Anal cancer screening results from 18-to-34-year-old men who have sex with men living with HIV.

Men who have sex with men living with HIV (MSM LWH) are at highest risk for human papillomavirus (HPV)-associated anal cancer. There is no consensus on the optimal screening initiation age. This study aimed to assess the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, which is a currently proposed screening age threshold. Between 2014 and 2020, 1255 18-to-34-year-old MSM LWH underwent anal cytology screening. 916 were co-tested for high-risk HPV (HR-HPV). 467 underwent high-resolution anoscopy (HRA) and biopsy. Cancer registry data were queried. Predictors of abnormal cytology (ie, ≥ASCUS) and histological high-grade squamous intraepithelial lesions (HSIL) were evaluated using unadjusted logistic regression models. Median age was 28 years (range, 18-34). 19% received at least one dose of HPV vaccine. Abnormal cytology rate was 65%. HR-HPV and HPV16 prevalence were 87% and 30%. Biopsy results were benign (10%), LSIL (43%) and HSIL (47%). No cases of prevalent or incident anal cancers were detected. Findings were similar between age subgroups (18-24, 25-29 and 30-34) except for a higher prevalence of AIN 3 in the 30-34 group (19%). Abnormal cytology was significantly associated with HR-HPV infection. Histological HSIL was associated with HR-HPV infection and cytological LSIL or worse. The absence of anal cancer in a large cohort of MSM LWH under the age of 35, despite high prevalence of anal HR-HPV infection and precancer, supports an age-based anal cancer screening strategy for MSM LWH.

Comparing Anal Cancer Screening Algorithms Using Cytology and Human Papillomavirus DNA Testing in 3 High-Risk Populations.

BACKGROUND: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. METHODS: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). RESULTS: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36). CONCLUSIONS: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.

Anaesthesia, pain and recovery profiles in children following dental extractions.

The aim of this prospective cohort study was to describe the anaesthetic practices, rates of postoperative pain and the recovery trajectory of children having urgent dental extractions at our institution. Demographic, anaesthetic and surgical details of children undergoing dental extractions were obtained by case note review. Parent-proxy pain scores were collected via telephone on the day of surgery and on postoperative days, as well as details of analgesia given, behavioural disturbance, and nausea and vomiting. Follow-up was continued until each child no longer had pain. Datasets were analysed for 143 patients. Fasting times were prolonged, with 81 children (56.6%) fasted for over four hours from fluids. Moderate or severe pain was recorded in 14 children (9.8%) postoperatively on the day of surgery, with higher rates in children who had a greater number of teeth extracted. Low rates of moderate to severe pain were observed during follow-up, affecting six children (4.2%) on postoperative day 1 and three children (2.1%) on postoperative day 2 with primarily simple analgesia administered at home. Only eight children (5.6%) had nausea and/or vomiting on the day of surgery. Rates of reported behavioural disturbance at home were low, extending beyond the second postoperative day in only two children (1.4%), and only four children (2.8%) attended a dentist during the follow-up period. In conclusion, the low rates of pain and nausea and vomiting reported in the days following surgery for urgent dental procedures suggest that children can be cared for at home with simple analgesia.

Sensitive CometChip assay for screening potentially carcinogenic DNA adducts by trapping DNA repair intermediates.

Genotoxicity testing is critical for predicting adverse effects of pharmaceutical, industrial, and environmental chemicals. The alkaline comet assay is an established method for detecting DNA strand breaks, however, the assay does not detect potentially carcinogenic bulky adducts that can arise when metabolic enzymes convert pro-carcinogens into a highly DNA reactive products. To overcome this, we use DNA synthesis inhibitors (hydroxyurea and 1-ß-d-arabinofuranosyl cytosine) to trap single strand breaks that are formed during nucleotide excision repair, which primarily removes bulky lesions. In this way, comet-undetectable bulky lesions are converted into comet-detectable single strand breaks. Moreover, we use HepaRG™ cells to recapitulate in vivo metabolic capacity, and leverage the CometChip platform (a higher throughput more sensitive comet assay) to create the 'HepaCometChip', enabling the detection of bulky genotoxic lesions that are missed by current genotoxicity screens. The HepaCometChip thus provides a broadly effective approach for detection of bulky DNA adducts.

