Unfavorable Clinical Outcome In Patients Research Articles

Prolonged Venous Transit Is Associated With Lower Likelihood of Favorable Clinical Recovery in Reperfused Anterior Circulation Large‐Vessel Occlusion Stroke

Background Unfavorable clinical outcomes in patients with acute ischemic stroke caused by large‐vessel occlusions despite successful reperfusion have been associated with poor venous outflow. The objective of this study is to assess the relationship between prolonged venous transit (PVT), a novel perfusion imaging surrogate for poor venous outflow, and likelihood of favorable clinical recovery. Methods In this retrospective review of prospectively collected data of consecutive patients (2017–2022) with successfully reperfused, anterior circulation acute ischemic stroke caused by large‐vessel occlusions, we assessed the association between PVT+, defined as time to maximum ≧10‐second timing delays within either the posterior superior sagittal sinus, torcula, or both regions on pretreatment perfusion imaging, and favorable clinical outcomes defined as 90‐day modified Rankin Scale score of 0 to 2. Patients were dichotomized into PVT+ and PVT− for analysis. Multivariable logistic regression analyses for favorable recovery were performed with demographic variables and stroke characteristics. Results A total of 127 consecutive patients (median age, 71 [interquartile range 61—77] years; 59.1% women) were included, and 40 of 127 (31.5%) were PVT+. PVT+ (adjusted odds ratio [aOR], 0.23 [95% CI, 0.07–0.81]; P = 0.02) and advanced age (aOR, 0.92 [95% CI, 0.88–0.97]; P = 0.01) were significantly associated with the primary outcome. Conclusion PVT+ was associated with a lower likelihood of achieving favorable clinical recovery in successfully reperfused patients with acute ischemic stroke caused by large vessel occlusion. PVT may serve as a clinically useful adjunctive imaging parameter.

Exploiting mechanoregulation via FAK/YAP to overcome platinum resistance in ovarian cancer

Cancer cells mechanically interact with the tumor microenvironment during cancer development. Mechano-reciprocity has emerged as a crucial factor affecting anti-cancer drug resistance during adjuvant therapy. Here, we investigated the focal adhesion kinase (FAK)/Yes-associated protein (YAP) signaling axis as a prospective strategy for circumventing cisplatin resistance in ovarian cancer (OC). The Cancer Genome Atlas (TCGA) data analysis revealed that FAK overexpression significantly correlated with unfavorable clinical outcomes in patients with ovarian cancer. AFM indentation experiments showed that cell elasticity depends on FAK activity. Notably, the combination of FAK inhibition and cisplatin treatment led to a 69 % reduction in the IC50 of cisplatin. This combined treatment also increased apoptosis compared to the individual treatments, along with the upregulation of the pro-apoptotic factor BAX and cleaved PARP. Suppressing FAK expression sequestered YAP in the cytosol, potentially reducing cellular proliferation and promoting apoptosis. Moreover, reduced FAK expression sensitized drug-resistant OC cells to cisplatin treatment owing to a decrease in nuclear tension, allowing the relocation of YAP to the cytosol. In a mouse model, the co-administration of an FAK inhibitor and cisplatin significantly suppressed tumor growth and increased apoptotic events and DNA fragmentation. Our findings suggest that drug resistance can be attributed to the perturbation of mechanosensing signaling pathways, which drive the mechanical reinforcement of cancer cells. OC cells can restore their sensitivity to cisplatin treatment by strategically reducing YAP localization in the nucleus through FAK downregulation.

Expression of NAP1L5 in Patients with First Diagnosis of Acute Myeloid Leukemia and its Clinical Significance.

