Thrombocytopenia Research Articles

Comparative Analysis of Traditional and Pharmacometric-Based Pharmacoeconomic Modeling in the Cost-Utility Evaluation of Sunitinib Therapy.

Cost-utility analyses (CUAs) increasingly use models to predict long-term outcomes and translate trial data to real-world settings. Model structure uncertainty affects these predictions. This study compares pharmacometric against traditional pharmacoeconomic model evaluations for CUAs of sunitinib in gastrointestinal stromal tumors (GIST). A two-arm trial comparing sunitinib 37.5 mg daily with no treatment was simulated using a pharmacometric-based pharmacoeconomic model framework. Overall, four existing models [time-to-event (TTE) and Markov models] were re-estimated to the survival data and linked to logistic regression models describing the toxicity data [neutropenia, thrombocytopenia, hypertension, fatigue, and hand-foot syndrome (HFS)] to create traditional pharmacoeconomic model frameworks. All five frameworks were used to simulate clinical outcomes and sunitinib treatment costs, including a therapeutic drug monitoring (TDM) scenario. The pharmacometric model framework predicted that sunitinib treatment costs an additional 142,756 euros per quality adjusted life year (QALY) compared with no treatment, with deviations - 21.2% (discrete Markov), - 15.1% (continuous Markov), + 7.2% (TTE Weibull), and + 39.6% (TTE exponential) from the traditional model frameworks. The pharmacometric framework captured the change in toxicity over treatment cycles (e.g., increased HFS incidence until cycle 4 with a decrease thereafter), a pattern not observed in the pharmacoeconomic frameworks (e.g., stable HFS incidence over all treatment cycles). Furthermore, the pharmacoeconomic frameworks excessively forecasted the percentage of patients encountering subtherapeutic concentrations of sunitinib over the course of time (pharmacoeconomic: 24.6% at cycle 2 to 98.7% at cycle 16, versus pharmacometric: 13.7% at cycle 2 to 34.1% at cycle 16). Model structure significantly influences CUA predictions. The pharmacometric-based model framework more closely represented real-world toxicity trends and drug exposure changes. The relevance of these findings depends on the specific question a CUA seeks to address.

Peripheral blood cell count composite score as a prognostic factor in patients with colorectal cancer

Objective: To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system. Methods: This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis. Results: The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×109/L, 1.41×109/L, and 355×109/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS (P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival (P<0.05), but not progression-free survival (P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%-75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion: This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Molecular mechanism and structure-guided humanization of a broadly neutralizing antibody against SFTSV.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a high mortality rate of up to 30%. The envelope glycoproteins of SFTSV, glycoprotein N (Gn) and glycoprotein C (Gc), facilitate the recognition of host receptors and the process of membrane fusion, allowing the virus to enter host cells. We previously reported a monoclonal antibody, mAb 40C10, capable of neutralizing different genotypes of SFTSV and SFTSV-related viruses. However, the specific neutralization mechanism is poorly understood. In this study, we elucidated the high-resolution structure of the SFTSV Gn head domain in complex with mAb 40C10, confirming that the binding epitope in the domain I region of SFTSV Gn, and it represented that a novel binding epitope of SFTSV Gn was identified. Through in-depth structural and sequence analyses, we found that the binding sites of mAb 40C10 are relatively conserved among different genotypes of SFTSV and SFTSV-related Heartland virus and Guertu virus, elucidating the molecular mechanism underlying the broad-spectrum neutralizing activity of mAb 40C10. Furthermore, we humanized of mAb 40C10, which is originally of murine origin, to reduce its immunogenicity. The resulting nine humanized antibodies maintained potent affinity and neutralizing activity. One of the humanized antibodies exhibited neutralizing activity at picomolar IC50 values and demonstrated effective therapeutic and protective effects in a mouse infection model. These findings provide a novel target for the future development of SFTSV vaccines or drugs and establish a foundation for the research and development of antibody therapeutics for clinical applications.

Contusion expansion, low platelet count andbifrontal contusions are associated with worse patient outcome following traumatic brain injury-a retrospective single-center study.

