Predictive Value of Various Atypical Cells for the Detection of Human Papillomavirus in Cervical Smears.

It is thought that numerous genotypes of human papillomavirus (HPV) are associated with various atypical cells, such as multinucleated cells, koilocytes, binucleated cells, parakeratotic cells, and giant cells, in the cervix. We previously showed the specificity of HPV genotypes for koilocytes and multinucleated cells. Therefore, in this study, we analyzed the association among HPV genotypes and binucleated cells, parakeratotic cells, and giant cells in Papanicolaou (Pap) smears. We detected HPV genotypes and atypical cells in 651 cases of liquid-based cytology with an abnormal Pap smear. The HPV genotypes associated with atypical cells were evaluated using stepwise logistic regression with backward elimination and a likelihood ratio test for model construction. Polymerase chain reaction was used to determine the HPV genotypes in whole liquid-based cytology samples and microdissected cell samples from Pap smear slides. Binucleated cells were significantly associated with HPV genotype 42. Moreover, parakeratotic cells were significantly associated with certain HPV genotypes, such as HPV40. However, it was difficult to detect specific HPV genotypes by the manual microdissection-polymerase chain reaction method despite the presence of binucleated cells and parakeratotic cells. Thus, the presence of binucleated cells, parakeratotic cells, and giant cells in Pap smears may not be predictive of cervical lesions above low-grade squamous intraepithelial lesions or infection with highly carcinogenic HPV genotypes.

Cytological features of human papillomavirus-infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2.

In reflex cytology, the presence of prominent nucleoli in immature metaplastic squamous cells (IM) may be underdiagnosed due to variations in interpretation. The aim of this study is to identify human papillomaviruses (HPVs) that infect IM clusters in cervical intraepithelial neoplasia 2 (CIN2) on Papanicolaou (Pap) smears to determine the cytological features of lesion-derived cells. Thirty-two patients with a simultaneous diagnosis of CIN2 on biopsy and high-grade squamous intraepithelial lesions (HSIL) on cytology as well as with IM clusters on HSIL smears were included. CIN2 tissues and HSIL and IM clusters on Pap smears were isolated by manual microdissection, and HPV types were identified by PCR-based genotyping. The nuclear area within the IM clusters was also measured. The median nuclear area of HPV-negative IM clusters was 48 µm2 , with a coefficient of variation (CV) of 0.20; those of HPV-positive clusters were 66 µm2 and 0.34, respectively. The cut-off values of the nuclear area and CV for HPV positivity were 62 µm2 and 0.25, respectively. IM clusters composed of cells with a nuclear area of more than twice that of neutrophils or cells with a wide variation in nuclear sizes are likely to be neoplastic cells caused by HPV.

Granulocyte colony-stimulating factor priming improves embryos and pregnancy rate in patients with poor ovarian reserve: a randomized controlled trial.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) administration increased ovarian preantral follicles and anti-Müllerian hormone (AMH) in animal models with diminished ovarian reserve. We investigated whether G-CSF priming before treatment with assisted reproductive technology (ART) improved embryo development and pregnancy rate while increasing serum AMH in patients with poor ovarian reserve. METHODS: In this prospective randomized open-label controlled trial, 100 patients 20 to 42 years old with AMH below 2 ng/mL were randomized to priming or control groups (50 patients each). None had over 1 ART failure, day-3 follicle-stimulating hormone (FSH) above 30 IU/L, uterine anomalies, or a partner with azoospermia. All patients initially underwent conventional infertility treatment for 2 consecutive cycles in which the priming group but not controls received a subcutaneous G-CSF priming injection during the early luteal phase. Each group then underwent 1 cycle of in vitro fertilization/intracytoplasmic sperm injection and fresh embryo transfer (IVF/ICSI-fresh ET), followed by cryopreserved ET if needed until live birth or embryo depletion. AMH was measured before and after priming. RESULTS: Fertilization rate, embryonic development, and implantation rate by fresh ET were significantly improved by priming. Clinical and ongoing pregnancy rates by IVF/ICSI-fresh ET were significantly higher with priming (30% and 26% in 47 ART patients; 3 delivered with conventional treatment) than in controls (12% and 10% in 49 ART patients; 1 dropped out). With priming, significantly more patients achieved cryopreservation of redundant blastocysts. The cumulative live birth rate was 32% in 50 patients with priming, significantly higher than 14% in 49 controls (relative risk, 2.8; 95% confidence interval, 1.04-7.7). Infants derived from priming had no congenital anomalies, while infant weights, birth weeks, and Apgar scores were similar between groups. Among 4 variables (age, day-3 FSH, AMH, and priming), logistic regression significantly associated age and priming with cumulative live birth. Priming significantly increased serum AMH. No adverse effects of priming were observed. CONCLUSION: G-CSF priming improved embryonic development and pregnancy rate during ART treatment and increased AMH in patients with poor ovarian reserve. Enhanced preantral follicle growth likely was responsible. TRIAL REGISTRATION: UMIN registration in Japan (UMIN000013956) on May 14, 2014.  https://www.umin.ac.jp/ctr/index.htm .

