Favorable Prognosis Research Articles

Safety and risk analysis of total resection surgery for thoracic and lumbar spinal tumors: a decadal analysis of 103 cases

Study designRetrospective cohort study.PurposeTo explore the complications and risk factors for total resection (TR) of primary thoracic and lumbar spinal tumors over the past decade at our institution.MethodsPatients meeting inclusion criteria (primary spinal tumors, thoracic or lumbar location, TR at our center) were included. Demographic characteristics, surgical data, perioperative complications and management results were reviewed. Patients were stratified by tumor site, the number of excised segments, and recurrence status to elucidate distinctive characteristics.ResultsThe cohort comprised 103 patients, with a mean age of 35.8 years. On average, 1.83 vertebral segments were resected per patient. Perioperative complications were substantial, totaling 166 events, with 71 classified as major and 95 as minor, yielding an average of 1.61 complications per patient. No perioperative deaths occurred, but 79 patients (76.7%) experienced at least one complication. Multiple vertebral sections correlated with a higher complication rate (P = 0.031), and lumbar surgeries exhibited elevated risks of large vascular injury (P = 0.001), neurological deterioration, and cerebrospinal fluid leakage compared to thoracic cases. Conversely, thoracic spinal procedures showed a higher rate of pleural effusion (P = 0.004). Binary logistics stepwise regression identified multi-segmental resection as the independent risk factor for major perioperative complications.ConclusionsTR of primary spinal tumors is associated with a high perioperative complication rate, although most events have a favorable prognosis. Complication characteristics vary based on the surgical site, number of excised segments, and surgical history. A nuanced preoperative evaluating approach considering patient age, surgical segments, and extent of resection is crucial.

Prognostic Factors for Patients with Small-Cell Lung Cancer Treated with Chemoimmunotherapy: A Retrospective Multicenter Study

Background: This study aimed to investigate prognostic factors for predicting the survival of patients with extensive-disease-stage small-cell lung cancer treated with chemoimmunotherapy. Methods: Patients were classified according to overall survival (OS): favorable corresponded to an OS ≥ 24 months, moderate corresponded to an OS of 6–24 months, and poor corresponded to an OS < 6 months. Multivariate Cox regression analyses were used to evaluate prognostic factors. Results: Of 130 patients, the proportions of performance status decline and liver metastasis were significantly higher in the poor-prognosis group. With regard to the laboratory findings, neutrophil/lymphocyte ratios and albumin levels differed significantly among the groups. Multivariate analysis showed that the independent prognostic factors for OS were liver metastasis and decreased albumin levels (<3.5 mg/dL). After classifying the patients into three groups according to the quantities of these prognostic factors, the OS differed significantly among the groups (18.3 vs. 13.5 vs. 3.8 months; p < 0.001). The incidence of immune-related adverse events (irAEs) was higher in patients without these prognostic factors than in those with both (36% vs. 5%; p = 0.01). Conclusion: Liver metastasis and decreased albumin levels are independent unfavorable prognostic factors. Patients with both prognostic factors showed unfavorable OS; however, patients without these factors may have a favorable prognosis but be at greater risk of irAEs.

Association of Radioactive Iodine Administration With Outcome Among Patients With Low-Risk Differentiated Thyroid Cancer: A Real-World Data Analysis.

