The Role of Trans Oral Robotic Surgery in the Carcinoma of Unknown Primary: A New Evidence in the Horizon?

The detection of the primary site in Carcinoma of Unknown Primary (CUP) is a challenging task which can significantly alter the course of management and also prognosis. Various modalities have been assessed with varying sensitivity and specificity. Imaging and cytological diagnosis have formed a key part of the diagnostic algorithm of CUP. Trans Oral Robotic Surgery offers the advantage of being both diagnostic as well as therapeutic with promising sensitivity and specificity and can form an integral part in the management of CUP. A prospective study was carried out at a tertiary care centre over a period of one year. Patients with unilateral neck swelling which was histopathologically proven squamous cell carcinoma neck metastasis were included in the study. They were evaluated with endoscopy and radiology according to the standard algorithm. When these failed to detect the primary, the patients underwent ipsilateral radical tonsillectomy and tongue base mucosal wedge biopsy via TORS. Post-operative histopathological examination was done on the resected specimens to detect the primary site. Transoral Robotic Surgery was able to localise primary in 50% of the patients enrolled in the study. Out of the primary site identified by TORS; 55.56% were located in the tonsil and 44.4% in the tongue base. TORS can offer promising detection rates of the occult primary in CUP and should form an integral part of the diagnostic algorithm.

A comprehensive review of acute cardio-renal syndrome: need for novel biomarkers.

Cardiorenal syndrome represents a wide-spectrum disorder involving the heart and kidneys as the primary affected organs. India has an increasingly high burden of acute CRS, coinciding with the rise in global statistics. Up to 2022, approximately 46.1% of all cardiorenal patients have been diagnosed with acute CRS in India. Acute CRS involves a sudden deterioration of kidney functionalities, referred to as acute kidney injury (AKI) in acute heart failure patients. The pathophysiology of CRS involves hyperactivation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) following acute myocardial stress. The pathological phenotype of acute CRS is associated with perturbed inflammatory, cellular, and neurohormonal markers in circulation. These complications increase the risk of mortality in clinically diagnosed acute CRS patients, making it a worldwide healthcare burden. Hence, effective diagnosis and early prevention are crucial to prevent the progression of CRS in AHF patients. Present biomarkers, such as serum creatinine (sCr), cystatin C (CysC), glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum and/or urine neutrophil gelatinase-associated lipocalin (NGAL), B-type natriuretic peptide (BNP), and NT-proBNP, are clinically used to diagnose AKI stages in CRS patients but are limitedly sensitive to the early detection of the pathology. Therefore, the need for protein biomarkers is emerging for early intervention in CRS progression. Here, we summarized the cardio-renal nexus in acute CRS, with an emphasis on the present clinicopathological biomarkers and their limitations. The objective of this review is to highlight the need for novel proteomic biomarkers that will curb the burgeoning concern and direct future research trials.

Wound alpha defensin levels are significantly higher in patients with fracture related infection: A pilot, prospective cohort study.

BACKGROUND: In absence of frank purulence, wound cultures represent 'gold-standard' for diagnosis of fracture related infection (FRI). However, these are time-intensive, and may be falsely negative, necessitating the need for accurate and rapid biomarker-based diagnosis. We conducted this study to determine the accuracy of 3 wound-based biomarkers for the diagnosis of FRI. METHODS: This was a prospective cohort study on adult patients who underwent an operative procedure for an upper or lower limb fracture. Wound fluid levels of alpha-defensin (AD), neutrophil elastase (NE) and IL-6 were evaluated on post-operative day 2, and patients were followed up for one month. Patients were categorized as cases (FRI) or controls (no FRI), on the basis of the consensus definition of FRI. Univariate analysis, along with receiver operating characteristic (ROC) analysis was performed. RESULTS: 48 patients were included. AD levels showed a 2.6-fold elevation in cases (n = 26, Median = 23.74 µg/ml) as compared to controls (n = 22, Median = 8.78 µg/ml). The area under the curve for this variable was 0.71 (95% Confidence Intervals = 0.56 - 0.86). The levels of NE and IL-6 were not significantly different between cases and controls. CONCLUSION: Wound AD levels are significantly elevated in patients with FRI. However, these results need to be validated in a larger cohort of patients before it can be used as a biomarker of FRI.

Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM. METHODS AND RESULTS: Here, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect. CONCLUSIONS: Our study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.

miR-30c and miR-181a synergistically modulate p53-p21 pathway in diabetes induced cardiac hypertrophy.

p53-p21 pathway mediates cardiomyocyte hypertrophy and apoptosis and is upregulated in diabetic cardiomyopathy (DbCM). We investigated role of microRNAs in regulating p53-p21 pathway in high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis. miR-30c and miR-181a were identified to target p53. Cardiac expression of microRNAs was measured in diabetic patients, diabetic rats, and in HG-treated cardiomyocytes. Effect of microRNAs over-expression and inhibition on HG-induced cardiomyocyte hypertrophy and apoptosis was examined. Myocardial expression of p53 and p21 genes was increased and expression of miR-30c and miR-181a was significantly decreased in diabetic patients, DbCM rats, and in HG-treated cardiomyocytes. Luciferase assay confirmed p53 as target of miR-30c and miR-181a. Over-expression of miR-30c or miR-181a decreased expression of p53, p21, ANP, cardiomyocyte cell size, and apoptosis in HG-treated cardiomyocytes. Concurrent over-expression of these microRNAs resulted in greater decrease in cardiomyocyte hypertrophy and apoptosis, suggesting a synergistic effect of these microRNAs. Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53-p21 pathway in DbCM.

Benefits of hemicraniectomy seen many years after malignant stroke in a young patient.

The benefits of hemicraniectomy for malignant middle cerebral artery (MCA) stroke may not be apparent in the 3- to 6-months in which final outcomes are assessed in research studies. We present the case of a 15-year-old who underwent hemicraniectomy for malignant MCA stroke and was significantly disabled 3 and 6 months after event. Over the long-term she was able to graduate from university, play tennis, and live an independent life. Although functional independence with only minor disability is relatively rare in adult hemicraniectomy patients, this outcome may be more easily achieved in children during a longer period of follow-up.

Modulation of gene expression by Polyalthia longifolia in postmenopausal women with coronary artery disease: an in vitro study.

Chronic underlying inflammation is involved in the pathophysiology of coronary artery disease (CAD). Polyalthia longifolia var. pendula bark extract (PLE) is known to exhibit anti-inflammatory activity and has high content of phytosteroids. Since phytosteroids mimic estrogen structurally, we postulated that PLE may provide protection in postmenopausal women against CAD. Thus the effect of PLE has been explored on expression of estrogen receptors (ERalpha and ERbeta) and inflammatory inducible nitric oxide synthase (iNOS) genes in vitro in peripheral blood mononuclear cells (PBMCs) obtained from postmenopausal women. A total of 20 postmenopausal women were included in the present study. Group I (N = 10) included women with angiographically proven CAD, and group II (N = 10) is composed of equal number of age-matched healthy postmenopausal females as controls. Significantly low levels of serum 17-beta estradiol were observed in subjects of group I as compared to group II (p < 0.01). A marked increase in L: -citrulline levels (p > 0.05) and significantly augmented levels of reactive nitrogen intermediates (p < 0.05) were observed in group I subjects. PLE significantly attenuated PMA-induced expression of both ERalpha and ERbeta receptors and inflammatory iNOS gene in vitro in a dose- and time-dependent manner and had an additive effect on these genes when compared with tamoxifen. Ours is the first report to demonstrate that PLE contains certain bioactive principles, which possess anti-inflammatory and estrogenic properties, and thereby hold the promise to be screened for their anti-atherogenic potential in experimental animals to favorably alter several other markers of cardiovascular risk.