Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.

A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors.

Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice.

A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens.

Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination.

Feedback inhibition of humoral immunity by antibodies was first documented in 19091. Subsequent studies showed that, depending on the context, antibodies can enhance or inhibit immune responses2,3. However, little is known about how pre-existing antibodies influence the development of memory B cells. Here we examined the memory B cell response in individuals who received two high-affinity anti-SARS-CoV-2 monoclonal antibodies and subsequently two doses of an mRNA vaccine4-8. We found that the recipients of the monoclonal antibodies produced antigen-binding and neutralizing titres that were only fractionally lower compared than in control individuals. However, the memory B cells of the individuals who received the monoclonal antibodies differed from those of control individuals in that they predominantly expressed low-affinity IgM antibodies that carried small numbers of somatic mutations and showed altered receptor binding domain (RBD) target specificity, consistent with epitope masking. Moreover, only 1 out of 77 anti-RBD memory antibodies tested neutralized the virus. The mechanism underlying these findings was examined in experiments in mice that showed that germinal centres formed in the presence of the same antibodies were dominated by low-affinity B cells. Our results indicate that pre-existing high-affinity antibodies bias germinal centre and memory B cell selection through two distinct mechanisms: (1) by lowering the activation threshold for B cells, thereby permitting abundant lower-affinity clones to participate in the immune response; and (2) through direct masking of their cognate epitopes. This may in part explain the shifting target profile of memory antibodies elicited by booster vaccinations9.

Domain-wall dynamics in Bose-Einstein condensates with synthetic gauge fields.

Interactions in many-body physical systems, from condensed matter to high-energy physics, lead to the emergence of exotic particles. Examples are mesons in quantum chromodynamics and composite fermions in fractional quantum Hall systems, which arise from the dynamical coupling between matter and gauge fields1,2. The challenge of understanding the complexity of matter-gauge interaction can be aided by quantum simulations, for which ultracold atoms offer a versatile platform via the creation of artificial gauge fields. An important step towards simulating the physics of exotic emergent particles is the synthesis of artificial gauge fields whose state depends dynamically on the presence of matter. Here we demonstrate deterministic formation of domain walls in a stable Bose-Einstein condensate with a gauge field that is determined by the atomic density. The density-dependent gauge field is created by simultaneous modulations of an optical lattice potential and interatomic interactions, and results in domains of atoms condensed into two different momenta. Modelling the domain walls as elementary excitations, we find that the domain walls respond to synthetic electric field with a charge-to-mass ratio larger than and opposite to that of the bare atoms. Our work offers promising prospects to simulate the dynamics and interactions of previously undescribed excitations in quantum systems with dynamical gauge fields.

Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost.

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1-3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

Transition from an atomic to a molecular Bose-Einstein condensate.

Molecular quantum gases (that is, ultracold and dense molecular gases) have many potential applications, including quantum control of chemical reactions, precision measurements, quantum simulation and quantum information processing1-3. For molecules, to reach the quantum regime usually requires efficient cooling at high densities, which is frequently hindered by fast inelastic collisions that heat and deplete the population of molecules4,5. Here we report the preparation of two-dimensional Bose-Einstein condensates (BECs) of spinning molecules by inducing pairing interactions in an atomic condensate near a g-wave Feshbach resonance6. The trap geometry and the low temperature of the molecules help to reduce inelastic loss, ensuring thermal equilibrium. From the equation-of-state measurement, we determine the molecular scattering length to be + 220(±30) Bohr radii (95% confidence interval). We also investigate the unpairing dynamics in the strong coupling regime and find that near the Feshbach resonance the dynamical timescale is consistent with the unitarity limit. Our work demonstrates the long-sought transition between atomic and molecular condensates, the bosonic analogue of the crossover from a BEC to a Bardeen-Cooper-Schrieffer (BCS) superfluid in a Fermi gas7-9. In addition, our experiment may shed light on condensed pairs with orbital angular momentum, where a novel anisotropic superfluid with non-zero surface current is predicted10,11, such as the A phase of 3He.

Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.

Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD+ depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD+ levels with NAD+ or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention.

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.

Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor-based combination therapy.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)-associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor-based combination therapy (PCT). METHODS: HPV status was assessed using quantitative polymerase chain reaction in 87 patients with advanced PSCC treated with PCT. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in the HPV+ and HPV- groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC. RESULTS: Among patients receiving first-line PCT, ORR (91.7% vs. 64.6%, p = .014) and DCR (100.0% vs. 79.2%, p = .025) in the HPV+ group were higher compared to the HPV- group. Kaplan-Meier curves demonstrated that the HPV+ group exhibited superior PFS (p = .005) and OS (p = .004) for patients in the first-line setting. However, these advantages of HPV infection were not observed in multi-line PCT (p > .050). HPV status remained an independent prognostic factor for predicting better ORR (p = .024), PFS (p = .002), and OS (p = .020) in the multivariate analyses. Landmark analyses showed that the HPV-induced superiority of PFS occurred at an early stage (within 3 months) and OS occurred at a relatively late stage (within 9 months). Bioinformatic analyses identified potential immune-activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+ tissues. CONCLUSIONS: HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first-line PCT because of the possible stimulation of the antitumor immune microenvironment. PLAIN LANGUAGE SUMMARY: Human papillomavirus (HPV) infection may induce better objective response rate, progression-free survival (PFS), and overall survival (OS) for advanced penile squamous cell carcinoma (PSCC) patients receiving first-line programmed cell death protein 1 inhibitor-based combination therapy (PCT) instead of multi-line PCT. HPV infection-induced PFS advantage occurs at an early stage (within 3 months) whereas OS superiority occurs at a relatively late stage (within 9 months). Antitumor immune microenvironment could be stimulated by HPV infection in advanced PSCC tissues.

