Significant response to pembrolizumab plus lenvatinib in Epstein-Barr-virus-associated intrahepatic cholangiocarcinoma: a case report.

BACKGROUND: The prognosis for advanced intrahepatic cholangiocarcinoma (iCCA) is poor, and there remains an urgent need to develop efficient systemic therapy. The efficacy of Pembrolizumab immunotherapy combined with lenvatinibin in iCCA is still unclear. The role of Epstein-Barr-virus (EBV) as a biomarker in iCCA for response to immunotherapy needs further exploration. CASE PRESENTATION: We report a case of a 60-year-old female with EBV-associated advanced iCCA (EBVaiCCA) who progressed after first-line therapy. She accomplished an available response to the combination therapy of pembrolizumab with lenvatinib, with overall survival of 20 months. CONCLUSIONS: As far as we know, this is the first case report about the application of Pembrolizumab with lenvatinib for EBVaiCCA patients. This case indicates that the combination of immunotherapy and antiangiogenic therapy provides a glimmer of hope for advanced EBVaiCCA patients.

Recruitment or activation of mast cells in the liver aggravates the accumulation of fibrosis in carbon tetrachloride-induced liver injury.

Liver diseases caused by viral infections, alcoholism, drugs, or chemical poisons are a significant health problem: Liver diseases are a leading contributor to mortality, with approximately 2 million deaths per year worldwide. Liver fibrosis, as a common liver disease characterized by excessive collagen deposition, is associated with high morbidity and mortality, and there is no effective treatment. Numerous studies have shown that the accumulation of mast cells (MCs) in the liver is closely associated with liver injury caused by a variety of factors. This study investigated the relationship between MCs and carbon tetrachloride (CCl4)-induced liver fibrosis in rats and the effects of the MC stabilizers sodium cromoglycate (SGC) and ketotifen (KET) on CCl4-induced liver fibrosis. The results showed that MCs were recruited or activated during CCl4-induced liver fibrosis. Coadministration of SCG or KET alleviated the liver fibrosis by decreasing SCF/c-kit expression, inhibiting the TGF-ß1/Smad2/3 pathway, depressing the HIF-1a/VEGF pathway, activating Nrf2/HO-1 pathway, and increasing the hepatic levels of GSH, GSH-Px, and GR, thereby reducing hepatic oxidative stress. Collectively, recruitment or activation of MCs is linked to liver fibrosis and the stabilization of MCs may provide a new approach to the prevention of liver fibrosis.

Can rectal MRI and endorectal ultrasound accurately predict the complete response to neoadjuvant immunotherapy for rectal cancer?

Background: Standardized assessments of clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have been established, but their utility and accuracy remain unclear. This study aimed to evaluate the clinical diagnostic value of rectal magnetic resonance imaging (MRI) and endorectal ultrasonography (ERUS) for the determination of cCRs after neoadjuvant immunotherapy and to investigate the concordance between cCR and pathological complete response (pCR). Methods: Ninety-four patients with rectal cancer treated with neoadjuvant radiotherapy with or without immunotherapy were included. The sensitivity, specificity, and accuracy of each evaluation method were calculated. Results: Combined MRI and ERUS assessments found cCR in seven of the 94 patients in our cohort. In the non-immunotherapy group, the sensitivity, specificity, and accuracy of MRI for diagnosing cCR were 50.0%, 85.2%, and 77.1%, respectively, whereas those of ERUS were 50.0%, 92.6%, and 82.9%, respectively; those of combined MRI and ERUS were 25.0%, 96.3%, and 87.5%, respectively. In the immunotherapy group, the sensitivity, specificity, and accuracy with which MRI identified CR were 51.7%, 76.7%, and 64.4%, respectively; those of ERUS were 13.8%, 90.0%, and 52.5%, respectively, and those of combined MRI and ERUS were 10.3%, 96.7%, and 54.2%, respectively. We also found that 32 of 37 patients with pCR did not meet the cCR evaluation criteria. Of these pCR patients, 78.4% (29/37) received immunotherapy. In the entire cohort, there were five pCRs among the seven cCRs. Of the four cCRs that occurred in the immunotherapy group, three were pCRs. Conclusions: Rectal MRI and/or ERUS did not provide sufficiently accurate assessments of cCR in patients with rectal cancer receiving neoadjuvant therapy, especially immunotherapy, and cCR did not predict pCR.

Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy.

Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin.

Application of Real-Time Sound Touch Elastography for Evaluating Chronic Kidney Disease of Transplanted Kidneys.

BACKGROUND: If chronic allograft nephropathy can be detected early and treated, the long-term survival rate of the transplanted kidney may be effectively improved. PURPOSE: To compare the application value of real-time sound touch elastography (STE), strain elastography, and color Doppler flow imaging in evaluating chronic kidney disease of transplanted kidneys. MATERIALS AND METHODS: A total of 101 patients with renal transplantation were divided into a normal group (serum creatinine <134 mol/L, 58 patients) and a chronic allograft nephropathy group after renal transplantation over 6 months (serum creatinine >134 mol/L, 43 patients). The maximum elastic modulus (Emax) was determined, and receiver operator characteristics were used to compare the diagnostic efficacy of STE ultrasound. RESULTS: Emean, Emax, B/A (the strain rate of the internal oblique muscle tissue/ the strain rate of the central renal cortex) of cortical standard strain ratio in strain elastography, and resistance index (RI) between normal and chronic allograft nephropathy groups have statistical significance (P < .05). Emax is superior to B/A and arcuate artery RI in the chronic cortex in the diagnosis of renal dysfunction, and the area under the receiver operator characteristics curve is 0.88. The estimated glomerular filtration rate was negatively correlated with renal cortex Emax, B/A, and arcuate artery RI, among which Emax was the strongest (r = - 0.713, P < .001). The renal cortical Emax cut-off was 30.95 kPa, the sensitivity was 92%, the specificity was 88%, and the accuracy was 88%. CONCLUSION: The STE technique to evaluate chronic renal dysfunction after renal transplantation is more sensitive than traditional strain-type elastography and hemodynamic parameters, with renal function decline, renal cortex Emax, renal cortical B/A, and arcuate artery RI gradually increased, and renal cortex Emax was particularly obvious.

Pretreatment high cholesterol and low neutrophils predict complete pathological response after neoadjuvant short­course radiotherapy followed by chemotherapy and immunotherapy in locally advanced rectal cancer.

The present study was aimed at looking for hematological indicators that could predict pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with short-course radiotherapy (SCRT) followed by chemotherapy and immunotherapy. A total of 171 patients were enrolled in this observational retrospective study. Pretreatment values of albumin, total cholesterol, lactate dehydrogenase, neutrophil, platelet and lymphocytes were available. Univariate and multivariate logistics analyses were used to determine the prognostic factor for pCR. SCRT followed by chemotherapy and immunotherapy was demonstrated to double the pCR rate (50.5%) compared with long-course chemoradiotherapy. For the former group, baseline high platelet to lymphocyte ratio (P=0.047), high cholesterol (P=0.026) and low neutrophils (P=0.012) level were associated with high pCR rate and baseline high cholesterol (P=0.016) and low neutrophils (P=0.020) level were the independent prognostic factors for pCR. In conclusion, pretreatment high cholesterol and low neutrophils were the independent prognostic predictors of pCR in patients with LARC treated with SCRT followed by chemotherapy and immunotherapy. Clinical trial no. NCT04928807, June 16, 2021.

Gut Streptococcus is a microbial marker for the occurrence and liver metastasis of pancreatic cancer.

