A Randomized Trial of Valganciclovir Prophylaxis Versus Preemptive Therapy in Kidney Transplant Recipients.

SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .

A successful nursing education promotes newly graduated nurses' job satisfaction one year after graduation: a cross-sectional multi-country study.

BACKGROUND: Job satisfaction is a key factor for the successful transition of newly graduated nurses (NGNs) and for retaining NGNs in their workplaces. However, there is limited evidence of the relationship between satisfaction regarding the nursing education program and NGNs' job satisfaction in the first year after graduation. Therefore, this study aims to examine the association of the nursing education related factors and NGNs' job satisfaction. METHODS: A cross-sectional study design with the utilization of data collected from the same respondents one year earlier as educational factors was applied. The data were collected from NGNs (n = 557) in 10 European countries using an electronic survey between February 2019 and September 2020, and analyzed in detail for four countries (n = 417). Job satisfaction was measured with three questions: satisfaction with current job, quality of care in the workplace, and nursing profession. Nursing education related factors were satisfaction with nursing education program, level of study achievements, nursing as the 1st study choice, intention to stay in nursing, and generic nursing competence. The data were analyzed statistically using logistic regression. RESULTS: Most of the NGNs in the 10 countries were satisfied with their current job (88.3%), the quality of care (86.4%) and nursing profession (83.8%). Finnish, German, Lithuanian and Spanish NGNs' satisfaction with the nursing education program at graduation was statistically significantly associated with their job satisfaction, i.e., satisfaction with their current job, the quality of care, and the nursing profession. Moreover, NGNs who had fairly often or very often intention to stay in nursing at graduation were more satisfied with their current job, with the quality of care, and with the nursing profession compared with NGNs who had never or fairly seldom intention to stay in nursing at graduation. CONCLUSIONS: Nursing education plays a significant role in NGNs' job satisfaction one year after graduation, indicating the importance to start career planning already during nursing education. Both nursing education providers and healthcare organizations could plan in close collaboration a transition program for NGNs to ease the transition phase and thus increase the NGNs' job satisfaction and ultimately the high-quality care of the patients.

Methylation analysis as an auxiliary tool in cytological diagnostics of infrequent anogenital lesions - a pilot study.

Methylation silencing of certain cellular genes is a sign of carcinogenesis progression and therefore tests that detect methylation could be used in the diagnosis or staging of malignant diseases. In the diagnosis of squamous cell carcinomas of the cervix which are almost 100% caused by long-term infection with highrisk human papillomavirus (HR-HPV), methylation silencing of certain cellular genes is a highly specific marker of advanced dysplastic lesions and appears to result from aberrant activation of the methyltransferase DNMT1 by viral oncoproteins E6 and E7. A methylation test performed on a cervicovaginal cytology specimen allows to increase the diagnostic value of this non-invasive test and to select patients with severe squamous cell lesions for follow-up. Other less frequent anogenital malignancies that are induced by HR-HPV to a lesser extent can also be detected by cytological examination - glandular lesions of various origins, most commonly cervical and endometrial adenocarcinomas and anal carcinoma. The aim of our pilot study was to evaluate the utility of a methylation test for the diagnosis of these malignancies in a cohort of 50 liquid-based cervicovaginal cytologies with glandular lesion and 74 liquid-based anal cytologies from HIV-positive men having sex with men who are at high risk for anal cancer development.

SARS-CoV-2 RNA may rarely be present in a uterine cervix LBC sample at the asymptomatic early stage of COVID 19 disease.

