Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

Decoding the genetic landscape of autism:A comprehensive review

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD,influencing both diagnosis and therapeutic strategies.AIM To explore the genetic architecture of ASD,elucidate mechanistic insights into genetic mutations,and examine gene-environment interactions.METHODS A comprehensive systematic review was conducted,integrating findings from studies on genetic variations,epigenetic mechanisms(such as DNA methylation and histone modifications),and emerging technologies[including Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-Cas9 and single-cell RNA sequencing].Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD,yet many cases remain unexplained by known factors,suggesting undiscovered genetic components.Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving.Epigenetic modifications,particularly DNA methylation and non-coding RNAs,also play significant roles in ASD pathogenesis.Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments.Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice.Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies,ultimately enhancing outcomes for individuals affected by ASD.

Gastrointestinal tolerability of organic infant formula compared to traditional infant formula: A systematic review

BACKGROUND Infants'nutrition significantly influences their growth,development,and overall well-being.With the increasing demand for organic infant formula driven by the perception of health benefits and growing awareness of natural feeding options,it is crucial to conduct a comparative analysis of the gastrointestinal tolerability between organic and traditional infant formulas.AIM To provide a concise and precise analysis of the gastrointestinal tolerability of organic infant formula compared to traditional infant formula.Due to limited direct comparisons,the review synthesizes available literature on each formula type,presenting insights into their potential effects on infants'digestive health.METHODS An extensive literature search was conducted,compiling studies on organic and traditional infant formulas,their compositions,and reported effects on gastrointestinal tolerability.We searched academic databases such as PubMed and Google Scholar and specialized nutrition,paediatrics,and infant health journals using relevant keywords till October 1,2023.RESULTS Although specific comparative studies are scarce and formula heterogeneity is a significant limitation,this systematic review provides an in-depth understanding of organic infant formulas'composition and potential benefits.While scientific evidence directly comparing gastrointestinal tolerability is limited,organic formulas strive to use carefully selected organic ingredients to imitate breast milk composition.Potential benefits include improved lipid profiles,higher methionine content,and decreased antibiotic-resistant bacteria levels.Understanding the gastrointestinal tolerability of organic and traditional infant formulas is crucial for parents and healthcare providers to make informed decisions.CONCLUSION Despite limitations in direct comparisons,this systematic review provides insights into the composition and potential benefits of organic infant formulas.It emphasizes the need for further research to elucidate their gastrointestinal effects comprehensively.

Examining the Types and Consequences of Female Genital Mutilation in Somalia: A Cross-Sectional Study on the Burden and Impact of Acute and Long-Term Complications

Background: In Africa, female genital mutilation (FGM) is a widespread and harmful practice, with Somalia having the highest incidence at 98%. This practice has severe and long-lasting physical and mental health consequences. The aim of the study was to evaluate the different types of FGM;immediate and long-term complications associated with the practice, and identify factors related to its prevalence. Method: In a one-year cross-sectional hospital-based study, data were collected from females aged 18 - 50 with a history of FGM. Face-to-face semi-structured questionnaires were used for data collection. Data analysis was performed using SPSS version 26, utilizing univariate and bivariate analyses to identify correlations between variables, which were presented in tables. Results: In a study involving 255 female participants, 65.5% were between 18 and 30 years old. The majority (82.7%) were married, while 47.1% were illiterate. FGM cases were more prevalent in rural areas (61.6%). Among the participants, 45.1% were employed. Type 3 FGM was the most common (44.3%), followed by Type 2 (32.2%) and Type 1 (23.9%). In terms of short-term complications experienced by circumcised women, the most common were bleeding, reported by 29.8% of participants, followed by infection (25.1%), and urinary retention (19.2%). Among the long-term complications observed, recurrent vaginal infections were the most prevalent, affecting 29.8% of the surveyed females. This was episiotomy during delivery (22.3%) and genital scarring (10.2%). Conclusion: The study reveals that Type 3 FGM is highly prevalent among the surveyed females, contributing to an increased risk of recurrent vaginal infections, prolonged second stage of labor, higher likelihood of episiotomy during delivery, and genital scarring. These findings emphasize the urgent need for effective preventive strategies and implementation from both international and local organizations to eliminate the harmful practice of FGM.

Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock:An Indian perspective

BACKGROUND Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters.Despite standard therapy,the outcomes are poor.Newer adjuvant therapy,such as CytoSorb®extracorporeal haemoadsorption device,has been investigated and shown promising outcome.However,there is a lack of some guidance to make clinical decisions on the use of CytoSorb®haemoadsorption as an adjuvant therapy in septic shock in Indian Setting.Therefore,this expert consensus was formulated.AIM To formulate/establish specific consensus statements on the use of CytoSorb®haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario.METHODS We performed a comprehensive literature on CytoSorb®haemoadsorption in sepsis,septic shock in PubMed selecting papers published between January 2011 and March 20232021 in English language.The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps.Using a modified Delphi approach combining evidence appraisal and expert opinion,the following topics related to CytoSorb®in septic shock were addressed:need for adjuvant therapy,initiation timeline,need for Interleukin-6 levels,duration of therapy,change of adsorbers,safety,prerequisite condition,efficacy endpoints and management flowchart.Eleven expert members from critical care,emergency medicine,and the intensive care participated and voted on nine statements and one open-ended question.RESULTS Eleven expert members from critical care,emergency medicine,and the intensive care participated and voted on nine statements and one open-ended question.All 11 experts in the consensus group(100%)participated in the first,second and third round of voting.After three iterative voting rounds and adapting two statements,consensus was achieved on nine statements out of nine statements.The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb®for all indications in the open-ended question(Q10)focusing on“future recommendations for CytoSorb®therapy”.CONCLUSION This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb®haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

Early efficacy of individual regimens containing bedaquiline in patients with drug resistant tuberculosis

Objective:To evaluate early efficacy of sputum conversion within 6 months of individual regimens containing bedaquiline in patients with drug resistant tuberculosis.Methods:We conducted a retrospective study among patients with drug resistant tuberculosis who were receiving individual regimens containing bedaquiline.The primary outcome was sputum conversion of both smear and culture within 6 months of treatment.We used medical records of drug resistant tuberculosis patients from January 2020 to December 2021.The study was conducted at Dr.Soetomo Hospital,Indonesia from August to October 2022.Results:In this study,44 eligible drug resistant tuberculosis patients were initiated on regimens containing bedaquiline.There were 52.3%males and the median age was 45.5 years.The rates of previous treatment(70.5%)and lung cavity(36.4%)were high.The most common companion drugs included clofazimine,cycloserine,levofloxacin,and linezolid.Sputum smear and culture conversion was seen in 79.4%and 82.1%at the 2nd month,respectively.More than 97%patients had smear and culture conversion at the end of 6 months.Conclusions:Among drug resistant tuberculosis patients,individual regimens containing bedaquiline were associated with high rates of smear and culture conversion at the end of 6 months.Early efficacy of regimens containing bedaquiline can be used to predict cure rate at the end of treatment.

Cardiometabolic effects of breastfeeding on infants of diabetic mothers

BACKGROUND Breast milk is the best and principal nutritional source for neonates and infants.It may protect infants against many metabolic diseases,predominantly obesity and type 2 diabetes.Diabetes mellitus(DM)is a chronic metabolic and microvascular disease that affects all the body systems and all ages from intrauterine life to late adulthood.Breastfeeding protects against infant mortality and diseases,such as necrotizing enterocolitis,diarrhoea,respiratory infections,viral and bacterial infection,eczema,allergic rhinitis,asthma,food allergies,malocclusion,dental caries,Crohn's disease,and ulcerative colitis.It also protects against obesity and insulin resistance and increases intelligence and mental development.Gestational diabetes has short and long-term impacts on infants of diabetic mothers(IDM).Breast milk composition changes in mothers with gestational diabetes.AIM To investigate the beneficial or detrimental effects of breastfeeding on the cardiometabolic health of IDM and their mothers.METHODS We performed a database search on different engines and a thorough literature review and included 121 research published in English between January 2000 and December 15,2022,in this review.RESULTS Most of the literature agreed on the beneficial effects of breast milk for both the mother and the infant in the short and long terms.Breastfeeding protects mothers with gestational diabetes against obesity and type 2 DM.Despite some evidence of the protective effects of breastfeeding on IDM in the short and long term,the evidence is not strong enough due to the presence of many confounding factors and a lack of sufficient studies.CONCLUSION We need more comprehensive research to prove these effects.Despite many obstacles that may enface mothers with gestational diabetes to start and maintain breastfeeding,every effort should be made to encourage them to breastfeed.

Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions

BACKGROUND Gas-related complications present a potential risk during transoral endoscopic resection of upper gastrointestinal submucosal lesions.Therefore,the identification of risk factors associated with these complications is essential.AIM To develop a nomogram to predict risk of gas-related complications following transoral endoscopic resection of the upper gastrointestinal submucosal lesions.METHODS We collected patient data from the First Affiliated Hospital of the Army Medical University.Patients were randomly allocated to training and validation cohorts.Risk factors for gas-related complications were identified in the training cohort using univariate and multivariate analyses.We then constructed a nomogram and evaluated its predictive performance based on the area under the curve,decision curve analysis,and Hosmer-Lemeshow tests.RESULTS Gas-related complications developed in 39 of 353 patients who underwent transoral endoscopy at our institution.Diabetes,lesion origin,surgical resection method,and surgical duration were incorporated into the final nomogram.The predictive capability of the nomogram was excellent,with area under the curve values of 0.841 and 0.906 for the training and validation cohorts,respectively.CONCLUSION The ability of our four-variable nomogram to efficiently predict gas-related complications during transoral endoscopic resection enhanced postoperative assessments and surgical outcomes.

Clinical characteristics and outcomes of nosocomial COVID-19 in Turkey:A retrospective multicenter study

Objective:To identify the clinical characteristics and outcomes of hospital-acquired SARS-CoV-2 infection during the vaccination period nationwide in Turkey.Methods:COVID-19 patients followed in the pandemic services across Turkey between January 1,2021,and March 31,2022 were investigated retrospectively.Nosocomial COVID-19 was defined as a patient neither diagnosed with COVID-19 nor suspected COVID-19 at the hospital admission and was confirmed COVID-19≥5 days after hospital admission.The primary outcome of this study was in-hospital mortality;demographic features and vaccination status was compared between survivors and non-survivors.Results:During the study period,15573 COVID-19 patients were followed in 18 centers and 543(3.5%)patients were nosocomial COVID-19.Most patients with nosocomial COVID-19(80.4%)were transferred from medical wards.162(29.8%)of the patients with nosocomial COVID-19 admitted to the intensive care unit due to disease severity and 138(25.4%)of the patients died during hospital stay.Advanced age(≥65 years)and number of comorbid diseases(≥2)was found to be associated with mortality in nosocomial COVID-19(OR 1.74,95%CI 1.11-2.74 and OR 1.60,95%CI 1.02-2.56,respectively).Vaccination was associated with survival in nosocomial COVID-19(OR 0.25,95%CI 0.16-0.38).Conclusions:Patients with nosocomial COVID-19 had increased admission to intensive care units and higher mortality rate.Vaccination can decrease the in-hospital mortality rate.

Fecal calprotectin in pediatric gastrointestinal diseases:Pros and cons

BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

Microphallus early management in infancy saves adulthood sensual life:A comprehensive review

Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected individuals.This article comprehensively reviews micropenis,its etiology,epidemiology,and various treatment options.We conducted a thorough literature review to collect relevant information on micropenis and microphallus,as well as related disorders.Our primary databases were PubMed,Medline,and Google Scholar.We searched for articles published in English between 2000 and 2023.Our analysis included 67 review articles,56 research studies,11 case reports,one guideline,and one editorial.Our search terms included"microphallus","micropenis","congenital hypogonadotropic hypogonadism","androgen insensitivity syndrome","pediatric management of micropenis","testosterone therapy",and"psychosocial implications of micropenis".We focused on diagnosing micropenis and related conditions,including hormonal assessments,medical and surgical treatment options,psychosocial and psychological well-being,sexual development of adolescents,and sociocultural influences on men's perceptions of penile size.Additionally,we explored parenting and family dynamics in cases of micropenis and disorders of sex development,implications of hormonal treatment in neonates,and studies related to penile augmentation procedures and their effectiveness.The article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with micropenis.Surgical procedures,such as penile lengthening and girth enhancement,and non-surgical approaches like hormonal therapy are explored.The significance of psychological support,education,and lifestyle modifications is emphasized.Early management and comprehensive care are crucial for individuals with micropenis,from infancy to adolescence and beyond.A multidisciplinary approach involving urologists,endocrinologists,and mental health professionals is recommended.Regular assessment of treatment effectiveness and the need for updated guidelines are essential to provide the best possible care.Healthcare professionals should prioritize early diagnosis,and neonatologists should measure stretched penile length in neonates.A collaborative effort is needed among professionals,parents,and affected individuals to create a supportive environment that recognizes worth beyond physical differences.Continuous research and evidencebased updates are crucial for improving care standards.

