Worse Prognosis Research Articles

Real-world switching patterns and associated characteristics in patients with psoriasis treated with biologics.

Multiple parameters define the treatment course with biologics for a psoriatic patient while treatment switches are often associated with worse prognosis. The purpose of this study was to describe the switching patterns of biologics for psoriasis in the Greek market landscape and to detect associated factors that may impact the evolvement of selected therapy. This is a retrospective cohort study using data recorded in the nationwide digital prescription database of Greece. Patients with a diagnosis for psoriasis, with or without concomitant psoriatic arthritis (PsA), who had initiated a biologic treatment between January 1st 2016 and December 31st 2020 were included. Overall, 6,772 biologic-naïve patients were included. Patients treated with infliximab demonstrated the highest switching rates while those treated with ustekinumab and secukinumab the lowest. Secukinumab and brodalumab had the lowest rates of switch or re-initiation 12 months after initiation. Switches from secukinumab to brodalumab and ustekinumab and from adalimumab to secukinumab and ustekinumab were more frequently observed. The risk was significantly higher for patients with concurrent PsA and for women, while patients treated with brodalumab, secukinumab and ustekinumab demonstrated a lower risk compared to adalimumab. Antibodies against interleukins have lower switching rates compared to more traditional biologics. The time to switch is longer for the first transition highlighting the necessity to establish long term therapeutic options early in the treatment course. Concurrent PsA or gender may have a significant impact in outcome, thus they need to be considered before the launch of a selected therapy.

The Presence of Small-Size Circulating Tumor Cells Predicts Worse Prognosis in Non-Small Cell Lung Cancer Patients.

The Presence of Small-Size Circulating Tumor Cells Predicts Worse Prognosis in Non-Small Cell Lung Cancer Patients.

Transcriptomics profiling of Parkinson’s disease progression subtypes reveals distinctive patterns of gene expression

Background Parkinson’s Disease (PD) varies widely among individuals, and Artificial Intelligence (AI) has recently helped to identify three disease progression subtypes. While their clinical features are already known, their gene expression profiles remain unexplored. Objectives The objectives of this study were (1) to describe the transcriptomics characteristics of three PD progression subtypes identified by AI, and (2) to evaluate if gene expression data can be used to predict disease subtype at baseline. Design This is a retrospective longitudinal cohort study utilizing the Parkinson’s Progression Markers Initiative (PPMI) database. Methods Whole blood RNA-Sequencing data underwent differential gene expression analysis, followed by multiple pathway analyses. A Machine Learning (ML) classifier, namely XGBoost, was trained using data from multiple modalities, including gene expression values. Results Our study identified differentially expressed genes (DEGs) that were uniquely associated with Parkinson’s disease (PD) progression subtypes. Importantly, these DEGs had not been previously linked to PD. Gene-pathway analysis revealed both distinct and shared characteristics between the subtypes. Notably, two subtypes displayed opposite expression patterns for pathways involved in immune response alterations. In contrast, the third subtype exhibited a more unique profile characterized by increased expression of genes related to detoxification processes. All three subtypes showed a significant modulation of pathways related to the regulation of gene expression, metabolism, and cell signaling. ML revealed that the progression subtype with the worst prognosis can be predicted at baseline with 0.877 AUROC, yet the contribution of gene expression was marginal for the prediction of the subtypes. Conclusion This study provides novel information regarding the transcriptomics profiles of PD progression subtypes, which may foster precision medicine with relevant indications for a finer-grained diagnosis and prognosis.

