Immunohistochemical evaluation of E-cadherin in oral epithelial dysplasia and squamous cell carcinoma.

Aim: To evaluate the expression of E-cadherin (E-cad) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Material and Method: Immunohistochemistry was used to detect E-cad expression in 20 cases each of normal oral mucosa, oral epithelial dysplasia and squamous cell carcinoma. Statistical Analysis Used: Inferential statistical methods for statistical analysis used were Chi-square test for comparison of the frequency between different severity of dysplasia and OSCC. Results: Upon assessing the expression of E-cad in OED and OSCC, increase in E-cad immunoreactivity was seen in early lesions. However, the expression of E-cad decreased significantly as the grade of dysplasia increased. Conclusion: We observed a significant decrease in E-cad expression from dysplasia to poorly differentiated squamous cell carcinoma suggesting that loss of expression of E-cad is closely related to carcinoma.

Real-World Study of Characteristics and Treatment Outcomes Among Patients with KRAS p.G12C-Mutated or Other KRAS Mutated Metastatic Colorectal Cancer.

BACKGROUND: The KRAS p.G12C mutation has recently become an actionable drug target. To further understand KRAS p.G12C disease, we describe clinicopathologic characteristics, treatment patterns, overall survival (OS), and real-world progression-free survival (rwPFS) in patients with metastatic colorectal cancer (mCRC), KRAS p.G12C mutations (KRAS G12C), and other KRAS mutations (KRAS non-G12C) using a de-identified database. PATIENTS AND METHODS: Clinical and tumor characteristics, including treatments received, genomic profile, and clinical outcomes were assessed for patients from a US clinical genomic database with mCRC diagnosed between January 1, 2011, and March 31, 2020, with genomic sequencing data available. RESULTS: Of 6477 patients with mCRC (mCRC cohort), 238 (3.7%) had KRAS G12C and 2947 (45.5%) had KRAS non-G12C mutations. Treatment patterns were generally comparable across lines of therapy (LOT) in KRAS G12C versus KRAS non-G12C cohorts. Median (95% CI) OS after the first LOT was 16.1 (13.0-19.0) months for the KRAS G12C cohort versus 18.3 (17.2-19.3) months for the KRAS non-G12C cohort, and 19.2 (18.5-19.8) months for the mCRC overall cohort; median (95% CI) rwPFS was 7.4 (6.3-9.5), 9.0 (8.2-9.7), and 9.2 (8.6-9.7) months, respectively. The different KRAS non-G12C mutations examined did not affect clinical outcomes. Median OS and rwPFS for all cohorts declined with each subsequent LOT. CONCLUSIONS: Patients with KRAS p.G12C-mutant mCRC have poor treatment outcomes, and outcomes appear numerically worse than for those without this mutation, indicating potential prognostic implications for KRAS p.G12C mutations and an unmet medical need in this population.

Migraine Characteristics, Comorbidities, Healthcare Resource Utilization, and Associated Costs of Early Users of Erenumab in the USA: A Retrospective Cohort Study Using Administrative Claims Data.

INTRODUCTION: Erenumab is indicated for migraine preventive treatment in adults. The objective of this study was to provide descriptive information on real-world use of erenumab including patient profile and treatment patterns. METHODS: We completed a retrospective review of US data (through May 2019) from the IBM MarketScan® Early View Databases, identifying adult patients newly treated with erenumab with a migraine claim in the year prior to first erenumab claim (index) and at least 1 year of continuous pre-index medical and pharmacy insurance coverage, to assess pre- and post-erenumab migraine characteristics, comorbidities, healthcare resource utilization, and associated costs. All data were summarized using descriptive statistics. RESULTS: A total of 9753 patients met inclusion criteria. The average (SD) age was 46 (12) years, 85% of patients were female, and 64% had at least one claim for chronic migraine; 70% of erenumab users had an initial dose of 70 mg; 77% of patients in the 6-month follow-up sample (n = 4437) remained on their initial erenumab dose. Persistence at 6-month follow-up was 47.3% with a mean (95% CI) proportion of days covered of 0.68 (0.67, 0.68). In the post-erenumab period, claims for comorbidities of non-migraine headaches and anxiety were reduced and there was a shift to decreased use of acute and preventive medications. Reductions in overall use and associated cost of healthcare resources such as inpatient hospitalization and outpatient office visits were minimal, with slightly more pronounced reductions in the subgroup of patients that were persistent to erenumab. CONCLUSIONS: We observed reductions in claims for important migraine characteristics, comorbidities, and a shift to decreased use of acute and preventive migraine medications-observations indicative of the real-world effectiveness of erenumab. Further examination is required as persistence to erenumab, which may be influenced by dose titration, appears to be an important factor in changes to healthcare resource utilization and costs.

