Cause Of Poor Outcome Research Articles

Apolipoprotein E mimetic peptide COG1410 alleviates blood‑brain barrier injury in a rat model of ischemic stroke.

Blood‑brain barrier (BBB) damage is one of the main causes of poor outcomes and increased mortality rates following cerebral ischemia‑reperfusion injury. ApolipoproteinE (ApoE) and its mimetic peptide have been previously reported to exhibit potent neuroprotective properties in various central nervous system disease models. Therefore, the present study aimed to investigate the possible role of the ApoE mimetic peptide COG1410 in cerebral ischemia‑reperfusion injury and its potential underlying mechanism. Male SD rats were subjected to 2h middle cerebral artery occlusion followed by 22h reperfusion. Evans blue leakage and IgG extravasation assays results revealed that COG1410 treatment significantly reduced BBB permeability. In addition, insitu zymography and western blotting were used to prove that COG1410 was able to downregulate the activities of MMPs and upregulate the expression of occludin in the ischemic brain tissue samples. Subsequently, COG1410 was found to significantly reverse microglia activation while also suppressing inflammatory cytokine production, according to immunofluorescence signal of Iba‑1 and CD68 and protein expression of COX‑2. Consequently, this neuroprotective mechanism mediated by COG1410 was further tested using the BV2 cell line invitro, which was exposed to oxygen glucose deprivation followed by reoxygenation. The mechanism of COG1410 was found to be mediated, as least partly, through the activation of triggering receptor expressed on myeloid cells 2. In conclusion, the data suggest that COG1410 can alleviate BBB injury and neuroinflammation following ischemic stroke.

Anterior Pituitary Endocrine Dysfunctions in Patients with Traumatic Brain Injury in the Neurosurgical Units of the Yaounde Central and General Hospitals: A Cross-Sectional Study

Background: Post-traumatic endocrine dysfunction (PTED) is an important and relatively common complication of TBI (traumatic brain injury). It is usually undiagnosed and untreated making it a major cause of poor outcome in TBI patients as it can lead to death, delayed recovery, cognitive impairment, depression, sexual dysfunctions and infertility. Study Design: Analytic cross-sectional study at the Yaounde Central and General Hospitals from January 2022 to April 2022. Objective: The main aim of this study was to evaluate the endocrine dysfunctions and factors associated to their occurrence in patients presenting TBI at the neurosurgical units of the Yaounde Central and General Hospitals. Methods: Patients were enrolled at the neurosurgical units Data was collected with the help of a questionnaire after obtaining their informed consent alongside with blood samples in the morning (between 8AM and 10AM) for screening of anterior hypothalamo-pituitary axis hormones (FSH, LH and TSH) and relative peripheral hormones (cortisol, T4, oestrogene in women and testosterone in men) using fluorescence immunoassay. The study population was made up of all patients diagnosed with TBI during the study period at study sites. Patients taking medications affecting the hypothalamo-pituitary axis were excluded. Variables of interest included socio-demographic variables, clinical variables and paraclinical variables. Data was inserted and analyzed using the software Statistical Package for Social Sciences (SPSS) version 26.0. Association between variables was done using Fisher’s exact test. The association measure used was odd’s ratio (OR) with confidence interval (CI) of 95%. Results: A total of 33 participants were enrolled, out of which 26 responding to our inclusion criteria were retained and 7 excluded because they were on medications affecting the hypothalamo-pituitary axis. The median age of participants was 34 (26.75–41.25) years. There was a predominance of the male population with a sex ratio of 12:1. A total of 17 participants developed PTED (65.38%). The PTED encountered were FSH deficiency (12 patients at 46.1%), LH deficiency (10 patients at 38.4%), morning cortisol deficiency (5 patients at 19.2%), TSH deficiency (7 patients at 26.9%), testosterone deficiency (5 patients at 19.2%) and multiple deficiencies (12 patients at 46.1%). PTED was also found in 6 patients with severe TBI, 6 patients with moderate TBI and 5 patients with mild TBI (35.3%, 35.3% and 29.4%). In ≤7 days from TBI, 11 patients suffered PTED (64.7%) while after 7 days post-TBI, only 6 patients suffered PTED (35.3%). Tiredness was the most frequent symptom observed in 15 patients with PTED (88.2%). No factors associated to the occurrence of PTED were found in this study (p-values were all >0.05). Conclusion: This study suggests that PTED is a common condition amongst sufferers of TBI. PTED occurs in both genders and the most frequent types of anterior pituitary endocrine dysfunctions were hypogonadism, hypothyroidism and lastly corticotropic insufficiency. Most patients with PTED had associated CT-scan lesions. No factors was significantly associated to the occurrence of PTED probably due to small sample size.

