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Non-Small Cell Lung Cancer: Targetable Variants in Concurrent Tissue and Liquid Biopsy Testing in a North Indian Cohort

Asian Pac J Cancer Prev. 2023 Oct 1;24(10):3467-3475. doi: 10.31557/APJCP.2023.24.10.3467.

ABSTRACT

OBJECTIVES: Testing for EGFR, ALK, ROS1 and MET alterations in paired tissue and plasma samples of treatment-naïve patients of NSCLC and correlating their status with overall survival.

MATERIALS AND METHODS: One hundred treatment-naïve patients were recruited after obtaining informed consent. Ten ml of blood was collected within a period of two weeks from histological diagnosis, prior to the start of any treatment. DNA & RNA extraction was done from formalin-fixed paraffin embedded (FFPE) tissue and total cell-free nucleic acid extraction was done from plasma samples. EGFR mutation, ALK, ROS1 and MET rearrangements were tested by ARMS (Amplification Refractory Mutation System) PCR. All statistical analyses were conducted in R version 4.1.1.

RESULTS: A total of 61 cases showed molecular alterations in tissue samples which included EGFR mutations (47), ALK rearrangements (12), ROS1 fusion (2). MET alteration was not detected. Forty-three cases showed EGFR mutations in plasma, 26 of which were concurrently positive in tissue. Concordance observed was 62%. ALK-EML4 rearrangement, ROS1 fusion and MET were not detected in plasma samples. Sensitivity and specificity for detection of EGFR mutation in plasma were 55.3% and 67.9% respectively. Univariate Cox regression analysis showed a positive association between EGFR mutation in tissue and overall survival (HR = 0.4; 95% CI: 0.2-0.7; p = 0.003) and improved overall survival in those who received targeted therapy (HR = 0.29; 95% CI: 0.1-0.8; p = 0.02).

CONCLUSION: Concurrent testing in tissue and liquid biopsy in NSCLC increased the detection of EGFR mutations (47% to 64%). This has substantial implications in deciding treatment and administration targeted therapy and the consequent overall survival.

PMID:37898852 | DOI:10.31557/APJCP.2023.24.10.3467

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Factors Affecting Non-Histologically Proven Invasive Cancer of the Uterine Cervix that Had an Abnormal Pap Smear: Results of the CCS Program

Asian Pac J Cancer Prev. 2023 Oct 1;24(10):3429-3436. doi: 10.31557/APJCP.2023.24.10.3429.

ABSTRACT

BACKGROUND: Cervical cancer (CC) ranks fourth among cancers diagnosed around the world, but early detection and treatment can reduce invasive cervical cancer and mortality. Screening programs (CCSP), such as the one covering Thailand’s 75 provinces, use histology to confirm cases. The study determined the incidence rate (IR) and investigated the factors associated with non-histologically proven invasive cancer of the uterine cervix (non-HPICUC) with an abnormal pap smear from the CCSP at Mahasarakham Hospital, Thailand.

METHODS: The CCSP was used to analyse a retrospective cohort of 288 women between 30 and 60 years of age. All abnormal pap smears were followed up until April 30, 2022. We estimated the IR and assessed the relationship between various independent variables and non-HPICUC using the generalised linear model (GLM) for testing association data. We reported the adjusted RR and 95% confidence intervals (95%CI).

RESULTS: 260 non-HPICUC cases had abnormal CCSP pap smears for an overall IR of 90.0 (95% CI: 86.3 – 93.2). After adjusting the model for all variables, age at recruitment and pregnancy had a statistically significant association with non-HPICUC (p-value < 0.05). We found that the risk of non-HPICUC increased 1.02 times for every 20-year increment in age compared to below that age (adjusted RR=1.02, 95% CI: 1.01 – 1.04). Pregnancy at risk for non-HPICUC was 0.89 times compared to non-pregnancy (adjusted RR=0.89, 95% CI: 0.80 – 0.99). Pathological vaginal discharge (PVD) did not have a statistically significant association with non-HPICUC (p-value = 0.094); notwithstanding, women with PVD had 1.08 times the risk of non-HPICUC compared to women without PVD (adjusted RR=1.08, 95% CI: 0.97 – 1.20).

