS: This study included a total of 252 patients with chest tumors with PICC placement who were treated from March 2018 to December 2021 in a tertiary hospital in Shanghai, China. Investigators used univariate analysis and multivariate logistic regression to identify the risk factors. RESULTS: Among the included patients, 40.8% had skin injuries (n = 103). Skin injury occurred between 2 and 361 days after PICC placement, with a median time of 56.0 days (interquartile range, 20.75-99.25 days). Skin injury may occur during catheter retention and be concentrated in the first 3 months after PICC placement; the occurrence trajectory of skin injury exhibits a downward trend. Logistic regression analysis shows that skin injury is more likely to occur if the patient has a history of smoking, allergy history, use of recombinant human endostatin, or an excessive duration of catheter retention. CONCLUSIONS: The incidence of PICC-related skin injury in patients with chest tumors remains high. Medical practitioners should be aware of its characteristics and risk factors and adopt effective solutions early to mitigate the occurrence of skin injury and improve patients' safety.

Comparison of robotic camera holders with human assistants in endoscopic surgery: a systematic review and meta-analysis.

BACKGROUND: Robotic camera holders can overcome the shortcomings of human assistants, such as shaking and accidental rotation in endoscopic surgery. Robotic camera holder is not affected by the operation time and surgical position and reduces the size of the team. However, there is still controversy over the practicality of robotic camera holders. MATERIAL AND METHODS: We searched PubMed, Web of Science, Embase, Cochrane Library PubMed, Embase, Cochrane Library and Web of Science. The last database search was performed on 30 April 2022. Two reviewers independently reviewed the studies. RESULTS: A total of eight studies (n = 698, 354 controls and 344 robotic camera holders) were included in our analysis. The results showed that the robotic camera holder significantly outperformed human assistants on the frequency of lens cleaning (SMD, -0.48; 95% CI, -0.90 to -0.05) and inappropriate movements (MD, -3.57; 95% CI, -4.93 to -2.21). There was no difference in total operation time (MD, 6.99; 95% CI, -2.47 to 16.72), preparation time (MD, 2.43; 95% CI, -0.32 to 5.18) or blood loss (MD, 34.47; 95% CI, -8.05 to 76.98) between the robotic camera holder and human assistant. However, the robotic camera holder was significantly slower in the core operation (MD, 5.06; 95% CI, 1.18 to 8.94), and surgeons had mixed reviews of robotic systems. CONCLUSIONS: The robotic camera holder provided the surgeon with a highly stable environment. Although the robotic camera holder will not increase the total time, it still needs to improve the core operation time. There is much room for improvement in robotic camera holders. Further development of devices with intuitive control systems and a greater range of motion will be required to accommodate more complex surgeries.

Clinical Features of Recurrence After Hepatic Resection for Early-Stage Hepatocellular Carcinoma and Long-Term Survival Outcomes of Patients with Recurrence: A Multi-institutional Analysis.

BACKGROUND: A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most HCCs, even at an early stage, eventually recur after resection. This study investigates clinical features of initial recurrence and long-term prognosis of patients with recurrence after curative resection for early-stage HCC. PATIENTS AND METHODS: From a multicenter database, patients who underwent curative hepatic resection for early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0/A] were extracted. Time to initial recurrence, patterns of initial recurrence, and treatment modalities for recurrent tumors were investigated. Univariate and multivariate analysis were used to identify independent risks associated with postoperative recurrence, as well as post-recurrence survival (PRS) for patients with recurrence. RESULTS: Among 1424 patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) early recurrence (≤ 2 years after surgery) and 271 (39.9%) late recurrence (> 2 years). Independent risks of postoperative recurrence included cirrhosis, preoperative alpha-fetoprotein level > 400 ug/L, tumor size > 5 cm, multiple tumors, satellites, microvascular invasion, and intraoperative blood transfusion. Multivariate analysis revealed that receiving irregular recurrence surveillance, initial tumor beyond Milan criteria, early recurrence, BCLC stage B/C of the recurrent tumor, and noncurative treatments were independently associated with poorer PRS. CONCLUSIONS: Nearly half of patients with early-stage HCC experienced recurrence after resection. Understanding recurrence risks may help identify patients at high risk of recurrence who may benefit from future adjuvant therapies. Meaningful survival even after recurrence can still be achieved by postoperative regular surveillance and curative treatment.

Rice NIN-LIKE PROTEIN 3 modulates nitrogen use efficiency and grain yield under nitrate-sufficient conditions.

Nitrogen (N) is an essential macronutrient for crop growth and yield. Improving the N use efficiency (NUE) of crops is important to agriculture. However, the molecular mechanisms underlying NUE regulation remain largely elusive. Here we report that the OsNLP3 (NIN-like protein 3) regulates NUE and grain yield in rice under N sufficient conditions. OsNLP3 transcript level is significantly induced by N starvation and its protein nucleocytosolic shuttling is specifically regulated by nitrate. Loss-of-function of OsNLP3 reduces plant growth, grain yield, and NUE under sufficient nitrate conditions, whereas under low nitrate or different ammonium conditions, osnlp3 mutants show no clear difference from the wild type. Importantly, under sufficient N conditions in the field, OsNLP3 overexpression lines display improved grain yield and NUE compared with the wild type. OsNLP3 orchestrates the expression of multiple N uptake and assimilation genes by directly binding to the nitrate-responsive cis-elements in their promoters. Overall, our study demonstrates that OsNLP3, together with OsNLP1 and OsNLP4, plays overlapping and differential roles in N acquisition and NUE, and modulates NUE and the grain yield increase promoted by N fertilizer. Therefore, OsNLP3 is a promising candidate gene for the genetic improvement of grain yield and NUE in rice.

Citronellal alleviates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and apoptosis via Na+ /H+ exchanger-1 inhibition.

The medical usage of Doxorubicin (DOX) as a chemotherapeutic agent is restricted owing to its cardiotoxic properties. This study was designed to explore the effect and underlying mechanisms of Citronellal (CT) on DOX-related cardiotoxicity in rats. Rats were divided into six groups: control, DOX, CT, Lithium chloride (LiCl) (a Na+/H+exchanger-1 [NHE1] activator), DOX + CT, and DOX + CT + LiCl. To induce cardiotoxicity, a cumulative dose of 15 mg/kg DOX was intraperitoneally injected into rats. CT (150 mg/kg) and LiCl (1 mg/kg) were given daily by oral gavage for 6 weeks. CT improved cardiac functional parameters and attenuated the cardiac pathological changes induced by DOX. Further study indicated that CT administration regulated the levels of oxidative stress and apoptosis-related factors and in myocardial tissues, reducing cell per-oxidative damage and apoptosis. Besides this, CT attenuated DOX-induced NHE1 upregulation, and the preventive effects of CT against DOX-induced cardiotoxicity were abrogated by the concurrent administration of LiCl. These results demonstrate that CT could ameliorate DOX-induced cardiotoxicity by inhibiting the NHE1-mediated oxidative stress, apoptosis in rats.

Preferences of gastric cancer survivors for follow-up care-a multicenter discrete choice experiment study.

PURPOSES: The purposes of this discrete choice experiment are as follows: (1) to investigate the preferences of gastric cancer survivors for follow-up care, and (2) to quantify the importance of follow-up care-related characteristics that may affect the gastric cancer survivors' choices of their follow-up, so as to provide references for the development of the follow-up strategy of gastric cancer survivors. METHODS: Discrete choice experimental design principle was applied to develop the survey instrument. All questionnaires were filled out by the respondents and collected on site. A mixed logit model was used to estimate gastric cancer survivors' preferences. Willingness to pay estimates and simulations of follow-up uptake rates were calculated. RESULTS: All six attributes are significantly important for the follow-up care of gastric cancer survivors (p < 0.05). Achieving very thorough follow-up contents was the most valued attribute level (coefficient = 1.995). Specialist doctors are the most preferred providers followed by specialist nurses, and gastric cancer survivors were willing to pay more for these attribute levels. Changes in attribute levels affected uptake rate of follow-up. When the multiple attribute levels were changed at the same time, a very thorough follow-up content was provided by the same specialist doctor (specialist nurse), and the probability of receiving follow-up increases by 95.82% (94.90%). CONCLUSIONS: The characteristics of follow-up care in our study reflect the health management services' expectations of gastric cancer survivors. A dedicated specialist nurse involved in follow-up care should be developed to contribute to solve the complex and multifaceted personal needs of gastric cancer survivors.

