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Cureus May 2024Introduction Dengue fever, caused by the dengue virus transmitted by Aedes aegypti mosquitoes, is a significant public health concern globally. Its resurgence in recent...
Introduction Dengue fever, caused by the dengue virus transmitted by Aedes aegypti mosquitoes, is a significant public health concern globally. Its resurgence in recent years, particularly in low- and middle-income countries, has led to increased morbidity and mortality rates. Atypical manifestations, involving the cardiac, liver, gut, renal, blood, bone, nervous, and respiratory systems, in dengue, can complicate both diagnosis and management. This study aimed to investigate the incidence of lung manifestations in dengue-infected individuals and their correlation with patient outcomes. Background The prevalence of dengue fever has risen dramatically over the past two decades, with Asia bearing the brunt of the burden, particularly India. The pathophysiology of lung complications in dengue remains unclear but is thought to be related to capillary leak syndrome and thrombocytopenia. Studies suggest that respiratory symptoms may be associated with severe cases and increased mortality rates. Despite limited research in India, understanding lung manifestations in dengue is crucial for improving diagnostic accuracy and patient care. Methods A retrospective study was conducted at K.S. Hegde Hospital, a tertiary care facility located in Mangalore, India, involving patients aged 18 years and above diagnosed with dengue fever between January and December 2019. Data gathered comprised patient demographics, clinical symptoms, laboratory findings, imaging results including radiographs, computed tomography (CT) scans of the chest (if accessible), ultrasound examinations of the chest and abdomen, and 2D echocardiograms, as well as patient outcomes. Diagnosis of lung manifestation was established through clinical assessment, chest X-ray interpretation, and ultrasound of the chest. Statistical analysis was conducted using SPSS Statistics (version 20), with a significance set at p<0.05. Results Out of 255 dengue cases, 10.19% (n=26) exhibited pulmonary manifestations, with pleural effusion being the most common. Older age (>50 years) and comorbidities were associated with a higher incidence of lung involvement. Respiratory symptoms, such as breathlessness, were more prevalent in patients with pulmonary complications. Laboratory parameters indicated distinct profiles in patients with lung manifestations, including elevated total count, urea, bilirubin, and liver enzymes, and reduced platelet counts. Mortality rates were higher in patients with lung involvement, older age, and comorbidities. Discussion The study findings highlight the importance of recognizing respiratory symptoms in dengue fever, particularly in older patients and those with underlying health conditions. The association between pulmonary involvement and adverse outcomes underscores the need for early detection and appropriate management strategies. Future research should focus on elucidating the pathophysiology of lung complications in dengue and developing targeted interventions to improve patient outcomes. Conclusion Lung manifestations in dengue fever represent a significant clinical challenge and are associated with increased morbidity and mortality. Early recognition of respiratory symptoms, along with prompt diagnostic evaluation and appropriate management, is essential for improving patient prognosis. Further studies are warranted to deepen our understanding of lung involvement in dengue and optimize therapeutic approaches to mitigate its impact on patient outcomes.
PubMed: 38903312
DOI: 10.7759/cureus.60655 -
Oncology Research and Treatment Jun 2024
Introduction: The development of secondary hypogammaglobulinemia (sHGG) because of tumor treatment and/or the primary underlying hematologic disorder holds... Introduction: The development of secondary hypogammaglobulinemia (sHGG) because of tumor treatment and/or the primary underlying hematologic disorder holds substantial clinical significance. B-cell-derived malignancies and anti-CD20 monoclonal antibodies (mAb) represent important risk factors for the development of sHGG. In addition, the occurrence of acute thrombocytopenia (AT) induced by anti-CD20 therapy is a known, albeit rare, phenomenon. Case Presentation: A 54-year-old patient experiencing the first relapse of classical follicular lymphoma has commenced salvage therapy following the R-DHAP protocol. After rituximab infusion, platelet count dropped from 116x10^9/L to 13x10^9/L within 24 hours. Reduced IgG levels indicated moderate HGG, thus we immediately administered intravenous immunoglobulins (IVIg). Within five days after initiation of IVIg, platelet count increased and stabilized at >50x10^9/L. Conclusions: It seems possible that anti-CD20 mAb act like or activate similar mechanisms as autoantibodies in immune thrombocytopenia (ITP). Assuming that anti-CD20 therapy-induced AT is an ITP-like condition, HGG could be considered a potential risk factor. Thus, appropriate treatment of HGG with IVIg prior to anti-CD20 mAb therapy could potentially alleviate anti-CD20 therapy-induced AT. .PubMed: 38901415
DOI: 10.1159/000539919 -
Clinical Neurology and Neurosurgery Jun 2024The objective of this study was to determine risk factors predictive of external ventricular drain (EVD)-related hemorrhage and the association of such hemorrhages with...
