Negative Prognostic Factor Research Articles

Is There Anything New in Canine AGASACA?

Apocrine gland anal sac adenocarcinoma (AGASACA) is a locally invasive tumor with a high potential for early metastasis. The most recent studies indicate that 23.4–83% of dogs have metastases to the iliosacral lymph nodes (LNs), and 2.1–31% have distant metastases to other organs at the time of first presentation. Usually, only one anal sac is affected, but bilateral involvement has been reported in 4–20% of dogs. About 16–53% of dogs present with paraneoplastic hypercalcemia. The most recent studies show an overall improvement in median survival time (MST) (15–28 months) for dogs with different stages of AGASACA treated with surgery and adjuvant therapy compared to those treated with chemotherapy alone (6.9 to 8.7 months). The highest MST (22–32 months) was reported when radiation therapy (RT) was selected as a sole or adjunctive treatment. Several studies have been published to identify the subset of tumors with more aggressive behavior and higher metastatic potential. The main negative prognostic factors are the size of the primary tumor, metastatic regional lymphadenopathy at first presentation, the size and the number of the metastatic lymph nodes, distant metastases at the time of diagnosis, and the histological characteristics of the primary tumor. In this critical review, the latest advancements in histological diagnosis, staging, treatment, and prognosis of AGASACA are described. The aim is to provide a full overview of this neoplasm, focusing on the latest advancements on prognostic variables and treatments.

Targeted SPP1 Inhibition of Tumor-Associated Myeloid Cells Effectively Decreases Tumor Sizes.

Secreted phosphosprotein 1 (SPP1)High tumor-associated macrophages (TAM) are abundant tumor myeloid cells that are immunosuppressive, pro-tumorigenic, and have a highly negative prognostic factor. Despite this, there is a lack of efficient TAM-specific therapeutics capable of reducing SPP1 expression. Here, on a phenotypic screen is reported to identify small molecule SPP1 modulators in macrophages. Several hits and incorporated them into a TAM-avid systemic nanoformulation are identified. It is shown that the lead compound (CANDI460) can down-regulate SPP1 in vitro and in vivo and lead to tumor remissions in different murine models. These findings are important as they offer a promising avenue for developing novel therapeutic strategies targeting TAM.

Characterization of risk factors for early ambulation in paraplegic dogs with absent pain perception undergoing decompressive surgery for thoracolumbar intervertebral disk extrusions

BackgroundCurrent literature warrants surgical decompression in paraplegic dogs with absent pain perception (APP), but the rate of ambulatory dogs with APP following thoracolumbar (TL) IVDE surgery in a clinical setting remains unknown. Furthermore, the outcome of paraplegic APP French Bulldogs (FBs) is anecdotally considered poor. The aims of this study were threefold within a large population of TL-IVDE paraplegic dogs with APP undergoing decompressive surgery: (1) to characterize early spontaneous pelvic limb movement and ambulation following surgery; (2) to identify risk factors for the recovery of ambulation; and (3) to compare the outcome of FBs and Dachshunds presenting with APP.MethodsA single-center, retrospective case series of dogs with paraplegia and APP diagnosed with TL-IVDE based on CT or MRI, all undergoing surgical decompression (hemilaminectomy ± durotomy). Two main groups were defined: ambulatory and non-ambulatory. These were further characterized depending on the presence of pain perception and spontaneous movement. The outcome was obtained at 4–8 weeks postoperatively. Statistical analysis was performed comparing ambulatory and non-ambulatory dogs and comparing rates of ambulation on FBs vs. Dachshunds.ResultsA total of 127 cases were included, with 77 out of 127 (60.6%) being ambulatory at recheck and 9 out of 127 (7.1%) being ambulatory despite APP. The remaining case distribution of non-ambulatory cases was: with APP (32 out of 127; 25.2%), with pain perception (5 out of 127; 3.9%), and with spontaneous movement (5 out of 127; 3.9%). Multivariate analysis revealed two negative factors for the recovery of ambulation: dogs undergoing hemilaminectomy alongside durotomy (p = 0.003) and dogs presenting with spinal shock (lower motor neuron signs with a lesion higher than the L3–L4 intervertebral disk) characterized by reduced/absent withdrawal reflex (p = 0.008). No difference was found between Dachshunds (n = 41, 73.2% ambulatory) and FBs (n = 33, 63.6% ambulatory) in terms of recovery of ambulation, with only 2 out of 33 (6.1%) FBs developing myelomalacia.ConclusionEarly recovery of ambulation alone (60.6%) and ambulation alongside pain perception (53.5%) occurred in the majority of surgically managed TL-IVDE-affected dogs with APP. Negative prognostic factors for recovery of ambulation were durotomy performed alongside hemilaminectomy, and dogs presenting with spinal shock with reduced/absent withdrawal reflexes, the latter translating to a reduced/absent withdrawal reflexes with a lesion higher than L3–L4 intervertebral disk. Finally, no indications of a worse prognosis for recovery of ambulation or a higher rate of development of myelomalacia in FBs when compared to Dachshunds were found.

