Cervical Sites Research Articles

O-254 Oral dydrogesterone (OD) versus micronized vaginal progesterone (MVP) for luteal phase support (LPS): impact on endometrium and genital tract microbiota

Abstract Study question Is there a difference in the endometrial transcriptome and/or reproductive tract microbiota composition when OD versus MVP is used as LPS for fresh embryo transfer? Summary answer Endometrial transcriptome signatures and microbiota composition at the vaginal, cervical or intra-uterine site presented no significant differences following OD versus MVP. What is known already Adequate LPS is crucial to achieve a successful pregnancy following ovarian stimulation (OS) and fresh embryo transfer. OD has been proven to be non-inferior compared to MVP in two phase III clinical RCTs. Additionally, a combined individual participant data and aggregate data meta-analysis showed an odds ratio in favor of OD for live birth. Little information is available on the potential differences at the molecular level of the reproductive organs following the administration of either LPS strategies. Given the potential immunomodulating properties of OD, of main interest is the endometrial functionality and microbiota composition of the female genital tract. Study design, size, duration Thirty oocyte donors were planned to have two OS-cycles followed by one week of LPS (OD or MVP) in a randomized, cross-over, double-blind, double-dummy fashion. An endometrial biopsy, as well as vaginal/cervical/intra-uterine samples were collected. Endometrial RNA-sequencing was performed, raw reads were processed using STAR/htseq-count, differential gene expression was evaluated with EdgeR. Microbiota profiles were obtained by 16S-rRNA-sequencing using the DADA2-pipeline with RDP-classifier. Comparative analysis of genera relative abundances was performed in R. Participants/materials, setting, methods All oocyte donors were <35 years old, had regular menstrual cycles, no intra-uterine contraceptive device, AMH within normal range and BMI≤ 29 kg/m2. OS was performed in a GnRH antagonist protocol followed by dual triggering (1000U hCG + 0.2mg triptorelin) as soon as ≥ 3 follicles of 20mm were present. Following oocyte retrieval, subjects initiated LPS consisting of MVP 200 mg (Utrogestan®) or OD 10 mg (Duphaston®), both three times daily. Main results and the role of chance Subject and stimulation characteristics were comparable between the groups. For endometrial RNA-sequencing, 21 pairs (n = 42 biopsies) were available with the same oocyte donor having a biopsy after OD as well as after MVP (the remaining 9 subjects were excluded due to late follicular progesterone elevation/drop-out after one cycle). After correction for multiple hypothesis testing, no differentially expressed genes could be withheld and the principal component analysis plot showed one mixed OD/MVP cluster (PCA1 25% variance, PCA2 16% variance). The average Euclidean distance between samples of the OD group was significantly lower than for the MVP group (respectively 12.1 vs 18.8, comparison of the two-group wise Euclidean distributions results in p = 6.98e-14 using the Mann-Whitney test). Microbiota profiling was performed before and after OD/MVP (4 collections per subject). Samples with insufficient high-quality reads were excluded, resulting in 42 intra-uterine samplings, 82 cervical and 84 vaginal swabs used for analysis. No difference was seen at any site of the female reproductive tract following OD versus MVP in microbiota diversity, richness, genera abundances (delta contrasts [Mann–Whitney U test], padj > 0.1), nor community composition (dbRDA genus-level Euclidean distances in vagina [R2= 0.22%, padj=0.26], cervix [R2= 0.36%, padj=0.20], uterus [R2= -0.06%, padj=0.45]). Limitations, reasons for caution Sample size was limited. Whole tissue endometrial transcriptomics was performed on individual biopsies without accounting for the potential bias of different tissue compartment compositions among biopsies. As it was a double blind, double dummy study design, the impact of not administering medication via the vaginal route could not be evaluated. Wider implications of the findings This is the first molecular study comparing OD/MVP. Results show that there is no difference between OD/MVP’s ability to give rise to the receptive state, which corresponds with the clinical trial data. As the inter-sample distance of RNA-profiles was smaller following OD, interindividual variations could be lower for this approach. Trial registration number EUDRACT 2018-000105-23

Abstract 3253: Probing the effects of retinoblastoma binding protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells

Abstract RBBP6 is considered a potential cancer biomarker due to its association with cell proliferation and the fact that it is overexpressed at cervical cancer sites where there is marked apoptosis and elevated p53. More information is emerging regarding the role of RBBP6 in cancer treatment, specifically its potential to sensitize cancer cells to radiation and certain chemotherapeutic agents via BCL-2 gene regulation. Cisplatin is an FDA-approved chemotherapeutic agent that still presents with acquired resistance in certain cervical cancer cases through p53 repression and BCL-2 upregulation, which is why there is ongoing research in trying to understand the molecular mechanisms involved in the response of cervical cancer cells to this drug. The present study therefore aims to investigate the possible relationship between cisplatin and RBBP6 expression in cervical cancer cells. RBBP6 was silenced in Hela, CaSki and Vero cells using the RNAi technology, followed by measurement of wild-type p53 and BCL-2 at mRNA level using qPCR. Cells co-treated with cisplatin and siRBBP6 were therefore analyzed for apoptosis induction and real time growth monitoring using flow cytometry and the xCELLigence system, respectively. Cancer cells in the co-treatment group showed a reduction in apoptosis compared to cisplatin-only group and real time growth monitoring revealed a reduced growth rate in RBBP6-knockdown cells treated with cisplatin. Although wild-type p53 remained unchanged in the co-treatment group of cancer cells, BCL-2 was completely repressed, suggesting that RBBP6 is necessary for the responsiveness of cervical cancer cells to via BCL-2 downregulation. Findings from this study suggest that RBBP6 expression promotes sensitivity of HeLa cells to cisplatin through BCL-2 downregulation. Knockdown of RBBP6 limits apoptosis induction and delays cell growth inhibition in response to cisplatin. The knowledge obtained here has the potential to help improve cisplatin efficacy through personalized administration based on the expression profile of RBBP6 among individual patients. Citation Format: Pontsho Moela, Harshini Mehta, Melvin Ambele. Probing the effects of retinoblastoma binding protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3253.