The objective of this study was to assess the expression levels of NAP1L5 in individuals diagnosed with acute myeloid leukemia (AML) and to investigate its clinical and prognostic significance in those with primary AML. Between June 2021 and June 2023, the Department of Hematology at the First Affiliated Hospital of Bengbu Medical University collected 100 bone marrow specimens from primary AML patients and 30 from individuals with idiopathic thrombocytopenic purpura (ITP) for this medical research study. The researchers gathered comprehensive clinical data from patients diagnosed with acute myeloid leukemia (AML). Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the mRNA levels of NAP1L5 in both the ex-perimental and the control group. The investigation involved analyzing the association between NAP1L5 expres-sion related to AML, clinical features, and overall prognosis. The study employed the Kaplan-Meier method to evaluate the impact of NAP1L5 expression on the overall survival time (OS) in AML patients, while the Cox hazard regression model was used to identify significant prognostic factors. NAP1L5 was found to be significantly more expressed in individuals with AML compared to those with ITP. Patients diagnosed with AML and exhibiting elevated NAP1L5 expression levels correlated with older age, ineffective response to chemotherapy, and a more unfavorable prognosis compared to those with lower NAP1L5 expression. Additionally, the group with high expression demonstrated a noticeably decreased overall survival (OS), compared to the group with low expression. Furthermore, a significant association was observed between the elevated NAP1L5 expression levels and an unfavorable clinical outcome in patients diagnosed with AML. The initial exploration of the elevated expression of NAP1L5 in AML and its clinical significance offers potential targets for AML treatment and prognostic evaluation.

Is HALP score a predictor of poor prognosis in patients with hematologic malignancies admitted to the intensive care unit?

BackgroundThe Hemoglobin, Albumin, Lymphocyte, Platelet Score (HALP) is a novel predictive biomarker that has surfaced in the literature in recent years. It has been applied to the prediction of many clinical outcomes related to different neoplasms. Each of these inflammatory and nutritional markers is taken into account by the HALP score, which provides an overall prognosis for patients with cancer.MethodsRetrospective data was collected on the demographics of patients hospitalized to our hospital's intensive care unit (ICU) for hematologic malignancies between January 2014 and March 2021. To measure the prognostic value of the HALP score, it was retrospectively calculated for patients with hematologic malignancies on the first day of ICU admission.This study looked into the link between the HALP score and general prognostic characteristics because it has been suggested that the HALP score is a relevant prognostic marker.ResultsPatients with an HALP score <37.10 had significantly higher APACHE II scores (p < 0.001). They also had significantly higher rates of qSOFA score ≥2 (89.3%), as well as statistically significantly higher rates of intubation (96%) and death (96.1%) (p < 0.001). Our study found that a HALP score <37.1 was associated with a 47.04-fold increase in mortality risk.ConclusionIn patients with hematologic malignancies, the prognosis is strongly correlated with the HALP score. When validated in large cohorts, the HALP score, APACHE II, and q SOFA scores, either individually or collectively, can be used to guide prognostic evaluation of patients and act as a reliable predictor of unfavorable clinical outcomes in patients with hematologic malignancies.

Sarcopenia is a possible risk factor for amputation after peripheral arterial interventions.

Sarcopenia has been demonstrated to be related to unfavorable clinical outcomes in patients with vascular diseases. The purpose of this study is to evaluate the relationship between sarcopenia and clinical results in patients with peripheral arterial disease who underwent endovascular therapy (EVT). This single-center retrospective study involved patients with PAD who underwent peripheral EVT at Ankara City Hospital, between January 2018 and December 2021. Two groups of patients were created: sarcopenic and non-sarcopenic patients according to computed tomography angiography muscle measurements. Primary outcome measures were major and minor amputation and survival. Mortality, amputation, and clinical characteristics were compared between the two patient groups. Hazard ratios (HRs) for amputation were calculated for each risk factor via univariate and multivariate analyses. Secondary outcomes included length of hospital stay and post-procedural complications. The mean follow-up period was 29.9 ± 9months for all patients. A total number of 100 patients (mean age 63.5 ± 9.2years) were involved in the study cohort. A significant association was identified between mortality and sarcopenia (p < .001). The mortality rate in the group with sarcopenia was significantly higher than the other group; 65.7% (23 patients) versus (20%, 13 patients) (p < .001). The major amputation rate in the group with sarcopenia was 57.1%, the major amputation rate in the group without sarcopenia was calculated as 15.4%, revealing that the major amputation rate was detected to be significantly higher in the sarcopenia group (p < .001). Multivariate regression analyses showed that only sarcopenia (HR, 0.52; 95% CI, 0.21-1.27; p = 0.15) was independently associated with major amputation in patients with PAD after EVT. Kaplan-Meier analysis revealed a statistically significant difference between the survival curves of sarcopenia and non-sarcopenia patients (p < .001). Sarcopenia seems to be a possible risk factor associated with amputation in patients with PAD who undergo EVT. The results of this study imply that sarcopenia is a possible risk factor for overall survival in patients with PAD.