Circ_0091537 promotes gefitinib chemoresistance in non-small cell lung cancer by mediating the miR-520h/YAP1 network.

Chemoresistance is the leading cause of poor outcomes of non-small cell lung cancer (NSCLC). Circular RNA (circRNA) plays a vital role in NSCLC resistance progression. Our study aimed to uncover the role of circRNA PDZ domain containing 8 (circ_0091537) in NSCLC with gefitinib resistance. The expression of circ_0091537, microRNA-520h (miR-520h), and Yes-associated protein 1 (YAP1) mRNA were detected using quantitative real-time PCR. Cell viability and cell proliferation were assessed by MTT assay and colony formation assay. Colony formation ability was detected by colony formation assay. Cell cycle distribution and cell apoptosis were determined by flow cytometry assay. Cell migration and cell invasion were detected by transwell assay. The potential relationship between miR-520h and circ_0091537 or YAP1 was verified by dual-luciferase reporter assay. Tumor formation assay in nude mice was performed to test the role of circ_0091537 in vivo . Circ_0091537 and YAP1 were upregulated, while miR-520h was downregulated in gefitinib-resistant NSCLC cells. Circ_0091537 knockdown inhibited gefitinib resistance in NSCLC cells and then inhibited NSCLC cell growth, migration, and invasion. MiR-520h was a target of circ_0091537, and miR-520h inhibition reversed the effects of circ_0091537 knockdown. Moreover, YAP1 was a target of miR-520h, and circ_0091537 competitively combined with miR-520h to enrich YAP1 expression. MiR-520h restoration impaired gefitinib resistance and suppressed NSCLC cell proliferation, migration, and invasion by repressing YAP1. Circ_0091537 overexpression weakened gefitinib sensitivity in vivo to promote tumor growth. Circ_0091537 strengthens gefitinib chemoresistance to promote NSCLC progression by mediating the miR-520h/YAP1 network, suggesting that circ_0091537 may be a key indicator in resistance to treatment of NSCLC.

MRI radiomic features of peritumoral edema may predict the recurrence sites of glioblastoma multiforme.

As one of the most aggressive malignant tumor in the central nervous system, the main cause of poor outcome of glioblastoma (GBM) is recurrence, a non-invasive method which can predict the area of recurrence pre-operation is necessary.To investigate whether there is radiological heterogeneity within peritumoral edema and identify the reproducible radiomic features predictive of the sites of recurrence of glioblastoma(GBM), which may be of value to optimize patients' management. The clinical information and MR images (contrast-enhanced T1 weighted and FLAIR sequences) of 22 patients who have been histologically proven glioblastoma, were retrospectively evaluated. Kaplan-Meier methods was used for survival analysis. Oedematous regions were manually segmented by an expert into recurrence region, non-recurrence region. A set of 94 radiomic features were obtained from each region using the function of analyzing MR image of 3D slicer. Paired t test was performed to identify the features existing significant difference. Subsequently, the data of two patients from TCGA database was used to evaluate whether these features have clinical value. Ten features with significant differences between the recurrence and non-recurrence subregions were identified and verified on two individual patients from the TCGA database with pathologically confirmed diagnosis of GBM. Our results suggested that heterogeneity does exist in peritumoral edema, indicating that the radiomic features of peritumoral edema from routine MR images can be utilized to predict the sites of GBM recurrence. Our findings may further guide the surgical treatment strategy for GBM.