Despite the generally favourable long-term prognosis of low-risk differentiated thyroid cancer (DTC), questions remain about disease-free survival (DFS) after initial treatment, particularly regarding the use of radioactive iodine (RAI). Although there are RCT trial confirming that RAI ablation therapy is not superior to follow-up in terms of the 3-year DFS rate in low-risk thyroid cancer, its longer-term prognosis remains to be established. The objective of this study was to assess the impact of RAI ablation on the presence of structural persistent/recurrent disease in patients with low-risk DTC. We retrospectively identified 720 low-risk DTC patients who had undergone total or near-total thyroidectomy (TT) at a tertiary medical centre between January 2008 and July 2018. Propensity scores were calculated using a multivariable logistic regression model that accounted for age, sex, tumour size, neck dissection, multifocality, capsular invasion and lymph node (LN) metastasis. We compared DFS between patients who received RAI and those who did not using log-rank tests and multivariate Cox analyses. Subgroup analyses were also conducted. Of the total cohort, 180 (25.0%) patients received RAI, while 540 (75.0%) did not before matching. The median follow-up duration was 59.5 months. After matching, the RAI group comprised 135 (39.8%) patients and the non-RAI group comprised 204 (60.2%) patients. In the entire cohort, the 5-year DFS rate was 97.6% for patients receiving RAI compared to 96.8% for those not receiving RAI (p = 0.704). In the matched cohort, the rates were 98.5% and 95.6%, respectively (p = 0.090). Matched multivariate Cox analysis demonstrated that RAI was neither significantly nor independently associated with DFS (hazard ratio [HR] = 0.29; 95% CI 0.06-1.37; p = 0.118). Further subgroup analyses reaffirmed that RAI ablation did not significantly reduce the risk of developing structural persistent/recurrent disease. Administering RAI ablation following TT did not result in improved DFS for low-risk DTC patients. Our findings suggest that decisions regarding RAI should be made judiciously to avoid overtreatment in this clinical scenario.

Prognosis prediction via histological evaluation of cellular heterogeneity in glioblastoma

Glioblastomas (GBMs) are the most aggressive types of central nervous system tumors. Although certain genomic alterations have been identified as prognostic biomarkers of GBMs, the histomorphological features that predict their prognosis remain elusive. In this study, following an integrative diagnosis of 227 GBMs based on the 2021 World Health Organization classification system, the cases were histologically fractionated by cellular variations and abundance to evaluate the relationship between cellular heterogeneity and prognosis in combination with O-6-methylguanine-DNA methyltransferase gene promoter methylation (mMGMTp) status. GBMs comprised four major cell types: astrocytic, pleomorphic, gemistocytic, and rhabdoid cells. t-distributed stochastic neighbor embedding analysis using the histological abundance of heterogeneous cell types identified two distinct groups with significantly different prognoses. In individual cell component analysis, the abundance of gemistocytes showed a significantly favorable prognosis but confounding to mMGMTp status. Conversely, the abundance of epithelioid cells was correlated with the unfavorable prognosis. Linear model analysis showed the favorable prognostic utility of quantifying gemistocytic and epithelioid cells, independent of mMGMTp. The evaluation of GBM cell histomorphological heterogeneity is more effective for prognosis prediction in combination with mMGMTp analysis, indicating that histomorphological analysis is a practical and useful prognostication tool in an integrative diagnosis of GBMs.

Favorable Prognosis in Patients With Multiple Myeloma and Lenalidomide-Induced Skin Rash: A Multicenter Retrospective Study.

Although lenalidomide is an essential treatment for multiple myeloma (MM), skin rashes are a common adverse event. This retrospective study aimed to examine the association between skin rash development during lenalidomide treatment and the prognosis of relapsed/refractory MM. All patients who received lenalidomide at 10 hospitals between July 2009 and December 2015 were included in the study. The relationship of skin rash development with disease progression and survival was evaluated. Multivariate analysis was performed to identify factors affecting disease progression or survival, including skin rash. Of the 245 patients analyzed, 70 developed skin rashes. The median progression-free survival (PFS) of patients with skin rashes was 22.4 months, whereas the median PFS for patients who did not develop skin rashes was 10.5 months (p = 0.003). The median overall survival for patients with and without skin rash was 42.6 and 24.6 months, respectively (p = 0.013). Multivariate regression analysis showed that skin rash was an independent prognostic factor for PFS (p = 0.009). In this study, patients with skin rashes during lenalidomide treatment had significantly better PFS than those without such symptoms, indicating that lenalidomide-associated skin rashes may be a predictor of clinical outcomes in patients with MM.

The Effect of Systemic Inflammatory Response on Mechanical Thrombectomy is Partly Mediated by Pre-thrombectomy Cerebral Edema in Acute Stroke Patients.