OBJECTIVE
The objective of this study was to determine risk factors predictive of external ventricular drain (EVD)-related hemorrhage and the association of such hemorrhages with mortality, discharge disposition, length of stay (LOS), and total cost.
METHODS
After Institutional Review Board approval, data was collected retrospectively for adult patients requiring EVD placement from 2015 to 2018 at the authors' institution. Collected data included demographic patient information, peri-procedural factors, and relevant post-procedural measures. Computerized tomography (CT) images and associated radiologic reports were independently reviewed, identifying hemorrhages accompanying EVD placement.
RESULTS
From this 487-patient sample, 85 (17.5 %) patients had hemorrhages, including asymptomatic hemorrhages identified on imaging alone. A univariable analysis of patient parameters in the overall cohort was performed to identify possible predictors of hemorrhage. Age (p = 0.002), Charlson Comorbidity Index (CCI) (p < 0.001), platelet count (p = 0.002), presence of uremia (p = 0.035), and the number of times the EVD was replaced (p < 0.001) were associated with hemorrhage in univariable models. The experience of the resident surgeon based on post-graduate year (PGY level) and the number of attempts/passes needed for EVD placement were not associated with hemorrhage risk. Significant predictor of hemorrhage confirmed in a multivariable analysis only included the number of times the EVD was replaced (OR = 2.78, adjusted p < 0.001). Outcomes between EVD-related hemorrhage versus no hemorrhage groups, including mortality, discharge disposition, LOS, and cost, were compared. EVD-related hemorrhage was found to be associated with increased mortality (OR = 3.58, adjusted p < 0.001) and decreased likelihood of discharge home (OR = 0.13, adjusted p = 0.030) in the associated multivariable regressions.
CONCLUSION
The number of times an EVD was replaced was associated with EVD-related hemorrhage outcome. EVD-related hemorrhage is associated with increased mortality and a decreased likelihood of being discharged home.
PubMed: 38901374
DOI: 10.1016/j.clineuro.2024.108386 -
Thrombosis Research Jun 2024Intracerebral hemorrhage (ICH) of undetermined etiology occurs infrequently in young and middle-aged adults. We hypothesized that slight decreases in coagulation factors...
BACKGROUND
Intracerebral hemorrhage (ICH) of undetermined etiology occurs infrequently in young and middle-aged adults. We hypothesized that slight decreases in coagulation factors and formation of less compact fibrin clots prone to faster lysis predispose to this type of ICH.
METHODS
We recruited 44 consecutive patients aged <50 years following ICH of unknown cause at least 3 months since the event. Subjects free of ICH (n = 47) matched for age, sex, BMI, and hypertension served as the control group. We assessed plasma fibrin clot permeability, turbidity and fibrinolytic capacity, along with thrombin generation, coagulation factors (F) II, FV, FVII, FVIII, FIX, FX, FXI, antithrombin, and fibrinolysis proteins.
RESULTS
ICH patients (median age 41 years, 45.5 % women) had 8.4 % lower FII (p = 0.0001) and 10.1 % lower FVII activity (p = 0.0003), 9.4 % higher antithrombin activity (p = 0.0004) and 13.5 % lower platelet count (p = 0.02). Other factors and thrombin generation did not differ between the two groups. The ICH survivors were characterized by impaired fibrin polymerization reflected by 10.1 % longer lag phase of the turbidimetry curve (p = 0.0002), decreased fiber density indicated by 11.8 % lower maximum absorbance (p = 0.004), as well as 11.1 % shorter clot lysis time (p = 0.014) and 10.0 % faster increase of maximal D-Dimer levels (p = 0.000001).
CONCLUSIONS
We demonstrated a prohemorrhagic fibrin clot phenotype, along with lower FII, FVII and higher antithrombin activity in adults below 50 years of age who suffered from ICH of unknown cause, which might indicate novel mechanisms contributing to ICH in younger individuals.
