Medicine-Both a Science (Care) and an Art (CARE).

This Viewpoint discusses the concept of CARE (compassion, assistance, respect, and empathy) as a way physicians can practice the art of medicine in the current era of care that increasingly incorporates predictive analytics and artificial intelligence.

Identifying Gaps in Pelvic Pain Education: A Scoping Review and Structured Analysis of Obstetrics and Gynecology Training Milestones.

OBJECTIVE: Several clinical practice guidelines on the evaluation and management (EM) of chronic pelvic pain (CPP) have been published; however, it is not known whether obstetrics and gynecology (OBGYN) educational milestones are aligned with current practice recommendations. Therefore, this scoping review and structured analysis aims to identify gaps between clinical guidelines for the EM of CPP and OBGYN training milestones published by educational authorities like the Accreditation Council for Graduate Medical Education (ACGME) and the AAGL. DATA SOURCES: The literature search was performed in MEDLINE, PubMed Central, and Bookshelf on the PubMed interface from January 2018 to September 2022. Peer-reviewed publications were included if they were a systematic review of recent practice guidelines and focused on female CPP. Publications that focused on a single pelvic pain condition or focused on a specific treatment were excluded. METHODS OF STUDY SELECTION: Two reviewers extracted the data and appraised the study quality following the Critical Appraisal Skills Programme Checklist for systematic reviews. Four articles met inclusion criteria for thematic analysis. A reflexive thematic analysis via the inductive approach was performed to develop clinical themes common to all review articles and presumed important in the EM of CPP. Pelvic pain experts and Delphi methodology was used to assess validity and relevance of each theme in OBGYN training. Validated themes were used in a strengths weaknesses opportunities threats (SWOT) analysis of the ACGME and the AAGL Milestones used for training OBGYN residents and fellows. A SWOT analysis is an organizational tool used to analyze processes in terms of strengths, weaknesses, opportunities for improvement, and threats to implementing a potential change. TABULATION, INTEGRATION, AND RESULTS: Twelve clinical themes were conceptualized and achieved ≥ 90% consensus as being important in the EM of CPP. Clinical themes pertained to pathophysiology, biopsychosocial approach, trauma-informed care, history and physical examination, diagnostic testing, multimodal/multidisciplinary management, pain education, and medical and surgical management. SWOT analysis showed that the ACGME Milestones lacked milestones specific to CPP, while the AAGL Milestones had 6 CPP-focused competencies with multiple milestones. Milestones on trauma-informed care and application of biopsychosocial assessment were notably absent. CONCLUSION: OBGYN educational milestones published by the ACGME and the AAGL are not yet aligned with current clinical guidelines for the EM of CPP.

Time to move beyond surgical classification systems for endometriosis.

Endometriosis is a common condition associated with chronic pelvic pain and infertility. Its pathogenesis is poorly understood, diagnosis relies on laparoscopy, and staging is based on extent of disease. Unfortunately, the current staging systems do not correlate well with pain severity and impact, nor do they predict prognosis, i.e., treatment success and recurrence of disease. In this article, we discuss the strengths and limitations of current staging systems and propose modifications that will enable better classification systems to be developed in the future.

Reproductive response of crossbred Bos taurus × Bos indicus cows to biostimulation by pre-pubertal and pubertal teasers.

Although the beneficial effect of biostimulation on reproduction has been reported, the influence of selectivity and social factors on the response to biostimulation has not received sufficient research attention in both Bos indicus and Bos indicus influenced cattle. Furthermore, 'green and cheap' strategies to improve cattle reproduction are currently in demand while Bos indicus influenced cattle with inferior reproductive performance, and farmers with economic limitations are common in tropical zones. Hence, to assess the reproductive response of crossbred taurus × indicus cows to biostimulation by pre-pubertal (PPM) or pubertal (PM) teasers males, two trials of 2 years each were conducted. Trial 1 n = 187 cows (Year 1:85 cows exposed to PPM and Year 2:102 cows exposed to PM). Trial 2 n = 196 cows (Year 1:101 cows exposed to PPM and Year 2:95 cows exposed to PM). The effect of exposing cows to PPM and PM on the intervals calving to first service (ICFS), calving to conception (ICC) and economic cost of days open (ECDO) was analysed using Kruskal-Wallis ANOVA and the effect of exposing cows to PPM and to PM on reproductive status at 90 days (RS90) and proportion of cows requiring hormonal protocols (PRH) was compared using χ2 analysis. Both ICFS and ICC were shorter (p < .0001) for PM-exposed females (96.12 ± 4.1 and 110.93 ± 2.9 days; respectively) compared with those PPM-exposed (134.41 ± 3.3 and 135.64 ± 2.4 days; respectively). With RS90, more (p < .0001) PM-exposed cows (50.7%) were pregnant compared with PPM-exposed cows (16.1%). The PRH was greater (p < .0001) in PPM-exposed cows (79.0%) compared with PM-exposed (27.9%). The ECDO was less (p < .0001) in PM-exposed cows (US$ 142.9 ± 3.8) compared with PPM-exposed (US$ 176.3 ± 2.9). In conclusion, cows exposed to PM had shorter ICFS and ICC compared with cows exposed to PPM. More cows exposed to PM were pregnant after 90 days, and PRH was less than cows exposed to PPM. Cows exposed to PM had a reduced ECDO than those exposed to PPM.

