Oncologic outcomes of neoadjuvant chemotherapy and lymph node dissection with partial cystectomy for muscle-invasive bladder cancer.

Background: Partial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS). Methods: We identified 2,832 patients with cT2-4N0M0 bladder cancer (BCa) who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS in treatment modalities in PC patients. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy [≥10 lymph node (LN) yield], and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients. Results: Two hundred and thirty-one patients received multi-agent NAC with PC. NAC treatment with PLND was associated with significantly improved OS (P<0.001). Median OS was 43.9 months in patients treated with PC alone, while median OS was not reached in PC patients treated with NAC & PLND. Furthermore, patients who received NAC without any PLND had a median OS of 50.6 months, while those treated with PLND without NAC had a median OS of 76.5 months. This persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10 LN. Conversely, age >80 years old, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND [odds ratio (OR) 0.719, P=0.005], while NAC was more likely administered to PC patients diagnosed from 2016-2019 (OR 5.295, P<0.001). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR 2.189, P<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR 1.745, P=0.003; OR 2.465, P<0.001, respectively). Conclusions: Despite guideline recommendations, the utilization of NAC and PLND with PC remains insufficient. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation.

Deformation-Induced Crystal Growth or Redissolution, and Crystal-Induced Strengthening or Ductilization in Metallic Glasses Containing Nanocrystals.

It is generally known that the incorporation of crystals in the glass matrix can enhance the ductility of metallic glasses (MGs), at the expense of reduced strength, and that the deformation of MGs, particularly during shear banding, can induce crystal formation/growth. Here, we show that these known trends for the interplay between crystals and deformation of MGs may hold true or become inverted depending on the size of the crystals relative to the shear bands. We performed molecular dynamics simulations of tensile tests on nanocrystal-bearing MGs. When the crystals are relatively small, they bolster the strength rather than the ductility of MGs, and the crystals within a shear band undergo redissolution as the shear band propagates. In contrast, larger crystals tend to enhance ductility at the cost of strength, and the crystal volume fraction increases during deformation. These insights offer a more comprehensive understanding of the intricate relationship between deformation and crystals/crystallization in MGs, useful for fine-tuning the structure and mechanical properties of both MGs and MG-crystal composites.

Income Disparities in Survival and Receipt of Neoadjuvant Chemotherapy and Pelvic Lymph Node Dissection for Muscle-Invasive Bladder Cancer.

Background: Muscle-invasive bladder cancer (MIBC) is a potentially fatal disease, especially in the setting of locally advanced or node-positive disease. Adverse outcomes have also primarily been associated with low-income status, as has been reported in other cancers. While the adoption of neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) and pelvic lymph node dissection (PLND) has improved outcomes, these standard-of-care treatments may be underutilized in lower-income patients. We sought to investigate the economic disparities in NAC and PLND receipt and survival outcomes in MIBC. Methods: Utilizing the National Cancer Database, a retrospective cohort analysis of cT2-4N0-3M0 BCa patients with urothelial histology who underwent RC was conducted. The impact of income level on overall survival (OS) and the likelihood of receiving NAC and PLND was evaluated. Results: A total of 25,823 patients were included. This study found that lower-income patients were less likely to receive NAC and adequate PLND (≥15 LNs). Moreover, lower-income patients exhibited worse OS (Median OS 55.9 months vs. 68.2 months, p < 0.001). Our findings also demonstrated that higher income, treatment at academic facilities, and recent years of diagnosis were associated with an increased likelihood of receiving standard-of-care modalities and improved survival. Conclusions: Even after controlling for clinicodemographic variables, income independently influenced the receipt of standard MIBC treatments and survival. Our findings identify an opportunity to improve the quality of care for lower-income MIBC patients through concerted efforts to regionalize multi-modal urologic oncology care.

Coccidioidomycosis in Oklahoma: A retrospective case series.

