ABSTRACT
Renal cell carcinoma (RCC) remains incurable in advanced stages. Biomarkers have proven to be quite useful in cancer therapeutics. Herein, we provide a comparative/integrative statistical analysis of seminal immunohistochemistry (IHC) findings for Wilms' Tumor 1 antigen (WT1) and thymine dimers (TDs), emerging as atypical, yet promising, potential biomarkers for RCCs. We assessed WT1/TD reactivity in adult RCC tumor cells, tumor microenvironment (TME), and tumor-adjacent healthy renal tissue (HRT). WT1 positivity was scarce and strictly nuclear in tumor cells, whereas TD-reactive tumor tissues were prevalent. We report statistically significant positive correlations between the density of reactive RCC cellularity and the intensity of nuclear staining for both biomarkers (WT1 - rho = 0.341, p-value = 0.036; TDs - rho = 0.379, p-value = 0.002). RCC stromal TME TD-positivity was much more frequent than WT1 reactivity, apparently proportional to that of the proper RCC cellularity and facilitated by extensive RCC inflammatory infiltration. TDs exhibited nuclear reactivity for most TME cell lines, while RCC TME WT1 expression was rare and inconsistent. In HRTs, TDs were entirely restricted to renal tubular cells, the likely cellular progenitor of most conventional RCC subtypes. In lieu of proper validation, these early findings have significant implications regarding the origins/biology of RCCs and may inform RCC therapeutics, both accounting for the high frequency of immunotherapy-permissive frameshift indels in RCCs, but also hinting at novel predictive clinical tools for WT1-targeted immunotherapy. Overall, the current study represents a meek yet hopefully significant step towards understanding the molecular biology and potential therapeutic targets of RCCs.
ABSTRACT
BACKGROUND: Premature newborns are at a significant risk for Systemic Inflammatory Response Syndrome SIRS, a condition associated with high morbidity and mortality. This study aimed to evaluate the predictive and diagnostic capability of laboratory markers like Neutrophil to Lymphocyte Ratio (NLR), derived Neutrophil to Lymphocyte Ratio (dNLR), Platelet-to-Lymphocyte Ratio (PLR), and Neutrophil-to-Lymphocyte-to-Platelet Ratio (NLPR) in diagnosing SIRS in premature newborns. METHODS: Premature newborns with and without SIRS were evaluated in a prospective design during a one-year period. Among 136 newborns, early and 72 h post-birth analyses were performed. RESULTS: At 24 h, NLR's cutoff value was 8.69, yielding sensitivity and specificity rates of 52.77% and 83.47% (p = 0.0429), respectively. The dNLR showed a cutoff of 5.61, with corresponding rates of 63.27% and 84.15% (p = 0.0011), PLR had a cutoff of 408.75, with rates of 51.89% and 80.22% (p = 0.1026), and NLPR displayed a cutoff of 0.24, with rates of 75.85% and 86.70% (p = 0.0002). At 72 h, notable sensitivity and specificity improvements were observed, particularly with NLPR having a cutoff of 0.17, showing sensitivity of 77.74% and specificity of 95.18% (p < 0.0001). NLR above the cutoff indicated a 33% increase in SIRS risk, with a hazard ratio (HR)of 1.33. The dNLR was associated with a twofold increase in risk (HR 2.04). NLPR demonstrated a significant, over threefold increase in SIRS risk (HR 3.56), underscoring its strong predictive and diagnostic value for SIRS development. CONCLUSION: Integrating these findings into clinical practice could enhance neonatal care by facilitating the early identification and management of SIRS, potentially improving outcomes for this vulnerable population.
ABSTRACT
This study presents a systematic review of the literature on individuals' health-related quality of life (HRQoL) following radical cystectomy for muscle-invasive bladder cancer (MIBC), utilizing the Short Form-36 Health Survey (SF-36) as a primary assessment tool. The review was designed as an exhaustive literature search across three major databases including PubMed, Scopus, and Embase up to December 2023, using the PRISMA guidelines. The selection process refined 2281 identified articles down to 11 studies meeting our inclusion criteria. These studies encompassed a diverse demographic and clinical profile of 774 participants, with follow-up durations ranging from 3 to 130 months, thereby offering insights into both short-term and long-term HRQoL outcomes. The results highlighted significant alterations in individuals' HRQoL across various domains post-radical cystectomy. Notably, the Physical Functioning (PF) and Bodily Pain (BP) domains generally scored higher, indicating a moderate to high perceived physical health status. However, the Role Physical (RP) and Role Emotional (RE) domains showed variability, reflecting the challenges in daily role fulfillment and emotional adjustment post-surgery. A marked variability in physical recovery was observed, with studies reporting significant differences in PF and RP scores between patient groups. The General Health (GH) and Vitality (VT) domains sometimes reflected perceived deteriorations, whereas the Mental Health (MH) scores suggested that many patients maintained or achieved high levels of well-being post-operatively. The conclusions drawn from this systematic review underscore the profound and multi-faceted impact of radical cystectomy on HRQoL, varying widely between studies, being influenced by geographic factors, surgical methods, and the time of evaluation. The findings emphasize the necessity for holistic patient care approaches that address both physical and emotional rehabilitation, aiming to improve HRQoL outcomes.
