Efficacy and safety of glucocorticoids in the treatment of COVID-19: a systematic review and meta-analysis of RCTs.

In the realm of acute respiratory infections, coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a global public health challenge. The application of corticosteroids (CSs) in COVID-19 remains a contentious topic among researchers. Accordingly, our team performed a comprehensive meta-analysis of randomized controlled trials (RCTs) to meticulously evaluate the safety and efficacy of CSs in hospitalized COVID-19 patients. To explore efficacy of CSs in the treatment of COVID-19 patients, we meticulously screened RCTs across key databases, including PubMed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, as well as China's CNKI and Wanfang Data. We focused on assessing the 28 days mortality rates. We evaluated the data heterogeneity using the Chi-square test and I2 values, setting significance at 0.1 and 50%. Data from 21 RCTs involving 5721 participants were analyzed. The analysis did not demonstrate a significant association between CSs intervention and the 28 days mortality risk in hospitalized COVID-19 patients (relative risk [RR] = 0.93; 95% confidence interval [95% CI]: 0.84-1.03; P = 0.15). However, subgroup analysis revealed a significant reduction in 28 days mortality among patients with moderate-to-severe COVID-19 (RR at 0.85; 95% CI: 0.76-0.95; P = 0.004). Specifically, short-term CS administration (≤ 3 days) was associated with a substantial improvement in clinical outcomes (RR = 0.24; 95% CI: 0.09-0.63; P = 0.004), as was longer-term use (≥ 8 days) (RR = 0.88; 95% CI: 0.77-0.99; P = 0.04). Additionally, in patients with moderate-to-severe COVID-19, the administration of dexamethasone increased the number of 28 days ventilator-free days (Mean Difference = 1.92; 95% CI: 0.44-3.40; P = 0.01). Methylprednisolone also demonstrated significant benefits in improving clinical outcomes (RR = 0.24; 95% CI: 0.09-0.63; P = 0.004). Our meta-analysis demonstrated that although there is no significant difference in 28 days mortality rates among hospitalized COVID-19 patients, the use of CSs may be beneficial in improving clinical outcomes in moderate or severe COVID-19 patients. There was no significant increase in the occurrence of adverse events associated with the use of CSs. Our meta-analysis provides evidence that while CSs may not be suitable for all COVID-19 patients, they could be effective and safe in severely ill COVID-19 patients. Consequently, it is recommended to administer CSs for personalized treatments in COVID-19 cases to improve the clinical outcomes while minimizing adverse events.

Comprehensive Collection of Whole-Slide Images and Genomic Profiles for Patients with Bladder Cancer.

Bladder cancer is one of the leading causes of cancer-related mortality in the urinary system. Understanding genomic information is important in the treatment and prognosis of bladder cancer, but the current method used to identify mutations is time-consuming and labor-intensive. There are now many novel and convenient ways to predict cancerous genomics from pathological slides. However, the publicly available datasets are limited, especially for Asian populations. In this study, we developed a dataset consisting of 75 Asian cases of bladder cancers and 112 Whole-Slide Images with one to two images obtained for each patient. This dataset provides information on the most frequently and clinically significant mutated genes derived by whole-exome sequencing in these patients. This dataset will facilitate exploration and development of novel diagnostic and therapeutic technologies for bladder cancer.

Alterations of lung microbiota in lung transplant recipients with pneumocystis jirovecii pneumonia.

BACKGROUND: Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow. METHODS: In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables. RESULTS: BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3+CD45+, CD3+CD4+ and CD3+CD8+ T cells were deeply implicated in the alterations of lung microbiota in LTRs. CONCLUSIONS: This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.

Prediction and related genes of cancer distant metastasis based on deep learning.

