Etoposide-based Combination Chemotherapy in Malignant Histiocytosis

We investigated the responses of patients with malignant histiocytosis (MH) to the treatment of epotoside-based regimen.Of 11 evaluable cases,9(81. 8%)achieved complete remission and 1 partial remission.7 complete remission cases (77. 7%) received only one therapeutic course.The side effects were mild and welltolerated. We conclude that etoposide-containing regimen is highly effective and can be used as first-line treatment for MH and is worthy of further study.

Hepatic perivascular epithelioid cell tumors:Benign,malignant,and uncertain malignant potential

In 2013,the World Health Organization defined perivascular epithelioid cell tumor(PEComa)as“a mesenchymal tumor which shows a local association with vessel walls and usually expresses melanocyte and smooth muscle markers.”This generic definition seems to better fit the PEComa family,which includes angiomyolipoma,clear cell sugar tumor of the lung,lymphangioleiomyomatosis,and a group of histologically and immunophenotypically similar tumors that include primary extrapulmonary sugar tumor and clear cell myomelanocytic tumor.Clear cell tumors with this immunophenotypic pattern have also had their malignant variants described.When localizing to the liver,preoperative radiological diagnosis has proven to be very difficult,and most patients have been diagnosed with hepatocellular carcinoma,focal nodular hyperplasia,hemangioma,or hepatic adenoma based on imaging findings.Examples of a malignant variant of the liver have been described.Finally,reports of malignant variants of these lesions have increased in recent years.Therefore,we support the use of the Folpe criteria,which in 2005 established the criteria for categorizing a PEComa as benign,malignant,or of uncertain malignant potential.Although they are not considered ideal,they currently seem to be the best approach and could be used for the categorization of liver tumors.

Recurrent multisystem Langerhans cell histiocytosis involving the female genitalia: A case report

BACKGROUND Langerhans cell histiocytosis(LCH)is a histiocytic proliferative disease caused by clonal proliferation of Langerhans cells,which is currently defined as an inflam-matory myeloid tumor.It is rare in adults,with an incidence of 1–2 per million,and is highly heterogeneous in clinical presentation,with unpredictable disease progression and outcome.CASE SUMMARY A 52-year-old postmenopausal female patient presented to the gynecology department in July 2023 with bilateral vulvar masses.She was diagnosed with recurrent multisystem LCH.The patient had previously been diagnosed with a single-system and single-focal LCH in October 2021 due to a right maxillofacial mass,which resolved after surgical treatment.A chemotherapy regimen was developed after multidisciplinary consultation.Six cycles of chemotherapy resulted in partial remission,and maintenance chemotherapy is currently being administered.CONCLUSION Recurrent LCH involving the bilateral vulva has been poorly reported.Compre-hensive imaging and pathological evaluation is important for diagnosis.The model of joint multidisciplinary specialist diagnosis and treatment is worthy of clinical application.

Clinical analysis of multiple primary gastrointestinal malignant tumors:A 10-year case review of a single-center

BACKGROUND Multiple primary malignant tumors(MPMTs)was first described by Billroth as early as 1889,with the first report published by Warren and Gates in 1932.Since then,numerous cases have been reported.A literature review of 1104269 patients with cancer revealed that the incidence of MPMTs ranged from 0.73 to 11.7%.In recent years,however,there has been a significant upward trend in the incidence of this phenomenon,which may be associated with many different factors,including the advancement of modern diagnostic procedures facilitating the examination and diagnosis of more MPMTs,increased exposure to chemotherapy and radiotherapy that exacerbate the risk of new malignant tumors in patients with cancer,and prolonged survival of patients with cancer allowing sufficient time for the development of new primary cancers.AIM To analyze the incidence,clinical features,treatment factors,prevalence,and prognosis of patients with MPMTs in the gastrointestinal tract treated in a single center.Additionally,we analyzed the different tumor combinations,time interval between the occurrence of tumors,and staging.METHODS This retrospective cohort study analyzed 8059 patients with pathologically confirmed gastrointestinal malignant tumors treated at the Gansu Province Hospital in Lanzhou,Gansu,China between June 2011 and June 2020.Of these,85 patients had MPMTs.The clinical features,treatment factors,prevalence,and prognosis of this latter cohort were analyzed.RESULTS The incidence of MPMTs in patients with gastrointestinal malignant tumors was 1.05%(85/8059),including 83 double primary malignant tumors and two triple primary malignant tumors of which 57(67.06%)were synchronous MPMTs(SMPMTs)and 28(32.94%)were metachronous MPMTs(MMPMTs).The most frequent associations were found between the rectum colon cancers within the SMPMT category and the gastric-colon cancers within the MMPMT category.For the MMPMTs,the median interval was 53 months.The overall 1-,3-and 5-year survival rates from diagnosis of the first primary cancer were 91.36%,65.41%,and 45.97%,respectively;those from diagnosis of the second primary cancer were 67.90%,29.90%,and 17.37%,respectively.CONCLUSION MPMTs in the gastrointestinal tract have a high incidence and poor prognosis.Thus,it is necessary to perform both gastroscopy and colonoscopy in patients with gastrointestinal tumors.Multidisciplinary comprehensive diagnosis and treatment may improve the diagnosis rate and treatment efficiency of MPMTs.

