Kaplan-Meier Survival Analysis Research Articles

Labyrinthine cor triatriatum sinister in fetal hypoplastic left heart syndrome is associated with poor outcomes.

A subset of hypoplastic-left-heart-syndrome (HLHS) fetuses have a complex cor-triatriatum sinister that we named "labyrinthine-cor (L-cor)". We sought to determine the prevalence of L-cor in HLHS fetuses and hypothesized that it is associated with increased mortality. This single-center retrospective cohort study included all HLHS fetuses from January 2010-December 2020. Fetuses with other hypoplastic-left-heart variants, inadequate images, lack of follow-up and fetal atrial-septal interventions were excluded. RAS was defined as the ratio of pulmonary-vein forward-to-reverse velocity-time-integral (VTI)≤5 and severe-RAS defined as VTI-ratio <3. Kaplan-Meier survival-analysis was performed for the primary outcome of transplant-free survival for 62weeks after gestational-age of 30weeks (∼1year). Of the 156 consecutive fetuses with HLHS, 11 (7.7%) had L-cor and 8/11 (72.7%) of these had RAS. When compared to HLHS-RAS without L-cor, fetuses with HLHS-RAS and L-cor were less likely to survive to 28days (87% vs. 62.5%, p=0.017) and to 1year (69.6% vs. 25%, p=0.029). When comparing by survival analysis, fetuses with severe-RAS with L-cor had lower survival compared severe-RAS without L-cor (p=0.020). L-cor in fetal HLHS is associated with increased mortality. Recognition of this finding is important for prognostication and atrial-septal-intervention planning.

Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study

BackgroundFamilial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event.MethodsAll ACS patients were screened at the Second Affiliated Hospital of Xi’an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded.ResultsThe prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan–Meier survival analysis (HR = 1.282, log-rank test: P > 0.05).ConclusionsFH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.

Comprehensive Study of Chromosomal Copy Number Variations and Genomic Variations Predicting Overall Survival in Myelodysplastic Syndromes

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia. The disease progression is majorly affected by genetic defects. However, about 40–50% of patients with MDS present with a normal karyotype and develop different courses of disease. Hence, there remains a room to advance the biological understanding and find molecular prognostic markers for cytogenetically normal MDS. Methods: We performed a high-resolution CGH + SNP array along with next-generation sequencing (NGS) of 77 primary diagnosed MDS patients, and also they were clinically followed up. Results: Our study revealed 82 clinically significant genomic lesions (losses/gains) in 49% of MDS patients. CGH + SNP array reduced the proportion of normal karyotype by 30%. SNP array in combination with NGS confirmed the biallelic loss of function of the TP53 gene (2/6), which is a clinically relevant biomarker and new genetic-based MDS entity, i.e., MDS-biTP53, as per the new WHO classification 2022. Genomic region 2p22.3 presented with frequent lesions and also with a more hazard ratio (2.7, 95% CI: 0.37–21) when analyzed by Kaplan-Meier survival analysis. Conclusion: CGH + SNP array changed the cytogenetic and IPSS-R risk group in 18% and 13% of patients, respectively, with an improved prediction of prognosis. This study emphasizes the cytogenetic heterogeneity of MDS and highlights that abnormality with chromosome 2 may have a diagnostic and prognostic impact.

Transcriptome profiling and metabolic pathway analysis towards reliable biomarker discovery in early-stage lung cancer.