Cancer metastasis is one of the main causes of cancer progression and difficulty in treatment. Genes play a key role in the process of cancer metastasis, as they can influence tumor cell invasiveness, migration ability and fitness. At the same time, there is heterogeneity in the organs of cancer metastasis. Breast cancer, prostate cancer, etc. tend to metastasize in the bone. Previous studies have pointed out that the occurrence of metastasis is closely related to which tissue is transferred to and genes. In this paper, we identified genes associated with cancer metastasis to different tissues based on LASSO and Pearson correlation coefficients. In total, we identified 45 genes associated with bone metastases, 89 genes associated with lung metastases, and 86 genes associated with liver metastases. Through the expression of these genes, we propose a CNN-based model to predict the occurrence of metastasis. We call this method MDCNN, which introduces a modulation mechanism that allows the weights of convolution kernels to be adjusted at different positions and feature maps, thereby adaptively changing the convolution operation at different positions. Experiments have proved that MDCNN has achieved satisfactory prediction accuracy in bone metastasis, lung metastasis and liver metastasis, and is better than other 4 methods of the same kind. We performed enrichment analysis and immune infiltration analysis on bone metastasis-related genes, and found multiple pathways and GO terms related to bone metastasis, and found that the abundance of macrophages and monocytes was the highest in patients with bone metastasis.

Surgical resection of soft tissue metastasis in cancers: A single-center study of 77 cases over a 7-year period.

INTRODUCTION: Soft tissue metastasis (STM) of cancers, encompassing skeletal muscle and subcutaneous tissue metastasis, is less common due to unique homeostatic conditions. With longer life expectancy and the advent of new imaging modalities, clinical physicians will increasingly encounter and manage such cases. This study retrospectively reviewed cases of STM in visceral cancers who underwent surgery at Fudan University Shanghai Cancer Center over a 7-year period. METHODS: Data were collected through a comprehensive review of medical records, including demographic variables, primary tumor characteristics, surgical data, tumor pathology, and outcomes. Survival analysis was performed using Kaplan-Meier curves. RESULTS: The study included 77 cases with a median follow-up period of 854 days. The most common primary tumor sites were the lung (11) and breast (10). The abdominal wall was the most frequent site of metastasis. The combination of visceral metastasis, age over 52 years, and a history of primary tumor correlates with a poorer prognosis. Surgical-related metastases are associated with a higher degree of differentiation. Additionally, we have identified a better prognosis for patients with cancer of unknown primary (CUP) exhibiting potential resectable soft tissue metastases. CONCLUSION: The combination of visceral metastasis, age over 52 years, and a history of primary tumor suggest a poorer prognosis. While no significant impact on survival was observed for patients with lymph node metastasis. Surgical-related metastases are associated with a higher degree of differentiation. CUP patients with potentially resectable soft tissue metastases should be considered for surgical intervention.

Differentiation between lung allograft rejection and infection using donor-derived cell-free DNA and pathogen detection by metagenomic next-generation sequencing.

Background: In lung transplant recipients (LTRs), the primary causes of mortality are rejection and infection, which often present similar symptoms, making differentiation challenging. This study aimed to explore the diagnostic efficacy of plasma donor-derived cell-free DNA (dd-cfDNA) in conjunction with metagenomic next-generation sequencing (mNGS) for pathogen detection in differentiation between lung allograft rejection and infection in LTRs experiencing new-onset pulmonary complications. Methods: We conducted a retrospective study on 188 LTRs who underwent lung or heart-lung transplantation at our institution from 2015 to 2021. The LTRs were categorized into three groups: stable, rejection, and infection. We measured plasma dd-cfDNA levels and utilized both mNGS and culture methods to identify pathogens in the bronchoalveolar lavage fluid (BALF). Results: The rejection group exhibited the highest levels of plasma dd-cfDNA (median 1.34 %, interquartile range [IQR] 1.06-2.19 %) compared to the infection group (median 0.72 %, IQR 0.62-1.07 %) and the stable group (median 0.69 %, IQR 0.58-0.78 %) (both p < 0.001). Within the infection group, a significantly higher level of dd-cfDNA was observed in the cytomegalovirus infection subgroup (p < 0.001), but not in the fungal (p > 0.05) or bacterial infection subgroups (p > 0.05), when compared to the stable group. Elevated dd-cfDNA levels, in combination with negative mNGS results, strongly indicated lung allograft rejection, with a positive predictive value and negative predictive value of 88.7 % and 99.2 %, respectively. Conclusions: Plasma dd-cfDNA in combination with BALF pathogen detection by mNGS shows satisfactory accuracy in differentiating lung allograft rejection from infectious complications.

FGFR3 mutation characterization identifies prognostic and immune-related gene signatures in bladder cancer.

