Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychoso...Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.展开更多
Objectives This study aimed to analyze the prevalence of long-term central line-associated bloodstream infections(CLABSI)among hospitalized adults with cancer in Italy and compare the characteristics of patients who r...Objectives This study aimed to analyze the prevalence of long-term central line-associated bloodstream infections(CLABSI)among hospitalized adults with cancer in Italy and compare the characteristics of patients who required long-term central venous access device(LCVAD)substitution due to prior CLABSI with those who had never experienced CLABSI.Methods The study was conducted in hospitals across northern and central Italy using a multicenter,observational,cross-sectional design from March to September 2021.A total of 174 adults with cancer were included.Data were collected through electronic case report forms,including demographic,clinical,treatment-related,and catheter-related variables.Propensity score matching(PSM)was used to compare the characteristics of patients who underwent LCVAD substitution due to previous CLABSI with those who never experienced CLABSI.Multiple correspondence analysis(MCA)was conducted to explore the patterns within matched subgroups.Results The prevalence of CLABSI was 3%,and 5.2%of patients required LCVAD substitution due to prior CLABSI.After applying PSM,the groups were successfully balanced for sex,age,presence of metastases,comorbidities,BMI,received treatments,corticosteroid therapy,ongoing antibiotics,hormone therapy,type of LCVAD,lumens,and utilization frequency.Hematologic cancer was more frequent in the CLABSI group(44.4%)compared to the non-infective group(0),with a statistically significant difference(P=0.045).MCA revealed potential patterns among matched subgroups but did not identify statistically significant associations:patients with previous LCVAD substitution were more frequently associated with a history of prior infections,ongoing antibiotic therapy,and unspecified primary lesion locations;conversely,patients who never experienced CLABSI tended to cluster around characteristics such as hormone therapy and corticosteroid therapy.Conclusions These findings emphasize the importance of continuous monitoring,individualized infection prevention strategies in oncology nursing practice.Future research with larger datasets is needed to validate these findings and develop tailored interventions to reduce CLABSI risks.展开更多
Living donor kidney transplantation(LDKT)has evolved into a globally adopted clinical practice,driven by improvements in donor selection,immunological compatibility,and perioperative care.These advances have contribut...Living donor kidney transplantation(LDKT)has evolved into a globally adopted clinical practice,driven by improvements in donor selection,immunological compatibility,and perioperative care.These advances have contributed to enhanced donor safety and improved early graft outcomes.Still,its uptake remains limited worldwide,influenced by differences in clinical infrastructure,surgical expertise,and programmatic priorities.A central procedural consideration in LDKT is the choice of kidney for procurement,right or left.Left donor nephrectomy is generally preferred due to favorable vascular anatomy,yet right-sided procurement is often necessary in the presence of anatomical variations.While some studies report higher rates of early complications with right-sided nephrectomy,including delayed graft function and early graft loss,long-term outcomes appear comparable.The evaluation of laterality,however,varies significantly across centers and is often shaped more by institutional practice than by comparative evidence.In this editorial,we review key clinical and technical advances that have improved the safety and outcomes of LDKT,including immunological matching,donor selection,perioperative strategies,and early graft performance.We then critically examine the role of kidney laterality in donor nephrectomy,highlighting how anatomical complexity and procedural risk continue to shape clinical decision-making.展开更多
Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given th...Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.展开更多
Cardiovascular complications remain a leading cause of morbidity and mortality in liver transplantation(LT),exposing the limitations of current risk assessment strategies.YKL-40,a glycoprotein involved in inflammation...Cardiovascular complications remain a leading cause of morbidity and mortality in liver transplantation(LT),exposing the limitations of current risk assessment strategies.YKL-40,a glycoprotein involved in inflammation,endothelial dysfunction,and fibrotic remodeling,has emerged as a biomarker associated with adverse cardiovascular outcomes and liver disease severity.Its inclusion in structured cardiovascular assessment frameworks may improve transplantspecific risk scores and support earlier identification of high-risk LT recipients.Mechanistically,YKL-40 contributes to vascular injury and myocardial dysfunction via nuclear factor-κB and STAT3 signaling,and is under investigation as a biomarker in preclinical studies aimed at cardiovascular risk modulation in LT.Integration of YKL-40 into predictive models,particularly those supported by artificial intelligence,may enhance individualized perioperative decision-making.This editorial outlines translational directions for integrating YKL-40 into cardiovascular risk models and therapeutic research,supporting its clinical adoption in precision-guided LT care.展开更多
Hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT)presents a significant challenge,with recurrence rates ranging from 8%to 20%globally.Current biomarkers,such as alpha-fetoprotein(AFP)and des-gamm...Hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT)presents a significant challenge,with recurrence rates ranging from 8%to 20%globally.Current biomarkers,such as alpha-fetoprotein(AFP)and des-gamma-carboxy prothrombin(DCP),lack specificity,limiting their utility in risk strati-fication.YKL-40,a glycoprotein involved in extracellular matrix remodeling,hepatic stellate cell activation,and immune modulation,has emerged as a promising biomarker for post-LT surveillance.Elevated serum levels of YKL-40 are associated with advanced liver disease,tumor progression,and poorer post-LT outcomes,highlighting its potential to address gaps in early detection and personalized management of HCC recurrence.This manuscript synthesizes clinical and mechanistic evidence to evaluate YKL-40’s predictive utility in post-LT care.While preliminary findings demonstrate its specificity for liver-related pathologies,challenges remain,including assay standardization,lack of pro-spective validation,and the need to distinguish between malignant and non-malignant causes of elevated levels.Integrating YKL-40 into multi-biomarker panels with AFP and DCP could enhance predictive accuracy and enable tailored therapeutic strategies.Future research should focus on multicenter studies to validate YKL-40’s clinical utility,address confounding factors like graft rejection and systemic inflammation,and explore its role in predictive models driven by emerging technologies such as artificial intelligence.YKL-40 holds transformative potential in reshaping post-LT care through precision medicine,providing a pathway for better outcomes and improved management of high-risk LT recipients.展开更多
Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
BACKGROUND Heart transplantation is the last and best option for end-stage heart failure management.Early mortality rates have significantly decreased,enabling patients to survive longer with fewer complications,a tre...BACKGROUND Heart transplantation is the last and best option for end-stage heart failure management.Early mortality rates have significantly decreased,enabling patients to survive longer with fewer complications,a trend observed even in our setting.The primary shared challenge has centered on achieving surgical success and immediate survival.The question arises about the medium-and long-term survival of patients with heart transplant in Mexico.AIM To present the results of the medium and long-term follow-up of heart transplant patients.METHODS This was a retrospective study of a single medical unit,and we selected patients who received heart transplants from July 21,1988 to September 30,2023.Selection criteria encompassed age,sex,and primary indication for heart transplantation across all groups.Patients with incomplete information or who died within 30 postoperative days were excluded.Data of primary pathology,ischemic,extracorporeal circulation,aortic cross-clamping times,length of ventilatory support,stay in postoperative therapy,hospitalization,and functional class were analyzed.RESULTS The causes of morbidity,mortality,and percentage of survival at 1,5,and 10 years were examined.Overall,257 heart transplants were performed during the study period.Of the total cases,22 with incomplete data and 47 who died within 30 postoperative days were excluded for the middle-and long-term survival analyses.Of the remaining 188 patients,heart transplantation was performed(males:146,females:42).The average age of the participants was 44.43±14.48 years.The primary indications included ischemic cardiomyopathy(42.55%)and dilated cardiomyopathy(39.36%).The mean durations of mechanical ventilator support,intensive care stay,and hospital stay were 57.55±103.50 hours,9.96±8.59 days,and 19.49±18.23 days,respectively.One-,five-,and ten-year survival rates were 90.7%,71.3%,and 60.3%,respectively.Of the patients,94%and 6%were in functional classes I and II,respectively.Infection and neurological hemorrhagic or ischemic stroke(26%)were the main causes of mortality in the first year.Subsequently,chronic rejection manifesting as graft vasculopathy increased in frequency(30%).CONCLUSION In our setting,heart transplantation yields medium-and long-term survival and quality of life outcomes comparable to those achieved by other international centers.展开更多