Earlier diagnosis of lung cancer is crucial for reducing mortality and morbidity in high-risk patients. Liquid biopsy is a critical technique for detecting the cancer earlier and tracking the treatment outcomes. However, noninvasive biomarkers are desperately needed due to the lack of therapeutic sensitivity and early-stage diagnosis. Therefore, we have utilized transcriptomic profiling of early-stage lung cancer patients to discover promising biomarkers and their associated metabolic functions. Initially, PCA highlights the diversity level of gene expression in three stages of lung cancer samples. We have identified two major clusters consisting of highly variant genes among the three stages. Further, a total of 7742, 6611, and 643 genes were identified as DGE for stages I-IIIrespectively. Topological analysis of the protein-protein interaction network resulted in seven candidate biomarkers such as JUN, LYN, PTK2, UBC, HSP90AA1, TP53, and UBB cumulatively for the three stages of lung cancers. Gene enrichment and KEGG pathway analyses aid in the comprehension of pathway mechanisms and regulation of identified hub genes in lung cancer. Importantly, the medial survival rates up to ~ 70months were identified for hub genes during the Kaplan-Meier survival analysis. Moreover, the hub genes displayed the significance of risk factors during gene expression analysis using TIMER2.0 analysis. Therefore, we have reason that these biomarkers may serve as a prospective targeting candidate with higher treatment efficacy in early-stage lung cancer patients.

What explains the recovery speed of financial markets from banking crises?

Less is studied about the determinants of the impact of banking crises on the recovery speed of financial markets. In this paper, based on the members from Asian Infrastructure Investment Bank (AIIB), we measure the recovery speed of financial markets from banking crises by financial stress index (FSI). Then the Kaplan-Meier (K-M) survival analysis methodology is applied to depict the stylized features of the recovery speed of financial markets. Further, the Cox proportional hazards model is introduced to investigate the effect of a variety of influencing factors on the recovery speed of financial markets from banking crises. The results indicate that certain factors, such as stationary macroeconomic environment, sound government finance, stable exchange rate regime, moderately open financial market, global financial market with high panic prior to banking crises, and expansionary monetary policy with the price rule after banking crises, contribute to fast recovery of financial markets.

Intraventricular or intrathecal polymyxin B for treatment of post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria: a 8-year retrospective study.

Post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a life-threatening complication. This study aimed to assess the current practices and clinical outcomes of intravenous (IV) combined with intraventricular (IVT)/intrathecal (ITH) polymyxin B in treating CRGNB intracranial infection. A retrospective study was conducted on patients with post-neurosurgical intracranial infection due to CRGNB from January 2013 to December 2020. Clinical characteristics and treatment outcomes were collected and described. Kaplan-Meier survival and multivariate logistic regression analyses were performed. The study included 114 patients, of which 72 received systemic antimicrobial therapy combined with IVT/ITH polymyxin B, and 42 received IV administration alone. Most infections were caused by carbapenem-resistant Acinetobacter baumannii (CRAB, 63.2%), followed by carbapenem-resistant Klebsiella pneumoniae (CRKP, 31.6%). Compared with the IV group, the IVT/ITH group had a higher cerebrospinal fluid (CSF) sterilization rate in 7 days (p < 0.001) and lower 30-day mortality (p = 0.032). In the IVT/ITH group, patients with CRKP infection had a higher initial fever (p = 0.014), higher incidence of bloodstream infection (p = 0.040), lower CSF sterilization in 7 days (p < 0.001), and higher 30-day mortality (p = 0.005) than those with CRAB infection. Multivariate logistic regression analysis revealed that the duration of IVT/ITH polymyxin B (p = 0.021) was independently associated with 30-day mortality. Intravenous combined with IVT/ITH polymyxin B increased CSF microbiological eradication and improved clinical outcomes. CRKP intracranial infections may lead to more difficult treatment and thus warrant attention and further optimized treatment.

Prognostic biomarker HIF1α and its correlation with immune infiltration in gliomas.

