Optimal size threshold for PIRADSv2 category 5 upgrade and its positive predictive value: is it predictive of "very high" likelihood of clinically-significant cancer?

AIM: To identify the optimal size metric and threshold for Prostate Imaging Reporting and Data System (PIRADS) 5 upgrade, calculate its positive predictive value (PPV) for clinically-significant prostate cancer (csPCA), and determine if it is indicative of a "very high" likelihood of csPCA. MATERIALS AND METHODS: One hundred and forty-three PIRADS 4 or 5 lesions were evaluated. Lesion diameters were used to calculate lesion volume (LV). Pearson correlation between maximum lesion diameter (MLD) and LV was calculated. Area under the curve (AUC) for discriminating csPCA (Gleason grade ≥ 3 + 4) was calculated using MLD and LV. Optimal size thresholds (using Youden index) and highly predictive size thresholds were identified for the whole prostate (WP), peripheral zone (PZ), and transitional zone (TZ). RESULTS: There was high correlation between MLD and LV (r=0.77-0.81), with comparable AUCs for MLD and LV in the identification of csPCA in the WP (0.73, 0.72), PZ (0.73, 0.73), and TZ (0.79, 0.75). Optimal MLD thresholds were 1.4, 1.4, and 1.6 cm in the WP, PZ, and TZ respectively, with PPVs of 76%, 81%, and 69%, respectively. An MLD threshold of 2.7 cm would be needed in the WP to achieve a PPV approaching 90%, with sensitivity decreasing to 10%. CONCLUSIONS: There is high correlation between MLD and LV with comparable discrimination of csPCA using each. PIRADSv2's 1.5 cm MLD threshold is near the optimal threshold for PIRADS 5 upgrade but has moderate PPV. A much higher threshold would be needed to increase its PPV, with significant sacrifice in sensitivity.

The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Association between the prevalence of dental caries in children and factors related to their mothers.

OBJECTIVES: We assessed the association between the socio-economic, behavioural, psychological and oral health status factors of Korean mothers with the status of dental caries in their children using nationwide representative data from the Fourth Korean National Health and Nutrition Examination Survey. METHODS: Children were categorized into child (CG, 6-11 years) and adolescent (AG, 12-18 years) groups. Responses from both the child and his/her mother were included in the analysis. The data for mother-child pairs were analysed using the chi-square test and multiple logistic regression of complex samples along with other covariates, including frequency of daily tooth brushing, tooth brushing before going to bed, regular dental check-up and unmet dental care needs. RESULTS: The prevalence of dental caries in the CG was 2.4 times higher in children with mothers having ≥1 permanent tooth caries than in those with mothers having no caries (P < 0.001). In the AG, the risk of permanent tooth caries was higher in children with mothers who received less education and experienced stress (P < 0.05), and the risk was also higher (2.4 times) in children with mothers with ≥1 active permanent tooth caries than in those whose mothers did not have caries (P < 0.001). CONCLUSIONS: The mothers' oral health status was significantly associated with the existence of dental caries in their children, even after adjusting for child-related variables. Strategies for promoting oral health in children and adolescents by including individual and family factors based on the sociocultural background of the country will be necessary.

Liver Transplantation in a Patient With CD40 Ligand Deficiency and Hyper-IgM Syndrome: Clinical and Immunological Assessments.

Monoclonal antibodies that disrupt CD40-CD40 ligand (CD40L) interactions are likely to have use in human transplantation. However, the extent of the immunosuppressive effects of CD40-CD40L blockade in humans is unknown. Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency syndrome characterized by defects in the CD40-CD40L pathway, severe immune deficiency (IgG), and high or normal IgM levels. However, the effects of CD40L deficiency on T- and natural killer (NK)-cell function is not established. Here, we present a patient with HIGM syndrome who underwent liver transplantation for hepatitis C virus infection. Posttransplantation, NK-cell antibody-dependent cytokine release (γ-interferon) to alloantigens and T cell responses to viral antigens and mitogens were assessed and showed normal CD4+ , CD8+ , and NK-cell responses. We also examined antibody-dependent cellular cytotoxicity against a CD40+ and HLA-expressing cell line. These experiments confirmed that the patient's NK cells were equivalent to those of normal subjects in mediating antibody-dependent cellular cytotoxicity despite the absence of CD40-CD40L interactions. Mitogenic stimulation of the patient's peripheral blood mononuclear cells showed no expression of CD40L on T and NK cells compared with increased expression in normal subjects. Taken together, these data suggest that absence of CD40L expression is responsible for aberrant B cell immunity but had little impact on NK- and T cell immune responses in vitro.

DNA methylation analysis for the diagnosis of thyroid nodules - a pilot study with reference to BRAF(V) (600E) mutation and cytopathology results.

OBJECTIVE: Promoter hypermethylation and the BRAF(V) (600E) mutation are both involved in thyroid tumorigenesis. We conducted a pilot study on the diagnosis of thyroid nodules by analysis of promoter hypermethylation status with reference to BRAF(V) (600E) mutation and cytopathology results using formalin-fixed, paraffin-embedded (FFPE) tissues and liquid-based preparation (LBP) thyroid fine needle aspiration (FNA) samples to predict more reliably the possibility of papillary carcinoma. METHODS: We initially performed MethyLight analysis for 30 genes that are known to be hypermethylated in malignancies using 164 papillary carcinomas and 77 benign tissue samples. Five genes selected from the tissue analysis were subsequently analysed in 75 surgically proven benign and 66 surgically proven papillary carcinoma LBP FNA samples. Samples that showed two or more positive results among the five genes were classified as methylation positive. We also analysed the BRAF(V) (600E) mutation status of the FNA samples. RESULTS: We identified five genes that were significantly hypermethylated in malignant tissues: PTGS2, HOXA1, TMEFF2, p16 and PTEN. With respect to diagnostic potential, results obtained using the BRAF(V) (600E) mutation test combined with cytological examination were not significantly different from those obtained with cytological examination only. Combining methylation analyses with cytological examination or performing all three tests for diagnoses did not improve significantly the negative predictive values and sensitivity, but a significant decrease in positive predictive value and specificity was observed. CONCLUSION: Further studies are needed on larger samples to assess the potential value of methylation analysis of thyroid FNA.

Two-year experience of using the measles, mumps and rubella vaccine as intralesional immunotherapy for warts.

BACKGROUND: The currently available treatments for warts, including cryosurgery, laser surgery, electrosurgery, and topical keratolytic applications, are often very painful and can induce disfiguring scars. Recently, intralesional immunotherapy with skin test antigens and vaccines has been shown to be effective in the management of warts. AIMS: To evaluate the efficacy of a new intralesional immunotherapy for warts, using the measles, mumps and rubella (MMR) vaccine. METHODS: A retrospective study was performed, and we enrolled 136 patients with various types of warts into the study, which was for a duration of 2 years. Patients were treated for a total of six times at 2-week intervals. The treatment response was classified as one of three levels, based on reduction in the size and number of warts, and patients with complete response (CR) were checked for recurrence. Clinical evaluations were carried out using photographs and medical records. RESULTS: Over half (51.5%) of patients experienced > 50% reduction in the size and number of warts, and 46.7% who had distant warts (in different locations) showed good response. Common warts showed significantly higher treatment response than other types of warts (P < 0.05). However, other clinical variables did not have any effect on efficacy. Almost all the patients reported mild pain during the injection, but other side effects were rarely observed. Only 5.6% of patients who experienced CR had recurrence of warts after 6 months. CONCLUSIONS: We suggest that intralesional immunotherapy with MMR vaccine is a tolerable and effective method for patients who are sensitive to pain, concerned about side effects, or have common warts. Treatment response is improved by increasing the number of injections.

An extremely energetic cosmic ray observed by a surface detector array.

Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle's energy as [Formula: see text] (~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

The influence of patient position on withdrawal force of thoracic epidural catheters.

We investigated the forces required to remove thoracic epidural catheters to determine the effect of patient position on removal. Eighty-four patients undergoing open thoracotomy and thoracic patient-controlled epidural analgesia were enrolled. Catheterisation was performed under fluoroscopic guidance before surgery, and the patients were allocated to one of three position groups for removal: prone; sitting; and lateral. On the third postoperative day, the peak tension during withdrawal in the assigned position was measured. No differences in mean (SD) forces were found between groups: prone 1.61 (0.39) N, supine 1.62 (0.61) N and lateral 1.36 (0.56) N (p = 0.140). The withdrawal forces required to remove thoracic epidural catheters were not affected by the position. Thus, the position for removal can be determined by patient's choice and clinical judgement.

Clinical predictors of apnoea-hypopnoea during propofol sedation in patients undergoing spinal anaesthesia.

This study assessed the relationship between the occurrence of apnoea-hypopnoea during propofol sedation for spinal anaesthesia and two different predictive tests of sleep apnoea: the STOP-Bang score (snoring while sleeping, daytime tiredness, observed breathing stoppages, high blood pressure-body mass index, age, neck circumference, gender); and the obstructive sleep apnoea (OSA) score. Thirty-four middle-aged men not diagnosed with obstructive sleep apnoea received propofol infusions adjusted to produce a bispectral index of 70-75. ApnoeaLink(TM) was used to estimate the incidence of apnoea-hypopnoea. The median (IQR [range]) apnoea-hypopnoea index was 17 (8-24 [0-70]) events.h(-1) and correlated weakly with the STOP-Bang score (p = 0.022, r = 0.423) and moderately with the OSA score (p < 0.001, r = 0.693). Severe apnoea-hypopnoea developed more frequently in patients with a higher OSA score (34.5% vs 0%) or higher STOP-Bang score (27.6% vs 6.9%). Both assessment tools have some predictive value for the occurrence of apnoea-hypopnoea during propofol sedation in patients undergoing spinal anaesthesia.

Rapid direct identification of Cryptococcus neoformans from pigeon droppings by nested PCR using CNLAC1 gene.

Isolation and identification of Cryptococcus neoformans and pathogenic yeast-like fungi from pigeon droppings has been taken for a long time and requires various nutrients for its growth. In this study, we attempted to establish a rapid direct identification method of Cr. neoformans from pigeon dropping samples by nested-PCR using internal transcribed spacer (ITS) CAP64 and CNLAC1 genes, polysaccharide capsule gene and laccase-associated gene to produce melanin pigment, respectively, which are common genes of yeasts. The ITS and CAP64 genes were amplified in all pathogenic yeasts, but CNLAC1 was amplified only in Cr. neoformans. The ITS gene was useful for yeast genotyping depending on nucleotide sequence. Homology of CAP64 genes among the yeasts were very high. The specificity of PCR using CNLAC1 was demonstrated in Cr. neoformans environmental strains but not in other yeast-like fungi. The CNLAC1 gene was detected in 5 serotypes of Cr. neoformans. The nested-PCR amplified up to 10(-11) µg of the genomic DNA and showed high sensitivity. All pigeon droppings among 31 Cr. neoformans-positive samples were positive and all pigeon droppings among 348 Cr. neoformans-negative samples were negative by the direct nested-PCR. In addition, after primary enrichment of pigeon droppings in Sabouraud dextrose broth, all Cr. neoformans-negative samples were negative by the nested-PCR, which showed high specificity. The nested-PCR showed high sensitivity without culture of pigeon droppings. Nested-PCR using CNLAC1 provides a rapid and reliable molecular diagnostic method to overcome weak points such as long culture time of many conventional methods.