BACKGROUND: Coccidioidomycosis is a systemic fungal disease endemic to arid regions of the Western Hemisphere. In the south-western US, Coccidioides spp. may account for up to 20%-25% of all cases of community acquired pneumonia. Clinical manifestations vary widely, from asymptomatic infection to life-threatening disease, especially in immunocompromised hosts. OBJECTIVES: The primary objective of the study was to characterise cases of coccidioidomycosis in an area of the United States not considered traditionally endemic for the disease. METHODS: We performed a single-centre retrospective study of all cases of coccidioidomycosis from 1 January 2000 to 31 December 2020, in the University of Oklahoma Health Sciences Medical Center. RESULTS: A total of 26 patients were included for analysis. The central nervous system (CNS) and the lungs were the sites most frequently involved. Twenty (77%) had travelled to a coccidioidomycosis endemic region. Most were male (81%) with a median age of 42 years (range: 3-78 years). The majority (46%) were Caucasians, 19% were African American, 19% Hispanic, and 12% Native American. The most common comorbidities were diabetes mellitus and acquired immunodeficiency syndrome, identified in 27% and 23% of patients, respectively. Patients on immunosuppressive therapy accounted for 12% of all cases. CONCLUSION: Our study is one of the largest single-centre case series of coccidioidomycosis from a non-endemic area. Diabetes mellitus was the most frequent comorbidity. Compared to other case series of coccidioidomycosis, our patient population had higher rates of immunosuppression and had both a higher rate of disseminated disease and overall mortality.

Sorting and simultaneous quantitation of intact mixed-cell samples via capillary isotachophoresis.

A great need currently exists for rapid, inexpensive, and accurate methods for microbial analysis in the medical, food, industrial, and water quality fields. Here, a novel capillary isotachophoresis (CITP) method is presented for the focusing, sorting, and quantitation of intact cells in mixed samples based on their electrophoretic mobility ranges. Using a series of ion spacers dissolved in the sample, this technique results in several efficient cell peaks in the electropherogram corresponding to specific cell electrophoretic mobility ranges. The concentrations of different species in mixed-cell samples are determined from the cell peak areas and the known peak response factors for the cell species using a series of linear equations. Method design and optimization are discussed, including the choice of running buffer, pH, and ion spacers. Mixed-cell samples of up to four different species were focused and quantified as a proof-of-principle of the method. When sample cell concentrations were toward the middle of the linear response range, accuracies between 1% and 11% and relative standard deviations of 1%-14% were obtained, depending on the number of cell species in the mixture. This work provides a useful basis for future studies of cell quantitation using CITP, which could be potentially applied to a variety of fields including cell growth studies, microbial contamination testing, and sterility testing.

Trends of Lymph Node Outcomes in Partial Cystectomy for Muscle-Invasive Urothelial Carcinoma of the Bladder.

INTRODUCTION: Local tumor invasion depth has been associated with lymph node metastasis in urothelial carcinoma, and, for muscle-invasive bladder cancer (MIBC), pelvic lymph node dissection (PLND) is a critical step in curative surgery. Gold standard treatment includes radical cystectomy (RC), but partial cystectomy (PC) is an important bladder-preserving modality reserved for patients with certain favorable prognostic indicators. There is poor evidence concerning the utility of PLND in PC and we seek to further define its role by comparing survival outcomes when PLND was cursory or omitted. METHODS: A retrospective analysis of 13,652 cT2N0M0 patients who underwent PC or RC between 2004 and 2016 was performed using the National Cancer Database. Patients undergoing PC were stratified by the presence of PLND as well as by node yield >15. The primary outcome was overall survival, analyzed using the Kaplan-Meier Method and multivariable Cox-proportional hazards regression. Multivariable models were adjusted for confounding clinicopathologic variables. RESULTS: From 2004 to 2016, PLND in PC increased from 44% to 57% with RC remaining over 90%. Compared to RC, PC was approximately twice as likely to be performed at community centers and approached laparoscopically/robotically (P < .001). When stratifying PC PLND yield into 1 to 15 and > 15 compared to PC without PLND, the adjusted hazard ratios for overall mortality were 0.78 and 0.54, respectively (P < .05). CONCLUSIONS: PC patients had a significantly lower rate of PLND compared to RC and improved survival when performed versus PC alone. Furthermore, increased node yield was associated with a larger reduction of adjusted mortality hazard. For MIBC patients that are appropriately selected for PC, high-yield PLND should be prioritized given the significantly improved survival outcomes.

Evaluating the baseline hemoglobin, albumin, lymphocyte, and platelet (HALP) score in the United States adult population and comorbidities: an analysis of the NHANES.