Preferential Tissue Sites of Different Cancer-Risk Groups of Human Papillomaviruses.

The oncogenic potential of human papillomavirus (HPV) may be used to determine the tissue tropism of each HPV type. Cervical cancer develops in the squamo-columar junction of the cervices, and most lesions are induced by high-risk (HR) HPV types. This suggests that HR types preferentially infect the cervix, whereas the preferential infection site for low-risk (LR) types is not well defined. The determination of HPV tropism when using cytology samples can be uncertain since it is difficult to avoid contamination of cell samples between the cervix and the vagina. Herein, cell samples were carefully collected by independently scraping the cervix and vagina, after which the HPV types were determined. HPV tissue tropism was determined by considering what HPV types were positive at only one of the sites (the cervix or the vagina) as the viruses that preferentially infected that site. This method revealed that all LR types were only identified in vaginal samples, whereas 87% of HR types were identified in cervical sites. Thus, LR types may preferentially infect the vagina, whereas HR types infect the cervix. These findings suggest that preferential tissue tropism of certain HPV types is a probable factor for malignant progression.

Urodynamic effect of vibegron on neurogenic lower urinary tract dysfunction in individuals with spinal cord injury: A retrospective study.

STUDY DESIGN: A Retrospective study. OBJECTIVES: To investigate the effects of vibegron on urodynamic parameters of individuals with spinal cord injury (SCI). SETTING: The National Hospital Organization, Murayama Medical Center, Japan. METHODS: We retrospectively analyzed the urodynamic parameters of 31 individuals with SCI within one year after injury, who were diagnosed with neurogenic lower urinary tract dysfunction (NLUTD) according to a urodynamic study (UDS), and prescribed vibegron between December 2018 and December 2020. Treatment criteria were as follows: cystometric capacity of <200 mL, bladder compliance of <20 mL/cmH2O, and/or presence of detrusor overactivity in the first UDS. We compared urodynamic data before and after vibegron treatment. RESULTS: Vibegron administration increased the maximum cystometric capacity (MCC) (median, from 185.0 to 340.0 mL, P = 0.001), bladder compliance (median, from 8.3 to 20.0 mL/cmH2O, P < 0.001). CONCLUSION: Vibegron therapy improved the bladder capacity and bladder compliance of individuals with NLUTD and SCI.

Effects of the menstrual cycle on cytological false-negatives in women with persistent cervical intraepithelial neoplasia.

OBJECTIVES: False-negatives on cytology may be observed during follow-ups for patients with persistent cervical intraepithelial neoplasia (CIN); however, the underlying reasons are unknown, and the relationship between the intra-individual variability of false-negatives and the menstrual cycle phase has not been elucidated. Therefore, this study aimed to determine whether the menstrual cycle influences cytological results to maximise the accuracy of such tests. METHODS: A total of 154 liquid-based cytological (LBC) samples were obtained during follow-ups for 26 patients with CIN, and the relationship between cytological results and the menstrual cycle, which was classified into six phases, was analysed. RESULTS: All LBC smears were satisfactory, and 20 of 154 (13.0%) specimens were negative for intraepithelial lesions or malignancy (NILM). A statistically significant association was observed between the cytological results and the phase of the menstrual cycle, χ2 (2) = 19.322, P < 0.01. The association was moderately strong (Cramer's V = 0.354). The value of adjusted residuals showed a statistically significant increase in the NILM percentage as a cytological result during the early secretory phase (P < 0.01) and a statistically significant decrease in NILM during the menstrual and proliferative phases (P < 0.01). CONCLUSIONS: The present study revealed that false-negative cytological results were found to more likely to occur during the early secretory phase. More careful and precise microscopic observation of Pap smears collected at the early secretory phase may contribute to a reduction in the occurrence of false-negatives and improve cytological sensitivity.