To explore the effect of baseline Systemic Inflammatory Response reflected by platelet-to-lymphocyte ratio (PLR) and pre-thrombectomy cerebral edema reflected by Net Water Uptake (NWU) on futile recanalization in patients with Acute Ischemic Stroke (AIS) after successful thrombectomy, and to investigate the potential mediating role of baseline cerebral edema. 134 Patients with anterior circulation ischemic stroke receiving successful thrombectomy were retrospectively studied. Their demographic and clinical characteristics were collected at admission, and the NWU was quantitatively calculated based on baseline computed tomography (CT). The predictive value of PLR for futile recanalization and the relationship between PLR, NWU, and futile recanalization using mediation analysis were explored. Patients were followed up for 90 days and were divided into a futile recanalization group and a favorable prognosis group [90-day modified Rankin Scale score of 0-2]. High baseline PLR, NWU, no first-pass reperfusion, and large baseline ischemic core volume were independent predictors of futile recanalization after successful thrombectomy in patients with AIS. Mediation analysis results indicate that PLR may partially mediate the occurrence of futile recanalization through NWU. Baseline PLR and NWU were independent predictors of futile recanalization, and higher PLR and NWU values were associated with a higher likelihood of futile recanalization. The findings suggest that early cerebral edema reflected by a high NWU value may be a mediator of PLR-affecting prognosis.

Mammary myofibroblastoma of the male breast: a case report and literature review.

Mammary myofibroblastoma (MFB) is a rare benign spindle cell tumour predominantly affecting males, but also observed in postmenopausal females. Its diagnosis remains challenging owing to overlapping histological features with malignant lesions and limited tissue sampling in core biopsies. We present a case of incidentally discovered mammary MFB in a 63-year-old man and review its clinical, radiological and histopathological characteristics. The patient, who had a history of distal pancreatectomy and splenectomy, presented with an incidental left anterior chest wall nodule discovered on computed tomography scan. Clinical examination revealed a benign left retroareolar lump, confirmed by breast ultrasound and mammography. Ultrasound-guided core biopsy demonstrated characteristic spindle cells, prompting immunohistochemical staining confirming the diagnosis of MFB. The lesion was surgically excised with clear margins. Mammary MFB is commonly seen in postmenopausal women and older men, presenting as painless, mobile breast lumps. Imaging findings are nonspecific, resembling fibroadenomas or fat necrosis. Histologically, MFB lacks mammary ducts or lobules and displays characteristic spindle cells with collagenous stroma. Immunohistochemistry aids in differentiating it from other spindle cell tumours. Surgical excision is curative, with no reported cases with recurrence. Mammary MFB should be considered in the differential diagnosis of breast masses in males and postmenopausal women. Despite the challenges in diagnosis, its benign nature and favourable prognosis warrant timely recognition and appropriate management through surgical excision. Further research is needed to establish clear management guidelines and explore its underlying pathogenesis.

The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far. We recruited five PM-ccRCC patients and investigated the genomic, single-cell transcriptomic, and drug sensitivity profiles of their patient-derived cells (PDCs). The PM depicted both expected and novel genomic alterations. Further, the transcriptomics differed from both primary and metastatic ccRCC, with upregulations of the PI3K/mTOR and - supporting the clinical observations - angiogenesis pathways. Data integration at pathway level showed that transcriptomics explained drug sensitivities the best. Accordingly, PM-ccRCC PDCs shared sensitivity to many PI3K/mTOR inhibitors. Altogether, we show distinct genomic and transcriptomic signatures in PM-ccRCC, highlight the superiority of transcriptomics in interpreting drug sensitivities, and encourage the use of TKIs and PI3K/mTOR inhibitors in PM-ccRCC.

An integrated approach to secondary prevention of cervical intraepithelial neoplasia

Secondary prevention of cervical precancer is aimed at preventing recurrence of cervical intraepithelial neoplasia (CIN) after excisional treatment. Recurrence of CIN after surgical treatment occurs in 8.1–14.4% of cases, which increases the risk of developing cervical cancer (CC). Despite the high effectiveness of local surgical treatment of patients with high-grade intraepithelial lesions (HSIL), an increased risk of late diagnosis of cervical cancer has been proven in comparison with the risk in the general population. The review article presents current data on factors that increase the potential risk of recurrence of precancer. Human papillomavirus (HPV) persistence is considered one of the leading predictors of relapse of CIN2+, regardless of the type of excision treatment. The combination of persistent high-risk (HR) HPV and a positive sectional margin significantly increases the risk of persistent/recurrent CIN2+. A negative co-test after conization during follow-up contributes to a favorable prognosis and the development of HSIL is observed less frequently than in the population. Only an integrated approach, including detection of cervical HPV HR infection after excisional treatment of CIN, assessment of the radicality of resection and timely measures to eliminate ineffective treatment, as well as subsequent active monitoring of patients, allows avoiding its recurrence and progression of cervical precancer

Myocarditis Associated with COVID-19 Vaccination.

Myocarditis after the COVID-19 vaccine is one of the important adverse events following immunization, observed mainly after mRNA-based vaccines. Importantly, post-vaccination myocarditis was less common than myocarditis after SARS-CoV-2 infection, as it was scored at 19.7 per 1,000,000 doses and 2.76 per 1000 infections. Predominantly, its course was benign and, compared with the myocarditis after COVID-19 infection, significantly fewer patients developed heart failure or died among patients with post-vaccination myocarditis. The group at highest risk of myocarditis related to COVID-19 vaccination were young males who received a second dose of an mRNA vaccine. It was observed that, among mRNA vaccines, specifically mRNA-1273 was associated with a higher risk of myocarditis. The mechanism underlying myocarditis after COVID-19 vaccination is still under investigation and certain processes are being considered. Currently, some follow-up assessments of patients who developed vaccine-induced myocarditis are available and suggest a favorable prognosis. The aim of this review is to discuss the most recent data on myocarditis after COVID-19 vaccination considering its epidemiology, clinical presentation, diagnosis, management, relative risk of myocarditis compared with SARS-CoV-2 infection, potential underlying mechanism, and follow-up data of patients who developed post-vaccination myocarditis.

Comparative analysis of tertiary lymphoid structures for predicting survival of colorectal cancer: A whole-slide images-based study

Abstract Background Tertiary lymphoid structures (TLS) are major component in immune microenvironment, correlating with a favorable prognosis in colorectal cancer. However, the methods used to define and characterize TLS were not united, hindering its's clinical application. This study aims to seek a more stable method to characterize TLS and clarify its prognostic value in larger multicenter cohorts. Methods A total of 1609 patients from four hospitals and the TCGA database were analyzed. We quantified the number and maximum length of TLS along the invasive margin of tumor using hematoxylin and eosin (HE)-stained whole-slide images (WSIs). Additionally, the length of the invasive margin was determined to calculate the TLS density. The prognostic value of the TLS for overall survival was evaluated. In addition, we examined the association between TLS density and immune cell infiltration using immunohistochemistry-stained WSIs. The performance for predicting overall survival was measured using hazard ratios (HR) with 95% confidence intervals (CI). Results Among the three TLS quantification methods, TLS density has the strongest discriminative performance. Survival analysis indicated that higher TLS density correlated with better overall survival (HR for high vs. low 0.57 [95% CI 0.42–0.78] in primary cohort; 0.49 [0.35–0.69] in validation cohort; 0.35 [0.18–0.67] in TCGA cohort). A high TLS density was associated with a high level of CD3+ T cells infiltration. Conclusions Based on this comparative multicenter analysis, TLS density was identified as a simple, robust, and effective immune prognostic index for colorectal cancer.

