STAT1-Deficient HPV E6/E7-Associated Cancers Maintain Host Immunocompetency against Therapeutic Intervention.

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1-/- mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1-/- host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1-/- induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1-/- mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1-/- mice maintains immunocompetency in CRT/E7 treatments.

Abnormal p53 expression is associated with poor outcomes in grade I or II, stage I, endometrioid carcinoma: a retrospective single-institute study.

OBJECTIVE: The Cancer Genome Atlas study revealed an association between copy-number high (p53 abnormal) genetic mutation and poor prognosis in endometrial cancer in 2013. This retrospective study investigated outcomes in patients with abnormal p53 expression and stage I, low-grade endometrial endometrioid carcinoma (EEC). METHODS: We enrolled women with stage I, grade 1 or 2 EEC who received comprehensive staging and adjuvant therapy between January 2019 and December 2022 at MacKay Memorial Hospital, Taipei, Taiwan. Pathologists interpreted immunohistochemistry stains of cancerous tissues to detect p53 mutation. We compared recurrence, survival, progression-free survival, and overall survival between p53 abnormal and p53 normal groups. RESULTS: Of the 115 patients included, 26 had pathologically confirmed abnormal p53 expression. Of these 26 patients, five (19.2%) experienced recurrence, and two died due to disease progression. By contrast, no patients in the normal p53 group experienced disease recurrence or died due to disease progression. Significant intergroup differences were discovered in recurrent disease status (19.4% vs. 0%, p<0.001), mortality (7.7% vs. 0%, p<0.001), and progression-free survival (p<0.001). The overall survival (p=0.055) also showed powerful worse trend. CONCLUSION: For patients with stage I, low-grade EEC, abnormal p53 expression may be used as an indicator of poor prognosis. Therefore, we suggest considering aggressive adjuvant therapies for these patients.

FLT3L-induced virtual memory CD8 T cells engage the immune system against tumors.

BACKGROUND: Previous research in FMS-like tyrosine kinase 3 ligands (FLT3L) has primarily focused on their potential to generate dendritic cells (DCs) from bone marrow progenitors, with a limited understanding of how these cells affect CD8 T cell function. In this study, we further investigated the in vivo role of FLT3L for the immunomodulatory capabilities of CD8 T cells. METHODS: Albumin-conjugated FLT3L (Alb-FLT3L) was generated and applied for translational medicine purposes; here it was used to treat naïve C57BL/6 and OT1 mice for CD8 T cell response analysis. Syngeneic B16ova and E.G7ova mouse models were employed for adoptive cell transfer to evaluate the effects of Alb-FLT3L preconditioning of CD8 T cells on tumor progression. To uncover the underlying mechanisms of Alb-FLT3L modulation, we conducted bulk RNA-seq analysis of the CD44high CD8 T cells. STAT1-deficient mice were used to elucidate the functional roles of Alb-FLT3L in the modulation of T cells. Finally, antibody blockade of type one interferon signaling and in vitro coculture of plasmacytoid DCs (pDCs) with naive CD8 T cells was performed to determine the role of pDCs in mediating regulation of CD44high CD8 T cells. RESULTS: CD44high CD8 T cells were enhanced in C57BL/6 mice administrated with Alb-FLT3L. These CD8 T cells exhibited virtual memory features and had greater proliferative and effective functions. Notably, the adoptive transfer of CD44high naïve CD8 T cells into C57BL/6 mice with B16ova tumors led to significant tumor regression. RNA-seq analysis of the CD44high naïve CD8 T cells revealed FLT3L to induce CD44high CD8 T cells in a JAK-STAT1 signaling pathway-dependent manner, as supported by results indicating a decreased ability of FLT3L to enhance CD8 T cell proliferation in STAT1-deficient mice as compared to wild-type control mice. Moreover, antibody blockade of type one interferon signaling restricted the generation of FLT3L-induced CD44high CD8 T cells, while CD44 expression was able to be induced in naïve CD8 T cells cocultured with pDCs derived from FLT3L-treated mice. This suggests the crucial role of pDCs in mediating FLT3L regulation of CD44high CD8 T cells. CONCLUSIONS: These findings provide critical insight and support the therapeutic potential of Alb-FLT3L as an immune modulator in preconditioning of naïve CD8 T cells for cancer immunotherapy.

