SARS-CoV-2 omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry.

BACKGROUND: COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. METHODS: OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. FINDINGS: At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [50·7%] of 1902 patients with sex data were female and 938 [49·3%] were male). Overall, 317 (16·6%; 95% CI 14·8-18·5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the pre-vaccination phase (191 [19·1%; 95% CI 16·4-22·0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16·8%; 13·8-20·3] of 653 patients, p=0·24), but significantly lower in the omicron phase (16 [6·2%; 3·5-10·2] of 256 patients, p<0·0001). In the alpha-delta phase, 84 (18·3%; 95% CI 14·6-22·7) of 458 unvaccinated patients and three (9·4%; 1·9-27·3) of 32 unvaccinated patients in the omicron phase had sequelae. Patients who received a booster and those who received two vaccine doses had a significantly lower prevalence of overall COVID-19 sequelae than unvaccinated or partially vaccinated patients (ten [7·4%; 95% CI 3·5-13·5] of 136 boosted patients, 18 [9·8%; 5·8-15·5] of 183 patients who had two vaccine doses vs 277 [18·5%; 16·5-20·9] of 1489 unvaccinated patients, p=0·0001), respiratory sequelae (six [4·4%; 1·6-9·6], 11 [6·0%; 3·0-10·7] vs 148 [9·9%; 8·4-11·6], p=0·030), and prolonged fatigue (three [2·2%; 0·1-6·4], ten [5·4%; 2·6-10·0] vs 115 [7·7%; 6·3-9·3], p=0·037). INTERPRETATION: Unvaccinated patients with cancer remain highly vulnerable to COVID-19 sequelae irrespective of viral strain. This study confirms the role of previous SARS-CoV-2 immunisation as an effective measure to protect patients from COVID-19 sequelae, disruption of therapy, and ensuing mortality. FUNDING: UK National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.

Intra- and interhost genomic diversity of monkeypox virus.

The impact and frequency of infectious disease outbreaks demonstrate the need for timely genomic surveillance to inform public health responses. In the largest known outbreak of mpox, genomic surveillance efforts have primarily focused on high-incidence nations in Europe and the Americas, with a paucity of data from South-East Asia and the Western Pacific. Here we analyzed 102 monkeypox virus (MPXV) genomes sampled from 56 individuals in Melbourne, Australia. All genomes fell within the 2022 MPXV outbreak lineage (B.1), with likely onward local transmission detected. We observed within-host diversity and instances of co-infection, and highlight further examples of structural variation and apolipoprotein B editing complex-driven micro-evolution in the current MPXV outbreak. Updating our understanding of MPXV emergence and diversification will inform public health measures and enable monitoring of the virus' evolutionary trajectory throughout the mpox outbreak.

The Reemergence of Syphilis Among Females of Reproductive Age and Congenital Syphilis in Victoria, Australia, 2010 to 2020: A Public Health Priority.

BACKGROUND: Syphilis notifications in Victoria, Australia, have been increasing over the past decade, with an increase in infectious syphilis (syphilis of less than 2 years in duration) cases in females of reproductive age and an associated reemergence of congenital syphilis (CS). Before 2017, there had been 2 CS cases in the preceding 26 years. This study describes the epidemiology of infectious syphilis among females of reproductive age and CS in Victoria. METHODS: Routine surveillance data provided by mandatory Victorian syphilis case notifications were extracted and grouped into a descriptive analysis of infectious syphilis and CS incidence data from 2010 to 2020. RESULTS: In 2020, infectious syphilis notifications in Victoria were approximately 5 times more than 2010 (n = 289 in 2010 to n = 1440 in 2020), with a more than 7-fold rise among females (n = 25 in 2010 to n = 186 in 2020). Females made up 29% (n = 60 of 209) of Aboriginal and Torres Strait Islander notifications occurring between 2010 and 2020. Between 2017 and 2020, 67% of notifications in females (n = 456 of 678) were diagnosed in low-caseload clinics, at least 13% (n = 87 of 678) of all female notifications were known to be pregnant at diagnosis, and there were 9 CS notifications. CONCLUSIONS: Cases of infectious syphilis in females of reproductive age and CS are on the rise in Victoria, necessitating sustained public health action. Increasing awareness among individuals and clinicians, and health system strengthening, particularly targeting primary care where most females are diagnosed before pregnancy, are required. Treating infections before or promptly during pregnancy and undertaking partner notification and treatment to reduce risk of reinfection are critical to reducing CS cases.