Lymph Node Tuberculosis in Otolaryngological Practice: A Study of 68 Cases at the Sourô Sanou University Hospital of Bobo Dioulasso, Burkina Faso

Introduction: Lymph node tuberculosis (LNTB) frequently affects peripheral cervical lymph node body sites. We aimed to study epidemiology and diagnostic and therapeutic characteristics of LNTB patients in ENT routine practice. Methods: We conducted a cross-sectional prospective study in the ENT and cervicofacial surgery department at the Sourô Sanou University Hospital of Bobo Dioulasso, Burkina Faso, for a period of 36 months. Results: There were 68 cases with LNTB, of which 54.4% were mostly men. The mean age and the median age were calculated at 37 ± 6.8 and 42 years, respectively. The patient’s age ranged between 3 and 81 years, and the most represented age group was from 30 to 60 years (62%). According to geographical origin, most patients (79%) originated from rural areas. In 6 cases (9%), patients reported diabetes and 12 patients were HIV positives (18%). Most clinical features leading to the ENT consultation were cervical lymph nodes (82%) and cervical scrofuloderma (18%). For the multiple locations, the lymphadenopathies involved mostly the transversal cervical chain (56%) and spinal chain (50%). Histopathology examination was the mostly diagnosed methods used in 68%. A 6-month anti-tuberculous treatment was given with a follow-up of 6 months without any relapse in 62 cases (97%). Conclusion: The frequency of 68 cases of LNTB in 3 years is underappreciated. Among all lymph node sites, transversal cervical chain and cervical spinal chain were mostly affected. Further advanced studies are recommended to determine the prevalence and contributing factors of LNTB in the study area.

Medicaid expansion and 2-year survival in women with gynecologic cancer: a difference-in-difference analysis

The Affordable Care Act implemented optional Medicaid expansion starting in 2014, but the association between Medicaid expansion and gynecologic cancer survival is unknown. To evaluate the impact of Medicaid expansion by comparing 2-year survival among gynecologic cancers before and after 2014 in states that did and did not expand Medicaid using a difference-in-difference analysis. We searched the National Cancer Database for women aged 40 to 64 years, diagnosed with a primary gynecologic malignancy (endometrial, ovarian, cervical, vulvar, and vaginal) between 2010 and 2016. We used a quasiexperimental difference-in-difference multivariable Cox regression analysis to compare 2-year survival between states that expanded Medicaid in January 2014 and states that did not expand Medicaid as of 2016. We performed univariable subgroup difference-in-difference Cox regression analyses on the basis of stage, income, race, ethnicity, and geographic location. Adjusted linear difference-in-difference regressions evaluated the proportion of uninsured patients on the basis of expansion status after 2014. We evaluated adjusted Kaplan-Meier curves to examine differences on the basis of study period and expansion status. Our sample included 169,731 women, including 78,669 (46.3%) in expansion states and 91,062 (53.7%) in nonexpansion states. There was improved 2-year survival on adjusted difference-in-difference Cox regressions for women with ovarian cancer in expansion than in nonexpansion states after 2014 (hazard ratio, 0.88; 95% confidence interval, 0.82-0.94; P<.001) with no differences in endometrial, cervical, vaginal, vulvar, or combined gynecologic cancer sites on the basis of expansion status. On univariable subgroup difference-in-difference Cox analyses, women with ovarian cancer with stage III-IV disease (P=.008), non-Hispanic ethnicity (P=.042), those in the South (P=.016), and women with vulvar cancer in the Northeast (P=.022), had improved 2-year survival in expansion than in nonexpansion states after 2014. In contrast, women with cervical cancer in the South (P=.018) had worse 2-year survival in expansion than in nonexpansion states after 2014. All cancer sites had lower proportions of uninsured patients in expansion than in nonexpansion states after2014. There was a significant association between Medicaid expansion and improved 2-year survival for women with ovarian cancer in states that expanded Medicaid after 2014. Despite improved insurance coverage, racial, ethnic, and regional survival differences exist between expansion and nonexpansion states.