Multisystemic recurrent Langerhans cell histiocytosis misdiagnosed with chronic inflammation at the first diagnosis:A case report

BACKGROUND Langerhans cell histiocytosis(LCH)is characterized by diabetes insipidus and is an uncommon occurrence.Pathological biopsies still have a certain degree of diagnostic probability.We present a case in which LCH initially affected the pituitary gland.This resulted in a misdiagnosis of chronic inflammation upon pathological examination.CASE SUMMARY A 25-year-old female exhibited symptoms of diabetes insipidus.Magnetic resonance imaging revealed an enhanced foci in the pituitary gland.After surgical resection of the pituitary lesion,the pathological diagnosis was chronic inflam-mation.However,the patient later experienced bone destruction in the skull and lower limb bones.After the lower limb bone lesion was compared with the initial pituitary lesion,the final diagnosis was modified to LCH.The patient was treated with multiple chemotherapy courses.However,the patient’s condition gradually worsened,and she eventually passed away at home.CONCLUSION LCH should be considered when patients exhibit diabetes insipidus and absence of high signal intensity in the pituitary gland on sagittal T1-weighted image and abnormal enhancement in the pituitary region.

Laparoscopic spleen-preserving total pancreatectomy for the treatment of low-grade malignant pancreatic tumors:Two case reports and review of literature

BACKGROUND Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors,such as intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms.However,there is limited literature on laparoscopic spleen-preserving total pancreatectomy(LSpTP)due to technical difficulties.CASE SUMMARY Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging,showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas.We performed L-SpTP with preservation of the splenic vessels,and the postoperative pathology report revealed IPMN with invasive carcinoma.Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body.L-SpTP was performed,and intraoperatively,the splenic vein was injured and required ligation.Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia.Both patients were discharged on postoperative day 7,and there were no major complications during the perioperative period.CONCLUSION We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors,but more case studies are needed to evaluate its safety,efficacy,and long-term outcomes.

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential

BACKGROUND Up until now,no research has been reported on the association between the cli-nical growth rate of multilocular cystic renal neoplasm of low malignant potential(MCRNLMP)and computed tomography(CT)imaging characteristics.Our study sought to examine the correlation between them,with the objective of distin-guishing unique features of MCRNLMP from renal cysts and exploring effective management strategies.AIM To investigate optimal management strategies of MCRNLMP.METHODS We retrospectively collected and analyzed data from 1520 patients,comprising 1444 with renal cysts and 76 with MCRNLMP,who underwent renal cyst decom-pression,radical nephrectomy,or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution.Detection of MC-RNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology.RESULTS Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP.Precisely,it comprises 1.48%of all cases involving simple renal cysts,5.26%of those with complex renal cysts,and a noteworthy 12.11%of renal tumors coexisting with renal cysts,indicating a statistically significant difference(P=0.001).Moreover,MCRNLMP constituted a significant 22.37%of the patient po-pulation whose cysts demonstrated a rapid growth rate of≥2.0 cm/year,whereas it only represented 0.66%among those with a growth rate below 2.0 cm/year.Of the 76 MCRNLMP cases studied,none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis.In the remaining 67 patients,who were actively monitored over a 3-year postoperative period,only one showed suspicious recurrence on CT scans.CONCLUSION MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators.In treating MCRNLMP,partial nephrectomy is preferred,while radical nephrectomy should be minimi-zed.After surgery,active monitoring is advisable to prevent unnecessary nephrectomy.