OBJECTIVE: Currently, it is thought that uterine cervix mucosal samples present a low risk of SARS-CoV-2 exposure. So far, there is no evidence of SARS-CoV-2 detection in Papanicolaou (Pap) smears. Nevertheless, clinicians could be exposed unaware to the coronavirus while performing and handling a Pap smear. We aimed to retrospectively evaluate the presence of SARS-CoV-2 RNA in cervical liquid-based cytology (LBC) samples in women who tested positive for a nasopharyngeal COVID-19 PCR test. METHODS: From our laboratory database, we identified patients with data on a cervical cancer screening LBC sample paired with a positive nasopharyngeal COVID-19 PCR test. Relevant LBC samples taken within an incubation period of 14 days and post-onset RNA shedding interval of 25 days were subsequently tested for SARS-CoV-2 RNA using RT-PCR tests. RESULTS: The study group consisted of 102 women. Of those, 23 LBC samples were tested. SARS-CoV-2 RNA was detected in one LBC sample from a 26-year-old asymptomatic woman taken six days before reporting headaches and knee arthralgia with a positive nasopharyngeal SARS-CoV-2 RT-PCR test. CONCLUSIONS: It is possible to detect SARS-CoV-2 RNA in cervical LBC samples at an early asymptomatic stage of COVID-19. In general, this finding is infrequent in asymptomatic women who tested SARS-CoV-2 positive within an incubation of 14 days and a post-onset RNA shedding period of 25 days. We fully support the current thinking that cervical LBC samples from asymptomatic women pose a low risk of SARS-CoV-2 exposure and can be handled in the frame of good microbiological practice and procedures.

Clinical learning environment and graduating nursing students' competence: A multi-country cross-sectional study.

The purpose of this study was to explore nursing students' perceptions of their final clinical learning environment and its association with their self-assessed competence, satisfaction with nursing education, and turnover intentions at graduation in six European countries. A multi-country comparative cross-sectional study was conducted with nursing students (n = 1746) from the Czech Republic, Finland, Italy, Portugal, Slovakia, and Spain using the Nurse Competence Scale and the Clinical Learning Environment and Supervision scale. Nursing students' overall perceptions of their final clinical learning environment and supervision were positive in all the countries studied. The correlation between the students' perceptions of their final clinical learning environment and competence was statistically significant and positive. Satisfaction with the nursing program and clinical practicum and no consideration of career change were related to positive perceptions of the final clinical learning environment. Highlighting the importance of the supervisory relationship and pedagogical atmosphere, nursing students' positive perceptions of the final clinical learning environment and supervision contribute to a better level of self-assessed competence and satisfaction with the nursing program and clinical practicum, leading to lower turnover intentions.

Undiagnosed cryptococcal meningoencephalitis with extensive hypoxic-ischemic brain injury mimicking grade 3 diffuse axonal injury.

In this article, we report the autopsy findings of a 50-year-old immunocompetent woman, who was hospitalized with an altered state of consciousness. Examinations, including cerebrospinal fluid analysis, carried out during hospitalization failed to identify the infectious agent causing progressive loss of consciousness and quadriparesis. The patient died within 8 days of admission to the hospital. Post-mortem microscopic and culture examination revealed Cryptococcus species. Death was attributed to cryptococcal meningoencephalitis. Histologic examination revealed accumulation of cryptococcus mimicking erythrocytes and extensive hemorrhage in hematoxylin and eosin-stained sections of the brain. Multifocal obliteration of the vascular bed by yeast was accompanied by hypoxic-ischemic brain injury mimicking traumatic diffuse axonal injury.

The newly proposed International Endocervical Adenocarcinoma Criteria and Classification and its relevance to cervical cytology screening assessed in a prospective 2-year study of 118 cases.

BACKGROUND: It is generally acknowledged that interobserver variability for the histological diagnosis of endocervical adenocarcinoma (EA) subtypes is suboptimal. The recently proposed International Endocervical Adenocarcinoma Criteria and Classification (IECC) system is based on the presence of associated human papilloma virus (HPV) infection. It recognises HPV-associated EAs and non-HPV-associated EAs. METHODS: This prospective cytology-histology and molecular genetics-based study investigated the potential effect of IECC being applied to Papanicolaou (Pap) test with regard to the diagnostic accuracy of severe glandular lesions reported at least as adenocarcinoma in situ (AIS). RESULTS: Out of 118 liquid-based cytology Pap tests with AIS+ lesion, complete information on follow-up biopsy and HPV status was available in 51 cases. AIS and EA category correlated with histologically confirmed AIS/EA in 88.5% (23/26) and 70.5% (12/17) of cases, respectively. Interestingly, 93% (40/43) of cases diagnosed as AIS/EA were HPV positive and 7% (3/43) were HPV negative (originating in the cervix, endometrium and adnexa). CONCLUSIONS: Our findings suggest that this approach could possibly divide Pap tests containing severe glandular lesion into two groups: (a) robust diagnosis of HPV-associated EA and (b) non-HPV associated glandular lesions of heterogeneous origin, requiring further clinical preoperative diagnostic workup.