Evaluation of the genotoxicity of cell phone radiofrequency radiation in male and female rats and mice following subchronic exposure.

The National Toxicology Program tested two common radiofrequency radiation (RFR) modulations emitted by cellular telephones in a 2-year rodent cancer bioassay that included interim assessments of additional animals for genotoxicity endpoints. Male and female Hsd:Sprague Dawley SD rats and B6C3F1/N mice were exposed from Gestation day 5 or Postnatal day 35, respectively, to code division multiple access (CDMA) or global system for mobile modulations over 18 hr/day, at 10-min intervals, in reverberation chambers at specific absorption rates of 1.5, 3, or 6 W/kg (rats, 900 MHz) or 2.5, 5, or 10 W/kg (mice, 1,900 MHz). After 19 (rats) or 14 (mice) weeks of exposure, animals were examined for evidence of RFR-associated genotoxicity using two different measures. Using the alkaline (pH > 13) comet assay, DNA damage was assessed in cells from three brain regions, liver cells, and peripheral blood leukocytes; using the micronucleus assay, chromosomal damage was assessed in immature and mature peripheral blood erythrocytes. Results of the comet assay showed significant increases in DNA damage in the frontal cortex of male mice (both modulations), leukocytes of female mice (CDMA only), and hippocampus of male rats (CDMA only). Increases in DNA damage judged to be equivocal were observed in several other tissues of rats and mice. No significant increases in micronucleated red blood cells were observed in rats or mice. In conclusion, these results suggest that exposure to RFR is associated with an increase in DNA damage. Environ. Mol. Mutagen. 61:276-290, 2020. © 2019 Wiley Periodicals, Inc.

Cancer-associated thrombosis.

Venous thromboembolic events are common in patients with malignancy, producing both morbidity and mortality. Although the underlying mechanisms by which cancer might promote a procoagulant state are multifaceted and incompletely understood, recent translational research has significantly advanced our understanding of the relationship between cancer and thrombosis. The occurrence of a thromboembolic event in a patient with an active malignancy should be regarded as a life-threatening complication, and decisions regarding prevention and treatment are usually complex. Outcomes may be improved by an evidence-based approach to management with consideration of practice guidelines.

Therapy of parapneumonic effusions in children: video-assisted thoracoscopic surgery versus conventional thoracostomy drainage.

OBJECTIVE: Controversy surrounds the optimal treatment of parapneumonic effusions. This trial of pediatric patients with community-acquired pneumonia and associated parapneumonic processes compared primary video-assisted thoracoscopic surgery with conventional thoracostomy drainage. DESIGN: A prospective, randomized trial was conducted at DeVos Children's Hospital (Grand Rapids, MI) between November 2003 and May 2005. All of the patients under 18 years of age with large parapneumonic effusions were approached for enrollment in the study. After enrollment, each patient was randomly assigned to receive either video-assisted thoracoscopic surgery or thoracostomy tube drainage of the effusion. Subsequent therapies (fibrinolysis, imaging, and further drainage procedures) were similar for each group per protocol. RESULTS: Eighteen patients were enrolled in the study: 10 in video-assisted thoracoscopic surgery and 8 in conventional thoracostomy. The groups were demographically similar. No mortalities were encountered in either group, and everyone was discharged from the hospital with acceptable outcomes. Yet, there were multiple variables that demonstrated statistical difference. Hospital length of stay, number of chest tube days, narcotic use, number of radiographic procedures, and interventional procedures were all less in the patients who underwent primary video-assisted thoracoscopic surgery. In addition, no patient in the video-assisted thoracoscopic surgery group required fibrinolytic therapy, which was also statistically different from the thoracostomy drainage group. CONCLUSIONS: The outcomes of this study strongly suggest that primary video-assisted thoracoscopic surgery for evacuation of parapneumonic effusions is superior to conventional thoracostomy drainage.