People with genetic kidney diseases on kidney replacement therapy have different clinical outcomes compared to people with other kidney diseases.

Despite increasing awareness of genetic kidney disease prevalence, there is limited population-level information about long term outcomes of people with genetic kidney disease receiving kidney replacement therapy. This analysis included people who commenced kidney replacement therapy between 1989 and 2020 as recorded in the Australian and New Zealand Dialysis and Transplant registry. Genetic kidney diseases were subclassified as majority and minority monogenic. Non-genetic kidney diseases were included as the comparator group. Primary outcome measures were 10-year mortality and 10-year graft failure. Cox proportional hazard regression were used to calculate unadjusted and adjusted hazard ratios (AHRs) for primary outcomes. There were 59,231 people in the dialysis subgroup and 21,860 people in the transplant subgroup. People on dialysis with genetic kidney diseases had reduced 10-year mortality risk (majority monogenic AHR: 0.70, 95% CI 0.66-0.76; minority monogenic AHR 0.86, 95% CI 0.80-0.92). This reduced 10-year mortality risk continued after kidney transplantation (majority monogenic AHR: 0.82, 95% CI 0.71-0.93; minority monogenic AHR 0.80, 95% CI 0.68-0.95). Majority monogenic genetic kidney diseases were associated with reduced 10-year graft failure compared to minority monogenic genetic kidney diseases and other kidney diseases (majority monogenic AHR 0.69, 95% CI 0.59-0.79). This binational registry analysis identified that people with genetic kidney disease have different mortality and graft failure risks compared to people with other kidney diseases.

MD-ALL: an integrative platform for molecular diagnosis of B-acute lymphoblastic leukemia.

B-acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEPs) and various genetic lesions. With the application of transcriptome sequencing (RNA-seq), multiple novel subtypes have been identified, which lead to an advanced B-ALL classification and risk-stratification system. However, the complexity of analyzing RNA-seq data for B-ALL classification hinders the implementation of the new B-ALL taxonomy. Here, we introduce MD-ALL (Molecular Diagnosis of ALL), an integrative platform featuring sensitive and accurate B-ALL classification based on GEPs and sentinel genetic alterations from RNA-seq data. In this study, we systematically analyzed 2,955 B-ALL RNA-seq samples and generated a reference dataset representing all the reported B-ALL subtypes. Using multiple machine learning algorithms, we identified the feature genes and then established highly sensitive and accurate models for B-ALL classification using either bulk or single-cell RNA-seq data. Importantly, this platform integrates multiple aspects of key genetic lesions acquired from RNAseq data, which include sequence mutations, large-scale copy number variations, and gene rearrangements, to perform comprehensive and definitive B-ALL classification. Through validation in a hold-out cohort of 974 samples, our models demonstrated superior performance for B-ALL classification compared with alternative tools. Moreover, to ensure accessibility and user-friendly navigation even for users with limited or no programming background, we developed an interactive graphical user interface for this MD-ALL platform, using the R Shiny package. In summary, MD-ALL is a user-friendly B-ALL classification platform designed to enable integrative, accurate, and comprehensive B-ALL subtype classification. MD-ALL is available from https://github.com/gu-lab20/MD-ALL.

MD-ALL: an Integrative Platform for Molecular Diagnosis of B-cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEPs) and various genetic lesions. With the application of transcriptome sequencing (RNA-seq), multiple novel subtypes have been identified, which lead to an advanced B-ALL classification and risk-stratification system. However, the complexity of analyzing RNA-seq data for B-ALL classification hinders the implementation of the new B-ALL taxonomy. Here, we introduce MD-ALL (Molecular Diagnosis of ALL), a user-friendly platform featuring sensitive and accurate B-ALL classification based on GEPs and sentinel genetic alterations. In this study, we systematically analyzed 2,955 B-ALL RNA-seq samples and generated a reference dataset representing all the reported B-ALL subtypes. Using multiple machine learning algorithms, we identified the feature genes and then established highly accurate models for B-ALL classification using either bulk or single-cell RNA-seq data. Importantly, this platform integrates the key genetic lesions, including sequence mutations, large-scale copy number variations, and gene rearrangements, to perform comprehensive and definitive B-ALL classification. Through validation in a hold-out cohort of 974 samples, our models demonstrated superior performance for B-ALL classification compared with alternative tools. In summary, MD-ALL is a user-friendly B-ALL classification platform designed to enable integrative, accurate, and comprehensive B-ALL subtype classification.

