Search

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP ( P < .05). After dividing the 179 patients into 4 subgroups, the “FP without GH” subgroup suffered the worst oncological outcomes ( P < .001). The Cox multivariate regression analysis showed that “FP without GH” ( P < .001), tumor multifocality ( P = .005), and pathological stage ( P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of “flank pain without gross hematuria” was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC.

Abstract Background Video-assisted thoracic surgery decortication for phase 3 thoracic empyema is widely accepted, but its optimal timing has not been established. We aim to investigate and assess this timing, in terms of overall survival, for chronic empyema. Methods Two hundred four patients with pneumonia-caused phase 3 empyema were treated with video-assisted thoracic surgery decortication over 10-years at Changhua Christian Hospital. The 90-day post-operative survival status was analyzed, and we compared the survivor group versus the non-survivor group. A receiver operating characteristic curve was used to identify the optimal decortication timing. Results A comparison between survivors and non-survivors showed statistical differences among age (p=0.004), presence of cardiovascular disease (p=0.018), presence of end-stage renal disease (p=0.002), duration to surgery (p=0.013), length of intensive care unit stay (p=0.010), and overall length of hospital stay (p=0.015). ROC curve analysis determined the cut-off for video-assisted thoracic surgery decortication, based on optimal 90-day post-operative survival, to be 7.5 days after hospitalization; mortality increases threefold thereafter (14.2% vs 44.6%, p7.5 days negatively impacted 90-day post-operative survival. Conclusions Patients receiving decortication surgery within 7.5 days of hospital admission had better overall survival.

The root is the main site of nitrogen (N) acquisition and aluminum (Al) toxicity. The objective of this study is to investigate whether liming and cultivation of an Al-tolerant rice (Oryza sativa L.) cultivar can improve root growth, thereby increasing N acquisition by rice plants in acid paddy soil. Two rice cultivars (‘B690’, Al-sensitive, and ‘Yugeng5’, Al-tolerant) were cultivated with 15N-labeled urea, and with or without lime in an acid paddy soil (pH 4.9) in pots. We examined root and shoot growth, soil pH, soil exchangeable Al, N uptake, 15N distribution in plant-soil system, and fertilizer N recovery efficiency. Results showed that liming improved the root growth of ‘B690’ by decreasing soil exchangeable Al concentrations, in both N-limited and N-fertilized soils. Liming enhanced the N uptake of ‘B690’ only in the absence of N fertilizer. The root weight of ‘Yugeng5’ was greater than that of ‘B690’ without lime, but the two cultivars showed similar N uptake. The fertilizer N recovery efficiency and N loss did not differ significantly between limed and non-limed conditions, or between the two rice cultivars. Thus, liming an Al-sensitive rice cultivar and cultivating an Al-tolerant one improves root growth, but does not enhance fertilizer N recovery efficiency in the present acid paddy soil.

Background: This study tested whether combined dapagliflozin (DAPA) and roxadustat (ROX) therapy was superior to a singular therapy in protecting heart and kidney functions in rats with cardiorenal syndrome (CRS). Methods and results: An in vitro study demonstrated that the cell survival (PI3K/Akt/mTOR)/cell stress (ERK1/2, JNK/p-38) signaling was significantly activated by combination therapy with ROX-DAPA (all p

Background: Many patients who recovered from COVID-19 still suffer from chronic fatigue syndrome (CFS). It was observed that patients with comorbidities were more prone to developing CFS. This research investigates the risk of post-COVID-19 CFS to assist healthcare professionals in reducing the risk of CFS. Methods: A retrospective cohort study is conducted to investigate the risk of post-COVID-19 CFS based on the TriNetX-sourced electronic health records. Factors including age, sex, race, vaccination, and severity of COVID-19 are analysed. Propensity score matching was applied to balance COVID-19 and non-COVID-19 cohorts. Kaplan-Meier analysis and Cox proportional hazard model were used to perform the relationship between COVID-19 and CFS risk. Results: This research involved 3227281 patients with COVID-19 and 3227281 with non-COVID-19 between 1st January 2020 and 31st December 2023. The incidence of CFS was higher in the COVID-19 group compared to the non-COVID-19 group at 1 follow-up intervals (HR 1.59, 95 % CI = 1.54–1.63). Subgroup analysis revealed increased CFS risk across different age groups (>18), sexes, races, and comorbid conditions, with notable variations. Conclusions: COVID-19 patients have a higher risk of developing CFS compared to individuals without COVID-19. The increased risk is particularly significant in adults aged 18 years and older.