Impact of family socio-economic status on the prognosis of heart transplantation in children

BackgroundLow family socio-economic status is a known factor that can contribute to increased mortality for patients with cardiovascular disease. However, in developing countries, the prognostic impact of socio-economic level on pediatric HTx is unclear.MethodsWe conducted a retrospective cohort analysis of children younger than 18 years who underwent heart transplantation (HTx) at our center from October 1, 2005, to May 31, 2023. To assess the impact of socio-economic status, we followed up with the discharged children until September 30, 2023, monitoring for all-cause mortality and unplanned readmission events. To evaluate the relationship between socio-economic status and prognosis, we assigned a composite score based on an assessment of household income, parental education level, and occupation. The Cox proportional hazards model and the Kaplan-Meier method were utilized for this analysis.Results64 children (median age at operation 14 years, IQR 13–15) were enrolled and one case died in hospital due to primary graft dysfunction, 63 (98.4%) children had a median follow-up of 60 months (IQR 5.9-113.9). During the follow-up period, 10 (15.9%) children died, and 20 (31.7%) children had 25 unplanned readmissions. Children had higher all-cause mortality and more unplanned readmissions in families with low socio-economic status (n = 33) than middle (n = 10) or high (n = 20) family socio-economic status. Hazard ratios were 5.99,(95%CI:2.28–10.64, P = 0.003) for all-cause mortality for low versus high family socio-economic status, and 2.53 (95%CI:1.04–9.43, P = 0.029) for middle versus high family socio-economic status.ConclusionsLower family socio-economic status is associated with a worse prognosis than high family socio-economic status. Measures to alleviate economic disparities are needed to improve the prognosis of pediatric HTx.

Diagnostic and prognostic values of tsRNAs in lung cancer: a meta-analysis

BackgroundLung cancer (LC) is the leading cause of cancer-related death in humans. tRNA-derived small RNA (tsRNA) is a novel biomarker that plays a crucial role in the genesis and development of LC. In this study, we aimed to investigate the value of differentially expressed tsRNAs in LC through meta-analysis.MethodsPubMed and Web of Science were searched for articles published up to January 10, 2024. Diagnostic odds ratios (DORs) and areas under the receiver operating characteristic curve (AUCs) were used to evaluate the potential of tsRNAs as diagnostic markers for LC. Furthermore, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to analyze association of tsRNAs with LC prognosis.ResultsIn total, 12 studies were included in the analysis. Our results indicated that the combined DOR of total tsRNAs for LC diagnosis was 7.32; the AUC was 0.81. Subgroup analysis revealed that high levels of tsRNAs in serum had good diagnostic efficacy (DOR = 16.56, AUC = 0.88). Moreover, a high tsRNAs level was associated with a worse prognosis in LC patients (HR = 1.59, 95% CI: 1.33–1.90).ConclusionOur findings suggest that a high tsRNAs level has potential value for diagnosis and prognosis of LC patients. However, further high-quality studies are needed to validate our results.

Utilizing TP53 hotspot mutations as effective predictors of gemcitabine treatment outcome in non-small-cell lung cancer

TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis. In addition, clinical data from NSCLC patients were collected to evaluate both their TP53 status and their response to gemcitabine, thereby facilitating further validation. Subsequently, NSCLC cell lines with different TP53 status (A549 and H1299) were subjected to gemcitabine treatment to investigate the association between TP53 mutations and gemcitabine response. According to the dataset, NSCLC cell lines carrying TP53 mutations displayed heightened sensitivity to gemcitabine. From a clinical standpoint, patients exhibiting TP53 hotspot mutations demonstrated prolonged overall survival upon gemcitabine treatment. In vitro, overexpressing various hotspot TP53 mutations significantly sensitized H1299 cells to gemcitabine. Moreover, the knockdown of TP53 in A549 cells notably augmented sensitivity to gemcitabine treatment, as evidenced by cell viability and reproductive cell death assays. Conversely, the overexpression of wild-type TP53 in H1299 cells led to an increased resistance against gemcitabine. Gemcitabine is a treatment option for patients with non-small cell lung cancer (NSCLC) who carry TP53 hotspot mutations. This potential effectiveness might arise from its ability to disrupt DNA damage repair processes, leading to G2/M phase cell cycle arrest or an augmentation of mitotic abnormalities, eventually cause cell death. As a result, when planning treatment strategies for NSCLC patients possessing TP53 hotspot mutations, gemcitabine should be considered to incorporate into the indication.