Echinococcus multilocularis: Diagnostic problem in a liver core biopsy.

Echinococcus multilocularis causes an aggressive form of hydatidosis whose histomorphological picture is generally not well recognized. We report a case of 39-year-old women presenting with poorly circumscribed nodules in the right hepatic lobe. Owing to the clinical suspicion of focal nodular hyperplasia and hepatocellular adenoma, a core biopsy was performed. The histological findings of necrotic fibrous tissue infiltrated by narrow epithelial cords and small cysts containing cytokeratin positive material were in concordance with the diagnosis of cholangiocarcinoma. Subsequent examination of the surgically resected necrotic nodules with a vital tissue at the periphery corresponded to a reparative fibrosis accompanied by a striking ductular proliferation. Serological and molecular genetic work-up led to the diagnosis of Echinococcus multilocularis. The aim of this report is to point out the unusual histological features of the solid foci of alveolar hydatidosis, which consisted of necrotic fibrous tissue with ductular reaction. Such findings in a core biopsy may simulate regressively altered carcinoma.

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Viral load and duration of BK polyomavirus viraemia determine renal graft fibrosis progression: histologic evaluation of late protocol biopsies.

BACKGROUND: Polyomavirus BK (BKV) infection of the renal allograft causes destructive tissue injury with inflammation and subsequent fibrosis. METHODS: Using a prospective cohort of patients after kidney transplantation performed between 2003 and 2012, we investigated the role of BKV viraemia in the development and progression of interstitial fibrosis and tubular atrophy (IFTA). The primary outcome was moderate-to-severe IFTA assessed by protocol biopsy at 36 months. RESULTS: A total of 207 consecutive recipients were enrolled. Of these, 57 (28%) developed BKV viraemia with 10 (5%) cases of polyomavirus-associated nephropathy (PVAN). Transient (<3 months) BKV viraemia occurred in 70% of patients, and persistent (≥3 months) BKV viraemia in 30%. A high viral load (≥10 000 copies/mL) was detected in 18% and a low viral load (<10 000 copies/mL) in 61%, while the viral load could not be determined in 21%. Moderate-to-severe IFTA was significantly increased in high [71%; odds ratio (OR) = 12.1; 95% confidence interval (CI) 1.62-90.0; P = 0.015] or persistent BKV viraemia (67%; OR = 6.33; 95% CI 1.19-33.7; P = 0.031) with corresponding rise in 'interstitial fibrosis + tubular atrophy' scores. Only patients with transient low BKV viraemia showed similar incidence and progression of IFTA to the no-BKV group. Persistent low BKV viraemia was uncommon yet the progression of fibrosis was significant. Only recipients with PVAN experienced inferior graft survival at 5 years. CONCLUSIONS: These data suggest that only transient low BKV viraemia does not negatively affect the progression of allograft fibrosis in contrast to excessive risk of severe fibrosis after high or persistent BKV viraemia.

Syringocystadenoma Papilliferum of the Anogenital Area and Buttocks: A Report of 16 Cases, Including Human Papillomavirus Analysis and HRAS and BRAF V600 Mutation Studies.

Syringocystadenoma papilliferum (SCAP) is a benign tumor most commonly located on the head and neck area often associated with nevus sebaceus. In its usual location, the human papillomavirus (HPV) DNA and mutations in the RAS/mitogen-activated protein kinase signaling pathway have been detected in SCAP. We studied 16 cases of SCAP in the anogenital areas and buttock where this neoplasm is rare and attempted to find out whether SCAP in these sites have different histopathological and molecular biological features. It seems that there is no significant difference between the morphology of anogenital SCAP and SCAP in other locations. Several tumors in our cohort demonstrated features resembling those seen in warts, but HPV DNA was not found in these lesions. On the contrary, we identified DNA of HPV high-risk types in some tumors without HPV-related morphology. Our study confirms the role of HRAS and BRAF V600 mutations in the pathogenesis of SCAP, including SCAP in the anogenital areas and buttock.

The detection of DNA methylation of tumour suppressor genes in cervical high-grade squamous intraepithelial lesion: A prospective cytological-histological correlation study of 70 cases.

BACKGROUND: DNA methylation has been suggested as one of the epigenetic changes promoting carcinogenesis. The aim of this study was to prospectively evaluate the methylation status of CADM 1, MAL and hsa-miR-124 genes in high-grade squamous intraepithelial lesion (HSIL) liquid-based cytology (LBC) samples with a histological correlation. METHODS: Seventy histologically confirmed cases of HSIL paired with prior screening LBC diagnosis of HSIL within a 3-month interval were selected. Histologically, the lesions were reviewed and assessed including: (a) number of blocks harbouring dysplastic squamous epithelium; (b) number of blocks containing glandular extension of dysplastic epithelium; and (c) the depth of glandular extension (which was assessed semi-quantitatively as graded 1-3). Human papillomavirus (HPV) subtyping was performed from residual LBC materials using the LINEAR ARRAY HPV Genotyping Test and in-house polymerase chain reaction targeting the HPV E1 gene. The detection of methylation silencing of tumour suppressor genes CADM1, MAL and hsa-miR-124 was performed by multiplex methylation-specific real-time polymerase chain reaction. RESULTS: A positive methylation status was detected in 41 cases (58.6%). The number of blocks with HSIL varied from one to 13. Glandular extension was seen in 44 cases with the number of blocks involved ranging from one to 10. The depth of HSIL glandular extension varied. CONCLUSION: The DNA methylation test allows HSIL lesions to be divided into two distinct groups of methylated HSIL in significantly older patients and unmethylated HSIL in younger patients. This study was not able to prove that methylation status in cervical HSIL correlates with the size of the lesion (measured by the number of blocks involved) or with HSIL propensity for endocervical glandular extension, nor with HPV type or multi-infection.

Quality of life in patients with diabetic foot ulcer in Visegrad countries.

AIMS AND OBJECTIVES: To identify the quality of life of patients with diabetic foot ulcers in the Visegrad countries. BACKGROUND: The diabetics with foot ulcers are principally evaluated on the basis of physical parameters, but this does not always reveal much about the patient's experience of life with ulceration. DESIGN: The cross-sectional study. METHODS: The standardised generic questionnaire World Health Organization Quality of Life-BREF was used. The sample was made up of 525 participants and the calculations were performed using the IBM spss statistical program. RESULTS: The significant negative correlations between demographic data such as age, duration of diabetes mellitus, duration of diabetic ulceration treatment and a lower level of quality of life were found across the sample. The statistically significant differences according to clinical characteristics such as Wagner classification, frequency of foot ulcers, present peripheral vascular disease and pain in terms of quality of life were also revealed. Significant differences of quality of life among Visegrad countries were revealed: Hungary's participants had a worse quality of life than others, while Slovak participants expressed lower satisfaction with their health than Czech. CONCLUSIONS: Socio-demographic factors and clinical characteristics influence the quality of life of patients with diabetic foot ulcer. Significant differences between patients of Visegrad countries were found in all domains of quality of life: physical, psychological, social and environmental. RELEVANCE TO CLINICAL PRACTICE: The quality of life of patients with diabetic foot ulcer reflects the conditions and healthcare system in each of the Visegrad countries. We have to respect socio-demographic factors and clinical characteristics in nursing care. This could have an impact on managing patient care not only with regard to their diabetic foot ulcer but also with regard to the patient as a personality with their own problems in relation to physical, psychosocial and environmental conditions.

The efficacy of diabetic foot care education.

AIMS AND OBJECTIVES: To survey the efficacy of education about factors that influence the learning process and behaviour of diabetics following a nursing interventional project in diabetic foot care education. BACKGROUND: Educating diabetics can change their behaviour, which may contribute to the prevention of diabetic foot ulcer and amputation. However, there is little information on the factors that contribute to effectiveness of foot care education. DESIGN: Survey. METHODS: The data before education were collected by using structured assessment based on a practical reasoning scheme. The interventional diabetic foot care education project immediately followed. We used verbal and written patient education material. After education (six months), we used a questionnaire by postadministration. The data were analysed using content analysis, descriptive statistics and inferential statistics. RESULTS: We discovered a rise of knowledge, willingness and motivation to learn and to change the behaviour of diabetics after education. The clinical parameters (weight, Body Mass Index, blood pressure) demonstrated a statistically significant positive change six months after education. CONCLUSION: The findings after education show a rise in knowledge, willingness and motivation, which are important factors that contribute to changing behaviour of diabetics in diabetic foot care. After education, we identified better results in terms of weight and blood pressure, both of which play a role in the prevention of diabetic ulcer. RELEVANCE TO CLINICAL PRACTICE: The education valuable tool ensures knowledge, motivation and willingness to change behaviour in order to prevent diabetic foot complications of diabetics. By using structured assessment, nurses are able to modify their educational interventions.

Prevalence of oral and anal human papillomavirus infection in Czech predominantly HIV-positive men having sex with men - data from a previously unreported population.

BACKGROUND: HIV-positive men who have sex with men (MSM) are more likely to experience human papillomavirus (HPV) infection. The persistent HPV infection is the major factor in the development of anal and oropharyngeal neoplasms. Data on the prevalence of anal and oral HPV in MSM are almost absent from the countries of Central and Eastern Europe. We conducted a cross-sectional study focused on the prevalence of oral and anal HPV infections and the relationship between current anal and oral HPV intrapersonal infection in a Czech population of predominantly HIV-positive MSM. METHODS: Oral gargle and anal swab samples from 205 predominantly HIV-positive MSM from the Czech Republic were analysed for HPV infection using PCR. Selected sociodemographic and clinical data were correlated with HPV detection using generalized linear models and multivariate analysis. RESULTS: HPV infection was detected in 183 (96.8%) anal and 48 (23.6%) oral samples. The most common type of HR-HPV was HPV16 in both anal (25.4%) and oral (2.5%) samples. Multiple anal HPV infections and the presence of vaccine-targeted HR-HPV types were significantly correlated with abnormal anal cytology and HIV status. CONCLUSION: The prevalence of anal HPV infection in Czech predominantly HIV-positive MSM ranks among the highest reported, while oral HPV prevalence is consistent with MSM populations. Minimal overlap of oral and anal HPV types within a patient was observed.

Graduating Nursing Students' Empowerment and Related Factors: Comparative Study in Six European Countries.

New nurses are needed in healthcare. To meet the role expectations of a registered nurse, nursing students must feel empowered at graduation. However, there are only a few studies focusing on nursing students' empowerment. This study aims to describe and analyze graduating nursing students' level of empowerment in six European countries and potential related factors. A comparative and cross-sectional study was performed in the Czech Republic, Finland, Italy, Portugal, Slovakia, and Spain with graduating nursing students (n = 1746) using the Essential Elements of Nurse Empowerment scale. Potentially related factors included age, gender, a previous degree in health care, work experience in health care, graduation to first-choice profession, intention to leave the nursing profession, level of study achievements, satisfaction with the current nursing programme, clinical practicums, theoretical education, and generic competence measured with the Nurse Competence Scale. The data were analysed statistically. Graduating nursing students' self-assessed level of empowerment was moderate, with statistical differences between countries. Those with high empowerment had no intention to leave the nursing profession, had a higher level of study achievements, and a higher self-assessed generic competence level. The results suggest that empowerment needs to be enhanced during nursing education. Further research is needed to understand the development of empowerment during the early years of a nursing career.

Nursing students' self-directed learning abilities and related factors at graduation: A multi-country cross-sectional study.

AIM: To describe nursing students' level of self-directed learning abilities and identify possible factors related to it at graduation in six European countries. DESIGN: A cross-sectional comparative design across the countries. METHODS: The study was conducted from February 2018 to September 2019. Nursing students (N = 4,135) from the Czech Republic, Finland, Italy, Portugal, Slovakia and Spain were invited to respond to the research instruments (the Self-Rating Scale of Self-Directed Learning and the Nurse Competence Scale) at graduation. The data were analysed using the chi-square test, Pearson correlation coefficient and the linear model. RESULTS: The nursing students' (N = 1,746) overall self-directed learning abilities were at high level in all countries. Statistically significant differences occurred between countries. Spanish nursing students reported the highest level of self-directed learning abilities while students from the Czech Republic reported the lowest. Higher level of self-directed learning abilities was related to several factors, particularly with the self-assessed level of competence and country.

Multiple (familial) trichoepitheliomas: a clinicopathological and molecular biological study, including CYLD and PTCH gene analysis, of a series of 16 patients.