Constructing tin oxides Interfacial Layer with Gradient Compositions for Efficient Perovskite/Silicon Tandem Solar Cells with Efficiency Exceeding 28.

Atomic layer deposition (ALD) growth of conformal thin SnOx films on perovskite absorbers offers a promising method to improve carrier-selective contacts, enable sputter processing, and prevent humidity ingress toward high-performance tandem perovskite solar cells. However, the interaction between perovskite materials and reactive ALD precursor limits the process parameters of ALD-SnOx film and requires an additional fullerene layer. Here, it demonstrates that reducing the water dose to deposit SnOx can reduce the degradation effect upon the perovskite underlayer while increasing the water dose to promote the oxidization can improve the electrical properties. Accordingly, a SnOx buffer layer with a gradient composition structure is designed, in which the compositionally varying are achieved by gradually increasing the oxygen source during the vapor deposition from the bottom to the top layer. In addition, the gradient SnOx structure with favorable energy funnels significantly enhances carrier extraction, further minimizing its dependence on the fullerene layer. Its broad applicability for different perovskite compositions and various textured morphology is demonstrated. Notably, the design boosts the efficiencies of perovskite/silicon tandem cells (1.0 cm2) on industrially textured Czochralski (CZ) silicon to a certified efficiency of 28.0%.

SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer.

BACKGROUND: The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC. METHOD: Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer. RESULTS: Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer. CONCLUSION: Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.

Tunable multiple nonvolatile resistance states in a MnSe-based van der Waals multiferroic tunnel junction.

Two-dimensional (2D) van der Waals (vdW) multiferroic tunnel junctions (MFTJs) composed of a ferromagnetic metal and a ferroelectric barrier have controllable thickness and clean interface and can realize the coexistence of tunneling magnetoresistance (TMR) and tunneling electroresistance (TER). Therefore, they have enormous potential application in nonvolatile multistate memories. Here, using first principles combined with non-equilibrium Green's function method, we have systematically investigated the spin-dependent transport properties of Fe3GeTe2/MnSe/Fe3GeTe2 vdW MFTJs with various numbers of barrier layers. By controlling the polarization orientation of the ferroelectric barrier MnSe and the magnetization alignment of the ferromagnetic electrodes Fe3GeTe2, the MnSe-based MFTJs exhibit four nonvolatile resistance states, with the TMR (TER) becoming higher and reaching a maximum of 1.4 × 106% (4114%) as the MnSe layers increase from a bilayer to a tetralayer. Using asymmetric Cu and Fe3GeTe2 as the electrodes, the TER can be further improved from 349% to 618%. Moreover, there is a perfect spin filtering effect in these MFTJs. This work demonstrates the potential applications of MnSe-based devices in multistate nonvolatile memories and spin filters, which will stimulate experimental studies on layer-controllable spintronic devices.

Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas.

In zebrafish, Müller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision1. In mammals, however, MG do not spontaneously re-enter the cell cycle to generate a population of stem or progenitor cells that differentiate into retinal neurons. Nevertheless, the regenerative machinery may exist in the mammalian retina, as retinal injury can stimulate MG proliferation followed by limited neurogenesis2-7. Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of ß-catenin stimulates MG proliferation in the absence of injury in mouse retinas8. Here we report that following gene transfer of ß-catenin, cell-cycle-reactivated MG can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of transcription factors essential for rod cell fate specification and determination. MG-derived rods restored visual responses in Gnat1rd17Gnat2cpfl3 double mutant mice, a model of congenital blindness9,10, throughout the visual pathway from the retina to the primary visual cortex. Together, our results provide evidence of vision restoration after de novo MG-derived genesis of rod photoreceptors in mammalian retinas.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Surface Molecular Engineering for Fully Textured Perovskite/Silicon Tandem Solar Cells.