PubMed: 38901058
DOI: 10.1016/j.thromres.2024.109062 -
The New England Journal of Medicine Jun 2024Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal...
BACKGROUND
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells.
METHODS
We conducted a phase 1-2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP. CM313 was administered intravenously at a dose of 16 mg per kilogram of body weight every week for 8 weeks, followed by a 16-week follow-up period. The primary outcomes were adverse events and documentation of two or more consecutive platelet counts of at least 50×10 per liter within 8 weeks after the first dose of CM313. The status of peripheral-blood immune cells in patients and changes in the mononuclear phagocytic system in passive mouse models of ITP receiving anti-CD38 therapy were monitored.
RESULTS
Of the 22 patients included in the study, 21 (95%) had two consecutive platelet counts of at least 50×10 per liter during the treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17 to 24). The median time to the first platelet count of at least 50×10 per liter was 1 week (range, 1 to 3). The most common adverse events that occurred during the study were infusion-related reaction (in 32% of the patients) and upper respiratory tract infection (in 32%). After CD38-targeted therapy, the percentage of CD56CD16+ natural killer cells, the expression of CD32b on monocytes in peripheral blood, and the number of macrophages in the spleen of the passive mouse models of ITP all decreased.
CONCLUSIONS
In this study, anti-CD38 targeted therapy rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets, maintained long-term efficacy by clearing plasma cells, and was associated with mainly low-grade toxic effects. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and others; ClinicalTrials.gov number, NCT05694767).
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Female; Middle Aged; Animals; Mice; Antibodies, Monoclonal; Male; ADP-ribosyl Cyclase 1; Aged; Adult; Platelet Count
PubMed: 38899695
DOI: 10.1056/NEJMoa2400409 -
Cureus May 2024Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious...
Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious adverse effect of phenytoin. This case report presents the case of a patient with severe thrombocytopenia induced by phenytoin for the treatment of tonic-clonic seizures. A 63-year-old male received 300 mg/day of phenytoin for the treatment of tonic-clonic seizures. Seven days after receiving the first dose of phenytoin, he was diagnosed with severe thrombocytopenia (platelet count 44 x 10/L) without hemorrhage. Phenytoin was discontinued, and seizures were controlled with levetiracetam. Seven days after stopping phenytoin, his daily platelet count improved from 44 to 177 x 10/L. The Naranjo algorithm score of 7 was at a probable level for phenytoin-induced thrombocytopenia. Thrombocytopenia is a serious adverse drug reaction that can result in life-threatening bleeding. Phenytoin-induced thrombocytopenia commonly begins 1-90 days after administration, and the recovery time is 3-21 days. The potential mechanism of phenytoin-induced thrombocytopenia is drug-induced immune thrombocytopenia. Drugs that enhance the concentration of phenytoin epoxide may be a contributing factor in phenytoin-induced thrombocytopenia. Phenytoin-induced thrombocytopenia is a rare but serious hematological complication. It should be recognized early, particularly in patients with a high risk of hemorrhage or concurrently with medications that increase phenytoin epoxide. Regularly consecutive complete blood count tests may be essential in order to detect an early decrease in platelet count in these patients.
PubMed: 38899236
DOI: 10.7759/cureus.60669 -
Zhen Ci Yan Jiu = Acupuncture Research Jun 2024To observe the effect of acupuncture and moxibustion on arterial elasticity in patients with early carotid atherosclerosis. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To observe the effect of acupuncture and moxibustion on arterial elasticity in patients with early carotid atherosclerosis.
METHODS
A total of 62 patients with early carotid atherosclerosis were randomly divided into a blank group (12 cases, 1 cases dropped-off), a sham-acupuncture group (25 cases, 5 cases dropped-off) and an acupuncture group (25 cases, 3 cases dropped-off). Patients in the acupuncture group received acupuncture treatment, including ①acupuncture:Baihui (GV20), Yintang (GV24), Renying (ST9), Neiguan (PC6), Yanglingquan (GB34);②moxibustion:Yinqiguiyuan (Zhongwan [CV12], Xiawan [CV10], Qihai [CV6], Guanyuan [CV4]), Sihua (Geshu [BL17], Danshu [BL19]);③Intradermal needle:Xinshu (BL15), Danshu (BL19). Patients in the sham acupuncture group received placebo acupuncture, moxibustion, an intradermal needle, and the acupoints were the same as the acupuncture group. The above treatments were performed twice a week for 12 weeks. No intervention was given to the patients in the blank group. Diet and lifestyle education was given to the three groups. The ultrafast pulse wave velocity, including beginning-systolic pulse wave velocity (BS) and end-systolic pulse wave velocity (ES), was observed before treatment and 1, 2, 3 months after treatment in the three groups. The blood lipid level and platelet count (PLT) at each time point were observed. The safety of the treatments was also evaluated.