Intensive sampling of the umbra and penumbra improves clinically significant prostate cancer detection and reduces risk of grade group upgrading at radical prostatectomy.

PURPOSE: Our objective is to evaluate the clinically significant prostate cancer detection rate of overlapping and perilesional systematic biopsy cores and its impact on grade group (GG) concordance at prostatectomy. MATERIALS AND METHODS: Biopsy maps of those undergoing MRI-targeted (TB) and systematic biopsy (SB) were reviewed to reclassify systematic cores. Perilesional (PL) cores were defined as adjacent cores within 10 mm of the target lesion ("penumbra") whilst overlap (OL) cores were defined as cores within the ROI itself ("umbra"). All other cores were designated as distant cores (DC). The incremental csPCa detection rate (GG ≥ 2) and the rate of GG upgrading on prostatectomy as OL, PL and DC sequentially added to TB were determined. RESULTS: Out of the 398 patients included, the median number of OL and PL cores was 5 (IQR 4-7) and 5 (IQR 3-6) respectively. OL cores detected more csPCa than PL cores (31 vs 16%, p < 0.001). OL and PL cores improved the csPCa detection rate of TB from 34 to 39% (p < 0.001) and 37% (p = 0.001) respectively. TB+OL+PL had greater csPCa detection compared to just TB+OL (41 vs 39%, p = 0.016) and TB+PL (41 vs 37%, p < 0.001). Of the 104 patients who underwent prostatectomy, GG upgrading rate for TB+OL+PL was lower compared to TB (21 vs 36%, p < 0.001) and was not significantly different compared to TB+OL+PL+DC (21 vs 19%, p = 0.500). CONCLUSION: A biopsy strategy incorporating both intensive sampling of the umbra and penumbra improved csPCa detection and reduced risk of GG upgrading at prostatectomy.

Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

Natural immunity to SARS-CoV-2 and breakthrough infections in vaccinated and unvaccinated patients with cancer.

BACKGROUND: Consolidated evidence suggests spontaneous immunity from SARS-CoV-2 is not durable, leading to the risk of reinfection, especially in the context of newly emerging viral strains. In patients with cancer who survive COVID-19 prevalence and severity of SARS-CoV-2 reinfections are unknown. METHODS: We aimed to document natural history and outcome from SARS-CoV-2 reinfection in patients recruited to OnCovid (NCT04393974), an active European registry enrolling consecutive patients with a history of solid or haematologic malignancy diagnosed with COVID-19. RESULTS: As of December 2021, out of 3108 eligible participants, 1806 COVID-19 survivors were subsequently followed at participating institutions. Among them, 34 reinfections (1.9%) were reported after a median time of 152 days (range: 40-620) from the first COVID-19 diagnosis, and with a median observation period from the second infection of 115 days (95% CI: 27-196). Most of the first infections were diagnosed in 2020 (27, 79.4%), while most of reinfections in 2021 (25, 73.5%). Haematological malignancies were the most frequent primary tumour (12, 35%). Compared to first infections, second infections had lower prevalence of COVID-19 symptoms (52.9% vs 91.2%, P = 0.0008) and required less COVID-19-specific therapy (11.8% vs 50%, P = 0.0013). Overall, 11 patients (32.4%) and 3 (8.8%) were fully and partially vaccinated against SARS-CoV-2 before the second infection, respectively. The 14-day case fatality rate was 11.8%, with four death events, none of which among fully vaccinated patients. CONCLUSION: This study shows that reinfections in COVID-19 survivors with cancer are possible and more common in patients with haematological malignancies. Reinfections carry a 11% risk of mortality, which rises to 15% among unvaccinated patients, highlighting the importance of universal vaccination of patients with cancer.