BACKGROUND: Immunotherapy and FGFR3-targeted therapy play an important role in the management of locally advanced and metastatic bladder cancer (BLCA). Previous studies indicated that FGFR3 mutation (mFGFR3) may be involved in the alterations of immune infiltration, which may affect the priority or combination of these two treatment regimes. However, the specific impact of mFGFR3 on the immunity and how FGFR3 regulates the immune response in BLCA to affect prognosis remain unclear. In this study, we aimed to elucidate the immune landscape associated with mFGFR3 status in BLCA, screen immune-related gene signatures with prognostic value, and construct and validate a prognostic model. METHODS: ESTIMATE and TIMER were used to assess the immune infiltration within tumors in the TCGA BLCA cohort based on transcriptome data. Further, the mFGFR3 status and mRNA expression profiles were analyzed to identify immune-related genes that were differentially expressed between patients with BLCA with wild-type FGFR3 or mFGFR3 in the TCGA training cohort. An FGFR3-related immune prognostic score (FIPS) model was established in the TCGA training cohort. Furthermore, we validated the prognostic value of FIPS with microarray data in the GEO database and tissue microarray from our center. Multiple fluorescence immunohistochemical analysis was performed to confirm the relationship between FIPS and immune infiltration. RESULTS: mFGFR3 resulted in differential immunity in BLCA. In total, 359 immune-related biological processes were enriched in the wild-type FGFR3 group, whereas none were enriched in the mFGFR3 group. FIPS could effectively distinguish high-risk patients with poor prognosis from low-risk patients. The high-risk group was characterized by a higher abundance of neutrophils; macrophages; and follicular helper, CD4, and CD8 T-cells than the low-risk group. In addition, the high-risk group exhibited higher expression of PD-L1, PD-1, CTLA-4, LAG-3, and TIM-3 than the low-risk group, indicating an immune-infiltrated but functionally suppressed immune microenvironment. Furthermore, patients in the high-risk group exhibited a lower mutation rate of FGFR3 than those in the low-risk group. CONCLUSIONS: FIPS effectively predicted survival in BLCA. Patients with different FIPS exhibited diverse immune infiltration and mFGFR3 status. FIPS might be a promising tool for selecting targeted therapy and immunotherapy for patients with BLCA.

Comparison of pneumonitis risk between immunotherapy alone and in combination with chemotherapy: an observational, retrospective pharmacovigilance study.

Importance: Checkpoint inhibitor pneumonitis (CIP) is a rare but serious adverse event that may impact treatment decisions. However, there is limited information comparing CIP risks between immune checkpoint inhibitor (ICI) monotherapy and combination with chemotherapy due to a lack of direct cross-comparison in clinical trials. Objective: To determine whether ICI combination with chemotherapy is superior to ICI in other drug regimens (including monotherapy) in terms of CIP risk. Study Design and Methods: This observational, cross-sectional and worldwide pharmacovigilance cohort study included patients who developed CIP from the World Health Organization database (WHO) VigiBase and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Individual case safety reports (ICSR) were extracted from 2015 to 2020 in FAERS and from 1967 to 2020 in VigiBase. Timing and reporting odds ratio (ROR) of CIP in different treatment strategies were used to detect time-to-onset and the risk of pneumonitis after different immunotherapy regimens. Results: A total of 93,623 and 114,704 ICI-associated ICSRs were included in this study from VigiBase and FAERS databases respectively. 3450 (3.69%) and 3278 (2.86%) CIPs occurred after therapy initiation with a median of 62 days (VigiBase) and 40 days (FAERS). Among all the CIPs, 274 (7.9%) and 537 (16.4%) CIPs were associated with combination therapies. ICIs plus chemotherapy combination was associated with pneumonitis in both VigiBase [ROR 1.35, 95% CI 1.18-1.52] and FAERS [ROR 1.39, 95% CI 1.27-1.53]. The combination of anti-PD-1 antibodies and anti-CTLA-4 antibodies with chemotherapy demonstrated an association with pneumonitis in both VigiBase [PD-1+chemotherapy: 1.76, 95% CI 1.52-2.05; CTLA-4+chemotherapy: 2.36, 95% CI 1.67-3.35] and FAERS [PD-1+chemotherapy: 1.70, 95% CI 1.52-1.91; CTLA-4+chemotherapy: 1.70, 95% CI 1.31-2.20]. Anti-PD-L1 antibodies plus chemotherapy combinations did not show the association. Conclusion: Compared to ICI in other drug regimens (including monotherapy), the combination of ICI plus chemotherapy is significantly associated with higher pneumonitis toxicity. Anti-PD-1/CTLA4 medications in combination with chemotherapy should be obviated in patients with potential risk factors for CIP. Trial Registration: clinicaltrials.gov, ChiCTR2200059067.