Pulse oximetry in pediatric care:Balancing advantages and limitations

BACKGROUND Pulse oximetry has become a cornerstone technology in healthcare,providing non-invasive monitoring of oxygen saturation levels and pulse rate.Despite its widespread use,the technology has inherent limitations and challenges that must be addressed to ensure accurate and reliable patient care.AIM To comprehensively evaluate the advantages,limitations,and challenges of pulse oximetry in clinical practice,as well as to propose recommendations for optimizing its use.METHODS A systematic literature review was conducted to identify studies related to pulse oximetry and its applications in various clinical settings.Relevant articles were selected based on predefined inclusion and exclusion criteria,and data were synthesized to provide a comprehensive overview of the topic.RESULTS Pulse oximetry offers numerous advantages,including non-invasiveness,real-time feedback,portability,and costeffectiveness.However,several limitations and challenges were identified,including motion artifacts,poor peripheral perfusion,ambient light interference,and patient-specific factors such as skin pigmentation and hemoglobin variants.Recommendations for optimizing pulse oximetry use include technological advancements,education and training initiatives,quality assurance protocols,and interdisciplinary collaboration.CONCLUSION Pulse oximetry is crucial in modern healthcare,offering invaluable insights into patients’oxygenation status.Despite its limitations,pulse oximetry remains an indispensable tool for monitoring patients in diverse clinical settings.By implementing the recommendations outlined in this review,healthcare providers can enhance the effectiveness,accessibility,and safety of pulse oximetry monitoring,ultimately improving patient outcomes and quality of care.

Metabolomic changes in children with autism

BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book chapter.METHODS A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January 2024.Inclusion criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.

Correlation between severity of endoscopic findings and apnea-hypopnea index in patients with gastroesophageal reflux disease and obstructive sleep apnea

AIM: To assess the relationship between severity of gastroesophageal reflux disease and apnea-hypopnea index (AHI) as an indicator of the severity of obstructive sleep apnea. METHODS: Data of 57 patients with proven obstructive sleep apnea and gastroesophageal reflux disease were analyzed. Patients were divided into two groups according to severity of the sleep apnea: 'mild-moderate' (A)-AHI 5≥5-30, n=27, 'severe' (B)-AHI >30, n=30. All patients underwent apnea monitoring during the night, upper panendoscopy and were asked about typical reflux symptoms. RESULTS: All examined patients in both groups showed a significant overweight and there was a positive correlation between body mass index and the degree of sleep apnea (P = 0.0002). The occurence of erosive reflux disease was significantly higher in 'severe' group (P = 0.0001). Using a logistic regression analysis a positive correlation was found between the endoscopic severity of reflux disease and the AHI (P = 0.016). Forty-nine point five percent of the patients experienced the typical symptoms of reflux disease at least three times a week and there was no significant difference between the two groups. CONCLUSION: A positive correlation can be found between the severity of gastroesophageal reflux disease and obstructive sleep apnea.

Comparison of Effectiveness of Gefitinib, Erlotinib, and Afatinib in Advanced Non-small Cell Lung Cancer Patients with EGFR Mutation Positive in Indonesian Population

Background and objective EGFR-tyrosine kinase inhibitors(EGFR-TKIs) were used to treat non-small cell lung cancer(NSCLC) patients with EGFR mutation positive. This study aims to compare the effectiveness of first line TKIs;gefitinib, erlotinib, and afatinib in the treatment of advanced stage NSCLC patients with EGFR mutation positive in the Indonesian population.Methods A retrospective cohort study of 88 NSCLC patients with EGFR mutation positive treated with gefitinib(n=59), erlotinib(n=22), and afatinib(n=7) was performed in national cancer hospital in Indonesia.Inclusion criteria were stage IIIb or IV NSCLC with adenocarcinoma subtype. Subjects less than 18 years or with a history of other malignancy were excluded. Outcomes were treatment response, progression-free survival(PFS), and mortality rate. Results Complete response, partial response, and stable disease were shown in 1.1%, 35.2%, and 31.8% of subjects, respectively. There were 31.8% of subjects developed progressive disease during treatment. Regarding EGFR mutation positive profile, a total of 56.8% subjects had deletion in exon 19, 42% subjects had mutation in exon 21, and rare mutation in exon 18 was found in 3.4% of total subjects. Demography and clinical characteristics had no significant association with the risk of progressive disease. The median PFS of subjects was 11 months(95%CI: 6.8-15.2 months). There was no statistical difference of PFS between treatment groups.Conclusion Gefitinib, erlotinib, and afatinib have similar effectiveness in advanced stage NSCLC with EGFR mutation positive. Afatinib tends to be associated with longer PFS but further investigation is required.

