Effects of the number of neoadjuvant therapy cycles on clinical outcomes, safety, and survival in patients with metastatic colorectal cancer undergoing metastasectomy

The controversial outcomes in patients with metastatic colorectal cancer(mCRC)highlight the need for developing effective systemic neoadjuvant treatment strategies to improve clinical results.The optimal treatment cycles in patients with mCRC for metastasectomy remain undefined.This retrospective study compared the efficacy,safety,and survival of cycles of neoadjuvant chemotherapy/targeted therapy for such patients.Sixty-four patients with mCRC who received neoadjuvant chemotherapy/targeted therapy following metastasectomy were enrolled between January 2018 and April 2022.Twenty-eight patients received 6 cycles of chemotherapy/targeted therapy,whereas 36 patients received≥7 cycles(median,13;range,7–20).Clinical outcomes,including response,progression-free survival(PFS),overall survival(OS),and adverse events,were compared between these two groups.Of the 64 patients,47(73.4%)were included in the response group,and 17(26.6%)were included in the nonresponse group.The analysis revealed chemotherapy/targeted therapy cycle and pretreatment serum carcinoembryonic antigen(CEA)level as independent predictors of the response as well as overall survival and chemotherapy/targeted therapy cycle as an independent predictor of progression(all p<0.05).Furthermore,our results revealed shorter operation time,lower estimated operative blood loss,higher response rate,lower progression rate,and higher survival rate in≥7 cycles of chemotherapy/targeted therapy group(all p<0.05),but no statistical differences in adverse events were observed between the two groups(all p>0.05).The median OS and PFS were 48 months(95%CI,40.855–55.145)and 28 months(95%CI,18.952–37.48)in the≥7-cycle group and 24 months(95%CI,22.038–25.962)and 13 months(95%CI,11.674–14.326)in the 6-cycle group,respectively(both p<0.001).The oncological outcomes in the≥7-cycle group were significantly better than those in the 6-cycle group,without significant increases in adverse events.However,prospective randomized trials are mandatory to confirm the potential advantages of cycle numbers of neoadjuvant chemotherapy/targeted therapy.

Efficacy and safety of anti-vascular endothelial growth factor agents on corneal neovascularization: A meta-analysis

BACKGROUND Corneal neovascularization(CoNV)is the second major cause of blindness.Vascular endothelial growth factor(VEGF)inhibitors,e.g.,bevacizumab,have been used to prevent CoNV.AIM We conducted an updated systematic review and meta-analysis of clinical trials to examine the efficacy and safety of anti-VEGF in CoNV.METHODS A literature search was conducted using three electronic databases.Mean difference(MD),standard mean difference(SMD),and relative risk(RR)are used to estimate the effect size.RESULTS Nine randomized controlled and three non-randomized trials were obtained.The pooled results demonstrated a significant reduction of CoNV area/Length(SMD=-1.17,95%CI:-1.58 to-0.75),best corrected visual acuity(MD=-0.54,95%CI:-0.91 to-0.17),and graft rejection(RR=0.44,95%CI:0.24 to 0.8)and failure(RR=0.39,95%CI:0.19 to 0.78)rates in the anti-VEGF group than the placebo group.A non-significant reduction of the epithelial defect was also observed in the bevacizumab group compared with the placebo(RR=0.56,95%CI:0.30 to 1.06).Compared with a placebo,the unsynthesizable trials also support that bevacizumab improves visual acuity,CoNV,graft rejection,and failure rates.Trials reporting other comparisons revealed the superiority of combined remedy with bevacizumab compared to other treatments in reducing CoNV.CONCLUSION Anti-VEGF agents,mainly bevacizumab,are an effective and safe treatment for CoNV of all causes and prevent corneal graft rejection and failure in corneal transplantation.

