Clinical impact and prognostic role of KRAS/BRAF/PIK3CA mutations in stage I colorectal cancer

Stage I colorectal carcinoma has excellent prognosis, with 5-year survival rate up to 95%. The occurrence of lymphovascular invasion, tumor budding, high number of PDC, or lymph node micrometastases is associated with tumor progression. The aim of this study was to evaluate the mutational status of 62 stage I colorectal carcinomas (CRC) (taken from 37 patients surviving more than five years since the initial diagnosis and from 25 patients who died of disease) and to correlate it with histopathological features and the clinical outcome. Mutations of KRAS, NRAS, BRAF, and PIK3CA genes were analyzed through Myriapod Colon Status Kit, using the high-throughput genotyping platform Sequenom MassARRAY System. Mutations in those genes were found in 31 cases (50%) and mainly in those with poor prognosis. The most frequent mutations occurred at codons 12 and 13 of the KRAS gene (40% of cases). We found concomitant PIK3CA mutations in 5 cases (8%). The presence of PIK3CA mutations was mainly observed in tumors with poor prognosis and with unfavorable histopathological prognostic features. High PDC grade (P = 0 0112), the presence of tumor budding (P = 0 0334), LVI (P < 0 0001), KRAS mutations (P = 0 0228), PIK3CA mutations (P = 0 0214), multiple genetic mutations in KRAS and PIK3CA genes (P = 0 039), and nodal micrometastases (P < 0 0001) were significant prognostic variables for CSS. The presence of LVI was the only independent and statistically significant prognostic variable for CSS in our cohort of pTNM stage I CRCs. The analysis of KRAS/PIK3CA mutational status may be used to identify patients with stage I CRC at high risk of bad outcome and who may need additional treatments, including biological therapies

Identifying culturally appropriate strategies for coronary heart disease secondary prevention in a regional Aboriginal Medical Service

Aboriginal Australians experience high rates of coronary heart disease (CHD) at an early age, highlighting the importance of effective secondary prevention. This study employed a two-stage process to evaluate CHD management in a regional Aboriginal Medical Service. Stage 1 involved an audit of 94 medical records of clients with documented CHD using the Audit and Best Practice in Chronic Disease approach to health service quality improvement. Results from the audit informed themes for focus group discussions with Aboriginal Medical Service clients (n = 6) and staff (n = 6) to ascertain barriers and facilitators to CHD management. The audit identified that chronic disease management was the focus of appointments more frequently than in national data (P < 0.05), with brief interventions for lifestyle modification occurring at similar or greater frequency. However, referrals to follow-up support services for secondary prevention were lower (P < 0.05). Focus groups identified psychosocial factors, systemic shortcomings, suboptimal medication use and variable awareness of CHD signs and symptoms as barriers to CHD management, whereas family support and culturally appropriate education promoted health care. To optimise CHD secondary prevention for Aboriginal people, health services require adequate resources to achieve best-practice systems of follow up. Routinely engaging clients is required to ensure services meet diverse community needs

"Is this case of a very rare disease work-related?" A review of reported cases of Pacinian neuroma.

Objective In response to a request for a medicolegal opinion from an orthopaedic technician with pacinian neuroma of the hand, we conducted a systematic review of reported cases designed to assess whether this rare disease could be considered to be work-related.Methods We used Medline, Embase, Google Scholar, Google, and a manual search to identify reports of histologically confirmed pacinian neuroma of the hand manifesting after 15 years of age. Cases with available information (from article/authors) on personal history were considered eligible. We tabulated information on age/gender; localization and histopathologic features; signs/symptoms; history of local trauma; occupation, sports/hobbies or other physical exposures; right- or left-handedness; and outcome.Results We found 44 eligible cases (including the present referral). Of these, 21 (48%) followed a trauma [<6 months from onset/presentation (N=7); 0.5\u20132 years from onset (N=6); 652 years from onset (N=7); and timing unknown (N=1)] involving the same anatomic site. Three of these 21 traumas definitely occurred at work, and a further 2 cases occurred at the site of definite work-related repetitive microtrauma.Conclusions The results reinforce the concept that pacinian neuroma of the hand can follow local trauma or repetitive microtrauma. Implicated traumas were either recent or remote, and they sometimes occurred while performing manual tasks at work. We concluded that the referred case could plausibly be considered work-related

An integrated and coordinated approach to preventing recurrent coronary heart disease events in Australia: Policy statement from the Australian Cardiovascular Health and Rehabilitation Association

• Implementing existing knowledge about cardiac rehabilitation (CR) and heart failure management could markedly reduce mortality after acute coronary syndromes and revascularisation therapy. • Contemporary CR and secondary prevention programs are cost-effective, safe and beneficial for patients of all ages, leading to improved survival, fewer revascularisation procedures and reduced rehospitalisation. • Despite the proven benefits attributed to these secondary prevention interventions, they are not well attended by patients. • Modern programs must be flexible, culturally safe, multifaceted and integrated with the patient's primary health care provider to achieve optimal and sustainable benefits for most patients

Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response

In difference to other solid malignancies, the identification of biomarkers for the prediction of malignant melanoma (MM) response to immunotherapy is limited. The aim of the current study was to evaluate the immunohistochemical (IHC) expression of MMR proteins in a cohort of MM metastatic patients receiving anti PD-1 treatments. The therapeutic response of patients was also retrospectively assessed. The cohort of the current study included 14 patients with advanced MM that had received anti PD-1 from January 2014 to December 2016 (12 males, 2 females; average age, 71 years; age range, 47-88 years). IHC analysis of MLH1, PMS2, MSH2 and MSH6 proteins was performed on paraffin-embedded primary tumor samples from each patient and on the 23 available metastasis specimens obtained from the Division of Pathology (University of Modena and Reggio Emilia). The results revealed that 7% of the primary melanoma tissue obtained from the patient cohort exhibited the loss of expression of at least one MMR protein. Three samples from one patient, including one primary melanoma and two metastases, exhibited no MSH6 expression and had the most successful response to anti PD-1 treatment, with a progression-free survival and overall survival of 956 and 2,546 days, respectively. In conclusion, the assessment of MMR protein expression represents a potential predictive marker that may have critical importance for patients with primary and metastatic MM, primarily as criterion for the adoption of immunotherapy treatments

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study.

Purpose Lung cancer relapse may be associated with the presence of a small population of cancer stem cells (CSCs) with unlimited proliferative potential. Our study assessed the relationship between CSCs and the relapse rate in patients harboring adenocarcinoma (ADL) and squamous cell carcinoma of the lung (SCCL). Experimental design This is an observational prospective cohort study (NCT04634630) assessing the influence of CSC frequency on relapse rate after major lung resection in 35 patients harboring early (I-II) (n = 21) and locally advanced (IIIA) (n = 14) ADL and SCCL. There was a 2-year enrollment period followed by a 1-year follow-up period. Surgical tumor specimens were processed, and CSCs were quantified by cytofluorimetric analysis. Results Cancer stem cells were expressed in all patients with a median of 3.1% of the primary cell culture. Primary analysis showed no influence of CSC frequency on the risk of relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.85-1.30). At secondary analysis, patients with locally advanced disease with higher CSC frequency had an increased risk of relapse (HR = 1.26, 95% CI = 1.14-1.39), whereas this was not observed in early-stage patients (HR = 0.90, 95% CI = 0.65-1.25). Conclusion No association was found between CSC and relapse rates after major lung resection in patients harboring ACL and SCCL. However, in locally advanced-stage patients, a positive correlation was observed between CSC frequency and risk of relapse. These results indicate a need for further molecular investigations into the prognostic role of CSCs at different lung cancer stages

Educational interventions on pregnancy vaccinations during childbirth classes improves vaccine coverages among pregnant women in Palermo’s province

Maternal immunization is considered the best intervention in order to prevent influenza infection of pregnant women and influenza and pertussis infection of newborns. Despite the existing recommendations, vaccination coverage rates in Italy remain very low. Starting from August 2018, maternal immunization against influenza and diphtheria-tetanus-pertussis were strongly recommended by the Italian Ministry of Health. We conducted a cross sectional study to estimate the effectiveness of an educational intervention, conducted during childbirth classes in three general hospitals in the Palermo metropolitan area, Italy, on vaccination adherence during pregnancy. To this end, a questionnaire on knowledge, attitudes, and immunization practices was structured and self-administered to a sample of pregnant women attending childbirth classes. Then, an educational intervention on maternal immunization, followed by a counseling, was conducted by a Public Health medical doctor. After 30 days following the interventions, the adherence to the recommended vaccinations (influenza and pertussis) was evaluated. At the end of the study 326 women were enrolled and 201 responded to the follow-up survey. After the intervention, among the responding pregnant women 47.8% received influenza vaccination (+44.8%), 57.7% diphtheria-tetanus-pertussis vaccination (+50.7%) and 64.2% both the recommended vaccinations (+54.8%). A significant association was found between pregnant women that received at least one vaccination during pregnancy and higher educational level (graduation degree/master’s degree), employment status (employed part/full-time) and influenza vaccination adherence during past seasons (at least one during last five years). The implementation of vaccination educational interventions, including counseling by healthcare professionals (HCPs), on maternal immunization during childbirth courses improved considerably the vaccination adherence during pregnancy

Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation

In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of β1-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from primary human squamous cell carcinoma of the skin (cSCC). RAD cells expressed higher levels of survivin, a KSC marker, as compared to non-rapidly adhering (NRAD) cells. Moreover, RAD cells proliferated to a greater extent and were more efficient in forming colonies than NRAD cells. RAD cells also migrated significantly better than NRAD cells. When seeded in a silicone chamber and grafted onto the back skin of NOD SCID mice, RAD cells formed tumors 2–4 fold bigger than those derived from NRAD cells. In tumors derived from RAD cells, the mitotic index was significantly higher than in those derived from NRAD cells, while Ki-67 and survivin expression were more pronounced in RAD tumors. This study suggests that SCC RAD stem cells play a critical role in the formation and development of epithelial tumors