Cortical contusions are common in moderate-severe traumatic brain injury (TBI). Cortical contusions often expand, potentially causing neuro-worsening several hours to days post-trauma. While contusion expansion (CE) may affect outcome, potential clinical and radiological markers that can predict CE have been insufficiently explored. In the present single-center retrospective observational cohort study, we evaluated clinical outcome by the Glasgow Outcome Scale extended (GOSE) scale and evaluated risk factor for CE. Adult TBI patients > 18years of age, and of all injury severities, were included. Main variables of interest were low platelet count, defined as < 150 × 109/L, presence of bifrontal contusions and CE, defined as absolute contusion volume increase in cm3. Factors associated with CE and clinical outcome according to GOSE were analyzed. Between 2012-2022, 272 patients were included. Contusion size on admission correlated positively with CE, as did the Marshall and Rotterdam radiological classification scores. Bifrontal contusions were significantly larger at admission, experienced larger CE, and had a worse outcome than contusions in other locations. Patients with a platelet count < 150 × 109/L experienced a greater volume CE and had a worse outcome when compared to patients with a normal platelet count. In a multivariate analysis, CE remained significantly associated with a poor outcome six months post- injury. Contusion volume at admission, Marshall CT classification and Rotterdam CT score, positively correlated to CE. Bifrontal contusions and a platelet count < 150 × 109/L were associated with CE, and a poor clinical outcome. Large CE volumes were associated with a worse clinical outcome, and CE was per se associated with outcome in a multivariate analysis. Management of these risk factors for CE in the acute post-injury setting may be needed to attenuate contusion expansion and to improve clinical outcome in TBI patients suffering from cortical contusion injuries.

Coronary endoluminal imaging guided percutaneous drug-coated balloons intervention for patients with thrombocytopenia and acute coronary syndrome: a case report

Coronary endoluminal imaging guided percutaneous drug-coated balloons intervention for patients with thrombocytopenia and acute coronary syndrome: a case report

Cross-sectional screening for inflammation in tinnitus with near-normal hearing

Tinnitus is the perception of sound without an external stimulus. Recently, inflammation has been implicated in the pathophysiology of tinnitus. In tinnitus animal models, cytokine levels are increased throughout the whole auditory pathway, and microglia and astrocytes are activated. However, only a few human studies on inflammation in tinnitus were conducted, which generally did not account for confounders such as hearing loss, anxiety and depression. The current study therefore aimed to evaluate the association between inflammation and tinnitus specifically in participants with (near-)normal hearing and without signs of anxiety or depression.In this cross-sectional study, fifty tinnitus participants and fifty healthy controls completed a tinnitus questionnaire and underwent audiometric testing. Complete blood count measures were determined in blood plasma, as well as cytokine concentrations by using the enzyme-linked immunosorbent assay (ELISA) technique.Platelet count and cytokine concentrations of IL-10 and IFN-γ were lower in participants with tinnitus compared to controls, and male sex, lower MCV, lower platelet count, and lower IL-10 and IFN-γ concentrations were significant predictors of tinnitus presence.The current study shows that inflammatory parameters are altered in tinnitus patients after exclusion of important confounders such as hearing loss, anxiety, depression, and inflammatory diseases.

Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer

Introduction Ado-trastuzumab emtansine (T-DM1) is employed in the treatment of patients with HER2-positive breast cancer. The most common side effects are fatigue, diarrhoea, anaemia, transaminase elevation and drug-induced thrombocytopenia. This report describes a patient with metastatic breast cancer who developed drug-induced lupus due to T-DM1. Case Report A 54-year-old woman was diagnosed with breast cancer in March 2018. She underwent modified radical mastectomy and axillary lymph node dissection (pT2N1aM0). Following supraclavicular lymph node metastasis in May 2018, she received 8 cycles of docetaxel, trastuzumab, and pertuzumab. In December 2020, the patient presented with axillary and intra-abdominal lymph node metastases, along with bone metastases observed on PET/CT scan. Treatment with T-DM1 and zoledronic acid was initiated. After 18 months on T-DM1, she developed drug-induced lupus. Her symptoms resolved with hydroxychloroquine treatment and discontinuation of T-DM1. Discussion Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.