Background: Empyema is a serious infection in pleural space. Finding out seasonal variations of empyema and its pathogens can help in providing preventive measures, and implicating future researches. Methods: This study is a 10-year observational study in a single center. Patients with empyema thoracis receiving thoracoscopic decortication between January 2012 and December 2021 were included in the study. Results: There were 1082 empyema patients enrolled in this study. No seasonal variation was noted (spring = 25.7 %, summer =25.5 %, autumn = 24.8 %, winter = 24.0 %). However, we observed seasonal variations in pathogens. Streptococcus species had slightly higher prevalence in winter and spring than summer and autumn (54.3 % vs. 45.7 %) without significant difference (p = 0.251). On the contrary, Staphylococcus species occurred more often in summer and autumn than winter and spring (61.5 % vs. 38.5 %) (p = 0.035). Klebsiella species were more likely found in autumn (34.9 %) (p = 0.050), and Pseudomonas species showed no peak prevalence in any season (p = 0.423). The incidence of Streptococcus species increased over the years. Conclusions: Although no seasonal variation was found in severe empyema patients requiring surgery, there were seasonal variations for the pathogens in Taiwan. The medical community should focus on Streptococcus species in winter and spring and Staphylococcus species in summer and autumn.

Abstract Background Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton’s jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI. Methods A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-β)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI. Results The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-β-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function. Conclusion This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.

With the increasing prevalence of end-stage kidney disease, the number of patients requiring hemodialysis (HD) continues to rise. While life-sustaining, HD is often associated with adverse effects such as muscle loss, physical deconditioning, fatigue, and compromised health-related quality of life (HRQoL). Recent research suggests that intradialytic exercise (IDE) and home-based exercise (HBE) may mitigate these adverse effects and improve patient outcomes. However, the existing literature mainly focuses on the outcomes of both exercises, whereas the comparison of types is often omitted. Hence, this review consolidates findings from studies investigating the effectiveness, implementation, safety, feasibility, and adherence of different types of IDE and HBE in HD patients. Overall, the current literature bolsters the significance of IDE and HBE for improving health in HD patients. IDE and HBE enhance physical function, cardiopulmonary capacity, HRQoL, and cognitive well-being. Some research proposed an indirect link between IDE and survival rates. Despite these benefits, challenges remain in implementing these exercise modalities, including patient adherence and the feasibility of routine exercise during HD sessions. Integrating these exercises into routine care allows healthcare providers to enhance outcomes for HD patients. Further research is suggested to optimize exercise protocols and explore long-term effects and cost-effectiveness.

This study tested the hypothesis that ITRI Biofilm prevents adhesion of the chest cavity. Combined extracorporeal shock wave (ECSW) + bone marrow-derived autologous endothelial progenitor cell (EPC) therapy was superior to monotherapy for improving heart function (left ventricular ejection fraction [LVEF]) in minipigs with ischemic cardiomyopathy (IC) induced by an ameroid constrictor applied to the mid-left anterior descending artery. The minipigs ( n = 30) were equally designed into group 1 (sham-operated control), group 2 (IC), group 3 (IC + EPCs/by directly implanted into the left ventricular [LV] myocardium; 3 [+]/3[–] ITRI Biofilm), group 4 (IC + ECSW; 3 [+]/[3] – ITRI Biofilm), and group 5 (IC + EPCs–ECSW; 3 [+]/[3] – ITRI Biofilm). EPC/ECSW therapy was administered by day 90, and the animals were euthanized, followed by heart harvesting by day 180. In vitro studies demonstrated that cell viability/angiogenesis/cell migratory abilities/mitochondrial concentrations were upregulated in EPCs treated with ECSW compared with those in EPCs only (all P s < 0.001). The LVEF was highest in group 1/lowest in group 2/significantly higher in group 5 than in groups 3/4 (all P s < 0.0001) by day 180, but there was no difference in groups 3/4. The adhesion score was remarkably lower in patients who received ITRI Biofilm treatment than in those who did not (all P s