Background: Pediatric brain tumors (PBT) are among the most common childhood neoplasms worldwide, but their management in low- and middle-income countries (LMICs) remains under-documented. Limited access to specialize...Background: Pediatric brain tumors (PBT) are among the most common childhood neoplasms worldwide, but their management in low- and middle-income countries (LMICs) remains under-documented. Limited access to specialized care, diagnostic tools, and adjuvant therapies poses significant challenges in sub-Saharan Africa, including Togo. Objective: This study reviews the management of pediatric brain tumors in Togo. Methods: We conducted a retrospective study in the neurosurgery department at Sylvanus Olympio Teaching Hospital between November 2017 and December 2022. Demographic, clinical, radiographic, operative, pathology, and outcome data were collected and analyzed. Results: Eighteen patients had histologically verified brain tumors. Ages ranged from 1 to 15 years (mean: 7.73 ± 4.28), with a sex ratio of 1. Symptoms of raised intracranial pressure were present in 83.4% of cases. The mean interval to presentation was 22 ± 5.32 months. Tumors were supratentorial in 66.7% of cases. Total tumor removal was achieved in 61.1%. Astrocytoma was the most common histological diagnosis, followed by ependymoma and medulloblastoma. Five patients (27.8%) died within the first month post-surgery. The estimated 5-year survival rate was 43% ± 5.4%. Conclusion: Delayed diagnosis, insufficient infrastructure, and limited access to radiotherapy and chemotherapy contribute to poor outcomes. Improving neurosurgical capacity, infrastructure, and financial support could enhance survival and outcomes for pediatric brain tumor patients in Togo.展开更多
Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prom...Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.展开更多
BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metasta...BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.展开更多
Objective:Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide.The identification of new simple,inexpensive and highly accurate markers for HCC diagnosis and screening is needed.This case-control...Objective:Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide.The identification of new simple,inexpensive and highly accurate markers for HCC diagnosis and screening is needed.This case-control study evaluates the role of annexin A2 and voltage-gated calcium channelsα2δ1 subunit as serum biomarkers for HCC diagnosis.Methods:The study comprised three groups:group 1,50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection;group 2,25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC;and group 3,15 healthy controls.All participants were subjected to clinical and laboratory investigations,and radiological scanning.The serum levels of alpha-fetoprotein(AFP),annexin A2,and theα2δ1 subunit were evaluated by using ELISA technique.Results:The serum levels of annexin A2 significantly increased in patients with HCC(10.4±2.5 ng/m L;P<0.001)or with cirrhosis(9.31±1.8 ng/m L;P<0.001)comparing to that of healthy controls(0.296±0.09 ng/m L).However,there was no significant difference in serum annexin A2 levels in patients with HCC comparing to those with cirrhosis.Serumα2δ1 subunit significantly increased in patients with HCC(20.12±3.7 ng/m L)comparing to that in patients with cirrhosis(10.41±3.4 ng/m L,P<0.001)and healthy controls(10.2±2.9 ng/m L,P<0.001).Conclusions:The serumα2δ1 subunit may function as a new biomarker for HCC diagnosis.Conversely,serum annexin A2 has low diagnostic value as an HCC marker,especially in patients with underlying cirrhosis.展开更多
Objective:To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh(northern Sumatra Island,Indonesia),the region that was most severely affected by th...Objective:To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh(northern Sumatra Island,Indonesia),the region that was most severely affected by the earthquake and tsunami of 26 December 2004.Methods:A communitybased,cross-sectional study was conducted among 535 healthy inhabitants in nine regencies(Kabupaten or Kotamadya)of Aceh that were selected randomly from November 2014 to March 2015.A set of validated,pre-tested,structured questionnaires was used to guide the interviews.The questionnaires covered a range of explanatory variables and one outcome variable(attitude to dengue vaccination).Multi-step logistic regression analysis and Spearman's rank correlation were used to test the role of explanatory variables for the outcome variable.Results:More than 70%of the participants had a poor attitude towards dengue vaccination.Modifiablc determinants associated with poor attitude to dengue vaccination were low education level,working as farmers and traditional market traders,low socioeconomic status and poor knowledge,attitude and practice regarding dengue fever(P<0.05).The KAP domain scores were correlated strongly with attitude to dengue vaccination,r_s=0.25,r_S=0.67 and r_s=0.20,respectively(P<0.001).Multivariate analysis found that independent predictors associated with attitude towards dengue vaccination among study participants were only sex and attitude towards dengue fever(P<0.001).Conclusions:This study reveals that low KAP regarding dengue fever,low education level and low socioeconomic status are associated with a poor attitude towards dengue vaccination.Therefore,inhabitants of suburbs who are working as larmers or traditional market traders with low socioeconomic status are the most appropriate target group for a dengue vaccine introduction program.展开更多