Persistent Salmonella enterica serovar Typhi sub-populations within host interrogated by whole genome sequencing and metagenomics.

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever and, in some cases, chronic carriage after resolution of acute disease. This study examined sequential isolates of S. Typhi from a single host with persistent asymptomatic infection. These isolates, along with another S. Typhi isolate recovered from a household contact with typhoid fever, were subjected to whole genome sequencing and analysis. In addition, direct sequencing of the bile fluid from the host with persistent infection was also performed. Comparative analysis of isolates revealed three sub-populations of S. Typhi with distinct genetic patterns. Metagenomic sequencing recognised only two of the three sub-populations within the bile fluid. The detection and investigation of insertion sequences IS10R and associated deletions complemented analysis of single nucleotide polymorphisms. These findings improve our understanding of within-host dynamics of S. Typhi in cases of persistent infection and inform epidemiological investigations of transmission events associated with chronic carriers.

Albumin and interferon-ß fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8+ T cell-mediated antitumor immunity.

BACKGROUND: Type I interferons (IFN) promote dendritic cells maturation and subsequently enhance generation of antigen-specific CD8 +T cell for the control of tumor. Using type I interferons as an adjuvant to vaccination could prove to be a potent strategy. However, type I interferons have a short half-life. Albumin linked to a protein will prolong the half-life of the linked protein. METHODS: In this study, we explored the fusion of albumin to IFNß (Alb-IFNß) for its functional activity both in vitro and in vivo. We determined the half-life of Alb-IFNß following treatment in the serum, tumor, and tumor draining lymph nodes in both wild type and FcRn knockout mice. We characterized the ability of Alb-IFNß to enhance antigen-specific CD8+ T cells using ovalbumin (OVA) or human papillomavirus (HPV) E7 long peptides. Next, we evaluated the therapeutic antitumor effect of coadministration of AlbIFNß with antigenic peptides against HPVE7 expressing tumor and the treatment's ability to generate HPVE7 antigen specific CD8+ T cells. The contribution of the antitumor effect by lymphocytes was also examined by an antibody depletion experiment. The ability of Alb-IFNß to serve as an adjuvant was tested using clinical grade therapeutic protein-based HPV vaccine, TACIN. RESULTS: Alb-IFNß retains biological function and does not alter the biological activity of IFNß. In addition, Alb-IFNß extends half-life of IFNß in serum, lymph nodes and tumor. The coadministration of Alb-IFNß with OVA or HPVE7 antigenic peptides enhances antigen-specific CD8 +T cell immunity, and in a TC-1 tumor model results in a significant therapeutic antitumor effect. We found that CD8 +T cells and dendritic cells, but not CD4 +T cells, are important for the observed antitumor therapeutic effect mediated by Alb-IFNß. Finally, Alb-IFNß served as a potent adjuvant for TA-CIN for the treatment of HPV antigen expressing tumors. CONCLUSIONS: Overall, Alb-IFNß serves as a potent adjuvant for enhancement of strong antigen-specific CD8 +T cell antitumor immunity, reduction of tumor burden, and increase in overall survival. Alb-IFNß potentially can serve as an innovative adjuvant for the development of vaccines for the control of infectious disease and cancer.

Prolactin Assay Interference by Macroprolactin.

BACKGROUND: Macroprolactinemia is a common presentation especially in gynecology and fertility clinics. However, with this clinical condition, there is a potential for misdiagnosis and unnecessary investigations/treatments due to lack of awareness of its prevalence and diagnostic approaches amongst trainees and physicians. METHODS: In this paper, we discuss the causes of hyperprolactinemia, its pathobiology, and an approach to macro-prolactinemia including relevant clinical chemistry methods and their limitations through the case of a 45-year-old female with a history of irregular menstrual cycles, who was seen in the endocrine clinic. RESULTS: Patient did not have a history of infertility, galactorrhea, visual-disturbance, or headaches. Her physical examination and routine clinical chemistry investigations were unremarkable. Her initial prolactin level was 4,836 mIU/L (109 - 557) with subsequent results demonstrating diminishing levels of prolactin a month apart (1,023 mIU/L). Polyethylene glycol (PEG) precipitation test demonstrated the presence of macroprolactin with a 3% post-PEG recovery of prolactin and 111 mIU/L post-PEG prolactin concentration. CONCLUSIONS: Patient's post-PRL results and clinical course confirmed the presence of macroprolactin to be the cause of factitious hyperprolactinemia. A sound approach to macroprolactinemia is critical in clinical and laboratory practices.