Longitudinal study on locations of injury among junior high school, high school, and university badminton athletes at Japanese national-level competitions.

[Purpose] The aim of study was to examine incidence of injury according to location of injury to develop an injury prevention program for elite badminton players of junior high school, high school, and university. [Participants and Methods] We conducted a prospective longitudinal study, between April 2012 and March 2013, on 133 national-level badminton players attending junior high school, high school, and university. Injury rates in athletes per 1,000 exposures were calculated based on gender and school age for the five most common injury locations, in addition, severity, type and circumstance were investigated. [Results] Injury rates in athletes per 1,000 exposures were the highest in the racket-side (RS) shoulder/clavicle among the female university students (4.35), RS thigh of high school females (2.21), and lumbar spine/lower back of males of all school ages and junior high school females (1.83-1.25). Significantly higher injury rates were noted for the overuse of the lumbar spine/lower back and RS shoulder/clavicle, trauma of the RS thigh and ankle, and injury, when compared with slight injury of the RS ankle. [Conclusion] Injury prevention programs should be developed for RS shoulder/clavicle overuse in university females, RS thigh trauma in high school females, and lumbar spine/lower back in males of all school ages and junior high school females.

Trapa bispinosa Roxb. extract lowers advanced glycation end-products and increases live births in older patients with assisted reproductive technology: a randomized controlled trial.

BACKGROUND: Advanced glycation end-products (AGE), which accumulate with insulin resistance and aging, impair folliculogenesis and may decrease endometrial receptivity. Hishi (Trapa bispinosa Roxb.) extract, a safe herbal medicine, strongly inhibits AGE formation in vitro. We determined whether Hishi lowers AGE and increases live births in older assisted reproductive technology (ART) patients. METHODS: This prospective randomized open-label controlled trial included 64 patients 38 to 42 years old undergoing ART with or without Hishi extract between June 11, 2015 and July 12, 2019. None had over 2 ART failures, diabetes, uterine anomalies, or exhausted ovarian reserve. After allocation, the Hishi group received Hishi extract (100 mg/day) until late pregnancy or failure. The control group received no extract. Both groups underwent 1 cycle of conventional infertility treatment; 1 long-protocol cycle of ovarian stimulation, oocyte retrieval, in vitro fertilization/intracytoplasmic sperm injection, and fresh embryo transfer (ET); and, if needed, cryopreserved ET until live birth or embryo depletion. Serum AGE were measured before and during ART, as were AGE in follicular fluid (FF). RESULTS: Cumulative live birth rate among 32 Hishi patients was 47%, significantly higher than 16% among 31 controls (p<0.01; RR, 4.6; 95% CI, 1.4 - 15.0; 1 control dropped out). Live birth rate per ET, including fresh and cryopreserved, was significantly higher with Hishi (28% in 47 ET vs. 10% in 49 ET; p<0.05; RR, 3.4; 95% CI, 1.1-10.4). Among variables including age, day-3 FSH, anti-Müllerian hormone, and Hishi, logistic regression identified only Hishi as significantly associated with increased cumulative live birth (p<0.05; OR, 5.1; 95% CI, 1.4 - 18.3). Hishi significantly enhanced oocyte developmental potential, improved endometrial receptivity in natural cycles, and decreased AGE in serum and FF. Larger serum AGE decreases with Hishi were associated with more oocytes becoming day-2 embryos. CONCLUSIONS: Hishi decreased AGE in serum and FF and improved oocyte developmental potential and endometrial receptivity, increasing live births in older patients. Treatment of infertility by AGE reduction represents a new addition to infertility treatment. Therapeutic trials of Hishi for other AGE-associated diseases might be considered. TRIAL REGISTRATION: UMIN registration in Japan ( UMIN000017758 ) on June 1, 2015. https://www.umin.ac.jp/ctr/index.htm.

Effectiveness of negative pressure wound therapy for the wound of ileostomy closure: a multicenter, phase II randomized controlled trial.