Certain glioma subtypes, such as glioblastoma multiforme or low-grade glioma, are common malignant intracranial tumors with high rates of relapse and malignant progression even after standard therapy. The overall survival (OS) is poor in patients with gliomas; hence, effective prognostic prediction is crucial. Herein, the present study aimed to explore the potential role of hypoxia-inducible factor 1 subunit alpha (HIF1α) in gliomas and investigate the association between HIF1α and infiltrating immune cells in gliomas. Data from The Cancer Genome Atlas were evaluated via RNA sequencing, clinicopathological, immunological checkpoint, immune infiltration and functional enrichment analyses. Validation of protein abundance was performed using paraffin-embedded samples from patients with glioma. A nomogram model was created to forecast the OS rates at 1, 3 and 5 years after cancer diagnosis. The association between OS and HIF1α expression was estimated using Kaplan-Meier survival analysis and the log-rank test. Finally, HIF1α expression was validated using western blotting, reverse transcription-quantitative PCR, Cell Counting Kit-8 and Transwell assays. The results demonstrated that HIF1α expression was significantly upregulated in gliomas compared with normal human brain glial cells. Immunohistochemistry staining demonstrated differential expression of the HIF1α protein. Moreover, glioma cell viability and migration were inhibited via HIF1α downregulation. HIF1α impacted DNA replication, cell cycling, DNA repair and the immune microenvironment in glioma. HIF1α expression was also positively associated with several types of immune cells and immunological checkpoints and with neutrophils, plasmacytoid dendritic cells and CD56bright cells. The Kaplan-Meier survival analyses further demonstrated a strong association between high HIF1α expression and poor prognosis in patients with glioma. Analysis of the receiver operating characteristic curves demonstrated that HIF1α expression accurately differentiated paired normal brain cells from tumor tissues. Collectively, these findings suggested the potential for HIF1α to be used as a novel prognostic indicator for patients with glioma and that OS prediction models may help in the future to develop effective follow-up and treatment strategies for these patients.

Long-Term Follow-Up of Myopic Glaucoma: Progression Rates and Associated Factors.

In the group of glaucoma patients with myopia, the more severe the degree of myopia, the faster the loss of visual acuity and central visual field defect. Longitudinal observational study. To investigate the progression rate of myopic glaucoma and associated factors by long-term analysis of its clinical course. Patients who had had at least 5 years of follow-up and a spherical equivalent of -0.5 diopters or less were included in this study. They were divided into 3 myopia groups according to myopic grade, namely mild myopia (-0.5 to -3.0 diopters), moderate myopia (-3.0 to -6.0 diopters), and high myopia (-6.0 diopters or more), and the clinical course, progression rate, and associated factors were compared among the groups and analyzed. A total of 121 eyes of 121 patients with glaucoma with myopia were included in the study. The average follow-up period was 10.4 ± 2.9 years. In the analysis of progression rate, the change rate of average retinal nerve fiber layer (RNFL) thickness (-0.75 μm/y in mild myopia, -0.82 μm/y in moderate myopia, -0.84 μm/y in high myopia) and the mean deviation change (-0.30 dB/y in mild myopia, -0.37 dB/y in moderate myopia, -0.39 dB/y in high myopia) both tended to be faster as the myopic grade increased. In a Kaplan-Meier survival analysis, the high myopia groups demonstrated a significantly faster VA loss (of more than 3 lines) and a higher incidence of newly developed central visual field defect (CVFD) than did the mild and moderate myopia groups. Longer axial length (odds ratio: 1.72, CI: 1.03-3.07, P = 0.047) and RNFL defect extending to the macula (odds ratio: 4.14, CI: 1.54-12.30, P = 0.007) were significantly associated with newly developed CVFD. In patients with myopic glaucoma, the higher the degree of myopia, the faster the rate of visual acuity loss and CVFD occurrence. Occurrence of CVFD was associated with longer axial length and widening of RNFLr defect to the macula.

High-Volume Hospital Had Lower Mortality of Severe Intracerebral Hemorrhage Patients.

Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH. We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients' survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death. Among 9,086 ICH patients who admitted to hospital during 18-month period, 6,756 (74.4%) and 2,330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72-0.91; p < 0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p < 0.05). The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.

