Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.

Brentuximab Vedotin Monotherapy and Combined with Low Dose Donor Lymphocyte Infusion to Control Minimal Residual Disease and Sustain Clinical Remission in a Child with Relapsed Anaplastic Large Cell Lymphoma

Minimal residual disease (MRD) appears to have a strong negative predictive value for disease recurrence in children with anaplastic large cell lymphoma (ALCL). Brentuximab vedotin (BV) can be a therapeutic option for MRD-positive patients to achieve molecular remission and to decrease risk of subsequent relapse. We here report a 4-year-old child with ALCL progression during relapse treatment who received BV as a bridging therapy before haploidentical hematopoietic stem-cell transplantation, and as a maintenance therapy post-transplant alone or combined with simultaneous low dose donor-lymphocyte infusions. MRD monitoring showed a complete molecular response and reflected both BV efficiency and graft-versus-lymphoma effect.

Application of donor dendric cell mediated recipieut lymphocyte reaction after related kidney transplantation in individualized immunosuppressive therapy

Objective To explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells ( Dcs) in renal allograft recipients to guide individualized immunosuppressive therapy. Methods From Jan. 2008 to Jan. 2010,30 recipients received living related kidney transplantation were successively and divided into

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

Impact of Regular Blood Donation on Body Iron Stores at Saudi Blood Donors

Introduction: One of the most frequent observations in long-term blood donation is chronic iron deficiency, which can develop into anaemia. The majority of blood screening methods employed by blood banks do not incorporate iron-status markers, which may result in potential subclinical iron deficiency. The aim of this study was to evaluate the effects of repeated blood donation on the levels of iron in the body and to guide blood donors in preventing the depletion of iron stores. Methods: Regular blood donors were categorised into distinct groups according to the number of donations they gave, and then the correlation between these groups and their bodies’ iron levels was examined. Different parameters were employed to identify iron deficiency and iron depletion in blood donors: serum ferritin, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total iron-binding capacity (TIBC), and serum iron. Results: The study included 300 individuals who regularly and willingly donated blood. There were no iron insufficiency cases among those donating blood for the first time (Group I). However, 15.5% of individuals who had donated once before (Group II) had ferritin levels of 15 - 30 μg/dl (ng/ml), indicating reduced iron stores. The rate increased to 18% (37 out of 206 individuals) among regular blood donors (Groups III, IV, and V). Iron deficiency (depletion) prevalence among regular blood donors in Groups III, IV, and V was 5.9% (12 out of 206) and 50.4% (100 out of 206). Donors who had donated blood most frequently had the lowest levels of haematological markers MCH, MCHC, and TIBC. Provide the p-values representing the differences between the means of MCV, MCH, iron, TIBC, and ferritin levels when comparing donor groups with the control group (Group I) based on the frequency of donations. Indicate statistically significant differences where the p-value is less than 0.0125. This significance level is adjusted based on the Bonferroni method, considering multiple independent tests. The result shows that the Iron parameter for the comparison between Group I and Group III and Group I and Group IV suggests a statistically significant difference in iron levels between these donor groups. Conclusion: The findings of this study show that a higher times of donations lads to a higher occurrence of depleted iron stores and subsequent erythropoiesis with iron deficiency by one donor from every three healthy donors. The iron and ferritin concentrations were within the normal range in group one (Control group) and reduced in the other four groups (G-2 to G-5). However, the level of haemoglobin remained within an acceptable range for blood donation. This outcome suggests that it may be necessary to reassess the criteria for accepting blood donors. The average serum ferritin levels were examined in all five groups (G-1 to G-5), both for males and females, and significant variations were seen among the groups under study. This study found that 35% of the individuals who regularly donate blood have iron-deficient anaemia (sideropenia). This suggests that it would be beneficial to test for serum ferritin at an earlier stage, ideally after three donations.

T lymphocyte proportion in Alzheimer’s disease prognosis

Bai et al investigate the predictive value of T lymphocyte proportion in Alzheimer's disease(AD)prognosis.Through a retrospective study involving 62 AD patients,they found that a decrease in T lymphocyte proportion correlated with a poorer prognosis,as indicated by higher modified Rankin scale scores.While the study highlights the potential of T lymphocyte proportion as a prognostic marker,it suggests the need for larger,multicenter studies to enhance generalizability and validity.Additionally,future research could use cognitive exams when evaluating prognosis and delve into immune mechanisms underlying AD progression.Despite limitations inherent in retrospective designs,Bai et al's work contributes to understanding the immune system's role in AD prognosis,paving the way for further exploration in this under-researched area.