RESULTS
Compared with those before treatment, the BS and ES values of both sides in the acupuncture group decreased at 2 and 3 months after treatment (<0.05). Compared with the blank group, the bilateral ES of the acupuncture group were decreased at 2 months after treatment (<0.05), and the bilateral BS and ES were decreased at 3 months (<0.05). Compared with the sham-acupuncture group, the acupuncture group showed a decrease in left BS and left ES after 3 months of treatment (<0.05), and the overall decrease on the left side of the acupuncture group was better than that on the right side. There were no significant differences between three groups in the levels of blood lipid and PLT at each time point. No serious adverse safety events occurred in the three groups during the treatment.
CONCLUSIONS
Acupuncture and moxibustion therapy can improve arterial elasticity in patients with early carotid atherosclerosis, and it is safe and effective.
Topics: Humans; Moxibustion; Male; Female; Middle Aged; Acupuncture Therapy; Aged; Acupuncture Points; Carotid Artery Diseases; Elasticity; Adult; Carotid Arteries
PubMed: 38897805
DOI: 10.13702/j.1000-0607.20230354 -
International Immunopharmacology Jun 2024Delayed cerebral ischemia (DCI) is a common and serious complication of subarachnoid hemorrhage (SAH). Its pathogenesis is not fully understood. Here, we developed a...
BACKGROUND
Delayed cerebral ischemia (DCI) is a common and serious complication of subarachnoid hemorrhage (SAH). Its pathogenesis is not fully understood. Here, we developed a predictive model based on peripheral blood biomarkers and validated the model using several bioinformatic multi-analysis methods.
METHODS
Six datasets were obtained from the GEO database. Characteristic genes were screened using weighted correlation network analysis (WGCNA) and differentially expressed genes. Three machine learning algorithms, elastic networks-LASSO, support vector machines (SVM-RFE) and random forests (RF), were also used to construct diagnostic prediction models for key genes. To further evaluate the performance and predictive value of the diagnostic models, nomogram model were constructed, and the clinical value of the models was assessed using Decision Curve Analysis (DCA), Area Under the Check Curve (AUC), Clinical Impact Curve (CIC), and validated in the mouse single-cell RNA-seq dataset. Mendelian randomization(MR) analysis explored the causal relationship between SAH and stroke, and the intermediate influencing factors. We validated this by retrospectively analyzing the qPCR levels of the most relevant genes in SAH and SAH-DCI patients. This experiment demonstrated a statistically significant difference between SAH and SAH-DCI and normal group controls. Finally, potential small molecule compounds interacting with the selected features were screened from the Comparative Toxicogenomics Database (CTD).
RESULTS
The fGSEA results showed that activation of Toll-like receptor signaling and leukocyte transendothelial cell migration pathways were positively correlated with the DCI phenotype, whereas cytokine signaling pathways and natural killer cell-mediated cytotoxicity were negatively correlated. Consensus feature selection of DEG genes using WGCNA and three machine learning algorithms resulted in the identification of six genes (SPOCK2, TRRAP, CIB1, BCL11B, PDZD8 and LAT), which were used to predict DCI diagnosis with high accuracy. Three external datasets and the mouse single-cell dataset showed high accuracy of the diagnostic model, in addition to high performance and predictive value of the diagnostic model in DCA and CIC. MR analysis looked at stroke after SAH independent of SAH, but associated with multiple intermediate factors including Hypertensive diseases, Total triglycerides levels in medium HDL and Platelet count. qPCR confirmed that significant differences in DCI signature genes were observed between the SAH and SAH-DCI groups. Finally, valproic acid became a potential therapeutic agent for DCI based on the results of target prediction and molecular docking of the characterized genes.