Management of patients with stercoral perforation of the sigmoid colon:Report of five cases

到我们的知识，冒号的粪的穿孔很少比 90 个案例在文学报导到日期为止与少数被看见。我们探索了管理的原则与这个条件在五个病人阻止逼近的死亡。五个病人，二男性和三女性，其中部的年龄是 64 年，支撑了 S 字形的冒号的粪的穿孔。长期的便秘是在这些病人之中的普通症状。三个病人经历了一个 Hartmannos 过程和另外一个二与吻合和转移结肠开口术与部分结肠切除术被对待。有一外科的死亡，另外的病人让一所平静医院留下来。与广泛的腹洗室年龄一起阻止或对待任何联系败血的及时干预和在主要粪的溃疡地点的结肠的织物结合了移开 diseased 的外科的干预为腹膜炎的好攻击的治疗是在抢救与冒号的粪的穿孔介绍的病人的关键治疗形式。

Early detection of diabetic kidney disease: Present limitations and future perspectives

Diabetic kidney disease(DKD) is one of the most common diabetic complications, as well as the leading cause of chronic kidney disease and end-stage renal disease around the world. To prevent the dreadful consequence, development of new assays for diagnostic of DKD has always been the priority in the research field of diabetic complications. At present, urinary albumin-to-creatinine ratio and estimated glomerular filtration rate(eG FR) are the standard methods for assessing glomerular damage and renal function changes in clinical practice. However, due to diverse tissue involvement in different individuals, the so-called "non-albuminuric renal impairment" is not uncommon, especially in patients with type 2 diabetes. On the other hand, the precision of creatinine-based GFR estimates is limited in hyperfiltration status. These facts make albuminuria and eG FR less reliable indicators for early-stage DKD. In recent years, considerable progress has been made in the understanding of the pathogenesis of DKD, along with the elucidation of its genetic profiles and phenotypic expression of different molecules. With the help of ever-evolving technologies, it has gradually become plausible to apply the thriving information in clinical practice. The strength and weakness of several novel biomarkers, genomic, proteomic and metabolomic signatures in assisting the early diagnosis of DKD will be discussed in this article.

Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening

AIM: To assess the cost-effectiveness of two populationbased hepatocellular carcinoma(HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography(AUS).METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per lifeyear gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental costeffectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening.CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval.

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.

Evaluation of dynamic stereopsis in intermittent exotropia patients

AIM: To delineate the characteristics of the dynamic stereopsis test and analyze related parameters in intermittent exotropia [X(T)] patients. METHODS: Fifty-seven X(T) patients and 55 normal subjects were enrolled in this study. The normal and X(T) groups were used to test the reproducibility and reliability of the dynamic stereopsis test, and Bangerter filters with densities of 0.2 were then used to simulate suppression to test for traditional and dynamic stereopsis. In the X(T) group, the measurements included 1) dynamic stereopsis test comprising three parts: motion+disparity, motion only and disparity only; 2) ocular deviation angle; 3) Bagolini striated lens test; 4) disease course; and 5) Titmus stereopsis test. RESULTS: The test-retest reliability of the dynamic stereopsis method was 0.901 in the normal and X(T) groups, and none of the X(T) patients were able to pass the static and dynamic stereopsis tests after using the 0.2 Bangerter filter. The accuracy rate was greater than 80% in the normal group and 31.81%, 36.36%, and 45.45% for the motion+disparity, motion-only and disparityonly components of the traditional test for X(T) patients diagnosed with stereoblindness via traditional tests,respectively. Patients with a long disease course(>1 y) had worse dynamic stereopsis than those with a short disease course(<1 y; P<0.05, Chi-square test). The deviation angle was not correlated with the motion+disparity, disparityonly, or the motion-only test components(all P>0.05, Chisquare test). CONCLUSION: Dynamic stereopsis is preserved in certain X(T) patients diagnosed with stereoblindness via traditional tests. A long disease course was shown to be a negative factor for dynamic stereopsis in X(T) patients which might be associated with worse progression, and provide good references clinically.

