Indian Journal of Medical Research最新文献

Background objectives: The World Health Organization (WHO) has endorsed thermal ablation (thermocoagulation) as an efficient and safe modality for treatment of cervical pre-cancer lesions. More evidence is being looked up by WHO through rigorous studies for health delivery models using screen-and-treat strategies incorporating thermal ablation and studies comparing it against the conventional standard modality cryotherapy. The objective of this study was to assess the acceptability of thermal ablation both among the providers and clients and compare the same with cryotherapy.

Methods: A randomized control trial was conducted for one year from September 2019 to October 2020 after obtaining ethics approval. Computer-generated random number table was used for randomization, and eligible candidates were divided into two groups following informed consent. Women with visual inspection with acetic acid (VIA) positive cervical lesions in Group A received cryotherapy and Group B received thermal ablation. After the procedure, the acceptability of the provider and the client were assessed using the International Agency for Research on Cancer-validated questionnaire for both the procedures. Immediate side effects and problems at six weeks and at six months were assessed as well. Efficacy was decided by the absence of VIA positivity at six months.

Results: The overall VIA positivity in this study was 11.8 per cent. Thermal ablation (thermocoagulation) had better provision and client acceptability than cryotherapy (significant difference). The efficacy of thermal ablation was 97.6 per cent, while, it was 92 per cent for cryotherapy (not significant).

Interpretation conclusions: In the context of screen-and-treat programme in settings such as India, thermal ablation appears to be a better method of treatment than cryotherapy for cervical pre-cancerous lesions particularly in terms of better provision and client acceptability.

Background objectives: Early warning systems (EWS) involve serial observations (track) with criteria (trigger) to timely identify patients at risk of complications. Carle designed a statistically based clinically modified obstetric early warning score (Carle's OEWS). This study evaluated Carle's OEWS and its individual components for predicting admission to the obstetric critical care unit (OCCU). Maternal near-miss and maternal mortality were the secondary outcomes.

Methods: A prospective observational study was conducted among 1250 pregnant women with a period of gestation ≥28 week admitted in the labour wards of a tertiary centre over 18 months. The physiological parameters of OEWS were recorded and aggregate score was calculated at admission and at regular intervals thereafter, till discharge or OCCU admission.

Results: The area under receiver operating characteristic (ROC) curve of OEWS was 0.975 for predicting OCCU admission, 0.971 for near-miss, and 0.996 for predicting maternal mortality and was significant for all outcomes. All individual parameters, except diastolic blood pressure, had a significant relative risk for predicting OCCU requirement.

Interpretation conclusions: Carle's OEWS is a useful screening tool for predicting obstetric OCCU admission and can be routinely used in labour wards to ensure timely intervention.

Background objectives: Semaphorins were initially characterized as axon guidance factors but were subsequently implicated in the regulation of immune responses, angiogenesis, organ formation and a variety of other physiological and developmental functions. Various semaphorins enhance or inhibit tumour progression through different mechanisms. The objective of this study was to assess the expression of various semaphorins and vascular endothelial growth factor (VEGF) gene transcripts as well as the serum level of Sema3A in individuals with laryngeal squamous cell carcinoma (LSCC).

Methods: Tissue expression of Sema3A, Sema3C, Sema4D, Sema6D and VEGF was determined in both tumour tissues and tissues around the tumour from 30 individuals with pathologically confirmed LSCC using quantitative real-time PCR. Furthermore, the serum level of Sema3A in these individuals was assessed using enzyme-linked immunosorbent assay.

Results: Sema3C gene transcript showed a significant increase (P=0.001), while Sema4D was observed with a significant decrease in tumour samples compared to non-tumoural tissues (P≤0.01). The expression of the Sema3C gene was found to be associated with the stage of LSCC tumour as it was statistically significant for tumours with stage IV (P<0.01). The serum level of Sema3A was not found to be significant between cases and controls.

Interpretation conclusions: Increased expression of Sema3C but decreased expression of Sema4D in tumour tissue of LSCC may introduce these two growth factors as crucial mediators orchestrating tumour growth in individuals with LSCC. This result could open a new vision for the treatment of this malignancy.