Amelanotic primary cervical malignant melanoma:A case report and review of literature

BACKGROUND Primary malignant melanoma of the cervix(PMMC)is an extremely rare disease that originates from primary cervical malignant melanoma and frequently re-presents a challenge in disease diagnosis due to unclarified clinical and histo-logical presentations,particularly those without melanin.CASE SUMMARY Here,we report a case of amelanotic PMMC,with a history of breast cancer and thyroid carcinoma.The patient was finally diagnosed by immunohistochemical staining and staged as IB2 based on the International Federation of Gynecology and Obstetrics with reference to National Comprehensive Cancer Network guide-lines and was treated with radical hysterectomy,bilateral salpingo-oophorectomy and pelvic lymphadenectomy.She then received combination therapy consisting of immunotherapy with tislelizumab and radiofrequency hyperthermia.She has remained free of disease for more than 1 year.CONCLUSION The differential diagnosis process reenforced the notion that immunohisto-chemical staining is the most reliable approach for amelanotic PMMC diagnosis.Due to the lack of established therapeutic guidelines,empirical information from limited available studies does not provide the rationale for treatment-decision making.By integrating'omics'technologies and patient-derived xenografts or mini-patient-derived xenograft models this will help to identify selective thera-peutic window(s)and screen the appropriate therapeutics for targeted therapies,immune checkpoint blockade or combination therapy strategies effectively and precisely that will ultimately improve patient survival.

Cost analysis of radical resection of malignant breast tumors under the China Healthcare Security Diagnosis Related Groups payment system

BACKGROUND Breast cancer is one of the most common malignant tumors in women worldwide and poses a severe threat to their health.Therefore,this study examined patients who underwent breast cancer surgery,analyzed hospitalization costs and structure,and explored the impact of China Healthcare Security Diagnosis Related Groups(CHS-DRG)management on patient costs.It aimed to provide medical institutions with ways to reduce costs,optimize cost structures,reduce patient burden,and improve service efficiency.AIM To study the CHS-DRG payment system’s impact on breast cancer surgery costs.METHODS Using the CHS-DRG(version 1.1)grouping criteria,4073 patients,who underwent the radical resection of breast malignant tumors from January to December 2023,were included in the JA29 group;1028 patients were part of the CHS-DRG payment system,unlike the rest.Through an independent sample t-test,the length of hospital stay as well as total hospitalization,medicine and consumables,medical,nursing,medical technology,and management expenses were compared.Pearson’s correlation coefficient was used to test the cost correlation.RESULTS In terms of hospitalization expenses,patients in the CHS-DRG payment group had lower medical,nursing,and management expenses than those in the diagnosis-related group(DRG)non-payment group.For patients in the DRG payment group,the factors affecting the total hospitalization cost,in descending order of relevance,were medicine and consumable costs,consumable costs,medicine costs,medical costs,medical technology costs,management costs,nursing costs,and length of hospital stay.For patients in the DRG nonpayment group,the factors affecting the total hospitalization expenses in descending order of relevance were medicines and consumable expenses,consumable expenses,medical technology expenses,the cost of medicines,medical expenses,nursing expenses,length of hospital stay,and management expenses.CONCLUSION The CHS-DRG system can help control and reduce unnecessary medical expenses by controlling medicine costs,medical consumable costs,and the length of hospital stay while ensuring medical safety.

Response letter to “Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the outcomes?” with imaging aspects

Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.

Long-term outcomes after endoscopic removal of malignant colorectal polyps:Results from a 10-year cohort