BACKGROUND: The American Society of Surgery and American Society for Surgical Infections issued guidelines for surgical site infections (SSIs) in December 2016. These guidelines recommend a purse-string suture (PSS) for stoma closure as it facilitates granulation and enables open wound drainage. This study investigated the effect of using negative pressure wound therapy (NPWT) along with standard PSS and aimed to determine the optimal period of NPWT use. METHODS: The patients were divided into three groups as follows: Group A, postoperative wound management alone with gauze exchange as the representative of conventional PSS; Group B, the performed management was similar to that of Group A plus NPWT for 1 week; and Group C, the performed management was similar to that of Group A plus NPWT for 2 weeks. Regarding objective measures, the wound reduction rate was the primary outcome, and the incidence of SSIs, length of hospital stay, and wound healing duration were the secondary outcomes. RESULTS: In total, 30 patients (male: 18, female: 12) were enrolled. The average age was 63 (range: 43-84) years. The wound reduction rate was significantly higher in Group B than in Group A on postoperative days (PODs) 7 (66.1 vs. 48.4%, p = 0.049) and 10 (78.6 vs. 58.2%, p = 0.011), whereas no significant difference was observed on POD 14. Compared with Group A, Group C (POD 7: 65.9%, POD 10: 69.2%) showed an increase in the wound reduction rate on POD 7, although the difference was not significant (p = 0.075). SSIs were observed in Groups B (n = 2) and C (n = 2) (20%) but not in Group A (0%). CONCLUSIONS: The most effective duration of NPWT use for ileostomy closure with PSS in terms of the maximum wound reduction rate was from PODs 3 to 10. However, NPWT did not shorten the wound healing duration. NPWT may reduce the wound size but should be used with precautions for SSIs. The small sample size (30 cases), the use of only one type of NPWT system, and the fact that wound assessment was subjective and not blinded were the limitations of this study. Further studies are needed to confirm our findings. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000032174 (10/04/2018).

Koilocytic changes are not elicited by human papillomavirus genotypes with higher oncogenic potential.

Koilocytes are considered a common cytopathological effect in patients with human papillomavirus (HPV) infection. Thus, we aimed to elucidate whether koilocytes are common to all HPV infections. Liquid-based cytology samples from 651 patients with abnormal Papanicolaou (Pap) test results were used to analyze the presence of koilocytes and HPV genotype. HPV genotype was determined in complete liquid cytology samples and microdissected cell samples from Pap smear slides using the uniplex E6/E7 polymerase chain reaction method, which can detect 39 mucosal HPV genotypes. Koilocytes were found in 29.3% (191) of all patients. Logistical regression analysis of diverse HPV genotypes revealed that infections with low-risk HPV types (HPV-6b, HPV-40, HPV-42, HPV-61, HPV-74, HPV-89, and HPV-90), probably high-risk HPV types (HPV-53 and HPV-66), and high-risk types (HPV-39 and HPV-56) were significantly associated with the presence of koilocytes. However, HPV-16, HPV-18, and HPV-52, which have higher oncogenic potential, were not found to be associated with koilocytes. These results were confirmed by HPV genotyping using microdissected koilocytes in 27 patients.Most common high-risk types belonging to α-9 and α-7 genotypes appear to rarely induce koilocytic changes. Therefore, koilocytes may provide additional useful information for predicting the risk of progression to high-grade lesions.

A study of the relationship between nuclear contour thickening, nuclear enlargement and human papillomavirus infection in squamous cells.

OBJECTIVE: To investigate the relationship between the morphological features of nuclear enlarged cells and human papillomavirus (HPV) infection in negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cells of undetermined significance (ASC-US). METHODS: In total, 128 Papanicolaou specimens comprising 41 ASC-US cases and 87 NILM cases were examined. Cell morphological analysis was performed using both area ratio (nuclear area in cells with nuclear enlargement/nuclear area in normal intermediate cells) and nuclear contour thickening. High-risk HPV was detected using the Uniplex E6/E7 polymerase chain reaction assay and logistic regression analyses of factors related to high-risk HPV infection were performed. RESULTS: Nuclear contour thickening was present in 57.7% (64/111 cells) of high-risk HPV positive cases and 21.8% (69/317 cells) of high-risk HPV negative cases. There was a statistically significant association (P = 0.01) between high-risk HPV infection and nuclear contour thickening. Nuclear contour thickening was approximately one-third higher in NILM cases than in ASC-US cases (odds ratio, 0.371; 95% confidence interval, 0.208-0.662) and three times higher in high-risk HPV-positive cases than in high-risk HPV-negative cases (odds ratio, 2.831; 95% confidence interval, 1.591-5.039). CONCLUSION: Our results suggest that nuclear contour thickening in nuclear enlarged cells in NILM and ASC-US cases may be a cellular finding associated with HPV infection.