Expression patterns and clinical significance of estrogen receptor in non-small cell lung cancer.

BACKGROUND: Lung cancer death remains the highest among all malignancies. Gender differences show women have an increased cancer incidence while men have worse outcomes. These observations identified that some lung carcinomas express estrogen receptors (ER). This is a promising target as antiestrogen drugs can reduce tumors and improve survival. However, there is a limited understanding of ER distribution and its clinical significance to properly design antiestrogen drug clinical trials. Thus, we comprehensively analyzed ERα and ERß expression patterns by gender, cancer cell type, and receptor location in lung cancer. METHODS: We conducted a systematic review using the PubMed database from all-time through October 2022, using MeSH terms with the keywords "lung cancer," "estrogen receptor," and "immunohistochemistry." We identified 120 studies with 21 reports being evaluated based on our inclusion criteria. RESULTS: We examined 4874 lung cancers from 5011 patients. ERß is the predominant form of ER expressed, mainly found in the nucleus. The ERß positivity rate is 51.5% in males versus 55.5% in females and was not statistically different. In contrast, ERα is predominately extranuclear in location, and ERα expression varies by gender. Males had a positivity rate of 31% versus 26.6% in females, which is statistically different. ERα is associated with a worse prognosis in some studies, while it had no effect in others. Overall, ERß was associated with a better prognosis. CONCLUSION: We characterized ER expression patterns in 4874 lung cancers. Over 50% expressed ERß with equal rates in both sexes and was associated with a better prognosis. ERα expression was slightly higher in males (31%) than females (26.6%) and was associated with a poor prognosis. Our findings suggest estrogen signaling may be a promising drug target in lung cancer.

Efectividad de las vacunas contra SARS-CoV-2 en hospitalizados con fallas vacunales en 10 hospitales de la CCINSHAE / Effectiveness of SARS-CoV-2 vaccines in hospitalized patients with vaccine failures in 10 CCINSHAE hospitals

Resumen: Objetivo: Evaluar la efectividad de las vacunas contra SARS-CoV-2 para evitar muerte e intubación en pacientes hospitalizados con Covid-19. Material y métodos: Se presentó un análisis de 3 565 hospitalizaciones por SARS-CoV-2 de personas mayores de 20 años de edad, reportadas con fines de salud pública por 10 hospitales de especialidad. Se comparó a los egresados por mejoría (2 094) con los fallecidos (1 471) en modelos mixtos de regresión logística ajustados por edad, sexo, número de comorbilidades y el hospital como variable aleatoria. Resultados: Un esquema completo de vacunación, con cinco tipos de vacunas disponibles, tuvo un efecto protector para muerte o intubación (RM: 0.67, IC95%: 0.54,0.83, 33% de protección); y para muerte (RM: 0.80, IC95%: 0.64,0.99, 20% de protección) estos datos se compararon con los que no habían sido vacunados. Todas las vacunas aplicadas mostraron un efecto protector con un RM<0.8, con intervalos de confianza variables. Conclusiones: El antecedente de vacunación reduce los riesgos de ser intubado y morir, aun en pacientes previamente vacunados y hospitalizados con Covid-19 grave.

Abstract: Objective: To evaluate the effectiveness of SARS-CoV-2 vaccines to avoid death and intubation in hospitalized patients with Covid-19. Materials and methods: We present an analysis of 3 565 hospitalizations for SARS-CoV-2 in people over 20 years of age, reported for public health purposes by 10 specialty hospitals, comparing those discharged for improvement (2 094) with those who died (1 471) in mixed models of logistic regression adjusted for age, sex, number of comorbidities and the reporting hospital as a random variable. Results: A complete vaccination schedule, with five types of vaccine available, had a protective effect for death or intubation (OR: 0.67, CI95%: 0.54,0.83, 33% protection) and for death (OR: 0.80, CI95%: 0.64,0.99, 20% protection) compared to those who had not been vaccinated. All the applied vaccines in the Mexican program showed a protective effect with an OR<0.8, with variable confidence intervals. Conclusions: Even in patients previously vaccinated and hospitalized with severe Covid-19, a history of vaccination reduces the risks of being intubated and dying.

Are Unilateral Devices Valid for Power Output Determination in Cycling? Insights From the Favero Assioma Power Meter.

PURPOSE: Some power meters are available in both bilateral and unilateral versions. However, despite the popularity of the latter, their validity remains unknown. We aimed to analyze the validity of a unilateral pedal power meter for estimating actual ("bilateral") power output (PO). METHODS: Thirty-three male cyclists were assessed at different POs (steady cycling at 100-500 W, as well as all-out sprints), pedaling cadences (70, 85, and 100 repetitions·min-1), and cycling positions (seated and standing). The PO estimated by a left-only power meter (Favero Assioma Uno) was compared with the actual PO computed by a bilateral power meter (Favero Assioma Duo), and the level of bilateral asymmetry (most- vs least-powerful leg) with the latter system was also computed. RESULTS: Nonsignificant differences, high intraclass correlation coefficients (≥.90), and low coefficients of variation (consistently ≤5% except for low PO levels, ie, 5%-7% at 100 W) were found between Favero Assioma Uno and Favero Assioma Duo. However, although a strong intraclass correlation coefficient (.995) was found between both legs, asymmetry values of 4% to 6% were found for all conditions except when pedaling at the lowest PO (100 W), in which asymmetry increased up to 10% to 13%. CONCLUSIONS: Although cyclists tend to present some level of bilateral asymmetry during cycling (particularly at low PO), Favero Assioma Uno provides overall valid estimates of actual PO and is, therefore, an economical alternative to bilateral power meters. Caution is needed, however, when interpreting data at the individual level in cyclists with high levels of asymmetry.

Validity of the Favero Assioma Duo Power Pedal System for Measuring Power Output and Cadence.

Cycling power meters enable monitoring external loads and performance changes. We aimed to determine the concurrent validity of the novel Favero Assioma Duo (FAD) pedal power meter compared with the crank-based SRM system (considered as gold standard). Thirty-three well-trained male cyclists were assessed at different power output (PO) levels (100-500 W and all-out 15-s sprints), pedaling cadences (75-100 rpm) and cycling positions (seating and standing) to compare the FAD device vs. SRM. No significant differences were found between devices for cadence nor for PO during all-out efforts (p > 0.05), although significant but small differences were found for efforts at lower PO values (p < 0.05 for 100-500 W, mean bias 3-8 W). A strong agreement was observed between both devices for mean cadence (ICC > 0.87) and PO values (ICC > 0.81) recorded in essentially all conditions and for peak cadence (ICC > 0.98) and peak PO (ICC > 0.99) during all-out efforts. The coefficient of variation for PO values was consistently lower than 3%. In conclusion, the FAD pedal-based power meter can be considered an overall valid system to record PO and cadence during cycling, although it might present a small bias compared with power meters placed on other locations such as SRM.

A novel cancer preventative botanical mixture, TriCurin, inhibits viral transcripts and the growth of W12 cervical cells harbouring extrachromosomal or integrated HPV16 DNA.

BACKGROUND: The phytochemical mixture TriCurin (curcumin, epigallocatechin gallate (EGCG) and resveratrol) eliminates human papillomavirus (HPV) (+) cancer cells in vitro and in vivo. In this study, we further evaluate TriCurin. METHODS: The activity of TriCurin and its individual compounds was assayed on W12 cells, derived from a cervical precancer containing episomal and integrated HPV16 DNA, using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, microscopy and reverse transcription-polymerase chain reaction (RT-PCR), and on HeLa cells by gene expression analysis. The stability and toxicity of TriCurin microemulsion were tested in an organotypic cervical tissue model. RESULTS: TriCurin and its individual compounds inhibit the growth of W12 cells, episomal, type 1 and 2 integrants; the relative order of activity is TriCurin, EGCG, curcumin, or resveratrol. RT-PCR shows that TriCurin activates p53 and suppresses HPV16 mRNAs E1, E2, E4, E6 and E7 at 24 h in W12 cells. Gene expression analysis shows that TriCurin activates pro-apoptotic genes and represses anti-apoptotic genes in HeLa cells. TriCurin in a microemulsion is stable and non-toxic to cervical tissue. The combination of TriCurin and tanshinone IIA exhibits additional synergy against HeLa cells. CONCLUSIONS: TriCurin, and the combination of TriCurin with tanshinone IIA, are effective against HPV (+) cells. The phytochemical mixture, in the microemulsion-based cream, is a promising therapeutic for the prevention and treatment of cervical cancer.

Age-associated trends of vulvar cancer in the US.

OBJECTIVE: Medical societies have over the years moved away from recommending routine pelvic examinations in older, asymptomatic women above age 65. Consequently, vulvar examination is a largely neglected component of the physical examination, unless sent to a specialist for gynecological evaluation. In recognition of these recommendations, we analyzed US trends in vulvar cancer incidence, age, and stage at diagnosis, survival, and association with human papillomavirus (HPV). METHODS: Cases of vulvar and cervical cancer from 1992 to 2014 were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results and Centers for Disease Control's data on age at diagnosis, stage of disease, and HPV-association were analyzed and compared. Incidence and mortality rates were extracted and calculated. RESULTS: From 1992-2014, there was a 14.3% increase in vulvar cancer rates. The absolute average incidence rate was 2.25, with HPV still being seen in vulvar carcinomas in women 65 years and above. Cervical cancer mortality rates declined by 34.2%, while vulvar cancer death rates were unchanged. We show increased intervals for cervical cancer screening is associated with later stage vulvar cancer detection. The proportion of vulvar cancer cases diagnosed in women age <50 steadily decreased, from 42.05% of cases in 1992-1996 to 19.75% of total cases in 2012-2015. Meanwhile, vulvar cancer cases diagnosed in women > 65 yo increased from 36.62% of cases in 1992-1996 to 49.82% of cases in 2012-2015. CONCLUSION: The incidence of vulvar cancer increases with age, with the median age of diagnosis 67 years, with HPV (+) tumors occurring into 70's and 80's. Though medical societies do not routinely recommend an external genital examination in women 65 years and above, we show this is a missed opportunity to improve cancer outcomes in some older females.

Video Summary:http://links.lww.com/MENO/A678.

Prevalence of occult microscopic endometriosis in clinically negative peritoneum during laparoscopy for chronic pelvic pain.

OBJECTIVE:  To determine the prevalence of occult microscopic endometriosis in patients with chronic pelvic pain and negative laparoscopy. METHODS: A retrospective cross-sectional study included women who underwent laparoscopic evaluation for chronic pelvic pain by three fellowship-trained gynecologic surgeons at a community hospital from January 2011 to December 2016. The aim was to evaluate the prevalence of microscopic endometriosis in this population. RESULTS:  In 142 patients with clinically negative peritoneum on laparoscopy, 39% had occult microscopic endometriosis. Cramping pain score during menses was found to be lower in the positive biopsy group (6.9 vs 8.0, P=0.046). No differences were appreciated in age of menarche, pain during various parts of the menstrual cycle, or duration of symptoms. The biopsy-positive group had a younger age at time of evaluation, although not statistically significant (P=0.179). Current use of hormones affected neither biopsy results nor menstrual or pain characteristics. Detection was similar between robotic and laparoscopic cases and operative morbidity was minimal. CONCLUSION: Occult microscopic endometriosis may be present in approximately 39% of patients with clinically negative appearing peritoneum undergoing laparoscopy for chronic pelvic pain. Given this, biopsies should be performed in patients undergoing laparoscopy who do not have visible lesions.

Evaluating the discordant relationship between Tarlov cysts and symptoms of pudendal neuralgia.

BACKGROUND: Pudendal neuralgia is a painful neuropathic condition involving the pudendal nerve dermatome. Tarlov cysts have been reported in the literature as another potential cause of chronic lumbosacral and pelvic pain. Notably, they are often located in the distribution of the pudendal nerve origin at the S2, S3, and S4 sacral nerve roots and it has been postulated that they may cause similar symptoms to pudendal neuralgia. Literature has been inconsistent on the clinical relevance of the cysts and if they are responsible for symptoms. OBJECTIVE: To evaluate the prevalence of S2-S4 Tarlov cysts at the pudendal nerve origin (S2-S4 sacral nerve roots) in patients specifically diagnosed with pudendal neuralgia, and establish association of patient symptoms with location of Tarlov cyst. STUDY DESIGN: A retrospective study was performed on 242 patients with pudendal neuralgia referred for pelvic magnetic resonance imaging from January 2010 to November 2012. Dedicated magnetic resonance imaging review evaluated for presence, level, site, and size of Tarlov cysts. Among those with demonstrable cysts, subsequent imaging data were collected and correlated with the patients' clinical site of symptoms. Statistical analysis was performed using χ2, Pearson χ2, and Fisher exact tests to assess significance. RESULTS: Thirty-nine (16.1%) patients demonstrated at least 1 sacral Tarlov cyst; and of the 38 patients with complete pain records, 31 (81.6%) had a mismatch in findings. A total of 50 Tarlov cysts were identified in the entire patient cohort. The majority of the Tarlov cysts were found at the S2-S3 level (32/50; 64%). Seventeen patients (44.7%) revealed unilateral discordant findings: unilateral symptoms on the opposite side as the Tarlov cyst. In addition, 14 (36.8%) patients were detected with bilateral discordant findings: 11 (28.9%) had bilateral symptoms with a unilateral Tarlov cyst, and 3 (7.9%) had unilateral symptoms with bilateral cysts. Concordant findings were only demonstrated in 7 patients (18.4%). No significant association was found between cyst size and pain laterality (P = .161), cyst volume and pain location (P = .546), or cyst size and unilateral vs bilateral pain (P = .997). CONCLUSION: The increased prevalence of Tarlov cysts is likely not the etiology of pudendal neuralgia, yet both could be due to similar pathogenesis from part of a focal or generalized condition.

Successful Treatment of Penile Numbness and Erectile Dysfunction Resulting From Pudendal Nerve Entrapment.

Pudendal nerve decompression surgery has not been studied or reported for the treatment of penile numbness in the absence of pain. Herein, we report a case of a male patient with chronic numbness of the penis and erectile dysfunction in the absence of pelvic pain who was found to have pudendal nerve entrapment. This patient was treated with surgical decompression of the pudendal nerves that resulted in the return of genital sensation and erections. Thus, we propose that pudendal nerve entrapment may be considered as a cause of penile numbness and that pudendal nerve decompression surgery in these patients may be effective.

Fluorescence microscopy of H&E stained cervical biopsies to assist the diagnosis and grading of CIN.

BACKGROUND: Prevention of cervical cancer is based upon the accurate diagnosis and grading of cervical lesions identified during screening. The pathological classification of cervical intraepithelial neoplasia (CIN) is problematic, as it relies on subjective criteria and is known to have high interobserver variability and low reproducibility. These limitations can result in either over or under treatment of patients. Biomarkers to improve CIN diagnosis have not overcome all these challenges. MAIN BODY: Here we review the use of a promising optical imaging method using eosin-based fluorescence spectroscopy. This technique is able to perform fluorescent analysis of cervical biopsies directly from hematoxylin and eosin (H&E) stained tissues. Eosin is a brominated derivative of fluorescein. Fluorescence characteristics of protein-eosin complexes can demonstrate tissue changes associated with dysplasia and cancer. In this article we review the progress made towards developing eosin-based fluorescence spectroscopy. We describe the various morphologies seen among the CIN grades with this optical method and highlight the progress made to quantitate the spectral image characteristics. CONCLUSION: Eosin-based fluorescence spectroscopy can be used to directly examine H&E stained tissue slides. Relevant areas can be imaged and spectral analysis done to obtain objective data to identify and grade cervical lesions.

Unique synergistic formulation of curcumin, epicatechin gallate and resveratrol, tricurin, suppresses HPV E6, eliminates HPV+ cancer cells, and inhibits tumor progression.

Curcumin (from curry) (C) is highly potent against cervical cancer cells (CCC), but poor bioavailability has limited its clinical use. Similar natural polyphenols resveratrol (from grapes) (R), and epicatechin gallate (from green tea) (E) also display activity against CCC. By treating CCC (HeLa) with C, E, or R, or combinations of these compounds, we computed combination indices and observed a strong synergism among C, E, and R at the unique molar ratio 4:1:12.5. This combination, named as TriCurin, rapidly down regulated HPV18 E6 and NF-kB expression while concomitantly inducing the tumor suppressor protein p53 in HeLa cells. In the mouse c-Ha-ras and HPV16 E6, E7-expressing TC-1 CCC, both C and TriCurin elicited suppression of E6, induction of both p53 and acetyl-p53 (activated p53), and activation of caspase-3, but the TriCurin-evoked changes were several-fold greater than that produced by curcumin (4.7-fold for E6 inhibition, and 2-fold, 6-fold, and 1.7-fold for the induction of p53, acetyl-p53, and active caspase-3, respectively). Consequently, TriCurin was more potent in killing TC-1 and HeLa cells. Intralesional TriCurin treatment of tumors generated in mice by subcutaneously implanting the TC-1 CCC caused an 80-90% decrease in tumor growth. The ability of C to eliminate HeLa cells was significantly stabilized when delivered as TriCurin than when delivered alone. Topical application of TriCurin dispersed in a cream base afforded efficient transfer of C across the skin. Subcutaneous TriCurin injection yielded no adverse effect in tumor-naïve healthy mice. Thus, TriCurin is a safe and promising therapeutic agent against HPV-associated disease.

TriCurin, a novel formulation of curcumin, epicatechin gallate, and resveratrol, inhibits the tumorigenicity of human papillomavirus-positive head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and epicatechin gallate from green tea. Cell viability, clonogenic survival, and tumorsphere formation were inhibited and significant apoptosis was induced by TriCurin in UMSCC47 and UPCI:SCC090 HPV-positive HNSCC cells. Moreover, TriCurin decreased HPV16E6 and HPV16E7 and increased p53 levels. In a pre-clinical animal model of HPV-positive HNSCC, intra-tumoral injection of TriCurin significantly inhibited tumor growth by 85.5% compared to vehicle group (P < 0.05, n = 7). Our results demonstrate that TriCurin is a potent anti-tumor agent for HPV-positive HNSCC. Further development of TriCurin as a novel anti-cancer therapeutic to manage the HPV-positive HNSCC population is warranted.

When and how to excise vaginal mesh.

PURPOSE OF REVIEW: Since 2011, there has been increasing attention paid to the use of synthetic grafts (mesh) in pelvic reconstructive surgery. Although synthetic grafts are considered permanent implants to improve outcomes, the use of this material has created inadvertent complications such as erosion, chronic pain, and dyspareunia. Patient evaluation is complex and surgical techniques carry risks not yet completely understood. This review summarizes current opinions in synthetic graft excision for the treatment of mesh-related complications. RECENT FINDINGS: Recent studies reveal excisions are being increasingly performed and graft placement is decreasing. Patients of lower-volume surgeons have a higher risk of complication and need for excisional procedures. Pain is becoming the most common indication for vaginal mesh excision and that pain is mostly elicited with palpation of the mesh arms. Explantation is technically challenging and carries significant risks. SUMMARY: Vaginal synthetic graft complications are increasingly being managed by surgical excision. Careful evaluation of patient symptoms and objective findings should help guide management. Surgeons considering operative management should counsel patients regarding the risks of excision including but not limited to hemorrhage, nerve damage, muscular injury, and recurrent symptoms.

Novel p53 therapies for head and neck cancer.

Inactivation of the tumor suppressor p53 is the predominant pathogenetic event in head and neck squamous cell carcinoma (HNSCC). The p53 pathway in HNSCC can be compromised through multiple mechanisms including gene mutations, hyperactivation of endogenous negative p53 regulators and by the human papillomavirus E6 protein. Inactivation of p53 is associated with poor clinical response and outcome; therefore, restoration of the p53 signaling cascade may be an effective approach to ablate HNSCC cells. Viral approaches to restore p53 activity in HNSCC have been well-studied and shown modest activity in clinical trials. Recent work has focused on high-throughput screens and rational designs to identify and develop small molecules to rescue p53 function. Several p53-targeting small molecules have demonstrated very promising activity in pre-clinical studies but have yet progressed to the clinical setting. Further development of p53 therapies, in particular chemical approaches, should be prioritized and evaluated in the HNSCC setting.

Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and eosin fluorescence.

BACKGROUND: Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. METHODS: Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450-490 nm with emission captured at 515-565 nm. The 32-bit grayscale fluorescence images were used for image analysis. RESULTS: We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. CONCLUSION: Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis.