Methods: In 2018, a retrospective cohort study stretching from January to April was conducted. This study involved a review of data obtained from the National AIDS Registry. A total of 1,073 AIDS cases diagnosed from 1 January 2010 to 31 December 2014 were selected, and follow-up procedures were conducted until 31 March 2015 (a 3-month follow-up). The Kaplan-Meier plot and Cox's proportional hazard regression were used for data analyses.
Results: 564 (52.5%) patients died due to AIDS, while the remaining 509 (47.4%) were censored. The overall median survival time was 11 months. The probability of survival in 1-year, 2-year, 3-year, 4-year and 5-year periods were 49.1%, 47.8%, 47.3%, 47.0% and 46.7%, respectively. Multiple Cox regression revealed that the significant prognostic factors were age 30-49 years [adjusted hazard ratio (Adj. HR) 1.57; 95% CI: 1.14, 2.16; P = 0.006], male (Adj. HR 1.39; 95% CI: 1.07, 1.79; P = 0.012), unemployed (Adj. HR 1.40; 95% CI: 1.12, 1.75; P = 0.003) and HIV-TB co-infection (Adj. HR 1.78; 95% CI: 1.37, 2.31; P < 0.001).
Conclusion: The overall median survival time among AIDS patients in North-East Peninsular Malaysia was revealed to be short, in comparison to the other studies. The chances for survival can be improved with more emphasis on early detection (to ensure early treatment) and social support, particularly for HIV-TB co-infected patients, as well as for younger and unemployed patients.
METHODS: An observational study was conducted among those who underwent surgery for meningioma. Eighteen subjects were recruited each for low- and high-grades, respectively. Magnetic resonance imaging (MRI) prior to surgery was employed for interpreting the Edema index and MRI after surgery was used to determine residual tumour.
RESULTS: Median age was 50 years, male to female ratio was 1:3.5, 69.4% had peritumoural brain Edema and 75% had reported gross resection. Among the reported gross total resection cases, 40.7% had residual tumour. Analysis showed statistically significant association between peritumoural brain Edema (P = 0.027) and tumour volume (P = 0.001) with high-grade meningioma, however multivariate analysis did not present any association. No association was noted between judgement of tumour resection by surgeons and peritumoural brain Edema.
CONCLUSION: Odds ratio for peritumoural brain Edema remained high and the tumour volume exhibited marginal P-value marginal significance for prediction of high grade meningioma. These two factors may still contribute to the tumour grade and should be included in further studies on the prognosis of meningioma.
METHODS: A total of 74 patients with histologically proven HGGs treated between January 2008 and December 2014, who fulfilled the inclusion criteria, were enrolled. Kaplan-Meier survival estimates and Cox proportional hazard regression were used.
RESULTS: Significant longer survival time (months) was observed in the FG group compared with the conventional group (12 months versus 8 months, P < 0.020). Even without adjuvant therapy, HGG patients from FG group survived longer than those from the conventional group (8 months versus 3 months, P = 0.006). No significant differences were seen in postoperative Karnofsky performance scale (KPS) between the groups at 6 weeks and 6 months after surgery compared to pre-operative KPS. Cox proportional hazard regression identified four independent predictors of survival: KPS > 80 (P = 0.010), histology (P < 0.001), surgical method (P < 0.001) and adjuvant therapy (P < 0.001).
CONCLUSION: This study showed a significant clinical benefit for HGG patients in terms of overall survival using FG surgery as it did not result in worsening of post-operative function outcome when compared with the conventional surgical method. We advocate a further multicentered, randomised controlled trial to support these findings before FG surgery can be implemented as a standard surgical adjunct in local practice for the benefit of HGG patients.
Methods: A combination of top-down approach and activity-based costing was applied. The standard operating procedure (SOP) for CRC was developed for each stage according to national data and guidelines at the University of Malaya Medical Centre (UMMC). The unit cost was calculated and incorporated into the treatment pathway in order to obtain the total cost of managing a single CRC patient according to the stage of illness. The cost data were represented by means and standard deviation and the results were demonstrated by tabulation. All cost data are presented in Malaysian Ringgit (RM). The cost difference between early stage (Stage I) and late stage (Stage II-IV) was analysed using independent t-test.