Pancreatic lipase and alpha-glucosidase inhibitors screening from Schisandra chinensis based on spectrum-effect relationship and ultra-high-performance liquid chromatography-tandem mass spectrometry.

As a traditional Chinese medicine, Schisandra chinensis has a potential weight-loss effect by delaying carbohydrate absorption and improving lipid metabolic disorders. However, its active components are still unclear and require in-depth research. In this study, the active components of Schisandra chinensis responsible for pancreatic lipase and alpha-glucosidase inhibitory activity were screened and identified based on a spectrum-effect relationship study in combination with ultra-performance liquid chromatography-tandem mass spectrometry analysis. The ultra-high-performance liquid chromatography fingerprints of 17 batches of Schisandra chinensis were established, and 14 common peaks were specified by similarity analysis. The half-maximal inhibition concentration values for pancreatic lipase and alpha-glucosidase inhibition were separately measured by enzymatic reactions. Using multivariate statistical methods including principal component analysis, partial least square analysis, and grey relational analysis, the correlation models between the peak areas of 14 common peaks and half-maximal inhibition concentration values were constructed, and the chromatographic peaks making a great contribution to efficacy were screened out. Peak1, Peak2, Peak4, Peak6, Peak9, Peak10, Peak11, and Peak13 were responsible for alpha-glucosidase inhibitory activity, while Peak1, Peak4, Peak6, Peak9, Peak10, and Peak11 for pancreatic lipase inhibitory activity. Finally, the 70% ethanol extracts of Schisandra chinensis were characterized by ultra-high-performance liquid chromatography-tandem mass spectrometry analysis, and 14 lignans were identified to further elucidate the active constituents of Schisandra chinensis. The positive results suggested the proposed strategy is simple and effective to screen active components from complex medicinal plants.

Association of liver abnormalities with in-hospital mortality in patients with COVID-19.

BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

Rice NIN-LIKE PROTEIN 4 plays a pivotal role in nitrogen use efficiency.

Nitrogen (N) is one of the key essential macronutrients that affects rice growth and yield. Inorganic N fertilizers are excessively used to boost yield and generate serious collateral environmental pollution. Therefore, improving crop N use efficiency (NUE) is highly desirable and has been a major endeavour in crop improvement. However, only a few regulators have been identified that can be used to improve NUE in rice to date. Here we show that the rice NIN-like protein 4 (OsNLP4) significantly improves the rice NUE and yield. Field trials consistently showed that loss-of-OsNLP4 dramatically reduced yield and NUE compared with wild type under different N regimes. In contrast, the OsNLP4 overexpression lines remarkably increased yield by 30% and NUE by 47% under moderate N level compared with wild type. Transcriptomic analyses revealed that OsNLP4 orchestrates the expression of a majority of known N uptake, assimilation and signalling genes by directly binding to the nitrate-responsive cis-element in their promoters to regulate their expression. Moreover, overexpression of OsNLP4 can recover the phenotype of Arabidopsis nlp7 mutant and enhance its biomass. Our results demonstrate that OsNLP4 plays a pivotal role in rice NUE and sheds light on crop NUE improvement.

Preferences of first-degree relatives of gastric cancer patients for gastric cancer screening: a discrete choice experiment.

BACKGROUND: It is very necessary to implement gastric cancer screening in China to reduce the mortality of gastric cancer, but there are no national screening guidelines and programs. Understanding of individual preferences is conducive to formulating more acceptable screening strategies, and discrete choice experiments can quantify individual preferences. In addition, the first-degree relatives of gastric cancer patients are at high risk for gastric cancer. Compared with those without a family history of gastric cancer, the risk of gastric cancer in first-degree relatives of gastric cancer patients is increased by 60%. Therefore, a discrete choice experiment was carried out to quantitatively analyse the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening to serve as a reference for the development of gastric cancer screening strategies. METHODS: A questionnaire was designed based on a discrete choice experiment, and 342 first-degree relatives of gastric cancer patients were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model. RESULTS: The five attributes included in our study had a significant influence on the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening (P < 0.05). Participants most preferred the sensitivity of the screening program to be 95% (coefficient = 1.424, P < 0.01) with a willingness to pay 2501.902 Yuan (95% CI, 738.074-4265.729). In addition, the participants' sex and screening experiences affected their preferences. An increase in sensitivity 35 to 95% had the greatest impact on the participants' willingness to choose a gastric cancer screening program. CONCLUSION: The formulation of gastric cancer screening strategies should be rooted in people's preferences. The influence of sex differences and screening experiences on the preferences of people undergoing screening should be considered, and screening strategies should be formulated according to local conditions to help them play a greater role.