Effect of mobile interventions with nicotine replacement therapy sampling on long-term smoking cessation in community smokers: A pragmatic randomized clinical trial.

INTRODUCTION: Mobile interventions enable personalized behavioral support that could improve smoking cessation (SC) in smokers ready to quit. Scalable interventions, including unmotivated smokers, are needed. We evaluated the effect of personalized behavioral support through mobile interventions plus nicotine replacement therapy sampling (NRT-S) on SC in Hong Kong community smokers. METHODS: A total of 664 adult daily cigarette smokers (74.4% male, 51.7% not ready to quit in 30 days) were proactively recruited from smoking hotspots and individually randomized (1:1) to the intervention and control groups (each, n=332). Both groups received brief advice and active referral to SC services. The intervention group received 1-week NRT-S at baseline and 12-week personalized behavioral support through SC advisor-delivered Instant Messaging (IM) and a fully automated chatbot. The control group received regular text messages regarding general health at a similar frequency. Primary outcomes were carbon monoxide-validated smoking abstinence at 6 and 12 months post-treatment initiation. Secondary outcomes included self-reported 7-day point-prevalence and 24-week continuous abstinence, quit attempts, smoking reduction, and SC service use at 6 and 12 months. RESULTS: By intention-to-treat, the intervention group did not significantly increase validated abstinence at 6 months (3.9% vs 3.0%, OR=1.31; 95% CI: 0.57-3.04) and 12 months (5.4% vs 4.5%, OR=1.21; 95% CI: 0.60-2.45), as were self-reported 7-day point-prevalence abstinence, smoking reduction, and SC service use at 6 and 12 months. More participants in the intervention than control group made a quit attempt by 6 months (47.0% vs 38.0%, OR=1.45; 95% CI: 1.06-1.97). Intervention engagement rates were low, but engagement in IM alone or combined with chatbot showed higher abstinence at 6 months (adjusted odds ratios, AORs=4.71 and 8.95, both p<0.05). CONCLUSIONS: Personalized behavioral support through mobile interventions plus NRT-S did not significantly improve abstinence in community smokers compared to text only messaging. The suboptimal intervention engagement needs to be addressed in future studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04001972.

Legacy of culture heritage building revitalization: place attachment and culture identity.

Introduction: Cultural heritage buildings are revitalized to promote culture instead of being neglected or demolished. For locals, the revitalization of heritage buildings symbolizes a commitment to the community and a taste of collective memory. The study attempts to test the effectiveness of heritage cultural building on visitors' post-experience behavior through cultural identity and place attachment. "Cultural activities engagement" and "knowledge transfer" serves as moderating attributes. Their moderating the effects on cultural identity and place attachment are examined, respectively. Method: A valid sample size of 348 from four heritage buildings located in Hong Kong: Tai Kwun, Police Married Quarters (PMQ), Mei Ho House and The Mills. A data analysis platform for PLSSEM is chosen for this study. Results: Results demonstrate that the effectiveness of heritage building revitalization on visitors' local cultural identity and emotions leading to place attachment. Discussion: In our study, the effectiveness of heritage building encompasses three elements which includes appearance and components; technology and planning as well as contribution. Knowledge transfer positively moderates the effectiveness of heritage building revitalization and cultural identity. However, cultural activity engagement negatively moderates place attachment. Findings also exhibit that place attachment in heritage building revitalization leads to a positive experience extension. For the practical contribution, the study provides insights to policy makers and planners for historic building design such as appearance and components, technology in facilitating local visitors' local identity.

Blood Biomarkers Predict Cardiac Workload Using Machine Learning.