Results: The cost per patient increased with stage of CRC, from RM13,672 (USD4,410.30) for stage I, to RM27,972 (USD9,023.20) for Stage IV. The early stage had statistically significant lower cost compared to late stage t(2) = -4.729, P = 0.042. The highest fraction of the cost was related to surgery for Stage I, but was superseded by oncology day care treatment for Stages II-IV. CRC is a costly illness. From a provider perspective, the highest cost was found in Stages III and IV. The early stages conserved more resources than did the advanced stages of cancer.
Conclusion: Early diagnosis and management of CRC, therefore, not only affects oncologic prognosis, but has implications for health care costs. This adds further justification to develop and implement CRC screening programmes in Malaysia.
Methods: The study analysed 54 decompensated liver cirrhotic patients including 17 females and 37 males between May 2016 and May 2017 at the Haji Adam Malik General Hospital, Medan, Indonesia. Ferritin levels were, then, divided into trichotomous cut-off value (< 200 ng/mL, n = 22; 200-400 ng/mL, n = 5; and > 400 ng/mL, n = 27). Data was analysed using SPSS version 12.0 (continuous variables were assessed by the Kruskal-Wallis test and Chi-square test was used for categorical variables). In addition, Spearman correlation test was used to determine any significant correlation between ferritin levels and CTP score.
Results: Based on data analysis, gender and CTP score were related to higher ferritin levels (P = 0.002 and P = 0.018, respectively). Furthermore, a significant correlation between serum ferritin levels and CTP score was obtained in to moderate degree (P = 0.000; r = 0.487).
Conclusions: There might be a significant role of serum ferritin levels in predicting mortality and prognosis among decompensated liver cirrhosis patients but it still needs further attention.
METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
METHODS: We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset.
FINDINGS: Associations exceeding the genome-wide significance threshold (p<5 × 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4·21 × 10(-19), odds ratio [OR] 1·84 [95% CI 1·61-2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection.
INTERPRETATION: To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL.
FUNDING: Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).
METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL.
FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants.
INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention.
FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.
MATERIALS AND METHODS: An online search was done for studies reporting incidental prostate cancer in cystoprostatectomy specimens. After following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines we identified a total of 34 reports containing 13,140 patients who underwent radical cystoprostatectomy for bladder cancer with no previous history of prostate cancer. A cumulative analysis was performed on the available data regarding prevalence, clinicopathological features and oncologic outcomes. RevMan, version 5.3 was used for data meta-analysis.
RESULTS: Of the 13,140 patients incidental prostate cancer was detected in 3,335 (24.4%). Incidental prostate cancer was significantly associated with greater age (Z = 3.81, p = 0.0001, d = 0.27, 95% CI -0.14-0.68), lymphovascular invasion of bladder cancer (Z = 2.07, p = 0.04, r = 0.14, 95% CI 0.09-0.18) and lower 5-year overall survival (Z = 2.2, p = 0.03). Among patients with clinically significant and insignificant prostate cancer those with clinically significant prostate cancer significantly more frequently showed a positive finding on digital rectal examination (Z = 3.12, p = 0.002, r = 0.10, 95% CI 0-0.19) and lower 5-year overall survival (Z = 2.49, p = 0.01) whereas no effect of age was observed (p = 0.15). Of 1,320 patients monitored for biochemical recurrence prostate specific antigen recurrence, defined as prostate specific antigen greater than 0.02 ng/ml, developed in 25 (1.9%) at between 3 and 102 months.
CONCLUSIONS: This meta-analysis suggests that incidental prostate cancer detected during histopathological examination of radical cystoprostatectomy specimens might be linked with adverse characteristics and outcomes in patients with invasive bladder cancer.
MATERIALS AND METHODS: We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured.
RESULTS: We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele.
CONCLUSIONS: Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients.