Global burden, risk factors, and temporal trends of ureteral cancer: a comprehensive analysis of cancer registries.

BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

Lower baseline testosterone level is related to earlier development of castration resistance in metastatic prostate cancer: a multi-center cohort study.

Purpose: In the era of concurrent combination therapy in metastatic hormone sensitive prostate cancer, the impact of the testosterone level before initiating androgen deprivation therapy on treatment outcome is still uncertain. We aimed to investigate its effect on time-to-castration-resistance in a metastatic hormone sensitive prostate cancer cohort. Methods: This is a multi-center retrospective study of 5 databases from China, Japan, Austria and Spain including 258 metastatic hormone sensitive prostate cancer patients with androgen deprivation therapy initiated between 2002 and 2021. Baseline testosterone was divided into high and low groups using 12 nmol/L as cutoff level. Primary outcome was time-to-castration-resistance. Secondary outcomes were survival functions. Kaplan-Meier method was employed to evaluate the correlation between baseline testosterone and time-to-castration-resistance. Subgroup analysis was performed to elucidate the effect of upfront combination-therapy and metastatic volume. Results: Median age was 72 years. Median follow-up time was 31 months. Median pre-treatment prostate-specific-antigen level was 161 ng/mL. Majority of case were graded as International-Society-of-Urological-Pathology grade 5 (63.6%). 57.8% patients had high volume disease and 69.0% received upfront combination treatment. 44.6% of the cohort developed castration-resistance. The low testosterone group demonstrated shorter mean-time-to-castration-resistance (19.0 vs 22.4 months, p=0.031). The variance was more significant in patients without combination therapy (13.2 vs 26.3 months, p=0.015). Cancer-specific and overall survival were inferior in the low baseline testosterone level group without receiving combination therapy (p=0.001). Conclusions: Lower pre-treatment testosterone level is correlated to shorter time-to-castration resistance and worse survival in metastatic prostate cancer patients without upfront combination therapy. Those with low baseline testosterone should be encouraged to adopt combination therapy to delay progression.

Incidence, risk factors, and temporal trends of penile cancer: a global population-based study.

OBJECTIVES: To examine the global disease burden and country-specific trends of penile cancer incidence by age group and investigate its associations with several factors. MATERIALS AND METHODS: The Global Cancer Observatory database was interrogated for penile cancer incidence. The 10-year cancer incidence rates were collected from the Cancer Incidence in Five Continents Plus. The country-specific data were extracted from the World Health Organization Global Health Observatory and Global Burden of Disease databases for conducting risk factors analysis. The penile cancer incidence was presented using age-standardised rates. Its associations with various factors were examined by linear regression, while the incidence trend was estimated using joinpoint regression and presented as average annual percentage change with 95% confidence intervals in different age groups. RESULTS: There were an estimated 36 068 new cases of penile cancer in 2020. There was a considerable geographical disparity in the disease burden of penile cancer, with South America reporting the highest incidence. Overall, alcohol drinking, human immunodeficiency virus (HIV) infection, and unsafe sex were positively associated with a higher penile cancer incidence, while circumcision was found to be a protective factor. There has been a mixed trend in penile cancer incidence overall, but an increasing trend was found among younger males. CONCLUSIONS: There was a global variation in the penile cancer burden associated with prevalence of alcohol drinking, HIV infection, unsafe sex, and circumcision. The increasing penile cancer incidence in the younger population is worrying and calls for early detection and preventive interventions.

Psychological Health of Surgeons in a Time of COVID-19: A Global Survey.

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores. RESULTS: A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.

Worldwide Distribution, Risk Factors, and Temporal Trends of Testicular Cancer Incidence and Mortality: A Global Analysis.