Dyslipidemia versus obesity as predictors of ischemic stroke prognosis: a multi-center study in China

BackgroundThis multicenter observational study aimed to determine whether dyslipidemia or obesity contributes more significantly to unfavorable clinical outcomes in patients experiencing a first-ever ischemic stroke (IS).MethodsThe study employed a machine learning predictive model to investigate associations among body mass index (BMI), body fat percentage (BFP), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) with adverse outcomes in IS patients. Extensive real-world clinical data was utilized, and risk factors significantly linked to adverse outcomes were identified through multivariate analysis, propensity score matching (PSM), and regression discontinuity design (RDD) techniques. Furthermore, these findings were validated via a nationwide multicenter prospective cohort study.ResultsIn the derived cohort, a total of 45,162 patients diagnosed with IS were assessed, with 522 experiencing adverse outcomes. A multifactorial analysis incorporating PSM and RDD methods identified TG (adjusted odds ratio (OR) = 1.110; 95% confidence interval (CI): 1.041–1.183; P < 0.01) and TC (adjusted OR = 1.139; 95%CI: 1.039–1.248; P < 0.01) as risk factors. However, BMI, BFP, and HDL showed no significant effect. In the validation cohort, 1410 controls and 941 patients were enrolled, confirming that lipid levels are more strongly correlated with the prognosis of IS patients compared to obesity (TC, OR = 1.369; 95%CI: 1.069–1.754; P < 0.05; TG, OR = 1.332; 95%CI: 1.097–1.618; P < 0.01).ConclusionThis study suggests that dyslipidemia has a more substantial impact on the prognosis of IS patients compared to obesity. This highlights the importance of prioritizing dyslipidemia management in the treatment and prevention of adverse outcomes in IS patients.Graphical abstract

CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy

Multiple myeloma (MM) is an incurable hematological malignancy of the plasma cells. The maintenance of protein homeostasis is critical for MM cell survival. Elevated levels of paraproteins in MM cells are cleared by proteasomes or lysosomes, which are independent but inter-connected with each other. Proteasome inhibitors (PIs) work as a backbone agent and successfully improved the outcome of patients; however, the increasing activity of autophagy suppresses the sensitivity to PIs treatment. The transcription levels of CRIP1 were explored in plasma cells obtained from healthy donors, patients with newly diagnosed multiple myeloma (NDMM), and relapsed/refractory multiple myeloma (RRMM) using Gene expression omnibus datasets. Doxycycline-inducible CRIP1-shRNA and CRIP1 overexpressed MM cell lines were constructed to explore the role of CRIP1 in MM pathogenesis. Proliferation, invasion, migration, proteasome activity and autophagy were examined in MM cells with different CRIP1 levels. Co-immunoprecipitation (Co-IP) with Tandem affinity purification/Mass spectrum (TAP/MS) was performed to identify the binding proteins of CRIP1. The mouse xenograft model was used to determine the role of CRIP1 in the proliferation and drug-resistance of MM cells. High CRIP1 expression was associated with unfavorable clinical outcomes in patients with MM and served as a biomarker for RRMM with shorter overall survival. Invitro and invivo studies showed that CRIP1 plays a critical role in protein homeostasis via the dual regulation of the activities of proteasome and autophagy in MM cells. A combined analysis of RNA-seq, Co-IP and TAP/MS demonstrated that CRIP1 promotes proteasome inhibitors resistance in MM cells by simultaneously binding to de-ubiquitinase USP7 and proteasome coactivator PA200. CRIP1 promoted proteasome activity and autophagosome maturation by facilitating the dequbiquitination and stabilization of PA200. Our findings clarified the pivotal roles of the CRIP1/USP7/PA200 complex in ubiquitin-dependent proteasome degradation and autophagy maturation involved in the pathogenesis of MM. A full list of funding sources can be found in the acknowledgements section.

