Search

The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) has currently been proposed as an indicator of inflammation. The aim of the present study was to assess the relationship between the monocyte-to-high-density lipoprotein cholesterol ratio and periodontal health and disease.A total of 90 patients were selected for the study - 30 healthy patients (group I) and 60 periodontitis patients (groups II and III). All the patients were subjected to blood sampling and serum malondialdehyde (MDA), high-density lipoprotein cholesterol (HDL) levels and monocyte counts were estimated.Monocyte-to-high-density lipoprotein cholesterol ratio was 80.64 ± 28.71 for patients with moderate periodontitis (group II), 95.14 ± 53.21 in severe periodontitis (group III), and 14.28 ± 16.05 for the healthy patients. Monocyte-to-high-density lipoprotein cholesterol ratio values were found to be statistically significantly higher than the control group (Malondialdehyde and MHR are increased in periodontal disease and correlate with severity of the periodontal disease.Monocyte-to-high-density lipoprotein cholesterol ratio is a novel, readily available inflammatory and oxidative stress marker in patients with periodontitis and can be useful to evaluate periodontitis and disease severity.

Background Colostomy reversal is a common procedure. Patients often have baseline comorbidities associated with postoperative morbidity. We utilized a modified frailty index (mFI-5) to predict postoperative complications. Methods Patients who underwent elective, open Hartmann’s reversal were queried from the National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified to low, medium, or high frailty groups. Statistical analysis was performed using chi-squared, ANOVA, and logistic regression. Results There were 9272 patients with Hartmann’s reversal. 48.78%, 30.31%, and 12.89% had low, moderate, or high frailty, respectively. High frailty was associated with cardiac arrest, myocardial infarction, reintubation, prolonged intubation, early reoperation, and mortality. After multivariate analysis, high frailty was associated with prolonged intubation (OR 3.147, P = .001), reintubation (OR 2.548, P = .002), and reoperation (OR 1.67, P < .001). Conclusions Frailty was associated with greater risk of postoperative complications in patients undergoing Hartmann’s reversal. Frailty may be a useful adjunct to stratify for patients who are at risk for postoperative complications.

Minimally invasive dentistry was introduced to preserve the dentitition and the surrounding structures as much as possible. In the periodontal scenario, this technique aims at smaller incisions, minimal trauma and exposure compared to the standard protocol. To accomplish this, optical acuity a well specially designed instruments is required. It not only achieves good results but also saves time, and offers post-operative comfort to the patient. This review explores the history, and the use of minimally invasive surgery in periodontology and implant dentistry.

Summary Background Cabozantinib is approved for patients with metastatic renal cell carcinoma on the basis of studies done in clear-cell histology. The activity of cabozantinib in patients with non-clear-cell renal cell carcinoma is poorly characterised. We sought to analyse the antitumour activity and toxicity of cabozantinib in advanced non-clear-cell renal cell carcinoma. Methods We did a multicentre, international, retrospective cohort study of patients with metastatic non-clear-cell renal cell carcinoma treated with oral cabozantinib during any treatment line at 22 centres: 21 in the USA and one in Belgium. Eligibility required patients with histologically confirmed non-clear-cell renal cell carcinoma who received cabozantinib for metastatic disease during any treatment line roughly between 2015 and 2018. Mixed tumours with a clear-cell histology component were excluded. No other restrictive inclusion criteria were applied. Data were obtained from retrospective chart review by investigators at each institution. Demographic, surgical, pathological, and systemic therapy data were captured with uniform database templates to ensure consistent data collection. The main objectives were to estimate the proportion of patients who achieved an objective response, time to treatment failure, and overall survival after treatment. Findings Of 112 identified patients with non-clear-cell renal cell carcinoma treated at the participating centres, 66 (59%) had papillary histology, 17 (15%) had Xp11.2 translocation histology, 15 (13%) had unclassified histology, ten (9%) had chromophobe histology, and four (4%) had collecting duct histology. The proportion of patients who achieved an objective response across all histologies was 30 (27%, 95% CI 19–36) of 112 patients. At a median follow-up of 11 months (IQR 6–18), median time to treatment failure was 6·7 months (95% CI 5·5–8·6), median progression-free survival was 7·0 months (5·7–9·0), and median overall survival was 12·0 months (9·2–17·0). The most common adverse events of any grade were fatigue (58 [52%]), and diarrhoea (38 [34%]). The most common grade 3 events were skin toxicity (rash and palmar-plantar erythrodysesthesia; five [4%]) and hypertension (four [4%]). No treatment-related deaths were observed. Across 54 patients with available next-generation sequencing data, the most frequently altered somatic genes were CDKN2A (12 [22%]) and MET (11 [20%]) with responses seen irrespective of mutational status. Interpretation While we await results from prospective studies, this real-world study provides evidence supporting the antitumour activity and safety of cabozantinib across non-clear-cell renal cell carcinomas. Continued support of international collaborations and prospective ongoing studies targeting non-clear-cell renal cell carcinoma subtypes and specific molecular alterations are warranted to improve outcomes across these rare diseases with few evidence-based treatment options. Funding None.

Ocular coloboma is a common eye malformation resulting from incomplete fusion of the optic fissure during development. Coloboma is often associated with microphthalmia and/or contralateral anophthalmia. Coloboma shows extensive locus heterogeneity associated with causative mutations identified in genes encoding developmental transcription factors or components of signaling pathways. We report an ultra-rare, heterozygous frameshift mutation in FZD5 (p.Ala219Glufs*49) that was identified independently in two branches of a large family with autosomal dominant non-syndromic coloboma. FZD5 has a single-coding exon and consequently a transcript with this frameshift variant is not a canonical substrate for nonsense-mediated decay. FZD5 encodes a transmembrane receptor with a conserved extracellular cysteine rich domain for ligand binding. The frameshift mutation results in the production of a truncated protein, which retains the Wingless-type MMTV integration site family member-ligand-binding domain, but lacks the transmembrane domain. The truncated protein was secreted from cells, and behaved as a dominant-negative FZD5 receptor, antagonizing both canonical and non-canonical WNT signaling. Expression of the resultant mutant protein caused coloboma and microphthalmia in zebrafish, and disruption of the apical junction of the retinal neural epithelium in mouse, mimicking the phenotype of Fz5/Fz8 compound conditional knockout mutants. Our studies have revealed a conserved role of Wnt–Frizzled (FZD) signaling in ocular development and directly implicate WNT–FZD signaling both in normal closure of the human optic fissure and pathogenesis of coloboma.

As a novel technology that utilizes the endogenous immune defense system in bacteria, CRISPR/Cas9 has transcended DNA engineering into a more pragmatic and clinically efficacious field. Using programmable sgRNA sequences and nucleases, the system effectively introduces double strand breaks in target genes within an entire organism. The applications of CRISPR range from biomedicine to drug development and epigenetic modification. Studies have demonstrated CRISPR mediated targeting of various tumorigenic genes and effector proteins known to be involved in colon carcinomas. This technology significantly expands the scope of gene manipulation and allows for an enhanced modeling of colon cancers, as well as various other malignancies.

4579Background: Cabo shows robust clinical activity in advanced clear cell RCC. nccRCC, a heterogeneous mix of diseases, have been underrepresented in clinical trials and effective systemic therapy...

e12622Background: The rate of contralateral prophylactic mastectomy (CPM) in the United States has more than tripled in the past decade. The majority of women who undergo CPM have no major genetic ...

Colorectal cancer accounts for a significant proportion of cancer deaths worldwide. The need to develop more chemotherapeutic agents to combat this disease is critical. Cyclin dependent kinases (CDKs), along with its binding partner cyclins, serve to control the growth of cells through the cell cycle. A new class of drugs, termed CDK inhibitors, has been studied in preclinical and now clinical trials. These inhibitors are believed to act as an anti-cancer drug by blocking CDKs to block the uncontrolled cellular proliferation that is hallmark of cancers like colorectal cancer. CDK article provides overview of the emerging drug class of CDK inhibitors and provides a list of ones that are currently in clinical trials.

Background: Diabetes occurs in substantial number of patients following renal transplantation, contributing to mortality and morbidity in particular the cardiovascular disease and infection. The prevalence and risk factors in South Indian population is not precisely clear. Our study aimed at determining the prevalence, epidemiology, and risk factors in kidney transplant recipients with posttransplant diabetes mellitus (PTDM). Methodology: This is a single-center analytical, cross-sectional, and retrospective study of adult renal transplant recipients who underwent transplant between January 2014 and December 2016. Institutional ethics committee approval was obtained. Results: Of 149 patients transplanted, 115 were included for study. Twenty-six patients (22.6%) developed PTDM. The mean age of the PTDM group was 35.2 years and 76.92% were males. Univariate analysis revealed age (P < 0.001), sex (P < 0.04), smoking (P = 0.02), history of diabetes mellitus (P < 0.001), dialysis vintage (P < 0.04), and induction therapy (P < 0.01) to be significant risk factors. The dosage of tacrolimus and prednisolone at the time of discharge and at months 3 & 6 post-transplant was significantly higher in PTDM group. Multivariate logistic regression analysis indicated age (odds ratio [OR] = 3.77), male gender (OR = 2.35), family history (OR = 4.54), dialysis vintage of >1 year (OR = 1.75), and induction therapy (OR = 2.0) to be independent risk factors for PTDM. Conclusions: There is high risk of developing diabetes after transplant with one quarter of this south Indian cohort developing PTDM. Older age, male sex, family history of diabetes, dialysis vintage, and use of induction therapy were independent risk factors for PTDM.