Predicting perioperative outcomes of robot-assisted radical cystectomy: Data from the Asian Robot-Assisted Radical Cystectomy Consortium.

OBJECTIVES: To report the perioperative outcomes of robot-assisted radical cystectomy and elucidate their risk factors. METHODS: A review of the Asian Robot-Assisted Radical Cystectomy Consortium database from 2007 to 2020 was performed. The perioperative outcomes studied included complication rates, time to solid food intake, estimated blood loss, length of hospital stay, and 30-day readmission rates. RESULTS: Of 568 patients, the overall complication rate was 49.2%, comprising major complications in 15.6%. Preoperative hydronephrosis was associated with an increased risk of major complications (odds ratio 3.27, 95% confidence interval 1.48-7.26, P = 0.004) while neoadjuvant chemotherapy was protective (odds ratio 0.46, 95% confidence interval 0.25-0.84, P = 0.012). The median time to solid food intake was 4 days (interquartile range 3-7) and smoking was a risk factor (odds ratio 4.28, 95% confidence interval 2.36-7.79, P < 0.001) for prolonged time to solid food intake. Median length of hospital stay was 13 days (interquartile range 9-19), and diabetes mellitus (odds ratio 1.66, 95% confidence interval 1.08-2.56, P = 0.021), neoadjuvant chemotherapy (odds ratio 2.21, 95% confidence interval 1.46-3.33, P < 0.001), and orthotopic bladder substitute creation (odds ratio 2.82, 95% confidence interval 1.90-4.18, P < 0.001) were independent risk factors for prolonged length of hospital stay. The 30-day readmission rate was 23.4% and higher in those with bilateral hydronephrosis (odds ratio 4.58, 95% confidence interval 1.97-10.65, P < 0.001) and orthotopic bladder substitute creation (odds ratio 1.87, 95% confidence interval 1.16-3.02, P = 0.010). CONCLUSIONS: There are preoperative conditions which are significant risk factors for adverse perioperative outcomes in robot-assisted radical cystectomy. Most are potentially modifiable and can direct strategies to reduce surgical morbidity related to this major oncological procedure.

COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic.

The SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT-chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care.

COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study.

BACKGROUND: Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer. METHODS: In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission. FINDINGS: From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 [95% CI 6·56-10·02]; p<0·0001), being male (1·67 [1·19-2·34]; p=0·003), and the presence of other comorbidities such as hypertension (1·95 [1·36-2·80]; p<0·001) and cardiovascular disease (2·32 [1·47-3·64]). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 [0·81-1·72]; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks. INTERPRETATION: Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment. FUNDING: University of Birmingham, University of Oxford.

COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study.

BACKGROUND: Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK. METHODS: We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case-fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models. FINDINGS: 319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case-fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40-49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio [OR] 1·57, 95% CI 1·15-2·15; p<0·0043). Compared with the rest of the UKCCMP cohort, patients with leukaemia showed a significantly increased case-fatality rate (2·25, 1·13-4·57; p=0·023). After correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2·09, 95% CI 1·09-4·08; p=0·028). INTERPRETATION: Patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 infection and COVID-19 phenotypes. We generated individualised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk-benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies. FUNDING: University of Birmingham and University of Oxford.

Immune checkpoint blockade: releasing the breaks or a protective barrier to COVID-19 severe acute respiratory syndrome?

The rapid emergence of COVID-19 has sent shockwaves through healthcare systems globally, with cancer patients at increased risk. The interplay of the virus and host immune system has been implicated in the development of ARDS. Immunotherapy agents have the potential to adversely potentiate this phenomenon, requiring careful real-world observation.

Multiparametric MRI-ultrasonography software fusion prostate biopsy: initial results using a stereotactic robotic-assisted transperineal prostate biopsy platform comparing systematic vs targeted biopsy.