CircPRKD3-loaded exosomes concomitantly elicit tumor growth inhibition and glioblastoma microenvironment remodeling via inhibiting STAT3 signaling.

Glioblastoma stem cells (GSCs) and their exosomes (exos) are involved in shaping the immune microenvironment, which is important for tumor invasion and recurrence. However, studies involving GSC-derived exosomal circular RNAs (GDE-circRNAs) in regulating tumor microenvironment (TME) remain unknown. Here, we comprehensively evaluated the significance of a novel immune-related GDE-circRNA in glioma microenvironment. GDE-circPRKD3 was screened out through high-throughput sequencing and verified by RT-PCR, sanger sequencing and RNase R assays. A series of in vitro and in vivo experiments were performed to investigate the function of GDE-circPRKD3. RNA-seq, RNA immunoprecipitation, multicolor flow cytometry and western blotting were used to explore the regulation of GDE-circPRKD3 on STAT3 signaling-mediated TME remodeling. We have characterized a circRNA PRKD3 in GSC exosomes, and lower circPRKD3 expression predicts a worse prognosis for glioblastoma patients. Overexpression of GDE-circPRKD3 significantly impairs the biological competence of glioma and prolongs the survival of xenograft mice. GDE-circPRKD3 binds to HNRNPC in an m6A-dependent manner, accelerates mRNA decay of IL6ST and inhibits downstream target STAT3. Notably, GDE-circPRKD3 promotes CXCL10 secretion by reprogramming tumor-associated macrophages, which in turn recruits CD8+ tumor infiltrating lymphocytes against GBM. Moreover, brain-targeted lipid nanoparticle delivery of circPRKD3 combined with immune checkpoint blockade therapy achieves significant combinatorial benefits. This study provides a novel mechanism by which GDE-circPRKD3 relies on STAT3 signaling to remodel immunosuppressive TME and offers a potential RNA immunotherapy strategy for GBM treatment.

Clinical characteristics and prognosis of patients treated as invasive pulmonary aspergillosis outside of severe immunosuppression

This study aimed to identify clinical characteristics and develop a prognostic model for non-neutropenic patients with invasive pulmonary aspergillosis (IPA). A retrospective analysis of 151 IPA patients was conducted, with patients categorized into survival (n = 117) and death (n = 34) groups. Clinical data, including demographics, laboratory tests, and imaging, were collected. Multivariate Cox regression analysis identified glucocorticoid use (odds ratio [OR] = 30.223, 95% confidence interval [CI]: 2.676–341.306), intensive care unit admission (OR = 0.133, 95% CI: 0.023–0.758), and the arterial oxygen partial pressure/fractional inspired oxygen ratio (OR = 0.994, 95% CI: 0.990–0.999) as significant predictors of 28-day mortality. A prognostic model was developed based on these factors, showing high predictive accuracy (receiver operating characteristic curve area of 0.918). The model’s clinical applicability was validated through calibration curves, bootstrap internal validation, decision curve analysis, and clinical impact curves. Kaplan–Meier analysis further confirmed its utility, indicating a worse prognosis for high-risk patients within 50 days and the highest survival rate at 14 days. This novel model offers valuable insights for predicting survival in non-neutropenic IPA patients.

Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure.

Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia. A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m2, 20-25 kg/m2, and ≥25 kg/m2, respectively. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated. This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m2 [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90-0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30-2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34-2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61-8.08; p = 0.002). BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox.

Risk Factors and Outcome of Pneumatosis Intestinalis in Children

Objectives: Pneumatosis intestinalis (PI) is rare in childhood. The aetiology remains poorly understood. Our aim was to assess its associated risk factors and outcome. Methods: Retrospective data collection of all children (&gt;1 month of age) with radiological evidence of PI identified from 1991 to 2021 in a large children’s hospital. Poor outcome was defined as loss of enteral autonomy, or death within one month of PI diagnosis. Results: A total of 31 patients (21 male, 67.7%) were included, with a median age of 5 years. The underlying diagnosis was heterogenous. Cerebral palsy and acute lymphocytic leukaemia (ALL) were most common (5/31 for each, 16.13%). A share of 12/31 (38.7%) developed PI 2–15 months post-bone marrow transplantation (BMT). Most patients (n = 15, 48.4%) had no pre-existing gastroenterological disorder. In the majority (11/31, 35.5%), PI was an incidental finding. Abdominal pain was the most common presentation in symptomatic children (7/31, 22.6%). All (31/31, 100%) were managed conservatively with gut rest and antibiotics, and 6/31 (19.4%) had a poor outcome (1/31 permanent feeding intolerance, 5/31 died). When comparing patients who did well (group 1) to those with a poor outcome (group 2), worse prognosis was associated with a lower platelet count (p = 0.016), raised CRP (p = 0.008), higher creatinine (p = 0.006), and higher urea (p = 0.013). Conclusions: The overall prognosis of PI in childhood is good but associated with significant morbidity and mortality in a small number of patients. Our data suggest that lower platelet count, and higher urea, creatinine, and CRP levels might be risk factors.

Navigating through the diagnostic labyrinth of rare bifocal intracranial germ cell tumors: A case report

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Intracranial germ cell tumors (iGCTs) are a rare and heterogeneous group of neoplasms originating from germ cells within the central nervous system (CNS). These tumors are a subclass of CNS germ cell tumors (GCTs) that are typically observed in 1st to 2nd decades of life. They tend to occur in the midline, either at the pineal region or along the floor of the third ventricle/suprasellar region. Less commonly, both regions can be involved, presenting as bifocal tumors which usually carry a worse prognosis. Such bifocal lesions can be either two independent primary germinomas (GEs) (known as true bifocal GE) or it can be one primary GE with metastases (known as false bifocal GE). Bifocal presentation is mostly seen in GE, but some of the patients may have mixed GCT. Clinical features are mainly due to the mass effect and involvement of sellar and supra-sellar regions.&lt;br /&gt;&lt;strong&gt;Case Presentation:&lt;/strong&gt; A 21-year-old male presented with complaints of erectile dysfunction, lack of libido, headache, polydipsia,&lt;br /&gt;polyuria, diplopia, and recent onset blurring of vision over the past 6 months to 1 year. Radiological investigations revealed&lt;br /&gt;the presence of true bifocal iGCTs, which were confirmed to be &amp;beta;-human chorionic gonadotropin producing GEs upon&lt;br /&gt;histopathological and immunohistochemical analysis. The patient showed complete resolution of the tumor following treatment.&lt;br /&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Intracranial GEs are highly radiosensitive tumors often characterized by insidious symptoms, leading to a significant delay in diagnosis, with patients often seeking medical assistance only when their daily activities are severely impaired. However, this delay could be mitigated by obtaining a thorough patient history and maintaining a high index of suspicion for intracranial GEs, particularly in the appropriate age groups. Our case report emphasizes the importance of a multidisciplinary team approach in facilitating timely and informed decision-making for optimal patient management.&lt;/p&gt;

The language of glioblastoma: a tale of cytokines and sex hormones communication

Abstract Glioblastoma (GB) is the most aggressive and frequent tumor in the central nervous system and, in humans, represents the worst prognosis for cancer. GB develops a very complex microenvironment, recruiting and interacting with a variety of cells and soluble factors, including immune cells, cytokines, and sex hormones, that contribute to GB survival and progression. Recent evidence has shown a crosstalk between cytokine and sex hormone signaling in GB. This communication could provide GB resistance to treatments and malignancy. Then, how GB orchestrates this communication is a matter of interest. For instance, a critical interaction between tumor necrosis factor beta (TGF-β) and estrogen receptor signaling has been reported in regulating epithelial-mesenchymal transition, an essential step in GB progression. Furthermore, an inhibition of TGF-β signaling by androgen receptor has been reported to promote GB tumorigenesis in men. On the other hand, it has been described that cytokines regulate steroid hormone production in different organs, and this mechanism could be involved in GB development and progression. All these data suggest an intercommunication between the immune and endocrine systems in the tumor microenvironment. Thus, in this review, we focus on explaining the knowledge about this critical intercommunication system and its implication in GB progression.

Outcome of acute ischemic stroke with absent opacification of the cervical internal carotid artery at CT-angiography after endovascular treatment.

Purpose: Occlusion of the distal internal carotid artery can simulate a proximal occlusion of its cervical tract on CT angiography in patients with acute ischemic stroke, that is, pseudo-occlusion. As true and false carotid occlusions can present similarly on non-invasive imaging in patients undergoing endovascular treatment for stroke, our study aimed to evaluate clinical and technical differences of these conditions and the possible consequences of a misdiagnosis. Methods: We retrospectively reviewed consecutive patients who underwent mechanical thrombectomy for acute ischemic stroke at a single center between July 2015 and May 2022 and included patients with absent opacification of the cervical carotid artery on CT-angiography. Digital subtraction angiography (DSA) imaging and procedural data were evaluated to define the actual localization of the occlusion. We compared imaging and clinical data between patients with true and false carotid occlusion, including collateral circulation at CTA, revascularization grade, and clinical outcome at 3months. Results: A total of 116 patients were included, 63 (54%) of whom had true occlusion of cervical internal carotid artery. Compared to the pseudo-occlusion group, collateral circulation at CTA was moderate to good in 75% of cases (vs 32%; p < 0.0001) and the mean ASPECT score at 24h was 7 versus 2 (p < 0.0001). Modified Rankin scale 0-2 at 90days was more frequent in patients with true occlusion than those with pseudo-occlusion (48 vs 11%; p = 0.0002). Conclusion: Pseudo-occlusion of the cervical internal carotid artery in patients with acute ischemic stroke appears to be associated with worst prognosis and poorer collateral circulation in comparison with tandem occlusion.

Clinical significance of preoperative Glasgow prognostic score in patients with colorectal cancer and synchronous peritoneal metastases

AbstractBackgroundChemotherapy is the typical choice for treating colorectal cancer with synchronous peritoneal metastases. Nonetheless, surgical resection may be chosen if the metastases are resectable. Unfortunately, there is no reliable preoperative or intraoperative prognostic indicator. This study aimed to determine the prognostic significance of the preoperative Glasgow prognostic score (GPS) in colorectal cancer patients with synchronous peritoneal metastases.MethodsWe conducted a prospective study on 143 patients with colorectal cancer and concurrent peritoneal metastases. Our analysis included prognostic factors, such as the GPS, using data from the institutional observational study by the Japanese Society for Cancer of the Colon and Rectum.ResultsThe 3‐year survival rates for the GPS0 or 1 and GPS2 groups were 32.7% and 14.3%, respectively, with a significantly worse prognosis in the GPS2 group (p = 0.003). Multivariate analysis identified GPS2 (p = 0.006) and the peritoneal cancer index (PCI) (p = 0.029) or the Japanese surgical peritoneal metastasis grade (p = 0.009) as independent poor prognostic factors. Additionally, the GPS0 or 1 group with total resection of peritoneal metastases had a significantly better prognosis than the non‐resection group (p &lt; 0.001); however, there was no difference between the GPS2 group with total peritoneal resection and the non‐resection group (p = 0.713).ConclusionsPreoperative GPS2 is an independent poor prognostic factor in patients with colorectal cancer and synchronous peritoneal metastases, and surgical resection does not improve prognosis in patients with GPS2. Preoperative GPSs may be used as indicators for surgical resection of synchronous peritoneal metastases.

Development and external validation of a model for lung transplantation-free survival prediction of primary Sjögren's syndrome-associated interstitial lung disease: a prospective cohort study

BackgroundThe primary Sjögren's Syndrome-associated Interstitial Lung Disease (pSS-ILD) patients have a worse prognosis than pSS patients without pulmonary involvement. This study aims to establish a prediction nomogram for early prediction of lung transplantation (LTx)-free survival in pSS-ILD patients.MethodsThe training cohort comprised 260 patients from China-Japan Friendship Hospital between January 1, 2016, and June 30, 2022, while the external validation cohort consisted of 135 patients from Beijing Chaoyang Hospital between January 1, 2007, and December 31, 2012. Univariable Cox regression analysis and least absolute shrinkage and selection operator (LASSO) were employed for variable selection, and a nomogram model was developed to predict the 1 -, 3 -, 5-year LTx-free survival. Both discrimination and calibration of the nomogram were assessed using concordance index (C-index), area under the curve (AUC), calibration curve and decision curve analysis (DCA).ResultsMultivariable Cox regression demonstrated that elevated age, oxygenation index, CA125 and fibrosis score were independent risk factors for LTx-free survival in pSS-ILD patients. The C-index displayed of the training and validation cohorts were 0.812 and 0.809. The 1-, 3-, 5-year AUC values in training and validation cohorts were 0.781, 0.874, 0.909 and 0.793, 0.826, 0.863 respectively. Bias-corrected curve is close to the ideal curve and revealed a strong consistency between actual observation and prediction.

ACOX1 activates autophagy via the ROS/mTOR pathway to suppress proliferation and migration of colorectal cancer

Acyl-CoA oxidase 1 (ACOX1), a member of the acyl-coenzyme A oxidase family, is considered a crucial regulator whose dysregulation is implicated in the occurrence and progression of various cancers. This study aims to elucidate the impact of ACOX1 in CRC, shedding light on its potential as a therapeutic target. Through analysis of the GEO dataset, it was found that ACOX1 is significantly downregulated in colorectal cancer (CRC), and this lower expression level is associated with a worse prognosis. Additionally, in vitro as well as in vivo, ACOX1 overexpression dramatically reduced the proliferation and metastasis of CRC cells. Mass spectrometry revealed the crucial role of ACOX1 in fatty acid β-oxidation, as its overexpression led to a substantial increase in reactive oxygen species (ROS) derived from fatty acid β-oxidation. Further experiments demonstrated that ACOX1 overexpression, through modulation of fatty acid metabolism, increased ROS levels, reduced the phosphorylation activation of the key autophagy regulator mTOR, enhanced autophagy, and ultimately suppressed the growth and metastasis of CRC. In conclusions, ACOX1 expression is decreased in CRC. ACOX1 may regulate autophagy by reprogramming lipid metabolism to modulate the ROS/mTOR signaling pathway, consequently inhibiting the proliferation and migration of CRC.

Insights into the use of DNA content in head and neck squamous cell carcinoma as a method for patient stratification and targeted therapy: Revisiting old concepts and exploring new possibilities.

This review aimed to emphasize the implications of DNA content in head and neck squamous cell carcinoma (HNSCC), focusing on its predictive value, role in patient stratification, and potential as a therapeutic target for this malignancy. A narrative review of the literature was conducted through electronic database searches. In conventional HNSCC, aneuploid tumors are associated with increased lymph node metastasis, locoregional recurrences, poor response to radiotherapy and chemotherapy, and worse prognosis. Few studies specifically address the role of DNA content in young HNSCC patients. These studies reveal that young patients exhibit high DNA content abnormalities, suggesting significant genomic instability and potential genetic differences compared to older patients. Regarding HPV and DNA content, no difference was found between HPV-associated and HPV-independent tumors. More research is needed to understand the role of DNA content in histological subtypes, surgical margins, and targeted therapy. This review highlights the findings related to DNA content in HNSCC, suggesting its usefulness in patient stratification and outcome prediction.