INTRODUCTION: Rate pressure product (the product of heart rate and systolic blood pressure) is a measure of cardiac workload. Resting rate pressure product (rRPP) varies from one individual to the next, but its biochemical/cellular phenotype remains unknown. This study determined the degree to which an individual's biochemical/cellular profile as characterized by a standard blood panel is predictive of rRPP, as well the importance of each blood biomarker in this prediction. METHODS: We included data from 55,730 participants in this study with complete rRPP measurements and concurrently collected blood panel information from the Health Management Centre at the Affiliated Hospital of Hangzhou Normal University. We used the XGBoost machine learning algorithm to train a tree-based model and then assessed its accuracy on an independent portion of the dataset and then compared its performance against a standard linear regression technique. We further determined the predictive importance of each feature in the blood panel. RESULTS: We found a fair positive correlation (Pearson r) of 0.377 (95% CI: 0.375-0.378) between observed rRPP and rRPP predicted from blood biomarkers. By comparison, the performance for standard linear regression was 0.352 (95% CI: 0.351-0.354). The top three predictors in this model were glucose concentration, total protein concentration, and neutrophil count. Discussion/. CONCLUSION: Blood biomarkers predict resting RPP when modeled in combination with one another; such models are valuable for studying the complex interrelations between resting cardiac workload and one's biochemical/cellular phenotype.

Seizures in autoimmune encephalitis-A systematic review and quantitative synthesis.

OBJECTIVE: This study aimed to evaluate the proportion of patients with seizures and electroencephalography (EEG) abnormalities in autoimmune encephalitis (AE) and its most common subtypes. METHODS: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards and was registered with the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline All, Embase, and PsychINFO in Ovid from inception to June 2019 for articles pertaining to AE and seizure. Included studies reported seizure and/or EEG data in cohorts of ≥10 AE patients. Patient demographics, antibody type, seizure incidence, and EEG findings were extracted. Review of studies and data extraction were performed in duplicate. In addition to descriptive analysis, quantitative synthesis stratified by autoantibody subtype was performed with logistic regression and chi-square analyses. RESULTS: Our search yielded 3856 abstracts: 1616 were selected for full-text review and 118 studies met eligibility criteria. Of 3722 antibody-positive AE patients, 2601 (69.9%) had clinical seizures during the course of their illness. Of the 2025 patients with antibody-positive AE and available EEG data, 1718 (84.8%) had some EEG abnormality (eg, epileptiform discharges, slowing, and so on). Anti- N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE) was the most commonly reported type of AE (1985/3722, 53.3%). Of the anti-NMDARE patients with available seizure or EEG data, 71.8% (n = 1425/1985) had clinical seizures during their illness, and 89.7% (n = 1172/1306) had EEG abnormalities. For all AE patients and in the anti-NMDARE subpopulation, seizures were more common in younger patients (p < .05). SIGNIFICANCE: This systematic review provides an estimate of the proportion of AE patients with seizures, confirming the magnitude of seizure burden in this population. Prospective studies are needed to understand population-based prevalence of seizures, identify factors associated with seizures, and evaluate particular EEG findings as biomarkers of seizures and outcomes in AE.

A concept analysis of influence for nurse leaders.

BACKGROUND: To shape priorities for health and health care outcomes, it is essential for nurse leaders to be influential. The application and impact of influence are readily recognized, but not its characteristics. PURPOSE: The purpose of this project was to conduct a concept analysis of influence relative to nurse leaders. METHODS: The Walker and Avant method of concept analysis was utilized. FINDINGS: Attributes of influence include advocacy, communications skills, competency, confidence, credibility, and engagement. Antecedents of influence are authority, collaboration, integrity, and mentorship. Consequences of influence are action, change, commitment, compliance, decision-making, motivation, and resistance. DISCUSSION: By drawing upon a systematic understanding of the concept of influence, nurse leaders are urged to develop and leverage the attributes of influence to drive and achieve collective good for the future of health and health care in society.

Effectiveness of nicotine replacement therapy sample at outdoor smoking hotspots for initiating quit attempts and use of smoking cessation services: a protocol for a cluster randomised controlled trial.