Background: Gut microbiome plays an indispensable role in the occurrence and progression in various diseases. The incidence of pancreatic cancer (PC) and liver metastasis (PCLM) are high, most of them are found in advanced stage. Therefore, it is particularly necessary to search for predictive biomarkers, which are helpful for early detection and treatment, and thus improve the survival rate and quality of life of PC patients. Methods: We retrospectively analyzed 44 pancreatic cancer patients (P group, n = 44) and 50 healthy people (N group, n = 50) from March 21, 2021 and August 2, 2022. Among all PC patients, we divided them into liver metastasis group (LM group, n = 27) and non-liver metastasis group (non-LM group, n = 17). DNA was extracted and 16S ribosomal RNA (16S rRNA) gene sequencing was performed. SPSS was used for statistical analyses and all bioinformatics analyses were based on QIIME2, p < 0.05 were considered statistically significant. Results: The microbial richness and diversity of group P and LM were higher than that of group N and non-LM. LEfSe analysis found that Streptococcus was a significantly different microorganism, which was further identified by random forest (RF) model, and its ability to predict PC and PCLM was verified by ROC curve. Conclusion: We demonstrated significant differences in intestinal microbiome composition between PC patients and healthy people, and found that Streptococcus is a potential biomarker for early prediction of PC and PCLM, which is critical for early diagnosis of diseases.

Gentamicin alleviates cholestatic liver injury by decreasing gut microbiota-associated bile salt hydrolase activity in rats.

Intrahepatic cholestasis lacks effective therapeutic drugs. The gut microbiota-associated bile salt hydrolases (BSH) may be a potential therapeutic target. In this study, oral administration of gentamicin (GEN) decreased the serum and hepatic levels of total bile acid in 17α-ethynylestradiol (EE)-induced cholestatic male rats, significantly improved the serum levels of hepatic biomarkers and reversed the histopathological changes in the liver. In healthy male rats, the serum and hepatic levels of total bile acid were also decreased by GEN, the ratio of primary to secondary bile acids, and conjugated to unconjugated bile acids was significantly increased, and the urinary excretion of total bile acid was elevated. 16S rDNA sequencing of the ileal contents revealed that GEN treatment substantially reduced the abundance of Lactobacillus and Bacteroides both of which expressed BSH. Consistently, BSH activity analysis by the generation of d5-chenodeoxycholic acid from d5-taurochenodeoxycholic acid in situ showed BSH was significantly inhibited in the ileal contents of rats treated with GEN. This finding led to an increased proportion of hydrophilic conjugated bile acids and facilitated the urinary excretion of total bile acids, thereby decreasing serum and hepatic total bile acids and reversing liver injury related to cholestasis. Our results provide important evidence that BSH can be a potential drug target for treating cholestasis.

Remnant Cholesterol and Common Carotid Artery Intima-Media Thickness in Community Population with Normal Low-Density Lipoprotein Cholesterol.

INTRODUCTION: Remnant cholesterol is a risk factor for cardiovascular disease, especially when low-density lipoprotein cholesterol (LDL-C) levels are normal. However, there are few studies on the relationship between remnant cholesterol and subclinical atherosclerosis. Common carotid artery intima-media thickness (cIMT) is an imaging marker of subclinical atherosclerosis. This study aimed to investigate the relationship between remnant cholesterol and cIMT in a community population with normal LDL-C. METHODS: This study is a retrospective analysis; 1,101 community population with available carotid artery imaging and fasting lipid data with LDL-C <4.1 mmol/L were included in this analysis. Remnant cholesterol was calculated as total cholesterol minus LDL-C minus high-density lipoprotein cholesterol. Abnormal cIMT was defined as maximum cIMT value ≥1 mm. Logistic regression was used to assess the relationships between remnant cholesterol levels and abnormal cIMT. RESULTS: As the remnant cholesterol level increased from the lowest to the highest quartile, the rate of abnormal cIMT increased from 24.5% to 38.6% (p trend <0.001) in the community population with normal LDL-C level. In the unadjusted model, the odds ratios (ORs, 95% confidence intervals) in the highest quartile group were 1.937 (1.338-2.803) for abnormal cIMT compared with the lowest quartile. The multivariable-adjusted ORs (95% confidence intervals) for the highest versus lowest quartile of remnant cholesterol were 2.132 (1.420-3.202) for abnormal cIMT. CONCLUSION: Elevated fasting remnant cholesterol levels were positively associated with abnormal cIMT in community population with normal LDL-C levels. Remnant cholesterol may be an important indicator of risk stratification in community population with normal LDL-C level.