Methods of computed tomography screening and management of lung cancer in Tianjin: design of a population-based cohort study

Objective: European lung cancer screening studies using computed tomography(CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time(VDT) is more specific for early lung cancer detection than a diameter-based protocol. However, whether this also applies to a Chinese population is unclear. The aim of this study is to compare the diagnostic performance of a volume-based protocol with a diameter-based protocol for lung cancer detection and optimize the nodule management criteria for a Chinese population.Methods: This study has a population-based, prospective cohort design and includes 4000 participants from the Hexi district of Tianjin, China. Participants will undergo low-dose chest CT at baseline and after 1 year. Initially, detected lung nodules will be evaluated for diameter and managed according to a routine diameter-based protocol(Clinical Practice Guideline in Oncology for Lung Cancer Screening, Version 2.2018). Subsequently, lung nodules will be evaluated for volume and management will be simulated according to a volume-based protocol and VDT(a European lung nodule management protocol). Participants will be followed up for 4 years to evaluate lung cancer incidence and mortality. The primary outcome is the diagnostic performance of the European volume-based protocol compared to diameter-based management regarding lung nodules detected using low-dose CT.Results: The diagnostic performance of volume-and diameter-based management for lung nodules in a Chinese population will be estimated and compared.Conclusions: Through the study, we expect to improve the management of lung nodules and early detection of lung cancer in Chinese populations.

Differential expression of mucin 1 and mucin 2 in colorectal cancer

AIM To determine tissue expression(mRNA, protein) of two types of mucins [mucin 1(MUC1) and mucin 2(MUC2)] in patients with colorectal cancer(CRC).METHODS Expression of membrane-bound mucin(MUC1) and secretory mucin(MUC2) in CRC(mRNA, protein) were analyzed in tissue material including fragments of tumorsobtained from CRC patients(n = 34), and fragments of normal colorectal tissue from the same patients(control). The analysis was conducted using real-time quantitative polymerase chain reaction(RT-qPCR)(transcripts), immunohistochemistry(IHC)(apomucins), and the modern approach for morphometric analysis of IHC reaction(HSV filter software). Results on tissue expression of both mucins(mRNA, protein) were compared to histological alterations in colorectal cancer samples and correlated with selected clinical data in the patients. The statistical analysis was conducted using Statistica PL v. 12.0 software.RESULTS Significantly higher expression of the MUC1 mRNA in the CRC, compared with the control and the borderline correlation of mRNA expression with MUC1 protein levels in colorectal samples was observed. The expression of apomucins concerned cell membranes(MUC1) and cytoplasm(MUC2) and occurred both in control tissues and in most cancerous samples. There were no significant relationships between MUC1(mRNA, protein) and the clinicopathological data of patients. MUC2 protein expression was significantly lower as compared to the control, while MUC2 mRNA expression was comparable in both groups. The MUC1/MUC2 ratio was significantly higher in CRC tissues than in the control. The higher expression of MUC2 was a feature of mucinous CRC subtypes, and characterized higher histological stage of tumors. Negative correlations have been obtained between MUC2 and the Ki-67 antigen, as well as between MUC2 and p53 protein expressions in CRC.CONCLUSION A combination of tissue overexpression of MUC1, reduced MUC2 expression, and high ratio of MUC1/MUC2 is a factor of poor prognosis in CRC patients. MUC2 tissue expression allows to differentiate mucinous and nonmucinous CRC subtypes.