OBJECTIVE: To compare the detection rates of prostate cancer between systematic biopsy and targeted biopsy using a stereotactic robot-assisted transperineal prostate platform. MATERIALS AND METHODS: We identified consecutive patients with suspicious lesion(s) on multiparametric magnetic resonance imaging (mpMRI), who underwent both systematic and MRI-transrectal ultrasonography (US) fusion targeted biopsy using our proprietary transperineal robot-assisted prostate biopsy platform between January 2015 and January 2019 at our institution, for retrospective analysis. Comparative analysis was performed between systematic and targeted biopsy using McNemar's test, and the cohort was further stratified by prior biopsy status and Prostate Imaging Reporting and Data System (PI-RADS) v2.0 score. International Society of Urological Pathology (ISUP) grade group (GG) ≥2 cancers (previously known as Gleason grade ≥7) were considered to be clinically significant. RESULTS: A total of 500 patients were included in our final analysis, of whom 67 (13%) were patients with low-risk cancer on active surveillance. Of the 433 patients without prior diagnosis of cancer, 288 (67%) were biopsy-naïve. A total of 248 (57%) were diagnosed with prostate cancer, with 199 (46%) having clinically significant prostate cancer (ISUP GG ≥2). There were no statistically significant differences in the overall prostate cancer and clinically significant prostate cancer detection rate between systematic and targeted biopsy (51% vs 49% and 40% vs 38% respectively; P = 0.306 and P = 0.609). Of the 248 prostate cancers detected, 75% (187/248) were detected on both systematic and targeted biopsy, 14% (35/248) were detected on systematic biopsy alone and 11% (26/248) were detected on targeted biopsy alone. Of the 199 clinically significant cancers detected, 69% (138/199) were detected on both systematic and targeted biopsy, 17% (33/199) on systematic biopsy alone and 14% (28/199) on targeted biopsy alone. There were no statistically significant differences in the detection rate between systematic and targeted biopsy for both overall and clinically significant prostate cancer, even when the cohort was stratified by prior biopsy status and PI-RADS score. Targeted biopsy has greater sampling efficiency compared to systematic biopsy for both overall and clinically significant prostate cancer (23.2% vs 9.8%, P < 0.001 and 14.8% vs 5.6%, P < 0.001). CONCLUSIONS: Using our robot-assisted transperineal prostate platform, combined MRI-US targeted biopsy with concurrent systematic prostate systematic biopsy probably represents the optimal method for the detection of clinically significant prostate cancer.

Development of mussel-inspired 3D-printed poly (lactic acid) scaffold grafted with bone morphogenetic protein-2 for stimulating osteogenesis.

3D printing is a versatile technique widely applied in tissue engineering due to its ability to manufacture large quantities of scaffolds or constructs with various desired architectures. In this study, we demonstrated that poly (lactic acid) (PLA) scaffolds fabricated via fused deposition not only retained the original interconnected microporous architectures, the scaffolds also exhibited lower lactic acid dissolution as compared to the freeze-PLA scaffold. The 3D-printed scaffolds were then grafted with human bone morphogenetic protein-2 (BMP-2) via the actions of polydopamine (PDA) coatings. The loading and release rate of BMP-2 were monitored for a period of 35 days. Cellular behaviors and osteogenic activities of co-cultured human mesenchymal stem cells (hMSCs) were assessed to determine for efficacies of scaffolds. In addition, we demonstrated that our fabricated scaffolds were homogenously coated with PDA and well grafted with BMP-2 (219.1 ± 20.4 ng) when treated with 250 ng/mL of BMP-2 and 741.4 ± 127.3 ng when treated with 1000 ng/mL of BMP-2. This grafting enables BMP-2 to be released in a sustained profile. From the osteogenic assay, it was shown that the ALP activity and osteocalcin of hMSCs cultured on BMP-2/PDA/PLA were significantly higher when compared with PLA and PDA/PLA scaffolds. The methodology of PDA coating employed in this study can be used as a simple model to immobilize multiple growth factors onto different 3D-printed scaffold substrates. Therefore, there is potential for generation of scaffolds with different unique modifications with different capabilities in regulating physiochemical and biological properties for future applications in bone tissue engineering.

Low-risk non-muscle-invasive bladder cancer: Further prognostic stratification into the "very-low-risk" group based on tumor size.