Experimental constraints on left-right symmetric models from muon decay.

The TWIST Collaboration has completed a new measurement of the energy-angle spectrum of positrons from the decay of highly polarized muons. A simultaneous measurement of the muon decay parameters ρ, δ, and P(µ)(π)ξ tests the standard model in a purely leptonic process and provides improved limits for relevant extensions to the standard model. Specifically, for the generalized left-right symmetric model |(g(R)/g(L))ζ|<0.020 and (g(L)/g(R))m(2)>578 GeV/c(2), both 90% C.L.

Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders.

Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.

Neck circumference to thyromental distance ratio: a new predictor of difficult intubation in obese patients.

BACKGROUND: This study was performed to assess whether intubation is more difficult in obese patients and to assess the ability of a new index: the ratio of the neck circumference to thyromental distance (NC/TM), to predict difficult intubation in obese patients. METHODS: The incidence of difficult tracheal intubation in 123 obese (BMI≥27.5 kg m(-2)) and 125 non-obese patients was compared. Difficult intubation was determined using the intubation difficulty scale (IDS≥5). The NC/TM ratio was calculated and its ability to predict difficult intubation in obese patients was compared with that of established predictors including high BMI, the Mallampati score, the Wilson score, NC, width of mouth opening, sternomental distance, TM, and a previous history of difficult intubation. RESULTS: Difficult intubation was more frequent in obese patients than in non-obese patients (13.8% vs 4.8%; P=0.016). Multivariate analysis revealed that the Mallampati score, the Wilson score, and NC/TM independently predicted difficult intubation in obese patients. Among these three indices, NC/TM showed the highest sensitivity and a negative predictive value, and largest area under the curve on an ROC curve. CONCLUSIONS: Difficult intubation was more common in obese patients and the NC/TM was a better method for predicting difficult intubation than other established indices.

Changes in pulmonary artery pressures during ethanol sclerotherapy for arteriovenous malformations: identifying the most vulnerable period.

AIM: To evaluate the changes in pulmonary artery pressure (PAP) during ethanol embolization and to identify the most vulnerable period associated with cardiovascular collapse in patients with arteriovenous malformations (AVMs). MATERIALS AND METHODS: Twenty-three patients (30 sessions) with AVMs were enrolled. PAP was measured at the following times: baseline (T(baseline)); immediately before (T(pre)), and after (T(post)) bolus injection of absolute ethanol; at the time of maximum mean PAP value during a session (T(highest-ethanol)); 10 min after final injection (T(final)); after restoration of spontaneous breathing (T(resp)); at extubation (T(extubation)); 30 min after extubation (T(extubation-30)(min)); and at the time of maximum mean PAP after patient resumed spontaneous respiration (T(highest-resp)). Nitroglycerin was infused (range 0.5-3 µg/kg/min) in all patients to attenuate the effect of ethanol on pulmonary vasoconstriction. RESULTS: The PAPs of T(highest-ethanol), T(resp), T(extubation), and T(highest-resp) were significantly higher than the corresponding values for T(baseline) and T(final) (all p<0.05). The systolic and mean PAPs of T(highest-resp) were significantly higher than those at T(highest-ethanol) (both p<0.05). In 24 sessions (80%), the highest mean PAP was detected during the recovery period. CONCLUSION: The greatest rise in PAP was noted during the recovery period in patients undergoing ethanol embolotherapy. Therefore, PAP monitoring and nitroglycerin infusions are recommended during the recovery period because early detection of an increase in PAP and prompt management may prevent detrimental complications.

Risk scorecard to minimize impact of COVID-19 when reopening.