A retrospective observational study of the natural history of advanced non-small-cell lung cancer in patients with KRAS p.G12C mutated or wild-type disease.

INTRODUCTION: The KRAS p.G12C mutation, prevalent in non-small-cell lung cancer (NSCLC), has only recently become a viable target. Here we present results of the largest retrospective observational study analyzing KRAS p.G12C in patients with advanced NSCLC. MATERIALS AND METHODS: Adults with advanced NSCLC (All Advanced NSCLC cohort) and subcohorts with different mutation profiles (KRAS p.G12C [G12C] and KRAS/EGFR/ALK wild type [Triple WT]) diagnosed January 2011 to March 2019 were selected from a US clinico-genomic database; treatment-related characteristics, molecular profiles, real-world overall (rwOS) and progression-free survival (rwPFS) were analyzed. RESULTS: Demographics were similar across cohorts, with more smokers and nonsquamous cell carcinoma histology in the G12C cohort. KRAS p.G12C was nearly mutually exclusive (≤1.2 %) with known actionable driver mutations, but non-driver co-mutations were common (STK11, 21.5 %; KEAP1, 7.0 %; TP53, 48.0 %). Among G12C patients, 20 % had no documentation of receiving systemic therapy. Across treated G12C patients, 67 % received immune checkpoint inhibitors; first-line usage increased from 0% (2014) to 81 % (2019). Among G12C patients, median (95 % CI) rwOS was 12.0 (9.6-15.3), 9.5 (8.1-13.1), and 6.7 (5.9-10.7) months after first, second, and third line of therapy, respectively; median (95 % CI) rwPFS was 5.0 (4.4-5.8), 4.0 (2.8-5.3), and 3.1 (2.4-4.3) months. Outcomes for the G12C subcohort were similar to those for all patients (All Advanced NSCLC cohort). Mutations in STK11/KEAP1 were associated with poorer survival across all cohorts. CONCLUSION: The poor outcomes associated with KRAS p.G12C mutated advanced NSCLC indicate an unmet need for more effective novel treatments.

Lymphangioma of Gingiva: A Rare Case Report.

One of the unconventional congenital hamartomas of the lymphatic vessels, are termed as Lymphangiomas, with a common age of diagnosis from birth to early childhood. These occurrences are most commonly seen in the region of head and neck while still being uncommon in the oral cavity. Clinically they can be superficial or deep with superficial lesions showing a pebbly surface and deeper lesions being more diffuse. Excising the lesion surgically is considered the treatment of choice. Although majority of cases have a decent rate of prognosis, the recurrence rate however is notorious for being high due to its non-encapsulated and infiltrating nature where complete removal becomes difficult. In spite of the rarity of lymphangiomas in the oral cavity, the condition should be considered by the clinicians to initiate early and proper treatment to avoid complications. The following case report establishes a case of lymphangioma present on the lingual gingiva of a male in his twenties.

Management of ruptured sinus of valsalva for device closure in a patient with haemophilia.

The association of Hemophilia A and ruptured aneurysm of sinus of valsalva (RSOV) has never been reported to the best of our knowledge. We report the case of a 29-year-old male patient with Hemophilia type A who presented with a RSOV into right atrium (RA). The patient underwent device closure off the RSOV and received Factor VIII infusions to decrease blood loss. The peri-procedural management is being presented in this case report.

Comparison of calretinin expression in dentigerous cysts and ameloblastoma: An immunohistochemical study.

BACKGROUND: Calretinin is a calcium-binding protein of 29-kilodalton (kDa), which is widely expressed in normal human tissues and tumorigenic tissues. Its expression in the odontogenic epithelium during odontogenesis and in neoplastic odontogenic tissues has been demonstrated. Unicystic ameloblastoma poses a diagnostic challenge, as its histologic presentation can be sometimes mistaken for cystic odontogenic lesions. In the present study, an attempt is made to overcome the confusion encountered in the diagnosis of dentigerous cyst and unicystic ameloblastoma, using the expression of calretinin in both lesions and to compare this expression with conventional ameloblastoma to accurately diagnose and differentiate these lesions. MATERIALS AND METHODS: A total of eighty cases, in which twenty cases each of ameloblastoma, unicystic ameloblastoma, dentigerous cyst, and odontogenic keratocyst (OKC) were included in the study. Slides were made from the archival blocks of each case and were stained immunohistochemically with calretinin. RESULTS: Correlation between calretinin staining and histopathological diagnosis was done, and it was found that all twenty cases of ameloblastoma showed positivity for calretinin, whereas 17 of twenty cases of unicystic ameloblastoma showed positivity for calretinin staining. All the cases of OKC and dentigerous cyst were negative for calretinin. CONCLUSION: Calretinin may serve as an important diagnostic adjunct in the differential diagnosis of ameloblastoma and cystic odontogenic lesions.