Prognostic Characteristics of Metabolic Dysfunction-Associated Steatotic Liver in Patients with Obesity Who Undergo One Anastomosis Gastric Bypass Surgery: A Secondary Analysis of Randomized Controlled Trial Data.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and insulin resistance (IR). Identifying characteristics that predict a higher risk of fibrosis using noninvasive methods is particularly important. We performed a secondary analysis of data from an RCT of 48 patients after one anastomosis gastric bypass (OAGB) surgery, supplemented with specifically formulated probiotics and micronutrients or control treatment for 12 weeks. Patients were categorized using alanine aminotransferase (ALAT; >35 U/L for women, >50 U/L for men), higher NAFLD fibrosis score (NFS) > -1.455), and IR (HOMA-IR > 2.0). This trial was registered at Clinicaltrials.gov (ID: NCT03585413). Abnormal ALAT was associated with high triglycerides, blood pressure (BP), glucose, and fatty liver index (FLI). NFS > -1.455 was linked to higher age, body mass, waist circumference, and FLI, and lower albumin and platelet count. HOMA-IR > 2.0 was associated with higher BP and triglycerides, lower HDL-cholesterol, higher serum transaminases, and higher probabilities of steatosis and fibrosis. Twelve weeks postoperatively, patients with NFS > -1.455 showed greater reductions in body mass, systolic BP, serum insulin, and HbA1c, whereas those with NFS ≤ -1.455 showed improvements in FLI and lipid metabolism but had high glucose concentrations. Patients with HOMA-IR ≤ 2.0 also had high glucose concentrations. The evaluation of common biomarker scores for fibrosis and IR may help clinicians to recognize severe NAFLD and improve the outcomes of OAGB surgery.

Treatment opportunities for refractory immune thrombocytopenia

Background. Primary immune thrombocytopenia (ITP) is an orphan disease characterized by decreased platelet count in the peripheral blood which in some cases can cause bleeding of varying severity. Currently, the use of thrombopoietin receptor agonists (TPO-RAs) is recommended as the second line therapy for ITP as it allows to achieve high platelet response (PR), including complete, in 73 % of cases of chronic ITP and in 87 % of cases of newly diagnosed disease. The mechanism of action differs for different TPO-RAs. Given this fact, in cases of resistance or intolerance to therapy with one TPO-RA, attempts are made to switch to another. The effectiveness of this approach for overcoming ITP resistance varies from 50 to 93 % according to various publications. Aim. To assess the ability to achieve and maintain PR by switching from one TPO-RA to another in cases of resistance to the previous TPO-RA used in the second or subsequent lines of therapy. Materials and methods. The analysis included 59 patients who were resistant (in 2 cases intolerance was also noted) to TPO-RA therapy (received after standard therapy) who were prescribed TPO-RA treatment with a different mechanism of action: switch from romiplostim to eltrombopag (25 patients) or vice versa (34 patients). Both groups were comparable in terms of demographic characteristics and median platelet level at the time of TPO-RA switching. Results. PR was obtained in 76 % of cases, including complete response in 54 %, as a result of switching from one TPO-RA to another in 59 patients. Among 34 patients switched from eltrombopag to romiplostim, PR was achieved in 31 (91 %) patients, including complete response in 22 (65 %). Romiplostim was switched to eltrombopag in 25 patients, PR was achieved in 14 (56 %) with complete response in 10 (40 %). Conclusion. The study showed that PR can be achieved and maintained through switching from one TPO-RA to an alternative.

The role of arginase estimation to predict hypertensive disorder of pregnancy at an earlier stage.

To determine the significance of serum arginase estimation as a predictor of pregnancy-induced hypertension and preeclampsia at an early stage. The observational, cross-sectional study was conducted from October 15, 2021, to October 15, 2022, at the Department of Chemical Pathology, in collaboration with the Department of Obstetrics and Gynaecology, Pakistan Railway Hospital, Islamic International Medical College Trust, Rawalpindi, Pakistan, and comprised pregnant women with 20-25 weeks of gestation who were divided into three groups. Those having no complications were placed in control group A, those with pregnancy-induced hypertension in group B, and those with preeclampsia in group C. Serum arginase, uric acid, alanine transaminase, platelet count and spot urinary protein levels were measured for each subject. Data was analysed using SPSS 26. Of the 90 women, 30(33.3%) were in group A with mean age 27.27±2.90 years, 30(33.3%) were in group B with mean age 30.17±2.48 years, and 30(33.3%) were in group C with mean age 29.33±3.11 years. There were significant intergroup differences in the mean levels of serum arginase, serum uric acid, alanine transaminase, platelet count and spot urinary protein (p<0.05). A moderate to marked increase in serum arginase levels in pregnancy-induced hypertension and preeclampsia cases, combined with abnormal serum uric acid and alanine transaminase levels along with low platelet count suggested that serum arginase estimation could be used to predict hypertensive disorders of pregnancy at an early stage.

Storage properties of platelet concentrates from umbilical cord blood prepared using three different methods.

Thrombocytopenia, common in preterm newborns, may increase bleeding risk and is often treated with transfusions. Recent studies reveal that transfusing platelets at a high threshold worsens outcomes, possibly due to a "developmental mismatch" between adult-derived platelets and neonatal hemostatic system. Cord blood-derived platelet concentrates (CBPCs) could be an alternative for newborns. Our study aims to produce and evaluate the quality parameters of CBPCs during storage. Cord blood was collected from placentas after near-term and full-term pregnancies. Several production methods were attempted to obtain CBPCs, varying centrifugation settings, filtration, and dilution procedures. Adult-derived platelet concentrates (PCs) processed with the same methods, and standard PCs from five buffy-coats were used as controls. Storage tests were performed on days 2, 4-5, 7 from the collection. CBPCs parameters were compared with adult-derived PCs, and no significant differences were found for mean platelet volume (MPV), swirling, morphology, glucose, lactate, pCO2, and pO2. pH and bicarbonate were lower in CBPCs. Some significant differences between methods in CD62P expression and JC-1 ratio were observed. Compared with standard PCs, CBPCs showed lower platelet concentration, pH, and JC-1. Additionally, both in CBPCs as well as in control PCs, the apoptosis marker phosphatidylserine was elevated. CBPCs were of comparable quality to control PCs during storage. However, apoptosis markers in both groups were elevated, suggesting processing and storage of low volumes of PCs require further optimization. Also, filtration of low volumes leads to significant platelet loss, an issue that requires remedy.

Predicting Regression of Barrett's Esophagus-Can All the King's Men Put It Together Again?

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett's esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age (p < 0.007); lower platelet levels (p < 0.02); rectal p87 elevation in SR (p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) (p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR.

Construction and validation of a dynamic nomogram using Lasso-logistic regression for predicting the severity of severe fever with thrombocytopenia syndrome patients at admission

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression.MethodsAll eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model’s performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance.Results299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017–1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003–1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175–2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005–1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035–26.858; P < 0.001) and hemorrhage symptoms (OR, 3.414; 95% CI, 1.096–10.974; P = 0.035). The AUC-ROC, C-index, calibration plots, and DCA demonstrated the robust performance of the nomogram in predicting severity at admission, and Kaplan-Meier survival analysis indicated its utility in predicting 28-day mortality among SFTS patients. The dynamic nomogram is accessible at https://sfts.shinyapps.io/SFTS_severity_nomogram/.ConclusionThis study provided a practical and readily applicable tool for the early identification of high-risk SFTS patients, enabling the timely initiation of intensified treatments and protocol adjustments to mitigate disease progression.

To study the efficacy of romiplostim in chemotherapy-induced thrombocytopenia in head and neck cancer patients

Objectives Scheduled delivery of adequate dose of chemotherapy is important to replicate the results expected from original trials. In head and neck malignancies, undue delay of chemotherapy is likely to be associated with poor control or progression. Chemotherapy-induced thrombocytopenia (CIT) is one of the reasons to delay chemotherapy. Thrombopoietin agonists (TPO-A) have been found to increase platelet counts by increasing production and mobilization of platelets. Romiplostim is a TPO agonist, studied widely and found to have good impact on prevention and treatment of CIT. The purpose of this study was to analyze the use and effect of romiplostim in CIT in locally advanced head and neck cancer patients. Material and Methods It is a retrospective study regarding practices of romiplostim use in controlling CIT, among patients of locally advanced head and neck carcinoma undergoing induction chemotherapy at a tertiary care cancer center. Data regarding delays in chemotherapy, response assessment, and modification of chemotherapy doses were also noted. Results Out of a total of 110 patients of head and neck malignancy enrolled during the study period, 18 patients received romiplostim support at least once in chemotherapy cycles and were analyzed. All patients were locally advanced and planned for induction chemotherapy. Median platelet counts before starting romiplostim was 76,000 per cumm. A median delay of ten days was noted among these cases where romiplostim was introduced after the first cycle of chemotherapy. Patient receiving romiplostim after the second cycle (n = 6) showed a median delay of 11.5 days (6–18 days) in the initiation of subsequent chemotherapy. None of them was shifted out of chemotherapy plan due to low platelet count. No dose reduction was noted in any of the cases. Conclusion This study provides a good insight about feasibility of using romiplostim in this subset of patients without delay, dose reduction, or discontinuation of chemotherapy.

Taurolithocholic acid protects against viral haemorrhagic fever via inhibition of ferroptosis.

Bile acids are microbial metabolites that can impact infection of enteric and hepatitis viruses, but their functions during systemic viral infection remain unclear. Here we show that elevated levels of the secondary bile acid taurolithocholic acid (TLCA) are associated with reduced fatality rates and suppressed viraemia in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne haemorrhagic fever virus. TLCA inhibits viral replication and mitigates host inflammation during SFTSV infection in vitro, and indirectly suppresses SFTSV-mediated induction of ferroptosis by upregulating fatty acid desaturase 2 via the TGR5-PI3K/AKT-SREBP2 axis. High iron and ferritin serum levels during early infection were correlated with decreased TLCA levels and fatal outcomes in SFTSV-infected patients, indicating potential biomarkers. Furthermore, treatment with either ferroptosis inhibitors or TLCA protected mice from lethal SFTSV infection. Our findings highlight the therapeutic potential of bile acids to treat haemorrhagic fever viral infection.

Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis.

The aim of this study was to investigate iron status and iron deficiency in incident continuous ambulatory peritoneal dialysis (CAPD) patients and identify influencing factors. Patients with end-stage renal disease were enrolled. Clinical data of iron metabolism and biochemical and dialysis parameters during the first peritoneal dialysis evaluation were collected. Serum ferritin (SF) and transferrin saturation (TSAT) levels were evaluated, and independent influencing factors were identified by correlation and regression analyses. Of 1,128 adult CAPD patients, 41.2% had iron deficiency (ID), 15.7% had absolute iron deficiency, and 8.2% had functional iron deficiency. The average SF level was (276.8 ± 277.9) μg/L, and iron saturation was (29.8 ± 12.7)%. Additionally, 50.2 and 69.3% of patients reached targets in SF level and iron saturation recommended by the Chinese Society of Nephrology. SF level and TSAT were not correlated with estimated glomerular filtration rate, whereas negatively correlated with platelet count and inflammatory factors. Low platelet count, presence of diabetes mellitus and high interleukin 6 levels were independent factors of lower TSAT. ID is common in patients with CAPD. Women and those with thrombocytopenia, diabetes, and inflammation are at higher risk for iron storage or reduced iron utilization. In the initial CAPD stage, a reasonable iron supplement strategy may be established for CAPD patients with high-risk factors.

Leucocytosis during induction therapy with all-trans-retinoic acid and arsenic trioxide in acute promyelocytic leukaemia predicts differentiation syndrome and treatment-related complications.

All-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) represent the standard of care for low-intermediate risk acute promyelocytic leukaemia (APL). Leucocytosis during induction with ATRA-ATO represents a common complication with an incidence of up to 60%. To identify predictive factors for this complication, we studied a cohort of 65 low-intermediate risk APL patients treated with ATRA-ATO in three highly specialized Italian centres. Overall, 39/65 (60%) patients developed leucocytosis, with a peak in leucocyte count being most frequent in the second week from diagnosis. All cases were successfully managed with hydroxyurea. Predictive factors for leucocytosis in univariate analysis were lower platelet counts (odds ratio [OR] 0.98, 0.97-1.00, p = 0.018), lower fibrinogen levels (OR 0.36, 0.17-0.66, p = 0.003), higher bone marrow blast infiltration (OR 1.03, 1.01-1.07, p = 0.021) and CD117 expression by flow (OR 1.04, 1.01-1.08, p = 0.012). Multivariate analysis confirmed lower levels of fibrinogen at diagnosis as the strongest predictive factor for the development of leucocytosis (OR 0.36, 0.15-0.72, p = 0.009). Differentiation syndrome (DS) occurred only in patients developing leucocytosis showing a strict correlation with rising leucocytes counts (16/39 vs. 0/26, p < 0.001). In addition, other treatment-related complications including QTc prolongation, cardiac events, liver, and haematological toxicities were significantly more frequent in patients experiencing leucocytosis (22/39 vs. 3/26, p < 0.001). In conclusion, APL patients undergoing ATRA-ATO therapy with lower fibrinogen levels and platelet counts at diagnosis and with a massive bone marrow blast infiltrate should be carefully monitored for the development of leucocytosis during induction. DS and other treatment-related complications seem to occur almost exclusively in patients developing leucocytosis, who should necessarily receive DS prophylaxis and more intensive monitoring and supportive therapy to prevent treatment complications.