Accentuated Hippo pathway and elevated miR-132 and miR-195a lead to changes of uteri and ovaries in offspring mice following prenatal exposure to vinclozolin.

Vinclozolin (VCZ) has been identified as a broad-spectrum fungicide and an environmental endocrine disruptor. Also, the Hippo signaling pathway controls organ size by regulating cell proliferation and apoptosis, and moreover, overexpression of microRNA-132 (miR-132) and microRNA-195 (miR-195) inhibits cell proliferation and promotes apoptosis. So, in this study, the experimental mice were orally given 400 mg/kg/day VCZ (suspended in corn oil) at gestational day 12-18, while those of the control group were fed with corn oil of equal volume. Then unilateral ovaries and mid-uteri were isolated from 10 randomly-selected mice at the postnatal 1st week (7 days), 3rd week (20-21 days), and 7th week (48-49 days) respectively to observe gene levels, while 6 of the contralateral ovaries and uteri were subsequently examined for proteins respectively. Besides, 16 from both groups were determined with serum estradiol (E2) at week 7, of which 6 were randomized for histological observation. Here we found the levels of E2 reduced in VCZ-group at week 7, with fewer follicles and injured endometrium. Meanwhile, in VCZ mice of all ages, increased miR-132 and miR-195a, decreased G protein-coupled estrogen receptor (GPER), elevated phosphorylated large tumor suppressor (pLATS) and phosphorylated yes-associated protein (pYAP), and decreased yes-associated protein (YAP) were observed in their ovaries and uteri. These findings suggested ovarian and uterine dysplasia in the offspring induced by gestational VCZ-exposure were mainly attributed to higher miR-132 and miR-195a and accentuated Hippo-pathway.

Uric acid accumulation in the kidney triggers mast cell degranulation and aggravates renal oxidative stress.

The accumulation of uric acid (UA) in the body can lead to the occurrence of hyperuricemia or uric acid nephropathy. Mast cells (MCs) increase oxidative stress and release renin to promote the production of Ang II. The aim of this study was to investigate the effect of UA on MCs in rat kidneys and the association between MCs and renal injury. Our results show that UA accumulation in the kidney stimulated the degranulation of MCs and the release of renin to promote Ang II production, resulting in renal oxidative stress, mitochondrial structural damage, and microvascular system damage. The expression of urate-related transporters was regulated by the UA level and serum urinary toxins levels were substantially elevated in hyperuricemia. Administration of the MCs membrane stabilizer sodium cromoglycate (SCG) or the angiotensin receptor antagonist Valsartan decreased the production of renin and Ang II and relieved renal oxidative stress, mitigated mitochondrial structural damage and microvascular system damage, and promoted the excretion of UA and urinary toxins by increasing the expression of urate-related transporters. These results demonstrate that the accumulation of UA in the kidney can trigger the degranulation of MCs and promote the development of renal oxidative stress. Administration of SCG and Valsartan ameliorated UA-induced renal injury by inhibiting MCs degranulation and reducing renal oxidative stress by inhibiting renin and Ang II production and accelerating renal clearance of UA and uremic toxins.

Characterization of the renal tubular transport of creatinine by activity-based protein profiling and transport kinetics.