Pterostilbene Attenuates Subarachnoid Hemorrhage-Induced Brain Injury through the SIRT1-Dependent Nrf2 Signaling Pathway.

Neuroinflammatory injury, oxidative insults, and neuronal apoptosis are major causes of poor outcomes after subarachnoid hemorrhage (SAH). Pterostilbene (PTE), an analog of resveratrol, has been verified as a potent sirtuin 1 (SIRT1) activator. However, the beneficial actions of PTE on SAH-induced brain injury and whether PTE regulates SIRT1 signaling after SAH remain unknown. We first evaluated the dose-response influence of PTE on early brain impairment after SAH. In addition, EX527 was administered to suppress SIRT1 signaling. The results revealed that PTE significantly attenuated microglia activation, oxidative insults, neuronal damage, and early neurological deterioration. Mechanistically, PTE effectively enhanced SIRT1 expression and promoted nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation in nuclei. Furthermore, EX527 pretreatment distinctly repressed PTE-induced SIRT1 and Nrf2 activation and deteriorated these beneficial outcomes. In all, our study provides the evidence that PTE protects against SAH insults by activating SIRT1-dependent Nrf2 signaling pathway. PTE might be a therapeutic alternative for SAH.

Role of Autologous or Allogeneic Stem Cell Transplantation in Patients with Peripheral T Cell Lymphomas (PTCLs)

Background Peripheral T cell lymphomas (PTCLs) are heterogeneous group which present diverse clinical and molecular characteristics. Stem cell transplantation (SCT) has been known to improve survival outcomes. However, there are still no standard guidelines for choosing high-dose chemotherapy followed by autologous-SCT (auto-SCT) or allogeneic-SCT (allo-SCT) in patients with up-front or salvage setting. Methods We retrospectively analyzed data from 599 patients with PTCLs who underwent auto-SCT or allo-SCT over the past 10 years. Patients between 15 and 70 years were included in this study. Event-free survival (EFS) was determined from the date of SCT to the date of disease progression or death from any cause. Overall survival (OS) was determined from the date of SCT to the date of death or last follow-up. Results A total of 446 patients were analyzed, and the median age at the time of SCT was 49.6 (range, 15.2-69.7) years old. Histology subtypes were PTCL-NOS (n=184), NK/T lymphoma (n=89), angioimmunoblastic T lymphomas (AITL, n=79), anaplastic large cell lymphoma (ALCL, n=64), enteropathy-associated T cell lymphoma (EATL, n=15), and adult T cell leukemia/lymphoma (ATLL, n=15). Up-front SCT was conducted in 379 patients in which CR1 were 229 patients, PR1 were 89, and primary refractory were 61, respectively. As a part of front-line therapy, 302 patients received auto-SCT while 77 patients underwent allo-SCT. Auto-SCT showed significantly superior OS than allo-SCT in patients with CR1 or PR1 at the time of SCT (p=0.026). Survival outcomes in patients with primary refractory disease were also statistically superior in auto-SCT group (EFS, p=0.049; OS, p=0.018). In patients with CR≥2, PR≥2, patients who underwent salvage chemotherapy followed by auto-SCT reported better OS (p=0.011). However, in patients who underwent SCT in a relapsed state, allo-SCT group showed better survival tendency in terms of EFS (p=0.077) and OS (p=0.058). Majority cause of poor outcomes in allo-SCT group was treatment related mortality (TRM). In the allo-SCT group, total body irradiation (TBI) and CR or PR status at the time of SCT were identified as favorable factors in the multivariate analysis. Donor type and conditioning regimen were not affected the transplantation outcomes. Conclusion Auto-SCT was effected as a part of front-line therapy or as a part of salvage setting. Allo-SCT could be considered in relapsed state patients with TBI based conditioning regimen.

NUSAP1, a novel stemness-related protein, promotes early recurrence of hepatocellular carcinoma.