Histopathological bladder cancer gene mutation prediction with hierarchical deep multiple-instance learning.

Gene mutation detection is usually carried out by molecular biological methods, which is expensive and has a long-time cycle. In contrast, pathological images are ubiquitous. If clinically significant gene mutations can be predicted only through pathological images, it will greatly promote the widespread use of gene mutation detection in clinical practice. However, current gene mutation prediction methods based on pathological images are ineffective because of the inability to identify mutated regions in gigapixel Whole Slide Image (WSI). To address this challenge, hereby we propose a carefully designed framework for WSI-based gene mutation prediction, which consists of three parts. (i) The first part of cancerous area segmentation, based on supervised learning, quickly filters out a large number of non-mutated regions; (ii) the second part of cancerous patch clustering, based on the representations derived from contrastive learning, ensures the comprehensiveness of patch selection; and (iii) the third part of mutation classification, based on the proposed hierarchical deep multi-instance learning method (HDMIL), ensures that sufficient patches are considered and inaccurate selections are ignored. In addition, benefiting from a two-stage attention mechanism in HDMIL, the patches that are highly correlated with gene mutations can be identified. This interpretability can help a pathologist to analyze the correlation between gene mutation and histopathological morphology. Experimental results demonstrate that the proposed gene mutation prediction framework significantly outperforms the state-of-the-art methods. In the TCGA bladder cancer dataset, five clinically relevant gene mutations are well predicted.

Unitary p-wave interactions between fermions in an optical lattice.

Exchange-antisymmetric pair wavefunctions in fermionic systems can give rise to unconventional superconductors and superfluids1-3. The realization of these states in controllable quantum systems, such as ultracold gases, could enable new types of quantum simulations4-8, topological quantum gates9-11 and exotic few-body states12-15. However, p-wave and other antisymmetric interactions are weak in naturally occurring systems16,17, and their enhancement via Feshbach resonances in ultracold systems has been limited by three-body loss18-24. Here we create isolated pairs of spin-polarized fermionic atoms in a multiorbital three-dimensional optical lattice. We spectroscopically measure elastic p-wave interaction energies of strongly interacting pairs of atoms near a magnetic Feshbach resonance. The interaction strengths are widely tunable by the magnetic field and confinement strength, and yet collapse onto a universal curve when rescaled by the harmonic energy and length scales of a single lattice site. The absence of three-body processes enables the observation of elastic unitary p-wave interactions, as well as coherent oscillations between free-atom and interacting-pair states. All observations are compared both to an exact solution using a p-wave pseudopotential and to numerical solutions using an ab initio interaction potential. The understanding and control of on-site p-wave interactions provides a necessary component for the assembly of multiorbital lattice models25,26 and a starting point for investigations of how to protect such systems from three-body recombination in the presence of tunnelling, for instance using Pauli blocking and lattice engineering27,28.

Cardiovascular outcomes in obstructive sleep apnoea and implications of clinical phenotyping on effect of CPAP treatment.

BACKGROUND: There is a growing awareness of the heterogeneity of obstructive sleep apnoea (OSA). Clinical trials of CPAP treatment on cardiovascular protection have been mostly negative. We aimed to assess the association between polysomnographic parameters and incident major adverse cardiovascular events (MACEs), and to investigate if the CPAP effect could be better delineated among clinical subgroups. METHODS: This sleep cohort study was conducted using a clinical database and territory-wide electronic health administration data in Hong Kong. Cox regressions were used to calculate HRs. Latent class analysis was used to cluster patients with OSA according to clinical and polysomnographic features. RESULTS: Of 1860 eligible Chinese subjects who underwent polysomnography (2006-2013), 1544 (83%) had OSA. Over median follow-up of 8.3 years, 278 (14.9%) experienced MACEs. Apnoea-hypopnoea index (AHI) did not predict MACEs (HR: 0.95; 95% CI 0.76 to 1.17), whereas sleep time with oxygen saturation <90% (TST90) (HR: 1.41; 95% CI 1.10 to 1.81) was an independent predictor of MACEs, as were wake and nocturnal heart rate. In moderate-severe OSA (n=1108) who were indicated for CPAP treatment, regular CPAP was not associated with reduction of incident MACEs. Further cluster analysis identified a subgroup (n=333) who was younger, more obese, had more severe OSA (higher AHI and TST90) and more cardiovascular risks, in whom regular CPAP was associated with a lower risk of MACEs (HR:0.49, 95% CI 0.25 to 0.95). CONCLUSIONS: OSA-related TST90 and mean heart rate, but not AHI, were robust predictors of MACEs. A clinical phenotype subgroup who demonstrated beneficial effect of CPAP treatment was identified.