Serum creatinine is widely used to adjust the dosing of drugs eliminated by the kidney in patients with renal dysfunction, as it is a readily accessible indicator of kidney function. However, there are many limitations for drug dosage adjustment based on serum creatinine levels, one of which is the limited understanding of creatinine's tubular transport. Thus, we aimed to complement and advance the renal tubular transport of creatinine by activity-based protein profiling (ABPP) and transporter-overexpression technology. Renal tubular transporters were not identified via ABPP due to the low-affinity interaction between transporters and creatinine. The uptake of isotopically labeled d3-creatinine was significantly increased in OCT2-overexpressing cell lines (p<0.01), and the Km and Vmax of d3-creatinine uptake mediated by OCT2 was 3.1 mM and 408 pmol/mg protein/min, respectively. In the OCT2-overexpressing cell lines, the IC50 of creatinine for d3-creatinine uptake was 10.3 mM, and that of the OCT2 inhibitor cimetidine for d3-creatinine uptake was 99.04 µM. Different dosages of creatinine did not affect the renal excretion of d3-creatinine in mice (p>0.05), while cimetidine significantly reduced the renal excretion of d3-creatinine (p<0.01) without affecting the glomerular filtration rate. Molecular docking in silico showed that the OCT2 amino acid GLN242 could form a hydrogen bond of 2.5 Å with creatinine, and there may be a π-π interaction between TYR362 and creatinine. A site mutation experiment demonstrated that TYR362 and GLN242 were important sites for the OCT2-creatinine interaction. These results demonstrate that OCT2 mediates the renal tubular secretion of creatinine with low affinity and is a minor contributor to creatinine secretion.

Construction and Evaluation of a Novel Organic Anion Transporter 1/3 CRISPR/Cas9 Double-Knockout Rat Model.

BACKGROUND: Organic anion transporter 1 (OAT1) and OAT3 have an overlapping spectrum of substrates such that one can exert a compensatory effect when the other is dysfunctional. As a result, the knockout of either OAT1 or OAT3 is not reflected in a change in the excretion of organic anionic substrates. To date, only the mOAT1 and mOAT3 individual knockout mouse models have been available. METHODS: In this study, we successfully generated a Slc22a6/Slc22a8 double-knockout (KO) rat model using CRISPR/Cas9 technology and evaluated its biological properties. RESULTS: The double-knockout rat model did not expression mRNA for rOAT1 or rOAT3 in the kidneys. Consistently, the renal excretion of p-aminohippuric acid (PAH), the classical substrate of OAT1/OAT3, was substantially decreased in the Slc22a6/Slc22a8 double-knockout rats. The relative mRNA level of Slco4c1 was up-regulated in KO rats. No renal pathological phenotype was evident. The renal elimination of the organic anionic drug furosemide was nearly abolished in the Slc22a6/Slc22a8 knockout rats, but elimination of the organic cationic drug metformin was hardly affected. CONCLUSIONS: These results demonstrate that this rat model is a useful tool for investigating the functions of OAT1/OAT3 in metabolic diseases, drug metabolism and pharmacokinetics, and OATs-mediated drug interactions.

'FLARE' of tumor marker in advanced gastric cancer treated with first-line systemic therapy.

Background: Transient tumor marker elevations caused by chemotherapy were defined as 'Flare' and have been demonstrated in some solid tumors. In clinical practice, we observed that some patients were accompanied by elevated tumor markers during treatment, but subsequent imaging proved that the treatment they received was effective. Objectives: We aimed to study the Flare and the prognosis in advanced gastric cancer. Design: This is an observational retrospective study. A total of 167 patients were enrolled in this study. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA125 values were obtained before the first, second, third, fourth, fifth and sixth cycles of treatment, respectively. Methods: Imaging for the first efficacy assessment was reviewed according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria. Kaplan-Meier analyses and log-rank tests were performed for overall survival (OS) analyses. Univariate and multivariate Cox analyses were used to determine the prognostic factor for OS and progression-free survival (PFS). Results: 37.1% of patients were accompanied with at least one tumor marker Flare during the course of treatment. The median time to tumor marker peak was 24-30 days and the Flare duration lasted 49-53 days. Patients with tumor markers Flare had a worse OS. Flare may be associated with the use of 5-fluorouracil. Baseline CEA and CA125 levels were the independent prognostic factors for OS and baseline CA125 level was the independent prognostic factor for PFS. Conclusion: Initial elevation of tumor markers during treatment is not an indication of tumor progression. Patients with tumor markers 'Flare' may had a worse OS.