Uniplex E6/E7 PCR method detecting E6 or E7 genes in 39 human papillomavirus types.

We have developed a new human papillomavirus (HPV) assay using the uniplex E6/E7 polymerase chain reaction (PCR) method, which is able to detect E6 and E7 genes in 39 HPV types. We validated the assay for sensitivity and specificity using cloned HPV DNA and clinical samples. A comparative study using Genosearch-31 (GS-31) to determine HPV genotypes in clinical samples was also performed. E6 or E7 genes, measured by uniplex E6/E7 PCR, were detectable in 15 low-risk (HPV-6, -11, -40, -42, -44, -54, -55, -61, -62, -71, -74, -81, -84, -89, -90), 11 intermediate-risk (HPV-26, -30, -34, -53, -66, -67, -69, -70, -73, -82, -85), and 13 high-risk (HR) HPV types. The detection limit of this assay was 100 copies in all 39 HPV types and no cross-reactivity was observed with any type. This assay detected HPV in all 226 cervical cell samples, including 222 high-grade squamous intraepithelial lesions (HSIL) and 4 squamous cell carcinoma (SCC) cases, whereas GS-31 identified HPV in 99.6% (225/226) of the same samples. All SCC and 41.0% (90/222) of HSIL cases were infected with a single HPV type, while the remaining 59% of HSIL cases involved multiple HPV types. It was noted that high-risk and probably high-risk HPV types (HPV-66, -70 and -82) were identified, but no low-risk types were identified as a single-type infection in these HSIL and SCC cases. The uniplex E6/E7 PCR assay has high sensitivity, and can be useful tool in epidemiological studies or clinical follow-ups after surgery.

Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Arterial Hypertension.

Background The symptom for identification of pulmonary arterial hypertension (PAH) is dyspnea on exertion, with a concomitant decrease in exercise capacity. Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to exercise capacity and ventilatory efficiency in patients with hemodynamically normalized PAH after medical treatment. Methods and Results In total, 82 patients with PAH (age: median 46 [interquartile range, 39-51] years; male:female, 23:59) and mean pulmonary arterial pressure ≤30 mm Hg at rest were enrolled. The exercise capacity, indicated by the 6-minute walk distance and peak oxygen consumption, and the ventilatory efficiency, indicated by the minute ventilation versus carbon dioxide output slope, were assessed using cardiopulmonary exercise testing with a right heart catheter. The mean pulmonary arterial pressure was 21 (17-25) mm Hg, and the 6-minute walk distance was 530 (458-565) m, whereas the peak oxygen consumption was 18.8 (14.8-21.6) mLꞏmin-1ꞏkg-1. The multivariate model that best predicted 6-minute walk distance included peak arterial mixed venous oxygen content difference (ß=0.46, P<0.001), whereas the best peak oxygen consumption predictors included peak cardiac output (ß=0.72, P<0.001), peak arterial mixed venous oxygen content difference (ß=0.56, P<0.001), and resting mean pulmonary arterial pressure (ß=-0.25, P=0.026). The parameter that best predicted minute ventilation versus carbon dioxide output slope was the resting mean pulmonary arterial pressure (ß=0.35, P=0.041). Quadriceps muscle strength was moderately correlated with exercise capacity (6-minute walk distance; ρ=0.57, P<0.001; peak oxygen consumption: ρ=0.56, P<0.001) and weakly correlated with ventilatory efficiency (ρ=-0.32, P=0.007). Conclusions Central and peripheral factors are closely related to impaired exercise tolerance in patients with hemodynamically normalized PAH.

Changes in mental health and quality of life with dental implants as evaluated by General Health Questionnaire (GHQ) and Health Utilities Index (HUI).