Serum lipids as predictive markers for death by suicide

Serum lipid levels have been associated with an increased risk of suicidal behaviors. This retrospective cohort study aimed to investigate the association between serum lipid levels and death by suicide among suicide attempters according to sex. Suicide attempters visiting emergency departments between 2007 and 2011 were followed up until the date of all-cause death or December 31, 2012. Sex-stratified Cox proportional hazards regression and competing risk models were constructed to obtain the hazard ratios (HR) of serum lipid measures and suicide. For each significant lipid variable in the final models, Kaplan–Meier survival analysis and cumulative incidence function (CIF) were employed to compare the time to suicide between the high- and low-lipid groups based on the best cutoff point from the receiver operating characteristic curve. In 408 female attempters (65.8 %), the HR in the Cox regression model and subdistribution HR in the competing risk model for increased total cholesterol (TC) were 0.968 and 0.970, respectively. In the Kaplan-Meier survival analysis and CIF, increased death by suicide was demonstrated in the low-TC group (< 165 mg/dL). Lower serum TC levels among female suicide attempters may predict suicide. More careful monitoring is warranted in women with lower TC levels who recently attempted suicide.

Influence of abdominal fat distribution and inflammatory status on post-operative prognosis in non-small cell lung cancer patients: a retrospective cohort study

PurposeTo evaluate the influence of visceral fat area (VFA), subcutaneous fat area (SFA), the systemic immune-inflammation index (SII) and total inflammation-based systemic index (AISI) on the postoperative prognosis of non-small cell lung cancers (NSCLC) patients.Methods266 NSCLC patients received surgery from two academic medical centers were included. To assess the effect of abdominal fat measured by computed tomography (CT) imaging and inflammatory indicators on patients’ overall survival (OS) and progression-free survival (PFS), Kaplan–Meier survival analysis and Cox proportional hazards models were used.ResultsKaplan–Meier analysis showed the OS and PFS of patients in high-VFA group was better than low-VFA group (p < 0.05). AISI and SII were shown to be risk factors for OS and PFS (p < 0.05) after additional adjustment for BMI (Cox regression model II). After further adjustment for VFA (Cox regression model III), low-SFA group had longer OS (p < 0.05). Among the four subgroups based on VFA (high/low) and SFA (high/low) (p < 0.05), the high-VFA & low-SFA group had the longest median OS (108 months; 95% CI 74–117 months) and PFS (85 months; 95% CI 65–117 months), as well as the lowest SII and AISI (p < 0.05). Low-SFA was a protective factor for OS with different VFA stratification (p < 0.05).ConclusionVFA, SFA, SII and AISI may be employed as significant prognostic markers of postoperative survival in NSCLC patients. Moreover, excessive SFA levels may encourage systemic inflammation decreasing the protective impact of VFA, which may help to provide targeted nutritional support and interventions for postoperative NSCLC patients with poor prognosis.

Survival of Patients With Primary Cutaneous Melanoma (Stages 0-IIА and IIB-IIC), Depending on the Presence of the &lt;i&gt;BRAF&lt;/i&gt; Mutation in the Tumor and Surgical Treatment Option