Introduction: As a composite immunonutritional biomarker, the Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score has shown promise in assessing a patient's overall health status by integrating several routinely collected laboratory indicators. This biomarker has been examined in many different populations of patients and disease states (i.e., cancer), but an integrated, universal rubric using standardized thresholds has not thus far been developed. Pre-existing large population-based databases represent an ideal source to examine the distribution of HALP and the influence of diverse health statuses on this score. Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) between 2017-2020, evaluating 8,245 participants across numerous demographic, socioeconomic, and health-related variables. Univariate and multivariate linear regression analyses assessed the associations between HALP scores and these factors. Results: Our findings revealed significant associations between HALP scores and various demographic, socioeconomic, and health conditions. The median HALP score among the representative population was 49.0, with varying median scores across different groups and normal reference ranges for males and females. Multivariate regression analysis showed that anemia treatment, age over 65 years, weak/failing kidneys, and cancer were independent risk factors associated with lower HALP scores. Male participants demonstrated higher HALP scores than female participants, and age was inversely related to HALP. Moreover, HALP scores were negatively associated with the number of comorbidities. Conclusion/discussion: This study set out to explore the HALP score from a population-based perspective, uncovering notable associations that offer vital insights into the score's clinical relevance and future applications. By determining a median HALP score of 49.0 and normal reference ranges within our diverse, representative sample, we establish a robust foundation for researchers to refine optimal HALP applications and thresholds. Considering the growing focus on personalized medicine, HALP holds promise as a prognostic tool, enabling clinicians to comprehend their patients' immunonutritional status better and deliver customized care.

Prostate cancer cell-platelet bidirectional signaling promotes calcium mobilization, invasion and apoptotic resistance via distinct receptor-ligand pairs.

Platelets play a crucial role in cancer and thrombosis. However, the receptor-ligand repertoire mediating prostate cancer (PCa) cell-platelet interactions and ensuing consequences have not been fully elucidated. Microvilli emanating from the plasma membrane of PCa cell lines (RC77 T/E, MDA PCa 2b) directly contacted individual platelets and platelet aggregates. PCa cell-platelet interactions were associated with calcium mobilization in platelets, and translocation of P-selectin and integrin αIIbß3 onto the platelet surface. PCa cell-platelet interactions reciprocally promoted PCa cell invasion and apoptotic resistance, and these events were insensitive to androgen receptor blockade by bicalutamide. PCa cells were exceedingly sensitive to activation by platelets in vitro, occurring at a PCa cell:platelet coculture ratio as low as 1:10 (whereas PCa patient blood contains 1:2,000,000 per ml). Conditioned medium from cocultures stimulated PCa cell invasion but not apoptotic resistance nor platelet aggregation. Candidate transmembrane signaling proteins responsible for PCa cell-platelet oncogenic events were identified by RNA-Seq and broadly divided into 4 major categories: (1) integrin-ligand, (2) EPH receptor-ephrin, (3) immune checkpoint receptor-ligand, and (4) miscellaneous receptor-ligand interactions. Based on antibody neutralization and small molecule inhibitor assays, PCa cell-stimulated calcium mobilization in platelets was found to be mediated by a fibronectin1 (FN1)-αIIbß3 signaling axis. Platelet-stimulated PCa cell invasion was facilitated by a CD55-adhesion G protein coupled receptor E5 (ADGRE5) axis, with contribution from platelet cytokines CCL3L1 and IL32. Platelet-stimulated PCa cell apoptotic resistance relied on ephrin-EPH receptor and lysophosphatidic acid (LPA)-LPA receptor (LPAR) signaling. Of participating signaling partners, FN1 and LPAR3 overexpression was observed in PCa specimens compared to normal prostate, while high expression of CCR1 (CCL3L1 receptor), EPHA1 and LPAR5 in PCa was associated with poor patient survival. These findings emphasize that non-overlapping receptor-ligand pairs participate in oncogenesis and thrombosis, highlighting the complexity of any contemplated clinical intervention strategy.

Dendriform pulmonary ossification in a patient with sickle cell disease.

Dendriform pulmonary ossification (DPO) is a rare condition characterised by the formation of bones in lung tissues. This case report describes the first reported case of DPO in a patient with sickle cell disease (SCD), identifying DPO as a potential pulmonary consequence of SCD.

Correlates of successful transition in young adults with sickle cell disease.

The transition period from pediatric care to adult care for patients with sickle cell disease (SCD) is associated with increased mortality and morbidity. Identification of risk factors for unsuccessful transition may aid in developing strategies to improve the transition process and health outcomes in this population. We examined factors associated with unsuccessful transition from pediatric to adult care for patients with SCD at the Johns Hopkins Hospital. We found that public insurance and increased hospitalization rates were associated with poor transition to adult care. The findings provide possible areas of intervention.