INTRODUCTION: More than half of the smoking population in Hong Kong are unmotivated to quit. Only about 2% of tobacco users in the territory have ever used cessation aids such as nicotine replacement therapy (NRT). The present study aims to assess the effectiveness of delivering 1-week free NRT sample plus brief intervention to smokers at outdoor smoking hotspots on quit attempts and use of smoking cessation services. METHODS AND ANALYSIS: This is a two-arm, pragmatic, multisite, cluster randomised controlled trial (RCT) on the effectiveness of increasing quit attempts, use of cessation service and recruitment outcomes. Trained smoking cessation ambassadors will approach smokers at outdoor smoking hotspots, and deliver brief smoking cessation advice. Recruitment sessions are randomised to intervention or control group (allocation ratio 1:1). Participants in the intervention group (n=550) will receive 1-week free NRT sample (either patch or gum), brief medication advice from an onsite nurse and cessation service referral, whereas participants in control group (n=275) will only receive the brief advice and service referral. The primary outcomes are the proportion of participants who enrol in any cessation service in Hong Kong within 1 month of the recruitment, and the proportion of participants who report quit attempts at 1-month follow-up. Secondary outcomes include self-reported use of NRT, self-reported 7-day tobacco abstinence, 30-day abstinence at 3 months and 6 months, biochemically validated abstinence at 6 months, perceived importance, difficulty and confidence to quit (scale 0-10), and Incremental Behavior Change towards Smoking Cessation. Process outcomes include number of smokers who will be approached, will accept the brief smoking cessation advice or be recruited to participate in the RCT. ETHICS AND DISSEMINATION: The Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster approved the trial (UW 18-118). Findings will be disseminated through funding website, publication and conference presentations. TRIAL REGISTRATION NUMBER: NCT03717051.

Effectiveness of WhatsApp online group discussion for smoking relapse prevention: protocol for a pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Sustained psychosocial support via online social groups may help former tobacco users maintain abstinence. This study aims to examine the effectiveness of participating in a WhatsApp social group for long-term smoking cessation. DESIGN: Two-arm, open-labelled, pragmatic, individually randomized controlled trial. SETTING: All participants are service users of smoking cessation clinics, and all interventions are delivered via mobile phones. PARTICIPANTS: Participants included 1008 adult quitters who self-report no tobacco use in the past 3-30 days. INTERVENTIONS: The intervention group (n = 504) will join a WhatsApp social group to receive standardized and theory-based reminders of smoking relapse prevention and participate in discussion with other WhatsApp group members using their own mobile phones. All social groups will be led by counselors or specialist nurse practitioners. The control group (n = 504) will receive similar reminders via short messages to their own mobile phones but will not interact with other participants. The intervention duration for both groups is 8 weeks. Both groups will receive a booklet at baseline about how to prevent smoking relapse. MEASUREMENTS: The primary outcome is biochemically validated tobacco abstinence at 12 months after consent. COMMENTS: The findings will provide evidence concerning the utility of operating online social group discussion for prevention of smoking relapse and sustaining long-term abstinence.

Brief handgrip and isometric exercise intervention for smoking cessation: A pilot randomized trial.

INTRODUCTION: Isometric exercises reduce craving, negative affect, and withdrawal symptoms during smoking cessation. This randomized controlled trial (RCT) was the first to test if a brief intervention using a handgrip and isometric exercises including hand pushing/pulling was feasible and efficacious to increase tobacco abstinence at 6-month. METHODS: This was a single-blinded, 2-arm pilot RCT in 6 community-based smoking cessation clinics in Hong Kong. Smokers who consumed 10 or more cigarettes a day and were receiving cessation services were randomized to the exercise group (n = 108) who received a free handgrip and a leaflet about handgrip exercise, and watched a 5-minute video, or to the healthy-diet group (n = 100) who receive a similar dosage of intervention on healthy diet. The primary outcome was self-reported abstinence in the previous 4 weeks at 6-month follow-up. RESULTS: In the exercise group, about 36% reported doing the exercises when craving at 2-month follow-up. No significant difference in quit rate was found between groups (34% vs. 39%, OR = 0.80, P = .40). A posteriori analysis on the exercise group showed that self-reported exercises when craving (49% vs. 26%, OR = 2.69, 1.18-6.15, P = .02) and total adherence (including doing the exercises when craving, once a day, and/or for 2 weeks) (53% vs. 23%, OR = 3.70, 1.15-11.92, P = .03) were significantly associated with self-reported abstinence. CONCLUSIONS: The brief handgrip/isometric exercise intervention was feasible and achieved modest adherence without offering incentives or mandatory reminders. Preliminary evidence of benefits was observed in the intervention group if the exercises were done when craving. IMPLICATIONS: Our study indicates that a brief exercise intervention, including a free handgrip and educational video, was feasible for smokers receiving smoking cessation treatment. It was particularly efficacious in increasing tobacco abstinence when exercise adherence was high. TRIAL REGISTRATION: ClinicalTrial.gov (NCT02844296).

Thoughts About Real Nursing.

This essay presents thoughts about what constitutes real nursing and who may be considered a real nurse.

Use of standardized letters of recommendation for otolaryngology head and neck surgery residency and the impact of gender.

OBJECTIVES: To evaluate gender-based differences in narrative letters of recommendation (NLORs) and standardized letters of recommendation (SLORs) submitted for applicants to an otolaryngology head and neck surgery (OHNS) residency program. STUDY DESIGN: Retrospective review. METHODS: Nine hundred fifty-eight letters of recommendation (LORs) submitted to one OHNS program in 2013 to 2014 were analyzed. RESULTS: NLORs (n = 590) and SLORs (n = 368) were reviewed. Male writers composed over 85% of all LORs. Compared with male writers, female writers of LORs were more likely to compose a letter of minimal assurance (P < 0.025). Female writers of SLORs were more likely to rank applicants higher in communication skills (P < 0.035) and match potential (P < 0.045). Analysis of LORs by applicant gender revealed that female applicants were more likely than male applicants to be described as team players (P < 0.025) and less likely to receive a letter of minimal assurance (P < 0.001). Compared with SLORs, NLORs written for male applicants were more likely to reference their leadership potential (P < 0.001). Female applicants were less likely to be described as "bright" (P < 0.001) and more likely to have their appearance mentioned (P < 0.03) in NLORs when compared to SLORs. CONCLUSION: Although we found that SLORs reduce gender biases compared to NLORs, there remain significant differences in how female and male applicants are described. Greater awareness of historical biases likely has contributed to more equitable letter writing, although impactful gender biases remain when reviewing applicants. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:2738-2745, 2017.

Online Social Support for the Prevention of Smoking Relapse: A Content Analysis of the WhatsApp and Facebook Social Groups.

BACKGROUND: Online social groups have been increasingly used for smoking cessation intervention. INTRODUCTION: This study aimed to explore the social support components of the online discussion through WhatsApp and Facebook, how these components addressed the need of relapse prevention, and how the participants evaluated this intervention. MATERIALS AND METHODS: We coded and analyzed the posts (N = 467) by the 82 recent quitters in WhatsApp and Facebook social groups, who were recruited from the eight smoking cessation clinics in Hong Kong to participate in a pragmatic randomized trial of relapse prevention. Participants' postintervention feedback was collected from the 13 qualitative interviews after the intervention. RESULTS: The WhatsApp social groups had more participants' posts than the Facebook counterparts. The participants' posts in the online social groups could be classified as sharing views and experiences (55.5%), encouragement (28.7%), and knowledge and information (15.8%). About half of the participants' posts (52.9%) addressed the themes listed in the U.S. Clinical Practice Guideline for preventing smoking relapse. The participants perceived the posts as useful reminders for smoking cessation, but avoidance of reporting relapse, inactive discussions, and uninteresting content were barriers to the success of the intervention. DISCUSSION: Online social groups provided a useful platform for the delivery of cessation support and encouragement of reporting abstinence, which support relapse prevention. The effectiveness of such intervention can be improved by encouraging more self-report of relapse, active discussions, sharing of interesting content, and using an appropriate discussion platform. CONCLUSION: Quitters who participate in the online social groups can benefit from peer support and information sharing, and hence prevent smoking relapse.

