Cell and gene therapy in neuro-oncology.

The majority of primary brain tumors are gliomas, among which glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. GBM has a median survival of 18-24 months, and despite extensive research it remains incurable, thus novel therapies are urgently needed. The current standard of care is a combination of surgery, radiation, and chemotherapy, but still remains ineffective due to the invasive nature and high recurrence of gliomas. Gene therapy is a versatile treatment strategy investigated for multiple tumor types including GBM. In gene therapy, a variety of vectors are employed to deliver genes designed for different antitumoral effects. Also, over the past decades, stem cell biology has provided a new approach to cancer therapies. Stem cells can be used as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. Stem cell-based therapy allows targeted therapy that spares healthy brain tissue as well as establishes a long-term antitumor response by stimulating the immune system and delivering prodrug, metabolizing genes, or even oncolytic viruses. This chapter describes the latest developments and the current trends in gene and cell-based therapy against GBM from both preclinical and clinical perspectives, including different gene therapy delivery systems, molecular targets, and stem cell therapies.

Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases.

BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory disease characterized by relapsing eruptions of neutrophil-filled, sterile pustules on the palms and soles that can be clinically difficult to differentiate from non-pustular palmoplantar psoriasis (palmPP) and dyshidrotic palmoplantar eczema (DPE). OBJECTIVE: We sought to identify overlapping and unique PPP, palmPP, and DPE drivers to provide molecular insight into their pathogenesis. METHODS: We performed bulk RNA sequencing of lesional PPP (n = 33), palmPP (n = 5), and DPE (n = 28) samples, as well as 5 healthy nonacral and 10 healthy acral skin samples. RESULTS: Acral skin showed a unique immune environment, likely contributing to a unique niche for palmoplantar inflammatory diseases. Compared to healthy acral skin, PPP, palmPP, and DPE displayed a broad overlapping transcriptomic signature characterized by shared upregulation of proinflammatory cytokines (TNF, IL-36), chemokines, and T-cell-associated genes, along with unique disease features of each disease state, including enriched neutrophil processes in PPP and to a lesser extent in palmPP, and lipid antigen processing in DPE. Strikingly, unsupervised clustering and trajectory analyses demonstrated divergent inflammatory profiles within the 3 disease states. These identified putative key upstream immunologic switches, including eicosanoids, interferon responses, and neutrophil degranulation, contributing to disease heterogeneity. CONCLUSION: A molecular overlap exists between different inflammatory palmoplantar diseases that supersedes clinical and histologic assessment. This highlights the heterogeneity within each condition, suggesting limitations of current disease classification and the need to move toward a molecular classification of inflammatory acral diseases.

Mid-term clinical outcomes and cardiac function in patients receiving cardiac contractility modulation.

OBJECTIVES: To describe the mid-term clinical and functional cardiac contractility modulation therapy (CCM) recipients in an urban population with heart failure. BACKGROUND: CCM is a non-excitatory electrical therapy for patients with systolic heart failure with NYHA class III symptoms and ejection fraction (EF) 25-45%. How CCM affects a broad range of clinical measures, including diastolic dysfunction (DD) and weight change, is unexplored. METHODS: We reviewed 31 consecutive patients at our center who underwent CCM implant. NYHA class, hospitalizations, ejection fraction (EF), diastolic function, and weight were compared pre- and post-CCM implant. RESULTS: Mean age and follow-up time was 63 ± 10 years and 1.4 ± 0.8 years, respectively. Mean NYHA class improved by 0.97 functional classes (p < 0.001), and improvement occurred in 68% of patients. Mean annualized hospitalizations improved (0.8 ± 0.8 vs. 0.4 ± 1.0 hospitalizations/year, p = 0.048), and after exclusion of a single outlier, change in annualized days hospitalized also improved (total cohort 3.8 ± 4.7 vs. 3.7 ± 14.8 days/year; p = 0.96; after exclusion, 3.8 ± 4.7 vs. 1.1 ± 1.9 days/year, p < 0.001). Mean EF improved by 8% (p = 0.002), and among those with DD pre-CCM, mean DD improvement was 0.8 "grades" (p < 0.001). Mean weight change was 8.5 pounds lost, amounting to 4% of body weight (p = 0.002, p = 0.002, respectively), with 77% of patients having lost weight after CCM. Five patients (16%) experienced procedural complications; incidence skewed toward early implants. CONCLUSION: In an observational cohort, CCM therapy resulted in improvement in NYHA class, hospitalizations, systolic and diastolic function, and weight.