Early recurrence (within 2 years after resection) is the primary cause of poor outcomes among hepatocellular carcinoma (HCC) patients, and liver cancer stem cells are the main contributors to postsurgical HCC recurrence. Nucleolar and spindle-associated protein 1 (NUSAP1) has been reported to be involved in tumor progression. We investigated the function and clinical value of NUSAP1 in early recurrence of HCC. Data from public datasets and our cohort were used to assess the association between NUSAP1 expression and early HCC recurrence. Gain- and loss-of-function experiments were carried out in vivo and in vitro. The predictive effect of NUSAP1 on early HCC recurrence was further evaluated by a validation cohort. We found that elevated NUSAP1 expression in HCC specimens was correlated with poor outcome, especially in cases with postoperative early recurrence. Functional studies indicated that NUSAP1 significantly promotes HCC progression. A postsurgical recurrence murine model further revealed that upregulated NUSAP1 dramatically increased the likelihood of HCC early recurrence. RNA sequencing data revealed that the gene sets of cancer stemness and the signal transducer and activator of transcription 3 (STAT3) pathway were enriched by NUSAP1 overexpression. Mechanistically, NUSAP1 enhanced cancer stemness through stimulating STAT3 nuclear translocation and activation through receptor of activated protein C kinase 1 (RACK1). In a validation cohort with 112 HCC patients, NUSAP1 effectively predicted HCC early recurrence. Our results indicated that NUSAP1 promotes early recurrence of HCC by sustaining cancer stemness and could serve as a valuable predictive indicator for postsurgical intervention in HCC patients.

The Synergism of Natural Compounds and Conventional Therapeutics against Colorectal Cancer Progression and Metastasis.

Cancer progression and metastases are the leading causes of poor outcomes in patients with colon cancer. Colon cancer metastasis is a multigene, multistep, multistage complex process in which target genes, microRNAs, epithelial-stromal transformation, tumour stem cells, the tumour microenvironment, and various cell signalling pathways are implicated in the progression and metastasis of colon cancer. Although conventional therapies have made significant advances in treating the progression and metastasis of colorectal cancer, they have failed to improve survival outcomes. Natural compounds may have more significant potential in preventing and treating colon cancer. Active natural compounds exert their antitumor effects by inducing tumour cell differentiation, promoting tumour cell apoptosis, inhibiting tumour vascular growth, and regulating immunity. Natural compounds, combined with conventional therapies, can target mutant genes and various cellular signalling pathways, inhibit epithelial-stromal transformation, and improve the tumour microenvironment to inhibit tumour progression and metastasis. The synergism of natural compounds and conventional therapeutics has the potential to become a promising therapy for treating colorectal cancer progression and metastases.

TRPM2 mediates CaMKⅡ-Beclin-1 signaling in early cortical injury after induced subarachnoid hemorrhage in mice

BackgroundThough early brain injury (EBI) is the primary cause of poor outcomes among patients with subarachnoid hemorrhage (SAH), its exact molecular mechanisms remain unclear. Improved the understanding of how transient receptor potential melastatin-related 2 (TRPM2) is involved in SAH-induced EBI will help develop novel interventions. MethodsWild type (WT) male C57BL/6J mice were subjected to SAH for 12 h, 24 h or 48 h, after which neurological scores and pathological changes in the hippocampus (CA3, DG, and CA1) and temporal base cortex were observed. Expressions of TRPM2, Ca2+/calmodulin (CaM)-dependent protein kinase Ⅱ (CaMKⅡ), and Beclin-1 in hippocampus (CA3, DG, and CA1) and temporal base cortex were compared across post-SAH timepoints. TRPM2-deficient (TRPM2−/−) male C57BL/6 J mice and a CaMKⅡ inhibitor (KN-93) were used to analyze the effects oTRPM2 on the CaMKⅡ-Beclin-1 signaling post SAH. ResultsNeurological and temporal base cortex deterioration were more severe with increased time post-SAH induction, whereas hippocampal damage was not observed. Post-SAH, TRPM2-CaMKⅡ-Beclin-1 cascade was activated in the temporal base cortex, but not the hippocampus. Using TRPM2−/− mice and KN-93 administration, SAH-induced EBI was improved, and CaMKⅡ and Beclin-1 expressions in the temporal base cortex were significantly decreased compared with WT mice. TRPM2−/− mice also showed better neurological improvement compared with KN-93 treated mice. ConclusionTRPM2 mediates CaMKⅡ-Beclin-1 signaling that aggravates SAH-induced EBI in the temporal base cortex. TRPM2 may be an alternative therapy target in EBI after SAH. Data availabilityThe datasets generated and/or analysed during the current study are available from the corresponding author