Massive metastasis of breast cancer to female genital organs.

OBJECTIVE: Breast cancer metastasis to the female genital tract is rare, and the ovaries are the most frequent site of extragenital cancer metastasis. The uterus and cervix have been rarely reported as the site of metastasis. CASE REPORT: A 57-year-old woman diagnosed with invasive lobular carcinoma of the left breast 2 years prior was undergoing tamoxifen treatment. She presented with a right breast mass and postmenopausal bleeding. Synchronous right breast invasive lobular carcinoma with endometrium metastasis was diagnosed. The metastasis tumor involved the endometrium, myometrium, cervix, ovaries, and fallopian tubes. CONCLUSION: We noted the rarity of massive metastasis of the female genital tract from breast cancer. Gynecological surveillance and prompt evaluation of the endometrium led to timely diagnosis and treatment.

Greater fuel efficiency is potentially preferable to reducing NOx emissions for aviation's climate impacts.

Aviation emissions of nitrogen oxides (NOx) alter the composition of the atmosphere, perturbing the greenhouse gases ozone and methane, resulting in positive and negative radiative forcing effects, respectively. In 1981, the International Civil Aviation Organization adopted a first certification standard for the regulation of aircraft engine NOx emissions with subsequent increases in stringency in 1992, 1998, 2004 and 2010 to offset the growth of the environmental impact of air transport, the main motivation being to improve local air quality with the assumed co-benefit of reducing NOx emissions at altitude and therefore their climate impacts. Increased stringency is an ongoing topic of discussion and more stringent standards are usually associated with their beneficial environmental impact. Here we show that this is not necessarily the right direction with respect to reducing the climate impacts of aviation (as opposed to local air quality impacts) because of the tradeoff effects between reducing NOx emissions and increased fuel usage, along with a revised understanding of the radiative forcing effects of methane. Moreover, the predicted lower surface air pollution levels in the future will be beneficial for reducing the climate impact of aviation NOx emissions. Thus, further efforts leading to greater fuel efficiency, and therefore lower CO2 emissions, may be preferable to reducing NOx emissions in terms of aviation's climate impacts.

Determinants of Newly-Diagnosed Raised Blood Pressure: The Malaysian Context.

BACKGROUND: Raised blood pressure, also known as hypertension (HPT), has been a distressing health concern among Malaysians. An upward trend is found on the prevalence of newly-diagnosed HPT, contributing to the high number of overall hypertensive patients in Malaysia. To understand the cause and reduce the economic burden caused by HPT, current research aims to examine the dependency among sociodemographic and behavioural determinants of newly-diagnosed HPT among Malaysians. METHODS: The current study uses secondary data from the Fifth National Health and Morbidity Survey (NHMS V) 2015, a population based cross-sectional study. This study uses the Bayesian Network (BN) modelling to design and build a 'causal' model and identify potential determinants and their respective conditional probability on the prevalence of newly-diagnosed HPT among Malaysians. RESULTS: This study shows that Malaysians with newly-diagnosed HPT are directly affected by the age and body mass index (BMI). Additionally, household income, sex, marital status, ethnicity, strata, education levels, occupation, fruit intake, vegetable intake, smoking status, physical activity and plain water intake indirectly affect the incidence of the newly-diagnosed HPT. CONCLUSION: These results may be helpful in implementing appropriate policies to prevent and monitor the increasing prevalence of newly-diagnosed HPT among adults in Malaysia.

Outcomes in Advanced Stage Epithelial Ovarian, Fallopian Tubal, and Peritoneal Cancer after Primary Surgery and Adjuvant Chemotherapies: A Single-Institute Real-World Experience.