OBJECTIVES: The purpose of this study was to assess and compare the improvement in oral and systemic conditions and health-related quality of life in patients with missing teeth receiving dental implants and conventional treatment. METHODS: A total of 97 patients with missing teeth, of whom 59 received dental implants and 38 received conventional treatment, were included in this study. The patients were divided into two age groups for a more detailed analysis: a 30- to 59-year age group (young) and a >60-year age group. The changes in oral condition, mental health, and health utility level before and after (pre- and post-, respectively) the procedures were assessed using an original questionnaire, the General Health Questionnaire 12 (GHQ12), and Health Utilities Index Mark 3. RESULTS: Responses to the GHQ12 indicated that treatment with implants significantly improved the oral health of patients in all treatment groups, except for the young group receiving partial dentures (PD). The mental state improved with a lower GHQ score; in terms of pre- versus post-procedure, mental state improved after the procedure in the young group receiving full dentures (FD) (1.75 ± 2.12 vs. 0.88 ± 2.10, p < 0.05), in the old group receiving PD (2.61 ± 3.91 vs. 0.72 ± 1.71, p < 0.05), and in the old group receiving FD (2.63 ± 3.12 vs. 0.44 ± 0.27, p < 0.05). The sleep score also improved by implant in FD of the old group (2.00 vs. 1.00, p < 0.05); it also is better with a lower score. CONCLUSIONS: Recovery of oral function and oral stability in middle-aged people who did not receive implants was possible with PD. However, the results suggest that implant treatment in edentulous denture cases and particularly in elderly people with dentures has a certain efficacy on the physical condition mediated through an improvement in aspects of the mental state.

[Utility of target controlled infusion technique for deciding the fentanyl infusion rate for post-cholecystectomy pain management in a patient on anticoagulant therapy].

The fentanyl infusion rate was controlled by employing a target controlled infusion (TCI) technique under anticoagulant therapy for postoperative pain management. A 59-year-old woman with atrial fibrillation and mitral stenosis was scheduled for open cholecystectomy. Heparin was continuously infused for anticoagulant therapy. Sevoflurane and remifentanil were used for induction and maintenance of anesthesia. At completion of the operation, her consciousness was checked and the endotracheal tube was then removed under fentanyl TCI (effect-site concentration: Ce = 2.0 ng x ml(-1)). In this case, the spontaneous breathing rate was stable (10-12 x min(-1)) under fentanyl TCI. She had no complaints of pain(pain at rest: VAS 20 mm). The breathing rate in this case provided indication for postoperative pain management. The TIVAtrainer simulation makes the exchange from TCI infusion to continuous infusion easy. And the spontaneous breathing monitoring is useful for postoperative pain measurement of laparotomy cases.

Evaluation of pain severity in critically ill patients on mechanical ventilation.

OBJECTIVES: To elucidate how patients' illness severity, respiratory status, or haemodynamics are associated with the pain score of critically ill patients. METHODS: This was an observational study of patients on mechanical ventilation after surgeries. At rest and on turning, patient pain was evaluated using the Behavioural Pain Scale (BPS) and the Critical-Care Pain Observation Tool (CPOT). Related factors were collected from medical records and analysed. FINDINGS: Multiple logistic regression analysis was performed using data on 127 scenarios. An increase of >2 in BPS score on turning was affected by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR] = 0.864), systolic blood pressure at rest (OR = 1.032), BPS at rest (OR = 0.638), heart rate difference (OR = 1.124), and tidal volume difference (OR = 0.548). An increase of >2 in CPOT on turning score was associated with the APACHE II score (OR = 0.894), Sequential Organ Failure Assessment score (OR = 1.248), systolic blood pressure at rest (OR = 1.025), heart rate difference (OR = 1.096), and tidal volume difference (OR = 0.578). CONCLUSION: The Behavioural Pain Scale and the Critical-Care Pain Observation Tools were associated with illness severity and haemodynamics. A reduction in tidal volume may be useful in assessing pain.

Effects of Menstrual Cycle on Various Morphologies of High-Grade Squamous Intraepithelial Lesions in SurePath™ Liquid-Based Cervical Cytology.

INTRODUCTION: The morphology of high-grade squamous intraepithelial lesion (HSIL) on Papanicolaou (Pap) smears widely varied, including syncytial aggregates, sheets, and scattered single cells, and no particular cellular pattern is consistently observed. Therefore, this study aimed to determine whether the menstrual cycle affects the cellular pattern of HSILs, an effort to avoid false negatives due to the oversight of scattered small single HSIL cells in the cytological triage of human papillomavirus-positive women. METHODS: A total of 147 HSIL samples of liquid-based cytology (LBC) in patients with cervical intraepithelial neoplasia grade 2 or 3 were obtained, and then, the relationship between cellular patterns, such as single-cell-like and syncytial aggregates, and menstrual cycles classified into six phases was analyzed. If a syncytial aggregate was present, the number of cells constituting the aggregate was visually counted under the microscope. RESULTS: HSILs in scattered single cells and small sheets of <6 on LBC samples accounted for 43% (23/54) during the late proliferative phase of the menstrual cycle. A moderately strong statistically significant association was observed between cellular patterns and menstrual cycles (χ2 [3] = 9.423, p < 0.05) (Cramer's V = 0.253). The value of adjusted residuals showed a statistically significant increased proportion of single-cell-like patterns during the late proliferative phase (p < 0.01). CONCLUSIONS: The present study demonstrated that HSIL cells in Pap smears in the late proliferation phase have a high frequency of single-cell-like patterns. In human papillomavirus-positive Pap smears with a clean background and predominantly superficial cells, careful microscopic observation by targeting single HSIL cells can potentially reduce false negatives.