BACKGROUND Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging,and evidence regarding a surveillance-only strategy is limited.AIM To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps.METHODS A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020.Residual disease rate and nodal metastases after secondary surgery and local and distant recurrence rate for those with at least 1 year of follow-up were invest-igated.Event rates for categorical variables and means for continuous variables with 95%confidence intervals were calculated,and Fisher’s exact test and Mann-Whitney test were performed.Potential risk factors of adverse outcomes were RESULTS In total,135 lesions(mean size:22.1 mm;location:42%rectal)from 129 patients(mean age:67.7 years;56%male)were enrolled.The proportion of pedunculated and non-pedunculated lesions was similar,with en bloc resection in 82%and 47%of lesions,respectively.Tumor differentiation,distance from resection margins,depth of submucosal invasion,lymphovascular invasion,and budding were reported at 89.6%,45.2%,58.5%,31.9%,and 25.2%,respectively.Residual tumor was found in 10 patients,and nodal metastasis was found in 4 of 41 patients who underwent secondary surgical resection.Univariate analysis identified piecemeal resection as a risk factor for residual malignancy(odds ratio:1.74;P=0.042).At least 1 year of follow-up was available for 117 lesions from 111 patients(mean follow-up period:5.59 years).Overall,54%,30%,30%,11%,and 16%of patients presented at the 1-year,3-year,5-year,7-year,and 9-10-year surveillance examinations.Adverse outcomes occurred in 9.0%(local recurrence and dissemination in 4 patients and 9 patients,respectively),with no difference between patients undergoing secondary surgery and surveillance only.CONCLUSION Reporting of histological features and adherence to surveillance colonoscopy needs improvement.Long-term adverse outcome rates might be higher than previously reported,irrespective of whether secondary surgery was performed.

Efficacy and safety of percutaneous transhepatic biliary radiofrequency ablation in patients with malignant obstructive jaundice

BACKGROUND Percutaneous transhepatic cholangiodrainage(PTCD)and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice,yet the safety and effect of endobiliary radiofrequency ablation(EB-RFA)combined PTCD is rarely reported,in this article,we report our experience of EB-RFA combined PTCD in such patients.AIM To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice.METHODS Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected,the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases.The general conditions of all patients,preoperative tumour markers,total bilirubin(TBIL),direct bilirubin(DBIL),albumin(ALB),alkaline phosphatase(ALP),and glutamyl transferase(GGT)before and on the 7th day after the procedure,as well as perioperative complications,stent patency time and patient survival were recorded.RESULTS All patients successfully completed the operation,TBIL and DBIL decreased significantly in all patients at the 7th postoperative day(P=0.009 and 0.006,respectively);the values of ALB,ALP and GGT also decreased compared with the preoperative period,but the difference was not statistically significant.Perioperative biliary bleeding occurred in 2 patients,which was improved after transfusion of blood and other conservative treatments,pancreatitis appeared in 1 patient after the operation,no serious complication and death happened after operation.Except for 3 patients with loss of visits,the stent patency rate of the remaining 14 patients was 100%71%and 29%at the 1^(st),3^(rd),and 6^(th)postoperative months respectively,with a median survival of 4 months.CONCLUSION EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety,which is worthy of further clinical practice.

Unveiling hidden outcomes in malignant gastric outlet obstruction research–insights from a"Pancreas 2000"review

Malignant gastric outlet obstruction(mGOO)is a major condition affecting patients with periampullary tumors,including pancreatic cancer.The current treatment options include surgical gastroenterostomy,endoscopic stenting and more recently EUS-guided gastroenterostomy.Most studies comparing the outcomes of the three procedures focus on technical success,clinical success and safety.Several“occult”outcomes relevant to the patient’s viewpoints and perspective may ultimately impact on cancer-related and overall survival,such as body mass composition,nutritional biomarkers,chemotherapy tolerance and patient-reported quality of life.The aim of this review is to provide an overview of potential key outcomes that should be explored in future comparative research around mGOO treatment options.

Unraveling the nexus between cellular senescence and malignant transformation:a paradigm shift in cancer research

Cellular senescence, a natural process wherein cells cease division and undergo irreversible growth arrest, has long captivated the curiosity of scientists because of its many implications in aging and disease. Recent research has shed light on the nexus between cellular senescence and malignant transformation, thus leading to a paradigm shift in understanding cancer development and progression.

Advanced hepatocellular carcinoma in a patient with neurofibromatosis type 1 and malignant peripheral nerve sheath tumor

To the Editor: Neurofibromatosis type 1(NF-1), or Von Recklinghausen disease, is a genetic disorder inherited in an autosomal dominant pattern. It is caused by a mutation in the neurofibromin gene located on chromosome 17, accounting for 96% of all neurofibromatosis cases. This condition can affect multiple systems and often leads to the formation of tumors along the nervous system [1]. Patients with NF-1 may exhibit various symptoms, including Lisch nodules, neurofibromas, scoliosis, café au lait spots, learning disabilities, vision disorders, and epilepsy.