Accuracy of three digital waxing–guided trial restoration protocols for controlling the depths of tooth preparation for ceramic veneers

Statement of problemThe accuracy of digital waxing–guided trial restoration protocols that have been implemented with ceramic veneers has not been reported. PurposeThe purpose of this in vitro study was to evaluate the accuracy of 3 digital trial restorations fabricated from digital waxing for ceramic veneers. Material and methodsA uniform 0.3-mm digital waxing added to the facial surface of 30 maxillary central typodont incisors was created in a software program. The trial restorations were fabricated on typodont teeth with autopolymerizing acrylic resin by using a silicone index based on 3-dimensionally printed casts designed from the digital waxing. The 30 maxillary central incisors were divided into 3 groups: the depth cutter (0.5 mm, Komet) (DC) group, the round bur (1.5 mm, Diatech) (RB) group, and the specially designed calibrated depth bur (laser mark of 0.5 mm, Gaofeng) (CD) group. The 3 groups were randomly prepared with a random number table by 2 experienced prosthodontists aiming to produce an even facial clearance of 0.5 mm. The dimensional differences in the standard tessellation language (STL) files between the surfaces of the original teeth, digital waxing, trial restorations, and prepared teeth in the software program were measured and analyzed at the same 9 points on the labial surface. One-way ANOVA with a post hoc test was used to identify significant discrepancies between trial restorations and waxing and differences in the reduction depth of typodont teeth (RDT) and the reduction depth (RD) among the 3 techniques (α=.05). The mean relative differences (MRDs) were calculated to determine the accuracy (%). ResultsThe thickness of the trial restorations was significantly greater than that of the digital waxings, with a discrepancy of 0.20 ±0.14 mm, especially at the cervical site. With the use of a trial restoration, the RDTs of the middle (-0.01 ±0.11 mm) and cervical locations (0.09 ±0.20 mm) showed significantly smaller preparation depths than did the other locations. Significant differences in RD were found among the 3 guided techniques (P<.05). Group DC presented the most accurate result of 0.51 ±0.08 mm with an MRD of 2%, whereas the results of 0.57 ±0.10 mm with an MRD of 14% and 0.60 ±0.11 mm with an MRD of 20% were obtained from group RB and group DC, respectively. ConclusionsThe trial restoration was significantly thicker than its corresponding waxing. The DC technique presented the most accurate reduction result among the 3 protocols examined.

Circular Stapler Method for Avoiding Stricture of Cervical Esophagogastric Anastomosis

BackgroundThis study was performed to verify the superiority of a new “non-tensioning method” for avoiding stricture of the cervical esophagogastric anastomosis by circular stapling compared with the conventional method. MethodsIn total, 395 consecutive patients who underwent McKeown esophagectomy with gastric conduit (GC) reconstruction were reviewed. A 4 cm-wide GC was created and pulled up at the cervical site through the retrosternal route. The esophagogastrostomy site of the GC was planned as far caudally as possible on the greater curvature side. In the conventional technique, the stapler was fired while pulling the GC to avoid tissue slack. In the non-tensioning technique, the stapler was fired through the natural thickness of the stomach wall. The length of the blind end was changed from 4 to 2 cm in the non-tensioning technique. Anastomotic leakage and stricture formation were compared between the two techniques, and adjustment was performed using propensity score matching. ResultsThe conventional group comprised 315 patients, and the non-tensioning group comprised 80 patients. Anastomotic leakage occurred in 22 (7%) and 2 (2.5%) patients, respectively (P = 0.134) [and in 9 (2.9%) and 2 (2.5%) patients, respectively, if leakage at the blind end was excluded]. Anastomotic stricture occurred in 92 (29.2%) and 3 (3.8%) patients, respectively (P < 0.001). The propensity score-matching analysis including 79 pairs of patients confirmed a lower stricture rate in the non-tensioning than conventional group (2.5% vs. 29.1%, P < 0.001). ConclusionsThe non-tensioning technique significantly reduced the incidence of anastomotic stricture compared with the conventional technique.

MRI for in vivo Analysis of Ablation Zones Formed by Cooled Radiofrequency Neurotomy to Treat Chronic Joint Pain Across Multiple Axial Spine Sites.

PurposeRadiofrequency (RF) ablation is the targeted damage of neural tissues to disrupt pain transmission in sensory nerves using thermal energy generated in situ by an RF probe. The present study aims to evaluate the utility of magnetic resonance imaging (MRI) for in vivo quantitative assessment of ablation zones in human subjects following cooled radiofrequency neurotomy for chronic pain at spinal facet or sacroiliac joints. Ablation zone size and shape have been shown in animal models to be influenced by size and type of RF probe – with cooled RF probes typically forming larger, more spherical ablation zones. To date, MRI of RF ablation zones in humans has been limited to two single retrospective case reports.Patients and MethodsA prospective, open-label pilot study of MRI for evaluation of cooled radiofrequency ablation zones following standard of care procedures in adult outpatients was conducted. Adult subjects (n=13) received monopolar cooled RF (CRF) ablation (COOLIEF™, Avanos Medical) of sensory nerves at spinal facet or sacroiliac joints, followed by an MRI 2–7 days after the procedure. MRI data were acquired using both Short Tau Inversion Recovery (STIR) and contrast-enhanced T1-weighted (T1C) protocols. T1C MRI was used to calculate 3-dimensional ellipsoid ablation zone volumes (V), where well-defined regions of signal hyperintensity were used to identify three orthogonal diameters (T, D, L) and apply the formula V=π/6×T×D×L.ResultsAmong 13 patients, 96 CRF ablation zones were created at 4 different anatomic sites (sacroiliac, lumbar, thoracic and cervical). CRF ablation zone morphology varied by anatomical location and structural features of surrounding tissues. In some cases, proximity to bone and striations of surrounding musculature obscured ablation zone borders. The volumes of 75 of the 96 ablation zones were measurable from MRI, with values (mean±SD) ranging from 0.4679 (±0.29) cm3 to 2.735 (±2.62) cm3 for the cervical and thoracic sites, respectively.ConclusionIn vivo T1C MRI analysis of cooled RF ablation zones at spinal facet and sacroiliac joints demonstrated variable effects of local tissues on ablation zone morphology. Placement of the CRFA probe very close to bone alters the ablation zone in a negative way, causing non-spherical and incomplete lesioning. These new data may serve to inform practicing physicians about optimal cooled RF probe placement in clinical procedures.