Background: Cutaneous melanoma is an extremely aggressive disease with an unpredictable prognosis. Even among patients with similar tumor parameters and extent of surgical treatment, survival may vary. The extent of surgical resection of primary cutaneous melanoma is well-established, and a BRAF mutation in the tumor is an unfavorable prognostic factor for patient survival. The mutation presence is mainly used as a marker for prescribing targeted therapy. The impact of the extent of surgery and the method for restoring a tissue defect on survival of patients with similar stages remains unexplored. The impact of the BRAF mutation in the tumor on survival of patients with cutaneous melanoma depending on the surgery method has also not been studied. We analyzed the surgical treatment outcomes of 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) who were found to have the BRAF mutation and underwent different extents of tumor excision with closure of the surgical tissue defect.Objective: To analyze the impact of the BRAF mutation in the tumor on 5-year survival of patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC), depending on the extent of surgery and the method of replacing the tissue defect.Materials and methods: We used data from 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) and assessed their BRAF mutation status, extent of tumor excision, and method of closing the tissue defect. The patients were divided into 2 groups: the main group (wide excision of the tumor and plastic replacement of the tissue defect) and the comparison group (standard margin and linear closure of the tissue defect). After surgery, all the patients underwent tumor analysis for the BRAF p.V600E/K mutation using real-time PCR. DNA was isolated using the cobas® DNA Sample Preparation Kit on a cobas® z 480 analyzer. We used the following statistical methods: frequency analysis, z test to check the equality, and Kaplan-Meier survival analysis and such software as MedCalc 12.5 (1993-2013, MedCalc Software) and SPSS 26 (IBM Corp, 2019, IBM SPSS Statistics for Windows, Armonk, NY, USA). Results: Wide excision of primary cutaneous melanoma (stages 0-IIA and IIB-IIC) was found to increase 5-year progression-free survival in patients with subsequent plastic replacement of the tissue defect compared with patients with standard margin and linear closure of the tissue defect and 5-year overall survival in patients with stage 0-IIA melanoma. In patients with 0-IIA stage melanoma and positive BRAF mutation test results, wide excision with reconstructive and plastic defect closure improved the 5-year progression-free survival. Conclusions: The 5-year progression-free survival and 5-year overall survival increased by 20.9% (P = .005) and 13.0% (P = .031), respectively, in patients who underwent wide excision of primary cutaneous melanoma followed by plastic replacement of the tissue defect compared with patients with standard excision of primary tumors and linear closure of the tissue defect. The 5-year progression-free survival increased by 23.7% (P = .017) in patients with stage IIB-IIC melanoma, regardless of the BRAF mutation. In patients with 0-IIa stage melanoma and positive BRAF mutation test results who underwent wide excision, the 5-year progression-free survival increased by 20.7% (P = .047) compared with patients who underwent tumor excision with a standard margin.

Retrospective survival analysis of the use of uncemented modular tapered stems for revision in periprosthetic Vancouver B-type fractures. Is instability a threat to survival?

Introduction and objectivesPeriprosthetic hip fractures show increasing incidence and complexity, representing a challenge for the surgeon. We aimed to evaluate the survival of uncemented modular tapered stems in the treatment of periprosthetic Vancouver B2 and B3 type fractures and review the main complications and factors associated with decreased survival. Materials and methodsWe performed a retrospective study of patients submitted to revision arthroplasty for treatment of periprosthetic femoral stem Vancouver B2 and B3 type fractures with an uncemented modular fluted tapered stem (MRP-Titan). Demographic and radiographic parameters were analyzed. The survival rate (free of reoperation) was calculated at 2- and 5-years using the Kaplan–Meier survivorship analysis. ResultsThirty-nine patients were included with a mean age of 73.5 years and a mean follow-up of 5 years. Arthroplasty survivorship at 2 years was 73.7% and at 5 years was 67.5% (mean 8.4 years; range 6.7–10.2). Survivorship was inferior in the patients with episodes of instability (mean 2.5 years; range 0–5.42) (p<0.001). At least one episode of instability occurred in 26.3% of patients and 60% of these patients had a femoral head size 32mm or lower. At least one episode of instability occurred in 71.4% of patients with a greater trochanter fracture (p=0.008). The consolidation rate was 90.6% and the mortality rate was 23.7%. In the group of patients that died, 55.6% were submitted to at least one revision surgery (p=0.044). ConclusionSurvivorship of an uncemented modular stem (MRP-Titan) in revision for PHF is significantly reduced by episodes of instability.