Debulking surgery followed by systemic chemotherapy-including three-weekly intravenous paclitaxel and carboplatin (GOG-158)-is the cornerstone for advanced epithelial ovarian, fallopian tubal, and peritoneal cancer (EOC) treatment. In this scenario, Federation of Gynecology and Obstetrics (FIGO) stage, cell types, completeness of surgery, lymph nodes (LN) status, adjuvant chemotherapy regimens, survival status, progression-free survival (PFS), and overall survival (OS) of 192 patients diagnosed as having stage IIIA1-IVB EOC over January 2008-December 2017 were analyzed retrospectively. Of them, 100 (52.1%) patients had been debulked optimally. Of all cases, 64.1% and 10.9% demonstrated serous and clear-cell carcinoma. Moreover, the FIGO stage, surgery completeness, and LN status affected recurrence/persistence and mortality (all p < 0.001). Clear cell carcinoma led to shorter survival than serous carcinoma (p = 0.002). Adjuvant chemotherapy regimens were divided into five main groups according to previous clinical trials. However, choice of chemotherapy failed to demonstrate significant differences in patient outcomes. Similar results were found in the sub-analysis of optimally debulked cases, except that intraperitoneal chemotherapy could reduce mortality risk when compared with GOG-158 (p = 0.042). Notably, retroperitoneal LN dissection in all cases or optimally debulked cases reduced risks of recurrence/persistence and mortality, and prolonged PFS and OS significantly (all p < 0.05). Without optimal debulking, LN dissection led to little improvement in outcomes. Various modified chemotherapy regimens did not prolong PFS and OS or reduce recurrence/persistence and mortality risks. LN dissection is strongly recommended to improve the completeness of surgery and patient outcome. Clear cell type has a poorer outcome than serous type, which requires more aggressive treatment and follow-up.

Exposure to Tobacco, Environmental Tobacco Smoke and Nicotine in Pregnancy: A Pragmatic Overview of Reviews of Maternal and Child Outcomes, Effectiveness of Interventions and Barriers and Facilitators to Quitting.

The aim of this review of reviews was to collate the latest evidence from systematic reviews about the maternal and child health outcomes of being exposed to tobacco and nicotine during pregnancy; the effectiveness of interventions designed to reduce these exposures, and barriers to and facilitators of smoking cessation during pregnancy. Two databases were searched to obtain systematic reviews published from 2010 to 2019. Pertinent data from 76 articles were summarized using a narrative synthesis (PROSPERO reference: CRD42018085896). Exposure to smoke or tobacco in other forms during pregnancy is associated with an increased risk of obstetric complications and adverse health outcomes for children exposed in-utero. Counselling interventions are modestly effective, while incentive-based interventions appear to substantially increase smoking cessation. Nicotine replacement therapy is effective during pregnancy but the evidence is not conclusive. Predictors and barriers to smoking cessation in pregnancy are also discussed. Smoking during pregnancy poses substantial risk to mother's and child's health. Psychosocial interventions and nicotine replacement therapy (NRT) appear to be effective in helping pregnant women quit smoking. Barriers to smoking cessation must be identified and steps taken to eradicate them in order to reduce smoking among pregnant women. More research is needed on smoking cessation medications and e-cigarettes.

Improving health providers smoking cessation care in pregnancy: A systematic review and meta-analysis.

INTRODUCTION: Health providers are lacking in their provision of smoking cessation care during pregnancy. The aim of this study was to systematically review all available global studies on the effectiveness of interventions in improving health providers' provision of smoking cessation care during pregnancy. METHODS: Five databases were searched, Inclusion criteria included all intervention study types. Two reviewers screened abstracts and full texts independently. Interventions were characterized according to the Effective Practice Of Care taxonomy. Random-effects meta-analyses examined intervention effects on smoking cessation care components based on the 5As. Estimates were number of participants reporting each outcome, or mean score, transformed into Cohen's d. Crude meta-regressions, and meta-analysis subgrouping, were performed to examine whether intervention effects for 'Ask', 'Advise' and 'Assist' differed by intervention components. RESULTS: Of 3165 manuscripts, 16 fulfilled inclusion criteria. Pooled analysis showed significant small to large intervention effects on the different care components (Cohen's d ranging from 0.47 for 'Ask' (95%CI 0.13-0.81) to 1.12 (95%CI 0.45-1.79) for 'Setting a quit date'). Crude meta-regression suggested that for 'Ask', having a theoretical basis may improve effectiveness (Cohen's d difference 0.62, 95% CI 0.12-1.1). Subgrouping the meta-analysis suggested that audit and feedback possibly increases intervention effectiveness for 'Advise' and 'Assist'. CONCLUSION: Interventions designed to improve provision of smoking cessation care during pregnancy show a small increase in care components. Studies vary substantially in design, intervention components, and outcome measurement, impacting ability to synthesize available data. Audit and feedback and enhancing intervention design by using behaviour change theories may improve effectiveness. REGISTRATION: PROSPERO CRD42016030143.