CDKN2A/B deletion as an independent negative prognostic factor for allogeneic hematopoietic stem cell transplantation in childhood B cell precursor acute lymphoblastic leukemia.

CDKN2A/B deletion as an independent negative prognostic factor for allogeneic hematopoietic stem cell transplantation in childhood B cell precursor acute lymphoblastic leukemia.

The Pretreatment Neutrophil-to-Lymphocyte Ratio as a Near-Term Prognostic Indicator in Patients with Locally Advanced Hepatocellular Carcinoma Treated with Hepatic Arterial Infusion Chemotherapy: A Propensity Score Matching Cohort Study.

Aims/Background To investigate the predictive value of the pretreatment neutrophil-to-lymphocyte ratio (NLR) for estimating the near-term efficacy of hepatic arterial infusion chemotherapy (HAIC) in patients with locally advanced hepatocellular carcinoma (HCC). Methods In this retrospective study, data were collected from patients with locally advanced HCC treated with HAIC between January 2018 and June 2022. Patients were categorized based on their pretreatment NLRs and analyzed using propensity score matching (PSM). The primary endpoints in this study were objective response rate (ORR), progression-free survival (PFS), and safety. Results The optimal pretreatment NLR cutoff was 2.90 using the X-tile software (version 3.6.1; Yale Corp., New Haven, CT, USA), and 104 patients were included. These patients were divided into a high-NLR subgroup (>2.9; n = 44) and a low-NLR subgroup (≤2.9; n = 60). 43 matched pairs were analyzed following PSM. PFS (6.7 months vs. 3.8 months, p = 0.007) and ORR (69.8% vs. 37.2%, p = 0.002) were significantly higher in patients with a low pretreatment NLR than in patients with a high pretreatment NLR. Both univariate and multivariate regression analyses demonstrated that a high pretreatment NLR was an independent negative prognostic factor for ORR (hazard ratio [HR], 3.464; 95% CI, 1.383-8.678; p = 0.008) and PFS (HR, 1.634; 95% CI, 1.026-2.600; p = 0.038). No significant differences in the incidence of adverse events were observed between the groups. Conclusion Pretreatment NLR is a readily obtainable and effective biomarker for predicting the near-term efficacy of HAIC in patients with locally advanced HCC.

Preoperative malnutrition in elderly gastric cancer patients and adverse postoperative outcomes of radical gastrectomy

Malnutrition is not only a prevalent condition among the elderly but also a common comorbidity in elderly people with gastric cancer (GC). Malnutrition is closely linked to high rates of postoperative complications and poor wound healing in elderly GC patients, which may lead to a higher incidence and mortality rate of GC. Malnutrition decreases the physical function of elderly GC patients after surgery, severely affecting their postoperative life quality and hindering subsequent treatments. This retrospective study was conducted by Zhao et al , focusing on the clinical baseline data, postoperative complications, and hospitalization times of elderly GC patients who underwent curative gastrectomy. Additionally, the underlying causes of poor outcomes for patients were discussed. This study may provide a solid basis for the clinical treatment of elderly GC patients in the future. Therefore, malnutrition can serve as a negative prognostic factor for curative surgery in GC patients. Addressing malnutrition and its adverse effects can benefit elderly GC patients from surgical treatment.