Risk of De Novo Barrett's Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies with Long-Term Follow-Up.

BACKGROUND & AIMS: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric procedures worldwide. Gastroesophageal reflux disease (GERD) is a major concern in patients undergoing SG and is a risk factor for Barrett's esophagus (BE). We conducted a systematic review and meta-analysis to assess the incidence of and analyze predictive factors for post-SG BE. METHODS: A comprehensive literature search was conducted in April 2024, for studies reporting on incidence of BE, erosive esophagitis (EE), and hiatal hernia (HH) post-SG. Primary outcomes were post-SG pooled rates of de novo BE, EE, GERD symptoms, proton pump inhibitor use, and HH. Meta-regression analysis was performed to assess if patient and post-SG factors influenced the rates of post-SG BE. RESULTS: Nineteen studies with 2046 patients (79% females) were included. Mean age was 42.2 years (standard deviation, 11.1) and follow-up ranged from 2 to 11.4 years. The pooled rate of de novo BE post-SG was 5.6% (confidence interval, 3.5-8.8). Significantly higher pooled rates of EE (risk ratio [RR], 3.37], HH (RR, 2.09), GER/GERD symptoms (RR, 3.32), and proton pump inhibitor use (RR, 3.65) were found among patients post-SG. GER/GERD symptoms post-SG positively influenced the pooled BE rates, whereas age, sex, body mass index, post-SG EE, and HH did not. CONCLUSIONS: Our analysis shows that SG results in a significantly increased risk of de novo BE and higher rates of EE, proton pump inhibitor use, and HH. Our findings suggest that clinicians should routinely screen patients with SG for BE and future surveillance intervals should be followed as per societal guidelines.

Overactive Bladder (OAB) Symptoms in Patients Undergoing Flexible Cystoscopy.

OBJECTIVE: The objective is to measure the change in overactive bladder (OAB) symptoms in patients undergoing flexible cystoscopy in the early postoperative period using a validated OAB-V8 tool. PATIENTS AND METHODS: It was a prospective, cross-sectional, observational study conducted by a section of Urology at the Aga Khan University Hospital, Karachi. The total duration of the study was 12 months (July 2022 to June 2023). All adult patients who underwent flexible cystoscopy under local anesthesia for diagnostic and surveillance purposes were included in the study. OAB symptoms were evaluated using the validated eight-item OAB-V8 tool just before the cystoscopy and on postoperative days 1 and 4. Patients were categorized as either OAB-negative (<8) or OAB-positive (≥8) based on their sum scores. Mean sum scores of different variables and OAB subdomains were assessed. RESULTS: Sixty-three patients were included in the final analysis with a predominantly male population. The mean pre-cystoscopy (screen) score was 7.46 + 5.58, which increased to 9.89 + 6.82 on day 1 (p<0.01) before decreasing back to 7.68 + 5.7 on day 4 (p=0.08). Twenty-one patients (33.3%) were labeled OAB positive on day 0. Following cystoscopy, this number increased to 32 patients (50.8%) as 11 patients (26.2 %) developed de-novo OAB symptoms. The sub-group analysis showed an insignificant impact of age (p=0.5), gender (p=0.51), indication (p=0.22), and use of alpha-blocker (p= 0.30) on change in OAB score. CONCLUSION:  OAB symptoms are frequently encountered in patients undergoing awake (flexible) cystoscopy. This procedure can also trigger de novo OAB symptoms, albeit transiently, which typically resolve over time. This information could help in patient counseling, management, and the need for intervention in the future.

Steroid-Responsive Seronegative Immune-Mediated Necrotizing Myopathy Likely Triggered by Coxsackie B Virus: A Case Report.