Burden of Valvular Heart Diseases in Hispanic/Latino Individuals in the United States: The Echocardiographic Study of Latinos.

OBJECTIVE: To explore the burden and clinical correlates of valvular heart disease in Hispanics/Latinos in the United States. PATIENTS AND METHODS: A total of 1818 individuals from the population-based study of Latinos/Hispanics from 4 US metropolitan areas (Bronx, New York; Chicago, Illinois; San Diego, California; and Miami, Florida) underwent a comprehensive clinical and echocardiographic examination from October 1, 2011, through June 24, 2014. Logistic regression analysis was used to examine the associations of clinical and sociodemographic variables with valvular lesions. RESULTS: The mean age was 55.2±0.2 years; 57.4% were female. The prevalence of any valvular heart disease (AVHD) was 3.1%, with no considerable differences across sex, and a higher prevalence with increasing age. The proportion of US-born vs foreign-born individuals was similar in those with vs without AVHD (P=.31). The weighted prevalence of AVHD was highest in Central Americans (8.4%) and lowest in Mexicans (1.2%). Regurgitant lesions of moderate or greater severity were present in 2.4% of the population and stenotic lesions of moderate or greater severity in 0.2%. Compared with those without AVHD, individuals with AVHD were more likely to have health insurance coverage (59.6% vs 79.2%; P=.007) but similar income (P=.06) and educational status (P=.46). Univariate regression models revealed that regurgitant lesions were associated with lower body mass index whereas stenotic lesions were associated with higher body mass index. CONCLUSION: Our data provide the first population-based estimates of the prevalence of valvular heart disease in Hispanic/Latinos. Valvular heart disease is fairly common in the Hispanic/Latino population and may constitute an important public health problem.

State of the Art Management of Mechanical Heart Valves During Pregnancy.

PURPOSE OF THE REVIEW: To review the management of women with mechanical heart valves during pregnancy, from preconception counseling through delivery with a summary of the latest guidelines. RECENT FINDINGS: The hypercoagulability of pregnancy combined with the imperfect choices of anticoagulant agents contribute to a high risk of complications in pregnant women with mechanical heart valves. Valve thrombosis remains a major concern, much of which occurs during the first trimester transition to heparin-based products. The safest method of anticoagulation, with the best balance of maternal and fetal risk, is use of low-dose vitamin K antagonists, but only if therapeutic anticoagulation can be achieved with warfarin doses of ≤ 5 mg/day. Management of mechanical heart valves in pregnancy remains fraught with difficult decisions involving balancing of maternal and fetal risks as well as a high risk of maternal and fetal complications. Preconception counseling and planning is imperative. A risk-benefit discussion with the patient will help guide the choice of anticoagulation and outline the plan for safe delivery options. A multidisciplinary approach to management is advisable with close follow-up and care in a tertiary center.

Mucoepidermoid carcinoma of hard palate.

Salivary gland tumors are clinically diverse group of neoplasms, of which pleomorphic adenoma and mucoepidermoid carcinoma (MEC) are most common benign and malignant tumors, respectively. Besides the major salivary glands, these tumors can affect the minor salivary gland tissues in the posterior part of the hard palate. Minor salivary gland tumor accounts for about 15% of all the salivary gland neoplasm, of which MEC accounts to about 35.9%. MEC appears as asymptomatic swellings and shows a variety of biological behaviors and variable natural history. This article reports a case of MEC involving the posterior part of the hard palate. The lesion was treated by wide surgical excision with a regular follow-up and no recurrence was noted.

The blalock and taussig shunt revisited.

The systemic to pulmonary artery shunts are done as palliative procedures for cyanotic congenital heart diseases ranging from simple tetralogy of Fallots (TOFs)/pulmonary atresia (PA) to complex univentricular hearts. They allow growth of pulmonary arteries and maintain regulated blood flow to the lungs till a proper age and body weight suitable for definitive corrective repair is reached. We have reviewed the BT shunt with its anaesthtic considerations and management of associated complications.

Management of iatrogenic pulmonary artery injury during pulmonary artery banding.

Pulmonary Artery banding (PAB) is limited to selected patients who cannot undergo primary repair due to complex anatomy, associated co-morbidities, as a part of staged univentricular palliation, and for preparing the left ventricle prior to an arterial switch operation. We report a catastrophic iatrogenic complication in which the pulmonary artery was injured during the PAB. We discuss its multi-pronged management.

Higher number of live births is associated with left ventricular diastolic dysfunction and adverse cardiac remodelling among US Hispanic/Latina women: results from the Echocardiographic Study of Latinos.

INTRODUCTION: Female sex is a risk factor for heart failure with preserved ejection fraction (HFpEF). Previous literature suggests that some diastolic dysfunction (DD) develops during pregnancy and may persist postdelivery. Our objective was to examine the relationship between parity and cardiac structure and function in a population-based cohort. METHODS: Participants included 1172 Hispanic/Latina women, aged ≥45 years, enrolled in the Echocardiographic Study of Latinos from four US communities (Bronx, Miami, San Diego and Chicago). Standard echocardiographic techniques were used to measure cardiac volumes, left ventricular mass, systolic and diastolic function. Using sampling weights and survey statistics, multivariable linear and logistic regression models were constructed adjusting for age, body mass index, diabetes or prediabetes, systolic blood pressure, use of antihypertensive medications, smoking, total cholesterol and high-density lipoprotein cholesterol. RESULTS: In the target population, 5.0% were nulliparous (no live births) and 10.5% were grand multiparous (≥5 live births). Among the nulliparous women, 46% had DD as compared with 51%-58% of women with 1-4 live births and 81% of women with ≥5 live births (p<0.01). In full multivariate models, higher parity was significantly associated with greater left ventricular end-systolic volumes, end-diastolic volumes, left atrial volume indices and presence of DD (all p<0.01) but was not associated with ejection fraction. The log odds for having any grade of DD in grand-multiparous women was over three times that seen in nulliparous women (OR=3.4, 95% CI 1.5 to 7.9, p<0.01) in models further adjusted for income and education. CONCLUSIONS: Higher parity is associated with increased cardiac mass, volumes and the presence of DD. Further studies are needed to elucidate this apparent deleterious relation and whether parity can help explain the increased risk of HFpEF in women.

Diagnostic dilemma: Low oxygen saturation during cardiac surgery.

We report a case of rheumatic heart disease with severe mitral stenosis having cyanosis and low oxygen saturation on pulse oximetry. The findings of clinical examination and low values on pulse oximetry were inconsistent with the findings of normal partial pressure of oxygen and oxygen saturation on arterial blood gas analysis, leading to diagnostic dilemma. In such clinical scenario, the anesthesiologist should be aware and vigilant about the differential diagnosis of low oxygen saturation on pulse oximetry.

Racial Differences in the Association between Parity and Incident Stroke: Results from the REasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND: Circulatory and vascular changes across consecutive pregnancies may increase the risk of later-life cerebrovascular health outcomes. METHODS: The association between parity and incident stroke was assessed among 7674 white and 6280 black women, aged 45 years and older, and enrolled in the REasons for Geographic and Racial Differences in Stroke Study from 2003 to 2007. Parity was assessed at baseline, and incident stroke was ascertained from physician-adjudicated medical records through September 2014. Cox proportional hazards models were used to estimate hazard ratios (HR) for the association between parity and stroke, adjusting for baseline measures. RESULTS: At baseline, 12.7% of white women and 16.2% of black women reported 1 live birth, while 8.2% and 19.0%, respectively, reported 5 or more live births. Mean follow-up time was 7.5 years (standard deviation = 2.8); there were 447 incident strokes. A significant interaction between race and parity was detected (P = .05). Among white women, those with 5 or more live births had a higher stroke risk than those with 1 live birth (HR = 1.57; 95% confidence interval [CI] .93-2.65). However, the association was eliminated after adjustment for baseline characteristics (HR = 1.00, 95% CI .59-1.71). For black women, those with 5 or more live births had the highest stroke risk compared with those with 1 live birth (HR = 1.91, 95% CI 1.25-2.93), but the association was attenuated and no longer statistically significant after adjustment for confounders (HR = 1.40, 95% CI .89-2.18). CONCLUSIONS: In adjusted models, no statistically significantassociations were observed between parity and stroke risk in a diverse cohort of U.S. women. Further studies are needed to elucidate the role of lifestyle and psychosocial factors in the race-specific associations that were observed.