Vacuum filling of complex microchannels with liquid metal.

This paper describes the utilization of vacuum to fill complex microchannels with liquid metal. Microchannels filled with liquid metal are useful as conductors for soft and stretchable electronics, as well as for microfluidic components such as electrodes, antennas, pumps, or heaters. Liquid metals are often injected manually into the inlet of a microchannel using a syringe. Injection can only occur if displaced air in the channels has a pathway to escape, which is usually accomplished using outlets. The positive pressure (relative to atmosphere) needed to inject fluids can also cause leaks or delamination of the channels during injection. Here we show a simple and hands-free method to fill microchannels with liquid metal that addresses these issues. The process begins by covering a single inlet with liquid metal. Placing the entire structure in a vacuum chamber removes the air from the channels and the surrounding elastomer. Restoring atmospheric pressure in the chamber creates a positive pressure differential that pushes the metal into the channels. Experiments and a simple model of the filling process both suggest that the elastomeric channel walls absorb residual air displaced by the metal as it fills the channels. Thus, the metal can fill dead-ends with features as small as several microns and branched structures within seconds without the need for any outlets. The method can also fill completely serpentine microchannels up to a few meters in length. The ability to fill dense and complex geometries with liquid metal in this manner may enable broader application of liquid metals in electronic and microfluidic applications.

Taking the lead from premature babies regarding their care.

William was born at 26 weeks' gestation and, three weeks later, he is in a high-dependency ward breathing with the help of a continuous positive airway pressure (CPAP) machine. On the whiteboard next to his incubator, a nurse has written 'minimal handling'.

The Impact of Obsessive Compulsive Personality Disorder on Cognitive Behaviour Therapy for Obsessive Compulsive Disorder.

BACKGROUND: It is often suggested that, in general, co-morbid personality disorders are likely to interfere with CBT based treatment of Axis I disorders, given that personality disorders are regarded as dispositional and are therefore considered less amenable to change than axis I psychiatric disorders. AIMS: The present study aimed to investigate the impact of co-occurring obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD) on cognitive-behavioural treatment for OCD. METHOD: 92 individuals with a diagnosis of OCD participated in this study. Data were drawn from measures taken at initial assessment and following cognitive-behavioural treatment at a specialist treatment centre for anxiety disorders. RESULTS: At assessment, participants with OCD and OCPD had greater overall OCD symptom severity, as well as doubting, ordering and hoarding symptoms relative to those without OCPD; however, participants with co-morbid OCD and OCPD demonstrated greater treatment gains in terms of OCD severity, checking and ordering than those without OCPD. Individuals with OCD and OCPD had higher levels of checking, ordering and overall OCD severity at initial assessment; however, at post-treatment they had similar scores to those without OCPD. CONCLUSION: The implications of these findings are discussed in the light of research on axis I and II co-morbidity and the impact of axis II disorders on treatment for axis I disorders.

The association between obsessive compulsive disorder and obsessive compulsive personality disorder: prevalence and clinical presentation.