Clinical significance of c-Met and phospho-c-Met (Tyr1234/1235) in ovarian cancer.

OBJECTIVE: c-Met is expressed in human ovarian cancer tissues, and its phosphorylation activates signaling cascades that might affect the behavior of cancer cells. In this study, we evaluated the association of c-Met and phosphorylated c-Met (phospho-c-Met) expressions with the clinical outcomes of ovarian cancer patients. MATERIALS AND METHODS: Archived tissue from surgical specimens of 269 ovarian cancer patients who underwent a debulking operation in MacKay Memorial Hospital between 2004 and 2012 were collected. Tissue microarrays were stained with anti-Met and anti-phospho-Met (Tyr1234/1235) monoclonal antibodies. Immunostaining intensity was scored on a scale of 0-3+. High expression was defined as more than 50% of moderate and intense staining. Patients' clinical data were reviewed until April 2017 for analysis. RESULTS: The proportion of high c-Met expression was significantly higher in patients with cancer in early stages (Federation of Gynecology and Obstetrics stages I and II) and low histologic grades (grades 1 and 2) (79.70%, p = 0.0008 and 80.15%, p ≤ 0.0001, respectively). However, no association was found between phospho-c-Met and FIGO stage or the histologic grade. Ovarian clear cell carcinoma and mucinous carcinoma had much higher c-Met expression (95.16% and 87.10%, p ≤ 0.0001 and p = 0.0292, respectively). Although the overall survival did not differ significantly, low expressions of c-Met and phospho-c-Met were obviously associated with poor progression-free survival respectively (p = 0.0034, HR: 0.5264, 95% CI: 0.3326-0.8330 and p = 0.0136, HR: 0.5626, 95% CI: 0.3709-0.8535). CONCLUSION: Low c-Met expression was associated with poor clinical outcomes.

Trading off Aircraft Fuel Burn and NO x Emissions for Optimal Climate Policy.

Aviation emits pollutants that affect the climate, including CO2 and NO x, NO x indirectly so, through the formation of tropospheric ozone and reduction of ambient methane. To improve the fuel performance of engines, combustor temperatures and pressures often increase, increasing NO x emissions. Conversely, combustor modifications to reduce NO x may increase CO2. Hence, a technology trade-off exists, which also translates to a trade-off between short-lived climate forcers and a long-lived greenhouse gas, CO2. Moreover, the NO x-O3-CH4 system responds in a nonlinear manner, according to both aviation emissions and background NO x. A simple climate model was modified to incorporate nonlinearities parametrized from a complex chemistry model. Case studies showed that for a scenario of a 20% reduction in NO x emissions the consequential CO2 penalty of 2% actually increased the total radiative forcing (RF). For a 2% fuel penalty, NO x emissions needed to be reduced by >43% to realize an overall benefit. Conversely, to ensure that the fuel penalty for a 20% NO x emission reduction did not increase overall forcing, a 0.5% increase in CO2 was found to be the "break even" point. The time scales of the climate effects of NO x and CO2 are quite different, necessitating careful analysis of proposed emissions trade-offs.

Nicotine replacement therapy for smoking cessation during pregnancy.