Current status of endoscopic sleeve gastroplasty: An opinion review

Bariatric surgeries have been demonstrated to be safe and effective treatment options for morbid obesity patients, but operative risks and high health care costs limit their clinical application. Endoscopic bariatric therapies are emerging as valuable alternatives for patients with doubts about bariatric surgery or ineligible for it. Endoscopic sleeve gastroplasty(ESG), a relatively novel technique of endoscopic bariatric therapies, has gained standing in the past few years. The safety, feasibility, repeatability, and potential for reversibility of ESG have been proven by multicenter studies. Compared to other weight loss strategies, current evidence demonstrates that ESG offers satisfactory efficacy in weight loss. Even though it is inferior to laparoscopic sleeve gastrectomy, it has lower risks of adverse events than surgical interventions and intragastric balloon within oneyear follow-up. Furthermore, ESG may be the ideal weight control strategy for patients who have poor adherence to behavioral interventions. Even so, trends in decreased weight loss effect over time, post-procedure weight regain, postprocedure gut hormone alteration, and possible effects of race and ethnicity on ESG still remain undetermined due to very limited reports and very short followups. Further clinical trials are required to validate and answer these questions.

Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

AIM: A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori(H pylori)-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori-specific intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 (B7.2) and the infiltration of CD56 (+) natural killer (NK) cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT lymphoma.METHODS: Lymphoma biopsies from 26 patients who had participated in a prospective study of H pylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less after H pylorieradication were classified as H pyloridependent; others were classified as H pylori-independent.The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry.RESULTS: There were 16 H pylori-dependent and 10H pylori-independent cases. CD86 expression was detected in 11 (68.8%) of 16 Hpyiori-dependent cases but in none of 10 Hpylori-independent cases (P = 0.001).H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 (+) NK cells than H pylori-independent cases (2.8±1.4% vs 1.1±0.8%; P = 0.003). CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 (+)NK cells compared to CD86-negative cases (2.9±1.1% vs1.4±1.3%; P= 0.005).CONCLUSION: These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with H pylori-dependent state of early-stage high-grade gastric MALT lymphomas.

Delayed ischemic gangrene change of distal limb despite optimal decompressed colostomy constructed in obstructedsigmoid colon cancer:A case report

为解压缩创造喷水孔结肠开口术能为一个严重地削弱的案例向一个节省时间、有效的外科的过程提供一种完全妨碍的颜色表面的癌症。复杂并发症作为脱垂，收回，和 paracolostomal 脓肿被报导。然而，复杂并发症与一是化学家远侧的手足没被报导。我们为减轻恶意的 S 字形的冒号阻塞在减压结肠开口术以后报导批评 intra 腹的疾病的一个案例；一个潜在的致命的条件应该被警告。76 岁的男性与肮脏气味的呕吐为与妨碍的 S 字形的结肠肿瘤有关的症状访问了我们的紧急情况部门我们包含象粪便一样材料。对妨碍的 S 字形的损害近似的突现的喷水孔结肠开口术被创造，并且完全的冒号阻塞的分辨率被追求。不幸地，有有白细胞减少的高发烧的像板的腹部和骤起的广泛的腹的痛苦的膨胀随后发展了。如此的急腹症与 S 字形的肿瘤的切除术显示了第二等的剖腹术与一起一是近似地定位直到以前创造的结肠开口术的化学家冒号片断。最后，病人让一所平静手术后的医院留下来。在现在的文章，我们在喷水孔结肠开口术以后描述了远侧的手足局部缺血的骤起的一个突现的条件并且断定尽管有减压结肠开口术，那将高效地解决尖锐恶意的冒号阻塞；逼近是化学家肠可以与可能的不可逆的腹膜炎进行。任何病人，没有妨碍的损害的切除术，经历减压结肠开口术，应该经常与白血球计数和腹的条件调查被监视。

MicroRNA-22E Inhibits HER-3 Protein Expression to Facilitate Metastasis of Lung Adenocarcinomas