Developing large-scale monolithic perovskite/silicon tandem devices based on industrial Czochralski silicon wafers will likely have to adopt double-side textured architecture, given their optical benefits and low manufacturing costs. However, the surface engineering strategies that are widely used in solution-processed perovskites to regulate the interface properties are not directly applicable to micrometric textures. Here, we devise a surface passivation strategy by dynamic spray coating (DSC) fluorinated thiophenethylammonium ligands, combining the advantages of providing conformal coverage and suppressing phase conversion on textured surfaces. From the viewpoint of molecular engineering, theoretical calculation and experimental results demonstrate that introducing trifluoromethyl group provide more effective surface passivation through strong interaction and energy alignment by forming a dipole layer. Consequently, the DSC treatment of this bifunctional molecule enables the tandem cells based on industrial silicon wafers to achieve a certified stabilized power conversion efficiency of 30.89%. In addition, encapsulated devices display excellent operational stability by retaining over 97% of their initial performance after 600 h continuous illumination.

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-lactams, including penicillin, have been used for over 80 years in the treatment of group A Streptococcus (GAS) infections. Although -lactam-resistant GAS strains have not been identified in vitro tests, clinical treatment failures have been reported since the 1950s. The mechanism underlying the clinical failure of -lactam treatment in GAS infections remains unclear. Previous research has suggested that -lactam resistance in GAS in vivo is associated with reduced drug susceptibility of strains, bacterial inoculation effects, biofilm formation, the effect of coexisting bacteria, bacterial persistence, and bacterial internalization into host cells. This article reviews the main reports on -lactam treatment failure in GAS infections and analyzes the possible mechanisms of -lactam resistance in vivo. The findings aim to contribute to future research and clinical approaches in the field.

HER2-targeting antibody-drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: a multicenter, real-world study.

BACKGROUND: Phase II trials showed the efficacy of anti-HER2 RC48-ADC (disitamab vedotin) for HER2-positive metastatic urothelial carcinoma (UC). This study evaluated RC48 alone verses in combination with immunotherapy for locally advanced or metastatic UC using real-world data. METHODS: This retrospective, multicenter, real-world study included patients with locally advanced or metastatic UC who received RC48 in five hospitals in China between July 2021 and April 2022. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. RESULTS: Thirty-six patients were included. The patients were 47-87 years, and 26 (72.2%) were male. Eighteen patients received RC48 alone, and 18 received RC48 combined with a programmed death-1 antibody. The median PFS was 5.4 months. The median OS was not reached. The 6-month and 1-year PFS rates were 38.8% and 15.5%, respectively. The 1-year OS rate was 79.6%. Fourteen (38.9%) patients achieved a partial response, and the ORR was 38.9%. Eleven patients had stable disease, and the DCR was 69.4%. The median PFS for patients who received RC48 combined with immunotherapy and those who received RC48 alone was 8.5 and 5.4 months, respectively. The main treatment-related adverse events included anemia, hypoesthesia, fatigue, and elevated transaminase. No treatment-related death occurred. CONCLUSION: RC48 alone or combined with immunotherapy might benefit patients with locally advanced or metastatic UC, regardless of impaired renal function.

Regular gastroscopy and colonoscopy during the evaluation of urachal cancer: do we really need them?

PURPOSE: Urachal cancer is similar to gastrointestinal adenocarcinoma in histology, and gastroscopy/colonoscopy is often administered during perioperative evaluation. However, gastroscopy and colonoscopy have corresponding disadvantages. This study discusses whether gastroscopy/colonoscopy is truly necessary for patients with urachal cancer. PATIENTS AND METHODS: A total of 166 bladder adenocarcinoma cases diagnosed at Sun Yat-sen University Cancer Center were retrospectively reviewed and divided into two groups (urachal cancer and nonurachal cancer), and perioperative evaluations were retrieved. RESULTS: There were 78 patients with urachal cancer, the median age was 48 years, and 59 were male. Perioperative gastroscopy/colonoscopy revealed 5 intestinal polyps and 1 adenoma during these evaluations, and no primary gastrointestinal cancer was found. Meanwhile, preoperative imaging evaluation did not detect significant gastrointestinal lesions. For 88 patients with nonurachal cancer, including primary bladder adenocarcinoma and metastatic tumors from gastrointestinal cancer, the median age was 56 years, and 64 were male. Preoperative imaging evaluation demonstrated 36 cases of gastrointestinal lesions, and 32 were confirmed by gastroscopy/colonoscopy; the other 4 were negative. Another 4 cases of colon cancer were detected by regular colonoscopy for suspected primary bladder adenocarcinoma. In all, 35 cases of colon cancer and 1 case of gastric cancer were identified by endoscopic examination. The diagnostic consistency of imaging and gastrointestinal endoscopy was favorable (P < 0.001), and the negative predictive value and diagnostic efficiency of imaging were 96.9% and 94.6%, respectively. CONCLUSIONS: The vast majority of gastrointestinal cancer cases can be identified by assessment of the patient's clinical symptoms, meticulous physical examination, and imaging evaluation. We recommend that gastroscopy/colonoscopy only be applied to patients with urachal cancer when the above examinations are positive.

Effect of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma: a real-world retrospective study.

BACKGROUND: Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). METHODS: We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. RESULTS: Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84-21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08-0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. CONCLUSIONS: Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.