BACKGROUND: Testicular cancer is a common malignancy among young males in western countries. OBJECTIVE: To examine the global disease burden and trends of testicular cancer incidence and mortality by age and country, and their associations with human development index (HDI), gross domestic product (GDP), lifestyle habits, and metabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: We retrieved the Global Cancer Observatory database for the testicular cancer incidence and mortality in 2020; the World Bank for GDP per capita; the United Nations for HDI; the WHO Global Health Observatory for prevalence of smoking and alcohol drinking; and the Cancer Incidence in Five Continents, WHO mortality database, Surveillance, Epidemiology, and End Results programme and Nordic Cancer Registries (NORDCAN) for trend analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We presented the testicular cancer incidence and mortality using age-standardised rates. We examined their associations with HDI, GDP, smoking, alcohol drinking, physical inactivity, overweight, obesity, and medical conditions including diabetes, hypertension, and hypercholesterolaemia by linear regression. We estimated the 10-yr trend of incidence and mortality by joinpoint regression with average annual percentage change with 95% confidence intervals in different age groups. RESULTS AND LIMITATIONS: There was a wide variation in the testicular cancer burden with the highest mortality found in low-income countries, and the regions of Central America and South America, while the highest incidence was observed in high-income countries, especially in Western and Northern Europe. We found a positive association for HDI, GDP, alcohol drinking, inactivity, overweight, obesity, and hypercholesterolaemia with testicular cancer incidence, while a negative correlation was observed between GDP and mortality of testicular cancer. Globally, there was an overall increasing incidence trend of testicular cancer for the past decade, particularly in younger males; the mortality trends of testicular cancer were relatively stable. However, we did not analyse the trend of different stages and subtypes of testicular cancer due to data unavailability. CONCLUSIONS: There was a global variation in the testicular cancer burden associated with HDI, GDP, alcohol drinking, inactivity, overweight, obesity, and hypercholesterolaemia. Testicular cancer had an increasing incidence but decreasing mortality. The increasing testicular cancer incidence in the younger population is of concern and calls for early detection and preventive interventions. PATIENT SUMMARY: Globally, testicular cancer incidence had been increasing particularly in the younger population, although its deaths rates had been decreasing. Socioeconomic indices, alcohol drinking, inactivity, overweight, obesity, and high plasma lipid levels are associated with testicular cancer incidence and mortality.

Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey.

BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

Managing advanced prostate cancer in the Asia Pacific region: "Real-world" application of Advanced Prostate Cancer Consensus Conference 2019 statements.

AIM: The second Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2020) gathered insights into the real-world application in the Asia-Pacific (APAC) region of consensus statements from the 3rd Advanced Prostate Cancer Consensus Conference (APCCC 2019). METHODS: The 4-h our virtual meeting in October 2020 brought together 26 experts from 14 APAC countries to discuss APCCC 2019 recommendations. Presentations were prerecorded and viewed prior to the meeting. A postmeeting survey gathered views on current practice. RESULTS: The meeting and survey highlighted several developments since APAC APCCC 2018. Increased access and use in the region of PSMA PET/CT imaging is providing additional diagnostic and staging information for advanced prostate cancer and influencing local and systemic therapy choices. Awareness of oligometastatic disease, although not clearly defined, is increasing. Novel androgen receptor pathway antagonists are expanding treatment options. Cost and access to contemporary treatments and technologies continue to be a significant factor influencing therapeutic decisions in the region. With treatment options increasing, multidisciplinary treatment planning, shared decision making, and informed choice remain critical. A discussion on the COVID-19 pandemic highlighted challenges for diagnosis, treatment, and clinical trials and new service delivery models that will continue beyond the pandemic. CONCLUSION: APAC-specific prostate cancer research and data are important to ensure that treatment guidelines and recommendations reflect local populations and resources. Facilitated approaches to collaboration across the region such as that achieved through APAC APCCC meetings continue to be a valuable mechanism to ensure the relevance of consensus guidelines within the region.

Endoscopic Combined Intrarenal Surgery vs Percutaneous Nephrolithotomy for Large and Complex Renal Stone: A Systematic Review and Meta-Analysis.