MicroRNA-22 (miR-22), a short non-coding RNA that post-transcriptionally regulates mRNA stability and protein synthesis, has been shown to enhance metastatic potential and to suppress HER-3, an important mRNA marker for non-small cell lung cancer (NSCLC). However, the effect of miR-22 has not been investigated in lung adenocarcinoma (LADC), the most common type of NSCLC in the Far East. In this study, we analyzed the role of miR-22 expression in LADC patients. Expression of miR-22 was detected by reverse-transcription polymerase chain reaction (RT-PCR), and confirmed by cDNA sequencing. Signals of miR-22 in LADC sections were identified using in situ hybridization (ISH). The association between miR-22 expression and survival was evaluated by the log-rank test. Induction of miR-22 expression and the effect on HER-3 levels, as well as the subsequent cell behavior were also investigated In vitro. Two types of miR-22: miR-22 and miR-22H, were detected by RT-PCR. The miR-22H had extra 13 bases, 5’-TGTGTTCAGTGGT-3’, at the 3’-end, and this segment was named miR-22E. Using ISH, miR-22E overexpression was detected in 225 (83.0%) of 271 LADC patients. A significant difference was found in cumulative survival between patients with high miR-22E levels and those with low miR-22E levels (p In vitro, epidermal growth factor induced miR-22, but reduced HER-3 expression. Expression of miR-22 increased cell movement ability. In conclusion, expression of miR-22 is closely associated with tumor recurrence, metastasis and overall survival in LADC patients by suppressing HER-3 protein expression to enhance epithelial-mesenchymal transition and metastasis.

亚太地区慢性乙型肝炎治疗共识(2012最新版)

自2008年至今,有大量关于慢性HBV感染的自然史和治疗的最新数据不断涌现。其中包括慢性HBV感染的无症状感染者,以社区为基础的队列研究,HBV基因型的作用,非药物诱导的自然HBV变异型毒株,无创性肝纤维化评估方法的应用,HBsAg定量在临床中的应用,更有效的新治疗药物和新治疗方案等等。来自亚太地区的专家审查和评估了相关数据,并共同商讨了近年来报道的最有意义的发现,基于此,对2008年版的亚太地区慢性乙型肝炎治疗共识进行修订,同时对2008年版治疗指南定义的关键词组进行了修订。修订后的指南包括以下几方面内容:一般治疗,肝纤维化评价适应证,何时开始治疗或停药,初始抗病毒治疗药物的选择,如何监测治疗中和治疗后的患者。关于特殊人群的治疗建议中包括了对妊娠妇女,已发生耐药,合并其他病毒感染,肝功能失代偿,接受免疫抑制治疗、化疗,肝移植或肝细胞癌患者的具体治疗建议。

Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma(HCC) recurrence for up to 3 year following curative resection. METHODS: A total of 143 patients(83.1% of the 172 participants in the phase Ⅱ study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase Ⅱ trial. Safety parameters and the following efficacy endpoints were investigated:(1) time to recurrence;(2) diseasefree survival; and(3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group:(1) the recurrence-free rate increased from 50% to 63%, and(2) time to recurrence at the 36 th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate(11 out of 54 patients). Additionally, subgroup analyses of patients with(1) multiple tumors or a single tumor ≥ 2 cm; and(2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage(56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.

Targeting c-Myc as a novel approach for hepatocellular carcinoma

Hepatocelluar carcinoma(HCC) is the most lethal cancer in the world.Most HCC over-express c-Myc,which plays a critical role in regulating cellular growth,differentiation and apoptosis in both normal and neoplastic cells. c-Myc is among the most frequently overexpressed genes in human cancers.Overexpression of c-Myc in hepatic cells leads to development of hepatocellular carcinoma.Here,we review the current progress in understanding physiologic function and regulation of c-Myc as well as its role in hepatic carcinogenesis and discuss the association of c-Myc activation in chronic hepatitis B infection and the upregulation of HIF-1/VEGF.We also explore the possibility of treating HCC by inhibiting c-Myc and examine the pros and cons of such an approach.Although this strategy is currently not available in clinics,with recent advances in better drug design,pharmacokinetics and pharmacogenetics,inhibition of c-Myc might become a novel therapy for HCC in the future.