Nicotine replacement therapy (NRT) is recommended in current Australian clinical guidelines for pregnant women who are unable to quit smoking unassisted. Clinicians report low levels of prescribing NRT during pregnancy, due to safety concerns and low levels of confidence in their ability to prescribe NRT. Animal models show that nicotine is harmful to the fetus, especially for brain and lung development, but human studies have not found any harmful effects on fetal and pregnancy outcomes. Studies of efficacy and effectiveness in the real world suggest that NRT use during pregnancy increases smoking cessation rates. These rates may be hampered by the fact that studies so far have used an NRT dose that does not adequately account for the higher nicotine metabolism during pregnancy and, therefore, does not adequately treat withdrawal symptoms. Further research is needed to assess the safety and efficacy of higher dosages of NRT in pregnancy, specifically of combination treatment using dual forms of NRT. As NRT is safer than smoking, clinicians need to offer this option to all pregnant women who smoke. A practical guide for initiating and tailoring the dose of NRT in pregnancy is suggested.

Prevention and Treatment of Smoking and Tobacco Use During Pregnancy in Selected Indigenous Communities in High-Income Countries of the United States, Canada, Australia, and New Zealand: An Evidence-Based Review.

Tobacco smoking during pregnancy is the most important modifiable risk factor for adverse pregnancy outcomes and long-term health complications for mother and baby. Tobacco use during pregnancy has decreased in high-income countries but not in Indigenous women in Australia, New Zealand, the United States, and Canada. This evidence-based review focuses on tobacco use among Indigenous pregnant women in high-income countries that share a history of European colonization. Indigenous women are more likely to use tobacco because of socioeconomic disadvantage, social norms, and poor access to culturally appropriate tobacco cessation support. Complications arising from tobacco smoking during pregnancy, such as low birth weight, prematurity, perinatal death, and sudden infant death syndrome, are much higher in Indigenous populations. Effective approaches to cessation in pregnant nonindigenous women involves behavioral counseling, with or without nicotine replacement therapy (NRT). Higher nicotine metabolism during pregnancy and poor adherence may affect therapeutic levels of NRT. Only two randomized trials were conducted among Indigenous women: neither found a statistically significant difference in cessation rates between the treatment and comparison arms. Considerations should be given to (1) whole life course approaches to reduce tobacco use in Indigenous women, (2) prohibiting tobacco promotion and reducing access to alcohol for minors to prevent smoking initiation in Indigenous youth, and (3) training health-care professionals in culturally appropriate smoking cessation care to improve access to services. It is critical to ensure acceptability and feasibility of study designs, consult with the relevant Indigenous communities, and preempt implementation challenges. Research is needed into the effect of reducing or stopping smoking during pregnancy when using NRT on subsequent maternal and infant outcomes.

Total knee replacement pre-operative education in a Singapore tertiary hospital: A best practice implementation project.

OBJECTIVES: To increase the competency of specialist outpatient clinic nurses in the provision of pre-operative total knee replacement (TKR) education, and ensure that all patients scheduled for elective TKR received the pre-operative education package. METHODS: The project was implemented in three phases. Phase 1 entailed a baseline audit that analysed 30 randomized TKR patients who received pre-operative education. In Phase 2, the gaps and barriers in the project were discussed. Using best practice recommendations from the Joanna Briggs Institute, the project team leader collated and standardized the pre-operative education tools, which consisted of a pictorial booklet, a video and home care advice. A teaching plan guided the nurses to increase their understanding and improve practice using the education tools. The usefulness of education strategies and tools was discussed and these were improved over the proposed timeline. Phase 3 entailed a post-implementation audit to evaluate the provision of pre-operative education. RESULTS: Post implementation, nurses' competency in the provision of pre-operative TKR education increased from 18% to 91%. The number of patients who received the structured pre-operative education package increased from 27% to 50%. CONCLUSION: Overall, there was improvement in the provision of pre-operative TKR education to patients by clinic nurses using evidence-based best practice and a standardized education package.

Cribriform morular variant of papillary thyroid carcinoma in a patient with an incidental neck lump: a case report and review of the literature.

The cribriform morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare morphologic entity that is associated with familial adenomatous polyposis (FAP). We report a case of a young lady with an incidentally discovered right-sided neck nodule on ultrasonography with a diagnosis of CMV-PTC confirmed on thyroidectomy and review the literature associated with the clinical presentation, imaging characteristics, pathological findings and the association with FAP.