Recurrent malignant hyperthermia after scoliosis correction surgery

Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hypermetabolic response,including high fever,tachycardia,and elevated end-tidal carbon dioxide(ETCO_(2)).The successful treatment lies in the timely recognition and early use of dantrolene.[1]As an inhibitor of Ca2+release through ryanodine receptor(RYR)channels,the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca2+signaling and a lifesaving treatment for MH.[2]Dominant mutations in the skeletal muscle RYR1 gene are well-recognized causes of both malignant hyperthermia susceptibility(MHS)and central core disease(CCD).

Prevalence of malignant neoplasms in celiac disease patients-a nationwide United States population-based study

BACKGROUND Celiac disease(CeD)is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals.Recent research has unveiled a heightened risk of developing specific malignant neoplasms(MN)and various malignancies,including gastrointestinal,lymphomas,skin,and others,in individuals with CeD.AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States.METHODS Using data from the National Inpatient Sample spanning two decades,from January 2000 to December 2019,we identified 529842 CeD patients,of which 78128(14.75%)had MN.Propensity score matching,based on age,sex,race,and calendar year,was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio.RESULTS Positive associations were observed for several malignancies,including small intestine,lymphoma,nonmelanoma skin,liver,melanoma skin,pancreas myelodysplastic syndrome,biliary,stomach,and other neuroendocrine tumors(excluding small and large intestine malignant carcinoid),leukemia,uterus,and testis.Conversely,CeD patients exhibited a reduced risk of respiratory and secondary malignancies.Moreover,certain malignancies showed null associations with CeD,including head and neck,nervous system,esophagus,colorectal,anus,breast,malignant carcinoids,bone and connective tissues,myeloma,cervix,and ovary cancers.CONCLUSION Our study is unique in highlighting the detailed results of positive,negative,or null associations between different hematologic and solid malignancies and CeD.Furthermore,it offers insights into evolving trends in CeD hospital outcomes,shedding light on advancements in its management over the past two decades.These findings contribute valuable information to the understanding of CeD’s impact on health and healthcare utilization.

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma

Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.

Results of Surgical Management of Malignant Obstruction of the Common Bile Duct in Yaoundé

Introduction: In Cameroon, surgery remains the only approach in malignant obstructions of the common bile duct (MOCBD) even in palliative situations. The aim of this work was to describe the modalities of surgical treatment of MOCBD, evaluate the results and detect the factors associated with postoperative morbidity and mortality. Patients and Methods: We conducted an analytical observational study, with retrospective data collection from the files of patients operated upon for MOCBD. This was done in four referral hospitals in the city of Yaoundé for a 42-month period spanning from January 1, 2020 to June 30, 2023. Demographic data, clinical presentation, surgical data, and 30-day postoperative outcomes were collected. Results: We collected 71 files. The sex ratio was 1.4 and the mean age was 56 ± 11 years. Fifty-three (53) patients (74.6%) were overweight or obese and 10 patients (14.1%) were hypertensive. A clinical cholestasis syndrome was present in 69 patients (97.2%). Fifty-five (55) patients (77.5%) had a cancer of the head of the pancreas, 8 patients (11.3%) had an extra-hepatic cholangiocarcinoma and 8 patients (11.3%) had an ampullary adenocarcinoma. Eight (8) resections (11.3%) with curative intent had been carried out and in 63 cases (88.7%), surgery was palliative. Postoperative morbidity was 55.7%, influenced by advanced WHO stage (p = 0.02). Postoperative mortality was 25.7%, associated with a high ASA score (p = 0.01). Conclusion: Pancreatic head cancer is the main etiology of malignant obstructions of the common bile duct in Cameroon. Surgical treatment is most often palliative. Postoperative morbidity and mortality are high, influenced by high WHO and ASA scores.

Research progress on venous thrombosis development in patients with malignant tumors

The coexistence of venous thromboembolism(VTE)within patients with cancer,known as cancer-associated thrombosis(CAT),stands as a prominent cause of mortality in this population.Over recent years,the incidence of VTE has demonstrated a steady increase across diverse tumor types,influenced by several factors such as patient management,tumor-specific risks,and treatment-related aspects.Furthermore,mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes.We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT.This review elucidates the risks,mechanisms,reliable markers,and risk assessment methodologies that can significantly guide effective interventions in clinical practice.