Nonalcoholic fatty liver disease:Updates in noninvasive diagnosis and correlation with cardiovascular disease

Nonalcoholic fatty liver disease(NAFLD)refers to the accumulation of fat(mainly triglycerides)within hepatocytes.Approximately 20%-30%of adults in the general population in developed countries have NAFLD;this trend is increasing because of the pandemicity of obesity and diabetes,and is becoming a serious public health burden.Twenty percent of individuals with NAFLD develop chronic hepatic inflammation[nonalcoholic steatohepatitis(NASH)],which can be associated with the development of cirrhosis,portal hypertension,and hepatocellular carcinoma in a minority of patients.And thus,the detection and diagnosis of NAFLD is important for general practitioners.Liver biopsy is the gold standard for diagnosing NAFLD and confirming the presence of NASH.However,the invasiveness of this procedure limits its application to screening the general population or patients with contraindications for liver biopsy.The development of noninvasive diagnostic methods for NAFLD is of paramount importance.This review focuses on the updates of noninvasive diagnosis of NAFLD.Besides,we review clinical evidence supporting a strong association between NAFLD and the risk of cardiovascular disease because of the cross link between these two disorders.

Endovascular interventions may save limbs in elderly subjects with severe lower extremity arterial disease

Endovascular intervention,such as percu-taneous transluminal angioplasty(PTA),improves claudication and saves limbs of patients with severe lower extremity arterial dis-ease(LEAD).[1]A previous study showed that the mortality among octogenarians was as high as 29%regardless of the type of intervention and that re-vascularization was associated with high peripro-cedural mortality.[2]A previous study had already shown that reconstructive surgery for elderly indi-viduals over 80 years old resulted in a significantly higher mortality rate than that for patients between 70 and 80 years old,whereas endovascular inter-vention and primarily conservative treatment had comparable prognoses.[3]Consistently,another study showed that the risks of both overall and am-putation-free survival were significantly lower with endovascular treatment than with bypass surgery in patients with critical limb ischemia.[4]A systematic review and meta-analysis of 27 studies(15 cohort and 12 randomized controlled trials)with 1642 pa-tients suggests that conservative treatment may be considered for nonreconstructable patients with critical limb ischemia;[5]however,because a high risk of bias and serious inconsistencies were found in the included studies,the meta-analysis provided low-quality evidence.In contrast,a small cohort study with 49 patients suggests that amputation im-proved quality of life and health status in fragile elderly individuals.

Organophosphate pesticides and new-onset diabetes mellitus:From molecular mechanisms to a possible therapeutic perspective

Organophosphate is a commonly used pesticide in the agricultural sector.The main action of organophosphate focuses on acetylcholinesterase inhibition,and it therefore contributes to acute cholinergic crisis,intermediate syndrome and delayed neurotoxicity.From sporadic case series to epidemiologic studies,organophosphate has been linked to hyperglycemia and the occurrence of newonset diabetes mellitus.Organophosphate-mediated direct damage to pancreatic beta cells,insulin resistance related to systemic inflammation and excessive hepatic gluconeogenesis and polymorphisms of the enzyme governing organophosphate elimination are all possible contributors to the development of newonset diabetes mellitus.To date,a preventive strategy for organophosphatemediated new-onset diabetes mellitus is still lacking.However,lowering reactive oxygen species levels may be a practical method to reduce the risk of developing hyperglycemia.