Using WhatsApp and Facebook Online Social Groups for Smoking Relapse Prevention for Recent Quitters: A Pilot Pragmatic Cluster Randomized Controlled Trial.

BACKGROUND: Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. OBJECTIVE: Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. METHODS: This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. RESULTS: Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators' posts (median 60, IQR 25 vs median 32, IQR 7; P=.05) and participants' posts (median 35, IQR 50 vs median 6, IQR 9; P=.07) than their Facebook counterparts, but the difference was insignificant. CONCLUSIONS: The intervention via the WhatsApp social group was effective in reducing relapse probably because of enhanced discussion and social support. Inactive discussion in the Facebook social group might have attributed to the lower effectiveness. CLINICALTRIAL: Clinicaltrials.gov NCT02007369; https://clinicaltrials.gov/show/NCT02007369 (Archived by WebCite® at http://www.webcitation.org/6c3RbltQG).

In need of each other: the moderator of task interdependence between LMX variability and justice.

AIM: This study examined how leader-member exchange differentiation could affect nurses' perception of organisational justice as well as the moderating effect of task interdependence on this link. BACKGROUND: Teams are essential to the health-care industry. However, the perception of injustice may lead to a high level of nurse turnover. METHOD: Data was collected from 187 nurses distributed in eight units in a mid-western hospital in the USA. Hierarchical linear modeling was used to analyze the cross-level interaction of leader-member exchange variability and task interdependence on individual-level perceptions of justice. RESULTS: Leader-member exchange variability was significantly related to distributive justice and interactional justice but not significantly related to procedural justice. The interaction term was significantly related to interpersonal justice, but not to procedural justice or distributive justice. CONCLUSION: This study showed that if leaders demonstrated a variation in treatment of different subordinates, nurses could perceive this as unfair regarding distribution and interaction; when the group was highly task interdependent, this kind of perception of 'unfairness,' particularly regarding interpersonal treatment, became even more salient. IMPLICATIONS FOR NURSING MANAGEMENT: Preferential and inconsistent treatment by them within the work group could introduce nurses' perceptions of unfair treatment. It is of crucial importance to provide training for supervisors on how to display relatively consistent behaviour towards nurses, particularly when the teams are highly task interdependent.

Novel technique for removal of misdirected laparoscopic Weck clips.

The Weck clip has emerged as an attractive option for laparoscopic vascular control. It is secure and easy to use. However, once fired, the clip can be difficult to remove. We describe a novel technique for the safe removal of misdirected Weck clips using the Harmonic scalpel.

Prognostic significance of HER2/neu, p53, and vascular endothelial growth factor expression in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung.

In this study, we investigated the prognostic value of HER2/neu, p53, and vascular endothelial growth factor in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung. We studied 100 patients and consisted of 50 cases with conventional adenocarcinoma and 50 cases with bronchioloalveolar carcinoma (32 nonmucinous and 18 mucinous subtypes). Representative sections were immunostained for HER2/neu, p53, and vascular endothelial growth factor. Positivity was scored quantitatively by three observers and correlated with multiple prognostic parameters including survival. In the conventional adenocarcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 19/50 (38%), 32/50 (64%), 33/50 (66%), respectively. In this group, p53 showed a significant correlation with recurrence while vascular endothelial growth factor correlated with angiolymphatic invasion (P < 0.05). HER2/neu, p53, and vascular endothelial growth factor expression was associated with significantly shorter survival (log rank, P < 0.05). Patient whose tumors coexpressed both p53 and HER2/neu had the worst outcome. In the bronchioloalveolar carcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 9/50 (18%), 3/50 (6%) and 12/50 (24%), respectively which was significantly less than in conventional adenocarcinoma (P < 0.05). HER2/neu positivity showed a significant correlation with shorter survival (log rank, P < 0.05) in nonmucinous type. In conclusion, vascular endothelial growth factor was associated with angiolymphatic invasion and poor prognosis in conventional adenocarcinoma. Also, in conventional adenocarcinoma, p53, and HER2/neu expression appeared to be poor prognostic markers, while in bronchioloalveolar carcinoma, only HER2/neu was associated with a poorer prognosis. This immunostaining pattern suggests that conventional adenocarcinoma has different molecular abnormalities than bronchioloalveolar carcinoma.