Effects of Menstrual Cycle on the Accumulation of Human Papillomavirus-Infected Cells Exfoliated from the Cervix That Drift into the Vagina.

Human papillomavirus (HPV) testing using self-collected vaginal specimens is the preferred choice to increase screening uptake. Although the HPV testing results of these samples depend on the cells that naturally exfoliate from the cervical lesion and drift into the vagina, the mechanism of when and how these exfoliated cells mix with the self-collected sample remains unclear. Hence, the study aimed to clarify the relationship between the vaginal drift of HPV-infected cells exfoliated from the cervix, and the menstrual cycle. A total of 180 scraped samples of the cervix and vagina were examined. The exfoliated cells were classified into two categories according to the HPV genotyping results of each sample: sufficient accumulation (same HPV types in cervical and vaginal samples) and insufficient accumulation (fewer HPV types in vaginal samples than in cervical samples, or HPV positivity in cervical samples and HPV negativity in vaginal samples). A moderately strong statistically significant association was observed between exfoliated cell accumulation and the menstrual cycle, and insufficient accumulation was statistically significantly increased at the early proliferative phases. Self-collection of vaginal samples at the early proliferation phase indicates insufficient sample quantities or lower viral load, thereby affecting HPV genotyping.

Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology.

BACKGROUND: Advanced glycation end-products (AGE) are pivotal in aging and diabetes. Aging and polycystic ovary syndrome, a diabetes-associated disease, often cause infertility. We examined how AGE accumulation affects assisted reproductive technology (ART) outcomes. METHODS: In this retrospective analysis, toxic AGE (TAGE), pentosidine (Pent) and carboxymethyl lysine (CML) in blood and follicular fluid (FF) were measured in 157 ART-patients. We analyzed associations of AGE with ART outcomes and pre-ART clinical factors. RESULTS: TAGE, Pent and CML in FF and TAGE in serum, showed significant negative correlations with estradiol and numbers of follicles larger than 12 mm in diameter, retrieved oocytes, fertilized oocytes and embryos. AGE, Pent in FF and TAGE in serum showed significant negative correlations with ongoing pregnancy. Areas under receiver-operating characteristic curves for AGE (0.709), Pent in FF (0.686) and TAGE in serum (0.667) were significantly larger than for the reference (0.5). Women with serum TAGE above 7.24 U/ml showed decreased oocyte numbers and ongoing pregnancy rates, even with younger age or lower Day-3 FSH. Serum TAGE correlated positively with leptin (R = 0.51), BMI, low-density lipoprotein, triglyceride, glucose, homeostasis model assessment-insulin resistance and insulin. CONCLUSIONS: Serum TAGE and FF Pent accumulations correlated highly with poor follicular and embryonic development and with a lower likelihood of ongoing pregnancy. Serum TAGE predicts poor ART outcomes independent of age and Day-3 FSH.

Profiles of Human Papillomavirus Detection of the Multinucleated Cells in Cervical Smears.

Many genotypes of human papillomaviruses (HPVs) may lead to morphological changes in cells, resulting in various atypical cells, such as multinucleated cells (MNCs) and koilocytes, in the cervix. However, the relationships between the profiles of HPV genotypes and MNCs are not exactly known. Thus, this study comprehensively profiles the HPV genotypes in MNCs using a microdissection method. HPV genotypes and MNCs were detected in 651 cases with an abnormal Pap smear by liquid-based cytology. Specific HPV genotypes were also detected, including HPV16, 34, and 56, which might be associated with MNCs. This result suggests that the high-risk HPV genotypes, such as HPV16 and 56, are associated with the atypical changes in MNC morphology from normal cervical cells. The results also show that MNCs may be a predictor of squamous intraepithelial lesion.