OBJECTIVE: To validate the significance of the entity of "very-low-risk" bladder cancer by analyzing the clinical outcomes of low-risk bladder cancer when further stratified by tumor size. METHODS: We accessed our prospectively maintained, single-institution, electronic bladder cancer registry to extract the clinicopathological data of patients who were diagnosed with primary, solitary, Ta, low-grade tumors that were <3 cm. Patients were divided into two prognostic groups based on tumor size (≤1.0 cm vs >1.0 cm). The survival data of the two groups were compared for recurrence, progression and mortality. RESULTS: A total of 165 patients were followed up for a median period of 79 months (interquartile range 47-118 months). A total of 45% (75/165) of the study cohort had tumors that were ≤1.0 cm. Recurrences were found in 40% (66/165) of the study cohort. On Kaplan-Meier analysis, patients with tumor size ≤1.0 cm had significantly longer time to recurrence (P < 0.001, log-rank test). Using multivariate Cox modeling, only tumor size >1.0 cm was significantly associated with shorter time to recurrence (HR 2.54, 95% CI 1.35-4.77, P = 0.004). Tumor size was not significantly associated with any differences in time to overall progression, muscle-invasive progression or overall mortality (P = 0.108, P = 0.362 and P = 0.225, respectively, log-rank test). CONCLUSIONS: Low-risk bladder cancer can be further stratified based on tumor size. Larger tumors (>1.0 cm) are significantly associated with shorter time to recurrence compared with smaller tumors (≤1.0 cm). However, there were no significant differences in the probability of developing disease progression or overall mortality between larger and smaller tumors.

Evolving trends in the surgical management of renal masses over the past two decades: A contemporary picture from a large prospectively-maintained database.

OBJECTIVES: To investigate the trends in the presentation and surgical management of renal tumors at Singapore General Hospital, Singapore. METHODS: We accessed our uro-oncological registry to extract the clinicopathological data of patients with renal tumors who underwent nephrectomy from 2000 to 2015. Binary logistic regression was used to identify predictors of nephron-sparing surgery utilization, Clavien-Dindo grade ≥III complications and progression to stage ≥3 chronic kidney disease. Cox regression models were created to evaluate the proportional hazards of the risk factors for overall survival and cancer-specific survival. RESULTS: A total of 1208 cases of nephrectomy were carried out between 2000 and 2015. The proportion of cT1a tumors increased from 2000-2004 to 2010-2015, which was accompanied by the doubling of utilization rates of nephron-sparing surgery and minimally invasive surgery. Charlson Comorbidity Index score <2, asymptomatic presentation, clinical T1a tumors and having an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 were all independent predictors of nephron-sparing surgery utilization. Age, symptomatic presentation and nephron-sparing surgery utilization were all significantly associated with greater odds of having Clavien-Dindo grade ≥III complications, whereas minimally invasive surgery was associated with decreased risk. The utilization of partial nephrectomy and minimally invasive surgery was significantly associated with a decreased risk of developing postoperative stage ≥3 chronic kidney disease. Both overall survival and cancer-specific survival were not significantly affected by whether nephron-sparing surgery was utilized. CONCLUSIONS: There has been an increasing proportion of small renal masses diagnosed incidentally with a shift towards nephron-sparing surgery for clinically localized tumors. With the adoption of nephron-sparing surgery, progression to stage 3 chronic kidney disease has decreased, without any compromise in oncological and survival outcomes.

Effect of Strontium Substitution on the Physicochemical Properties and Bone Regeneration Potential of 3D Printed Calcium Silicate Scaffolds.