Prognostic significance of thyroid transcription factor-1 expression in both early-stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung.

Thyroid transcription factor 1 (TTF-1) is a diagnostic immunohistochemical marker for primary pulmonary neoplasms, but its utility as a prognostic marker is not well established. Surgical specimens from 100 cases of pulmonary adenocarcinoma were retrieved from the hospital computer system, including 50 cases of conventional adenocarcinoma (CA) and 50 cases of bronchioloalveolar adenocarcinoma (BAC) (32 nonmucinous type and 18 mucinous type). Representative sections were immunostained for TTF-1. Positive immunohistochemical study was correlated with other prognostic parameters. In the CA group, strong or moderate TTF-1 expression was seen in 30 of 50 (60%) patients and was associated with significantly better survival compared with those patients having weak staining (7 cases; 14%) or negative staining (13 cases; 26%) (P <0.01; log-rank test). Spearman and Pearson's correlation showed no significant correlation between TTF-1 expression and tumor grade, size, recurrence, or vascular invasion; therefore, TTF-1 was considered an independent predictor of survival. In the BAC group, TTF-1 was strongly expressed in 34 of 50 cases (68%) and was negative in 16 of 50 cases (32%), including 14 mucinous BACs. Although TTF-1 immunoreactivity was not statistically associated with good survival in BAC patients, those patients with strong immunohistochemical expression showed a trend toward longer survival. Our results indicate that TTF-1 positivity is an independent predictor of better survival, especially in patients with CA. Mucinous and nonmucinous BACs exhibit disparate staining patterns with TTF-1, with nonmucinous BAC demonstrating greater positivity. Although nonmucinous BAC patients showing strong positive staining had longer survival, the difference was not statistically significant, which is probably related to the overall good survival of patients with early-stage BAC.

Prognostic value of immunohistochemical expressions of p53, HER-2/neu, and bcl-2 in stage I non-small-cell lung cancer.

The outcomes of patients with stage I non-small-cell lung cancer (NSCLC) vary greatly, with a 5-year survival rate of approximately 60%. This study evaluated a number of molecular markers that may aid in predicting prognosis in stage I NSCLC after surgical resection. Immunohistochemical (IHC) staining of p53, HER-2/neu, bcl-2 proteins was performed on paraffin-embedded sections from 85 stage I NSCLC patients who underwent surgery and were followed up for 32 to 44 (median, 39.0; mean, 37.1) months postoperatively. Differences in survival rates were evaluated by log rank test. The prevalence of p53, HER-2/neu, and bcl-2 expression in stage I NSCLC is 59%, 29%, and 46%, respectively. HER-2/neu expression is seen more frequently in adenocarcinomas, and bcl-2 is seen more frequently in squamous carcinomas. p53 and HER-2/neu expression in stage I NSCLC is associated with significantly short survival. Patients whose tumors were both p53 and HER-2/neu positive had the worst outcome, with a survival rate of only 20%, compared with 80% in those whose tumors were both p53 and HER-2/neu negative (P = .0003). The survival rates were 54% in patients who were p53 positive but HER-2/neu negative and 50% in those who were in p53 negative, HER-2/neu positive. The differences among these 4 groups were statistically significant (P =.001). Bcl-2 does not seem to be a prognostic factor for survival. Multivariate analysis showed that overexpression of p53 and HER-2/neu, presence of angiolymphatic invasion, and tumor size > 3.0 cm were independent factors predicting poor survival. p53 and HER-2/neu by IHC staining appear to be valuable prognostic markers in stage I NSCLC patients after surgery. The worst outcome was seen in patients who expressed both p53 and HER-2/neu, suggesting that these patients might benefit from additional adjuvant therapy.