Background: Managing complex and large renal stones with percutaneous nephrolithotomy (PCNL) is difficult because of the likelihood of residual stones and multiple access. Endoscopic combined intrarenal surgery (ECIRS) is introduced as an improvement to the procedure to manage stones in one session. The objective of this systematic review and meta-analysis is to compare the efficacy and safety between ECIRS and PCNL for treating large and complex renal stones. Materials and Methods: We conducted a systematic review in the Embase, Scopus, and MEDLINE databases based on the 2020 Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Eligible studies comprised both randomized and nonrandomized studies comparing ECIRS and PCNL. Results: A total of five nonrandomized studies and one randomized controlled trial were included. The analysis was divided into two subgroups based on the PCNL type, a conventional PCNL (cPCNL) and a mini-PCNL (mPCNL). The one-step stone-free rate (SFR) of ECIRS were significantly higher compared with both the cPCNL (odds ratio [OR] 5.14, 95% confidence interval [CI] 2.54 to 10.4, p < 0.001) and mPCNL (OR 4.27, 95% CI 2.57-7.1, p < 0.001). There were no significant differences in mean operative time and hemoglobin drop between both groups (p > 0.05). The use of auxiliary procedures was significantly higher in both PCNL groups compared with the ECIRS group (OR 0.19, 95% CI 0.13-0.30, p < 0.001). The overall complication rate of ECIRS was lower compared with PCNL (OR 0.43, 95% CI 0.21-0.85, p = 0.02), especially urosepsis, in which the incidence was lower compared with cPCNL (OR 0.14, 95% CI 0.02-0.78, p = 0.02), but not mPCNL (p > 0.05). Conclusion: ECIRS is an effective and safe treatment particularly for large and complex nephrolithiasis, with significantly higher one-step SFR, a lower necessity for auxiliary procedures, and a lower complication rate compared with PCNL.

European Association of Urology Section of Urolithiasis and International Alliance of Urolithiasis Joint Consensus on Retrograde Intrarenal Surgery for the Management of Renal Stones.

BACKGROUND: Retrograde intrarenal surgery (RIRS) has become the preferred treatment modality for nephrolithiasis. However, because of ongoing uncertainties regarding the optimal perioperative management, operative technique, and postoperative follow-up, as well as a lack of standardization for outcome reporting, consensus is needed to achieve more uniform clinical practice worldwide. OBJECTIVE: To develop recommendations for RIRS on the basis of existing data and expert consensus. DESIGN, SETTING, AND PARTICIPANTS: A protocol-driven, three-phase study was conducted by the European Association of Urology Section of Urolithiasis (EULIS) and the International Alliance of Urolithiasis (IAU). The process included: (1) a nonsystematic review of the literature to define domains for discussion; (2) a two-round modified Delphi survey involving experts in this field; and (3) an additional group meeting and third-round survey involving 64 senior representative members to formulate the final conclusions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The results from each previous round were returned to the participants for re-evaluation of their decisions during the next round. The agreement threshold was set at 70%. RESULTS AND LIMITATIONS: The panel included 209 participants who developed 29 consensus statements on the following topics of interest: (1) perioperative infection management; (2) perioperative antithrombotic therapy; (3) fundamentals of the operative technique; and (4) standardized outcome reporting. Although this consensus can be considered as a useful reference for more clinically oriented daily practice, we also acknowledge that a higher level of evidence from further clinical trials is needed. CONCLUSIONS: The consensus statements aim to guide and standardize clinical practice and research on RIRS and to recommend standardized outcome reporting. PATIENT SUMMARY: An international consensus on the best practice for minimally invasive surgery for kidney stones was organized and developed by two international societies. It is anticipated that this consensus will provide further guidance to urologists and may help to improve clinical outcomes for patients.

Comparative evaluation of a dual-target real-time RT-PCR assay for COVID-19 diagnosis and assessment of performance in pooled saliva and nasopharyngeal swab samples.

OBJECTIVES: Sensitive molecular diagnostic assays are essential for COVID-19 diagnosis. We evaluated the Hecin Scientific SARS-CoV-2 nucleic acid test kit, a dual-target real-time RT-PCR assay targeting the SARS-CoV-2 N and ORF1ab genes. METHODS: The Hecin test kit's diagnostic performance in detecting SARS-CoV-2 RNA was compared to the LightMix Modular SARS and Wuhan CoV E-gene kit (TIB Molbiol) and an in-house single-tube nested real-time RT-PCR using 296 clinical specimens, 11 proficiency testing samples, and 30 low-positive deep throat saliva and nasopharyngeal swab (NPS) samples pooled into negative samples in ratios of 1:5, 1:10, and 1:30. RESULTS: The limit-of-detection of the Hecin test kit was around 500 dC/mL for the N and ORF1ab targets. Sensitivity and specificity of the Hecin test kit were 98.1% (95% CI: 93.4-99.8%) and 100% (98.1-100%), respectively, when measured against the reference method. The Hecin test kit showed fair sensitivity (80%) in low-positive NPS samples pooled in ratios of 1:5 and 1:10. Its performance in pooled samples could be dramatically improved by adjusting the assay Ct cutoff. CONCLUSION: The Hecin test kit enables sensitive and specific detection of SARS-CoV-2 in clinical samples and pooled samples.

Differential role of sphingomyelin in influenza virus, rhinovirus and SARS-CoV-2 infection of Calu-3 cells.

Host cell lipids play a pivotal role in the pathogenesis of respiratory virus infection. However, a direct comparison of the lipidomic profile of influenza virus and rhinovirus infections is lacking. In this study, we first compared the lipid profile of influenza virus and rhinovirus infection in a bronchial epithelial cell line. Most lipid features were downregulated for both influenza virus and rhinovirus, especially for the sphingomyelin features. Pathway analysis showed that sphingolipid metabolism was the most perturbed pathway. Functional study showed that bacterial sphingomyelinase suppressed influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, but promoted rhinovirus replication. These findings suggest that sphingomyelin pathway can be a potential target for antiviral therapy, but should be carefully evaluated as it has opposite effects on different respiratory viruses. Furthermore, the differential effect of sphingomyelinase on rhinovirus and influenza virus may explain the interference between rhinovirus and influenza virus infection.

Flexible fibre optic vs digital ureteroscopy and enhanced vs unenhanced imaging for diagnosis and treatment of upper tract urothelial carcinoma (UTUC): results from the Clinical Research Office of the Endourology Society (CROES)-UTUC registry.

OBJECTIVES: To compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) undergoing kidney-sparing surgery (KSS) with fibre-optic (FO) vs digital (D) ureteroscopy (URS). To evaluate the oncological impact of image-enhancement technologies such as narrow-band imaging (NBI) and Image1-S in patients with UTUC. PATIENTS AND METHODS: The Clinical Research Office of the Endourology Society (CROES)-UTUC registry is an international, multicentre, cohort study prospectively collecting data on patients with UTUC. Patients undergoing flexible FO- or D-URS for diagnostic or diagnostic and treatment purposes were included. Differences between groups in terms of overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: The CROES registry included 2380 patients from 101 centres and 37 countries, of whom 401 patients underwent URS (FO-URS 186 and D-URS 215). FO-URS were performed more frequently for diagnostic purposes, while D-URS was peformed when a combined diagnostic and treatment strategy was planned. Intra- and postoperative complications did not differ between the groups. The 5-year OS and DFS rates were 91.5% and 66.4%, respectively. The mean OS was 42 months for patients receiving FO-URS and 39 months for those undergoing D-URS (P = 0.9); the mean DFS was 28 months in the FO-URS group and 21 months in the D-URS group (P < 0.001). In patients who received URS with treatment purposes, there were no differences in OS (P = 0.9) and DFS (P = 0.7). NBI and Image1-S technologies did not improve OS or DFS over D-URS. CONCLUSIONS: D-URS did not provide any oncological advantage over FO-URS. Similarly, no differences in terms of OS and DFS were found when image-enhancement technologies were compared to D-URS. These findings underline the importance of surgeon skills and experience, and reinforce the need for the centralisation of UTUC care.

Evaluation of an Automated High-Throughput Liquid-Based RNA Extraction Platform on Pooled Nasopharyngeal or Saliva Specimens for SARS-CoV-2 RT-PCR.

SARS-CoV-2 RT-PCR with pooled specimens has been implemented during the COVID-19 pandemic as a cost- and manpower-saving strategy for large-scale testing. However, there is a paucity of data on the efficiency of different nucleic acid extraction platforms on pooled specimens. This study compared a novel automated high-throughput liquid-based RNA extraction (LRE) platform (PHASIFY™) with a widely used magnetic bead-based total nucleic acid extraction (MBTE) platform (NucliSENS® easyMAG®). A total of 60 pools of nasopharyngeal swab and 60 pools of posterior oropharyngeal saliva specimens, each consisting of 1 SARS-CoV-2 positive and 9 SARS-CoV-2 negative specimens, were included for the comparison. Real-time RT-PCR targeting the SARS-CoV-2 RdRp/Hel gene was performed, and GAPDH RT-PCR was used to detect RT-PCR inhibitors. No significant differences were observed in the Ct values and overall RT-PCR positive rates between LRE and MBTE platforms (92.5% (111/120] vs. 90% (108/120]), but there was a slightly higher positive rate for LRE (88.3% (53/60]) than MBTE (81.7% (49/60]) among pooled saliva. The automated LRE method is comparable to a standard MBTE method for the detection of SAR-CoV-2 in pooled specimens, providing a suitable alternative automated extraction platform. Furthermore, LRE may be better suited for pooled saliva specimens due to more efficient removal of RT-PCR inhibitors.

Phylogenomic analysis of COVID-19 summer and winter outbreaks in Hong Kong: An observational study.

BACKGROUND: Viral genomic surveillance is vital for understanding the transmission of COVID-19. In Hong Kong, breakthrough outbreaks have occurred in July (third wave) and November (fourth wave) 2020. We used whole viral genome analysis to study the characteristics of these waves. METHODS: We analyzed 509 SARS-CoV-2 genomes collected from Hong Kong patients between 22nd January and 29th November, 2020. Phylogenetic and phylodynamic analyses were performed, and were interpreted with epidemiological information. FINDINGS: During the third and fourth waves, diverse SARS-CoV-2 genomes were identified among imported infections. Conversely, local infections were dominated by a single lineage during each wave, with 96.6% (259/268) in the third wave and 100% (73/73) in the fourth wave belonging to B.1.1.63 and B.1.36.27 lineages, respectively. While B.1.1.63 lineage was imported 2 weeks before the beginning of the third wave, B.1.36.27 lineage has circulated in Hong Kong for 2 months prior to the fourth wave. During the fourth wave, 50.7% (37/73) of local infections in November was identical to the viral genome from an imported case in September. Within B.1.1.63 or B.1.36.27 lineage in our cohort, the most common non-synonymous mutations occurred at the helicase (nsp13) gene. INTERPRETATION: Although stringent measures have prevented most imported cases from spreading in Hong Kong, a single lineage with low-level local transmission in October and early November was responsible for the fourth wave. A superspreading event or lower temperature in November may have facilitated the spread of the B.1.36.27 lineage.

Effectiveness of One-Stop Screening for Colorectal, Breast, and Prostate Cancers: A Population-Based Feasibility Study.

Colorectal cancer (CRC), prostate cancer (PC) and breast cancer (BC) are among the most common cancers worldwide with well-established screening strategies. We aim to investigate the effectiveness and compliance of a one-stop screening service for CRC, PC and BC. Asymptomatic subjects aged 50-75 years were invited. Eligible subjects were offered fecal immunochemical test (FIT) for CRC screening. Serum prostate specific antigen (PSA) and Prostate Health Index (PHI) were offered for male PC screening and mammogram (MMG) for female BC screening as a one-stop service. Colonoscopy was offered to FIT+ subjects, prostate biopsy to PSA/PHI+ (PSA>10/PHI≥35) males and breast biopsy to MMG+ (Breast Imaging-Reporting and Data System, BI-RADS≥4) females. From August 2018 to April 2020, 3165 subjects were recruited. All participants (1372 men and 1793 women) were willing to accept FIT for CRC screening, and PSA/PHI test or MMG as second cancer screening. 102 subjects diagnosed advanced neoplasms after colonoscopy. Thirty-three males diagnosed PC after prostate biopsy and 15 females diagnosed BC after breast biopsy. No major complication reported in first tier screening tests. Subjects who were willing to undergo CRC screening were highly likely to accept other cancer screening when offered in a one-stop program. In conclusion, the effectiveness and compliance of a one-stop service for CRC, PC, and BC screening among asymptomatic subjects were high. Future studies should be conducted to test various ways of integrating cancer screening programs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04034953.

Herb-drug interactions between androgenic Chinese herbal medicines and androgen receptor antagonist on tumor growth: Studies on two xenograft prostate cancer animal models.

Our previous study revealed that Epimedii Folium (EF) and Codonopsis Radix (CNR) significantly promoted tumor growth on a subcutaneous mouse model of prostate cancer (PCa) via enhancing the mRNA and protein expressions of androgen receptor (AR), while Astragali Radix (AGR) inhibited tumor growth via suppressing the protein expression of AR. In the present study, we aimed to investigate the potential interactions between EF, CNR or AGR and AR antagonist (abiraterone acetate [ABI]) on the tumor growth using subcutaneous and orthotopic PCa mouse models. EF, CNR, AGR and ABI were intragastrically given to mice once every 2 days for 4 weeks. The pharmacokinetics of ABI were evaluated in the plasma of rats when combined with EF, CNR, or AGR. Our results demonstrated that EF or CNR could weaken the anti-tumor effects of ABI via increasing the AR expression involving activation of the PI3K/AKT and Rb/E2F pathways and decreasing the bioavailability of ABI, while AGR could enhance the anti-tumor effects of ABI through suppressing the AR expression via inhibiting the activations of PI3K/AKT and Rb/E2F pathways and increasing the bioavailability of ABI. These findings imply that cautions should be exercised when prescribing EF and CNR for PCa patients.

Saliva viral load better correlates with clinical and immunological profiles in children with coronavirus disease 2019.

BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 20 20. NPS and saliva viral loads were correlated (r = 0.315, p = 0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r = -0.532, p < 0.001) and saliva (r = -0.417, p < 0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p < 0.05), and were inversely correlated with total lymphocyte (r = -0.43), CD3 (r = -0.55), CD4 (r = -0.60), CD8 (r = -0.41), B (r = -0.482), and NK (r = -0.416) lymphocyte counts (all p < 0.05). INTERPRETATION: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS.

Coronavirus Disease 2019 (COVID-19) Re-infection by a Phylogenetically Distinct Severe Acute Respiratory Syndrome Coronavirus 2 Strain Confirmed by Whole Genome Sequencing.

BACKGROUND: Waning immunity occurs in patients who have recovered from Coronavirus Disease 2019 (COVID-19). However, it remains unclear whether true re-infection occurs. METHODS: Whole genome sequencing was performed directly on respiratory specimens collected during 2 episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG, were analyzed. RESULTS: The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was evidence of acute infection including elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. The virus genome from the first episode contained a a stop codon at position 64 of ORF8, leading to a truncation of 58 amino acids. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. Compared to viral genomes in GISAID, the first virus genome was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020. CONCLUSIONS: Epidemiological, clinical, serological, and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among humans despite herd immunity due to natural infection. Further studies of patients with re-infection will shed light on protective immunological correlates for guiding vaccine design.

Unique Clusters of Severe Acute Respiratory Syndrome Coronavirus 2 Causing a Large Coronavirus Disease 2019 Outbreak in Hong Kong.

After 2 months of relative quiescence, a large coronavirus disease 2019 outbreak occurred in Hong Kong in July 2020 after gradual relaxation of social distancing policy. Unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic clusters have been identified among locally acquired cases, with most genomes belonging to cluster HK1, which is phylogenetically related to SARS-CoV-2 reported overseas.