Assessing colposcopic accuracy for high\u2010grade squamous intraepithelial lesion detection: a retrospective, cohort study

BackgroundInappropriate management of high-grade squamous intraepithelial lesions (HSIL) may be the result of an inaccurate colposcopic diagnosis. The aim of this study was to assess colposcopic performance in identifying HSIL+ cases and to analyze the associated clinical factors.MethodsRecords from 1130 patients admitted to Shenzhen Maternal and Child Healthcare Hospital from 12th January, 2018 up until 30th December, 2018 were retrospectively collected, and included demographics, cytological results, HPV status, transformation zone type, number of cervical biopsy sites, colposcopists’ competencies, colposcopic impressions, as well as histopathological results. Colposcopy was carried out using 2011 colposcopic terminology from the International Federation of Cervical Pathology and Colposcopy. Logistic regression modelling was implemented for uni- and multivariate analyses. A forward stepwise approach was adopted in order to identify variables associated with colposcopic accuracy. Histopathologic results were taken as the comparative gold standard.ResultsData from 1130 patient records were collated and analyzed. Colposcopy was 69.7% accurate in identifying HSIL+ cases. Positive predictive value, negative predictive value, sensitivity and specificity of detecting HSIL or more (HSIL+) were 35.53%, 64.47%, 42.35% and 77.60%, respectively. Multivariate analysis highlighted the number of biopsies, cytology, and transformation zone type as independent factors. Age and HPV subtype did not appear to statistically correlate with high-grade lesion/carcinoma.ConclusionEvidence presented here suggests that colposcopy is only 69.7% accurate at diagnosing HSIL. Even though not all HSIL will progress into cancer it is considered pre-cancerous and therefore early identification will save lives. The number of biopsies, cytology and transformation zone type appear to be predictors of misdiagnosis and therefore should be considered during clinical consultations and by way of further research.

The Microbial Composition of Lower Genital Tract May Affect the Outcome of in vitro Fertilization-Embryo Transfer.

Objective: This work was conducted in order to study the effect of the lower genital tract (vaginal and cervical canal) microbiota on pregnancy outcomes of reproductive-aged women receiving embryo transfer.Study design: A total of 150 reproductive-aged patients who received the first fresh in vitro fertilization-embryo transfer (IVF-ET) were included in the study. Samples from the vagina and cervical site of each patient were collected separately using sterile swabs before ET. Genomic DNA was pyrosequenced for the V3–V4 regions of the 16S ribosomal RNA gene. Further bioinformatics analysis was performed using QIIME and R package. Pregnancy outcomes were followed and analyzed to compare differences in microbial composition.Results: The cervical microbiota had a higher Shannon index than the vaginal microbiota, and the microbial composition was different between the two sites. However, the Sorenson index between the two sites within the same individual was 0.370 (0.309–0.400). A total of 89 patients achieved clinical pregnancy after ET, while 61 failed. The Shannon indices and the microbial community of both vaginal and cervical microbiota between pregnant and non-pregnant groups were not significantly different. The relative abundance of Lactobacillus in the vagina and cervical canal did not differ between the two groups. Linear discriminant analysis, random forest analysis, and receiver-operating characteristic curve analysis showed that Bifidobacterium, Prevotella, and Lactobacillus iners in the vagina, as well as Solanum torvum, Fusobacterium, and Streptococcus in the cervix, may be negatively associated with clinical pregnancy after IVF.Conclusion: The cervical microbiota was more diverse than the vaginal microbiota, but because of anatomical continuity, there was a correlation between the two sites. The microbial composition of the vagina and cervical canal may influence the outcome of IVF-ET, but more samples are needed to verify this conclusion.