RBIO-03. A SMALL ANIMAL RADIATION RESEARCH PLATFORM (FLASH-SARRP) TO MEASURE IMMUNOLOGICAL EFFECT OF ULTRA HIGH DOSE RATE (FLASH) RADIOTHERAPY

Abstract Patients who undergo radiation therapy (RT), particularly fractionated courses, often develop lymphopenia. Clinical outcome for various cancer types, including brain tumors, identifies lymphopenia as a negative prognostic factor. The mechanism for RT induced lymphopenia is unclear. Simulated models suggest the volume of blood flowing through a radiation field could play a crucial role in death of radiosensitive lymphocytes. FLASH RT is ultrahigh dose rate administration of RT, >100 times faster dose rate than standard RT that has been observed to improve the therapeutic ratio in preclinical models by preferential normal tissue sparing. Hypothesized mechanisms include chemical reactions depleting oxygen in well oxygenated normal cells creating radioresistance, differing pro-inflammatory signaling impacting tumor and normal tissue, and less impact on circulating immune cells consequent to decreased proportion exposed during a treatment session which may enhance antineoplastic response. We designed the novel FLASH kV x-ray cabinet system for preclinical laboratory research (FLASH-SARRP) to deliver ultra-high dose rates up to 100 Gy/s as well as conventional dose rates of 1.0 Gy/s to facilitate comparative studies. A custom designed docking system was developed to reproducibly position and immobilize mouse for stereotactic radiation of the brain. Dose and dose rate measurements were performed with calibrated Gafchromic EBT3 film in solid water with 0.025 mm additional copper filter. FLASH-SARRP system delivered kV x-rays at an average dose-rate of 79.2±2.1Gy/s corresponding to 10 mm depth in the immobilized mouse brain. For the delivery of 15 Gy, treatment duration was 0.2 seconds for FLASH RT administration whereas it was 244 seconds for conventional dose rate. We successfully designed a high-precision platform to study partial brain x-ray FLASH effects in mice and studies are ongoing to assess differential impact on normal brain tissue, circulating cytokines, and immune cell populations for single dose and fractionated administration of FLASH and standard radiotherapy.

BIOM-22. SPATIAL, SINGLE-CELL, AND BULK RNA SEQUENCING IDENTIFY MOLECULAR PROGRAMS UNDERLYING MENINGIOMA BRAIN INVASION

Abstract Brain invasion is a negative prognostic factor for meningiomas, but the molecular programs underlying meningioma brain invasion are poorly understood. To address this, we performed transcriptomic analyses of 3 independent datasets: Bulk RNA sequencing from 199 meningiomas (n=33 with brain invasion), single-cell RNA sequencing of 2 regionally distinct samples from the brain tumor interface (BTI) versus tumor core (TC) (n=22,118 single-cell transcriptomes), and spatial RNA sequencing from 6 samples with (n=4) versus without (n=2) brain invasion (n=18,471 spatial transcriptomes). Single-cell and spatial datasets were integrated with Harmony, cell interactions were defined using CellChat, and cross-platform comparisons were performed with the Seurat data integration pipeline. Bulk RNA sequencing revealed enrichment of 1835 genes in meningiomas with brain invasion compared to those without brain invasion, including glial markers (GFAP, NCAN) and markers of extracellular matrix remodeling (PDGFRA, COL9A1). Single-cell RNA sequencing comparison of BTI versus TC meningioma cells identified 2793 genes that were enriched in BTI cells, 268 of which were conserved across bulk and single-cell transcriptomes from brain-invasive meningiomas. Gene ontology enrichment analysis showed molecular programs underlying cell migration and regulation of neurogenesis at the BTI, while glycolysis and antigen presentation programs were enriched in the TC. Cholesterol, CSPG4, and LIF signaling were active in the TC, while SLIT signaling was enriched at the BTI. Spatial RNA sequencing showed enrichment of 439 genes at the BTI, and a conserved set of 12 genes were enriched in BTI meningioma cells across bulk, single-cell, and spatial datasets (TGM2, APOC1, IGFBP6, PLEKHO1, GFPT2, ZYX, IQGAP3, LUM, S100A11, ARPC1B, CDK1, CYCS). Comparison of tumor microenvironment monocytes at the BTI versus TC demonstrated enrichment of 1571 genes that were associated with macrophage migration and activation. These data elucidate molecular programs underlying meningioma brain invasion and provide insights into meningioma intratumor heterogeneity.

Assessment of Optimal Treatment Strategies and Their Outcomes in T3N1 Rectal Cancers.