Viral myositis can be mistaken for other types of myopathies, and the main causes of muscle damage are direct myotoxic effect and immune-mediated mechanisms. The biochemical parameters, electromyography (EMG), and muscle biopsy findings can be similar in viral myositis and idiopathic inflammatory myopathies. Viruses are rarely isolated from muscle biopsy specimens, so clinical evaluation and ancillary tests are necessary for a definitive diagnosis. Viral etiology is suspected when weakness occurs after a respiratory or gastrointestinal infection. Coxsackieviruses, particularly A9 and B5, can cause myositis and muscle necrosis. This is a case of a 47-year-old female with a history of alcoholic cirrhosis and a recent coxsackie B virus infection presented with weakness, numbness, and body pain. Creatine kinase levels were elevated but tests for extended myositis panel and antibodies were negative. A muscle biopsy revealed immune-mediated inflammatory myopathy. After a week without improvement, the patient received IV methylprednisolone followed by prednisone taper leading to improvement in symptoms. Prolonged myalgia has been observed in patients recovering from coxsackie A infections. The role of coxsackie B in causing myositis is still disputed and requires more reported data and guidelines. Clinicians should consider testing for coxsackie B as a potential cause of weakness. Awareness of potential complications like myositis can aid in effective patient management. More cases are needed to determine the significance of steroid use in managing coxsackie B-related muscle weakness.

Novel ocular observations in a child with Joubert syndrome type 6 due to pathogenic variant in TMEM67 gene.

Purpose: To describe unique ocular features in a child with Joubert syndrome type 6. Observations: A 4-year-old male patient presented with right microphthalmia and non-dilating pupil and left primary position nystagmus. Brain MRI revealed a "molar tooth sign" of the midbrain and a "batwing sign" of the fourth ventricle along with large retroorbital cysts bilaterally. The diagnosis of autosomal recessive Joubert syndrome type 6 due to homozygous pathogenic variant c.725A > G p. (Asn242Ser) in TMEM67 gene was confirmed by whole exome sequencing. Left eye had nystagmus and the left optic nerve and retina showed epipapillary and subretinal fibrosis, respectively. Scleral buckle was performed for left non-rhegmatogenous retinal detachment which then improved and has been stable. Conclusions and Importance: We present a rare case of JS with some unique ophthalmic features which expand clinical knowledge on this complex systemic and ocular entity.

Excitation functions of 72Ge(p,xn)72,71As reactions from threshold up to 45 MeV for production of the non-standard positron emitter 72As.

Nuclear reaction cross sections for the formation of 72As and 71As in proton-induced reactions on enriched 72Ge targets were measured up to 45 MeV utilizing three different cyclotrons at the Forschungszentrum Jülich. The stacked-thin sample activation technique in combination with high-resolution γ-ray spectrometry was used. The major γ-ray peaks of 72As and 71As formed via the 72Ge(p,n)72As and 72Ge(p,2n)71As reactions, respectively, were analyzed. The incident proton energy and flux on a foil were determined using several monitor reactions. Based on integrated counts, irradiation data and the nuclear decay data, the reaction cross sections were measured. All data describe the first measurements. Theoretical nuclear model calculations were then carried out by using the codes TALYS 1.96, EMPIRE 3.2 and ALICE-IPPE. A very good agreement between the measured data and calculated values was found. The new data enabled us to calculate the thick target yields and estimate the radionuclidic impurities for a given energy range. Over the optimum energy range Ep = 14 → 7 MeV, the calculated thick target yield of 72As amounts to 272 MBq/µAh with no 71As impurity at all. The 72Ge(p,n)72As reaction on the enriched 72Ge is thus very suitable for clinical scale production of 72As at a medical cyclotron.

Modulating a model membrane of sphingomyelin by a tricyclic antidepressant drug.

Tricyclic medicine such as amitriptyline (AMT) hydrochloride, initially developed to treat depression, is also used to treat neuropathic pain, anxiety disorder, and migraines. The mechanism of functioning of this type of drugs is ambiguous. Understanding the mechanism is important for designing new drug molecules with higher pharmacological efficiency. Hence, in the present study, biophysical approaches have been taken to shed light on their interactions with a model cellular membrane of brain sphingomyelin in the form of monolayer and multi-lamellar vesicles. The surface pressure-area isotherm infers the partitioning of a drug molecule into the lipid monolayer at the air water interface, providing a higher surface area per molecule and reducing the in-plane elasticity. Further, the surface electrostatic potential of the lipid monolayer is found to increase due to the insertion of drug molecule. The interfacial rheology revealed a reduction of the in-plane viscoelasticity of the lipid film, which, depends on the adsorption of the drug molecule onto the film. Small-angle X-ray scattering (SAXS) measurements on multilamellar vesicles (MLVs) have revealed that the AMT molecules partition into the hydrophobic core of the lipid membrane, modifying the organization of lipids in the membrane. The modified physical state of less rigid membrane and the transformed electrostatics of the membrane could influence its interaction with synaptic vesicles and neurotransmitters making higher availability of the neurotransmitters in the synaptic cleft.

Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer.

PURPOSE: Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI [TMB-H/microsatellite stable (MSS)]. EXPERIMENTAL DESIGN: We sequenced 3,244 tumors from 2,257 patients with prostate cancer. MSI-H/dMMR prostate cancer was defined as an MSIsensor score ≥10 or MSIsensor score ≥3 and <10 with a deleterious MMR alteration. TMB-H was defined as ≥10 mutations/megabase. PSA50 and RECIST responses were assigned. Overall survival and radiographic progression-free survival (rPFS) were compared using log-rank test. RESULTS: Sixty-three (2.8%) men had MSI-H/dMMR, and 33 (1.5%) had TMB-H/MSS prostate cancers. Patients with MSI-H/dMMR and TMB-H/MSS tumors more commonly presented with grade group 5 and metastatic disease at diagnosis. MSI-H/dMMR tumors had higher TMB, indel, and neoantigen burden compared with TMB-H/MSS. Twenty-seven patients with MSI-H/dMMR and 8 patients with TMB-H/MSS tumors received ICB, none of whom harbored polymerase epsilon (polE) catalytic subunit mutations. About 45% of patients with MSI-H/dMMR had a RECIST response, and 65% had a PSA50 response. No patient with TMB-H/MSS had a RECIST response, and 50% had a PSA50 response. rPFS tended to be longer in patients with MSI-H/dMMR than in patients with TMB-H/MSS who received immunotherapy. Pronounced differences in genomics, TMB, or MSIsensor score were not detected between MSI-H/dMMR responders and nonresponders. CONCLUSIONS: MSI-H/dMMR prostate cancers have greater TMB, indel, and neoantigen burden than TMB-H/MSS prostate cancers, and these differences may contribute to profound and durable responses to ICB.

Exploration of gut microbial diversity of pheasants through pyrosequencing of 16S rRNA gene.

Despite the diversity of microbiota in birds is similar to that of other animals, there is a lack of research on the gut microbial diversity of nondomesticated bird species. This study aims to address this gap in knowledge by analyzing the bacterial communities present in the gut of two important game bird species, the Ring-necked pheasant (Phasianus colchicus) and the Green pheasant (Phasianus versicolor) to understand the gut microbial diversity of these species. The gut microbiome of 10 individual pheasants from two different species was studied using pooled fecal samples. We used 16S rRNA gene sequencing on the Ion S5 XL System next-generation sequencing with Mothur and SILVA Database for taxonomic division. An average of 141 different operational taxonomic units were detected in the gut microbiome. Analysis of microbial classification revealed the presence of 191 genera belonging to 12 different phyla in both pheasants. Alpha diversity indices revealed that P. colchicus exhibited most prevalence firmicutes with bacillus species microbial community than P. versicolor. Alpha diversity indices indicated that P. colchicus had a more diverse community and P. versicolor had a greater diversity of evolutionary lineages, while both species had similar levels of species richness and sample inclusiveness. These findings may have implications for the health and well-being of pheasants, serving as a reference for their bacterial diversity. Additionally, they provide a baseline for future research and conservation efforts aimed at improving the health and well-being of these and possibly other avian species.

Immunization against dengue virus infection is coercive: A timely call.

Background: In context, the dengue virus causes dengue fever, which is spread by mosquito bites. About 22,000 people every year lose their lives as a direct result of it. Dengue fever has been on the rise recently, and its spread has alarmed health officials throughout the world. Discussion: Vaccination is essential for the prevention and management of dengue cases because there is currently no particular cure against dengue virus. The current dengue epidemic calls for urgent action in the form of immunization. However, there are serious drawbacks to using existing vaccines like Dengvaxia. Besides, the Qdenga vaccine has not yet been approved by the FDA in the United States. On the other hand, positive results from a phase II randomized and controlled clinical study of the TV005 tetravalent live-attenuated dengue vaccine were recently reported in Bangladesh. Only an effective vaccination can drastically lower dengue infection and mortality rates. Conclusion: The development of safe and effective vaccination, as well as their correct dissemination, is an essential requirement for the people of Bangladesh and the rest of the globe, and we concentrated on this critical problem in this article.

