Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Widening Time Disparities between Two Paradigms: Tama-REgistry of Acute Endovascular Thrombectomy

Background

The Tama-REgistry of Acute endovascular Thrombectomy (TREAT) is a multicenter registry of endovascular thrombectomy in the Tama area of Tokyo. The objective of this study was to confirm the real-world status of 2 paradigms of transportation.

Anosognosia in patients with Alzheimer's disease: current perspectives

Alzheimer?s disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self‐awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self‐underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub‐symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self‐awareness include ‘denying’ and ‘confabulation’, and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one?s own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective.     

Investigation of trends and characteristics in patients with obstructive sleep apnea

Background

Oral appliance (OA) therapy for obstructive sleep apnea (OSA) has only been part of Japan’s National Health care coverage plan since 2004. Subsequently, not enough time has passed to establish the medical trends and characteristics of OSA patients in Japanese Dental Hospitals.

Aim

The aim of this study was to investigate the medical trends and the characteristics in patients with OSA who visited our clinic, and to compare our findings with previous studies.

Setting and design

Epidemiological survey (retrospective study).

Materials and methods

Two hundred and one patients were recruited at the Internal Medicine Division in the Tsurumi University Dental Hospital from February 2006 to December 2008, consecutively. Patients received a medical interview, and a detailed sleep analysis that included a polysomnography (PSG) to verify the exact nature of their condition. The efficacy of OA was assessed in 49 patients who wore an OA and underwent PSG.

Results

Of all subjects, 141 patients visited the Prosthodontic Division to receive OA therapy, 38 patients were treated or received a follow up examination in the Internal Medicine Division. The dropout rate was 10.4% in the all subjects, 17.0% in patients who visited the Prosthodontic Division. The male-to-female ratio was 3.3:1, 3.0:1 in patients who visited the Prosthodontic Division. In addition, females had a lower rate of OAS severity than males. In our patients, the major complication was hypertension and cardiac disease. The success rate of OA was 75.5%.

Conclusion

This approach allowed us to reveal some of the trends and characteristics in our patients.     

Lymph node and pulmonary metastases after transplantation of oral squamous cell carcinoma cell line (HSC-3) into the subcutaneous tissue of nude mouse: detection of metastases by genetic methods using beta-globin and mutant p53 genes

We attempted to establish an in vivo experimental model of metastasis of oral caner. The HSC-3 cell line, originating from human oral squamous cell carcinoma, was transplanted into nude mice, and metastases to the lymph node and the lung were investigated using genetic analysis. The HSC-3 cells, transplanted subcutaneously into the lateral back of nude mice, and punctured repeatedly after cyst formation, could metastasize to the lymph node and the lung. Genetic analysis using human beta-globin gene demonstrated that the frequency of metastasis to the lymph node and the lung at 12 weeks after the transplantation was 45% and 40%, respectively. Mutant allele-specific amplification of p53 gene could also detect micrometastasis with almost equal sensitivity of polymerase chain reaction with beta-globin gene. Subcutaneous transplantation is easy with excellent reproducibility compared with intravenous or orthotopic transplantation, and we think that this experimental model can be one of standard models of cancer metastasis.     

Evaluation of 5-Fluorouracil Metabolic Enzymes as Predictors of Response to Adjuvant Chemotherapy Outcomes in Patients with Stage II/III Colorectal Cancer: A Decision-Curve Analysis

Background

The effectiveness of 5-fluorouracil (5-FU)-based adjuvant chemotherapy is reported in patients with colorectal cancer (CRC), but the usefulness of 5-FU metabolic enzymes as predictive biomarkers of the efficacy of this chemotherapy remains unclear.

Objective

This study aims to verify whether 5-FU metabolic enzymes are predictive biomarkers in the clinical setting of adjuvant chemotherapy for stage II/III CRC.

Methods

In total, 179 patients with stage II/III CRC who were treated at our institute between 2000 and 2010 were enrolled. Messenger RNA (mRNA) expression of major 5-FU metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase (TP), orotate phosphoribosyl transferase, and β-actin (control) was evaluated using the Danenberg Tumor Profile method. mRNA expression and other clinicopathological data were investigated with regard to CRC relapse.

Results

A total of 78 patients underwent surgery alone, while 101 underwent adjuvant chemotherapy (5-FU plus leucovorin [LV] or tegafur plus uracil /LV) following surgery. Relapse-free survival was longer and risk of recurrence was lower in association with high TP mRNA expression than in association with low TP mRNA expression in the adjuvant chemotherapy group (hazard ratio 0.66; 95 % confidence interval 0.47–0.92; p = 0.016), but not in the surgery alone group. mRNA expression of no other enzymes was associated with relapse in both groups. In decision-curve analyses, the predictive efficiency of TP mRNA expression plus clinicopathological factors was slightly better than that of clinicopathological factors only.

Conclusions

TP mRNA expression in tumors predicted the effects of adjuvant chemotherapy for stage II/III CRC, although the beneficial effects were marginal.     

Mild to Moderate Intrapulmonary Shunting in Pediatric Liver Transplantation: Is Screening Necessary?

Background

Despite reported associations between intrapulmonary vascular shunting (IPVS) and morbidity and mortality in pediatric liver transplantation (LT), there are no guidelines for screening.

Microclimate and development of pressure ulcers and superficial skin changes

This study aims to evaluate the microclimate and development of pressure ulcers and superficial skin changes. A prospective cohort study was conducted in an acute care ward in Indonesia. Risk factors for pressure ulcers and superficial skin changes were identified based on the Bergstrom Braden conceptual model. Microclimate data were collected every 3 days for 15 days while the development of pressure ulcers and superficial skin changes was observed every day. Pressure ulcers and superficial skin changes were developed in 20 of the 71 participants. Total mean difference in skin temperature was higher for patients with pressure ulcers and superficial skin changes (0·9 ± 0·6°C) compared with controls (0·6 ± 0·8°C) (P = 0·071). Binary logistic regression predictor values for pressure ulcers and superficial skin changes were 0·111 for type of sheet and 0·347 for Braden Scale results. In conclusion, difference in skin temperature seems to be a predictor for pressure ulcer development and superficial skin changes, while synthetic fibre sheets are able to maintain a beneficial microclimate.