Online MR evaluation of inter- and intra-fraction uterus motions and bladder volume changes during cervical cancer external beam radiotherapy

Purpose/objective(s)The purpose of the study was to assess the uterus motions and bladder volume changes of fractional movements in cervical sites throughout the external beam radiotherapy (EBRT) treatment.Materials/methodsA prospective online MR imaging tracking study was conducted in EBRT 43 patients with at least 4 scans during each treatment (before: ultrasound scan, MRI scan, CBCT scan, after: MRI scan) were included. In order to improve the treatment repeatability, each patient was instructed to empty the bladder and drink 500 ml water 1 h before CT simulation and each treatment. If the ultrasound scan result reached the CT simulation volume of bladder, the treatment began. Bladder was outlined on the T2 weighted axial sequence and CBCT image by the two observers to avoid the influence of contouring. The data of bladder volume and scanning time were accurately recorded. The bladder volumes, filling rates and uterus motion were retrospectively analyzed by MIM software.ResultsInter-fraction variation of the bladder volume was significant (p < 0.0001). Intra-fraction mean increase of the bladder volume was modest (30 cc) but significant (p < 0.001). Both inter- and intra-fraction of the uterus motion were significant. The average time between the pre-and post-fraction MRI scans was 27.82 ± 7.12 min (range 10–55 min) for IMRT plans and 24.14 ± 5.86 min (range7-38 min) for VMAT plan. Average bladder filling rate was 3.43 ml/min. The bladder filling rate did not change significantly with the course of treatment, but the bladder was more intolerant.ConclusionThis is the most detailed assessment of intra-fraction and inter-fraction motion during EBRT for cervical cancer. Finally, this study will inform appropriate treatment margins for online adaptive radiotherapy. We suggest that at least one image scan is needed before the EBRT. The portable US scanner provides a quick but unreliable measurement of the bladder volume. There is a significant statistical difference between the results of ultrasonic scanning and that of image scanning.

Effect of the Inoculation Site of Bovine and Avian Purified Protein Derivatives (PPDs) on the Performance of the Intradermal Tuberculin Test in Goats From Tuberculosis-Free and Infected Herds.

The single and comparative intradermal tuberculin (SIT and CIT) tests are used for the ante-mortem diagnosis of caprine tuberculosis (TB). The tuberculin injection site has been associated with a different performance of the test in cattle. In contrast to that required in cattle in Europe (cervical injection), it can be carried out in the scapular region in goats. Nevertheless, there are no previous data concerning the effect of the injection site on the performance of the test in goats. The aim of the present study was to evaluate the effect of two different inoculation sites (cervical and scapular) on the performance of the SIT/CIT tests. This was done by intradermally inoculating 309 goats from two infected herds and one TB-free herd with both avian and bovine PPDs in the mid-cervical and scapular regions. None of the animals from the TB-free herd had positive reactions, and the number of reactors was not significantly higher, regardless of the inoculation site, in the high and low prevalence herds. However, significantly higher increases in skin fold thickness were observed on the cervical site when compared to the scapular site after the avian and bovine PPD inoculations in the TB-free herd (p < 0.001) and after the bovine PPD injection in the high prevalence herd (p = 0.003). The presence of clinical signs was also more evident on the cervical site when using avian and bovine PPDs in the high prevalence herd (p < 0.01). In contrast, increases in higher skin fold thickness were observed on the scapular site when compared to the cervical site after the bovine and avian PPD inoculations were employed in the low prevalence herd (p < 0.01). These results suggest that the cervical injection of PPDs may improve the sensitivity of the intradermal tuberculin test in high TB prevalence caprine herds, mainly owing to the increased presence of local clinical signs and a better performance of the CIT test. Moreover, specificity was not affected when using standard interpretations, although further analyses in a great number of herds are required in order to confirm these findings.

Tissue Oxygen Saturation during Gastric Tube Reconstruction with Cervical Anastomosis for Esophagectomy: A Case Series

Background One cause of anastomotic leakage after radical esophagectomy is blood flow insufficiency at the cervical anastomosis site. . Methods Eighteen patients, who underwent radical esophagectomy with gastric tube reconstruction, were studied. The regional tissue oxygen saturation (rSO2) was measured at the tip (point pre 0) and 2, 4, and 6 cm on the distal side of the tip (point pre 1, pre 2, and pre 3, respectively) before the gastric tube was raised to the cervical site through the retrosternal route. After that, rSO2 was measured at the tip, 2 and 4 cm on the distal side of the tip (points post 0, post 1, and post 2), the actual anastomotic site (point AN), and the chest skin as an indicator of whole-body oxygenation. The relationship between rSO2 scores and the rate of anastomotic leakage was determined. Results The mean rSO2 at pre 0, pre 1, pre 2, and pre 3 were 48.9%, 52.3%, 54.8%, and 56.9%, respectively (p < 0.05). The mean rSO2 at post 0, post 1, and post 2 were 47.8%, 50.5%, and 52.3%, respectively, and the rSO2 at point AN was 52.1%. Anastomotic leakage was found in 6 patients. The rSO2 at points pre 0, pre 1, and pre 2, post 0 and point AN were significantly lower in patients with anastomosis leakage than those without (p < 0.05). Conclusion Tissue oxygen saturation monitoring was a useful indicator of blood flow insufficiency in the gastric tube during radical esophagectomy.