Background:This study compares the outcomes of a surgery first vs a neoadjuvant treatment strategy in T3N1M0 rectal cancers. Methods:This was a single-centre retrospective cohort study of patients admitted for curative treatment of T3N1 rectal cancer. Patients with pre-treatment T3N1 and pathological T3N1 disease were included in the study. Patients were divided into two groups depending on whether they had surgery or neoadjuvant therapy as their initial phase of treatment. Primary outcome measures were local recurrence and distant recurrence. Secondary outcomes were disease-free survival (DFS) and overall survival (OS). Tabulated results were analyzed with appropriate statistical tests. Results:One hundred and ten patients were initially selected. Fourty-eight were finally included after excluding patients who did not meet the staging criteria or were not eligible for curative treatment. Twenty-nine patients underwent surgery, and 19 patients with neoadjuvant therapy as their first treatment. No local recurrence was noted in either group, with a distant recurrence noted in group 2 (6.9%) and group 1 (5.26%) cases among the surgery-first and neoadjuvant-first groups, respectively. Disease-free survival and overall survival were 29.5 and 30 months for the surgery-first group and 22 and 22 months for the neo-adjuvant group, respectively. Conclusions:Outcomes in the surgery-first group were non-inferior to that of the neoadjuvant group. A threatened circumferential resection margin (CRM) on pretreatment staging warrants neoadjuvant therapy to ensure an R0 resection. Extramural vascular invasion (EMVI), being a negative prognostic factor, doesn't preclude a surgery-first approach.

Pre-operative collapsed disc is a negative prognostic factor of back-pain outcome in trans-foraminal endoscopic discectomy. A single cohort clinical study

PurposeTrans-foraminal endoscopic discectomy (TELD) is an alternative surgical technique for lumbar disc herniation (LDH). Compared with microscope-assisted open discectomy, TELD is expected to result in less postoperative low back pain (LBP) and has a lower likelihood of complications. However, some clinical analysis report patients still had persistent LBP at follow-up. Several studies have identified different known risk factors for LBP after TELD, including the preoperative presence of disc height loss and “microinstability” of the lumbar spine, which can be detrimental to a patient's successful outcome. MethodsWe conducted a retrospective review of a cohort of 86 patients with symptomatic LDH who underwent TELD surgery in a single Neurosurgery Unit from 2021 to 2023 and subjected themselves to a clinical and radiological follow-up program up to one year, focusing on the presence of collapsed disc (Group A) and the presence of normal intersomatic height (Group B) at the site of lumbar herniation. ResultsThe two groups demonstrated no significant differences in the pain and disability scales at the preoperative and postoperative phases, both after surgery and during follow-up. However, at the 1-year clinical evaluation, patients who had signs of a collapsed disc before surgery experienced less recovery on the ODI scale compared to the other group ConclusionOur study showed that the presence of severe intervertebral disc height loss, accompanied by pre-operative signs of a collapsed disc at the site of the LDH, may serve as a predictor of poor postoperative pain recovery.

HIV tropism to chemokine coreceptors. Features of the definition, the current state

HIV infection is a significant cause of death worldwide, the number of people with HIV infection in the Russian Federation as of 2022 amounted to 1163818 people. The determination of HIV tropism is necessary for the appointment of drugs from the group of penetration inhibitors, and also opens up new opportunities in the prediction and analysis of HIV infection in a patient.Aim. To present a description and assess the current state of methods for determining HIV tropism, to summarize known information about the influence of HIV tropism on the course of the disease, to identify topical issues related to HIV tropism and requiring solutions.Materials and methods. A review of domestic and foreign sources devoted to methods for determining the prevalence and clinical significance of HIV tropism was carried out.Results. For the effective administration of CCR5 antagonist drugs, preliminary analysis is necessary to establish the tropism of HIV by genotypic or phenotypic methods. The use of CCR5 antagonists is not possible if HIV can use the CXCR4 coreceptor. CXCR4 – tropism of HIV is associated with the duration of the disease, a decrease in the number of CD4 cells, AIDS, and is a negative prognostic factor. Human mutations affecting coreceptors can affect the course of infection and susceptibility to HIV.Conclusion. The determination of HIV tropism is a useful analysis, the importance of which will increase in connection with the development of new drugs from the group of penetration inhibitors. To increase the availability of HIV tropism analysis in the Russian Federation, the creation of genotypic test systems is required. To create proprietary algorithms used in genotypic analysis, as well as laboratory testing and development of new effective drugs from the group of penetration inhibitors, it is necessary to develop a phenotypic test system. The small study of the influence of other regions of the env gene on HIV tropism, the study of HIV tropism to alternative coreceptors are urgent issues that need to be addressed.