Hypervirulent Klebsiella pneumoniae have better clinical outcomes than classical Klebsiella pneumoniae for lower respiratory tract infection patients

BackgroundThe clinical outcomes and microbiological features of lower respiratory tract infections (LRTIs) caused by hypervirulent Klebsiella pneumoniae (hvKp) and classical Klebsiella pneumoniae (cKp) have not been well understood.MethodsThis study collected 287 non-repetitive Klebsiella pneumoniae isolates from 287 LRTI patients. All these strains underwent annotation for resistance and virulence factors, with 141 strains undergoing mouse infection experiments to assess their virulence. The primary clinical outcomes of these patients were evaluated, including intensive care unit (ICU) admission and in-hospital mortality rates.ResultsA total of 46 capsule serotypes were identified. Among these isolates subjected to mouse infection experiments, the proportions of strains exhibiting hypervirulent phenotypes were 92.6% (25/27), 92.1% (35/38), 80% (4/5), 25% (1/4), 10.5% (2/19), and 7.1% (1/14) for K2, K1, K20, K54, K47, and K25, respectively. Therefore, K1, K2, and K20 K. pneumoniae were defined as hvKp. In addition, the rates of ICU admission and in-hospital mortality for hvKp-infected patients were significantly lower than those of cKp-infected patients (51.4% vs. 65.9%, χ2 = 4.722, p = 0.03 and 8.6% vs. 29%, χ2 = 12.133, p < 0.001). Notably, among the cKp group, the cKp-ST11 subgroup had higher rates of ICU admission (77% vs. 58.5%, χ2 = 7.981, p = 0.005) and in-hospital mortality (44.8% vs. 18.5%, χ2 = 17.585, p < 0.001) than cKp-nonST11 subgroup.ConclusionsThese findings suggest that capsule serotype is a more accurate factor for the prediction of the virulence phenotype, while hvKp have better clinical outcomes than cKp for LRTI patients. Furthermore, the cKp-ST11 subgroup has the worst prognosis than cKp-nonST11 subgroup.

Robot-assisted “Bridge” approach pancreatosplenectomy for “shoulder” pancreatic cancer: a new technique

Pancreatic body/ tail cancer has a worse prognosis because of late detection and early invasion into important vessels. Our team proposed the concept of “shoulder” pancreatic cancer (PC) and invented a new approach named Retrograde artery first approach pancreatosplenectomy (RAFAPS). However, we found that in some cases this approach may not be perfect. We encountered a patient who had previously undergone laparoscopic radical operation for hilar cholangiocarcinoma caused RAFAPS could not be performed. Hence, we used a new procedure based on RAFAPS to finish the pancreatosplenectomy and named it “Bridge”. After the operation, the patient recovered smoothly. We report the new technique, aiming to provide the experience for the surgical treatment of “shoulder” PC.

Normalized Reflectivity of Middle Limiting Membrane on SD-OCT: A Measure of Acute Ischemia in CRVO

Purpose To validate the quantification of the prominent middle limiting membrane (PMLM) sign, a marker of mild-to-moderate acute ischemic damage on optical coherence tomography (OCT), by measuring middle limiting membrane (MLM) reflectivity in patients with central retinal vein occlusion (CRVO) and to investigate the prognostic impact of this measure. Methods Spectral Domain (SD)-OCT B-scans of 30 patients with CRVO, either sole CRVO or combined central retinal artery and vein occlusion (CCRAVO), were analyzed retrospectively and graded as PMLM present or absent. Normalized MLM reflectivity was calculated as a ratio of the maximum reflectivity within a MLM target layer and the average reflectivity of the retinal pigment epithelium (RPE). Results Discrimination between OCT B-scans graded as PMLM present or absent based on ROC analysis was far superior with normalized MLM reflectivity (AUC >0.90) than using MLM reflectivity without normalization (AUC = 0.70). Normalized MLM reflectivity was significantly higher in study eyes than healthy fellow eyes as well as in patients with CCRAVO versus sole CRVO. Although normalized MLM reflectivity correlated significantly with baseline and outcome BCVA, we found no significant difference comparing patients with ischemic CRVO versus non-ischemic CRVO. Conclusions Quantifying MLM reflectivity requires normalization due to shadowing, which is usually caused by retinal haemorrhages in CRVO. RPE reflectivity proved to be a suitable reference layer. Greater normalized MLM reflectivity as a measure of mild-to-moderate acute ischemic damage indicated a worse prognosis regarding visual function in CRVO, however, it allows no risk assessment regarding the development of capillary non-perfusion or anterior segment neovascularization.