Long non-coding RNA ZNF674-AS1 antagonizes oxaliplatin resistance of gastric cancer via regulating EZH2-mediated methylation of CHST7.

Chemoresistance leads the cause of poor outcome of patients with gastric cancer (GC). Long non-coding RNAs (LncRNAs) is intimately involved in the regulation of tumorigenesis and progression. Here, we demonstrated ZNF674-AS1 was down-regulated in oxaliplatin (OXA)-resistant tissues and cell lines, lower level of ZNF674-AS1 predicted poor prognosis of GC patients. Besides, forced expression of ZNF674-AS1 not only reduced cell viability, colony formation, expression of drug-resistant markers but also promoted cell apoptosis of OXA-resistant GC cells, exposed to oxaliplatin. Silence of ZNF674-AS1 exhibited an opposite effects on OXA resistance of GC cells. Further mechanistic research showed that ZNF674-AS1 interacted with EZH2, led to higher methylation level of target gene CHST7. In addition, functional experiments verified that depletion of CHST7 re-sensitized OXA-resistant GC cells to OXA. Thus, our results indicated that ZNF674-AS1 suppressed OXA resistance of GC through EZH2-mediated inhibition of CHST7, providing potential theoretic basis and therapeutic strategy for chemoresistant GC.

Prediction of Outcomes of Ultrasound-Guided Saline Enema in the Treatment of Pediatric Intussusception: A Retrospective Case-Control Study.

Outcomes of ultrasound-guided saline enema include successful treatment, unsuccessful treatment, or recurrence. This study aimed to investigate the value of ultrasonic parameters of the ileocecal region during hydrostatic reduction to predict enema outcomes. Ultrasound images of patients diagnosed with ileocolic intussusception and treated with ultrasound-guided saline enema at two different institutions between January 2019 and April 2021 were retrospectively analyzed to assess ileocecal-valve diameter (ICVD), intussusceptum thickness (IT), and the ratio of IT to ICVD (I/I). Logistic regression analysis was used to explore correlations between ICVD, IT, I/I, and patient characteristics (sex, age, symptom duration, and enema outcome). Of 291 patients with ileocolic intussusception (207 boys; mean ICVD, 8.6 [SD: 0.1]mm; mean IT, 26 [SD: 0.2]mm; mean I/I, 3.0 [SD: 0.01]), 268 had first successful reduction; 23, first failed reduction; 7, final failed reduction; and 41, early recurrence. Significant risk factors for failed reduction included symptom duration >24 hours (odds ratio [OR]=10, P=.012), ICVD≤ 8.5 mm (OR=8, P=.01), and I/I > 3.25 (OR=16, P < .001). Significant risk factors for early recurrence post-enema included age>1 year (OR=10, P=.028), ICVD > 8.5 mm (OR=4, P=.003), and I/I≤ 2.95 (OR=6, P < .001). ICVD and IT measured during ultrasound-guided hydrostatic reduction can predict enema outcomes. The mismatch between IT and ICVD is the primary cause of poor outcomes.

Omecamtiv mecarbil treatment improves post-resuscitation cardiac function and neurological outcome in a rat model.