Nuclear pore protein POM121 regulates subcellular localization and transcriptional activity of PPARγ

Manipulation of the subcellular localization of transcription factors by preventing their shuttling via the nuclear pore complex (NPC) emerges as a novel therapeutic strategy against cancer. One transmembrane component of the NPC is POM121, encoded by a tandem gene locus POM121A/C on chromosome 7. Overexpression of POM121 is associated with metabolic diseases (e.g., diabetes) and unfavorable clinical outcome in patients with colorectal cancer (CRC). Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor with anti-diabetic and anti-tumoral efficacy. It is inhibited by export from the nucleus to the cytosol via the RAS-RAF-MEK1/2-ERK1/2 signaling pathway, a major oncogenic driver of CRC. We therefore hypothesized that POM121 participates in the transport of PPARγ across the NPC to regulate its transcriptional activity on genes involved in metabolic and tumor control. We found that POM121A/C mRNA was enriched and POM121 protein co-expressed with PPARγ in tissues from CRC patients conferring poor prognosis. Its interactome was predicted to include proteins responsible for tumor metabolism and immunity, and in-silico modeling provided insights into potential 3D structures of POM121. A peptide region downstream of the nuclear localization sequence (NLS) of POM121 was identified as a cytoplasmic interactor of PPARγ. POM121 positivity correlated with the cytoplasmic localization of PPARγ in patients with KRAS mutant CRC. In contrast, POM121A/C silencing by CRISPR/Cas9 sgRNA or siRNA enforced nuclear accumulation of PPARγ and activated PPARγ target genes promoting lipid metabolism and cell cycle arrest resulting in reduced proliferation of human CRC cells. Our data suggest the POM121-PPARγ axis as a potential drugable target in CRC.

Unfavorable clinical outcomes in patients with good collateral scores following endovascular treatment for acute ischemic stroke of the anterior circulation: The UNCLOSE study

Background Patients with acute ischemic stroke secondary to large vessel occlusions and good collaterals are frequently associated with favorable outcomes after mechanical thrombectomy, although poor outcomes are observed also in this subgroup. We aimed to investigate the factors associated with unfavorable outcomes (modified Rankin Scale3–6) in this specific subgroup of patients. Methods In total, 219 patients (117 females) with anterior circulation stroke and good collaterals (American Society for Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grades 3–4), treated by mechanical thrombectomy between 2016 and 2021 at our institution were included in this study. Clinical files and neuroimaging were retrospectively reviewed. Univariate and multivariate analyses were performed to identify the predictors of unfavorable outcomes in the overall population (primary endpoint). Secondary endpoints focused on the analysis of the predictors of unfavorable outcomes in the subgroup of successfully recanalized patients, mortality, and symptomatic intracerebral hemorrhages in the overall population. Results Poor outcome was observed in 47% of the patients despite the presence of good collaterals. Older age ( p &lt; 0.001), higher baseline National Institute of Health stroke scale ( p &lt; 0.001), no intravenous thrombolysis administration ( p = 0.004), &gt; 3 passes ( p = 0.01), and secondary transfers ( p &lt; 0.001) were associated with the primary endpoint. The multivariate analysis showed a predictive effect of modified treatment in cerebral infarction 2b-3 and of first pass effect on symptomatic intracerebral hemorrhage. Conclusions Despite good collaterals, defined through the American Society for Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale, poor outcomes occurred in almost half of the patients. Patients with good collaterals not receiving intravenous thrombolysis were significantly associated with unfavorable outcomes, whereas first pass effect was not significantly correlated with clinical outcome in this specific cohort of patients. Different methods to assess collaterals should also be investigated.

Serial measurements of lymphocytes, D-dimer, LDH, and CRP do not improve the ability to predict COVID-19 adverse outcomes