ABSTRACT
The 2019 coronavirus disease (COVID-19) pandemic has had a profound influence on different sectors of society, including health. This study hypothesized a significant impact of the pandemic on the quality of life and psychosocial well-being of urothelial cancer patients, specifically anticipating a decrease in anxiety and depression scores as the pandemic progressed. The primary objectives were to assess longitudinal changes in quality of life indexes, evaluate Healthcare Anxiety and Depression Scale (HADS) score trends over three years (2020-2022), and identify any correlational patterns between the progression of the pandemic and anxiety, depression, and stress levels among this cohort. A cross-sectional analysis was conducted on Eastern Cooperative Oncology Group (ECOG) 1 and Tumor Node Metastasis (TNM) stage 1 bladder cancer patients from the Timis County Emergency Clinical Hospital in Romania. Sixty patients were evaluated each year from 2020 to 2022, utilizing a detailed selection process involving the review of both the hospital database and paper records. Key data included demographic information, medical history, and responses to the Patient Health Questionnaire (PHQ-9), Short Form (SF-36), HADS, and Generalized Anxiety Disorder (GAD-7) questionnaires. A total of 163 completed questionnaires were analyzed, providing insight into various aspects of patients' experiences during the pandemic. Notably, the mean hospitalization days ranged from 3.6 ± 2.1 days in 2020 to 4.0 ± 2.4 days in 2022 (p = 0.663). Concerns that current symptoms might be pandemic-related spiked to 63.5% in 2021, but reduced to 50.9% in 2022, with this fluctuation being significant (p = 0.026). The perception of decreased quality of or accessibility to medical care was significant over the years, with a decline to 52.7% in 2022 (p = 0.033). Quality of life assessments demonstrated an upward trend, from an average score of 55.9 ± 8.9 in 2020 to 59.3 ± 8.8 in 2022 (p = 0.049). Interestingly, anxiety levels, as indicated by the HADS survey, revealed a significant decline from a score of 7.8 in 2020 to 6.5 in 2022 (p = 0.008). On the other hand, GAD-7 scores displayed a downward trend over the years, potentially indicative of developed coping strategies (p = 0.034). This study provides a comprehensive insight into the fluctuating dynamics of psychosocial factors and quality of life among urothelial cancer patients during the pandemic years. It underscores a potential adaptive response, as evidenced by the decrease in anxiety levels and an upward trend in the quality of life scores over the period. These findings highlight the resilience and adaptability of this patient cohort amidst the challenges posed by the pandemic, potentially guiding future interventions and supports in similar health crises.
ABSTRACT
The COVID-19 pandemic caused major changes in the healthcare sector due to adaptations required to hospitalize and treat an impressive number of patients. This retrospective study intended to collect reliable information on urothelial cancer patients in Romania. The primary objective was to compare the pre-pandemic and pandemic periods to observe the differences that occurred in the management of patients with urothelial carcinoma. The secondary objective was to determine the risk factors for urothelial cancer progression in the study cohort correlated with the COVID-19 pandemic. All patients that were diagnosed and treated at our clinic with a diagnosis of urothelial carcinoma (transitional cell carcinoma) during 2019-2021 were included in the current study. A total of 1122 eligible unique cases were identified during the study period. The number of patients who underwent intervention in the pre-pandemic year was 421, followed by a 22.6% decrease in 2020 to 326 cases and a 13.1% increase in 2021 to 375 cases. The proportion of muscle-invasive bladder cancer (MIBC) cases was significantly higher during the pandemic years, from 30.5% MIBC cases in 2019 to 37.4% in 2020 and 39.4% in 2021, suggesting a delay in presentations during the pandemic. Stage III and IV (TNM) cases were significantly more frequent, even though approximately 40% of all patients were operated on in stage I. The number of cystectomies increased significantly, from 5.2% in 2019 and 4.3% in 2020 to 10.1% in 2021, while the number of elective surgeries decreased, although no significant difference was observed regarding the in-hospital mortality and disease progression at six months. Patients with stage III and IV at presentation had the highest likelihood of disease progression at six months (HR = 5.61). Distant invasion was the second highest risk factor (HR = 5.13), followed by MIBC type (HR = 2.49). Nevertheless, the duration of hospitalization and year of diagnosis during the COVID-19 pandemic were not significant risk factors for cancer progression at six months. It can be concluded that there was a significant delay in patient presentations in 2020, and we advocate for increased public health awareness for urothelial cancer and increased attention toward the screening and management of these patients in the following years.
