HUNCHEST-II contributes to a shift to earlier-stage lung cancer detection: final results of a nationwide screening program.

OBJECTIVES: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases. METHODS: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening. Screening outcomes were determined based on the volume, growth, and volume doubling time of pulmonary nodules or masses. The clinical stage distribution of screen-detected cancers was compared with two independent practice-based databases consisting of unscreened LC patients. RESULTS: The percentage of negative and indeterminate tests at baseline were 74.2% and 21.7%, respectively, whereas the prevalence of positive LDCT results was 4.1%. Overall, 76 LC patients were diagnosed throughout the screening rounds (1.8% of total participants), out of which 62 (1.5%) patients were already identified in the first screening round. The overall positive predictive value of a positive test was 58%. Most screen-detected malignancies were stage I LCs (60.7%), and only 16.4% of all cases could be classified as stage IV disease. The percentage of early-stage malignancies was significantly higher among HUNCHEST-II screen-detected individuals than among the LC patients in the National Koranyi Institute of Pulmonology's archive or the Hungarian Cancer Registry (p < 0.001). CONCLUSIONS: HUNCHEST-II demonstrates that LDCT screening for LC facilitates early diagnosis, thus arguing in favor of introducing systematic LC screening in Hungary. CLINICAL RELEVANCE STATEMENT: HUNCHEST-II is the so-far largest population-based low-dose CT screening program in Hungary. A positive test's overall positive predictive value was 58%, and most screen-detected malignancies were early-stage lesions. These results pave the way for expansive systematic screening in the region. KEY POINTS: • Conducted in 18 medical facilities, HUNCHEST-II is the so far largest population-based low-dose CT screening program in Hungary. • The vast majority of screen-detected malignancies were early-stage lung cancers, and the overall positive predictive value of a positive test was 58%. • HUNCHEST-II facilitates early diagnosis, thus arguing in favor of introducing systematic lung cancer screening in Hungary.

Computed Tomography Severity Index vs. Other Indices in the Prediction of Severity and Mortality in Acute Pancreatitis: A Predictive Accuracy Meta-analysis.

Background: The management of the moderate and severe forms of acute pancreatitis (AP) with necrosis and multiorgan failure remains a challenge. To predict the severity and mortality of AP multiple clinical, laboratory-, and imaging-based scoring systems are available. Aim: To investigate, if the computed tomography severity index (CTSI) can predict the outcomes of AP better than other scoring systems. Methods: A systematic search was performed in three databases: Pubmed, Embase, and the Cochrane Library. Eligible records provided data from consecutive AP cases and used CTSI or modified CTSI (mCTSI) alone or in combination with other prognostic scores [Ranson, bedside index of severity in acute pancreatitis (BISAP), Acute Physiology, and Chronic Health Examination II (APACHE II), C-reactive protein (CRP)] for the evaluation of severity or mortality of AP. Area under the curves (AUCs) with 95% confidence intervals (CIs) were calculated and aggregated with STATA 14 software using the metandi module. Results: Altogether, 30 studies were included in our meta-analysis, which contained the data of 5,988 AP cases. The pooled AUC for the prediction of mortality was 0.79 (CI 0.73-0.86) for CTSI; 0.87 (CI 0.83-0.90) for BISAP; 0.80 (CI 0.72-0.89) for mCTSI; 0.73 (CI 0.66-0.81) for CRP level; 0.87 (CI 0.81-0.92) for the Ranson score; and 0.91 (CI 0.88-0.93) for the APACHE II score. The APACHE II scoring system had significantly higher predictive value for mortality than CTSI and CRP (p = 0.001 and p < 0.001, respectively), while the predictive value of CTSI was not statistically different from that of BISAP, mCTSI, CRP, or Ranson criteria. The AUC for the prediction of severity of AP were 0.80 (CI 0.76-0.85) for CTSI; 0.79, (CI 0.72-0.86) for BISAP; 0.83 (CI 0.75-0.91) for mCTSI; 0.73 (CI 0.64-0.83) for CRP level; 0.81 (CI 0.75-0.87) for Ranson score and 0.80 (CI 0.77-0.83) for APACHE II score. Regarding severity, all tools performed equally. Conclusion: Though APACHE II is the most accurate predictor of mortality, CTSI is a good predictor of both mortality and AP severity. When the CT scan has been performed, CTSI is an easily calculable and informative tool, which should be used more often in routine clinical practice.

The effect of serum triglyceride concentration on the outcome of acute pancreatitis: systematic review and meta-analysis.

Elevated serum triglyceride concentration (seTG, >1.7 mM or >150 mg/dL) or in other words hypertriglyceridemia (HTG) is common in the populations of developed countries. This condition is accompanied by an increased risk for various diseases, such as acute pancreatitis (AP). It has been proposed that HTG could also worsen the course of AP. Therefore, in this meta-analysis, we aimed to compare the effects of various seTGs on the severity, mortality, local and systemic complications of AP, and on intensive care unit admission. 16 eligible studies, including 11,965 patients were retrieved from PubMed and Embase. The results showed that HTG significantly elevated the odds ratio (OR = 1.72) for severe AP when compared to patients with normal seTG (<1.7 mM). Furthermore, a significantly higher occurrence of pancreatic necrosis, persistent organ failure and renal failure was observed in groups with HTG. The rates of complications and mortality for AP were significantly increased in patients with seTG >5.6 mM or >11.3 mM versus <5.6 mM or <11.3 mM, respectively. We conclude that the presence of HTG worsens the course and outcome of AP, but we found no significant difference in AP severity based on the extent of HTG.

Preexisting Diabetes Elevates Risk of Local and Systemic Complications in Acute Pancreatitis: Systematic Review and Meta-analysis.

The prevalence of diabetes mellitus (DM) and acute pancreatitis (AP) increases continuously, therefore, to understand the effects of preexisting diabetes on AP is crucially needed. Here, we performed a systematic review and meta-analysis in which AP patients including DM and non-DM groups were sorted. Several outcome parameters were analyzed, and the odds ratio (OR) and standardized mean difference with 95% confidence intervals (CIs) were calculated.We found 1417 articles, of which 9 articles involving 354,880 patients were analyzed. More complications were seen in diabetic patients than in non-DM patients (OR, 1.553 [95% CI, 1.266-1.904]; P < 0.001). Intensive care unit admission (OR, 1.799 [95% CI, 1.442-2.243]; P < 0.001) and renal failure (OR, 1.585 [95% CI, 1.278-1.966]; P < 0.001) were more frequent in DM patients. There was a tendency of higher mortality and local complications (OR, 1.276 [95% CI, 0.991-1.643]; P = 0.059; and OR, 1.267 [95% CI, 0.964-1.659]; P = 0.090, respectively) in preexisting DM. Length of hospitalization was longer in DM patients (standardized mean difference, 0.217 [95% CI, 0.075-0.360]; P = 0.003). Preexisting DM negatively influences the outcome of AP and increases the risk of renal failure, local complications, and mortality.

Pancreatitis-Associated Genes and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the connection between pancreatic cancer (PC) and genetic variants associated with chronic pancreatitis via systematic review and meta-analysis. METHODS: The data search was performed in 3 major databases (PubMed, Embase, and Cochrane Library). The selected studies have looked into the presence of the pancreatitis-associated genes in patients with PC and in control subjects, the outcome being the frequency of the mutations in the 2 groups. For the binary outcomes, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: Ten articles proved to be eligible for the qualitative synthesis, and 8 articles were suitable for statistical analysis. Six case-control studies, comprising 929 PC cases and 1890 control subjects for serine protease inhibitor Kazal type 1 (SPINK1) mutations, and 5 case-control studies, comprising 1674 PC cases and 19,036 control subjects for CFTR mutations, were enrolled in our analysis. SPINK1 mutations showed no association with PC (OR, 1.52; 95% CI, 0.67-3.45; P = 0.315), whereas mutations in CFTR modestly increased the risk of PC (OR, 1.41; 95% CI, 1.07-1.84; P = 0.013). CONCLUSION: Our meta-analysis showed that mutations in CFTR modestly increase the risk of PC, whereas no association was found between SPINK1 and PC.

Association between AIRE gene polymorphism and rheumatoid arthritis: a systematic review and meta-analysis of case-control studies.

Autoimmune regulator (AIRE) is a transcription factor that functions as a novel player in immunological investigations. In the thymus, it has a pivotal role in the negative selection of naive T-cells during central tolerance. Experimental studies have shown that single nucleotide polymorphism (SNP) alters transcription of the AIRE gene. SNPs thereby provide a less efficient negative selection, propagate higher survival of autoimmune T-cells, and elevate susceptibility to autoimmune diseases. To date, only rheumatoid arthritis (RA) has been analysed by epidemiological investigations in relation to SNPs in AIRE. In our meta-analysis, we sought to encompass case-control studies and confirm that the association between SNP occurrence and RA. After robust searches of Embase, PubMed, Cochrane Library, and Web of Science databases, we found 19 articles that included five independent studies. Out of 11 polymorphisms, two (rs2075876, rs760426) were common in the five case-control studies. Thus, we performed a meta-analysis for rs2075876 (7145 cases and 8579 controls) and rs760426 (6696 cases and 8164 controls). Our results prove that rs2075876 and rs760426 are significantly associated with an increased risk of RA in allelic, dominant, recessive, codominant heterozygous, and codominant homozygous genetic models. These findings are primarily based on data from Asian populations.