We evaluated the discriminatory ability of variations in lymphocyte, D-dimer, C-reactive protein (CRP), and lactate dehydrogenase (LDH) serum levels at 48 to 72 hours of hospitalization compared with baseline measurements to predict unfavorable clinical outcomes in patients with COVID-19. We analyzed diagnostic test results based on a retrospective cohort to determine the ability of variations (gradients or ratios) in patients' lymphocyte, D-dimer, CRP, and LDH serum levels taken 48 to 72 hours after hospital admission to predict adverse outcomes such as death, mechanical ventilation, or intensive care unit (ICU) admission developing. Among 810 patients (56.1% men, age 61.6 ± 16.2 years), 37.5% had at least one adverse outcome; 28.2% required ICU admission, 26.5% required mechanical ventilation, and 19.4% died during hospitalization. In comparing baseline measurements with measurements at 48 to 72 hours, D-dimer, lymphocyte delta, LDH, and CRP had similar discriminatory ability (area under the receiver operating characteristic curve [AUC] 0.57 vs. 0.56, 0.53 vs. 0.57, 0.64 vs. 0.66, and 0.62 vs. 0.65, respectively). Measuring serum risk markers upon hospital admission can be used to evaluate risk of adverse outcomes in hospitalized patients with COVID-19. Repeating these measurements at 48 to 72 hours does not improve discriminatory ability.

Low Lymphocyte-to-Monocyte Ratio as a Possible Predictor of an Unfavourable Clinical Outcome in Patients with Acute Ischemic Stroke after Mechanical Thrombectomy.

Although considerable progress has been made in the treatment of acute ischemic stroke (AIS), the clinical outcome of patients is still significantly influenced by the inflammatory response that follows stroke-induced brain injury. The aim of this study was to evaluate the potential use of complete blood count parameters, including indices and ratios, for predicting the clinical outcome in AIS patients undergoing mechanical thrombectomy (MT). This single-centre retrospective study is consisted of 179 patients. Patient data including demographic characteristics, risk factors, clinical data, laboratory parameters on admission, and clinical outcome were collected. Based on the clinical outcome assessed at 3 months after MT by the modified Rankin Scale (mRS), patients were divided into two groups: the favourable group (mRS 0-2) and unfavourable group (mRS 3-6). Stepwise multivariate logistic regression analysis was used to detect an independent predictor of the unfavourable clinical outcome. An unfavourable clinical outcome was detected after 3 months in 101 patients (54.4%). Multivariate logistic regression analysis confirmed that the lymphocyte-to-monocyte ratio (LMR) was an independent predictor of unfavourable clinical outcome at 3 months (odds ratio = 0.761, 95% confidence interval 0.625-0.928, and P = 0.007). The value of 3.27 was chosen to be the optimal cut-off value of LMR. This value could predict the unfavourable clinical outcome with a 74.0% sensitivity and a 54.4% specificity. The LMR at the time of hospital admission is a predictor of an unfavourable clinical outcome at 3 months in AIS patients after MT.

Targeting tumor-intrinsic PD-L1 suppresses the progression and aggressiveness of head and neck cancer by inhibiting GSK3β-dependent Snail degradation.

PD-L1 is an immune checkpoint protein that allows cells to evade T-cell-mediated immune responses. Herein, we uncover a tumor-intrinsic mechanism of PD-L1 that is responsible for the progression and aggressiveness of HNC and reveal that the extracts of a brown alga can target the tumor-intrinsic signaling pathway of PD-L1. The biological functions of PD-L1 in the proliferation and aggressiveness of HNC cells in vitro were examined by metabolic activity, clonogenic, tumorigenicity, wound healing, migration, and invasion assays. The clinical importance of PD-L1 in the prognosis of patients with HNC was analyzed by immunohistochemistry. The relationship between PD-L1 and EMT was confirmed via western blotting, qPCR, and immunocytochemistry. Through our in silico approach, we found that PD-L1 was upregulated in HNC and was correlated with an unfavorable clinical outcome in patients with HNC. PD-L1 was crucial for promoting tumor growth, both in vitro and in vivo. High expression of PD-L1 was closely correlated with LN metastasis in OSCC. PD-L1 facilitated the cytoskeletal reorganization and aggressiveness of HNC cells. Moreover, PD-L1 enhanced the EMT of HNC cells by regulating the Snail/vimentin axis. Consistently, MEIO suppressed the PD-L1/Snail/vimentin axis, thereby inhibiting the aggressiveness of HNC cells. Inhibition of PD-L1 induced by PD-L1 silencing or MEIO treatment caused Snail degradation through a GSK3β-dependent mechanism. The tumor-intrinsic function of PD-L1 could be attributed to the regulation of the GSK3β/Snail/vimentin axis. The discovery of MEIO targeting the tumor-intrinsic function of PD-L1 may prove particularly valuable for the development of novel and effective anticancer drug candidates for HNCs overexpressing PD-L1.