ABSTRACT
Many elderly patients with severe SARS-CoV-2 infections and COVID-19 infections are admitted to intensive care units. Age was previously identified as an independent risk factor for death and contributed to the greater severity of COVID-19. The elderly may have diminished lung functions, poor reactions to artificial ventilation, and compromised immune systems. However, it is yet uncertain how each pandemic wave and the predominant SARS-CoV-2 strains contribute to varying results and how patient groups such as the elderly are impacted. Comparing six COVID-19 pandemic waves, the objective of this study was to examine the variation in case severity, symptomatology, ICU hospitalizations, and mortality among SARS-CoV-2-infected elderly individuals. The study followed a retrospective design, including 60 eligible patients older than 70 years in each of the six pandemic wave groups, after matching them by the number of comorbidities and gender. SARS-CoV-2 infection during the first, third, and fourth pandemic waves had a significantly higher risk of mortality for hospitalized patients. Confusion and dyspnea at admission were significant risk factors for ICU admission in elderly patients (ß = 1.92, respectively ß = 3.65). The laboratory parameters identified decreased lymphocytes (ß = 2.11), elevated IL-6 (ß = 1.96), and procalcitonin (ß = 2.46) as the most significant risk factors. The third and fourth COVID-19 waves had considerably more severe infections (31.7% and 26.7%) than the sixth wave (13.3%). Median ICU stay and percentage of patients receiving oxygen support also differed across pandemic waves. However, mortality rates between the six pandemic waves were similar. The average length of hospitalization varied dramatically among the six pandemic waves. Although senior patients are more likely to have worse COVID-19 outcomes after hospitalization, this risk is mitigated by the greater prevalence of comorbidities and frailty among the elderly. The six pandemic waves that were specifically evaluated did not reveal considerably disproportionate variations in terms of patient mortality; however, during the fourth pandemic wave, there were likely more hospitalized patients with severe COVID-19 in Romania. It is probable that certain circulating SARS-CoV-2 strains were more infectious, resulting in an increase in infections and a strain on healthcare systems, which might explain the variations found in our research.
ABSTRACT
Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are currently viewed as a heterogeneous series of cancers, with the same anatomical origin, but fundamentally different metabolisms and clinical behaviors. Thus, RCC pathological diagnosis/subtyping guidelines have become increasingly intricate and cumbersome, routinely requiring ancillary studies, mainly immunohistochemistry. Meanwhile, RCC-associated-antigen targeted systemic therapy has been greatly diversified and emerging, novel clinical applications for RCC immunotherapy have already reported significant survival benefits, at least in the adjuvant setting. Even so, systemically disseminated RCCs still associate very poor clinical outcomes, with currently available therapeutic modalities only being able to prolong survival. In lack of a definitive cure for advanced RCCs, integration of the amounting scientific knowledge regarding RCC pathogenesis into RCC clinical management has been paramount for improving patient outcomes. The current review aims to offer an integrative perspective regarding contemporary RCC clinical definitions, proper RCC clinical work-up at initial diagnosis (semiology and multimodal imaging), RCC pathological evaluation, differential diagnosis/subtyping protocols, and novel clinical tools for RCC screening, risk stratification and therapeutic response prediction.
ABSTRACT
BACKGROUND/AIM: Studies developed in the field of platelet-derived growth factors/platelet-derived growth factor receptors (PDGFs/PDGFRs) inhibition have focused on the therapeutic effects on tumor cells, neglecting their potential effects on tumor blood vessels. We herein propose a differential and critic assessment of platelet-derived growth factor B (PDGF-B) and platelet-derived growth factor receptor ß (PDGFRß) in renal cell carcinoma, correlated with the four main vascular patterns previously reported by our team. MATERIALS AND METHODS: PDGF-B and PDGFRß were evaluated on 50 archival paraffin embedded specimens related to vascular endothelial growth factor (VEGF), its inhibitory isoform VEGF165b and vascular patterns. RESULTS AND CONCLUSION: Our results support the involvement of VEGF165b in the phosphorylation of PDGFRß with an inhibitory effect on endothelial proliferation and migration. The simultaneous action of PDGF-B/PDGFRß and VEGF165b on the same type of receptor may explain the resistance to antiangiogenic therapy, which depends on the degree of modulation of PDGFRß phosphorylation.