CONCLUSION
This diagnostic model can identify SAH patients at high risk for DCI and may provide potential mechanisms and therapeutic targets for DCI. Valproic acid may be an important future drug for the treatment of DCI.
PubMed: 38897129
DOI: 10.1016/j.intimp.2024.112408 -
Journal of Computer Assisted Tomography Jun 2024Fluoroscopic-guided lumbar puncture (FG-LP) is a common neuroradiologic procedure. Traditionally, a minimum platelet count (MPC) of 50,000/μL for this procedure has...
PURPOSE
Fluoroscopic-guided lumbar puncture (FG-LP) is a common neuroradiologic procedure. Traditionally, a minimum platelet count (MPC) of 50,000/μL for this procedure has been required; however, we recently adopted a lower MPC threshold of 20,000/μL. The purpose of this study was to compare adverse events in patients undergoing FG-LP with MPCs above to those below the conventional 50,000/μL threshold.
MATERIALS
This was an institutional review board-approved, retrospective study on adult patients with hematologic malignancy undergoing FG-LP in the neuroradiology division between May 2021 and December 2022, after lowering the minimal required MPC to 20,000/μL. Recorded data included indication for FG-LP, preprocedure and postprocedure MPC, need for and number of platelet transfusions within 24 hours of FG-LP, presence of traumatic tap, FG-LP-related complications, and any platelet transfusion-related adverse event. Patients were classified into 2 groups based on MPC: (1) those above 50,000/μL and (2) those below 50,000/μL. Descriptive statistics were used comparing these 2 groups.
RESULTS
One hundred twenty-eight patients underwent FG-LP, with 46 having an MPC between 20,000 and 50,000/μL and 82 having an MPC above 50,000/μL. No postprocedural complications were encountered in either group. Traumatic taps occurred in 10/46 (22%) with MPC below 50,000/μL versus 10/82 (12%) in those with MPC above 50,000/μL. Forty of 46 patients (87%) were transfused with platelets within 24 hours prior to FG-LP. One patient developed a transfusion-related reaction.
CONCLUSION
Lowering the MPC threshold from 50,000/μL to 20,000/μL for FG-LP did not result in a higher incidence of spinal hematoma.
PubMed: 38896759
DOI: 10.1097/RCT.0000000000001633 -
Dermatology and Therapy Jun 2024Early prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12...
INTRODUCTION
Early prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12 efficacy based on week 4 responses in patients receiving abrocitinib 100 mg/day and assessed the effect of an abrocitinib dose increase on platelet counts.
METHODS
Analysis included the phase 3 trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), and TEEN (NCT03796676). For platelet counts and simulations, a phase 2 psoriasis trial (NCT02201524) and phase 2b (NCT02780167) and phase 3 (MONO-1, MONO-2, and REGIMEN (NCT03627767)) abrocitinib trials were pooled. A training-and-validation framework assessed potential predictors of response at week 4: score and score change from baseline in the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS), and percentage change from baseline in EASI. The dependent variables at week 12 were ≥ 75% improvement in EASI (EASI-75) and IGA score of 0 (clear) or 1 (almost clear) and ≥ 2-point improvement from baseline. The probability of each variable to predict week 12 EASI-75 and IGA responses was calculated.
RESULTS
In the training cohort (n = 453), 72% of the ≥ 50% improvement in EASI (EASI-50) at week 4 responders and 16% of the nonresponders with abrocitinib 100 mg achieved EASI-75 at week 12; 48% and 6% of the week 4 EASI-50 responders and nonresponders, respectively, achieved week 12 IGA response. Similar results occurred with week 4 IGA = 2, ≥ 4-point improvement from baseline in PP-NRS, or EASI = 8 responders/nonresponders. Platelet counts after an abrocitinib dose increase from 100 to 200 mg were similar to those seen with continuous dosing with abrocitinib 100 mg or 200 mg.
CONCLUSION
Achieving week 4 clinical responses with abrocitinib 100 mg may be useful in predicting week 12 responses. Week 4 nonresponders may benefit from a dose increase to abrocitinib 200 mg, and those that receive this dose increase are likely to achieve treatment success at week 12, with no significant impact on platelet count recovery. Video abstract available for this article.
CLINICAL TRIAL REGISTRATION
NCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767.
PubMed: 38896380
DOI: 10.1007/s13555-024-01183-3