Gut-derived fungemia due to Kodamaea ohmeri combined with invasive pulmonary aspergillosis: a case report.

BACKGROUND: Kodamaea ohmeri is a rare pathogen with high mortality and is found among blood samples in a considerable proportion; however, gastrointestinal infection of K. ohmeri is extremely rare. Invasive pulmonary aspergillosis is also an uncommon fungal; these two fungal infections reported concomitantly are unprecedented. CASE PRESENTATION: We described a case of a 37-year-old male who got infected with K. ohmeri and invasive pulmonary aspergillosis. We used the mass spectrometry and histopathology to identify these two fungal infections separately. For the treatment of K. ohmeri, we chose caspofungin. As for invasive pulmonary aspergillosis, we used voriconazole, amphotericin B, and then surgery. The patient was treated successfully through the collaboration of multiple disciplines. CONCLUSIONS: We speculate that the destruction of the intestinal mucosa barrier can make the intestine one of the ways for certain fungi to infect the human body.

A rapid and durable response to cabozantinib in an osimertinib-resistant lung cancer patient with MET D1228N mutation: a case report.

Osimertinib has efficacy superior to that of standard epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for the first-line treatment of patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, patients treated with osimertinib eventually acquire drug resistance. MET missense mutations have been demonstrated to mediate resistance to MET-TKIs, such as crizotinib. But the role of MET missense mutations in mediating EGFR TKI resistance is undefined. With the increasing use of next-generation sequencing (NGS) at diagnosis, many mechanisms of acquired resistance have been discovered in patients with activated tyrosine kinase receptors. Herein, we report the first case of MET D1228N mutation mediating acquired resistance to osimertinib in a MET TKI-naïve NSCLC. The patient with advanced lung adenocarcinoma harboring EGFR exon 19 deletion initially responded to osimertinib with progression-free survival (PFS) lasting 11 months and then developed resistance with an acquired mutation of MET D1228N. Subsequently, combination therapy of cabozantinib and osimertinib was administrated to the patient, and her clinical symptoms were rapidly relieved within one week with good tolerance. She remained on the combined treatment for 10 months. Finally, she achieved an overall survival (OS) of 25 months. Based on our findings, patient with MET D1228N mutant lung adenocarcinoma clinically benefited from combinatorial therapy of cabozantinib and osimertinib after osimertinib resistance.

Detecting ALK Rearrangement with RT-PCR: A Reliable Approach Compared with Next-Generation Sequencing in Patients with NSCLC.

BACKGROUND: Precise detection of anaplastic lymphoma kinase (ALK) rearrangement guides the application of ALK-targeted tyrosine kinase inhibitors (ALK-TKIs) in patients with non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS) has been widely used in clinics, but DNA-based NGS used to detect fusion genes has delivered false-negative results. However, fusion genes can be successfully detected at the transcription level and with higher sensitivity using RNA-based reverse transcription polymerase chain reaction (RT-PCR). OBJECTIVE: This study compared the performance of RT-PCR and NGS in the detection of echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion in Chinese patients with NSCLC. METHODS: Formalin-fixed paraffin-embedded tissues from 153 patients who were pathologically diagnosed as having NSCLC were collected from November 2017 to October 2019. Both DNA/RNA-based NGS and RNA-based RT-PCR were used to detect EML4-ALK fusion. For samples with discordant ALK status results, fluorescence in situ hybridization (FISH) or Sanger sequencing was used to further confirm the ALK status. RESULTS: In total, 124 samples were successfully analyzed using both NGS and RT-PCR. For 118 samples, results were consistent between NGS and RT-PCR, with 25 reported as ALK fusion positive and 93 as ALK fusion negative, achieving a concordance rate of 95.16%. Among the six samples with disconcordant results, five were positive using RT-PCR but negative using NGS, and one was positive using NGS but negative using RT-PCR. Four of six cases with disconcordant results (three RT-PCR positive and one NGS positive) were successfully validated using either FISH or Sanger sequencing. CONCLUSIONS: Compared with NGS, RT-PCR appears to be a reliable method of detecting EML4-ALK fusion in patients with NSCLC.

Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes.

Background: Of patients with upper urinary tract urothelial carcinoma (UTUC), 22-47% developed bladder recurrence after radical nephroureterectomy. Furthermore, the effect of surgery for UTUC-bladder cancer (BC) has not been well validated. The aim of this study was to assess the impact of standard primary BC surgical strategy on survival of patients diagnosed with UTUC-BC. Patients and Methods: A total of 676 UTUC-BC patients and 197,753 primary BC patients diagnosed from 2004 to 2016, were identified based on the SEER database. The Kaplan-Meier method and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). Multivariate Cox regression model and competing risks regression model were used to identify independent risk factors. Propensity score matching (PSM) was also performed to adjust potential confounding factors. Results: The baseline characteristics and survival outcomes of the two BC patient cohorts are quite different. For UTUC-BC patients, no significant difference in OS (NMIBC: p = 0.88; MIBC: p = 0.98) or cumulative incidence of CSM (NMIBC: p = 0.12; MIBC: p = 0.96) were noted for various surgical procedures. Local tumor treatment and partial cystectomy for UTUC-NMIBC patients produced lower 1-year (6.1%) and 3-year CSM (16.2%). Radical cystectomy for UTUC-MIBC patients produced lower 1-year (11.8%) but higher 3-year CSM (62.7%). After PSM for covariates, UTUC-BC patients still had a worse prognosis after surgery compared with primary BC patients. Based on regression models, older age, advanced T stage, N positive disease, M positive disease, and shorter interval between UTUC and BC were identified as independent risk factors for UTUC-BC patients. Conclusion: Standard primary BC surgical strategy did not provide significant survival benefit for UTUC-BC patients. Compared with primary BC patients, UTUC-BC patients had a worse prognosis after surgery, suggesting that current primary BC surgical guidelines are not entirely appropriate for UTUC-BC patients. Our findings underscore the continued importance and need for better prognosis and improved guidelines for management of UTUC-BC patients.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study.

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Comparison of different lymph node staging schemes in prostate cancer patients with lymph node metastasis.

PURPOSE: In addition to standard TNM N staging, lymph node ratio (LNR) and log odds of metastatic lymph node (LODDS) staging methods have been developed for cancer staging. We compared the prognostic performance of the total number of lymph nodes examined (TNLE), number of metastatic lymph node (NMLN), LNR, and LODDS in prostate cancer. METHODS: Data from 1400 patients diagnosed with prostate cancer between 2004 and 2009 who underwent lymphadenectomy were extracted from the Surveillance Epidemiology and End Results database. Kaplan-Meier methods and multivariable Cox regression analysis were used to evaluate the prognostic value of different lymph node staging schemes in patients with lymph node metastasis. RESULTS: Univariate analysis showed that age, T stage, radiotherapy history, Gleason score, LNR classification, LODDS classification, and NMLN except TNLE classification were significant prognostic factors for overall survival. In multivariate analysis, LNR classification, LODDS classification, and NMLN but TNLE classification remained significant prognostic factors for overall survival. LNR classification had the highest C-index (0.672; 95% confidence interval [CI]: 0.609-0.734) and the lowest Akaike information criterion (AIC) (4057.018), indicating the best prognostic performance. Scatter plots showed that LODDS increased with increasing LNR, exhibiting a strong overall correlation between these two lymph node staging methods (r2 = 0.9072). LNR and LODDS generally increased with increasing NMLN, although the correlation was relatively low. CONCLUSION: Our results indicate that LNR and LODDS may be better predictors of overall survival than the AJCC/UICC N category in patients undergoing curative surgery for prostate cancer.