Association between human glutathione S-transferase omega rs4925 polymorphism and bladder cancer

Glutathione S-transferases (GSTs) play an important role in the detoxification of polycyclic aromatic hydrocarbons and aromatic amines, the toxic substances contained in cigarettes. GST Omega 1 (GSTO1) not only utilizes glutathione in conjugation reaction but also contributes to the biotransformation of several xenobiotics. A single nucleotide polymorphism (Ala-140Asp) of GSTO1 gene causing variations in enzyme activity may influence individual susceptibility to bladder cancer (BC). It is hypothesized that genetic polymorphism of GSTO1 gene has an effect on BC risk in particular by interacting with cigarette smoking. A total of histopathologically confirmed 300 BC patients and 300 cancer-free controls were recruited from February 2002 to February 2009. Genotyping of the GSTO1 Ala140Asp polymorphism was determined using a polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method. The odds ratio (OR) and 95% confidence interval (CI) were calculated as a measure of the combined effect of cigarette smoking and the GSTO1 Ala140Asp polymorphism on BC risk. We found that study subjects with the GSTO1 Ala/Ala genotype have a significantly increased BC risk (OR = 1.5;95% CI = 1.1 - 2.7). A statistically significant increased BC risk was also found in ever smokers with the GSTO1 Ala/Ala genotype (OR = 4.9;95%CI = 2.8 - 9.7). In conclusion, this study provides an epidemiologic evidence of a significantly increased BC risk among ever smokers with the GSTO1 Ala/Ala genotype.

Anti-CD 20 monoclonal antibodies and associated viral hepatitis in hematological diseases

Over the past decade, the administration of anti-CD20 monoclonal antibodies such as rituximab has demonstrated various degrees of effectiveness and has improved patients' outcomes during the treatment of autoimmune hematological disorders and hematological malignancies. However, the depletion of B-cells, the distribution of T-cell populations, and the reconstruction of host immunity resulting from the use of anti-CD20 monoclonal antibodies potentially lead to severe viral infections, such as hepatitis B virus(HBV), hepatitis C virus(HCV), parvovirus B19, and herpes viruses, in patients who are undergoing immune therapy or immunochemotherapy. Of these infections, HBV- and HCV-related hepatitis are a great concern in endemic areas because of the high morbidity and mortality rates in untreated patients. As a result, prophylaxis against HBV infection is becoming a standard of care in these areas. Parvovirus B19, a widespread pathogen that causes red blood cell aplasia in immunocompromised hosts, also causes hepatitis in healthy individuals. Recently, its association with hepatitis was recognized in a patient treated with rituximab. In addition, adenovirus, varicella-zoster virus hepatitis E virus, and rituximab itself have been linked to the occurrence of hepatitis during or after rituximab treatments. The epidemiologies and pathogeneses of these etiologies remain unknown. Because of the increasing use of anti-CD20 monoclonal antibodies for the treatment of hematological malignancies or autoimmune hematological disorders, it is imperative that physicians understand and balance the risks of hepatotropic virusassociated hepatitis against the benefits of using antiCD20 monoclonal antibodies.

Community-centered Disease Severity Assessment of Metabolic Dysfunction-associated Fatty Liver Disease

Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAFLD between different items.We also aimed to investigate the associations between advanced fibrosis and risk factors.Methods:This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community.Patients were stratified following MAFLD diagnostic criteria,to group A(395 patients)for type 2 diabetes,group B(1,818 patients)for body mass index(BMI)>23 kg/m^(2),and group C(44 patients)for BMI≤23kg/m^(2) with at least two metabolic factors.Advanced fibrosis was defined as a fibrosis-4 index>2.67.Results:Between 2009 and 2020,1,948 MAFLD patients were recruited,including 478 with concomitant liver diseases.Advanced fibrosis was observed in 125 patients.A significantly larger proportion of patients in group C(25.0%)than in group A(7.6%)and group B(5.8%)had advanced fibrosis (p<0.01).Logistic regression analysis found that hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfection(odds ratio[OR]:12.14,95%confidence interval[CI]:4.04-36.52;p<0.01),HCV infection(OR:7.87,95%CI:4.78-12.97;p<0.01),group C(OR:6.00,95%CI:2.53-14.22;p<0.01),and TC/LDL-C(OR:1.21,95%CI:1.06-1.38;p<0.01)were significant predictors of advanced fibrosis.Conclusions:A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis.HCV infection was significantly associated with advanced fibrosis.