Individual breast milk consumption and exposure to PCBs and PCDD/Fs in Hungarian infants: a time-course analysis of the first three months of lactation.

Polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are persistent, bioaccumulative and toxic chemicals. These compounds are transferred to breast milk, therefore breastfed infants are at risk of being exposed to considerable amounts of PCBs and PCDD/Fs during this sensitive age. In the present study individual breast milk samples were collected at three time points (days 5, 12 and 84 postpartum) from 22 mothers who delivered their infants during 2007 in Baranya County, Hungary. Breast milk samples were analyzed for 17 PCDD/Fs, 12 dioxin-like (DL) PCBs and 7 non-dioxin-like (NDL) PCBs using high-resolution gas chromatography/high-resolution mass spectrometry. Each infant's daily breast milk consumptions have been measured biweekly over three months. The concentration of several PCB and PCDD congeners in breast milk decreased significantly during lactation, with a main decline between days 5 and 12. The total toxic equivalent (TEQ) concentrations, derived from PCDD/Fs and DL-PCBs, were 3.17±1.72, 2.70±1.57 and 2.41±1.47 pg TEQ/g fat at the three time points, respectively. The corresponding NDL-PCB concentrations were 33.5±29.2, 27.4±20.6 and 26.9±24.8 ng/g fat, respectively. The results highlight the importance of timing of breast milk sampling for consistent exposure assessment estimation. Levels of pollutants in Hungarian breast milk samples were at the lower concentration range when data from Europe are considered. This is the first study in Hungary where each infant's daily intakes of PCBs and PCDD/Fs via breast milk have been measured. The daily intakes of PCDD/Fs and DL-PCBs via breastfeeding per kg body weight were 11.79±6.42, 16.54±13.02 and 11.59±7.70 pg TEQ/kg bw on days 5, 12 and 84, respectively. The exposure was the highest on day 12 but at all three time points each infants' daily exposure to PCDD/Fs and DL-PCBs via breastfeeding exceeded the tolerable daily intake (TDI) of 2 pg TEQ/kg bw per day. These levels are still lower than corresponding levels recently measured in many European countries. Whether the milk-derived POP exposure levels of infants reported here constitute any health risk that may manifest later in life awaits further scrutiny.

Thrombosis preventive potential of chicory coffee consumption: a clinical study.

The protective effects of plant polyphenol intake on cardiovascular morbidity and mortality are widely acknowledged. Caffeine-free chicory coffee is a rich source of plant phenolics, including caffeic acid, which inhibits in vitro platelet aggregation, and also phenylpyruvate tautomerase enzymatic activity of the proinflammatory cytokine, macrophage migration inhibitory factor (MIF). To assess whether chicory coffee consumption might confer cardiovascular benefits a clinical intervention study was performed with 27 healthy volunteers, who consumed 300 mL chicory coffee every day for 1 week. The dietary intervention produced variable effects on platelet aggregation, depending on the inducer used for the aggregation test. Whole blood and plasma viscosity were both significantly decreased, along with serum MIF levels, after 1 week of chicory coffee consumption. Moreover, significant improvements were seen in red blood cell deformability. No changes in hematocrit, fibrinogen level or red blood cell counts were detected. The full spectrum of these effects is unlikely to be attributable to a single compound present in chicory coffee, nevertheless, the phenolics, including caffeic acid, are expected to play a substantial role. In conclusion, our study offers an encouraging starting-point to delineate the antithrombotic and antiinflammatory effects of phenolic compounds found in chicory coffee.

Longitudinal changes in macrophage migration inhibitory factor in breast milk during the first three months of lactation.

The presence of macrophage migration inhibitory factor (MIF) in breast milk has been reported before, but its concentration at distinct phases of lactation has not yet been delineated. We have measured the MIF content in the aqueous phase of 63 milk samples from 21 mothers at postpartum days 5, 12 and 84 by enzyme-linked immunosorbent assay. MIF declined consistently from 44.5±40.3 ng/ml at day 5 to 20.3±12.9 ng/ml at day 84, but no similar trend was found in the ng/mg protein values. MIF may play a relevant role in the complex immunological interface between the mother and her infant.