Prevalence and factors associated with falls in older adults in a Middle Eastern population: a retrospective cross-sectional study.

OBJECTIVE: The main objective was to determine the prevalence of falls and associated factors in older adults living in Qatar. STUDY DESIGN: Cross-sectional study. METHODS: This is a cross-sectional study of older adults aged ≥60 years with at least one encounter with primary health care corporation (PHCC) in Qatar during the period 2017-2022. Data on documented falls, demographic variables, and medical comorbidities were extracted from all PHCCs in Qatar. Descriptive and inferential statistics were used to address the aim of the study. RESULTS: A total of 68,194 older adults had at least one encounter with PHCC. The median age was 65.0 years, 58.9% were males, and 32.6% were Qatari nationality. A higher percentage of falls was found in individuals with hypertension (80%), diabetes (74.2%), and dyslipidemia (48.9%), which were also the most prevalent comorbidities. The prevalence of falls was 6.7% (95% CI 6.6-6.9). Compared to individuals aged 60-69 years, individuals aged 70-79, 80-89, and 90-99 had increased odds of falls by 1.6 (95% CI 1.5, 1.8), 2.5 (95% CI 2.2, 2.8), and 2.6 (95% CI 2.0, 3.3), respectively. Females and individuals of Qatari nationality had increased odds of fall by 1.5 (95% CI 1.4, 1.6) and 1.2 (95% CI 1.1, 1.3), respectively. Orthostatic hypotension, syncope, Parkinson's disease, and hip arthritis showed the strongest associations with falls. CONCLUSIONS: Given the growing population of older adults in the Middle East and North African region, falls is a public health concern. The risk factors identified in this study suggest the need for proactive healthcare strategies tailored to the unique needs of older adult populations.

iGATE analysis improves the interpretability of single-cell immune landscape of influenza infection.

Influenza poses a persistent health burden worldwide. To design equitable vaccines effective across all demographics, it is essential to better understand how host factors such as genetic background and aging affect the single-cell immune landscape of influenza infection. Cytometry by time-of-flight (CyTOF) represents a promising technique in this pursuit, but interpreting its large, high-dimensional data remains difficult. We have developed a new analytical approach, in silico gating annotating training elucidating (iGATE), based on probabilistic support vector machine classification. By rapidly and accurately "gating" tens of millions of cells in silico into user-defined types, iGATE enabled us to track 25 canonical immune cell types in mouse lung over the course of influenza infection. Applying iGATE to study effects of host genetic background, we show that the lower survival of C57BL/6 mice compared with BALB/c was associated with a more rapid accumulation of inflammatory cell types and decreased IL-10 expression. Furthermore, we demonstrate that the most prominent effect of aging is a defective T cell response, reducing survival of aged mice. Finally, iGATE reveals that the 25 canonical immune cell types exhibited differential influenza infection susceptibility and replication permissiveness in vivo, but neither property varied with host genotype or aging. The software is available at https://github.com/UmichWenLab/iGATE.

Impact of Patient Education Formats on Treatment Adherence and Denture Hygiene in Edentulous Patients: A Comparative Study.

BACKGROUND Effective communication and patient education are important in geriatric dental care. Memory decline complicates patient adherence. This study aimed to compare verbal, audio, and video patient education material (PEM) and adherence to dental prosthetic management in edentulous patients. MATERIAL AND METHODS 90 completely/partially edentulous patients (aged 40 to 70 years), were divided (simple random) into three groups (Gp) of 30 each . A total of 68 instructions were organized into 9 learning categories. For GpVi, a 20 minute video was shot using a Sony camera (PD170), with two actors depicting related PEM information. Patients were recalled after 1 day and 7days, to recall the PEM instructions. A Denture plaque Index (DPI) determined the efficiency of the instructions at both time intervals. Frequencies, means and standard deviations were derived for each group and then compared using Chi square, paired and unpaired t test and a Neuman-Keul post hoc pairwise test. All significant differences were kept at probability t value of ≤0.05. RESULTS PEM instructions related to patient individuality, proper tongue position and miscellaneous showed poor patient recall. At 1 day interval, audio was found to have better recall than video and verbal in 5 PEM instruction categories. At 7 day interval, video showed better recall than other two groups (P≤0.05). Despite improvements in patients recall, DPI revealed better denture hygiene maintenance in patients receiving instructions through video format (P≤0.05). CONCLUSIONS For all categories, no single media was considered to be sufficient, audio produced early better recall while video influenced long term recall and better denture hygiene maintenance.