Epithelial-mesenchymal transition classification of circulating tumor cells predicts clinical outcomes in progressive nasopharyngeal carcinoma.

BackgroundLiquid biopsy facilitates the enrichment and isolation of circulating tumor cells (CTCs) in various human cancers, including nasopharyngeal carcinoma (NPC). Characterizing CTCs allows observation of the evolutionary process of single tumor cells undergoing blood-borne dissemination, such as epithelial-mesenchymal transition. However, the prognostic value of phenotypic classification of CTCs in predicting the clinical outcomes of NPC remains poorly understood.Patients and methodsA total of 92 patients who met the inclusion criteria were enrolled in the present study. The CanPatrol™ CTC technology platform was employed to isolate CTCs, and an RNA in situ hybridization-based system was used for phenotypic classification. Kaplan–Meier survival curves were used for univariate survival analysis, and the log-rank test was performed for between-group comparisons of the survival curves.ResultsCTCs were detected in 88.0% (81/92) of the enrolled patients with NPC. The total CTC number did not vary between the T and N stages or between Epstein–Barr virus DNA-positive and -negative cases. The numbers of total CTCs and epithelial/mesenchymal (E/M) hybrid CTCs decreased significantly at 3 months post concurrent chemoradiotherapy (P=0.008 and P=0.023, respectively), whereas the numbers of epithelial or mesenchymal CTCs did not decrease. E/M hybrid-predominant cases had lower disease-free survival (P=0.043) and distant metastasis-free survival (P=0.046) rates than non-E/M hybrid-predominant cases.ConclusionCTC classification enables a better understanding of the cellular phenotypic alterations responsible for locoregional invasion and distant metastasis in NPC. E/M hybrid-predominant CTC distribution predicts unfavorable clinical outcomes in patients with progressive NPC.

Prognostic Impact of Myosteatosis on Mortality in Hospitalized Patients with COVID-19.

Body composition, including sarcopenia, adipose tissue, and myosteatosis, is associated with unfavorable clinical outcomes in patients with coronavirus disease (COVID-19). However, few studies have identified the impact of body composition, including pre-existing risk factors, on COVID-19 mortality. Therefore, this study aimed to evaluate the effect of body composition, including pre-existing risk factors, on mortality in hospitalized patients with COVID-19. This two-center retrospective study included 127 hospitalized patients with COVID-19 who underwent unenhanced chest computed tomography (CT) between February and April 2020. Using the cross-sectional CT images at the L2 vertebra level, we analyzed the body composition, including skeletal muscle mass, visceral to subcutaneous adipose tissue ratio (VSR), and muscle density using the Hounsfield unit (HU). Of 127 patients with COVID-19, 16 (12.6%) died. Compared with survivors, non-survivors had low muscle density (41.9 vs. 32.2 HU, p < 0.001) and high proportion of myosteatosis (4.5 vs. 62.5%, p < 0.001). Cox regression analyses revealed diabetes (hazard ratio [HR], 3.587), myosteatosis (HR, 3.667), and a high fibrosis-4 index (HR, 1.213) as significant risk factors for mortality in patients with COVID-19. Myosteatosis was associated with mortality in hospitalized patients with COVID-19, independent of pre-existing prognostic factors.