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of Escherichia coli. For in vitro experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)-stem cell factor receptor (c-kit)+stem cell antigen-1 (Sca-1)−, lin−c-kit+, and lin− cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of experiments, marrow lin−c-kit+ cells from green fluorescence protein (GFP)+ mice, i.v. challenged with heat-inactivated E. coli or saline for 24 h, were subcutaneously implanted in Matrigel plugs for 5 weeks. Marrow lin−c-kit+ cells from Sca-1 knockout (KO) mice challenged with heat-inactivated E. coli for 24 h were cultured in the Matrigel medium for 8 weeks. The marrow pool of EPCs bearing the lin−c-kit+Sca-1+VEGF receptor 2 (VEGFR2)+ (LKS VEGFR2+) and LKS CD133+VEGFR2+ surface markers expanded rapidly following septic infection, which was supported by both proliferative activation and phenotypic conversion of marrow stem/progenitor cells. Increase in marrow EPCs and their reprogramming for enhancing angiogenic activity correlated with cell-marked upregulation of Sca-1 expression. Sca-1 was coupled with Ras-related C3 botulinum toxin substrate 2 (Rac2) in signaling the marrow EPC response. Septic infection caused a substantial increase in plasma levels of IFN-γ, VEGF, G-CSF, and SDF-1. The early increase in circulating EPCs was accompanied by their active homing and incorporation into pulmonary microvasculature. These results demonstrate that the marrow EPC response is a critical component of the host defense system. Sca-1 signaling plays a pivotal role in the regulation of EPC response in mice with septic infection.

Background: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats. Methods: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 105/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 106/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction. Results: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p

Abstract Non–small cell lung cancer (NSCLC) is associated with a poor survival rate, even for patients with early-stage cancer. Identifying patients with pathological N0 NSCLC who may benefit from adjuvant chemotherapy treatment after surgery is essential. We conducted a retrospective cohort study used data from the Surveillance, Epidemiology, and End Results database and included 26,380 patients with pathological N0 NSCLC after surgery between January 2018, and December 2019. Among 26,380 patients, 24,273 patients received surgery alone and the other 2107 patients received surgery plus adjuvant chemotherapy. After 1:1 propensity score matching, both groups contained 2107 patients. Adjuvant chemotherapy did not show significantly better 24-month survival in T2aN0 NSCLC patients (83.41% vs. 82.91%, p = 0.067), although it did for T2bN0 patients (86.36% vs. 81.70%, p = 0.028). Poorly-differentiated NSCLC remained a high-risk factor for pT2N0, and adjuvant chemotherapy provided better 24-month survival after matching (86.36% vs. 81.70%, p = 0.029). In conclusion, when treating pN0 NSCLC, adjuvant chemotherapy had a beneficial effect when the tumor size was larger than 4 cm. The effect when the tumor size was between 3 and 4 cm was not remarkable. Poorly-differentiated NSCLC was a high-risk factor in the pT2N0 stage.