A dynamic predictive nomogram of long-term survival in primary gastric lymphoma: a retrospective study.

BACKGROUND: Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma (NHL). Due to the rarity of the disease, it is important to create a predictive model that provides treatment and prognosis for patients with PGL and physicians. METHODS: A total of 8898 and 127 patients diagnosed with PGL were obtained from the SEER database and from our Cancer Center as training and validation cohorts, respectively. Univariate and multivariate Cox proportional hazards models were used to investigate independent risk factors for the construction of predictive survival nomograms, and a web nomogram was developed for the dynamic prediction of survival of patients with PGL. The concordance index (C-index), calibration plot, and receiver operating characteristics (ROC) curve were used to evaluate and validate the nomogram models. RESULTS: There were 8898 PGL patients in the SEER cohort, most of whom were married men over the age of 60, 16.1% of the primary tumors were localized in the antrum and pylori of the stomach, which was similar to the composition of 127 patients in the Chinese cohort, making both groups comparable. The Nomogram of overall survival (OS) was compiled based on eight variables, including age at diagnosis, sex, race, marital status, histology, stage, radiotherapy and chemotherapy. Cancer-specific survival (CSS) nomogram was developed with eight variables, including age at diagnosis, sex, marital status, primary tumor site, histology, stage, radiotherapy and chemotherapy. The C-index of OS prediction nomogram was 0.948 (95% CI: 0.901-0.995) in the validation cohort, the calibration plots showed an optimal match and a high area below the ROC curve (AUC) was observed in both training and validation sets. Also, we established the first web-based PGL survival rate calculator ( https://yangjinru.shinyapps.io/DynNomapp/ ). CONCLUSION: The web dynamic nomogram provided an insightful and applicable tool for evaluating PGL prognosis in OS and CSS, and can effectively guide individual treatment and monitoring.

Relationship between obesity indicators and hypertension-diabetes comorbidity among adults: a population study from Central China.

OBJECTIVE: To identify the relationship between obesity indicators and hypertension-diabetes comorbidity (HDC) among adults in central China. DESIGN AND SETTING: A cross-sectional study was conducted from 1 June 2015 to 30 September 2018 in 11 districts of Hubei Province, China. PARTICIPANTS: A total of 29 396 participants aged 18 years or above were enrolled in the study. 2083 subjects with missing data were excluded. Eventually, 25 356 participants were available for the present analysis. MAIN OUTCOME MEASURES: Data were subjected to univariable and multivariable logistic regression to examine the association between obesity indicators (body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR)) and HDC prevalence. Crude odds ratio and adjusted OR (AOR) with associated 95% CI were calculated. RESULTS: Overall, 2.8% of the respondents had HDC. The odds of HDC prevalence increased with the BMI of the participants (18.5≤BMI (kg/m2)≤23.9-1; 24≤BMI (kg/m2)≤26.9-AOR: 5.66, 95% CI: 4.25 to 7.55; BMI (kg/m2)≥27-AOR: 7.96, 95% CI: 5.83 to 10.87). The risk of HDC also increased with the WHtR of participants (WHtR≤P25-1; P25≤WHtR≤P50-AOR: 1.73, 95% CI: 1.10 to 2.71; P50 ≤WHtR≤P75-AOR: 2.51, 95% CI: 1.60 to 3.92; WHtR≥P75-AOR: 3.22, 95% CI: 2.01 to 5.16). Stratified analysis by gender showed that high BMI and WHtR were risk factors of HDC in males and females. However, the odds of HDC prevalence increased only when WHtR≥P75 in males, whereas the probability of HDC increased when WHtR≥ P25 in females. CONCLUSION: High BMI and WHtR can increase the risk of HDC among Chinese adults. Reasonable control of BMI and WHtR may be beneficial in preventing HDC. Females should focus on maintaining an optimal WHtR earlier.