Role of EEG spindle-like activity in post cardiac arrest prognostication

AimEEG is considered in guidelines for poor outcome prognostication in comatose patients after cardiac arrest (CA), but elements related to favorable prognosis have also been increasingly described. While spindle EEG activity is known to herald good outcome in critically ill patients, its occurrence in CA has received limited attention, essentially in pediatric cohorts. We postulated that this feature is related to favorable outcome in adults. MethodsRetrospective assessment of comatose adults following CA in a prospective institutional registry (09.2021–09.2023). Spindle-like activity, noted prospectively on early (12–36 h) and late (36–72 h) routine EEGs, was tested using 2x2 tables and comparisons of proportions for the likelihood of favorable outcome (CPC 1–2 at 3 months), including combinations with existing benign EEG descriptions (Westhall: no malignant or highly malignant features; modified: also allowing background discontinuity, low voltage, inverse development). Spindles were correlated with peak serum neuron-specific enolase (NSE) at 24–48 h as a marker of neuronal damage. ResultsAmong 276 patients, spindle-like activity was observed in 66 (23.9 %) of them, more often in early EEGs. While, in isolation, this feature detected within 72 h showed high specificity for CPC 1–2 (82.2 %) and low sensitivity (36.8 %), its addition significantly enhanced sensitivity of modified benign EEG (from 90.5 % to 95.8 %; p < 0.001; specificity at 54.4 %). Patients with spindle-like activity had significantly lower NSE (median 25.7µg/l, interquartile range 16.1–24.4, vs. 39.4 µg/l, interquartile range 21.1–95.1; p < 0.001). ConclusionSpindle-like EEG activity may orient on prognostication of favorable outcome in adult post CA patients, and correlates with lower neuronal damage.

Comprehensive analysis of the expression level, prognostic value, and immune infiltration of cuproptosis-related genes in human breast cancer.

As a novel cell death form, cuproptosis results from copper combining with lipidated proteins in the tricarboxylic acid cycle. To the best of our knowledge no study has yet comprehensively analyzed the relationship between cuproptosis-related genes and breast cancer. The expression, prognostic value, mutations, chemosensitivity, and immune infiltration of cuproptosis-related genes in breast carcinoma patients were analyzed, PPI networks were constructed, and enrichment analyses were performed based on these genes. TIMER, UALCAN, Kaplan-Meier plotter, Human Protein Atlas, cBioPortal, STRING, GeneMANIA, DAVID, and R program v4.0.3 were used to accomplish the analyses above. Compared to normal breast tissues, FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, MTF1, and GLS were down-regulated in breast cancer tissues, while CDKN2A was up-regulated. High expression of FDX1, LIAS, DLD, DLAT, MTF1, GLS, and CDKN2A were associated with favorable overall survival. Cuproptosis-related genes showed a high alteration rate (51.3%) in breast cancer, contributing to worse clinical outcomes. The expression levels of FDX1, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A were associated positively with 1 or more immune cell infiltrations in breast cancer. Patients with high levels of B cell, CD4+ T cell, CD8+ T cell, and dendritic cell infiltration had a higher survival rate at 10 years. This study comprehensively investigated relationships between cuproptosis and breast cancer by bioinformatic analyses. We found that cuproptosis-related genes were generally lowly expressed in breast carcinoma tissue. As the critical gene of cuproptosis, high expression of FDX1 was related to favorable prognoses in breast cancer patients; thus, it might be a potential prognostic marker. Moreover, genes associated with cuproptosis were linked to immune infiltration in breast cancer and this relationship affected the prognosis of breast cancer.

Tertiary lymphoid structures associated with improved prognosis and reduced invasion in advanced extramammary Paget's disease.

We analysed the presence and significance of tertiary lymphoid structures (TLS), a known prognostic and predictive biomarker of response to immune checkpoint inhibitors, in advanced extramammary Paget's disease. Our findings showed that TLS are associated with a favourable prognosis and may play a role in inhibiting tumour invasion, indicating that EMPD is an immunologically active tumour. These results suggest that immune checkpoint inhibitors could be an effective treatment option for advanced EMPD. This study is the first report on TLS in EMPD.

Surgically managed incarcerated umbilical hernias in calves hold favorable prognosis: a retrospective analysis of 19 cases (2004-2021).

To describe the clinical signs, surgical management, postoperative complications, and outcomes following herniorrhaphy in calves with incarcerated umbilical hernias. This was a retrospective case series. The electronic medical record databases of 2 veterinary teaching hospitals were searched to identify the records of calves that underwent herniorrhaphy for correction of irreducible umbilical hernias between January 1, 2004, and December 31, 2021. Data collected included signalment, medical history, results of clinical examination and laboratory testing, ultrasonographic and surgical findings (incarceration vs strangulation), postoperative complications, and outcome. 19 calves with incarcerated umbilical hernias underwent surgical correction. The incarcerated gastrointestinal tract was identified as the abomasum in 11 calves and jejunum in 8 calves. In 9 calves, the intraoperative identification of strangulation led to 4 intestinal resections and 4 partial abomasectomies, with 1 calf being euthanized intraoperatively. Postoperative complications were reported in 3 calves that underwent intestinal resection. Sixteen calves (84%) survived to discharge and had a median survival time of 1,995 days after surgery. No statistically significant differences were observed between calves with or without gastrointestinal tract strangulation in the short-term survival rate, survival time, or number of lactations after surgery. This study demonstrated that herniorrhaphy for incarcerated umbilical hernias in calves is associated with a favorable prognosis. Postoperative complications are, however, more frequent in calves with strangulated gastrointestinal tract. Surgical intervention for incarcerated umbilical hernias in calves generally yields a positive prognosis, particularly in the absence of gastrointestinal tract strangulation, highlighting the importance of timely diagnosis and treatment.

In Silico Insights Reveal Fibronectin 1 as a Theranostic Marker in Gastric Cancer.

Gastric cancer (GC) is a complex and highly variable disease, ranking among the top five cancers diagnosed globally, and a leading cause of cancer-related deaths. Emerging from stomach lining cells amid chronic inflammation, it often advances to preneoplastic stages. Late-stage diagnoses and treatment challenges highlight the critical need for early detection and innovative biomarkers, motivating this study's focus on identifying theranostic markers through gene ontology analysis. By exploring deregulated biological processes, this study aims to uncover insights into cancer progression and associated markers, potentially identifying novel theranostic candidates in GC. Using public data from The Human Protein Atlas, this study pinpointed 299 prognostic genes, delineating 171 with unfavorable prognosis and 128 with favorable prognosis. Functional enrichment and protein-protein interaction analyses, supported by RNAseq results and conducted via Metascape and Cytoscape, highlighted five genes (vWF, FN1, THBS1, PCDH7, and F5) with promising theranostic potential. Notably, FN1 and THBS1 exhibited significant promise, with FN1 showing a 370% expression increase in cancerous tissue, and it is possible that FN1 can also indicate the stratification status in GC. While further validation is essential, these findings provide new insights into molecular alterations in GC and potential avenues for clinical application of theranostic markers.

Medial Joint Opening in the Operated Knee After Unilateral High Tibial Osteotomy: Risk of Osteoarthritis and Future Surgery in the Operated and Nonoperated Knee

Background: High tibial osteotomy (HTO) modifies the mechanics of the affected knee but can also affect the nonoperated knee. However, no research has reported on the prognosis and risk factors related to the nonoperated knee after unilateral HTO. Purpose: To assess the radiological parameters associated with osteoarthritis (OA) progression and the need for surgery in the nonoperated knee after unilateral HTO, with concurrent assessment of the operated knee. Study Design: Case series; Level of evidence, 4. Methods: The medical charts of 197 patients with knee OA who underwent unilateral HTO between March 2007 and December 2020 were retrospectively investigated. Radiological parameters such as the Kellgren-Lawrence grade, weightbearing line ratio, joint line convergence angle (JLCA), and joint line obliquity angle were assessed preoperatively and 1 year postoperatively. Results: The mean follow-up length for the 197 patients was 5.9 ± 3.2 years for the operated knee and 5.5 ± 3.2 years for the nonoperated knee. A smaller postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .027) and undergoing surgery (P = .006) in the nonoperated knee. Conversely, a larger postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .014) and conversion to arthroplasty (P = .027) in the operated knee. A postoperative JLCA >1.5° (P < .001) and <3.9° (P < .001) was needed to reduce the risk of undergoing surgery in the nonoperated knee and OA progression in the operated knee, respectively. Additionally, a pre- to postoperative change in the JLCA (ΔJLCA) between −5.6° and −1.7° (P = .021 and P = .004, respectively) was needed to reduce the risk of OA progression in both knees. Conclusion: A large medial joint opening (a small postoperative JLCA) in the operated knee after unilateral HTO was associated with a higher risk of OA progression and surgery in the nonoperated knee. Conversely, a small medial joint opening (a large postoperative JLCA) was associated with a higher risk of OA progression and conversion to arthroplasty in the operated knee. For a balanced medial joint opening, if the postoperative JLCA was between 1.5° and 3.9° or the ΔJLCA was between −5.6° and −1.7°, a favorable prognosis in both knees could be anticipated.