BackgroundMyocardial dysfunction is a major cause of poor outcomes in the post-cardiac arrest period. Omecamtiv mecarbil (OM) is a selective small molecule activator of cardiac myosin that prolongs myocardial systole and increases stroke volume without apparent effects on myocardial oxygen demand. OM administration is safe and improves cardiac function in patients with acute heart failure. Whether OM improves post-resuscitation myocardial dysfunction remains unclear. This study investigated the effect of OM treatment on post-resuscitation myocardial dysfunction and outcomes.Methods and resultsAdult male rats were resuscitated after 9.5 min of asphyxia-induced cardiac arrest. OM and normal saline was continuously intravenously infused after return of spontaneous circulation (ROSC) at 0.25 mg/kg/h for 4 h in the experimental group and control group, respectively (n = 20 in each group). Hemodynamic parameters were measured hourly and monitored for 4 h after cardiac arrest. Recovery of neurological function was evaluated by neurological functioning scores (0–12; favorable: 11–12) for rats 72 h after cardiac arrest. OM treatment prolonged left ventricular ejection time and improved post-resuscitation cardiac output. Post-resuscitation heart rate and left ventricular systolic function (dp/dt40) were not different between groups. Kaplan-Meier analysis showed non-statistically higher 72-h survival in the OM group (72.2% [13/18] and 58.8% [10/17], p = 0.386). The OM group had a higher chance of having favorable neurological outcomes in surviving rats 72 h after cardiac arrest (84.6% [11/13] vs. 40% [4/10], p = 0.026). The percentage of damaged neurons was lower in the OM group in a histology study at 72 h after cardiac arrest (55.5±2.3% vs. 76.2±10.2%, p = 0.004).ConclusionsOM treatment improved post-resuscitation myocardial dysfunction and neurological outcome in an animal model. These findings support further pre-clinical studies to improve outcomes in post-cardiac arrest care.

A Novel Coagulation Classification and Postoperative Bleeding in Severe Spontaneous Intracerebral Hemorrhage Patients on Antiplatelet Therapy.

Background and PurposeFor patients with severe spontaneous intracerebral hemorrhage on antiplatelet therapy (patients with APT-SICH), postoperative rebleeding (PR) is an important cause of poor outcomes after surgery. As impacted by coagulation disorder caused by APT, patients with APT-SICH are likely to suffer from PR. This study aimed to assess the risk of PR in patients with APT-SICH receiving emergency surgery using a novel coagulation classification.MethodsThis prospective, multicenter cohort study consecutively selected patients with APT-SICH between September 2019 and March 2021. The preoperative coagulation factor function was recorded, and the platelet function was assessed using thrombelastography. Based on platelet and coagulation factor function, a novel four-type coagulation classification, i.e., Type I (severe coagulation disorder), Type IIa (low platelet reserve capacity), Type IIb (normal coagulation), and Type III (hypercoagulation), was presented. The primary outcome was PR, defined as the rebleeding in the operative region or new intracerebral hemorrhage correlated with the operation.ResultsOf the included 197 patients with APT-SICH, PR occurred in 40 patients (20.3%). The novel coagulation classification categorized 28, 32, 122, and 15 patients into Type I, Type IIa, Type IIb, and Type III, respectively. The Type I patients had the highest incident rate of PR (39.3 per 100 persons), followed by the Type IIa patients (31.3 per 100 persons). In the PR-related analysis, the large hematoma volume (hazard ratio (HR): 1.02; 95% CI: 1.02–1.03; p < 0.001), Type I (HR: 9.72; 95% CI: 1.19–79.67; p = 0.034), and Type IIa (HR: 8.70; 95% CI: 1.09–69.61; p = 0.041) were correlated with the highest risk of PR. The coagulation classification could discriminate the PR patients from no PR (NPR) patients (p < 0.001), and it outperformed the conventional coagulation assessment (only considering platelet count and coagulation factor function) (c-statistic, 0.72 vs. 0.55).ConclusionThe novel coagulation classification could discriminate the patients with APT-SICH with the highest risk of PR preoperatively. For the Type I and Type IIa patients, emergency surgery should be performed carefully.

The impact of diabetes on young transplant recipients: An American perspective.