Background objectives: Acinetobacter baumannii has emerged as a nosocomial pathogen with a tendency of high antibiotic resistance and biofilm production. This study aimed to determine the occurrence of A. baumannii from different clinical specimens of suspected bacterial infections and furthermore to see the association of biofilm production with multidrug resistance and expression of virulence factor genes in A. baumannii.

Methods: A. baumannii was confirmed in clinical specimens by the detection of the blaOXA-51-like gene. Biofilm production was tested by microtitre plate assay and virulence genes were detected by real-time PCR.

Results: A. baumannii was isolated from a total of 307 clinical specimens. The isolate which showed the highest number of A. baumannii was an endotracheal tube specimen (44.95%), then sputum (19.54%), followed by pus (17.26%), urine (7.49%) and blood (5.86%), and <2 per cent from body fluids, catheter-tips and urogenital specimens. A resistance rate of 70-81.43 per cent against all antibiotics tested, except colistin and tigecycline, was noted, and 242 (78.82%) isolates were multidrug-resistant (MDR). Biofilm was detected in 205 (66.78%) with a distribution of 54.1 per cent weak, 10.42 per cent medium and 2.28 per cent strong biofilms. 71.07 per cent of MDR isolates produce biofilm (P<0.05). Amongst virulence factor genes, 281 (91.53%) outer membrane protein A (OmpA) and 98 (31.92%) biofilm-associated protein (Bap) were detected. Amongst 100 carbapenem-resistant A. baumannii, the blaOXA-23-like gene was predominant (96%), the blaOXA-58-like gene (6%) and none harboured the blaOXA-24-like gene. The metallo-β-lactamase genes blaIMP-1 (4%) and blaVIM-1(8%) were detected, and 76 per cent showed the insertion sequence ISAba1.

Interpretation conclusions: The majority of isolates studied were from lower respiratory tract specimens. The high MDR rate and its positive association with biofilm formation indicate the nosocomial distribution of A. baumannii. The biofilm formation and the presence of Bap were not interrelated, indicating that biofilm formation was not regulated by a single factor. The MDR rate and the presence of OmpA and Bap showed a positive association (P<0.05). The isolates co-harbouring different carbapenem resistance genes were the predominant biofilm producers, which will seriously limit the therapeutic options suggesting the need for strict antimicrobial stewardship and molecular surveillance in hospitals.

Background objectives: Microvessel density (MVD) is a surrogate measure of tumour angiogenesis, and is well known for over two decades to identify individuals with a high risk of recurrence with greater prevision than traditional markers. This study aims to assess the utility of MVD and its correlation with the Nottingham Prognostic Index (NPI) and other routine histopathological parameters in carcinoma breast.

Methods: This two year retrospective, cross-sectional and analytical study evaluated 143 women with breast cancer presenting to rural tertiary hospital in central India. These women were graded histopathologically, the immunophenotype was determined using ER (estrogen receptor), PR (progesterone receptor), Her2 neu (human epidermal growth factor receptor 2 neu) and Ki-67 proliferation index (Kiel-67) immunohistochemical markers and anti-CD34 antibody to stain the endothelial cell clusters displaying the microvessels. The NPI was generated for each participant based on the tumour size, histologic grade and involvement of lymph node. The parameters were compared with the CD34 scores. Differential and inferential statistics, including the independent t test, analysis of variance, Pearson's correlation coefficient, Spearman's rank correlation coefficient and point biserial correlation coefficient, were used for statistical analysis.

Results: This study showed that CD34 values ranged from 6-36 microvessels/hpf, with 24.16±6.77 microvessels/hpf as the mean. The mean microvessel counts showed a significant positive correlation with the Bloom-Richardson histological grade, vascular invasion, LN (lymph node) positivity and NPI. However, there was no significant correlation of CD34 values with the participant's age, tumour size neither any significant association of CD34 values with the individual's immunophenotype.