Googling endometriosis: a systematic review of information available on the Internet.

BACKGROUND: The demand for health information online is increasing rapidly without clear governance. OBJECTIVE: We aim to evaluate the credibility, quality, readability, and accuracy of online patient information concerning endometriosis. STUDY DESIGN: We searched 5 popular Internet search engines: aol.com, ask.com, bing.com, google.com, and yahoo.com. We developed a search strategy in consultation with patients with endometriosis, to identify relevant World Wide Web pages. Pages containing information related to endometriosis for women with endometriosis or the public were eligible. Two independent authors screened the search results. World Wide Web pages were evaluated using validated instruments across 3 of the 4 following domains: (1) credibility (White Paper instrument; range 0-10); (2) quality (DISCERN instrument; range 0-85); and (3) readability (Flesch-Kincaid instrument; range 0-100); and (4) accuracy (assessed by a prioritized criteria developed in consultation with health care professionals, researchers, and women with endometriosis based on the European Society of Human Reproduction and Embryology guidelines [range 0-30]). We summarized these data in diagrams, tables, and narratively. RESULTS: We identified 750 World Wide Web pages, of which 54 were included. Over a third of Web pages did not attribute authorship and almost half the included pages did not report the sources of information or academic references. No World Wide Web page provided information assessed as being written in plain English. A minority of web pages were assessed as high quality. A single World Wide Web page provided accurate information: evidentlycochrane.net. Available information was, in general, skewed toward the diagnosis of endometriosis. There were 16 credible World Wide Web pages, however the content limitations were infrequently discussed. No World Wide Web page scored highly across all 4 domains. CONCLUSION: In the unlikely event that a World Wide Web page reports high-quality, accurate, and credible health information it is typically challenging for a lay audience to comprehend. Health care professionals, and the wider community, should inform women with endometriosis of the risk of outdated, inaccurate, or even dangerous information online. The implementation of an information standard will incentivize providers of online information to establish and adhere to codes of conduct.

Pedal Edema as an Indicator of Early Heart Failure in the Community: Prevalence and Associations With Cardiac Structure/Function and Natriuretic Peptides (MESA [Multiethnic Study of Atherosclerosis]).

BACKGROUND: The prevalence of pedal edema (PE) and its associations with abnormal cardiac structure/function, natriuretic peptides, and incident heart failure (HF) is unknown, especially in community-dwelling adults without a history of cardiovascular disease. METHODS AND RESULTS: Out of 5004 MESA (Multiethnic Study of Atherosclerosis) participants who had cardiac magnetic resonance imaging, 4196 had complete data and were included in this analysis (3501 for the right ventricle analysis). Logistic regression and Cox proportional hazard analyses were used to assess the associations among self-reported PE, 2-pillow orthopnea, paroxysmal nocturnal dyspnea, left and right ventricular structure and function, natriuretic peptide levels, and incident HF. PE was present in 28% of the participants. PE was not associated with overt left or right ventricular systolic dysfunction (ejection fraction <50%). PE was associated with 2-pillow orthopnea (odds ratio 1.66; 95% confidence interval [CI], 1.30-2.12), paroxysmal nocturnal dyspnea (odds ratio 1.95; 95% CI, 1.55-2.44), and abnormal N-terminal pro-B-type natriuretic peptide levels (defined as >400 pg/mL; odds ratio 1.80; 95% CI, 1.21-2.68) in adjusted models. After a mean of 10.2 years of follow-up, 184/4196 (4.4%) participants had an adjudicated incident HF hospitalization. PE was associated with incident HF hospitalization in models adjusted for age, sex, and race (hazard ratio 1.44; 95% CI, 1.05-1.97). This association persisted after adding additional covariates, including comorbidities, baseline left ventricular ejection fraction, and antecedent myocardial infarction (hazard ratio 1.43; 95% CI, 1.02-1.99). The association of PE with incident HF was attenuated by further adjustment for N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: PE is prevalent in community-dwelling adults without clinically recognized cardiovascular disease and associated with future hospitalized HF.

Simulation in cardiac catheterization laboratory: Need of the hour to improve the clinical skills.

Simulation is an effective teaching tool to decrease the learning curve for novices without compromising patient safety. Simulation helps interventionalist in mentally translating a two dimentional, black and white image into a usable three dimentional model. It also bridges the gap in training diverse team members on new procedures and products. All simulators have collision detection, i.e., virtual contact forces generated from collision which updates haptic output with new calculations.