Colorectal cancer ranks third globally,with a high mortality rate.In the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of age.These sc...Colorectal cancer ranks third globally,with a high mortality rate.In the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of age.These screenings have allowed an early diagnosis and consequently an improvement in health indicators.Colon and rectal cancer(CRC)is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and mortality.This study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology,as well as a diagnosis of the epidemiological situation of CRC.Finally,the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.展开更多
Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma...Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma.A key aspect in identifying clear cell sarcoma is specific genetic alterations,notably the translocation of t(12;22)(q13;q13),a diagnostic hallmark of this sarcoma subtype,which is absent in malignant melanoma.Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.展开更多
BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combinat...BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.展开更多
Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expr...Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.展开更多
Rationale:Lepromatous leprosy can have many atypical presentations,obscuring early diagnosis.We present a case of lepromatous leprosy,presenting with atypical features,which made a diagnostic dilemma.Patient concerns:...Rationale:Lepromatous leprosy can have many atypical presentations,obscuring early diagnosis.We present a case of lepromatous leprosy,presenting with atypical features,which made a diagnostic dilemma.Patient concerns:A 48-year-old man presented with bilateral lower limb oedema and scaly“ichthyosis like”skin rash in both hands and feet,hepatosplenomegaly and pancytopenia,over a course of three months,without any classical features of leprosy.A skin biopsy revealed an unexpected diagnosis of borderline lepromatous leprosy.Diagnosis:Lepromatous leprosy.Interventions:Multi-drug regimen treatment with rifampicin,dapsone and clofazimine for lepromatous leprosy.Outcomes:The patient made a good clinical recovery.Lessons:In endemic settings,clinicians should be aware of similar atypical manifestations of leprosy to face the global challenge of eradicating this chronic deforming disease.展开更多
Background:Patients with cold tumors gain limited benefits from immune checkpoint blockade(ICB)therapy owing to low programmed cell death protein ligand 1(PD-L1)expression and minimal immune cell infiltration.Mild pho...Background:Patients with cold tumors gain limited benefits from immune checkpoint blockade(ICB)therapy owing to low programmed cell death protein ligand 1(PD-L1)expression and minimal immune cell infiltration.Mild photothermal therapy(PTT)using black phosphorus nanosheets(BPNSs)is a promising approach to enhance the efficacy of ICB therapy.However,to ensure that BPNS-based PTT-enhanced ICB therapy is clinically adaptable,a noninvasive,bedside-accessible imaging tool capable of monitoring the status of PD-L1 is imperative.We demonstrated that positron emission tomography(PET)using[64Cu]HKP2202 precisely delineated PD-L1 expression in tumors receiving PTT.Methods:BPNSs were modified with polyethylene glycol to prepare BPNS@PEG,which were then characterized.MC38 cells and tumor allografts were treated with BPNS@PEG followed by 808 nm near-infrared light expo-sure.PET using[64Cu]HKP2202 was performed to monitor PD-L1 expression in vivo.We also evaluated whether the efficacy of ICB therapy improved after delivering BPNS@PEG-based PTT.Results:BPNS@PEG had a well-defined lamellar structure with clear edges and an average size of 150 nm.PET and Western blotting assays indicated that PD-L1 expression was upregulated after BPNS@PEG and NIR-light treatment.Notably,the antitumor effect of anti PD-L1 therapy was enhanced in mice treated with BPNS@PEG-based PTT.Conclusions:BPNS@PEG had the capacity to convert cold tumors into hot tumors to facilitate the efficacy of ICB therapy.Importantly,the comple-mentary diagnostic PET radiotracer targeting PD-L1 allowed real-time moni-toring of PD-L1 expression in the tumor microenvironment to guide ICB administration,holding great potential to achieve efficient and precise tumor immunotherapy.展开更多
文摘Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.