Impact of age on surgical outcomes for world federation of neurosurgical societies grade I and II aneurysmal subarachnoid haemorrhage: a novel prognostic model using recursive partitioning analysis

This study aimed to evaluate age as a prognostic factor and develop a comprehensive prognostic model for patients undergoing clipping surgery for World Federation of Neurosurgical Societies (WFNS) grade I/II aneurysmal subarachnoid haemorrhage (SAH). We retrospectively investigated 188 patients with WFNS grade I/II SAH who underwent microsurgical clipping at our institute between December 2010 and January 2020. The data of 176 patients (75 with grade I and 101 with grade II) were analysed. Data on patient demographics, aneurysm characteristics, SAH factors, surgical details, and clinical outcomes were collected. Prognostic factors were assessed using bivariate and multivariable logistic regression analyses, and recursive partitioning analysis. Favourable outcomes (mRS 0–2) were observed in 76% of patients. Age, a significant negative prognostic factor in multivariable analysis (odds ratio 0.55, 95% confidence interval 0.40–0.76, p < 0.001), was cutoff at 70 years by the receiver operating characteristic curve. Patients aged ≤ 70 years had significantly better outcomes than those aged > 70 years (84% vs. 46%, respectively; p < 0.001). Epileptic seizures were significantly associated with poor outcomes in older adults (p < 0.001). A prognostic model (favourable, intermediate, and poor) based on age and postoperative adverse events showed significantly different outcomes between age groups (p < 0.001). Age was a stronger prognostic factor than WFNS grading for patients with grade I/II SAH undergoing microsurgical clipping. For patients aged ≤ 70 years, precise microsurgeries with fewer complications were associated with favourable outcomes beyond WFNS grade. For older patients, postoperative intensive seizure management may prevent poor outcomes.

Challenges in the treatment of soft-tissue plasmacytoma: a retrospective analysis of 120 patients with extramedullary multiple myeloma

PurposeDespite the development of novel drugs and the widespread use of hematopoietic cell transplantation, the prognosis of patients (pts) with multiple myeloma and extramedullary involvement (soft-tissue plasmacytoma, STP) is rather unfavorable.MethodsA retrospective analysis of 120 pts with STP treated between 2007 and 2022 was performed. The effects of demographic and clinical characteristics on treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated.ResultsThe rate of serological response to first-line STP treatment (at least partial remission) was 67%, and the rate of imaging response was 59%. With a median follow-up of 84.2 months, the median PFS was 10.5 months (primary STP: 20.2 months; secondary STP: 5.8 months), and the median OS was 24.5 months (primary STP: 34.5 months; secondary STP: 12.4 months). Based on the multivariate regression analysis, secondary STP (HRPFS 2.75; HROS 2.63) and organ involvement (HRPFS 1.45; HROS 1.68) were found to be negative prognostic factors of both PFS and OS. In a prognostic model, pts with at least one of these factors had a significantly worse PFS (HRPFS 3.31) and OS (HROS 3.45) than those with none risk factor.ConclusionIn pts with STP, risk-adapted treatment strategies including immunotherapies and cell therapies are urgently required.

Prognostic value of sarcopenia defined by the Sarcopenia Definitions and Outcomes Consortium criteria in patients with heart failure

Abstract Background Sarcopenia, the loss of skeletal muscle mass and function, is recognized as a negative prognostic factor in heart failure patients. Current guidelines, such as those by the Asian Working Group for Sarcopenia (AWGS), emphasize quantifying muscle mass using methods like bioelectrical impedance analysis or dual-energy X-ray absorptiometry, known for their precision. In contrast, the Sarcopenia Definitions and Outcomes Consortium (SDOC) focuses on functional parameters. However, its applicability and effectiveness as a prognostic indicator in heart failure remain uncertain. Purpose To determine the prognostic utility of sarcopenia determined by the SDOC diagnostic criteria in predicting all-cause mortality among older patients with heart failure, and to compare its prognostic predictability with that of the AWGS 2019 diagnostic algorithms. Methods This was a post-hoc analysis of the FRAGILE-HF study, a prospective, multicenter, observational study involving patients aged ≥65 years hospitalized for heart failure. Sarcopenia was diagnosed according to two definitions: AWGS 2019 guidelines criteria and the SDOC criteria, which diagnose sarcopenia based only on grip strength and gait speed. With SDOC criteria, patients were divided into three groups: sarcopenia (low grip strength and decreased gait speed), pre-sarcopenia (low grip strength or decreased gait speed), and non-sarcopenia (normal grip strength and normal gait speed) groups. Two logistic models for the primary outcome were constructed by adding the information on pre-sarcopenia and sarcopenia defined by AWGS 2019 and SDOC to the MAGGIC-HF risk score + log BNP, and prognostic predictability was compared by receiver operating characteristic curve areas under the curve (ROC-AUC) and net-reclassification improvement (NRI) between three models. The primary outcome was 2-year mortality. Results Of 1282 study patients, pre-sarcopenia and sarcopenia were diagnosed in 357 and 786 individuals, respectively, according to SDOC criteria. The Kaplan-Meier analysis revealed a significant stepwise association between the sarcopenic status and the primary outcome. The adjusted Cox proportional hazards analysis indicated a significant stepwise association between sarcopenic status and mortality risk (pre-sarcopenia, hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 0.66–2.28, P= 0.525; sarcopenia, HR: 1.89, 95% CI: 1.08–3.34, P= 0.027). No significant difference was observed in the prognostic capabilities between the two models adding sarcopenia defined by SDOC and AWGS 2019 diagnostic criteria to the model incorporating the MAGGIC-HF risk score + log BNP (NRI: -0.009, 95% CI: -0.193–0.174, P=0.920, with ROC-AUC of 0.697 for SDOC and 0.703 for AWGS 2019, P=0.675, respectively). Conclusion Diagnosing sarcopenia with the SDOC criteria, which does not include muscle mass, provides incremental prognostic information as same as that defined by AWGS 2019 criteria.Figure

Overexpression of Fibroblast Growth Factor 8 Is a Predictor of Impaired Survival in Esophageal Squamous Cell Carcinoma and Correlates with ALK/EML4 Alteration.

FGF8, ALK, and EML4 have been identified as promising biomarkers in a number of malignancies. The aim of this study was to examine the prognostic role of FGF8, ALK, and EML4 in esophageal squamous cell carcinoma (ESCC). Methods: Consecutive patients with ESCC who underwent upfront resection were included in this study. ALK and EML4 gene status was evaluated by fluorescence in situ hybridization (FISH) using a triple-color break-apart single-fusion probe and a probe against 2p11. FGF8, ALK, and EML4 protein expression was determined by immunohistochemistry. Results: A total of 122 patients were included in this study. Multivariate analysis revealed that FGF8 overexpression is an independent negative prognostic factor for patients' overall survival (OS) (p = 0.04). Furthermore, a significant correlation between the expression of FGF8, and ALK (p = 0.04) and EML4 (p = 0.01) alteration was found. Conclusions: FGF8 overexpression is an adverse independent prognostic factor in patients with upfront resected ESCC. Furthermore, FGF8 expression significantly correlates with ALK and EML4 amplification and may therefore qualify as a future therapeutic target.

The Critical Role of Stereotactic Body Radiation Therapy in Multimodal Treatment of Lung Metastasis from Bone and Soft Tissue Sarcomas.

Stereotactic body radiotherapy (SBRT) is increasingly used to treat lung metastasis (LM) in patients with soft tissue sarcoma (STS) and bone sarcoma (BS). This retrospective study evaluated the outcomes of patients with BS and STS treated with SBRT for LM between 2010 and 2023. We enrolled 102 patients (51 each with STS and BS), of whom 71 were males and 31 were females (median age, 40 years; range, 11-81 years). At diagnosis, 76 and 26 patients had localized and metastatic disease, respectively, with a median of 4 recurrences (range, 1-12). Before SBRT, 75 patients received chemotherapy and 52 underwent surgery for LM, with 276 nodules treated with SBRT (median dose, 48 Gy; range, 40-52). Local control of irradiated LM was 86% at 1 year and 78% at 2 years. By 31 December 2023 (median follow-up, 4.8 years), 60 patients had died and 42 survived (20 without ongoing disease). From the first LM relapse, the median overall survival (OS) was 4.8 years and the 5-year OS was 49% (95% confidence interval, 39-60%), with no difference between STS and BS; the median OS was 2.9 years and the 5-year OS was 36% after SBRT. Chemotherapy before SBRT was a negative prognostic factor by multivariate analysis. Long-term follow-up shows that SBRT as part of a multimodal treatment approach has reasonable survival rates in patients with LM due to sarcoma. Compared with historical results using only surgery and chemotherapy, SBRT has improved the 5-year OS.

Unscheduled Hospital Admission as a Prognostic Factor in the Oncologic Patient: A Retrospective Study.

Aims This research aimed to determine the correlation between survival, symptoms, and unscheduled admission in oncologic patients. Furthermore, this study aimed to develop a prognostic model that helps clinicians establish the indication of intervention by palliative care teams. Methodology A retrospective study of patients' digital clinical history registry was conducted to meet the two core objectives. The study population was patients with solid tumors undergoing unscheduled admissions to the oncology ward between January 1, 2018, and May 31, 2018. Demographic and clinical variables of those patients wereanalyzed. Specifically, the statistical analysis involved descriptive analysis, Kaplan-Meier curves, Log-Rank, andChi-Squared Automatic Interaction Detection decision tree modeling. Results The results were obtained from 100 admissions of patients with an average age of 64. Of the patient cases examined, 67% (n = 67) were male.In 72% (n = 72) of the cases, patients presented with Stage IV tumors, and the most frequent primary tumor location among the admissions was lung, at 29% (n = 29). Intervention by the palliative care team occurred for 38% (n = 38) of patients. Mortality at 30, 90, 180, and 365 days was 34% (n = 34), 56% (n = 56), 71% (n = 71), and 78% (n = 78), respectively. Hepatic metastasis was the main predictor of mortality at 30 days (65%, n = 13) and at 90 days (90%, n = 18). In the absence of hepatic metastasis, the presence of more than one symptom predicted a mortality rate of 70% at 30 days. The main factor associated with mortality at 180 and 365 days was the tumor stage, with stage IV tumors having the highest mortality rate (84.7%, n = 61, and 90.3%, n = 65, respectively). Among the Stage IV population, the primary site shows a significant impact on survival, with colorectal/reproductive tumors being associated with decreased mortality. Conclusion Unscheduled admission is a negative prognostic factor in oncologic patients. An unscheduled admission can be expected to result in low survival in an oncologic patient, especially in those presenting with stage IV; involving non-colorectal/reproductive primaries; or presenting with pain, dyspnea, cachexia, or delirium.

Bioinformatic analysis of neuropeptide related genes in patients diagnosed with invasive breast carcinoma

PurposeNeuropeptide receptors are expressed in many malignancies. Effectors involved in the action mechanisms of HCRTR1, HCRTR2, NPY4R (PPYR1) may be related to breast cancer (BC). Genes encoding these receptors and PPY and PTPN11 genes were aimed to examine via bioinformatics tools in the BRCA cohort. To our knowledge, this is the first study in which these receptor genes and PP, which have not found much research in BC, are examined together with PTPN11 and analyzed comprehensively in large patient cohorts from public databases. MethodscBioPortal was used for gene alteration analyses, GeneMania for association analyses with other genes, Kaplan-Meier Plotter for Overall Survival (OS) and Relapse Free Survival (RFS) analyses, UALCAN for methylation analyses, TIMER2.0 for expression analyses, The Human Protein Atlas database for expression validations, TIMER for immune infiltration analyses, WEKA 3.8.6 for diagnostic classification performances of the genes based on Random Forest Classifier and Enrichr-KG for Gene Ontology (GO) Biological Process (BP) and KEGG analysis. Results19 (1.9 %) nucleotide changes were found in 996 cases. Missense mutation is most common. Decreased expression levels of the HCRTR1 gene were associated with shorter OS and RFS, but decreased expression levels of the PTPN11 gene were associated with longer OS and RFS. Decreased expression levels NPY4R (PPYR1) gene were associated with shorter RFS. Increased expression levels of HCRTR2 and PPY genes were associated with longer RFS. HCRTR1 and NPY4R (PPYR1) genes were statistically hypermethylated; conversely HCRTR2 and PPY genes were hypomethylated. There was no significant change in PTPN11 gene promoter methylation level. HCRTR1, NPY4R (PPYR1) and PTPN11 gene expressions were downregulated; conversely, HCRTR2 and PPY gene expressions upregulated. Weak correlations were observed between NPY4R (PPYR1) gene expression and CD4+ T Cell, Neutrophil, Dendritic Cell and between PTPN11 gene expression and CD8+ T Cell, Macrophage, Neutrophil, Dendritic Cell infiltrations. Area under the receiver operating characteristics curve values of the 10-fold cross-validation and by splitting the dataset in a ratio of 80:20 models were 0.930 and 0.963 respectively. HCRTR2 and HCRTR1 belong to regulation of cytosolic calcium ion concentration, cellular calcium ion homeostasis GO BPs. ConclusionIn BC patients, increases in HCRTR2 and PPY gene expressions could be considered as positive prognostic factors. Decreases in HCRTR1 and NPY4R (PPYR1) gene expressions could be considered as negative prognostic factors. Decreased expression of PTPN11 gene may have a positive prognostic factor. Changes in existing genes are likely to be both a biomarker and therapeutic target for BC. However, experimental and clinical studies are needed to elucidate the mechanisms underlying these neuropeptide receptors in terms of breast carcinogenesis.