BACKGROUND: We present a novel approach for exiting coronavirus disease 2019 (COVID-19) lockdowns using a 'risk scorecard' to prioritize activities to resume whilst allowing safe reopening. METHODS: We modelled cases generated in the community/week, incorporating parameters for social distancing, contact tracing and imported cases. We set thresholds for cases and analysed the effect of varying parameters. An online tool to facilitate country-specific use including the modification of parameters (https://sshsphdemos.shinyapps.io/covid_riskbudget/) enables visualization of effects of parameter changes and trade-offs. Local outbreak investigation data from Singapore illustrate this. RESULTS: Setting a threshold of 0.9 mean number of secondary cases arising from a case to keep R < 1, we showed that opening all activities excluding high-risk ones (e.g. nightclubs) allows cases to remain within threshold; while opening high-risk activities would exceed the threshold and result in escalating cases. An 80% reduction in imported cases per week (141 to 29) reduced steady-state cases by 30% (295 to 205). One-off surges in cases (due to superspreading) had no effect on the steady state if the R remains <1. Increasing the effectiveness of contact tracing (probability of a community case being isolated when infectious) by 33% (0.6 to 0.8) reduced cases by 22% (295 to 231). Cases grew exponentially if the product of the mean number of secondary cases arising from a case and (1-probability of case being isolated) was >1. CONCLUSIONS: Countries can utilize a 'risk scorecard' to balance relaxations for travel and domestic activity depending on factors that reduce disease impact, including hospital/ICU capacity, contact tracing, quarantine and vaccination. The tool enabled visualization of the combinations of imported cases and activity levels on the case numbers and the trade-offs required. For vaccination, a reduction factor should be applied both for likelihood of an infected case being present and a close contact getting infected.

A new symptom-based questionnaire for predicting the presence of asthma.

BACKGROUND: Early diagnosis and treatment of asthma is important for improving health and minimizing the social and economic burden of the disease. A simple questionnaire would provide a convenient and timesaving tool to help physicians diagnose asthma. OBJECTIVE: The senior author developed a simple, pre-interview screening questionnaire--the Asthma Screening Questionnaire (ASQ)--consisting of 6 questions. The present report provides performance evidence that the ASQ is a reliable instrument for diagnosing asthma in adults. METHODS: Participants were asthmatics or controls, aged 18 to 65 years. All participants completed the questionnaire (self-administered and physician-administered), and underwent spirometry and a methacholine challenge test (if there was no reversibility during initial spirometry). Sensitivity, specificity, and positive and negative predictive values were calculated for each question, and the total scores of asthmatics were compared with those of controls. The degree of agreement between the self-administered and the physician-administered questionnaire was calculated. RESULTS: The main symptoms discriminating asthmatics from controls were cough more than average (88% vs 0%), cough from chest (72% vs 0%), shortness of breath with exercise (84% vs 16%), and chest tightness when lying down (72% vs 4%). A cutoff point of total score > or = 4 was associated with the highest combination of sensitivity (96%) and specificity (100%). Substantial agreement was observed between the self-administered and the physician-administered questionnaire (kappa statistic, 0.56-1.00; P<.0001). CONCLUSIONS: The ASQ is a simple, inexpensive, and efficient pre-interview screening tool to diagnose asthma.

Primary serous papillary carcinoma of the peritoneum mimicking pelvic actinomycosis: a case report and brief literature review.

Primary serous papillary carcinoma of the peritoneum is a rare tumor, histologically similar to primary ovarian carcinoma. Pelvic CT and MRI are helpful to diagnose primary carcinoma of the peritoneum. We present a case of primary serous carcinoma of the peritoneum mimicking pelvic actinomycosis in a 59-year-old woman. Pelvic CT and MRI suggested pelvic actinomycosis. Exploratory laparotomy was performed to remove the mass and the diagnosis was confirmed by pathology. A subtotal hysterectomy, left salpingo-oophorectomy and omentectomy were performed. Histopathology examination revealed peritoneal carcinomatosis and primary serous carcinoma of the peritoneum. Pelvic CT and MRI were limited in their ability to differentiate inflammation, such as actinomycosis, from primary carcinoma of the peritoneum.