基金part of a project that has received funding from the 5x1000 Humanitas funds。
文摘Objectives This study aimed to analyze the prevalence of long-term central line-associated bloodstream infections(CLABSI)among hospitalized adults with cancer in Italy and compare the characteristics of patients who required long-term central venous access device(LCVAD)substitution due to prior CLABSI with those who had never experienced CLABSI.Methods The study was conducted in hospitals across northern and central Italy using a multicenter,observational,cross-sectional design from March to September 2021.A total of 174 adults with cancer were included.Data were collected through electronic case report forms,including demographic,clinical,treatment-related,and catheter-related variables.Propensity score matching(PSM)was used to compare the characteristics of patients who underwent LCVAD substitution due to previous CLABSI with those who never experienced CLABSI.Multiple correspondence analysis(MCA)was conducted to explore the patterns within matched subgroups.Results The prevalence of CLABSI was 3%,and 5.2%of patients required LCVAD substitution due to prior CLABSI.After applying PSM,the groups were successfully balanced for sex,age,presence of metastases,comorbidities,BMI,received treatments,corticosteroid therapy,ongoing antibiotics,hormone therapy,type of LCVAD,lumens,and utilization frequency.Hematologic cancer was more frequent in the CLABSI group(44.4%)compared to the non-infective group(0),with a statistically significant difference(P=0.045).MCA revealed potential patterns among matched subgroups but did not identify statistically significant associations:patients with previous LCVAD substitution were more frequently associated with a history of prior infections,ongoing antibiotic therapy,and unspecified primary lesion locations;conversely,patients who never experienced CLABSI tended to cluster around characteristics such as hormone therapy and corticosteroid therapy.Conclusions These findings emphasize the importance of continuous monitoring,individualized infection prevention strategies in oncology nursing practice.Future research with larger datasets is needed to validate these findings and develop tailored interventions to reduce CLABSI risks.
文摘Living donor kidney transplantation(LDKT)has evolved into a globally adopted clinical practice,driven by improvements in donor selection,immunological compatibility,and perioperative care.These advances have contributed to enhanced donor safety and improved early graft outcomes.Still,its uptake remains limited worldwide,influenced by differences in clinical infrastructure,surgical expertise,and programmatic priorities.A central procedural consideration in LDKT is the choice of kidney for procurement,right or left.Left donor nephrectomy is generally preferred due to favorable vascular anatomy,yet right-sided procurement is often necessary in the presence of anatomical variations.While some studies report higher rates of early complications with right-sided nephrectomy,including delayed graft function and early graft loss,long-term outcomes appear comparable.The evaluation of laterality,however,varies significantly across centers and is often shaped more by institutional practice than by comparative evidence.In this editorial,we review key clinical and technical advances that have improved the safety and outcomes of LDKT,including immunological matching,donor selection,perioperative strategies,and early graft performance.We then critically examine the role of kidney laterality in donor nephrectomy,highlighting how anatomical complexity and procedural risk continue to shape clinical decision-making.
基金funded by grants Pronaii 302979A1-S-9005 CONACyT (México) from RMDA。
文摘Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.
文摘Cardiovascular complications remain a leading cause of morbidity and mortality in liver transplantation(LT),exposing the limitations of current risk assessment strategies.YKL-40,a glycoprotein involved in inflammation,endothelial dysfunction,and fibrotic remodeling,has emerged as a biomarker associated with adverse cardiovascular outcomes and liver disease severity.Its inclusion in structured cardiovascular assessment frameworks may improve transplantspecific risk scores and support earlier identification of high-risk LT recipients.Mechanistically,YKL-40 contributes to vascular injury and myocardial dysfunction via nuclear factor-κB and STAT3 signaling,and is under investigation as a biomarker in preclinical studies aimed at cardiovascular risk modulation in LT.Integration of YKL-40 into predictive models,particularly those supported by artificial intelligence,may enhance individualized perioperative decision-making.This editorial outlines translational directions for integrating YKL-40 into cardiovascular risk models and therapeutic research,supporting its clinical adoption in precision-guided LT care.
文摘Hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT)presents a significant challenge,with recurrence rates ranging from 8%to 20%globally.Current biomarkers,such as alpha-fetoprotein(AFP)and des-gamma-carboxy prothrombin(DCP),lack specificity,limiting their utility in risk strati-fication.YKL-40,a glycoprotein involved in extracellular matrix remodeling,hepatic stellate cell activation,and immune modulation,has emerged as a promising biomarker for post-LT surveillance.Elevated serum levels of YKL-40 are associated with advanced liver disease,tumor progression,and poorer post-LT outcomes,highlighting its potential to address gaps in early detection and personalized management of HCC recurrence.This manuscript synthesizes clinical and mechanistic evidence to evaluate YKL-40’s predictive utility in post-LT care.While preliminary findings demonstrate its specificity for liver-related pathologies,challenges remain,including assay standardization,lack of pro-spective validation,and the need to distinguish between malignant and non-malignant causes of elevated levels.Integrating YKL-40 into multi-biomarker panels with AFP and DCP could enhance predictive accuracy and enable tailored therapeutic strategies.Future research should focus on multicenter studies to validate YKL-40’s clinical utility,address confounding factors like graft rejection and systemic inflammation,and explore its role in predictive models driven by emerging technologies such as artificial intelligence.YKL-40 holds transformative potential in reshaping post-LT care through precision medicine,providing a pathway for better outcomes and improved management of high-risk LT recipients.
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
文摘BACKGROUND Heart transplantation is the last and best option for end-stage heart failure management.Early mortality rates have significantly decreased,enabling patients to survive longer with fewer complications,a trend observed even in our setting.The primary shared challenge has centered on achieving surgical success and immediate survival.The question arises about the medium-and long-term survival of patients with heart transplant in Mexico.AIM To present the results of the medium and long-term follow-up of heart transplant patients.METHODS This was a retrospective study of a single medical unit,and we selected patients who received heart transplants from July 21,1988 to September 30,2023.Selection criteria encompassed age,sex,and primary indication for heart transplantation across all groups.Patients with incomplete information or who died within 30 postoperative days were excluded.Data of primary pathology,ischemic,extracorporeal circulation,aortic cross-clamping times,length of ventilatory support,stay in postoperative therapy,hospitalization,and functional class were analyzed.RESULTS The causes of morbidity,mortality,and percentage of survival at 1,5,and 10 years were examined.Overall,257 heart transplants were performed during the study period.Of the total cases,22 with incomplete data and 47 who died within 30 postoperative days were excluded for the middle-and long-term survival analyses.Of the remaining 188 patients,heart transplantation was performed(males:146,females:42).The average age of the participants was 44.43±14.48 years.The primary indications included ischemic cardiomyopathy(42.55%)and dilated cardiomyopathy(39.36%).The mean durations of mechanical ventilator support,intensive care stay,and hospital stay were 57.55±103.50 hours,9.96±8.59 days,and 19.49±18.23 days,respectively.One-,five-,and ten-year survival rates were 90.7%,71.3%,and 60.3%,respectively.Of the patients,94%and 6%were in functional classes I and II,respectively.Infection and neurological hemorrhagic or ischemic stroke(26%)were the main causes of mortality in the first year.Subsequently,chronic rejection manifesting as graft vasculopathy increased in frequency(30%).CONCLUSION In our setting,heart transplantation yields medium-and long-term survival and quality of life outcomes comparable to those achieved by other international centers.
文摘Background: Pediatric brain tumors (PBT) are among the most common childhood neoplasms worldwide, but their management in low- and middle-income countries (LMICs) remains under-documented. Limited access to specialized care, diagnostic tools, and adjuvant therapies poses significant challenges in sub-Saharan Africa, including Togo. Objective: This study reviews the management of pediatric brain tumors in Togo. Methods: We conducted a retrospective study in the neurosurgery department at Sylvanus Olympio Teaching Hospital between November 2017 and December 2022. Demographic, clinical, radiographic, operative, pathology, and outcome data were collected and analyzed. Results: Eighteen patients had histologically verified brain tumors. Ages ranged from 1 to 15 years (mean: 7.73 ± 4.28), with a sex ratio of 1. Symptoms of raised intracranial pressure were present in 83.4% of cases. The mean interval to presentation was 22 ± 5.32 months. Tumors were supratentorial in 66.7% of cases. Total tumor removal was achieved in 61.1%. Astrocytoma was the most common histological diagnosis, followed by ependymoma and medulloblastoma. Five patients (27.8%) died within the first month post-surgery. The estimated 5-year survival rate was 43% ± 5.4%. Conclusion: Delayed diagnosis, insufficient infrastructure, and limited access to radiotherapy and chemotherapy contribute to poor outcomes. Improving neurosurgical capacity, infrastructure, and financial support could enhance survival and outcomes for pediatric brain tumor patients in Togo.
文摘Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.
文摘BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.
文摘Objective:Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide.The identification of new simple,inexpensive and highly accurate markers for HCC diagnosis and screening is needed.This case-control study evaluates the role of annexin A2 and voltage-gated calcium channelsα2δ1 subunit as serum biomarkers for HCC diagnosis.Methods:The study comprised three groups:group 1,50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection;group 2,25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC;and group 3,15 healthy controls.All participants were subjected to clinical and laboratory investigations,and radiological scanning.The serum levels of alpha-fetoprotein(AFP),annexin A2,and theα2δ1 subunit were evaluated by using ELISA technique.Results:The serum levels of annexin A2 significantly increased in patients with HCC(10.4±2.5 ng/m L;P<0.001)or with cirrhosis(9.31±1.8 ng/m L;P<0.001)comparing to that of healthy controls(0.296±0.09 ng/m L).However,there was no significant difference in serum annexin A2 levels in patients with HCC comparing to those with cirrhosis.Serumα2δ1 subunit significantly increased in patients with HCC(20.12±3.7 ng/m L)comparing to that in patients with cirrhosis(10.41±3.4 ng/m L,P<0.001)and healthy controls(10.2±2.9 ng/m L,P<0.001).Conclusions:The serumα2δ1 subunit may function as a new biomarker for HCC diagnosis.Conversely,serum annexin A2 has low diagnostic value as an HCC marker,especially in patients with underlying cirrhosis.
文摘Objective:To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh(northern Sumatra Island,Indonesia),the region that was most severely affected by the earthquake and tsunami of 26 December 2004.Methods:A communitybased,cross-sectional study was conducted among 535 healthy inhabitants in nine regencies(Kabupaten or Kotamadya)of Aceh that were selected randomly from November 2014 to March 2015.A set of validated,pre-tested,structured questionnaires was used to guide the interviews.The questionnaires covered a range of explanatory variables and one outcome variable(attitude to dengue vaccination).Multi-step logistic regression analysis and Spearman's rank correlation were used to test the role of explanatory variables for the outcome variable.Results:More than 70%of the participants had a poor attitude towards dengue vaccination.Modifiablc determinants associated with poor attitude to dengue vaccination were low education level,working as farmers and traditional market traders,low socioeconomic status and poor knowledge,attitude and practice regarding dengue fever(P<0.05).The KAP domain scores were correlated strongly with attitude to dengue vaccination,r_s=0.25,r_S=0.67 and r_s=0.20,respectively(P<0.001).Multivariate analysis found that independent predictors associated with attitude towards dengue vaccination among study participants were only sex and attitude towards dengue fever(P<0.001).Conclusions:This study reveals that low KAP regarding dengue fever,low education level and low socioeconomic status are associated with a poor attitude towards dengue vaccination.Therefore,inhabitants of suburbs who are working as larmers or traditional market traders with low socioeconomic status are the most appropriate target group for a dengue vaccine introduction program.
文摘Colorectal cancer ranks third globally,with a high mortality rate.In the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of age.These screenings have allowed an early diagnosis and consequently an improvement in health indicators.Colon and rectal cancer(CRC)is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and mortality.This study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology,as well as a diagnosis of the epidemiological situation of CRC.Finally,the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.
文摘Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma.A key aspect in identifying clear cell sarcoma is specific genetic alterations,notably the translocation of t(12;22)(q13;q13),a diagnostic hallmark of this sarcoma subtype,which is absent in malignant melanoma.Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.
文摘BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.
文摘Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.
文摘Rationale:Lepromatous leprosy can have many atypical presentations,obscuring early diagnosis.We present a case of lepromatous leprosy,presenting with atypical features,which made a diagnostic dilemma.Patient concerns:A 48-year-old man presented with bilateral lower limb oedema and scaly“ichthyosis like”skin rash in both hands and feet,hepatosplenomegaly and pancytopenia,over a course of three months,without any classical features of leprosy.A skin biopsy revealed an unexpected diagnosis of borderline lepromatous leprosy.Diagnosis:Lepromatous leprosy.Interventions:Multi-drug regimen treatment with rifampicin,dapsone and clofazimine for lepromatous leprosy.Outcomes:The patient made a good clinical recovery.Lessons:In endemic settings,clinicians should be aware of similar atypical manifestations of leprosy to face the global challenge of eradicating this chronic deforming disease.
基金National Natural Science Foundation of China,Grant/Award Number:82372002Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2022-RC350-04+7 种基金CAMS Innovation Fund for Medical Sciences,Grant/Award Numbers:2021-I2M-1-026,2022-I2M-2-002-2,2021-I2M-3-001National Key Research and Development Program of China,Grant/Award Number:2022YFE0111700Beijing Nova Program awarded to K.H.,Grant/Award Number:0104002Beijing Natural Science Foundation,Grant/Award Number:L234044Fundamental Research Funds for the Central Universities,Grant/Award Numbers:3332023044,3332023151CIRP Open Fund of Radiation Protection Laboratories“Technological innovation”special project of CNNC Medical Industry Co.Ltd,Grant/Award Number:ZHYLYB2021005China National Nuclear Corporation Young Talent Program。
文摘Background:Patients with cold tumors gain limited benefits from immune checkpoint blockade(ICB)therapy owing to low programmed cell death protein ligand 1(PD-L1)expression and minimal immune cell infiltration.Mild photothermal therapy(PTT)using black phosphorus nanosheets(BPNSs)is a promising approach to enhance the efficacy of ICB therapy.However,to ensure that BPNS-based PTT-enhanced ICB therapy is clinically adaptable,a noninvasive,bedside-accessible imaging tool capable of monitoring the status of PD-L1 is imperative.We demonstrated that positron emission tomography(PET)using[64Cu]HKP2202 precisely delineated PD-L1 expression in tumors receiving PTT.Methods:BPNSs were modified with polyethylene glycol to prepare BPNS@PEG,which were then characterized.MC38 cells and tumor allografts were treated with BPNS@PEG followed by 808 nm near-infrared light expo-sure.PET using[64Cu]HKP2202 was performed to monitor PD-L1 expression in vivo.We also evaluated whether the efficacy of ICB therapy improved after delivering BPNS@PEG-based PTT.Results:BPNS@PEG had a well-defined lamellar structure with clear edges and an average size of 150 nm.PET and Western blotting assays indicated that PD-L1 expression was upregulated after BPNS@PEG and NIR-light treatment.Notably,the antitumor effect of anti PD-L1 therapy was enhanced in mice treated with BPNS@PEG-based PTT.Conclusions:BPNS@PEG had the capacity to convert cold tumors into hot tumors to facilitate the efficacy of ICB therapy.Importantly,the comple-mentary diagnostic PET radiotracer targeting PD-L1 allowed real-time moni-toring of PD-L1 expression in the tumor microenvironment to guide ICB administration,holding great potential to achieve efficient and precise tumor immunotherapy.