The state of K2R grant funding by cancer type from the National Cancer Institute

Objectives: Given that K grant funding secured in early career correlates with success in achieving R funding, we aim to describe the state of K and R funding by cancer type through time, hypothesizing that those cancer sites receiving more K grant allocation also receive greater R grant allocation. Methods: We queried the National Cancer Institute (NCI) Research portfolio from 2007-2017 for K and R grant sums by year and 19 cancer sites. Yearly K grant amount means, medians and sums were summarized for each cancer site, and the sums trended over time, as were yearly K grant number of funded studies. R grant sums were similarly trended through time using linear regression with year as the independent variable. The relationship between K and R grant funding was assessed using a multivariable linear regression model with K grant yearly total by year interaction and adjusting for cancer site, after applying a Box-Cox transformation of R grant total amount to gain linearity. All statistical analyses were performed in R, version 4.0.2. Results: Median yearly number of funded K grants range from 0-85 and median total yearly dollar amounts range from $0-10.66 million. Breast, leukemia and lung (85, 47, 45 respectively) have the highest median number of K grants per year; and breast, lung, and brain ($10.66, 5.95, and 5.85 million) have the highest total yearly amount of K grant funding. Cervical, ovarian and uterine cancer sites ranked 11, 9, and 14 in median number of yearly funded K grants over the 19 cancer sites considered, and 14, 13, and 17 in yearly median K grant dollar amounts. By total yearly R grant medians, the highest funded three cancer sites were breast, lung, and colorectal, while cervix, ovary and uterus ranked 11, 10, and 16. The rates of change over time in K grant funding for cervix, ovarian, and uterine cancer were 0.008, 0.107, and -0.014, while the rates of change in R grant funding for these sites were -1.088, 0.987, and 0.186. They ranked thus 14, 7, and 15 in K grant growth across all sites, and 17, 7, and 12 in R grant growth across sites. K grant funding is significantly associated with growth in R grant funding (p=0.021) adjusting for all cancer sites. Download : Download high-res image (162KB) Download : Download full-size image Conclusions: Gynecologic cancers are being funded at a lower rate and dollar amount than other cancer types at the K grant level, and this correlates as well with lower rates and dollar amounts at the R grant level. Given early career investigators typically foster innovation, it behooves us to advocate for and mentor more K grant funding recipients in gynecologic cancers. K and R grant funding also demonstrate stagnant growth in gynecologic cancers, also a potential arena for advocacy for allotment of funding.

Performance of point-of-care tests for the detection of chlamydia trachomatis infections: A systematic review and meta-analysis

BackgroundChlamydia trachomatis (CT) is one of the most prevalent bacterial sexually transmitted infections (STIs) globally but has been inadequately detected for intervention. Introduction of point-of-care tests (POCTs) for CT is critical for filling the intervention gaps. We conducted a systematical review and meta-analysis on diagnostic performance of POCTs for CT to assist in guiding the application of these assays in CT screening and detection.MethodsWe searched PubMed/Medline and Embase databases, from January 2004 to May 2021, for studies reporting the performance of POCTs for identifying CT using specimens collected from urethral, vaginal, cervical, anorectal, or pharyngeal site or of urine. Two investigators independently screened and extracted data for controlling the quality of data extraction. Any discrepancies in study selection and data extraction were resolved through consensus. We only included studies with sufficient data to estimate sensitivity and specificity, and used laboratory-based nucleic acid amplification test (NAAT) as the reference standard. The main outcomes were pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs). Summary estimates were calculated using a random-effects model and summary receiver operator curves (SROCs) were generated using the Moses-Littenberg method. STATA 14.0 and Meta-DiSc 1.4 were used for statistical analysis. The study protocol is registered with PROSPERO, number CRD42019140544.FindingsOf 3,038 records identified, 39 studies (42,336 specimens) were included in the study, including 14 studies on evaluation of antigen detection (AD)-based and 25 on NAAT-based POCTs. The overall pooled sensitivity, specificity and DOR were 56% (95% CI 45%–67%), 99% (95% CI 98%–99%) and 86 (95% CI 46–163), respectively, for AD-based POCTs and corresponding values for NAAT-based POCTs were 94% (95% CI 91%–96%), 99% (95% CI 99%–99%) and 1,933(95% CI 1,018–3,669), respectively. The pooled sensitivity of AD-based POCTs varied across the types of specimens, indicating 46% for cervical swabs (95% CI 37%–56%; range 22.7%–71.4%), 52% for vaginal swabs (95% CI 34%–70%; range 17.1%–86.8%) and 57% for male urine (95% CI 36%–75%; range 20.0%–82.6%). For NAAT-based POCTs, the pooled sensitivity was 94% (95% CI 90%–96%) for cervical swabs, 94% (95% CI 86%–98%) for vaginal swabs, 95% (95% CI 91%–97%) for urine specimens and 93% (95% CI 87%–96%) for anorectal swabs.InterpretationNAAT-based POCTs for CT have a significantly better performance particularly in sensitivity for diagnosing the infection with CT than the AD-based POCTs. Screening strategy with AD-based POCTs may potentially result in a substantial under-detection of the infections.

Safety, Tolerability, and Effect of Nusinersen in Non-ambulatory Adults With Spinal Muscular Atrophy.

