A highly predictive autoantibody-based biomarker panel for prognosis in early-stage NSCLC with potential therapeutic implications

Background Lung cancer is the leading cause of cancer-related death worldwide. Surgical resection remains the definitive curative treatment for early-stage disease offering an overall 5-year survival rate of 62%. Despite careful case selection, a significant proportion of early-stage cancers relapse aggressively within the first year post-operatively. Identification of these patients is key to accurate prognostication and understanding the biology that drives early relapse might open up potential novel adjuvant therapies.Methods We performed an unsupervised interrogation of >1600 serum-based autoantibody biomarkers using an iterative machine-learning algorithm.Results We identified a 13 biomarker signature that was highly predictive for survivorship in post-operative early-stage lung cancer; this outperforms currently used autoantibody biomarkers in solid cancers. Our results demonstrate significantly poor survivorship in high expressers of this biomarker signature with an overall 5-year survival rate of 7.6%.Conclusions We anticipate that the data will lead to the development of an off-the-shelf prognostic panel and further that the oncogenic relevance of the proteins recognised in the panel may be a starting point for a new adjuvant therapy.Subject terms: Non-small-cell lung cancer, Tumour biomarkers     

Adequacy of central hemodynamics versus restoration of circulation in the survival of patients with acute aortic thrombosis

Acute aortic thrombosis is an infrequent clinical occurrence, but when it does occur, it is a true cardiovascular catastrophe. Our experience with 34 patients over a 12 year period was reviewed and factors influencing outcome were analyzed. Seventeen women and 17 men had various clinical presentations, although 74 percent of the patients had the classic picture of ischemia. Preoperative assessment of left ventricular function was carried out in all but one patient with intraoperative and perioperative monitoring to guide therapy in addition to revascularization procedures. While extent of the preexisting disease and number of additional operations did influence the outcome, the predominant factor for survival was the left ventricular functional state perioperatively. Fifteen of the 16 patients with adequate left ventricular function survived, whereas 15 of the 17 patients with a failing myocardium died (88 percent). Extraanatomic operations are preferable in patients with demonstrated inadequate left ventricular function. Expeditious restoration of circulation alone does not ensure a favorable outcome. The key to successful therapy is understanding, preventing, and effectively treating the mechanical and metabolic dysfunction of the heart. Review of the literature on acute aortic thrombosis revealed only few isolated case reports except for a recent report of eight patients. Our report of 34 patients over a 12 year period represents the largest experience to date from a single institution. Detailed analysis of hemodynamic parameters and the significance of determination of left ventricular function has not been reported so far in this subset of critically ill patients.     

Impact of oral potentially malignant disorders on quality of life

Background

Oral potentially malignant disorders (OPMDs) could have a significant psychological impact on patients, principally because of the unknown risk of malignant transformation, while the physical and functional impairments could differ. This study aimed to assess the impact of three different OPMDs and their disease stages on the quality of life (QoL) of affected patients.

Methods

Oral leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF) patients who were undergoing treatment at an oral medicine clinic of a dental teaching hospital in India were the study population. All subjects completed the recently developed OPMDQoL questionnaire and a short form 12 item (version 2) health survey questionnaire (SF‐12v2). OPMDQoL questionnaire consists of 20 items over four dimensions. A higher score denotes poor OHRQoL. SF‐12v2 has two components, a Physical Component Summary (PCS) and Mental Component Summary (MCS).

Results

A total of 150 subjects (50 each of OL, OLP and OSF) participated. OL patients (37.7 ± 7.9) reported significantly better OPMDQoL scores than OLP (47.3 ± 5.8) and OSF (45.4 ± 9.2) patients. OLP patients reported significant problems in obtaining a clear diagnosis for their condition, more so than the other OPMDs. OL patients reported fewer problems for the dimension, “physical impairment and functional limitations” than the OLP and OSF patients. A significant trend was observed with the overall OPMDQoL and MCS, deteriorating as the disease stage increased.

Conclusions

OLP and OSF have a significant impact on the QoL of affected individuals: OL less so. Increasing stage of the disease is associated with worsening QoL.     

SGLT1 inhibition boon or bane for diabetes-associated cardiomyopathy

Chronic hyperglycaemia is a peculiar feature of diabetes mellitus (DM). Sequential metabolic abnormalities accompanying glucotoxicity are some of its implications. Glucotoxicity most likely corresponds to the vascular intricacy and metabolic alterations, such as increased oxidation of free fatty acids and reduced glucose oxidation. More than half of those with diabetes also develop cardiac abnormalities due to unknown causes, posing a major threat to the currently available marketed preparations which are being used for treating these cardiac complications. Even though impairment in cardiac functioning is the principal cause of death in individuals with type 2 diabetes (T2D), reducing plasma glucose levels has little effect on cardiovascular disease (CVD) risk. In vitro and in vivo studies have demonstrated that inhibitors of sodium glucose transporter (SGLT) represent a putative therapeutic intervention for these pathological conditions. Several clinical trials have reported the efficacy of SGLT inhibitors as a novel and potent antidiabetic agent which along with its antihyperglycaemic activity possesses the potential of effectively treating its associated cardiac abnormalities. Thus, hereby, the present review highlights the role of SGLT inhibitors as a successful drug candidate for correcting the shifts in deregulation of cardiac energy substrate metabolism together with its role in treating diabetes-related cardiac perturbations.     

Efficacy and safety of Risankizumab in moderate to severe psoriasis: A systematic review and meta‐analysis

Monoclonal antibodies are explored for their therapeutic potential in Psoriasis. To evaluate Risankizumab in the moderate to severe psoriasis with regard to efficacy, tolerability, and safety PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov , databases were searched for relevant RCTs. The reference lists of relevant publications were also scanned manually to identify any further studies not indexed in the searched databases. Only RCT aiming to evaluate the role of Risankizumab in the treatment of moderate to severe psoriasis were considered eligible for this systematic review. Intervention group was patients taking Risankizumab and placebo or other monoclonal antibody was considered as control group. Cochrane review manager 5 (RevMan) version 5.3 was used for data synthesis and meta‐analysis. Quality assessment of included randomized controlled trials was done with Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB‐2). Overall Grading of evidence for study objectives was performed with GRADE Pro GDT software. A total of seven studies were included in analysis with total of 1533 and 710 patients in Risankizumab and standard care groups, respectively. Statistically significant increase in percentage of individual achieving PASI90 (OR = 11.01 (95% CI = 8.67‐13.99), DLQI‐01 (OR = 6.95 (95% CI = 5.53‐8.75), sPGA‐01 (OR = 14.22 (95% CI = 11.10‐18.22); sPGA‐0 (OR = 6.39 (95% CI = 4.79‐8.54) in risankizumab group as compared with control, with high quality of evidence. Increased risk of infections with risankizumab as compared with placebo (OR = 1.44 [95% CI = 1.13‐1.83], high quality evidence), while no difference in SAE among two groups. Analysis of all outcome data from RCTs. In the light of evidence from systematic review on effectiveness of Risankizumab, we propose treatment with risankizumab for psoriasis patients not responding to available treatment.     

The Soliga, an isolated tribe from Southern India: genetic diversity and phylogenetic affinities

India's role in the dispersal of modern humans can be explored by investigating its oldest inhabitants: the tribal people. The Soliga people of the Biligiri Rangana Hills, a tribal community in Southern India, could be among the country's first settlers. This forest-bound, Dravidian speaking group, lives isolated, practicing subsistence-level agriculture under primitive conditions. The aim of this study is to examine the phylogenetic relationships of the Soligas in relation to 29 worldwide, geographically targeted, reference populations. For this purpose, we employed a battery of 15 hypervariable autosomal short tandem repeat loci as markers. The Soliga tribe was found to be remarkably different from other Indian populations including other southern Dravidian-speaking tribes. In contrast, the Soliga people exhibited genetic affinity to two Australian aboriginal populations. This genetic similarity could be attributed to the 'Out of Africa' migratory wave(s) along the southern coast of India that eventually reached Australia. Alternatively, the observed genetic affinity may be explained by more recent migrations from the Indian subcontinent into Australia.