In this study, we synthesized strontium-contained calcium silicate (SrCS) powder and fabricated SrCS scaffolds with controlled precise structures using 3D printing techniques. SrCS scaffolds were shown to possess increased mechanical properties as compared to calcium silicate (CS) scaffolds. Our results showed that SrCS scaffolds had uniform interconnected macropores (~500 µm) with a compressive strength 2-times higher than that of CS scaffolds. The biological behaviors of SrCS scaffolds were assessed using the following characteristics: apatite-precipitating ability, cytocompatibility, proliferation, and osteogenic differentiation of human mesenchymal stem cells (MSCs). With CS scaffolds as controls, our results indicated that SrCS scaffolds demonstrated good apatite-forming bioactivity with sustained release of Si and Sr ions. The in vitro tests demonstrated that SrCS scaffolds possessed excellent biocompatibility which in turn stimulated adhesion, proliferation, and differentiation of MSCs. In addition, the SrCS scaffolds were able to enhance MSCs synthesis of osteoprotegerin (OPG) and suppress macrophage colony-stimulating factor (M-CSF) thus disrupting normal bone homeostasis which led to enhanced bone formation over bone resorption. Implanted SrCS scaffolds were able to promote new blood vessel growth and new bone regeneration within 4 weeks after implantation in critical-sized rabbit femur defects. Therefore, it was shown that 3D printed SrCS scaffolds with specific controllable structures can be fabricated and SrCS scaffolds had enhanced mechanical property and osteogenesis behavior which makes it a suitable potential candidate for bone regeneration.

Ccdc13 is a novel human centriolar satellite protein required for ciliogenesis and genome stability.

Here, we identify coiled-coil domain-containing protein 13 (Ccdc13) in a genome-wide RNA interference screen for regulators of genome stability. We establish that Ccdc13 is a newly identified centriolar satellite protein that interacts with PCM1, Cep290 and pericentrin and prevents the accumulation of DNA damage during mitotic transit. Depletion of Ccdc13 results in the loss of microtubule organisation in a manner similar to PCM1 and Cep290 depletion, although Ccdc13 is not required for satellite integrity. We show that microtubule regrowth is enhanced in Ccdc13-depleted cells, but slowed in cells that overexpress Ccdc13. Furthermore, in serum-starved cells, Ccdc13 localises to the basal body, is required for primary cilia formation and promotes the localisation of the ciliopathy protein BBS4 to both centriolar satellites and cilia. These data highlight the emerging link between DNA damage response factors, centriolar and peri-centriolar satellites and cilia-associated proteins and implicate Ccdc13 as a centriolar satellite protein that functions to promote both genome stability and cilia formation.

Long-term results of a randomized controlled trial of T2 versus T2-T3 ablation in endoscopic thoracic sympathectomy for palmar hyperhidrosis.

BACKGROUND: Despite good short-term results and patient satisfaction with endoscopic thoracic sympathectomy (ETS), there has been much debate on the level of sympathectomy for treatment of palmar hyperhidrosis (PH) in terms of long-term clinical outcomes. OBJECTIVE: The aim of the study was to analyze the long-term recurrence and compensatory hyperhidrosis (CH) rates of ETS, comparing single-level T2 against multi-level T2-T3 ablation in single patients. METHODS: Patients who had undergone treatment for PH with unilateral T2 and contralateral T2-T3 ablation in ETS were retrospectively reviewed. They were subjected to telephone interview using standardized set of interview script and questionnaire with a scoring system similar to hyperhidrosis disease severity scale. All patients were evaluated for comparison of symptom resolution, site and severity of CH, and satisfaction rates. To compare between T2 and T2-T3, the level of sympathectomy on one side is matched to the ipsilateral recurrence of PH and CH occurrence. RESULTS: Twenty-two patients with a mean age of 36.5 years could be reached. The mean follow-up was 8 years (range 38-153 months). The global recurrence rate for PH is 18%. CH was observed in 20 (91%) patients, and trunk compensation was the most common (18/22-82%), followed by lower limb (14/22-64%) and axilla (10/22-45%). Overall, 72.8% (16) of the patients were satisfied with the operation. Among the six patients who were not satisfied, two patients reported recurrence of symptoms, while four patients experienced some form of compensation. There was no absolute difference in the severity of sweating bilaterally for patients who reported recurrence of PH. The site and severity of CH were also bilaterally symmetrical for all patients. CONCLUSION: There was no difference in recurrence rates and CH between single-level (T2) and multi-level (T2-T3) ETSs in the long term.