Multiple familial trichoepitheliomas (MFT) constitute an autosomally inherited syndrome possibly related to Brooke-Spiegler syndrome (BSS). Although some early studies suggested a role for the PTCH gene on chromosome 9q22.3 in the etiopathogenesis of MFT, recent studies of occasional patients with the MFT clinical phenotype identified mutations in the CYLD gene on chromosome 16q12-q13, a gene responsible for BSS. A systematic investigation of PTCH and CYLD mutations in patients with MFT has never been performed. Our main objective was to collect a reasonably large series of patients with MFT to (1) study the clinicopathological spectrum of the disease, (2) determine whether the PTCH gene is implicated in the pathogenesis of MFT, and if so (3) determine the relative frequency of CYLD and PTCH mutations, (4) establish if there may be any possible genotype-phenotype correlations, and (5) study the spectrum of somatic mutations. Clinical analysis including family histories, histopathological investigations, and molecular genetic studies were performed. There were 9 female and 7 male patients ranging in age from 11 to 63 years. They presented with multiple, small, discrete and sometimes confluent, skin-colored to pink, asymptomatic nodules preferentially located on the face, being especially prominent and confluent in the nasolabial folds and inner aspects of the eyebrows. A total of 66 conventional trichoepitheliomas (TEs) were studied microscopically. Aside from typical features of TE, some also exhibited variant morphological patterns including areas reminiscent of other benign adnexal neoplasms and melanocytic hyperplasia. In none of the 9 patients tested was a germline mutation of the PTCH gene identified. Germline CYLD mutations were detected in 6 of 13 patients tested (identical in 2 unrelated patients) including 2 novel mutations, whereas the remaining 7 individuals showed wild-type alleles. Two patients with germline wild-type CYLD showed, however, a somatic mutation in the gene (1 duplication, 1 substitution mutation). Neither CYLD nor PTCH germline mutations were found in the 5 patients in whom both genes were analyzed. MFT seems to be a phenotypic variant of BSS. The PTCH gene is rarely, if ever, involved in the pathogenesis of MFT. Absence of a germline mutation of the CYLD gene in cases harboring a somatic mutation may be explained by large deletions in the gene or by mutation in intronic sequences or in the promoter region. Considering our 5 patients with no mutation in either gene, the final possibility is that another, as yet undescribed gene (neither CYLD nor PTCH) is implicated in the pathogenesis of some patients with MFT.

Prevalence of high-risk human papillomavirus DNA and mRNA and its association with abnormal anal cytology in the Czech male anal cancer screening cohort.

BACKGROUND: Anal cancer (AC) screening is justified in high-risk populations, particularly HIV-positive men having sex with men (MSM). HR-HPV testing could improve the efficiency of cytologically based screening of AC, as in the screening of biologically analogical cervical cancer. The specificity of HR-HPV testing is influenced by the prevalence of HR-HPV infection in the screened population. Reported anal HR-HPV DNA prevalence in MSM is high, but HR-HPV mRNA reflects rather long-term infections and is more specific for high-grade lesions. However, no data were published about HR-HPV DNA and mRNA prevalence in the Czech AC screening population. METHOD: Results of liquid-based anal cytology of 203 predominantly HIV-positive MSM from the Czech AC screening cohort were correlated with results of DNA and E6/E7 mRNA testing of 14 HR-HPV types, and HPV16 genotyping. Eighty-one MSM underwent a standard anoscopy. RESULTS: A total of 109 (53.7%) samples had abnormal cytology, with 12 (5.9%) ASC-H/HSIL, 67 (33.0%) samples cytologically negative, and 27 (13.3%) unsatisfactory. HR-HPV DNA was detected in 134 (66.0%) and HR-HPV RNA in 72 (35.5%) anal smears. HR-HPV mRNA and HPV16 mRNA positivity were associated with abnormal cytology (p = .0037, p = .0021). No significant association was found between HR-HPV DNA or HPV16 DNA positivity and abnormal cytology. No high-grade lesions were revealed by anoscopy. CONCLUSION: Prevalence of anal HR-HPV DNA among Czech MSM is high, however, the prevalence of HR-HPV mRNA is half and associated with abnormal cytology. Our results indicate an increased efficiency of cytological screening when combined with HR-HPV mRNA testing.