Reasons and effects of the decline of willing related potential living kidney donors

BACKGROUND Although the availability of related living donors(LDs)provides a better chance for receiving kidney transplantation(KT),the evaluation protocols for LD selection remain a safeguard for the LD’s safety.These protocols are variable from one center to another,resulting in variable rates of decline of the potential LDs(PLDs).The decline of willing PLDs may occur at any stage of evaluation,starting from the initial contact and counseling to the day of operation.AIM To identify the causes of the decline of PLDs,the predictors of PLD candidacy,and the effect on achieving LDKT.METHODS A retrospective study was performed on the willing PLDs who attended our outpatient clinic for kidney donation to their related potential recipients between October 2015 and December 2022.The variables influencing their candidacy rate and the fate of their potential recipients were studied.Two groups of PLDs were compared:Candidate PLDs after a completed evaluation vs non-candidate PLDs with a complete or incomplete evaluation.A multivariate logistic regression was performed to assess the factors contributing to the achievement of PLD candidacy.RESULTS Of 321 willing PLDs,257 PLDs(80.1%)accessed the evaluation to variable extents for 212 potential recipients,with a mean age(range)of 40.5±10.4(18-65)years,including 169 females(65.8%).The remaining 64 PLDs(19.9%)did not access the evaluation.Only 58 PLDs(18.1%)succeeded in donating,but 199 PDLs(62.0%)were declined;exclusion occurred in 144 PLDs(56.0%)for immunological causes(37.5%),medical causes(54.9%),combined causes(9.7%),and financial causes(2.1%).Regression and release occurred in 55 PLDs(17.1%).The potential recipients with candidate PLDs were not significantly different from those with non-candidate PLDs,except in age(P=0.041),rates of completed evaluation,and exclusion of PLDs(P<0.001).There were no factors that independently influenced the rate of PLD candidacy.Most patients who failed to have KT after the decline of their PLDs remained on hemodialysis for 6 mo to 6 years.CONCLUSION The rate of decline of willing related PLDs was high due to medical or immunological contraindications,release,or regression of PLDs.It reduced the chances of high percentages of potential recipients in LDKT.

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

Robotic surgery and liver transplantation:A single-center experience of 501 robotic donor hepatectomies

Background:Over the past two decades robotic surgery has been introduced to many areas including liver surgery.Laparoscopic liver surgery is an alternative minimally invasive approach.However,moving on to the complexity of living donor hepatectomies,the advantages of robotic versus laparoscopic approach have convinced us to establish the robotic platform as a standard for living donor hepatectomy.Methods:From November 2018 to January 2022,501 fully robotic donor hepatectomies,including 177 left lateral donor lobes,112 full left lobes and 212 full right lobes were performed.Grafts were donated to 296 adult recipients and 205 pediatric recipients.Donor age,sex,body weight,body mass index(BMI),graft weight,graft to body weight ratio(GBWR),operative time,blood loss,first warm ischemic time,pain score,length of intensive care unit(ICU)stay and hospital stay,and complications were retrospectively analyzed based on a prospectively kept database.Recipients were evaluated for graft and patient survival,age,sex,BMI,body weight,model of end-stage liver disease score,blood loss,transfusions,operative time,cold ischemic time,length of hospital stay and complications.Results:There was no donor mortality.Two cases needed to be converted to open surgery.The median blood loss was 60 mL(range 20-800),median donor operative time was 6.77 h(range 2.93-11.53),median length of hospital stay was 4 days(range 2-22).Complication rate in donors classified following ClavienDindo was 6.4%(n=32)with one grade Ⅲ complication.Three-year actual recipient overall survival was 91.4%;87.5% for adult recipients and 97.1% for pediatric recipients.Three-year actual graft overall survival was 90.6%;87.5% for adult recipients and 95.1% for pediatric recipients.In-hospital mortality was 6%,9.1%(27/296)for adult recipients and 1.4%(3/205)for pediatric recipients.The recipients’morbidity was 19.8%(n=99).Twenty-eight recipients(5.6%)had biliary and 22(4.4%)vascular complications.Six(12.0%)recipients needed to be re-transplanted.Conclusions:With growing experience it is nowadays possible to perform any donor hepatectomy by robotic approach regardless of anatomical variations and graft size.Donor morbidity and quality for life results are encouraging and should motivate other transplant centers with interest in minimally invasive donor surgery to adopt this robotic technique.

Correlation of neutrophil to lymphocyte ratio to severity of coronary artery disease and in-hospital clinical outcomes in patients with acute coronary syndrome: A prospective observational study

Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.

The prediction of donor number and acceptor number of electrolyte solvent molecules based on machine learning

Electrolyte solvents have a critical impact on the design of high performance and safe batteries.Gutmann's donor number(DN) and acceptor number(AN) values are two important parameters to screen and design superior electrolyte solvents. However, it is more time-consuming and expensive to obtain DN and AN values through experimental measurements. Therefore, it is essential to develop a method to predict DN and AN values. This paper presented the prediction models for DN and AN based on molecular structure descriptors of solvents, using four machine learning algorithms such as Cat Boost(Categorical Boosting), GBRT(Gradient Boosting Regression Tree), RF(Random Forest) and RR(Ridge Regression).The results showed that the DN and AN prediction models based on Cat Boost algorithm possesses satisfactory prediction ability, with R^(2) values of the testing set are 0.860 and 0.96. Moreover, the study analyzed the molecular structure parameters that impact DN and AN. The results indicated that TDB02m(3D Topological distance based descriptors-lag 2 weighted by mass) had a significant effect on DN, while HATS1s(leverage-weighted autocorrelation of lag 1/weighted by I-state) plays an important role in AN. The work provided an efficient approach for accurately predicting DN and AN values, which is useful for screening and designing electrolyte solvents.

Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.

Perceptions of Mothers with Preterm Babies towards Donor Breast Milk at Women and Newborn Hospital,Lusaka Zambia

Breast milk offers essential nutrients crucial for the development of the preterm immune system, thus reducing the incidence of infection and mortality often associated with prematurity. In the absence of breast milk, the preferred option is donated breast milk, the best alternative for hospitalized neonates whose mothers have insufficient breast milk or are unavailable. In Zambia, donor breast milk is unavailable. Instead, the protocol recommends the administration of formula milk. However, the use of formula milk in preterm babies is associated with an increased risk of necrotizing enterocolitis and sepsis. Zambia needs to establish a donor milk bank, hence the need to understand the perception of mothers towards donated breast milk. A qualitative descriptive case study utilized 10 focus group discussions with in-depth interviews, purposively selected using a variation strategy. Data was thematically analysed. Participants demonstrated potential acceptance to donor breast milk utilization, as more nutritional compared to formula despite lack of awareness. Concerns related to safety, quality, fear of disease transmission and discomfort feeding from a different bloodline were identified as hinderance to possible utilisation. These perceptions underscore the importance of educational initiatives aimed at dispelling myths and misconceptions surrounding donor breast milk and establishing donor breast milk programs. Therefore, the study recommends educational initiatives tailored to raise awareness to mothers about donor breast milk.

High donor-number and low content electrolyte additive for stabilizing zinc metal anode

The aqueous zinc ion batteries(AZIBs)are thought as promising competitors for electrochemical energy storage,though their wide application is curbed by the uncontrollable dendrite growth and gas evolution side reactions.Herein,to stabilize both zinc anodes and water molecules,we developed a modified electrolyte by adding a trace amount of N,N-diethylformanmide(DEF)into the ZnSO_(4)electrolyte for the first time in zinc ion batteries.The effectiveness of DEF is predicted by the comparison of donor number and its preferential adsorption behavior on the zinc anode is further demonstrated by several spectroscopy characterizations,electrochemical methods,and molecular dynamics simulation.The modified electrolyte with 5%v.t.DEF content can ensure a stable cycling life longer than 3400 h of Zn‖Zn symmetric cells and an ultra-reversible Zn stripping/plating process with a high coulombic efficiency of 99.7%.The Zn‖VO_(2)full cell maintains a capacity retention of 83.5%and a 104 mA h g^(-1)mass capacity after 1000cycles.This work provides insights into the role of interfacial adsorption behavior and the donor number of additive molecules in designing low-content and effective aqueous electrolytes.