Survey NEN / Inquérito NEN

Introduction: Although new treatments and diagnostic methods for Neuroendocrine Neoplasms (NEN) have been introduced, the level of access to them needs somehow to be further investigated. Objectives: to understand the aspects that influence the access to the diagnosis, follow-up and treatment of patients with NEN in Brazil. Methods: This is a cross-sectional electronic survey conducted by the Brazilian Group of Gastrointestinal Tumors (GTG) and containing sixteen questions sent to Brazilian Oncologists via messaging app, aiming to identify access profiles to diagnostic and follow-up tests among patients with NEN, in addition to proven effective treatments in the Public and Private Brazilian Health Care System. Descriptive analysis was used to report the outcomes.Results: The survey was carried out with 201 Oncologists. Since (31.8%) of the Oncologists responded that they have been trained for more than 15 years and have been working with clinical practice within the scope of the Brazilian National Health System and/or the Private Health Care. For follow-up, the most requested marker was Chromogranin A (39%). Regarding diagnosis, 35.8% of the 201 participants claim to ask for a slide review in their clinical practice, and their access to tomography and resonance (58%). When contextualizing the performance of PET Scan with Gallium 68, it is available in (15%), but a significant percentage did not have access in the Brazilian National Health System Service, corresponding to (95%). Subgroup analysis revealed statistically significant differences in the availability of Somatostatin Analogue, being offered in 56% in the Brazilian National Health System and 84% in the Private Health Care (p &lt; 0.05). Conclusion: This is the first Brazilian research that evaluated access to diagnostic and therapeutic tools in the Brazilian scenario, showing important access limitations, especially in the public sector. In view of the results presented, these restrictions can lead to unfavorable clinical outcomes in patients with NEN in Brazil.

Modified Recession Wedge Trochleoplasty

Background: Trochlear dysplasia represents one of the main anatomic risk factors for patellar instability, with risk of failure and unfavorable clinical outcomes in patients with unaddressed dysplasia undergoing patellar stabilization. Indications: Patients with trochlear dysplasia characterized by supratrochlear prominence (DeJour B or D) and recurrent patellar instability, especially following failed soft tissue or bony stabilization. This technique addresses an anterior trochlea without pathologic convexity, as convexity may require conversion to other techniques for groove deepening (eg, DeJour “thick flap” or Schottle “thin flap”). Technique Description: A 6-cm lateral parapatellar arthrotomy is created. A marking pen is used to identify the native center of the trochlea, as well as the location of the planned resection and bony hinge point laterally. An osteotome is used to remove a wedge of bone proximally, such that the posterior aspect of the osteotomy is in line with the anterior femoral cortex. A resection guide is then used to perforate the lateral cortex, with care to avoid damaging the cartilage, and carried laterally and distally to ensure the bony cuts are connected, creating the bony flap. To ensure that all bony bridges are eliminated, the arthroscope is placed into the osteotomy to visualize reduction of the trochlea with manual pressure. A knotless PEEK anchor loaded with 8 loaded sutures is then placed on the roof of the trochlear notch. Sutures are then secured using anchors placed at the center of the trochlea, at the superolateral corner and far lateral edge of the trochlea to reduce the osteotomy, with 2 to 3 sutures placed in each anchor depending on surgeon preference. Results: Trochleoplasty has been reported to decrease the rate of recurrent patellar dislocation while improving mean Kujala score and knee function. Benefits of trochleoplasty must be balanced against the high rate of potential complications, primarily pain and decreased knee range of motion, secondary to the technical challenges and steep learning curve inherent to effectively performing the procedure. Discussion/Conclusion: Patients with recurrent patellar instability with trochlear dysplasia and failed prior stabilization may experience improved stability and outcomes following trochleoplasty.

Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency

PurposeCarbamoyl phosphate synthetase 1 (CPS1) deficiency affects the first step of urea cycle and is a severe form of urea cycle disorder (UCD). The severity of hyperammonemic encephalopathy determines the clinical course of UCDs. Here, we describe the genetic and clinical characteristics of CPS1 deficiency in Korea. Patient and methodsThis study included seven patients with CPS1 deficiency genetically confirmed from January 1992 to September 2020. The peak ammonia level during the first crisis, the half time of peak ammonia level, the initial plasma amino acid levels, and neurological outcomes were compared between CPS1 deficiency and two common UCDs (i.e., 17 patients with argininosuccinate synthetase 1 deficiency and 24 patients with ornithine transcarbamylase deficiency). ResultEleven CPS1 mutations were identified, including 10 novel mutations. Eight mutations were missense. Six patients with CPS1 deficiency had neonatal type. The peak ammonia level, initial glutamate level, and accompanying rate of irreversible neurological damages were highest in patients with CPS1 deficiency. The patient with late-onset CPS1 deficiency responded dramatically to N-carbamylglutamate treatment. ConclusionThe clinical manifestations of CPS1 deficiency were the most severe among UCDs. Considering the high proportion of missense mutations, responsiveness to N-carbamylglutamate would be evaluated in a future study.