Abstract Given the rising prevalence of patients with diabetes and increasing treatment burden for patients with vision-threatening diabetic macular edema (DME), we aimed to explore the efficacy of modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor (VEGF) therapy under the Taiwan National Insurance Bureau reimbursement policy. We obtained data on 69 eyes treated with initial 4-monthly intravitreal injections of aflibercept or ranibizumab, plus individualized treat-and-extend regimen. At 12 months, the mean (SD) change in LogMAR best corrected visual acuity from baseline was − 0.28 (0.31) in all eyes, while that in the aflibercept and ranibizumab groups were − 0.30 (0.34) and − 0.25 (0.28), respectively. Central retinal thickness decreased by 137.2 (122.4) in all eyes, 138.1 (134.2) in the aflibercept group, and 136.2 (110.9) in the ranibizumab group. Additionally, the aflibercept group had a lower mean number of injections than the ranibizumab group (8.5 vs. 8.7). The last extended dosing interval of > 12 weeks was 31.0% and 16.7% of the eyes in the aflibercept and ranibizumab groups, respectively. The modified anti-VEGF regimens effectively managed DME in terms of functional and anatomical outcomes, and efficiently reduced the healthcare burden by reducing the number of injections and extending treatment intervals within 12 months.

Iron is an essential element for human health. In humans, dysregulated iron homeostasis can result in a variety of disorders and the development of cancers. Enhanced uptake, redistribution, and retention of iron in cancer cells have been suggested as an “iron addiction” pattern in cancer cells. This increased iron in cancer cells positively correlates with rapid tumor growth and the epithelial-to-mesenchymal transition, which forms the basis for tumor metastasis. However, the source of iron and the mechanisms cancer cells adopt to actively acquire iron is not well understood. In the present study, we report, for the first time, that the peptide hormone, prolactin, exhibits a novel function in regulating iron distribution, on top of its well-known pro-lactating role. When stimulated by prolactin, breast cancer cells increase CD44, a surface receptor mediating the endocytosis of hyaluronate-bound iron, resulting in the accumulation of iron in cancer cells. In contrast, macrophages, when treated by prolactin, express more ferroportin, the only iron exporter in cells, giving rise to net iron output. Interestingly, when co-culturing macrophages with pre-stained labile iron pools and cancer cells without any iron staining, in an iron free condition, we demonstrate direct iron flow from macrophages to cancer cells. As macrophages are one of the major iron-storage cells and it is known that macrophages infiltrate tumors and facilitate their progression, our work therefore presents a novel regulatory role of prolactin to drive iron flow, which provides new information on fine-tuning immune responses in tumor microenvironment and could potentially benefit the development of novel therapeutics.

Abstract Background This study tested the hypothesis that overexpression of cellular prion protein in endothelial progenitor cells (PrPcOE-EPCs), defined as “rejuvenated EPCs,” was superior to EPCs for salvaging the critical limb ischemia (CLI) induced after 28-day chronic kidney disease (CKD) induction in rat. Methods and Results Cell viability and flow cytometric analyses of early/late apoptosis/total-intracellular ROS/cell cycle (sub-G1, G2/M phase) were significantly higher in EPCs + H2O2 than in EPCs that were significantly reversed in PrPcOE-EPCs + H2O2 (all p

Multiple forms of interference and noise that impact the receiver’s capacity to receive and interpret satellite signals, and consequently the preciseness of positioning and navigation, may be present during the processing of Global Positioning System (GPS) navigation. The non-Gaussian noise predominates in the signal owing to the fluctuating character of both natural and artificial electromagnetic interference, and the algorithm based on the minimum mean-square error (MMSE) criterion performs well when assuming Gaussian noise, but drops when assuming non-Gaussian noise. The maximum correntropy criteria (MCC) adaptive filtering technique efficiently reduces pulse noise and has adequate performance in heavy-tailed noise, which addresses the issue of filter performance caused by the presence of non-Gaussian or heavy-tailed unusual noise values in the localizing measurement noise. The adaptive kernel bandwidth (AKB) technique employed in this paper applies the calculated adaptive variables to generate the kernel function matrix, in which the adaptive factor can modify the size of the kernel width across a reasonably appropriate spectrum, substituting the fixed kernel width for the conventional MCC to enhance the performance. The conventional maximum correntropy criterion-based extended Kalman filter (MCCEKF) algorithm’s performance is significantly impacted by the value of the kernel width, and there are certain predetermined conditions in the selection based on experience. The MCCEKF with a fixed adaptive kernel bandwidth (MCCEKF-AKB) has several advantages due to its novel concept and computational simplicity, and gives a qualitative solution for the study of random structures for generalized noise. Additionally, it can effectively achieve the robust state estimation of outliers with anomalous values while guaranteeing the accuracy of the filtering.