Assessment of compliance with oral nutritional supplementation and exploration of barriers and facilitators for patients after gastrectomy: A mixed-methods study.

AIMS: To evaluate the compliance of patients after gastrectomy in taking oral nutritional supplementation and to explore the promoting and hindering factors. DESIGN: A mixed-methods design with an explanatory sequential approach was employed. METHODS: We conducted a 12-week longitudinal study to evaluate the oral nutritional supplementation compliance of 122 patients after gastric cancer surgery and the factors that affected their compliance. After the quantitative phase, we selected the interview subjects and developed the interview outline based on the analysis of the quantitative results. In-depth interviews (n = 15) were conducted to explain and supplement the quantitative phase results. Data were collected from October 2019 to May 2020. RESULTS: The average overall compliance rate of oral nutritional supplementation in patients with gastric cancer over 12 weeks was 30.59%. Adverse reactions to oral nutritional supplementation, the identity of the main caregivers and the patient's financial ability were independent factors that affected patient compliance. In subsequent interviews, we extracted four themes: social support plays an important role in patients taking oral nutritional supplementation, adverse reactions discourage patients from continuing to take oral nutritional supplementation, patients' attitudes affect their motivation to take oral nutritional supplementation, and the different needs of patients for oral nutritional supplementation affect patient compliance. CONCLUSION: Patients' compliance with oral nutritional supplementation after gastric cancer surgery is very low. Health education should pay more attention to the management of adverse reactions and the role of patients' peers and family members. Oral nutritional supplementation products should be diversified to provide patients with more choices. IMPACT: This study clarifies the factors that hinder and promote oral nutritional supplementation compliance and provides an important reference for the establishment and revision of health education strategies for patients after gastric cancer surgery.

Efficacy of Conversion to Aflibercept for Diabetic Macular Edema Previously Refractory to Bevacizumab or Ranibizumab: A Meta-analysis of High-Quality Nonrandomized Studies.

Background: Aflibercept has been widely used in treating diabetic macular edema (DME). However, the effect of aflibercept in treating DME refractory to bevacizumab or ranibizumab has not been well established. Objective: To assess the therapeutic effect of switching from bevacizumab or ranibizumab to aflibercept in the treatment of refractory DME. Methods: Relevant studies were searched from 3 databases: the Cochrane Library, PubMed, and Web of Science. Data on changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events within the follow-up period were collected and pooled using weighted mean differences (WMDs) with corresponding 95% CIs in a random effects model. The between-study heterogeneity was tested using the χ2 test and the I2 statistic, and funnel plots were used to evaluate the publication bias. Results: A total of 11 nonrandomized trials met the inclusion criteria and were included in the meta-analysis. Our studies showed significant improvements in the BCVA (WMD = 100.55; 95% CI = 68.46 to 132.63; P < 0.01) and reduction in CMT (WMD = 0.09; 95% CI = 0.03 to 0.14; P < 0.01) after switching to aflibercept. Although a large amount of heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed the reliability and stability of our results. Conclusion and Relevance: There were significant improvements in both visual and anatomical outcomes after switching from bevacizumab or ranibizumab to aflibercept, without risk of adverse events. Thus, switching therapy may be a safe and effective treatment for patients with refractory DME.

A novel online calculator to predict perioperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma: an international multicenter study.