Conductivity Spectrum of Ultracold Atoms in an Optical Lattice.

We measure the conductivity of neutral fermions in a cubic optical lattice. Using in situ fluorescence microscopy, we observe the alternating current resultant from a single-frequency uniform force applied by displacement of a weak harmonic trapping potential. In the linear response regime, a neutral-particle analog of Ohm's law gives the conductivity as the ratio of total current to force. For various lattice depths, temperatures, interaction strengths, and fillings, we measure both real and imaginary conductivity, up to a frequency sufficient to capture the transport dynamics within the lowest band. The spectral width of the real conductivity reveals the current dissipation rate in the lattice, and the integrated spectral weight is related to thermodynamic properties of the system through a sum rule. The global conductivity decreases with increased band-averaged effective mass, which at high temperatures approaches a T-linear regime. Relaxation of current is observed to require a finite lattice depth, which breaks Galilean invariance and enables damping through collisions between fermions.

Log Odds Could Better Predict Survival in Muscle-Invasive Bladder Cancer Patients Compared with pN and Lymph Node Ratio.

Background: The aim of this study was to assess the prognostic value of lymph node-associated variables, pN, lymph node ratio (LNR) and log odds (LODDS), in patients with bladder cancer. Methods: In the discovery cohort, 3358 patients with muscle-invasive bladder cancer (MIBC) and treated with radical cystectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 173 patients with MIBC who underwent radical cystectomy at Shanghai Cancer Center between 2010 and 2013 were enrolled in the validation cohort. LNR and LODDS were calculated in two cohorts and prognostic value was compared between these two variables. Results: In the two cohorts, survival differences between LODDS, LNR and pN (from the 7th AJCC TNM system) cohorts were statistically significant. Univariate and multivariate analyses confirmed that LNR and LODDS were independent prognostic factors and LODDS was better at predicting prognosis than pN and LNR for patients with MIBC. Moreover, LODDS had a better discriminative ability and model fit, proven by the highest Harrell's concordance index and lowest AIC among the three variables. Furthermore, scatter plots of pN, LNR and LODDS revealed that several groups of LNR and pN were heterogeneous and could be better stratified by LODDS in terms of prognosis estimation. Conclusion: LODDS has significant prognostic value for patients with MIBC. Moreover, LODDS is better at predicting prognosis for MIBC patients compared with pN and LNR.

Prognosis of Patients With Testicular Carcinoma Is Dependent on Metastatic Site.

Background: Existing data on the association of metastatic sites and prognosis of patients with metastatic testicular malignancy are limited. In this study, the association of survival outcome and the prognostic value of different metastatic sites in patients with metastatic testicular cancer was investigated. Methods: A dataset from the Surveillance, Epidemiology and End Results (SEER) survey was selected for a retrospective metastatic testicular cancer cohort study. Patients with different metastatic sites were divided into corresponding groups for further analysis. Kaplan-Meier analysis with log-rank test was implemented for comparison of the survival distribution of cases. Multivariate Cox regression models were then applied to analyze the association of distant metastases with survival for all selected patients and subgroup based on different histological type with a single metastatic site. Results: A total of 1,661 patients treated for metastatic testicular malignant tumors between 2010 to 2016 were enrolled in this cohort study. Upon initial diagnosis, 61.9, 15.2, 6.7, 6.4, and 36.2% of patients were found to have lung, liver, bone, brain, and distant lymph nodes metastatic sites, respectively. Patients with lung, liver, or bone metastases showed more undesirable prognosis for overall survival (OS) and cancer-specific survival (CSS), in contrast with those with distant lymph node metastases (all P < 0.05). In comparison with patients with more than one metastatic site, those with a single metastasis had extended OS and CSS (both P < 0.001). In patients with a single metastatic site, Kaplan-Meier analysis and multivariate Cox regression demonstrated the association of bone and liver with the worst two groups of OS and CSS. Multivariate Cox models based on histological type showed different prognostic values of metastases in patients with seminoma or non-seminomatous germ cell tumors. Conclusion: There is much heterogeneity in the oncological outcome of site-specific metastatic patients. Metastatic profiles and the prognostic value of metastases are dependent on the histological type in TC patients. Distant lymph nodes and lung metastases indicate favorable prognostic factors, while bone and liver metastases indicate negative survival outcomes in TC.