Abstract Background MicroRNAs control gene expression by post-transcriptional inhibition. Dysregulation of the expressions of miR-199a/214 cluster has been linked to cardiovascular diseases. This study aimed at identifying potential microRNAs related to vascular senescence. Methods Seven candidate microRNAs (miR-19a, −20a, −26b, −106b, − 126, − 214, and − 374) related to cell proliferation were tested for their expressions under CoCl2-induced hypoxia in vascular smooth muscle cells (VSMCs). After identification of miR-214 as the candidate microRNA, telomere integrity impairment and cell cycle arrest were examined in VSMCs by using miR-214 mimic, AntagomiR, and negative controls. To investigate the clinical significance of miR-214 in vascular diseases, its plasma level from patients with carotid artery stenosis (CAS) was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results CoCl2 treatment for 48 h suppressed cell proliferation and angiogenesis as well as enhanced cell senescence in VSMCs. Besides, miR-214 level was elevated in both intracellular and exosome samples of VSMCs after CoCl2 treatment. Manipulating miR-214 in VSMCs demonstrated that miR-214 not only inhibited angiogenic and proliferative capacities but also promoted senescence through the suppression of quaking. Additionally, circulating miR-214 level was upregulated in CAS patients with high low-density lipoprotein cholesterol (LDL-C) value. Conclusion Our findings suggested that miR-214 plays a role in the modulation of VSMC angiogenesis, proliferation, and senescence with its plasma level being increased in CAS patients with elevated LDL-C value, implying that it may be a vascular senescence marker and a potential therapeutic target for vascular diseases.

Background: Extracellular fluid retained in the lungs lead to respiratory distress in both late preterm (LP) and term neonates. The relationship between urine parameters toward the diuresis and the duration of ventilation postnatally is unknown. To find the correlation between the diuretic phase with urine parameters in the first 4 days after birth and the duration of non-invasive ventilation (NIV). Methods: Serial measurements of urine osmolality (Uosm), urine sodium (UNa), and urine output (U/O) in neonates were collected at 5 time periods (T1:0–12 postnatal hours, T2:12–24 postnatal hours, T3:24–48 postnatal hours, T4:48–72 postnatal hours, T5:72–96 postnatal hours) were recorded. The correlations were analyzed in late preterm and term neonates. Results: Ninety-seven neonates were included. Negative correlation between Uosm and U/O were observed. LP neonates (n=26) and term neonates (n=71) had differences with Uosm at T2, UNa at T4, T5, and U/O at T2, T3. Factors of U/O < 1 ml/kg/hr at T1 (odds ratio (OR) = 20.0; 95% confidence interval (CI) 1.796-222.776; p = 0.015) or Uosm > 273 mOsm/L at T1 (OR = 9.0; 95% CI 1.031-78.574; p = 0.047) in LP neonates and UNa > 26.5 mEq/L at T5 (OR = 23.625; 95% CI 2.683-79.276; p < 0.01) in term neonates were associated with prolonged NIV use (> 120 hours). Conclusion: We speculate the significant correlation between Uosm/UNa and the diuretic phase. The LP neonates acquire earlier diuretic phase than the term neonates. The Uosm/UNa in the first few postnatal days had the correlation with the duration of NIV support. Keywords: Diuretic phase, Neonate, Non-invasive ventilation, Urine osmolality, Urine sodium

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.