Current status of neoadjuvant therapy for locally advanced rectal cancer in Wuhan Union Hospital Cancer Center.

BACKGROUND: To analyze and explore the evolution and short-term efficacy of neoadjuvant therapy for patients with mid and low LARC in Wuhan Union Hospital Cancer Center. METHODS: Patients diagnosed with rectal cancer from January 2015 to December 2021 were collected. The treatment patterns, short-term efficacy and treatment-related adverse events (AEs) of mid and low LARC patients who received neoadjuvant therapy were analyzed. The Chi-square test was used to compare the differences between groups. RESULTS: A total of 980 patients with mid and low LARC were enrolled, over time, the proportion of patients receiving neoadjuvant therapy gradually increased, and the treatment mode of direct surgery after diagnosis was gradually watered down. More than 80% of the patients implemented radiotherapy-based neoadjuvant therapy, and the proportion of patients receiving SCRT sequential systemic therapy gradually exceeded that of LCRT combined chemotherapy after 2020. Of all patients who completed radiotherapy and underwent surgery, 170 patients received long-course chemoradiotherapy (LCRT) combined with chemotherapy (Group C) and 98 patients received short-course radiotherapy (SCRT) combined with systemic therapy (chemotherapy with or without immunotherapy) (Group D). The pathological complete response (pCR) rate in Group D was significantly higher than that in Group C (38.8% vs. 19.4%, P = 0.001). The pCR rate in the SCRT plus immunotherapy group was better than that in the group without immunotherapy (49.2% vs. 21.6%, P = 0.007). 82.3% of the patients receiving immunotherapy were treated with SCRT sequential 2-cycle CapOX plus Camrelizumab treatment, and the pCR was as high as 52.9%. Immunotherapy did not increase the incidence of Grade 3-4 AEs. CONCLUSIONS: Neoadjuvant therapy based on radiotherapy is becoming used in patients with mid and low LARC. SCRT sequential systemic therapy is increasingly widely used in LARC patients in our center. Compared with the traditional LCRT or SCRT sequential chemotherapy, SCRT sequential chemotherapy plus immunotherapy has a remarkable pCR rate and manageable toxicity. Looking forward this new treatment mode will bring lasting survival benefits to patients.

The prognostic value of baseline hematological parameters of peripheral blood in metastatic gastric cancer treated with apatinib.

Background: There is strong evidence that apatinib is effective in the treatment of third- or later-line advanced metastatic gastric cancer (mGC). Hematology prediction index is a convenient and cheap method to predict the prognosis of disease. However, the prognosis of baseline hematological parameters of peripheral blood, such as neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen 125 (CA125) and albumin (ALB) on mGC treated with apatinib have not been identified. Methods: We retrospectively analyzed mGC received apatinib between 1 January 2014 and 30 June 2021. Survival analyses were performed using the Kaplan-Meier method and Cox-proportional hazards model. Results: A total of 117 patients were included in this study. The cutoff value of NLR, CA125 and ALB was 2.25, 19.24 U/ml and 37.60 g/L, respectively. The disease control rates (DCR) in the high and low NLR groups were 52.94% and 73.47% (P=0.024); 48.28% and 74.58% (P=0.003) in high and low CA125 groups; 72.97% and 41.86% (P=0.001) in high and low ALB groups. By survival analysis, increasing NLR (P=0.003), CA125 (P<0.001) and decreasing ALB (P<0.001) predicted a shorter PFS after apatinib. NLR (P=0.015), CA125 (P=0.004) and ALB (P=0.005) were significantly predictors for PFS in mGC treated with aptinib. Conclusion: Increasing NLR, CA125 and decreasing ALB were associated with poorer clinical efficiency and prognosis after apatinib treatment.