Development of a haematological indices-based nomogram for prognostic prediction and immunotherapy response assessment in primary pulmonary lymphoepithelioma-like carcinoma patients.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare yet aggressive malignancy. This study aims to investigate a deep learning model based on hematological indices, referred to as haematological indices-based signature (HIBS), and propose multivariable predictive models for accurate prognosis prediction and assessment of therapeutic response to immunotherapy in PPLELC. This retrospective study included 117 patients with PPLELC who received immunotherapy and were randomly divided into a training (n=82) and a validation (n=35) cohort. A total of 41 hematological features were extracted from routine laboratory tests and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to establish the HIBS. Additionally, we developed a nomogram using the HIBS and clinical characteristics through multivariate Cox regression analysis. To evaluate the nomogram's predictive performance, we used calibration curves and calculated the time-dependent area under the curve (AUC). Kaplan-Meier survival analysis was performed to estimate progression-free survival (PFS) in both cohorts. The proposed HIBS comprised 14 hematological features and showed that patients who experienced disease progression had significantly higher HIBS scores compared to those who did not progress (P<0.001). Five prognostic factors, including HIBS, tumor-node-metastasis (TNM) stage, presence of bone metastasis and the specific immunotherapy regimen, were found to be independent factors and were used to construct a nomogram, which effectively categorized PPLELC patients into a high-risk and a low-risk group, with patients in the high-risk patients demonstrating worse PFS (7.0 vs. 18.0 months, P<0.001) and lower overall response rates (22.2% vs. 52.7%, P<0.001). The nomogram showed satisfactory discrimination for PFS, with AUC values of 0.837 and 0.855 in the training and validation cohorts, respectively. The HIBS-based nomogram could effectively predict the PFS and response of patients with PPLELC regarding immunotherapy and serve as a valuable tool for clinical decision making.

Survival of cemented short Exeter femoral components in primary total hip arthroplasty.

The aim of this study was to report the long-term follow-up of cemented short Exeter femoral components when used in primary total hip arthroplasty (THA). We included all primary 394 THAs with a cemented short Exeter femoral component (≤ 125 mm) used in our tertiary referral centre between October 1993 and December 2021. A total of 83 patients (21%) were male. The median age of the patients at the time of surgery was 42 years (interquartile range (IQR) 30 to 55). The main indication for THA was a childhood hip disease (202; 51%). The median follow-up was 6.7 years (IQR 3.1 to 11.0). Kaplan-Meier survival analyses were performed to determine the rates of survival with femoral revision for any indication, for septic loosening, for fracture of the femoral component and for aseptic loosening as endpoints. The indications for revision were evaluated. Fractures of the femoral component were described in detail. The 20-year rate of survival was 85.4% (95% confidence interval (CI) 73.9 to 92.0) with revision for any indication, 96.2% (95% CI 90.5 to 98.5) with revision for septic loosening and 92.7% (95% CI 78.5 to 97.6) with revision for fracture of the femoral component. No femoral components were revised for aseptic loosening. There were 21 revisions of the femoral component; most (seven) as part of a two-stage management of infection. Fracture of the femoral component occurred in four THAs (1.0%) at 6.6, 11.6, 16.5, and 18.2 years of follow-up, respectively. Three of these were transverse fractures and occurred at the level of the lesser trochanter. In one THA, there was a fracture of the neck of the component. THAs using cemented short Exeter femoral components showed acceptable rates of survival of the femoral component at long-term follow-up, in this young cohort of patients. Although fracture is a rare complication of these components, surgeons should be aware of their incidence and possible risk factors.

Gluteus Repair Yields Satisfactory Clinically Significant Outcome Achievement by 1 Year in Mostly Partial-Thickness Tears With Preoperative Hip Abduction Weakness Associated With Delayed Achievement