Identification of severe fever with thrombocytopenia syndrome virus isolates in the northwest of Hubei Province, China

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease that is increasingly affecting human being worldwide. The clinical manifestations and mortality rates of SFTS can vary depending on the geographic region and the specific genotype of the SFTS virus (SFTSV). From July 2022 to August 2023, we collected serum samples from 83 patients with suspected SFTSV infection in the northwest of Hubei Province, China. From which, 13 patients tested positive for SFTSV. Phylogenetic analysis of the SFTSV L, M, and S gene segments was performed using the maximum likelihood method to determine the genetic diversity of the isolates. At least 2 SFTSV genotypes (A and F) were identified in the northwest of Hubei Province. The clinical manifestations and laboratory findings on the first day of admission were investigated. Results showed that bleeding and disturbance of consciousness, and significant elevated AST and APTT, are valuable for assessing the prognosis for SFTS patients. This study disclosed the genomic sequences and genotypes of SFTSV spreading in the northwest of Hubei Province for the first time, providing information of genetically etiology for SFTS in the local district. Furthermore, certain symptoms and/or laboratory findings may indicate adverse clinical outcomes, highlighting the importance of identifying the symptoms and monitoring specific laboratory markers. Future research is needed to investigate the threshold values of these markers and to closely observe the indicative symptoms in order to early identify and timely management of critically ill patients within clinical settings.

Bunyavirus SFTSV nucleoprotein exploits TUFM-mediated mitophagy to impair antiviral innate immunity

ABSTRACT Severe fever with thrombocytopenia syndrome is an emerging viral hemorrhagic fever caused by a tick-borne bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), with a high case fatality. We previously found that SFTSV nucleoprotein (NP) induces macroautophagy/autophagy to facilitate virus replication. However, the role of NP in antagonizing host innate immunity remains unclear. Mitophagy, a selected form of autophagy, eliminates damaged mitochondria to maintain mitochondrial homeostasis. Here, we demonstrate that SFTSV NP triggers mitophagy to degrade MAVS (mitochondrial antiviral signaling protein), thereby blocking MAVS-mediated antiviral signaling to escape the host immune response. Mechanistically, SFTSV NP translocates to mitochondria by interacting with TUFM (Tu translation elongation factor, mitochondrial), and mediates mitochondrial sequestration into phagophores through interacting with LC3, thus inducing mitophagy. Notably, the N-terminal LC3-interacting region (LIR) motif of NP is essential for mitophagy induction. Collectively, our results demonstrated that SFTSV NP serves as a novel virulence factor, inducing TUFM-mediated mitophagy to degrade MAVS and evade the host immune response. Abbreviation: 3-MA: 3-methyladenine; ACTB: actin beta; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4ʹ,6-diamidino-2-phenylindole, dihydrochloride; DMSO: dimethyl sulfoxide; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GFP: green fluorescent protein; HTNV: Hantan virus; IAV: influenza A virus; IFN: interferon; LAMP1: lysosomal associated membraneprotein 1; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule associatedprotein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; Mdivi-1: mitochondrial division inhibitor 1; MOI: multiplicity of infection; MT-CO2/COXII: mitochondrially encoded cytochrome C oxidase II; NP: nucleoprotein; NSs: nonstructural proteins; poly(I:C): polyinosinic:polycytidylic acid; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SFTSV: severe fever withthrombocytopenia syndrome virus; TCID50: 50% tissue culture infectiousdose; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20:translocase of outer mitochondrial membrane 20; TUFM: Tu translation elongationfactor, mitochondrial.

Establishment and validation of a clinical risk scoring model to predict fatal risk in SFTS hospitalized patients

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases.MethodsFrom January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance.ResultsThe multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452–4.360), elevated serum PT (p < 0.001, OR = 1.383, 95% CI 1.143–1.673), high viral load (p < 0. 001, OR = 1.496, 95% CI 1.290–1.735) and high level of serum urea (> 8.0 μmol/L) (p < 0.001, OR = 4.433, 95% CI 1.888–10.409). The AUC of the nomogram based on these four factors was 0.813 (95% CI, 0.758–0.868). The bootstrap resampling internal validation model performed well, and decision curve analysis indicated a high net benefit.ConclusionsThe nomogram based on age, elevated PT, high serum urea level, and high viral load can be used to help early identification of SFTS patients at risk of fatality.