Quality of Life in Living Kidney Donors Grenoble Teaching Hospital (France)

Context: Kidney transplantation is today the standard treatment for patients suffering from chronic end-stage renal failure. Living kidney donation offers many advantages for the recipient, but requires a subject without comorbidities to undergo surgery. The aim of this study was to assess the quality of life and psychosocial experience of living kidney donors after donation. Methods: This was a cross-sectional study with an analytical aim, involving living kidney donors during the period from January 2016 to April 2019 at CHUGA. (University Hospital Center of Grenoble Alpes in France). Results: Our study shows that out of 88 donors, 70 responded to our questionnaires, representing a prevalence of 80.5%. The average age of our donors was 55.6 years with a female predominance. Seven out of eight domains of the SF36 score had a good quality of life after donation and the donation did not alter their psychosocial experience. The majority of our donors expressed their pride and enthusiasm, did not regret having saved a life, and this experience was considered positive. Conclusion: Kidney donation does not have a negative impact on quality of life and psychosocial life. The majority of donors do not regret their donation. The dissemination of such results could make it possible to increase the number of kidney transplants from living donors in France, especially in our African countries where the management of ESRD remains a real public health problem.

Seroprevalence of Human Immunodeficiency Virus and Hepatitis B in Blood Donors at the N’Zérékoré Regional Blood Transfusion Centre in Guinea

Blood transfusion saves lives and reduces morbidity and mortality for a large number of diseases and clinical conditions, but it is not without danger. The aim of this study was to determine the seroprevalence of HIV and hepatitis B in blood donors received at the regional Blood Transfusion Centre of N’Zérékoré (Guinea). This was a 5-year retrospective analytical study. We included records of blood donors aged 18 to 60 years admitted to the N’Zérékoré Regional Blood Transfusion Centre for blood donation from January 2016 to December 2020. We performed a descriptive analysis followed by Chi-2 or Fish-er-exact tests and the Student or Wilcoxon test, followed by multivariate logistic regression. In this study, donor age ranged from 18 - 60 years, with a pre-dominance of donors aged 25 - 34 (44.2%). Male donors were the most represented in our study (79.0% versus 21.0% female). More than half of the donors were blood group O (55.6%). We observed a seroprevalence of 3.6% for HIV, 13.4% for HBsAg and 0.2% for co-infection. In our series, age 25 - 34 (OR = 1.89 and P = 0.001) and 35 - 44 for HIV (OR = 2.01 and P = 0.001), HBsAgserostatus (OR = 3.04 and P = 0.001) and blood donation history (OR of 3.04 and P = 0.001) were factors associated with HIV positivity (P < 0.05). In our study, HIV serostatus (OR = 3.04 and P = 0.001) and blood donation history (OR = 0.01 and P = 0.001) were factors associated with HBsAgseropositivity. We reported a high prevalence of HIV and HBsAg. Sex, serological status and blood donation history were associated factors.

Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

Predictive Value of the Neutrophil to Lymphocyte Ratio (NLR) to Predict the Development of Preeclampsia and Pregnancy Induced Hypertension at 1st Trimester

Introduction: Hypertensive disorder in pregnancy affects 4 to 6 percent of all pregnancies and carries risks for the both baby and the mother. Only a few groups of women who are at high-risk pregnancies are received prophylaxis Aspirin, more than 15 percent of women develop pre-eclampsia with a single minor risk factor. Methods: This descriptive cross-sectional study was conducted to compare the 1st trimester NLR value of normotensive, pregnancy induced hypertensive and pre-eclamptic pregnant women. The study was conducted with a sample of 416, antenatal patients who were admitted to ward 25, at Colombo North Teaching Hospital Ragama. Data was collected as separated three groups. NLR value was calculated separately and ANOVA test was used to analyze the 3 categorical data. Post HOC test was done to assess the multiple comparison. Results: The prevalence rates of pregnancy induced hypertension and pre-eclampsia among the pregnant women were 8.6% and 5.7%. The mean NLR values of normotensive group was 2.708, pregnancy induced hypertensive group was 2.650 and pre eclamptic group was 3.789. There was a significant difference in NLR value between pre eclamptic group and other two groups with P value of Conclusion: The 1st trimester NLR value of pre eclamptic patients significantly increased compared to normotensive women.

Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.