CONCLUSIONS: Based on an abnormal pap smear from the CCS Program at Mahasarakham Hospital Thailand, age and pregnancy are associated with an increased risk of non-HPICUC. High-risk groups with abnormal pap smears should be targeted for CC campaigns.

PMID:37898847 | DOI:10.31557/APJCP.2023.24.10.3429

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Epidemiology of Breast Cancer Mortality in Kazakhstan, trends and Geographic Distribution

Asian Pac J Cancer Prev. 2023 Oct 1;24(10):3361-3371. doi: 10.31557/APJCP.2023.24.10.3361.

ABSTRACT

BACKGROUND: According to the International Agency for Research on Cancer, ongoing demographic changes will lead to an increase in the number of deaths from breast cancer (BC) per year in the vast majority of regions. In 2040 it is expected that 1.04 million people worldwide will die from this malignancy, including 2,380 women in Kazakhstan.

METHODS: The retrospective study (2009-2018) was done using descriptive and analytical methods of oncoepidemiology. The extensive, crude and age-specific incidence rates are determined according to the generally accepted methodology used in sanitary statistics. The data were used to calculate the average percentage change (APС) using the Joinpoint regression analysis to determine the trend over the study period.

RESULTS: During 10 years 12,958 women died from BC. An average age of the death was 61.6 years (95%CI=60.6-62.6) and tended to increase (APC=+0.6%, R2=0.6117). Age-specific rates had a bimodal increase with peak rates at 70-74 years – 76.7±5.5 (APC=+3.4%, R2=0.2656) and 80-84 years – 78.0±9.1 (APC=+3.7%, R2=0.0875). The age-standardized rate was 13.9 per 100,000 of female population, and the trend has decreased. When compiling thematic maps, mortality rates were determined on the basis of standardized indicators: low – up to 12.5, average – from 12.5 to 15.2, high – above 15.2 per 100,000. The results of the spatial analysis showed the regions with a higher levels of BC mortality rate per 100,000: Pavlodar (16.9), Almaty (19.2) and Astana cities (19.3).

CONCLUSIONS: Age-standardized mortality rates had a strong downward trend (APC=-4.0%, R2=0.9218). The decrease mostly is due to a large coverage of the population by mammography screening and to an improvement in the effectiveness of breast cancer treatment.

PMID:37898839 | DOI:10.31557/APJCP.2023.24.10.3361

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Association of Single Nucleotide Polymorphism in VDR, GC Globulin and CYP2R1 with the Risk of Esophageal Cancer

Asian Pac J Cancer Prev. 2023 Oct 1;24(10):3353-3360. doi: 10.31557/APJCP.2023.24.10.3353.

ABSTRACT

BACKGROUND: The proactive role of vitamin D has been well determined in different cancers. The protein that encodes the components of the vitamin D metabolism could appear to play a pivotal role in vitamin D stability and its maintenance. A polymorphism in vitamin-D-receptor (VDR), carrier globulin/binding protein (GC) and cytochrome P-450 family 2, subfamily R, polypeptide 1 (CYP2R1) genes has been predicted to be associated with the development of cancer. This study was designed to detect the association of VDR, GC Globulin and CYP2R1 gene polymorphism with the risk of esophageal cancer in the North-east Indian population.

METHODS: To carry out the study, a total of 100 patients diagnosed with esophageal cancer and 101 healthy controls were enrolled. In a case-control manner, all samples were subjected to do genotype testing for known SNPs on the VDR (rs1544410), GC (rs4588), and CYP2R1 (rs10741657) genes using Restriction-fragment length polymorphism (RFLP) followed by Sanger sequencing. The collected demographic and clinical data were analysed using the statistical software package SPSS v22.0.

RESULTS: The VDR haplotype heterozygous TC was found strongly associated with the carcinoma group (OR:1.09, 95%CI:0.67-1.75). The risk factors analysis using the GC globulin rs4588 phenotype, found a positive correlation in terms of mutant AA’s harmful influence on the cancer cohort (OR = 1.125, OR=1.125, 95% CI, 0.573-2.206). The influence of the CYP2R1 rs10741657 polymorphism on the malignant cohort revealed that the GG mutant had a significant negative influence on the carcinoma, has an influential role in disease severity ( OR:1.736, at 95% CI; 0.368-8.180).

CONCLUSION: In conclusion, this study revealed the potential association of VDR gene polymorphism in the progression and development of esophageal cancer in north east Indian population cohort.

PMID:37898838 | DOI:10.31557/APJCP.2023.24.10.3353

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Assessment of bony changes in temporomandibular joint in patients using cone beam computed tomography – a cross sectional study

Head Face Med. 2023 Oct 28;19(1):47. doi: 10.1186/s13005-023-00392-z.

ABSTRACT

BACKGROUND AND AIM: The aim of this study is to evaluate the changes in the temporomandibular joint (TMJ) in patients with temporomandibular disorder (TMD) and the relationship between age, sex, and types of TMJ change using Cone Beam Computed Tomography (CBCT).

METHODS AND MATERIAL: CBCT records of 200 patients (123 women and 67 men) were retrieved and assessed. Right and left TMJs were evaluated separately, resulting in a total of 400 TMJs. The images were analyzed using On demand 3D Application The radiographic findings were classified as erosion, proliferative changes mainly, including flattening and osteophytes of the condyle, sclerosis, Ely cyst, hypoplasia and hyperplasia of the condyles, ankylosis, and joint cavity. Data analysis was performed using descriptive statistics, paired T-tests, and repeated measure ANOVA (Analysis of Variance) in SPSS Software.

RESULTS: The most prevalent types of condylar bony changes observed was osteophyte (63.5%) followed by flattening of the articular surface (42%), erosion (40%), ankylosis (10%) and sclerosis (10%). 7.5% of joints showed hyperplastic condyles but only 2% showed hypoplasia. The least prevalent change observed was Ely Cyst (1%). Osteophyte was the most prevalent change observed in all age groups and both sexes except for men aged 31 ~ 50, where flattening was more frequent. A statistically significant difference was found between sex and prevalence of erosion in the age group of 10 ~ 30 (P = 0.001); as well as between sex and condylar hyperplasia in the same age group.

CONCLUSION: Based on the findings of this research, the prevalence of bony changes of TMJ from highest to lowest is as follows: osteophyte, flattening of the articular surface, erosion, ankylosis, sclerosis, hyperplastic condyles, hypoplastic condyles and Ely Cyst. CBCT is an accurate 3 dimensional imaging modality for assessment of TMJ bony structures.

PMID:37898789 | DOI:10.1186/s13005-023-00392-z

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Time to death and its determinant factors of visceral leishmaniasis with HIV co-infected patients during treatment period admitted at Metema hospital, Metema, Ethiopia: a hospital-based cross-sectional study design

Trop Dis Travel Med Vaccines. 2023 Oct 29;9(1):18. doi: 10.1186/s40794-023-00203-y.

ABSTRACT

BACKGROUND: Visceral leishmaniasis is caused by the parasites Leishmania donovani spices complex that can spread to internal organs and the disease is fatal with a fatality rate of nearly 100% if left untreated. Visceral Leishmania-HIV (HIV1) coinfection disease is a new clinical form of leishmaniasis very serious disease in the endemic part of the world. It also served as the primary cause of death in the lowlands of Ethiopia with the endemic Humara and Metema that are located near the Sudanese border.

METHODS: A total of 153 visceral leishmaniases with HIV co-infection secondary data was taken from the medical chart of patients from January 2015 to January 2021 and a hospital-based cross-sectional study design was carried out to retrieve relevant information. The data entered by SPSS and analysed using STATA version 14 and R4.2.1 statistical software packages using a non-parametric Model, semi-parametric Cox proportional hazard survival models at 5% significance level.

RESULT: Among the total visceral leishmaniasis with HIV co-infected patients 3.27% were females and 96.73% were males, 19 (12.42%) patients died and 134(87.58%) patients were censored. The Cox proportional hazard model result indicates that severe acute malnutrition, baseline CD4+ cell count ≥100, and underweight significantly contributed to the survival time of a patient. Cox proportional hazard model shows that severe acute malnutrition (HR=4.40027, 95% CI= 2.455061 262.7934, P-value=0.007), baseline CD4+cell count ≥100 (HR=0.2714623, 95% CI= 0.0764089 0.9644395, P-value=0.044), and Underweight (HR=4.678169, 95% CI= 1.970097 11.10872, P-value=0.040) significantly contributed to a shorter survival time.

CONCLUSION: Visceral leishmaniases with HIV co-infected patients show a large number of deaths occurred in the earlier days of treatment this implies that Visceral leishmaniasis accelerates HIV replication and disease progression death. The researcher suggests that people be aware of the burden posed by those risk factors and knowledgeable about the diseases. So, the researcher recommended that to health workers implement primary health care in those patients and careful consideration of a neglected parasitic disease.

PMID:37898767 | DOI:10.1186/s40794-023-00203-y

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Short-term outcomes associated with the use of a new powered circular stapler for rectal reconstructions: a retrospective study comparing it to manual circular staplers using inverse probability of treatment weight analysis

BMC Surg. 2023 Oct 28;23(1):332. doi: 10.1186/s12893-023-02218-w.

ABSTRACT

BACKGROUND: The most common postoperative complication in malignant rectal surgery is anastomotic leakage (AL). AL after anterior or low anterior resection in rectal tumors is a fatal postoperative complication. Recently, the first automated suture circular stapler, which is expected to reduce the incidence of AL, (J&J). MATERIALS AND METHODS: This study included a total of 248 rectal tumor patients who underwent double stapler technique (DST) anastomotic procedures in the department of gastroenterological surgery /pediatric surgery at Gifu University School of Medicine from January 2017 to December 2021. The experience of a single institution utilizing the The Echelon circular™ stapler (ECP stapler:Manual VS Automatic) in rectal surgery cases was evaluated retrospectively from maintained database.

RESULT: One hundred thirty-nine patients (58.4%) were performed by manual circular stapling, 99 patients (41.6%) by powerd circular stapling. Diverting stoma was performed in 45 cases (32.4%) by manual circular stapling, 42 patients (42.4%) by powerd circular stapling Postoperative complications were occurred clavien-dindo grade II or higher in 57 cases (23.9%) and grade III or higher in 20 cases (8.4%). Anastomotic leakage occurred in 14 patients (5.9%) within all grades. After IPTW, the variables of patient characteristics was SMD ≤ 0.2 (Table.3), and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.57; 95% Confidence Interval(CI), 0.34-0.98; p = 0.041). In addition, there was no significant difference in postoperative complications in grade II or higher (OR, 0.88; 95%CI, 0.65-1.19; p = 0.417) and grade III or higher (OR, 0.46; 95%CI, 0.29-0.74; p = 0.001) were significantly remarkable lower in powered circular stapling group.

CONCLUSION: In this IPTW comparison of patients undergoing rectal reconstructions, the ECP trial cohort had lower risks of several surgical complications AL and statistically signifcant lower rates of ileus/bowel obstruction, infection, and bleeding as Clavien-Dindo ≥ grade II and III as compared with for whom manual circular staplers were used.

PMID:37898761 | DOI:10.1186/s12893-023-02218-w

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Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum

Alzheimers Res Ther. 2023 Oct 28;15(1):186. doi: 10.1186/s13195-023-01336-0.

ABSTRACT

BACKGROUND: Synapse loss is an early event that precedes neuronal death and symptom onset and is considered the best neuropathological correlate of cognitive decline in Alzheimer’s disease (AD). Vesicle-associated membrane protein 2 (VAMP-2) has emerged as a promising biomarker of AD-related synapse degeneration in cerebrospinal fluid (CSF). The aim of this study was to explore the CSF profile of VAMP-2 across the AD continuum in relation to core AD biomarkers, other synaptic proteins, neurogranin (Ng) and synaptosomal-associated Protein-25 kDa (SNAP-25) and cognitive performance.

METHODS: We developed a digital immunoassay on the Single Molecule Array platform to quantify VAMP-2 in CSF and used existing immunoassays to quantify Ng, SNAP-25 and core CSF AD biomarkers. The clinical study included 62 cognitively unimpaired AD biomarker-negative subjects and 152 participants across the AD continuum from the SPIN cohort (Sant Pau Initiative on Neurodegeneration). Cognitive measures of episodic, semantic, executive and visuospatial domains and global cognition were included. Statistical methods included χ2 tests, spearman correlation, and ANCOVA analyses.

RESULTS: The VAMP-2 assay had a good analytical performance (repeatability 8.9%, intermediate precision 10.3%). Assay antibodies detected native VAMP-2 protein in human brain homogenates. CSF concentrations of VAMP-2, neurogranin and SNAP-25 were lower in preclinical AD stage 1 compared to controls and higher at later AD stages compared to AD stage 1 and were associated with core AD biomarkers, particularly total tau (adj. r2 = 0.62 to 0.78, p < 0.001). All three synaptic proteins were associated with all cognitive domains in individuals on the AD continuum (adj. r2 = 0.04 to 0.19, p < 0.05).

CONCLUSIONS: Our novel digital immunoassay accurately measures VAMP-2 changes in CSF, which reflect AD biomarkers and cognitive performance across multiple domains.

PMID:37898760 | DOI:10.1186/s13195-023-01336-0

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A named General Practitioner (GP) is associated with an increase of hospital days in a single predictor analysis: a follow-up of 15 years

BMC Health Serv Res. 2023 Oct 28;23(1):1178. doi: 10.1186/s12913-023-10184-5.

ABSTRACT

BACKGROUND: Continuity of care constitutes the basis of primary health care services and is associated with decreased hospitalization. In Finland, accessibility to primary care and increased use of hospital services are recognized challenges for the health care system.

OBJECTIVES: The aim of the study was to determine whether having a named GP is associated with hospital service use.

METHODS: The data are part of the Health and Social Support study (HeSSup) based on a random Finnish working-age population sample. The cohort of the study comprised participants of postal surveys in 1998 (n = 25,898) who returned follow-up questionnaires both in 2003 and 2012 (n = 11,924). Background characteristics were inquired in the questionnaires, and hospitalization was derived from national registries (Hilmo-register).

RESULTS: A named GP was reported both in 2003 and 2012 only by 34.3% of the participants. The association between hospital days and a named GP was linearly rising and statistically significant in a single predictor model. The strongest associations with hospital use were with health-related factors, and the association with a named GP was no longer significant in multinomial analysis.

CONCLUSION: A named GP is associated with an increased use of hospital days, but in a multinomial analysis the association disappeared. Health related factors showed the strongest association with hospital days. From the perspective of the on-going Finnish health and social services reform, continuity of care should be emphasized.

PMID:37898748 | DOI:10.1186/s12913-023-10184-5

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Teaching of silver diamine fluoride for the management of dental caries and hypersensitivity – situation in the Southeast Asia dental schools

BMC Oral Health. 2023 Oct 29;23(1):815. doi: 10.1186/s12903-023-03502-0.

ABSTRACT

BACKGROUND: Using silver diamine fluoride (SDF) for caries management has raised dentists’ interests in Southeast Asia (SEA). However, information about the teaching of SDF in dental schools in SEA is limited. Therefore, this survey aimed to describe the extent to which SDF had been introduced into the education of undergraduate students in the dental schools in SEA.

METHODS: An online questionnaire survey was conducted on the duration, method, contents, and barriers regarding the teaching of SDF. Teachers in charge of undergraduate program in pediatric dentistry and those in community dentistry in all the 90 dental schools in SEA were approached and we required each department to reply once only. Descriptive statistics and Chi-square test were used to describe and assess the differences between the two departments in the teaching of SDF.

RESULTS: A total of 81 responses from the departments of 49 schools were received, giving a school-level response rate of 54% (49/90). SDF was taught in the undergraduate program in 86% (42/49) of the respondent schools, and 50% (21/42) of these schools had included SDF in the teaching for five or more years. Almost all (98%) of the departments taught SDF through lectures. Furthermore, 55% of them adopted SDF in clinical practice. Regarding the teaching content, the use of SDF for arresting cavitated caries lesion was the most commonly covered (82-97%), followed by for arresting early noncavitated lesions (69-82%), for preventing new caries development (66-79%) and for treating dental hypersensitivity (77%). There were variations in the post-treatment instruction taught. For the departments not teaching SDF, the most common reason (10/19, 53%) was that SDF was not available.

CONCLUSION: SDF is covered in the undergraduate program in most of the dental schools in SEA. The use of SDF to arrest cavitated caries lesions in primary teeth is usually taught. However, other applications of SDF, such as for prevention of caries and treatment of dental hypersensitivity, are less commonly mentioned in the teaching.

PMID:37898744 | DOI:10.1186/s12903-023-03502-0