Interpretations conclusions: A positive linear correlation of the microvessel counts and the NPI scores suggest that with an increase in tumour angiogenesis, there was increased proliferative potential. Based on the significant correlation between the microvessel counts and the vascular invasion of the tumour masses in this study, it can be assumed that there will be vascular invasion if the microvessel count is higher and vice-versa. Although it is established that angiogenesis and neovascularization are required for the expansion of the solid tumour tissue, the heterogeneous nature of this entity makes it difficult for obtaining a linear correlation. Hence, it is suggested that though neovascularization permits advanced tumour spread it, however, does not guarantee it.

Pre-eclampsia (PE), a multifactorial de novo hypertensive pregnancy disorder, is one of the leading causes of foeto-maternal morbidity and mortality. Currently, antihypertensive drugs are the first-line therapy for PE and evidence suggests that low-dose aspirin initiated early in high risk pregnancies may reduce the risk of development or severity of PE. However, an early prediction of this disorder remains an unmet clinical challenge. Several potential serum biomarkers associated with maternal immunoregulation and placental angiogenesis have been evaluated but are ineffective and inconsistent for early prediction. Although placental biomarkers would be more specific and sensitive in predicting the risk of PE, accessing the placenta during pregnancy is not feasible. Circulating placental exosomes (pEXO), originating from foeto-maternal interface, are being evaluated as the placenta's surrogate and the best source of non-invasive placental biomarkers. pEXO appear in the maternal circulation starting from six weeks of gestation and its dynamic biological cargo across pregnancy is associated with successful pregnancy outcomes. Therefore, monitoring changes in pEXO expression profiles could provide new insights into the prediction, diagnosis and treatment of PE. This narrative review comprehensively summarizes the available literature on the candidate predictive circulating biomarkers evaluated for PE to date. In particular, the review elucidates the current knowledge of distinct molecular signatures emanating from pEXO in pre-eclamptic women to support the discovery of novel early predictive biomarkers for effective intervention and management of the disease.

Background objectives: Polycystic ovary syndrome (PCOS) is characterized by chronic ovulatory dysfunction, hyperandrogenism and polycystic ovary morphology (PCOM). Although hyperandrogenism is one of the major features of PCOS, it is rarely observed in southeast Asia. Recently, however, there has been growing evidence on association of anti-Müllerian hormone (AMH) with PCOS. The objective of this study was to investigate the diagnostic potentials of AMH in PCOS individuals.

Methods: This case-control study included a total of 131 women with PCOS and 49 healthy controls who were enrolled after the exclusion of secondary causes of PCOS. Serum AMH was measured using an ultra-sensitive AMH ELISA kit in addition to other diagnostic biomarkers. Statistical analyses was carried out using the Student's t test, Wilcoxon rank-sum test, receiver operating characteristic (ROC) curve analysis, Spearman's rank correlation test and multivariable binary logistic regression analysis.

Results: The median AMH values were 8.5 ng/ml and 2.5 ng/ml in the study group and controls, respectively ( P <0.001). The normal cutoff value of 4.1 ng/ml for AMH was derived from ROC curve analysis. With a 4.1 ng/ml cut-off value, high levels of AMH was found in about 84 per cent of PCOS cases. However, no significant difference in AMH level was noted between age groups (<20 vs . ≥20 yr), body mass index (BMI) (<25 vs . ≥25 kg/m 2 ) and PCOM types. The area under the ROC curve (AUC) for AMH yielded diagnostic range values. In total PCOS cases, AUC was 0.93 (95% CI: 0.88 and 0.96), and in phenotype A PCOS cases, AUC was 0.96 (95% CI: 0.91 and 0.98). The correlation test also showed no association with BMI, the FG score, PCOM, free androgen index, androstenedione, dehydroepiandrosterone sulphate and luteinizing hormone. However, a weak correlation was observed with testosterone in total PCOS cases and with DHT as well as age in phenotype A PCOS cases. The prediction model for PCOS using multivariable binary logistic regression analysis showed AMH as the best marker.

Interpretation conclusions: The results of this study suggest that AMH can be considered as the most promising biomarker in PCOS women, particularly with phenotype A and phenotype D.