Our study aims to demonstrate the impact of diabetes, types I and II, on American young adults (18-40 years old) requiring kidney transplantation. Using the United Network for Organ Sharing database, we conducted a population cohort study that included all first-time, kidney-only transplant recipients during 2002-2019, ages 18-40 years old. Patients were grouped according to indication for transplant. Primary outcomes were cumulative all-cause mortality and death-censored graft failure. Death-censored graft failure and patient survival at 1, 5, and 10 years were calculated via the Kaplan-Meier method. Multivariate Cox regression was used to assess for potential confounders. Of 42 466 transplant recipients, 3418 (8.1%) had end-stage kidney disease associated with diabetes. At each time-point, cumulative mortality was higher in diabetics compared to patients with non-diabetic causes of renal failure. Conversely, cumulative graft failure was similar between the groups. Adjusted hazard ratios for all-cause mortality and graft failure in diabetics were 2.99 (95% CI 2.67-3.35; p < .01) and 0.98 (95% CI 0.92-1.05, p < .01), respectively. Diabetes mellitus in young adult kidney transplant recipients is associated with a nearly three-fold increase in mortality, reflecting a relatively vulnerable patient population. Identifying the underlying causes of poor outcomes in this population should be a priority for future study.

Tumor Location Causes Different Recurrence Patterns in Remnant Gastric Cancer.

Tumor recurrence is the principal cause of poor outcomes in remnant gastric cancer (RGC) after resection. We sought to elucidate the recurrent patterns according to tumor locations in RGC. Data were collected from the Shanghai Cancer Center between January 2006 and December 2020. A total of 129 patients with RGC were included in this study, of whom 62 had carcinomas at the anastomotic site (group A) and 67 at the non-anastomotic site (group N). The clinicopathological characteristics, surgical results, recurrent diseases, and survival were investigated according to tumor location. The time interval from the previous gastrectomy to the current diagnosis was 32.0±13.0 and 21.0±13.4 years in groups A and N, respectively. The previous disease was benign in 51/62 cases (82.3%) in group A and 37/67 cases (55.2%) in group N (P=0.002). Thirty-three patients had documented sites of tumor recurrence through imaging or pathological examinations. The median time to recurrence was 11.0 months (range, 1.0-35.1 months). Peritoneal recurrence occurred in 11.3% (7/62) of the patients in group A versus 1.5% (1/67) of the patients in group N (P=0.006). Hepatic recurrence occurred in 3.2% (2/62) of the patients in group A versus 13.4% (9/67) of the patients in group N (P=0.038). Patients in group A had significantly better overall survival than those in group N (P=0.046). The tumor location of RGC is an essential factor for predicting recurrence patterns and overall survival. When selecting an optimal postoperative follow-up program for RGC, physicians should consider recurrent features according to the tumor location.

Obstetric Hemorrhage during the Third Trimester of Pregnancy: Experience in a University Hospital in Guinea

Aims: Obstetric hemorrhage, especially during the 3rd trimester of pregnancy, causes maternal, fetal and neonatal mortality and morbidity. We attempted to characterize its clinical features in Guinea. The objectives of this study were to describe the socio-demographic characteristics of the patients, identify the causes and contributing factors, describe the management and evaluate the maternal-fetal prognosis in such patients. Methods: We retrieved and analyzed patients with 3rd trimester hemorrhage whom we managed at Ignace Deen National Hospital, Guinea during 1-year period (1st of December 2019-30th of November 2020). Results: We experienced recorded 401 patients with 3rd trimester obstetric hemorrhage out of 5468 deliveries during the corresponding period; the rate being 7.33%. The main causes were as follows: placental hematoma (65.33%), placenta previa (27.68%) and uterine rupture (6.99%). The socio-demographic profiles were as follows: the age group of 25 - 29 years (28.42%), married (94.51%), uneducated (50.12%), and with a liberal profession. (43.64%) and pauciparous (30.42%). The conditions were considered to be preventable by managing risk factors during the prenatal consultation (PNC): 7.73% underwent no PNC. Cesarean accounted for 84.78% of patients. Prognosis was as follows: 14 maternal deaths (3.45% of a fatality), 34.66% of anemia, and 16.95% of hemorrhagic shock. Fetal/neonatal prognoses were poor. Conclusion: Obstetric hemorrhage during 3rd trimester remains the main cause of poor outcomes in Guinea. This study identified that this type of hemorrhage still represents an important cause of maternal and fetal morbidity and mortality in developing countries.