Sex Differences in Mitral Annular Calcification and the Clinical Implications.

Background: Heterogeneous mechanisms may contribute to the occurrence of mitral annular calcification (MAC), however, little is known about the sex differences in MAC and the clinical implications of these differences. This study aimed to investigate clinical and imaging differences of MAC according to sex.Methods: In total, 537 patients (221 men) with MAC were identified by transthoracic echocardiography at a single center from January 2012 to June 2016. Moderate-to-severe MAC was defined as calcification extent ≥120° of the mitral annulus. Significant functional mitral stenosis (MS) was defined as a transmitral mean diastolic pressure gradient ≥5 mmHg.Results: Women more frequently had moderate-to-severe MAC and concomitant mitral regurgitation than men; however, significant functional MS was comparable between sexes. In the logistic regression analysis, old age, uncontrolled hypertension, end-stage renal disease (ESRD), and obstructive hypertrophic cardiomyopathy were significantly associated with moderate-to-severe MAC in women, whereas ESRD and moderate-to-severe aortic stenosis were in men. In the Cox regression analysis, significant functional MS was associated with all-cause death in both sexes, although an independent association was found in only women.Conclusion: Women had more extended MAC than men. Significant functional MS was independently associated with unfavorable clinical outcomes in patients with MAC, which was more pronounced in women than in men.

Risk factors for unfavorable clinical outcomes in patients with brain abscess in South Korea.

BackgroundBrain abscess can be life-threatening and manifest various neurological findings, although the mortality rate has decreased recently. We investigated the risk factors for unfavorable outcomes of patients with brain abscess.MethodsA retrospective cohort study examined patients with brain abscess seen from May 2005 to December 2018 in a tertiary care hospital in Seoul, South Korea. We reviewed the medical records for clinical findings, therapeutic modalities, and prognostic factors of brain abscess. Unfavorable clinical outcomes were defined as death, moderate to severe disability with neurological deficits, or vegetative state at 1 year or at the time of discharge from outpatient follow-up.ResultsThe study enrolled 135 patients: 65.2% were males; the mean age was 56 years. 35.6% had unfavorable outcomes. In multivariate analysis, higher Sequential Organ Failure Assessment (SOFA) (p < 0.001), pre-existing hemiplegia (p = 0.049), and higher Charlson comorbidity index (CCI) (p = 0.028) were independently associated with unfavorable outcomes.ConclusionsHigher SOFA, pre-existing hemiplegia and higher Charlson comorbidity index were significant risk factors for unfavorable clinical outcomes in patients with brain abscess.

Association of HLA class I homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer treated with chemo-immunotherapy or immunotherapy as first-line therapy

BackgroundHomozygosity at HLA-I locus has been reported to be an unfavorable predictive biomarker of second-line or beyond immunotherapy in patients with different types of cancer. The linkage between HLA-I zygosity and survival in NSCLC patients treated with first-line immunotherapy with or without chemotherapy has not been reported. MethodsNext generation sequencing with HLA genotyping was performed on patients with advanced NSCLC treated with immune checkpoint inhibitors with or without chemotherapy as first-line (N = 29). Progression free survival was compared between HLA-I homozygous (defined as homozygosity in at least one locus A, B, or C) and heterozygous patients. Kaplan-Meier curves were built, and log-rank test was used. ResultsAmong 29 enrollees, 25 patients (86.2%) were HLA-I heterozygous and four patients (13.8%) were HLA-I homozygous. Treatment response was not available in five patients with HLA-I heterozygosity. Among 20 patients with HLA-I heterozygosity, five patients (20.0%) had partial response, 10 patients (50.0%) had stable disease, two patients (8.0%) had non-complete response/non-progressive disease, and three patients (12.0%) had progressive disease. Among four patients with HLA-I heterozygosity, one patient (25.0%) had partial response, one patient (25.0%) had stable disease, and two patients (50.0%) had progressive disease. The median progression free survival was not reached in heterozygous group and was 2.97 months in homozygous group (Log-rank p = 0.68). ConclusionsWe observed a trend toward an inverse association between HLA-I homozygosity and survival outcomes in patients with NSCLC treated with first-line therapy in conjunction with immunotherapy. Further prospective studies to validate aforementioned relationship are warranted.