OBJECTIVES: The relationship between Obsessive Compulsive Disorder (OCD) and Obsessive Compulsive Personality Disorder (OCPD) has been the subject of interest for some time due to the historical assumption that OCPD causes OCD. This study systematically examined the association between OCD and OCPD in terms of prevalence and clinical presentation. The specificity of the association between OCD and OCPD was investigated relative to another axis I anxiety disorder (Panic disorder). DESIGN AND METHOD: Data for this study were drawn from measures taken at initial assessment at a specialist treatment centre for anxiety disorders. Of the 359 participants included in this study, 189 had a principal diagnosis of OCD, while 170 had a principal diagnosis of Panic disorder. Measures included SCID I and II interview modules and self-report measures of anxiety, depression, and OCD syptomatology. RESULTS: Significantly elevated rates of OCPD were found in OCD relative to Panic disorder. Regardless of axis I disorder, individuals with comorbid OCPD reported more severe depression relative to those without. Participants with both OCD and OCPD had greater self-reported OCD symptom severity, doubting, ordering, and hoarding symptoms at assessment relative to those without OCPD. Participants with OCD and comorbid OCPD also reported significantly higher levels of alcohol consumption. CONCLUSIONS: There appears to be a significant and specific association between OCD and OCPD. Co-occurring OCD and OCPD is associated with greater severity of impairment in terms of certain OCD symptoms. CLINICAL IMPLICATIONS: The significant and specific association between OCD and OCPD suggests that OCPD occurs more frequently with OCD than previously suggested. A comorbid OCPD diagnosis is associated with a greater degree of depression, regardless of axis I disorder, either OCD or Panic disorder. This is an important consideration, as depression can interfere with therapeutic progress (Foa, 1979). Participants with OCD and OCPD had greater self-reported OCD severity, along with doubting, ordering, and hoarding symptoms, relative to those without OCPD. In clinical practice, where OCD symptoms are severe, and the primary OCD symptoms include doubting, ordering, and hoarding, this may indicate a need to assess for comorbid OCPD. This may be useful in terms of including relevant information in formulation with the patient, and in addressing these issues in treatment. LIMITATIONS OF THE STUDY: There may have been a sampling issue, as the study compared patients from a specialist clinic for the treatment of OCD and Panic disorder. Furthermore, OCD referrals were primary, secondary, or tertiary, whereas Panic disorder referrals were primary or secondary from the immediate catchment area only. This suggests the possibility of greater severity of the OCD sample relative to Panic disorder patients. All participants who met criteria for OCD were assessed for OCPD regardless of whether or not this was indicated by the SCID II screener self-report measure, while participants with Panic disorder were interviewed for OCPD only if indicated by the SCID-II screener. Had participants with Panic disorder been assessed for OCPD regardless of whether or not this was indicated by the SCID-II screener, there is a possibility that a higher rate of OCPD in the Panic disorder sample may have been found.

Beliefs and experiences in hoarding.

Recent research suggests that hoarding problems may be relatively heterogeneous, with the suggestion that three belief dimensions may underpin hoarding experiences, namely harm avoidance, fear of material deprivation, and heightened "sentimentality" in relation to possessions. The role of these hypothesised belief dimensions in hoarding was evaluated in this study, together with the association between compulsive hoarding and OCD on several clinically relevant variables. As hypothesised, individuals with hoarding and co-existing OCD reported greater harm avoidance beliefs in relation to possessions compared with a group of hoarders without OCD. Contrary to expectation, however, the hoarding group without OCD did not report significantly stronger beliefs associated with material deprivation and attachment disturbance relative to the hoarding with OCD group. The comparison of the clinical presentation of participants across groups lends further support to the notion that hoarding should be considered a distinct clinical syndrome from OCD.

The impact of symptomatic hoarding in OCD and its treatment.

BACKGROUND: The value of defining subtypes in obsessive compulsive disorder (OCD) has become an important issue for recent debate. Probably the most robust example of subtyping is the identification of hoarding as being different both in terms of psychopathology and response to treatment. AIMS: To identify differences in psychopathology and treatment response in OCD patients with and without additional hoarding symptoms. METHOD: Patients who had undertaken CBT for OCD were selected as falling into either a high or a low hoarding group. The high hoarding group (n = 18) was selected on the basis of a high score on the hoarding subscale of a self-report measure of OCD symptoms in addition to reaching clinician judged "threshold" on the hoarding item of the Obsessive Compulsive Personality Disorder (OCPD) SCID-II module. The low hoarding group (n = 20) was selected on the basis of a low score on the hoarding subscale and a clinician judgement that the hoarding item of the OCPD SCID-II module was "absent". RESULTS: On some measures of pre-treatment psychopathology, patients with OCD with hoarding symptoms were more severely affected than those without hoarding symptoms. It was found that there was no difference in eventual treatment outcome between the two groups, although there was some evidence that the hoarding group showed greater symptom decreases. CONCLUSIONS: The presence of hoarding symptoms does not negatively impact on the treatment of OCD.

Service user perspectives of a psychoeducation group for individuals with a diagnosis of bipolar disorder: a qualitative study.

Group psychoeducation, incorporating cognitive-behavioral techniques, is increasingly used as part of the treatment package for bipolar disorder. The aim of this study was to explore service-users' perspectives of a psychoeducation group which was run in the context of a community mental health service. Semi-structured interviews were conducted with 11 participants who had completed a psychoeducation group for individuals with a diagnosis of bipolar disorder. The verbatim transcripts of those interviews were analyzed using IPA. Three superordinate themes emerged from the data, including the treatment of bipolar disorder, perception of others, and learning from the group. From the perspectives of the service-users, positive working alliances with mental health professionals and the need for a treatment strategy that matches the individual's own approach to their illness were highlighted as benefits of participation in the group.