BACKGROUND: To develop an easy-to-use model to predict the probability of perioperative blood transfusion (PBT) in patients undergoing liver resection for hepatocellular carcinoma (HCC). METHOD: 878 patients from Eastern Hepatobiliary Surgery Hospital of Shanghai were enrolled in the training cohort, while 691 patients from Tongji Hospital of Wuhan and 364 patients from two hospitals from Europe and America served as the Eastern and Western external validation cohorts, respectively. Independent predictors of PBT were identified and used for the nomogram construction. The predictive performance of the model was assessed using the concordance index (C-index) and calibration plot, and externally validated using the two independent cohorts. This model was compared with four currently available prediction risk scores. RESULTS: Eight preoperative variables were identified as independent predictors of PBT, which were incorporated into the new nomogram model, with a C-index of 0.833 and a well-fitted calibration plot. The nomogram performed well on the externally Eastern and Western validation cohorts (C-indexes: 0.786 and 0.777). The discriminatory ability of the nomogram was superior to the four currently available prediction scores (C-indexes: 0.833 vs. 0.671-0.770). The nomogram was programmed into an online calculator, which is available at http://www.asapcalculate.top/Cal3_en.html. CONCLUSION: A nomogram model, using an easy-to-access website, can be used to calculate the PBT risk and identify which patients undergoing HCC resection are at high risks of PBT and can benefit most by using blood conservation techniques.

Defining and predicting early recurrence after liver resection of hepatocellular carcinoma: a multi-institutional study.

BACKGROUND: A clear definition of "early recurrence" after hepatocellular carcinoma (HCC) resection is still lacking. This study aimed to determine the optimal cutoff between early and late HCC recurrence, and develop nomograms for pre- and postoperative prediction of early recurrence. METHODS: Patients undergoing HCC resection were identified from a multi-institutional Chinese database. Minimum P-value approach was adopted to calculate optimal cut-off to define early recurrence. Pre- and postoperative risk factors for early recurrence were identified and further used for nomogram construction. The results were externally validated by a Western cohort. RESULTS: Among 1501 patients identified, 539 (35.9%) were recurrence-free. The optimal length to distinguish between early (n = 340, 35.3%) and late recurrence (n = 622, 64.7%) was 8 months. Multivariable logistic regression analyses identified 5 preoperative and 8 postoperative factors for early recurrence, which were further incorporated into preoperative and postoperative nomograms (C-index: 0.785 and 0.834). The calibration plots for the probability of early recurrence fitted well. The nomogram performance was maintained using the validation dataset (C-index: 0.777 for preoperative prediction and 0.842 for postoperative prediction). CONCLUSIONS: An interval of 8 months was the optimal threshold for defining early HCC recurrence. The two web-based nomograms have been published to allow accurate pre- and postoperative prediction of early recurrence. These may offer useful guidance for individual treatment or follow up for patients with resectable HCC.

Association between body mass index and postoperative morbidity after liver resection of hepatocellular carcinoma: A multicenter study of 1,324 patients.

BACKGROUND: Morbidity remains a common problem following hepatic resection. The aim of this study was to investigate the association between preoperative body mass index (BMI) and morbidity in patients undergoing liver resection for hepatocellular carcinoma (HCC). METHODS: Patients were divided into three groups according to preoperative BMI: low-BMI (≤18.4 kg/m2), normal-BMI (18.5-24.9 kg/m2) and high-BMI (≥25.0 kg/m2). Baseline characteristics, operative variables, postoperative 30-day mortality and morbidity were compared. Univariable and multivariable analyses were performed to identify independent risk factors associated with postoperative morbidity. RESULTS: Among 1324 patients, 108 (8.2%), 733 (55.4%), and 483 (36.5%) were low-BMI, normal-BMI, and high-BMI, respectively. There were no differences in postoperative 30-day mortality among patients based on BMI (P = 0.199). Postoperative 30-day morbidity was, however, higher in low-BMI and high-BMI patients versus patients with a normal-BMI (33.3% and 32.1% vs. 22.9%, P = 0.018 and P < 0.001, respectively). Following multivariable analysis low-BMI and high-BMI remained independently associated with an increased risk of postoperative morbidity (OR: 1.701, 95%CI: 1.060-2.729, P = 0.028, and OR: 1.491, 95%CI: 1.131-1.966, P = 0.005, respectively). Similar results were noted in the incidence of postoperative 30-day surgical site infection (SSI). CONCLUSION: Compared with normal-BMI patients, low-BMI and high-BMI patients had higher postoperative morbidity, including a higher incidence of SSI after liver resection for HCC.