Undetectable pre-radical cystectomy circulating tumour DNA status predicts improved oncological outcomes.

To assess recurrence-free survival (RFS) in patients with undetectable tumour-informed circulating tumour DNA (ctDNA) before radical cystectomy (RC) and evaluate if those who converted from detectable to undetectable ctDNA status after RC have similar RFS outcomes as those with persistently undetectable ctDNA status. Patients who underwent RC had prospectively and longitudinally collected tumour-informed ctDNA analyses during 2021-2023. ctDNA status was informed from the pre-RC specimen. The minimal residual disease (MRD) window was defined as the initial 90 days after RC. RFS was evaluated using the Kaplan-Meier method. Cox regression analysis was performed to find predictors of disease recurrence. The cohort included 135 patients with 647 ctDNA analyses. The median (interquartile range [IQR]) age was 71 (63-77) years. Over a median (IQR) follow-up of 11 (7-18) months, 41 patients (30%) had a recurrence. Pre-RC undetectable ctDNA status was found in 54 patients (40%). The RFS rates at 6, 12, and 21 months were 98%, 93%, and 82%, respectively. Of 77 patients with undetectable ctDNA status at the MRD window available for conversion dynamics analysis, 43 had persistently undetectable ctDNA status (both at pre-RC and MRD window) and 31 converted from pre-RC detectable to MRD undetectable status (conversion group). The persistently undetectable group had significantly better RFS than the conversion group (log-rank, P < 0.001), with 12-month RFS rates of 97% vs 51%, and 18-month RFS rates of 88% vs 51%, respectively. On Cox multivariate analysis, only the conversion group status predicted disease recurrence. Patients with undetectable pre-RC ctDNA status have a favourable prognosis and may be candidates for treatment de-escalation. Those with persistently undetectable ctDNA had superior RFS compared to the conversion group. Pre-RC ctDNA status should be incorporated into trials examining ctDNA use in clinical decision-making.

Characteristics and Prognosis of Patients with Advanced Hepatocellular Carcinoma Treated with Atezolizumab/Bevacizumab Combination Therapy Who Achieved Complete Response.

To investigate the characteristics and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atz/Bev) who achieved a complete response (CR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 120 patients with Eastern Cooperative Oncology Group performance status (PS) 0 or 1 and Child-Pugh A at the start of Atz/Bev treatment were included. Barcelona Clinic Liver Cancer stage C was recorded in 59 patients. The CR rate with Atz/Bev alone was 15.0%. The median time to CR was 3.4 months, and the median duration of CR was 15.6 months. A significant factor associated with achieving CR with Atz/Bev alone was an AFP ratio of 0.34 or less at 3 weeks. Adding transarterial chemoembolization (TACE) in the six patients who achieved a partial response increased the overall CR rate to 20%. Among the 24 patients who achieved CR, the median progression-free survival was 19.3 months, the median overall survival was not reached, and 14 patients (58.3%) were able to discontinue Atz/Bev and achieve a drug-free status. Twelve of these patients developed progressive disease (PD), but eleven successfully received post-PD treatments and responded well. Achieving CR by mRECIST using Atz/Bev alone or with additional TACE can be expected to offer an extremely favorable prognosis.