Objective: Investigation of the safety, tolerability, and treatment effect of nusinersen treatment in non-ambulatory adults with spinal muscular atrophy (SMA).Methods: Non-ambulatory individuals, aged 18 years or older with genetically confirmed 5q SMA were enrolled. In participants with spinal fusion, fluoroscopy guided cervical C1–C2 lateral approach was used. Outcomes at 2, 6, 10, and 14 months post-treatment were compared with baseline assessment. Forced vital capacity (FVC) was the primary outcome, and RULM, HFMSE, the modified SMA-FRS, and ulnar nerve electrophysiology [compound muscle action potential (CMAP), single motor unit size, and motor unit number] were secondary. Adverse and serious adverse events and clinically significant vital sign or lab abnormalities were recorded.Results: Results from 12 women and 7 men (mean age: 39.7 ± 13.9, range: 21–64 years) were analyzed. No clinically significant changes of vital signs or laboratory parameters were observed. Five participants were hospitalized for pneumonia. Other adverse events included headache, back pain, cervical injection site pain, and upper respiratory and urinary tract infections. High baseline protein/creatinine ratio without significant change on treatment noted in 4 participants. FVC was feasible in all participants. HFMSE and RULM were not feasible in the majority of participants. FVC and functional outcomes were stable without improvement. CMAP and single motor unit potential sizes showed enlargement while motor unit numbers were stable.Conclusions: Nusinersen, including C1/C2 delivery, was safe overall and well-tolerated. Several outcome measures were limited by floor effect. Overall, treatment resulted in stability of motor outcomes, but motor unit and CMAP size were increased.

Health-related quality of life (SF-36) in back pain: a population-based study, Campinas, São Paulo State, Brazil

Our study aimed at assessing back pain impact over health-related quality of life (HRQoL). This is a cross-sectional population-based study that analyzed 1,192 adults. The dependent variables were the SF-36 scales and the main independent variables was back pain characterized by location, number of back pain region, intensity, frequency and limitations. Simple and multiple linear regression models were performed to estimate the crude and adjusted beta-coefficients (gender, age, schooling and co-morbidity conditions). Back pain prevalence were 35.4%. For HRQoL, comparing people with/without back pain, we found weak associations for the physical component (β = -3.6). However, strong associations were found for physical component (β = -12.4) when there were concomitant pain in cervical, dorsal and lumbar sites and also associations with mental health scales. Daily pain was associated with physical (β = -6.8) and mental (β = -2.7) components. Important impact on physical componente summary was found for intense/very intense pain (β = -7.9) and pain with severe limitation (β = -11.5). The impacts over HRQoL were strong when back pain was followed by (1) multiple back sites, (2) with pain in mental componente summary, (3) daily complaints, (4) very intense pain and (5) severe limitations; these results have revealed the importance to measure specific factors related to back pain.

Performance of Point-of-Care Tests for the Detection of Chlamydia Trachomatis Infections: A Systematic Review and Meta-Analysis

Background: Chlamydia trachomatis (CT) is the most prevalent sexually transmitted infection (STI) globally but has been inadequately detected for intervention. Introduction of point-of-care tests (POCTs) for CT is critical for filling the intervention gaps. We conducted a systematical review and meta-analysis on diagnostic performance of POCTs for CT to assist in guiding the application of these assays in CT screening and detection. Methods: We searched PubMed/Medline and Embase databases, from January 2004 to Nov 2020, for studies reporting the performance of POCTs for identifying CT using specimens collected from urethral, vaginal, cervical, anorectal, or pharyngeal site or of urine. Two investigators independently screened and extracted data for controlling the quality of data extraction. Any discordant data were discussed to meet consensus by involvement of the third investigator. We only included studies with sufficient data to estimate sensitivity and specificity, and used laboratory-based nucleic acid amplification test (NAAT) as the reference standard. The main outcomes were pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs). Summary estimates were calculated using a random-effects model and summary receiver operator curves (SROC) was generated using the Moses-Littenberg method. STATA 14.0 and Meta-DiSc 1.4 were used for statistical analysis. Findings: Of 2856 records identified, 37 studies (41,976 specimens) were included in the study, including 14 studies on evaluation of antigen detection (AD)-based and 23 on NAAT-based POCTs. The overall pooled sensitivity, specificity and DOR were 56% (95% CI 45%-67%), 99% (95% CI 98%-99%) and 86 (95% CI 46-163), respectively, for AD-based POCTs and corresponding values for NAAT-based POCTs were 94% (95% CI 92%-96%), 99% (95% CI 99%-100%) and 2,477 (95% CI 1,471-4,170), respectively. The pooled sensitivity of AD-based POCTs varied significantly across the types of specimens, 46% for cervical swabs (95% CI 37%-56%; range 22.7%-71.4%), 52% for vaginal swabs (95% CI 34%-70%; range 17.1%-86.8%) and 57% for male urine (95% CI 36%-75%; range 20.0%-82.6%). For NAAT-based POCTs, the pooled sensitivity was 93% (95% CI 87%-96%) for anorectal swabs, 94% (95% CI 92%-96%) for cervical swabs, 94% (95% CI 86%-98%) for vaginal swabs and 95% (95% CI 91%-97%) for urine specimens with a specificity ranging from 99% to 100%. Interpretation: NAAT-based POCTs for CT have a significantly better performance particularly in sensitivity for diagnosing the infection with CT than the AD-based POCTs. Funding Statement: The National Science and Technology Major Project for Belt and Road Initiative (2018ZX10101-001-001) and the Chinese Academy Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021) in China. Declaration of Interests: We declare no competing interests.