PurposeThe purposes of this study were (1) to define the time to achievement of clinically significant outcomes (CSOs) following primary gluteus medius and/or minimus (GM) repair and (2) to identify factors associated with delayed CSO achievement. MethodsPatients who underwent primary GM repair between January 2012 and June 2021 with complete preoperative, 6-month, 1-year, and 2-year Hip Outcome Score – Activities of Daily Living (HOS-ADL) were retrospectively identified. Cohort-specific minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were calculated. The time to achievement of MCID and PASS were analyzed using Kaplan-Meier survival analysis. Median time to MCID and PASS achievement were recorded. Multivariate stepwise cox regressions were used to identify factors associated with delayed CSO achievement. ResultsFifty GM repairs were identified (age 59.4 ± 9.7 years, BMI 27.9 ± 6.2 kg/m2, 94% female). Tears were Grade 1 in 39 cases, Grade 2 in 7 cases, and Grade 3 in 4 cases. Endoscopic repair was performed in 35 cases, and open repair was performed in 15 cases. Labral debridement and repair were each performed in 15 cases. Median time to CSO achievement was 5.7 months for MCID and 11.0 months for PASS. The 2-year cumulative probability of MCID and PASS achievement was 92.7% and 66.7%, respectively. Preoperative hip abduction weakness on physical exam was associated with delayed achievement of MCID (Hazard Ratio (HR) = 2.27, Confidence Interval (CI) 1.067 – 7.41, p = 0.039) and PASS (HR= 3.89, CI 1.341 - 11.283, p = 0.012). ConclusionsThis study demonstrated that in patients undergoing repair of primarily Grade 1 GM tears, most achieved MCID by 6 months and over half achieved PASS by 12 months. Preoperative hip abduction weakness on physical exam was associated with delayed CSO achievement. Level of EvidenceRetrospective Case Series, IV.

CytoSorb® in burn patients with septic shock and Acute Kidney Injury on Continuous Kidney Replacement Therapy is associated with improved clinical outcome and survival

BackgroundIn burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying metabolic changes in inflammatory and anti-inflammatory cytokines dysregulated production. MethodsA retrospectively observational study of 35 severe burn patients admitted to the Burn Center (Turin, Italy, from January 2017 to December 2022), who underwent CRRT for AKI-associated septic shock. Out of 35 patients, 11 were treated with CytoSorb® as adjunctive therapy to CRRT (Sorbent group) and 24 patients only with CRRT (Control group). ResultsThe application of CytoSorb® took place in a very dispersed way. Out of 11 patients, 7 started the CRRT together with the sorbent application. The patients of the sorbent group exhibited a significant reduction in norepinephrine use compared to that of the control group. A clinical improvement over the first 4 days of Cytosorb® was observed in both survivors and no survivors of the sorbent group, with significant norepinephrine decreased use on day 4 compared to day 1. In-hospital mortality was 45.4% and 70.8% in the sorbent and control group, respectively, and significantly better at Kaplan-Meier survival analysis at 270 days (p = 0.0445). In both groups, all survivor patients recovered renal function at discharge, whereas no survivors did not. ConclusionsAdjunctive treatment with CytoSorb® for burn patients with AKI-CRRT and septic shock poorly responsive to standard therapy led to a significant clinical improvement, and was associated with a lower mortality rate compared to CRRT alone.

Cuproptosis-related molecular classification and gene signature of hepatocellular carcinoma and experimental verification.

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor overall prognosis. Cuproptosis, a recently proposed mode of copper-dependent cell death, plays a critical role in the malignant progression of various tumors; however, the expression and prognostic value of cuproptosis-related regulatory genes in HCC remain unclear. Genomic, genetic, and expression profiles of ten key cuproptosis-related regulatory genes were analyzed using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset and protein expression data from the Human Protein Atlas (HPA) database. Unsupervised clustering of HCC patients based on these ten key cuproptosis-related regulatory genes was used to identify different HCC subtypes and analyze the differences in clinical and immune characteristics among subtypes. Subsequently, univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox analyses were used to establish a cuproptosis-related prognostic signature, and the accuracy of prognostic signature prediction was internally validated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic curve in TCGA training and testing cohorts. The prognostic signature was externally validated using TCGA-LIHC entire cohort and International Cancer Genome Consortium Liver Cancer (ICGC-LIRI) cohorts. Finally, the expression landscape of cuproptosis-related regulatory genes in prognostic signature was explored by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry (IHC) experiments. Ten cuproptosis-related genes were differentially expressed in normal and HCC tissues. Unsupervised clustering identified two subtypes and HCC patients with these two subtypes had different clinical prognoses and immune characteristics, as well as different degrees of response to immunotherapy. Lipoyltransferase 1 (LIPT1), dihydrolipoamide s-acetyltransferase (DLAT), and cyclin dependent kinase inhibitor 2A (CDKN2A) were selected to construct a prognostic signature, which significantly distinguished HCC patients with different survival periods in the TCGA training and testing cohorts and was well validated in both the TCGA-LIHC entire cohort and ICGC-LIRI cohort. The risk score of the prognostic signature was confirmed to be an independent prognostic factor, and nomograms were generated to effectively predict the probability of HCC patient survival. The qRT-PCR, western blotting and IHC results also revealed a significant imbalance in the expression of these cuproptosis-related genes in HCC. The classification and prognostic signature based on cuproptosis-related regulatory genes helps to explain the heterogeneity of HCC, which may contribute to the individualized treatment of patients with the disease.