Experience of microbiological monitoring of the respiratory tract microflora in patients with cystic fibrosis during therapy with the combination drug elexacaftor/tezacaftor/ivacaftor + ivacaftor

Bacterial complications of the respiratory tract are negative prognostic factors leading to a decrease in pulmonary function, duration, and quality of life of patients with cystic fibrosis. To date, a sufficient number of studies have not been accumulated to reliably prove or reject microbiological improvement during targeted therapy. The aim of the study was to collect continuous microbiological data from patients with cystic fibrosis in the Samara region receiving treatment with elexacaftor/tezacaftor/ivacaftor + ivacaftor from November-December 2021. The article presents eight clinical observations. At the time of therapy initiation, seven patients had chronic respiratory tract infection associated with Burkholderia cenocepacia ST 208, combined with chronic Pseudomonas aeruginosa infection in two of them. One patient had a chronic P. aeruginosa infection in association with Aspergillus fumigatus. Conclusion. An expansion of the species composition in the respiratory samples was demonstrated in all cases. The majority of patients showed microbiological improvement. Thus, biochemical and, as a result, microecological changes in the lungs against the normalization of chlorine channel function allow suggesting that key pathogens may be eradicated during the therapy with elexacaftor/tezacaftor/ivacaftor + ivacaftor.

Flow Cytometry for the Detection and Quantification of Mast Cells in Lymph Nodes: A Prospective Study in 64 Dogs With Mast Cell Tumour.

Nodal metastasis is a negative prognostic factor in dogs with mast cell tumours (MCTs), thus early detection enables more informed decision-making and provides valuable prognostic information. The aim of this study is to assess the concordance between histopathologic findings of LNs and cytology and flow cytometry (FC), respectively, and to evaluate the ability of FC to differentiate between metastatic (HN2-HN3) and non-metastatic (HN0-HN1) LNs. Overall, 117 LNs from 64 dogs with first occurring MCTs were submitted for cytology, histology and FC. LNs were cytologically and histologically classified according to Krick and Weishaar systems, respectively. Using FC, mast cells (MCs) were identified as IgE+ CD117+ CD5- CD21- cells and quantified as a percentage. When compared with histologic classification, cytology showed an accuracy of 88.2% in distinguishing between metastatic and non-metastatic LNs but did not detect 25.3% of metastatic cases. FC revealed an increase in the median percentages of MCs across histologic classes, progressing from HN0 to HN3. ROC curves pinpointed 0.3% as the optimal cut-off for distinguishing between metastatic and non-metastatic LNs, with an accuracy of 84.3%. A 1.1% cut-off proved valuable in identifying HN3 LNs. The combined interpretation of cytology and FC increased accuracy to 92.2%. An algorithm for guiding the combined interpretation of cytology and FC is suggested based on these findings. In conclusion, FC proves beneficial in enhancing the early detection of metastatic LNs, particularly when utilised alongside cytology. Histopathology remains essential for confirmation, enabling the discrimination of HN classes or, in doubtful cases, for the detection or exclusion of nodal metastases.