Compared hand hygiene compliance among healthcare providers before and after the COVID-19 pandemic: A rapid review and meta-analysis.

BACKGROUND: Hand hygiene (HH) is a cost-effective measure to reduce health care-associated infections. The overall characteristics and changes of hand hygiene compliance (HHC) among health care providers during the COVID-19 pandemic provided evidence for targeted HH intervention measures. AIM: To systematically review the literature and conduct a meta-analysis of studies investigating the rate of HHC and the characteristics of HH during the COVID-19 pandemic. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang Data, VIP, and CBM databases were searched. All the original articles with valid HHC data among health care providers during the COVID-19 pandemic (from January 1, 2020 to October 1, 2021) were included. Meta-analysis was performed using a DerSimonian and Laird model to yield a point estimate and a 95% CI for the HHC rate. The heterogeneity of the studies was evaluated using the Cochrane Q test and I2 statistics and a random-effects model was used to contrast between different occupations, the WHO 5-moments of HH and different observation methods. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. FINDINGS: Seven studies with 2,377 health care providers reporting HHC were identified. The estimated overall HHC was 74%, which was higher than that reported in previous studies (5%-89%). Fever clinic has become a new key place for HHC observation. Nurses had the highest HHC (80%; 95% CI:74%-87%) while auxiliary workers (70%; 95%CI:62%-77%) had the lowest. For the WHO 5-moments, the health care providers had the highest HHC after contact with the body fluids of the patients (91%; 95% CI:88%-94%), while before contact with patient's health care providers had the lowest HHC (68%; 95% CI:62%-74%) which was consistent with before the pandemic. There existed great HHC differences among different monitoring methods (automatic monitoring system:53%; 95% CI:44%-63% versus openly and secretly observation: 91%; 95% CI: 90%-91%). CONCLUSIONS: During the COVID-19 pandemic, the compliance of health care providers' HH showed a great improvement. The fever clinics have become the focused departments for HH monitoring. The HHC of auxiliary workers and the HH opportunity for "before contact with patients" should be strengthened. In the future, it will be necessary to develop standardized HH monitoring tools for practical work.

Prediction of central compartment nodal metastases in papillary thyroid cancer using TI-RADS score, blood flow, and multifocality.

BACKGROUND: The relationship between the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the risk of lymph node metastases in papillary thyroid cancer (PTC) could improve the detection rate of lymph node metastases in thyroid cancer and provide a scientific basis for clinical diagnosis. PURPOSE: To evaluate the risk of lymph node metastases of PTC associated with the score from ACR TI-RADS adjusted for other correlative factors. MATERIAL AND METHODS: A total of 560 patients with pathologically confirmed PTC were included in the study and classified into a metastases group and a non-metastases group. Clinical and pathological manifestations of the patients were collected. RESULTS: The median TI-RADS score was 13 (p25-p75 = 11-14) among the patients with lymph node metastases, higher than those without metastases 9 (8-10) (P < 0.001). Multiple logistic regression indicated that TI-RADS score (odds ratio [OR] = 2.204), male sex (OR = 2.376), multifocality (OR = 4.170), and rich blood flow (OR = 3.656) were risk factors for lymph node metastases in patients with thyroid carcinoma. Some related factors such as TI-RADS score, age(<45years old), male, multifocality and rich blood flow were related to lymph node metastases in the central area of the neck which could provide therapeutic strategy for further treatment. CONCLUSION: it is not just the TI-RADS score but also multifocality, blood flow, and sex that influence the prediction of the risk of PTC central lymph node metastases.