Motion-robust free-running volumetric cardiovascular MRI.

PURPOSE: To present and assess an outlier mitigation method that makes free-running volumetric cardiovascular MRI (CMR) more robust to motion. METHODS: The proposed method, called compressive recovery with outlier rejection (CORe), models outliers in the measured data as an additive auxiliary variable. We enforce MR physics-guided group sparsity on the auxiliary variable, and jointly estimate it along with the image using an iterative algorithm. For evaluation, CORe is first compared to traditional compressed sensing (CS), robust regression (RR), and an existing outlier rejection method using two simulation studies. Then, CORe is compared to CS using seven three-dimensional (3D) cine, 12 rest four-dimensional (4D) flow, and eight stress 4D flow imaging datasets. RESULTS: Our simulation studies show that CORe outperforms CS, RR, and the existing outlier rejection method in terms of normalized mean square error and structural similarity index across 55 different realizations. The expert reader evaluation of 3D cine images demonstrates that CORe is more effective in suppressing artifacts while maintaining or improving image sharpness. Finally, 4D flow images show that CORe yields more reliable and consistent flow measurements, especially in the presence of involuntary subject motion or exercise stress. CONCLUSION: An outlier rejection method is presented and tested using simulated and measured data. This method can help suppress motion artifacts in a wide range of free-running CMR applications.

Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.

PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.

The Effectiveness of Virtual Reality on Anxiety and Pain Management in Patients Undergoing Cardiac Procedures: A Systematic Review and Meta-Analysis.

Cardiac procedure-related anxiety and pain can adversely affect outcomes and lead to patient dissatisfaction. Virtual reality (VR) offers a promising alternative to traditional therapies for improving patient experience. Our objective is to synthesize evidence and assess the effectiveness of VR in reducing cardiac procedure-related anxiety and pain compared to standard of care. We conducted a comprehensive search across various online databases, including MEDLINE, EMBASE, CINAHL, Web of Sciences, and COCHRANE, to identify relevant randomized controlled trials (RCTs) focusing on VR, cardiac procedures, anxiety, and pain. We utilized a random-effect model to generate effect estimates reported as standardized mean differences (SMD) with a 95% confidence interval. Our review comprised 10 studies with a total of 621 participants (intervention arm: 301, control arm: 320). Overall, among the seven studies evaluating anxiety outcomes, no significant difference in anxiety reduction was observed between the intervention and control groups (standardized mean difference (SMD) -0.62, 95% CI -1.61, 0.37, p=0.22). However, studies using the same anxiety assessment tool demonstrated a significant improvement in the VR arm (SMD -1.01, 95% CI -1.98, -0.04, p=0.04). Conversely, the narrative synthesis of four studies examining pain revealed mixed results. Our findings suggest no significant difference in anxiety reduction between the VR and control groups. Future studies should employ standardized tools for assessing and reporting anxiety and pain to better understand the potential of VR in enhancing patient experience during cardiac procedures.

Mechanism and clinical role of TIMP-2 and IGFBP-7 in cardiac surgery-associated acute kidney injury: A review.

Acute kidney injury (AKI) is a common postoperative complication, but there is still a lack of accurate biomarkers. Cardiac surgery-associated AKI is the most common cause of major-surgery-related AKI, and patients requiring renal replacement therapy have high mortality rates. Early diagnosis, intervention, and management are crucial for improving patient prognosis. However, diagnosing AKI based solely on changes in serum creatinine level and urine output is insufficient, as these changes often lag behind actual kidney damage, making early detection challenging. Biomarkers such as tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) have been found to be significant predictors of moderate-to-severe AKI when combined with urine content analysis. This article reviews the mechanism of biomarkers TIMP-2 and IGFBP-7 in AKI and provides a comprehensive overview of the clinical effects of TIMP-2 and IGFBP-7 in cardiac surgery-associated AKI, including prediction, diagnosis, and progression.