Long term for patients with futile endovascular reperfusion after stroke.

With the progress of thrombectomy technology, the vascular recanalization rate of patients with stroke has been continuously improved, but the proportion of futile recanalization (FR) is still quite a few. The long-term prognosis and survival of patients with FR and its influencing factors remain unclear. Consecutive patients who received endovascular treatment (EVT) for ischemic stroke were enrolled between 2013 and 2021 from a single-center prospectively registry study. We evaluated the long-term outcome of these patients by Kaplan-Meier survival analysis, and the multivariable logistic regression curve was performed to analyze influencing factors. Among 458 patients with FR, 56.4% of patients survived at 1 year, and 50.4% at 2 years. In the multivariate regression analysis, age, premorbid modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), posterior circulation infarct, general anesthesia, symptomatic intracerebral hemorrhage (sICH), and decompressive craniectomy were found to be related to unfavorable outcomes in long-term. Age, premorbid mRS, NIHSS, general anesthesia, and sICH were predictors of long-term mortality. Futile recanalization accounts for a large proportion of stroke patients after thrombectomy. This study on the long-term prognosis of such patients is beneficial to the formulation of treatment plans and the prediction of therapeutic effects.

Ferroptosis-Related Genes Are Associated with Radioresistance and Immune Suppression in Head and Neck Cancer.

Background: Ferroptosis is associated with tumor development; however, its contribution to radioresistant head and neck cancer (HNC) remains unclear. In this study, we used bioinformatics analysis and in vitro testing to explore ferroptosis-related genes associated with HNCs radiosensitivity. Materials and Methods: GSE9714, GSE90761, and The Cancer Genome Atlas (TCGA) datasets were searched to identify ferroptosis-related differentially expressed genes between radioresistant and radiosensitive HNCs or radiation-treated and nonradiation-treated HNCs. A protein-protein interaction analysis on identified hub genes was then performed. Receiver operating characteristic curves and Kaplan-Meier survival analysis were used to assess the diagnostic and prognostic potential of the hub genes. Cell counting kit-8, transwell assay, and flow cytometry were applied to examine the role of hub gene collagen type IV, alpha1 chain (COL4A1) on the proliferation, migration, invasion, and apoptosis of TU686 cells. Results: Hub genes MMP10, MMP1, COL4A1, IFI27, and INHBA showed diagnostic potential for HNC and were negatively correlated with overall survival and disease-free survival in the TCGA dataset. Also, IL-1B, IFI27, INHBA, and COL4A1 mRNA levels were significantly increased in TCGA patients with advanced clinical stages or receiving radiotherapy, whereas COL4A1, MMP10, and INHBA expressions were negatively correlated with immune infiltration. Furthermore, the knockdown of COL4A1 inhibited cell proliferation, migration, and invasion while promoting apoptosis in TU686 cells. Conclusion: Ferroptosis-related hub genes, such as COL4A1, are potential diagnostic and prognostic indicators as well as therapeutic targets for HNC.