Second to fourth digit ratio： a predictor of adult lung function

Sex and sex hormones play a major role in lung physiology. It has been proposed that the ratio of the second to fourth digits （digit ratio） is correlated with fetal sex hormones. We therefore hypothesized that digit ratio might help predict lung function. We investigated the relationship between digit ratio and pulmonary function test （PFT） findings. A total of 245 South Korean patients （162 male, 83 female） aged from 34 to 90 years who were hospitalized for urological surgery were prospectively enrolled. Before administering the PFTs, the lengths of the second and fourth digits of the right hand were measured by a single investigator using a digital Vernier caliper. In males （n = 162）, univariate and multivariate analysis using linear regression models showed that digit ratio was a significant predictive factor of forced vital capacity （FVC） and forced expiratory volume in I second （FEV1） （FVC： r = 0.156, P = 0.047; FEVI： r = 0.160, P = 0.042）. In male ever-smokers （n = 69）, lung functions （FVC and FEV1） were correlated with smoking exposure rather than digit ratio. In female never-smokers （n = 83）, lung functions （FEV1 and FEVI/FVC ratio） were positively correlated with digit ratio on univariate analysis （FEVI： r = 0.242, P = 0.027; FEVI/FVC ratio： r = 0.245, P = 0.026）. Patients with lower digit ratios tend to have decreased lung function. These results suggest that digit ratio is a predictor of airway function.

High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson's disease

AIM： To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson＇s disease （WD） in Lithuania. METHODS： Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction （PCR） technique was used to detect the c.3207C〉A （p.H1069Q） mutation. Patients not homozygous for the c.3207C〉A （p.H1069Q） mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler （Biometra T3 Thermocycler, G0ttingen, Germany）. Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer （Applied Biosystems, Darmstadt, Germany）. RESULTS： Total of 13 WD patients （mean age 26.4 years; range 17-40; male/female 3/10） presented with hepatic disorders and 16 their first degree relatives （including 12 siblings） were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders （hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2）. Liver biopsy specimens were available in all of 13 WD patients （8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-1iver steatosis）. Twelve of 13 （92.3%） WD patients had the c.3207C〉A （p.HI069Q） mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C〉T （p.RI041W） or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder （Leipzig score 6）, no mutations were found. Out of 16 first degree WD relatives, 11 （68.7%） were heterozygous for the c.3207C〉A （p.H1069Q） mutation. Two patients with fulminant WD died from acute liver failure and ii are in full remission under peniciilamine or zinc acetate treatment. Three women with WD successfully delivered healthy babies. CONCLUSION： The c.3207C〉A （p.HI069Q） missense mutation is the most characteristic mutation for Lithuanian patients with WD. Even 92.3% of WD patients with hepatic presentation of the disease are homozygous or compound heterozygotes for the p.H1069Q mutation.

Clinical characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer hospital

Objectives:To evaluate the characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer hospital.Methods:Patients with pulmonary nodules 4–25 mm in diameter detected via computed tomography(CT)in 2013 were consecutively included.The analysis was restricted to patients with a histological nodule diagnosis or a 2-year follow-up period without nodule growth confirming benign disease.Patient information was collected from hospital records.Results:Among the 314 nodules examined in 299 patients,212(67.5%)nodules in 206(68.9%)patients were malignant.Compared to benign nodules,malignant nodules were larger(18.0 mm vs.12.5 mm,P<0.001),more often partly solid(16.0%vs.4.7%,P<0.001)and more often spiculated(72.2%vs.41.2%,P<0.001),with higher density in contrast-enhanced CT(67.0 HU vs.57.5 HU,P=0.015).Final diagnosis was based on surgery in 232 out of 314(73.9%)nodules,166 of which were identified as malignant[30(18.1%)stage III or IV]and 66 as benign.In 36 nodules(11.5%),diagnosis was confirmed by biopsy and the remainder verified based on stability of nodule size at follow-up imaging(n=46,14.6%).Among 65 nodules subjected to gene(EGFR)mutation analyses,28(43.1%)cases(EGFR19 n=13;EGFR21 n=15)were identified as EGFR mutant and 37(56.9%)as EGFR wild-type.Prior to surgery,the majority of patients[n=194(83.6%)]received a contrast-enhanced CT scan for staging of both malignant[n=140(84.3%)]and benign[n=54(81.8%)]nodules.Usage of positron emission tomography(PET)-CT was relatively uncommon[n=38(16.4%)].Conclusions:CT-derived nodule assessment assists in diagnosis of small to intermediate-sized malignant pulmonary nodules.Currently,contrast-enhanced CT is commonly used as the sole diagnostic confirmation technique for pre-surgical staging,often resulting in surgery for late-stage disease and unnecessary surgery in cases of benign nodules.