Relationship between disability and physical activity frequency after cervical spine surgery: A linear mixed model analysis.

BACKGROUND: There is a paucity of data on physical activity and its effects in patients after cervical spine surgery. OBJECTIVE: This study aimed to examine the association between physical activity and disability in patients after cervical spine surgery while also considering age, sex, pain, and central sensitization (CS)-related symptoms. METHODS: Participants included individuals with a cervical degenerative condition who had undergone surgery. Neck disability index, physical activity frequency, numerical rating scale for pain intensity, and short form of the CS inventory were recorded more than 1 year postoperatively. The linear mixed model was performed to examine the association between physical activity and disability. RESULTS: The responses of 145 participants were analyzed. The linear mixed model results showed that the stretching and light-intensity exercise frequency (ß=-0.14, p= 0.039) was independently associated with disability, adjusted for age, sex, pain, and CS-related symptoms. Conversely, other physical activities, such as walking and muscle strength exercises, were not associated with a disability. CONCLUSION: The findings emphasize the importance of performing regular physical activity, regardless of pain and CS-related symptoms.

External beam radiation therapy for recurrent or residual thyroid cancer: What is the best treatment time and the best candidate for long-term local disease control?

INTRODUCTION: Cervical disease control might be challenging in advanced thyroid cancer (DTC). Indications for cervical external beam radiation therapy (EBRT) are controversial. PURPOSE: To identify clinical and molecular factors associated with control of cervical disease with EBRT. METHODS: Retrospective evaluation and molecular analysis of the primary tumor DTC patients who underwent cervical EBRT between 1995 and 2022 was performed. RESULTS: Eighty adults, median age of 61 years, were included. T4 disease was present in 43.7%, lymph node involvement in 42.5%, and distant metastasis in 47.5%. Those with cervical progression were older (62.5 vs. 57.3, p = 0.04) with more nodes affected (12.1 vs. 2.8, p = 0.04) and had EBRT performed later following surgery (76.6 vs. 64 months, p = 0.05). EBRT associated with multikinase inhibitors showed longer overall survival than EBRT alone (64.3 vs. 37.9, p = 0.018) and better local disease control. Performing EBRT before radioiodine (RAI) was associated with longer cervical progression-free survival (CPFS) than was RAI before (67.5 vs. 34.5, p < 0.01). EBRT ≥2 years after surgery was associated with worse CPFS (4.9 vs. 34, p = 0.04). The most common molecular alterations were ERBB2, BRAF, FAT1, RET and ROS1 and TERT mutation was predictive of worse disease control after EBRT (p = 0.04). CONCLUSION: Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT.

Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers.

BACKGROUND: Hyperthermia is a well-accepted cancer therapy. Microwaves provide a very precise, targeted means of hyperthermia and are currently used to treat plantar warts caused by cutaneous-infective human papillomaviruses (HPVs). Other HPV genotypes infecting the anogenital mucosa cause genital warts or preneoplastic lesions or cervical cancer. Effective, non-ablative therapies for these morbid HPV-associated lesions are lacking. METHODS: The molecular consequences of microwave treatment were investigated in in vitro cultured three-dimensional HPV-positive cervical tumour tissues, and tissues formed from HPV-infected normal immortalised keratinocytes. Microwave energy delivery to tissues was quantified. Quantitative reverse transcriptase PCR was used to quantify mRNA expression. Immunohistochemistry and fluorescence immunostaining was used to assess protein expression. FINDINGS: Microwave energy deposition induced sustained, localised cell death at the treatment site. There was a downregulation in levels of HPV oncoproteins E6 and E7 alongside a reduction in cellular growth/proliferation and induction of apoptosis/autophagy. HSP70 expression confirmed hyperthermia, concomitant with induction of translational stress. INTERPRETATION: The data suggest that microwave treatment inhibits tumour cell proliferation and allows the natural apoptosis of HPV-infected cells to resume. Precision microwave delivery presents a potential new treatment for treating HPV-positive anogenital precancerous lesions and cancers. FUNDING: Funding was through an Innovate UK Biomedical Catalyst grant (ID# 92138-556187), a Chief Scientist Office grant (TCS/19/11) and core support from Medical Research Council (MC_ UU_12014) core funding for the MRC-University of Glasgow Centre for Virus Research.

Does Facet Distraction Affect Patient Outcomes After ACDF?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study is to determine if there is a correlation between the amount of facet distraction and postoperative patient-reported outcomes after ACDF. METHODS: A retrospective cohort analysis of patients undergoing 1 to 3 level ACDF for degenerative pathologies at a single academic center was performed. Each patient received upright, lateral cervical spine x-rays at the immediate postoperative time point from which interfacet distance (facet distraction) was measured. Patient-reported outcome measures including NDI, PCS-12, MCS-12, VAS Neck, and VAS Arm pain scores were obtained preoperatively and at short-term (<3 months) and long-term (>1 year) follow-up. Receiver operating curves were generated to evaluate the possibility of a critical interfacet distraction distance. Univariate and multivariate analysis were performed to compare outcomes between groups based on the degree of facet distraction. RESULTS: A total of 229 patients met the inclusion criteria. Receiver operating curves failed to yield a critical interfacet distraction distance associated with worse post-operative outcomes. Patients were instead grouped based on facet distraction distance below and above the third quartile (0.8mm-2.0 mm, 2.0mm-3.7 mm), with 173 and 56 patients in each respective group. Univariate analysis did not detect any statistically significant differences in outcome measures, recovery ratio, or % MCID achievement at short- and long-term follow-up between groups. Multivariate analysis also failed to demonstrate any significant differences between the facet distraction groups. CONCLUSION: Increased interfacet distance did not correlate with increased neck pain or disability after an ACDF.

HPV-related cervical diseases: Alteration of vaginal microbiotas and promising potential for diagnosis.

Vaginal microbiota is closely associated with women's health, however, the correlation between HPV-related cervical disease (HRCD) and vaginal microbiota is still obscure. In this study, patients with HRCD (n = 98) and healthy controls (n = 58) in Hangzhou were recruited, and their vaginal microbiota were collected and analyzed. The composition of the vaginal microbial community was explored, and a disease classification model was developed by random forest algorithm. The results suggested that the diversity of vaginal microbiota was significantly higher in HRCDs than that in healthy controls (p < 0.05). Firmicutes is the dominant phylum in vaginal microbiota, and Lactobacillus was identified as the most altered genus between two groups (p < 0.01). Kyoto Encyclopedia of Genes and Genomes analysis suggested the difference in vaginal microbial community functions between two groups. Furthermore, we identified 10 biomarkers as the optimal marker sets for the random forest model and found a higher probability of disease values in HRCD group in discovery cohort (p < 0.0001), with an area under the receiver operating characteristic curve reaching 89.7% (95% confidence interval: 78.3%-100%). We further validated the model in both validation and independent diagnosis cohorts, confirming its accuracy in the prediction of HRCD. In conclusion, this study revealed the community composition of vaginal microbiota in HRCDs and successfully constructed a diagnostic model for HRCD.

The psychological burden of disease among patients undergoing cervical spine surgery: Are we underestimating our patients' inherent disability?

BACKGROUND: Studies have utilized psychological questionnaires to identify the psychological distress among certain surgical populations. RESEARCH QUESTION: Is there an additional psychological burden among patients undergoing surgical treatment for their symptomatic degenerative cervical disease? MATERIALS AND METHODS: Patients>18 years of age with symptomatic, degenerative cervical spine disease were included and prospectively enrolled. Correlations and multivariable logistic regression analysis assessed the relationship between these mental health components (PCS, FABQ) and the severity of disability described by the NDI, EQ-5D, and mJOA score. Patient distress scores were compared to previously published benchmarks for other diagnoses. RESULTS: 47 patients were enrolled (age: 56.0 years,BMI: 29.7kg/m2). Increasing neck disability and decreasing EQ-5D were correlated with greater PCS and FABQ(all P<0.001). Patients with severe psychological distress at baseline were more likely to report severe neck disability, while physician-reported mJOA had weaker associations. Compared to historical controls of lumbar patients, patients in our study had greater levels of psychological distress, as measured by FABQ (40.0 vs. 17.6; P<0.001) and PCS (27.4 vs. 19.3;P<0.001). DISCUSSION AND CONCLUSION: Degenerative cervical spine patients seeking surgery were found to have a significant level of psychological distress, with a large portion reporting severe fear avoidance beliefs and catastrophizing pain at baseline. Strong correlation was seen between patient-reported functional metrics, but less so with physician-reported signs and symptoms. Additionally, this population demonstrated higher psychological burden in certain respects than previously identified benchmarks of patients with other disorders. Preoperative treatment to help mitigate this distress, impact postoperative outcomes, and should be further investigated. LEVEL OF EVIDENCE: Level III.

Current and future direction in treatment of HPV-related cervical disease.

Human papillomavirus (HPV) is the most common sexually transmitted virus in the world. About 70% of cervical cancers are caused by the most oncogenic HPV genotypes of 16 and 18. Since available prophylactic vaccines do not induce immunity in those with established HPV infections, the development of therapeutic HPV vaccines using E6 and E7 oncogenes, or both as the target antigens remains essential. Also, knocking out the E6 and E7 oncogenes in host genome by genome-editing CRISPR/Cas system can result in tumor growth suppression. These methods have shown promising results in both preclinical and clinical trials and can be used for controlling the progression of HPV-related cervical diseases. This comprehensive review will detail the current treatment of HPV-related cervical precancerous and cancerous diseases. We also reviewed the future direction of treatment including different kinds of therapeutic methods and vaccines, genome-editing CRISPR/Cas system being studied in clinical trials. Although the progress in the development of therapeutic HPV vaccine has been slow, encouraging results from recent trials showed vaccine-induced regression in high-grade CIN lesions. CRISPR/Cas genome-editing system is also a promising strategy for HPV cancer therapy. However, its safety and specificity need to be optimized before it is used in clinical setting.

PCNA in Cervical Intraepithelial Neoplasia and Cervical Cancer: An Interaction Network Analysis of Differentially Expressed Genes.

The investigation of differentially expressed genes (DEGs) and their interactome could provide valuable insights for the development of markers to optimize cervical intraepithelial neoplasia (CIN) screening and treatment. This study investigated patients with cervical disease to identify gene markers whose dysregulated expression and protein interaction interface were linked with CIN and cervical cancer (CC). Literature search of microarray datasets containing cervical epithelial samples was conducted in Gene Expression Omnibus and Pubmed/Medline from inception until March 2021. Retrieved DEGs were used to construct two protein-protein interaction (PPI) networks. Module DEGs that overlapped between CIN and CC samples, were ranked based on 11 topological algorithms. The highest-ranked hub gene was retrieved and its correlation with prognosis, tissue expression and tumor purity in patients with CC, was evaluated. Screening of the literature yielded 9 microarray datasets (GSE7803, GSE27678, GSE63514, GSE6791, GSE9750, GSE29570, GSE39001, GSE63678, GSE67522). Two PPI networks from CIN and CC samples were constructed and consisted of 1704 and 3748 DEGs along 21393 and 79828 interactions, respectively. Two gene clusters were retrieved in the CIN network and three in the CC network. Multi-algorithmic topological analysis revealed PCNA as the highest ranked hub gene between the two networks, both in terms of expression and interactions. Further analysis revealed that while PCNA was overexpressed in CC tissues, it was correlated with favorable prognosis (log-rank P=0.022, HR=0.58) and tumor purity (P=9.86 × 10-4, partial rho=0.197) in CC patients. This study identified that cervical PCNA exhibited multi-algorithmic topological significance among DEGs from CIN and CC samples. Overall, PCNA may serve as a potential gene marker of CIN progression. Experimental validation is necessary to examine its value in patients with cervical disease.

Does Paramedian Approach Preferentially Secure Optimal Drug Delivery Onto Ventral Epidural Space and Subsequent Superior Clinical Efficacy Over a Dorsal Midline Approach During Cervical Interlaminar Epidural Injection?

BACKGROUND: There is paucity in the literature directly comparing the clinical results between the paramedian and the midline interlaminar cervical epidural injections. OBJECTIVE: To compare the proportion of ventral epidural spread of injectate and consequent clinical outcome between the paramedian and midline approach during interlaminar epidural injection in patients with axial neck and/or interscapular pain triggered from the underlying cervical spine pathologic condition. STUDY DESIGN: Retrospective study. SETTING: Primary pain clinic and spine hospital. METHODS: Two hundred and twenty-three patients with axial neck and/or interscapular pain due to cervical problem underwent interlaminar epidural injection through either a paramedian approach (PM group, n = 93) or a midline approach (ML group, n = 130). We compared the portion of ventral epidural filling, Numeric Rating Scale (NRS), and McNab criteria between both groups. The NRS and McNab criteria were also separately compared between the ventrally spread (VS) group and non-ventral spread (non-VS) group inside each PM and ML group, respectively, at 2 weeks and 10 weeks post-injection. RESULTS: The PM group showed a significantly higher proportion of ventral spread, successful NRS reduction, and satisfactory McNab criteria than the ML group at 10 weeks. In the PM group, the VS group showed the same results as above compared to the non-VS group. LIMITATIONS: A retrospective analysis based on the relatively short-term follow-up period clinical results. CONCLUSIONS: The paramedian approach showed the better direct injectate transfer over the ventral epidural space and subsequently superior clinical efficacy for the patients suffering from axial neck and/or interscapular pain secondary to cervical spine problems.

Locking stand-alone cage versus anterior plate construct in anterior cervical discectomy and fusion: a systematic review and meta-analysis based on randomized controlled trials.

PURPOSE: To evaluate the efficacy of locking stand-alone cage (LSC) compared with anterior plate construct (APC) in anterior cervical discectomy and fusion (ACDF). METHODS: A comprehensive literature search was carried out in PubMed, Embase, Web of Science, and Cochrane Library to screen randomized controlled trials (RCTs) that directly compared LSC with APC in ACDF. The Cochrane Collaboration's tool was used for assessment of study quality. Data were analyzed with the Review Manager 5.3 software. RESULTS: A total of seven RCTs were included. The results revealed no significant differences between LSC and APC in ACDF regarding the fusion rate, Japanese Orthopaedic Association score, visual analogue scale score, neck disability index score, hospital stay, subsidence rate, cervical lordosis, segmental Cobb angle, and disc height. However, LSC was associated with a significantly shorter operation time, less blood loss, lower overall incidence of dysphagia, and lower adjacent-level ossification (ALO) rate compared with APC. CONCLUSION: In summary, LSC is not only a safe and effective device for ACDF but also has the advantages of significantly reduced operation time, blood loss, overall incidence of dysphagia, and ALO rate over APC. Therefore, LSC is a better alternative than APC for the patients undergoing ACDF procedures.

Assessing the epidemiological impact on cervical cancer of switching from 4-valent to 9-valent HPV vaccine within a gender-neutral vaccination programme in Switzerland.

BACKGROUND: An infection with high-risk human papillomavirus (HPV) is the obligatory aetiological factor for the development of cervical cancer. In Switzerland, the prevention strategy for cervical cancer is based on primary prevention via HPV vaccination and secondary prevention with an opportunistic screening programme for precancerous lesions. Vaccination is recommended to 11-26 years old male and female persons. The objective of the study was to assess the epidemiological impact on cervical cancer of switching from the currently implemented programme with the 4-valent vaccine to the 9-valent vaccine, in an 11-26 years old gender-neutral vaccination programme in Switzerland. METHODS: A previously validated dynamic transmission model of HPV infections was adapted and calibrated to the Swiss setting assuming an 80% coverage rate in HPV-vaccination and lifelong vaccine type-specific protection. A gender-neutral vaccination programme (males and females) for 11-26 years old with a 9-valent HPV vaccine was compared with the current 11-26 years old gender-neutral 4-valent vaccination programme. Sensitivity analyses were conducted in order to test the impact of lower vaccination coverage rates and a shorter duration of protection on the model outcomes. RESULTS: In Switzerland, a 9-valent gender-neutral vaccination programme would result in an additional prevention of 2979 cervical cancer cases, 13,862 CIN3 and 15,000 CIN2 cases, compared with the 4-valent gender-neutral vaccination programme over 100 years. These additional disease cases avoided would correspond to a 24, 36 and 48% cumulative incidence decrease in cervical cancer, CIN3 and CIN2 cases, respectively. It would also prevent additional 741 cervical cancer-related deaths over 100 years. A substantial additional reduction in cervical cancer and precancerous lesions burden is still observed when varying the vaccination coverage rate from 30 to 60% or reducing the duration of protection from lifelong to 20 years. CONCLUSIONS: The switch to the 9-valent vaccine in Switzerland to prevent cervical diseases showed an important contribution in terms of public health impact compared with the 4-valent vaccine in an 11-26 years old gender-neutral population, even with very conservative assumptions such as low coverage rates or low duration of protection and limiting analysis to only cervical disease.

Effects of malaria/helminthic coinfections on cervical cancer progression among sub Saharan African women on highly active antiretroviral therapy: A scoping review.

In Africa, the HIV prevalence in rural areas has begun to reach levels estimated within urban settings, where women are also more at risk for both malaria and intestinal parasitic infections. The objective of this review is to assess whether concomitant infections with malaria and/or helminthic diseases have an impact on cervical disease progression in women on HAART. This scoping review was conducted in August 2018. To conduct this scoping review, we searched the relevant studies in electronic databases such as PUBMED, Global Health, EMBASE, CINAHL and SCOPUS published in the year between 1960 and 2018 using the following search terms HAART AND malaria OR Helminth and Female OR women. Eight studies qualified for this review. The literature underscores the need for women on HAART with multiple co-infections to use adjuncts to retain immune recovery and undetectable HIV viral load, to reduce risk of cervical disease progression. A trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection was observed in one study. Given the public health impact of synergistic interactions between malaria and helminthic infections in HIV/HPV co-infected women on HAART, it is urgent that these interactions are elucidated.

Evidence-based use of arthroplasty in cervical degenerative disc disease.

INTRODUCTION: Cervical disc arthroplasty (CDA) was developed to decrease the rate of symptomatic adjacent-level disease while preserving motion in the cervical spine. METHODS: The objectives of this paper are to provide criteria for proper patient selection as well as to present a comprehensive literature review of the current evidence for CDA, including randomized studies, the most recent meta-analysis findings, and long-term follow-up clinical trials as well. RESULTS: Currently, there are several prospective randomized controlled studies of level I of evidence attesting to the safety and efficacy of CDA in the management of cervical spondylotic disease (CSD) for one- or two-level degenerative diseases. These as well as recent meta-analyses suggest that CDA is potentially similar or even superior to anterior cervical discectomy and fusion (ACDF) when considering several outcomes, including dysphagia and re-operation rate over medium-term follow-up. Less robust studies have also reported satisfactory clinical and radiological outcomes of CDA for hybrid procedures (ACDF combined with CDA), non-contiguous disease, and even for multilevel disease (more than 2 levels). CONCLUSIONS: Based on this evidence we conclude that CDA is a safe and effective alternative to ACDF in properly selected patients for one- or two-level diseases. Defining superiority of specific implants and detailing optimal surgical indications will require further well-designed long-term studies.

Clinical Efficacy of Cages in Anterior Cervical Fusion for Degenerative Cervical Disease

STUDY DESIGN: Review of the literature.OBJECTIVES: To present up-to-date information on the use of cages in anterior cervical fusion for degenerative cervical disease.SUMMARY OF LITERATURE REVIEW: The use of cages in anterior cervical fusion for degenerative cervical disease remains controversial.MATERIALS AND METHODS: Review of the relevant literature.RESULTS: The use of cages in anterior cervical fusion of one and multiple disc levels was effective in terms of biomechanical stability and clinical outcomes without complications at the donor site compared with use of an autograft. However, the use of only a cage had many drawbacks, so the combined use of a cage and a cervical plate is recommended.CONCLUSIONS: The use of cages in anterior cervical fusion was effective in terms of clinical outcomes, and the combined use of a cage and a cervical plate is recommended.

Clinical performance of the Cobas 4800 HPV test and the Aptima HPV assay in the management of women referred to colposcopy with minor cytological abnormalities.

BACKGROUND: The aim of this study was to evaluate the clinical performance of the Cobas 4800 HPV test and the Aptima HPV assay for the detection of CIN2+ disease in women referred to colposcopy with minor cytological abnormalities. METHODS: ThinPrep liquid-based cytology samples were collected from 562 women referred to colposcopy with minor cytological abnormalities. HPV testing by both assays was performed on these samples. Clinical performances for detection of histologically diagnosed CIN2+ and CIN3+ were calculated. RESULTS: HPV prevalence by the Cobas 4800 HPV test was 58.2% and 53.0% women tested positive with the Aptima HPV assay in the entire study population. The Aptima HPV assay and the Cobas 4800 HPV test displayed equivalent sensitivity of 90.2% (95%CI, 83.4-94.9) for the detection of CIN2+ disease. However, the Aptima HPV assay displayed greater specificity of 61.0% (95% CI, 54.0-68.0) when compared to the Cobas 4800 HPV test 53.0% (95% CI, 46.0-60.0), and this was significantly higher (P = .0004). The Aptima HPV assay also displayed higher specificity 76.5% (95% CI, 66.0-85.0) in the ASCUS category in comparison to the Cobas 4800 HPV test 65.0% (95% 54.0-75.0) which was statistically significant (P = .004). CONCLUSIONS: Both the tests displayed similar sensitivity. However, the Aptima HPV assay was significantly more specific in the identification of women with CIN2+ disease in a colposcopy referral population.

HDR syndrome in a Colombian woman with a genital tract malformation: first case report in Latin America / Síndrome HDR en una mujer colombiana con una malformación genitourinaria: primer reporte de caso en Latinoamérica

ABSTRACT Objectives Hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, also known as Barakat syndrome, is an autosomal dominant transmission hereditary disease with a wide range of penetrance and expressivity. Haploinsufficiency of the GATA3 two finger zinc transcription factor is believed to be its cause. This is the first time this orphan disease is reported in Latin America, so the publishing of this report is expected to raise awareness on these types of syndrome, that are usually underdiagnosed in our region, which in turn causes an increase in the years lost to disability (YLDs) rates, as well as higher costs to be assumed by public health systems. Methods A 36-year-old Colombian woman diagnosed with parathyroid gland agenesis was referred from the Endocrinology Service to the Outpatient Service. According to her medical record, in the past she had developed hypocalcaemia, left renal agenesis, hypoparathyroidism, bicornate uterus and sensorineural hearing loss. Through a genetic analysis a pathological mutation on the short arm of the GATA 3 gen (c.404dupC, p Ala136 GlyfsTER 167) was confirmed, which led to a HDR syndrome diagnosis. Discussion This case proves that there is a possibility that mutations described in other continents may be developed by individuals from our region. Regardless of ethnicity, Barakat syndrome should be considered as a possible diagnosis in patients presenting the typical triad that has been described for this condition, since there could be underdiagnosis of this disease in Latin-America due to the lack of knowledge on this condition in said region, and that genetic counseling in these patients is of great importance for the implications of the syndrome in future generations.(AU)

RESUMEN Objetivos El síndrome de hipoparatiroidismo, sordera neurosensorial y displasia renal (HDR) también llamado síndrome de Barakat, es una enfermedad hereditaria de transmisión autosómica dominante con amplia penetrancia y expresividad genética. El síndrome es causado por la haploinsuficiencia del factor de transcripción de dedos de Zinc GATA3. Esta es la primera vez que esta enfermedad huérfana es reportada en latinoamerica, y buscamos generar consciencia de la presencia de estas enfermedades, las cuales usualmente son infradiagnósticadas en nuestro medio y llevan a un aumento de años perdidos por discapacidad y costos para el sistema de salud pública. Métodos Una mujer colombiana de 36 años ingresó a consulta externa de genética referida por el servicio de endocrinología por una agenesia de paratiroides. La paciente tenía antecedentes de hipocalcemia, agenesia renal izquierda, hipoparatiroidismo, sordera neurosensorial y útero bicorneo. Se realizó un análisis genético que confirmo una mutación patológica en el brazo corto del gen GATA3 (c.404dupC, p Ala136 GlyfsTER 167) diagnóstica del síndrome de Barakat. Discusión Este caso demuestra la posibilidad de existencia de mutaciones descritas en otros continentes en nuestra población. Sin importar la etnia, el síndrome de Barakat debe ser estudiado en pacientes que presenten la triada típica, ya que podría existir un infra diagnóstico de la enfermedad secundario al desconocimiento de la misma en Latinoamérica y teniendo en cuenta la importancia que tiene la consejería genética en estos pacientes por las implicaciones de la enfermedad en futuras generaciones.(AU)

Hybrid Method of Transvertebral Foraminotomy Combined with Anterior Cervical Decompression and Fusion for Multilevel Cervical Disease.

Transvertebral foraminotomy (TVF) combined with anterior cervical decompression and fusion (ACDF) can be used to treat multilevel cervical spondylotic myelopathy and radiculopathy; however, the radiological outcomes and effectiveness of this hybrid procedure are unknown. We retrospectively assessed 22 consecutive patients treated with combined TVF and ACDF between January 2007 and May 2016. The Japanese Orthopedic Association (JOA) score and Odom's criteria were analyzed. Radiological assessment included the C2-7 sagittal Cobb angle (CA) and range of motion (ROM). The tilting angle (TA), TA ROM, and disc height (DH) of segments adjacent to the ACDF were also measured. Adjacent segment degeneration, which includes disc degeneration, was evaluated. The mean postoperative follow-up was 41.7 months. All surgeries were performed at two adjacent segments, with ACDF and TVF of the upper and lower segments, respectively. The JOA scores significantly improved. There were no significant differences in the C2-7 CA, C2-7 ROM, TA, and TA ROM, but there was a statistically significant decrease in DH of the lower adjacent segment to ACDF. Progression of disc degeneration was identified in two patients, with no progression in the criterion of adjacent segment degeneration over the follow-up. The TVF combined with ACDF produced excellent clinical results and maintained spinal alignment, albeit with a reduction in DH. TVF was safely performed at the lower segment adjacent to the ACDF, although this might result in earlier degeneration. In conclusion, this hybrid method is less invasive and beneficial for reduction of the number of fused levels.

HPV Genotyping and Clinical Studies of Women in Yan'an Area / 现代检验医学杂志

Objective To contrast HPV genotyping and clinical characteristics of women in Yan'an and provide data support for cervical cancer screening and prevention.Methods The genotyping of HPV infection was carried out by the method of PCR amplification and reverse hybridization.To statistical analysis clinical infection distribution data.Results Found 16.48％ (332 of 2014) were positive for HPV DNA in these women.HPV-16,52 and 53 were in the top three HPV high-risk types.HPV-81,6 and 44 were in the top three HPV low-risk types.There were 219 cases (65.96％) with pure high-risk type infection,74 cases (22.29％) with pure low-risk type infection and 39 cases (11.75％) with mixed infection in positive specimens.The HPV infection rate had showed first increasing then decreasing with age,and there were significant differences among the each groups (x2=34.238,P＜0.01).There were also differences in HPV positive detection rates in different occupations and there were significant differences among the each groups (x2=50.35,P＜0.01).There were also differences in HPV positive detection rates in different regions,and there were significant differences among the each groups (x2 =12.084,P＜0.05).Single infection was highest in HPV infection.Conclusion HPV infection was different in different populations,regions and ages,and it is of great significance to carry out HPV screening for early prevention and treatment of cervical cancer.

RNA-Seq Analysis of Differentiated Keratinocytes Reveals a Massive Response to Late Events during Human Papillomavirus 16 Infection, Including Loss of Epithelial Barrier Function.

The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from undifferentiated and differentiated cell populations of normal, spontaneously immortalized keratinocytes (NIKS) and NIKS stably transfected with HPV16 episomal genomes (NIKS16) were compared using next-generation sequencing (RNA-Seq). HPV16 infection altered expression of 2,862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNA-Seq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected). Of the top 966 genes altered (>log2 = 1.8, 3.5-fold change), 670 genes were downregulated and 296 genes were upregulated. HPV downregulated many genes involved in epithelial barrier function, which involves structural resistance to the environment and immunity to infectious agents. For example, HPV infection repressed expression of the differentiated keratinocyte-specific pattern recognition receptor TLR7, the Langerhans cell chemoattractant CCL20, and proinflammatory cytokines interleukin 1α (IL-1α) and IL-1ß. However, the type I interferon regulator IRF1, kappa interferon (IFN-κ), and viral restriction factors (IFIT1, -2, -3, and -5, OASL, CD74, and RTP4) were upregulated. HPV infection abrogated gene expression associated with the physical epithelial barrier, including keratinocyte cytoskeleton, intercellular junctions, and cell adhesion. Quantitative PCR (qRT-PCR) and Western blotting confirmed changes in expression of seven of the most significantly altered mRNAs. Expression of three genes showed statistically significant changes during cervical disease progression in clinical samples. Taken together, the data indicate that HPV infection manipulates the differentiating keratinocyte transcriptome to create an environment conducive to productive viral replication and egress.IMPORTANCE HPV genome amplification and capsid formation take place in differentiated keratinocytes. The viral life cycle is intimately associated with host cell differentiation. Deep sequencing (RNA-Seq) of RNA from undifferentiated and differentiated uninfected and HPV16-positive keratinocytes showed that almost 3,000 genes were differentially expressed in keratinocytes due to HPV16 infection. Strikingly, the epithelial barrier function of differentiated keratinocytes, comprising keratinocyte immune function and cellular structure, was found to be disrupted. These data provide new insights into the virus-host interaction that is crucial for the production of infectious virus and reveal that HPV infection remodels keratinocytes for completion of the virus replication cycle.