Herpes zoster of the trigeminal nerve with multi-dermatomal involvement: a case report of an unusual presentation

BackgroundHerpes zoster, also known as shingles, results from reactivation of the varicella-zoster virus. It commonly presents with burning pain and vesicular lesions with unilateral distribution and affects the thoracic and cervical sites in up to 60 and 20% of cases, respectively. The branches of the trigeminal nerves are affected in up to 20% of cases. Multidermatomal involvement of the trigeminal nerves has been only anecdotally described in immunocompetent subjects.Case presentationA 71-year-old previously healthy male presented with grouped vesicular and impetiginized lesions with crusts on the left half of the face of two-weeks duration. The lesions first developed on the left nasal tip and progressively worsened with unilateral appearance of vesicular lesions on the left forehead, face, ala nasi, nasal vestibulum and columella, as well as on the left side of hard and soft palate. The affected edematous erythematous areas corresponded to the distribution of the left ophthalmic (V1) and maxillary (V2) branches of the trigeminal nerve, including the infraorbital and nasopalatine nerves of the maxillary branch responsible for the oral cavity involvement. Viral DNA amplification by polymerase chain reaction confirmed the presence of Varicella zoster virus. The patient was started on oral valaciclovir with rapid recovery.ConclusionsAmong immunocompetent patients, herpes zoster is considered a self-limited localized infection. Our observation provides a rare but paradigmatic example of herpes zoster with involvement of both the ophthalmic and maxillary divisions of the trigeminal nerve in an immunocompetent patient. Immunocompetence status and age-specific screening should be warranted in case of atypical involvement and according to the patient’s history, while treatment with antiviral drugs should be rapidily initiated in patients at risk.

Aristocratic human papillomavirus drove cervical cancer: a study of the therapeutic potential of the combination of interferon with zinc.

Human papillomavirus (HPV) infection is related to cancer growth of vaginal, cervical, vulva, penile, anogenital, and non-genital oropharyngeal sites. HPV, as a sexually transmitted virus, infects all sexes similarly but with more significant pathological risks in women. This accounts for high mortality due to late detection and poor prognosis. The initial development and eventual progress of this cancer type depend entirely on three main oncogenes E5, E6 and E7, constitutively expressed to lead to carcinogenesis. Despite an opportunity for pharmacological therapy, there is still a shortage of medical treatment that may remove HPV from infected lesions. This study offers a concise summary of the nature of the issue and the current status of work on potential lead molecules and therapeutic approaches that show the capacity of HPV therapies to counteract the roles of deregulation of E5, E6, and E7.

Brachytherapy for Elderly Women with Gynecologic Cancer; Single Institutional Experience

To describe toxicity and disease outcomes in women ≥70 years old with gynecologic cancers treated with brachytherapy. We conducted an IRB approved, single-institution retrospective review of women ≥70 years old with gynecological cancers consecutively treated with intracavitary and/or interstitial brachytherapy (BT) from 2000-2019. Cancer, treatment characteristics, time to locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) from date of biopsy, Charleston comorbidity score (CCI), and toxicity were collected. Descriptive statistics were calculated and survival was analyzed by Kaplan-Meier (KM) method with log-rank testing to determine significance for univariate analysis. Of the 39 women identified, 21 (54%) were 70-79 years old and 18 (46%) were ≥80 years old. The majority had stage I-II cancers (n = 23, 59%) and 16 (41%) had stage III-IV cancers, with cervical cancer the most common primary (n = 31, 79%), followed by endometrial (n = 4, 10%) and vaginal/vulvar (n = 4, 10%) cancers. BT technique was intracavitary in 19 (49%) and interstitial in 20 (51%). Thirty-four (87%) received BT for primary treatment with or without external beam radiotherapy, and 5 (13%) at time of progression/recurrence. Fifteen (38%) women were treated using 2D planning, while the remainder used CT-based planning. Median follow-up was 30 months for all patients (3-177 months) At the time of analysis, 31 patients (79%) had died, 6 (15%) were alive, and 2 (5%) were lost to follow-up. Median OS by KM was 40 months. Median OS was 22 months for women ³80 and 59 months for women 70-79 (p<0.001). Median OS was 52 months for CCI <5 and 22 months for CCI ≥5 (p = 0.005). Median OS was 50 months in patients without documented recurrence and 29 months for patients who recurred (p = 0.022). Overall local control (LC) was 87% with 2 (5%) LRR, 7 (18%) DM, and 3 (8%) with both LRR and DM. Of the 5 LRR, 3 were vaginal/vulvar, and 2 were cervical primary disease sites. Patients with LRR had a lower average CCI 4.2 vs. 4.9 than those without LRR. Time to DM was shorter for vaginal/vulvar cancers (p = 0.013) and OTT >56 days (p = 0.006). Patients with DM had a lower average CCI 4.3 vs. 5.0 than those without DM. Thirteen patients (33%) experienced grade 3 toxicities including 8 (24%) acute and 7 (18%) late toxicities, there were no grade ≥4 toxicities. Elderly women with gynecological cancers treated with brachytherapy tolerated treatment well with no grade ≥4 toxicities recorded and excellent LC. While CCI ≥5 was a significant predictor for shorter OS, it was not associated with higher rates of LRR nor DM.