Impact of Frailty on Patient Outcomes after Hartmann's Reversal: A NSQIP Analysis.

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.

Monocyte-to-High-density Lipoprotein Cholesterol Ratio as a Novel Inflammatory Marker in Periodontal Disease: A Pilot Study.

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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 (p < 0.001). Monocyte-to-high-density lipoprotein cholesterol ratio also showed significantly positive correlation with the severity of periodontitis. CONCLUSION: Malondialdehyde and MHR are increased in periodontal disease and correlate with severity of the periodontal disease. CLINICAL SIGNIFICANCE: 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.

Cryotherapy: A Safe Approach to Pulmonary Hemorrhage During VV-ECMO.

The number of hospitals with veno-venous extracorporeal membrane oxygenation (VV-ECMO) capabilities is expanding. To support an ECMO program, centers must be equipped to handle associated complications such as pulmonary hemorrhage. We describe a case series of 4 patients with life-threatening pulmonary bleeding and central airway obstruction. A therapeutic approach of anticoagulation cessation coupled with cryoextraction via flexible bronchoscopy led to successful restoration of airway patency without any adverse events. A low threshold to stop anticoagulation with a strong consideration of bronchoscopy with cryotherapy for pulmonary toilet should be done in patients with pulmonary hemorrhage during VV-ECMO.

Kasabach-Merritt-like phenomenon in a massive uterine leiomyoma presenting with chronic disseminated intravascular coagulation: A case report.

Kasabach-Merritt phenomenon is a process where the presence of vascular irregularity within a Kaposiform hemangioendothelioma or tufted angioma leads to constitutive coagulation factor activation and the development of chronic disseminated intravascular coagulation (DIC). A similar phenomenon has been seen in other tumors but has rarely been described. A 42-year-old woman presented to the hospital following the development of worsening easy bruising and bleeding. She was ultimately found to have a massive uterine fibroid that led to constitutive coagulation cascade activation and subsequent chronic DIC. Following resection, she had complete resolution of DIC and made a full recovery. Although rare, the development of unexplained chronic DIC in a woman should prompt evaluation for the presence of massive uterine fibroids.

Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study.

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.

Pharmacological cyclin dependent kinase inhibitors: Implications for colorectal cancer.

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.

A secreted WNT-ligand-binding domain of FZD5 generated by a frameshift mutation causes autosomal dominant coloboma.

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.

The Value of the P Value.

Recently, the discussion on the implications of irreproducibility in the sciences has been brought into the spotlight. This topic has been discussed for years in the literature. A multitude of reasons have been attributed to this issue; one commonly labeled culprit is the overuse of the p value as a determinant of significance by the scientific community. Both scientists and statisticians have questioned the use of null hypothesis testing as the basis of scientific analysis. This survey of the current issues at hand in irreproducibility in research emphasizes potential causes of the issue, impacts that this can have for drug development and efforts been taken to increase transparency of findings in research.

Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Genetic Engineering: Robotic Genetic Surgery.

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.