Risk factors for poor prognosis in heart failure with particular attention to the elderly population

Background Heart failure (HF) is a leading cause of poor outcome. Age is considered one of the most critical risk factors for both the incidence and prognosis of HF. Therefore we aimed to assess the predictors of poor prognosis in HF patients with particular attention to the elderly population.

Management of Advanced Pulmonary Sarcoidosis.

The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "advanced pulmonary sarcoidosis" (APS), which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. Although APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes, including death. Here we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.

A causal inference approach to compare leukaemia treatment outcome in the absence of randomization and with dependent censoring

One cause of poor outcomes in children of low-income countries affected by acute lymphoblastic leukaemia (ALL) is loss to follow-up due to abandonment of treatment. Assuming this type of loss to follow-up as independent censoring, as in standard Kaplan-Meier estimates, ignores the likely association of abandonment with biologic and socio-economic factors related to outcome. Moreover, when comparing treatment protocols adopted in different time periods, possible imbalances in patients' characteristics must be considered. We aim to compare the outcome of children enrolled in two subsequent protocols for ALL treatment (2000-2007 and 2008-2015) in Honduras, taking both dependent censoring due to abandonment of treatment and imbalances between patient characteristics into account. Marginal structural models based on inverse probability of treatment and censoring (IPTC) weighting allow the estimation of potential event-free survival (EFS) as if no abandonment of treatment occurred and the whole cohort was exposed, or not, to both protocols. An Aalen additive model and a logistic-regression model were used to build abandonment and treatment weights, respectively. The two protocols recruited 514 and 717 patients. Measured baseline covariates in both protocols were gender, age, white blood cell count, central nervous system involvement, tumour histology and socio-economic status. The potential EFS is slightly higher under the more recent protocol in the first 3 years but no difference is estimated in the long period [survival difference at 5 years (95% confidence interval) = 0.1% (-0.97%; 1.13%)]. Both protocols would allow reducing the event rate by 12-13% if there was no abandonment of treatment. Using IPTC weighting, we found a similar potential effect of the two treatment protocols if the imbalance due to the different distribution of potential confounders and to abandonment of therapy was removed.

Anesthesia modality does not affect clinical outcomes of intra-arterial vasodilator treatment in patients with symptomatic cerebral vasospasms.

Background: Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral vasospasms can be treated with endovascular vasodilator therapy, which can either be performed in conscious sedation or general anesthesia. The aim of this study is to compare the effect of the anesthesia modality on long-term clinical outcomes in patients undergoing endovascular vasodilator therapy due to cerebral vasospasm and hypoperfusion. Methods: Modified Rankin Scale (mRS) scores were retrospectively analyzed at time of discharge from the hospital and six months after aneurysmal subarachnoid hemorrhage. Additionally, National Institutes of Health Stroke Scale (NIHSS) was assessed 24 hours before, immediately before, immediately after, and 24 hours after endovascular vasodilator therapy, and at discharge and six months. Interventional parameters such as duration of intervention, choice and dosage of vasodilator and number of arteries treated were also recorded. Results: A total of 98 patients were included in this analysis and separated into patients who had interventions in conscious sedation, general anesthesia and a mix of both. Neither mRS at discharge nor at six months showed a significant difference for functionally independent outcomes (mRS 0-2) between groups. NIHSS before endovascular vasodilator therapy was significantly higher in patients receiving interventions in general anesthesia but did not differ anymore between groups six months after the initial bleed. Conclusion: This study did not observe a difference in outcome whether patients underwent endovascular vasodilator therapy in general anesthesia or conscious sedation for refractory cerebral vasospasms. Hence, the choice should be made for each patient individually.