Home Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
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Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study

  • Huiping Xu , Beibei Zhang and Linjun Xie EMAIL logo
Published/Copyright: March 23, 2024

Abstract

Background

Since the outbreak of COVID-19 in December 2019, countries around the world, including China, have been administering COVID-19 vaccines in response to the pandemic. Our center has observed that treating patients with primary immune thrombocytopenia (ITP) has become more challenging in this context.

Methods

This study compared the treatment response of 25 de novo ITP patients who had received a COVID-19 vaccination (Group 1) with an equal number of de novo ITP patients randomly selected from the 2 years prior to the COVID-19 pandemic (Group 2) by using the Mann–Whitney U test and Fisher’s exact.

Results

Patients in both groups had predominantly female gender with similar age and baseline platelet counts. However, on Day 3, the median platelets were 22 and 49 × 109/L, and on Day 7, they were 74 and 159 × 109/L, respectively (P < 0.05). Compared to Group 2, Group 1 showed a suboptimal short-term response to glucocorticoid monotherapy, with a higher proportion of patients requiring combination therapy with other drugs including intravenous immunoglobulin, thrombopoietin receptor agonists, and rituximab. After subgroup analysis, a significant difference was observed in the proportion of patients requiring second-line therapy between the two groups.

Conclusions

Our study suggests that COVID-19 vaccination may lead to a lower response rate to first-line treatment in de novo ITP patients. Nevertheless, it is crucial to acknowledge the inherent limitations in this conclusion. Further studies are needed to confirm these findings and investigate the underlying mechanisms.

1 Introduction

In December 2019, a new type of coronavirus disease (COVID-19) caused by a novel coronavirus emerged in Wuhan, China, and has since become a global pandemic, infecting millions and causing numerous deaths worldwide. In response, various countries, including China, have launched mass vaccination campaigns against COVID-19. Against this backdrop, our center has noticed that the treatment of patients with primary immune thrombocytopenia (ITP) appears to be more challenging.

ITP is a bleeding disorder caused by accelerated platelet destruction and impaired megakaryocyte function. Glucocorticoids with or without intravenous immunoglobulin (IVIG) are first-line therapy options for ITP, but additional therapy may be required due to intolerance or relapse [1,2]. Although thrombocytopenia following COVID-19 vaccination has been reported, it is important to note that such cases are extremely rare and represent only a small proportion of the total number of people vaccinated globally [35]. Thrombosis and/or thrombocytopenia, which can occur after any COVID-19 vaccine, is associated with the activation of macrophages by the spike protein and triggers inflammation [6]. There is also evidence to suggest that the administration of COVID-19 vaccines may potentially increase the likelihood of developing ITP or exacerbate existing symptoms in individuals with pre-existing ITP [79].

The objective of our retrospective study is to compare the treatment response of patients with de novo ITP who have received the inactivated COVID-19 vaccine with a historical cohort of such patients before the COVID-19 pandemic. Although there are limitations to our retrospective study and the possibility of selection bias, our findings could have significant implications for the treatment of ITP patients who are vaccinated against COVID-19.

2 Methods

2.1 Post-COVID-19-vaccination cohort (Group 1)

We conducted a retrospective single-center analysis of all patients admitted with ITP (ICD-10 D69.3) to The First Hospital of Putian City Hematology Department from December 2020 to March 2023. Baseline clinical characteristics, treatment, and outcome were analyzed by reviewing electronic medical records. A total of 25 patients who had received the COVID-19 vaccine before admission and met the inclusion and exclusion criteria were included in Group 1.

2.2 Historical cohort (Group 2)

For the pre-pandemic comparison (Group 2), a cohort of 25 patients diagnosed with ITP and meeting the inclusion criteria was randomly selected from the medical records department spanning from January 2018 to December 2019 at the same hospital. Patients were assigned a unique identification number and selected using a computer-generated random number sequence. To ensure comparability with Group 1, patients in Group 2 did not receive the COVID-19 vaccine, which was not yet available during the study period.

2.3 Inclusion and exclusion criteria

The eligibility criteria for enrollment in both Group 1 and Group 2 entail a diagnosis of de novo ITP (diagnosed with ITP within the past 3 months), adult age (18 years or above), a platelet count less than 30 × 109/L at admission, and complete follow-up data for a minimum of 14 days. Moreover, Group 1 patients must also satisfy the supplementary criterion of having received COVID-19 vaccination before the onset of ITP.

Patients under 18 years old, those previously treated for ITP, with other autoimmune, infectious or serious medical conditions, abnormal liver/kidney function, and pregnant/lactating women are excluded from the study to ensure study results are not confounded by pre-existing conditions or treatments.

2.4 Diagnostic criteria and treatment response evaluation of ITP

The diagnosis of ITP was based on the Chinese ITP Diagnosis and Treatment Guidelines [2]. Responses recorded using standard international consensus definitions (response, ≥30 × 109/L and at least double baseline without bleeding; complete response, ≥100 × 109/L without bleeding; failure: loss of response and/or need for additional ITP-therapy). Glucocorticoids with or without IVIG defined as first-line therapy.

While our hospital has a wealth of experience in the treatment of ITP patients and consistently adheres to both local and international guidelines [1,2], this information is provided for context and is not directly relevant to the study design or findings.

2.5 Statistical analyses

The descriptive statistics used in the study were median and interquartile range (IQR), mean and standard deviation, or counts with percentages.

Since the sample size was small (less than 50), the normality of the data was determined using Shapiro–Wilk test, and P value >0.05 was considered as normally distributed. If the data of all groups are normally distributed and have equal variances, the appropriate test to compare the difference between the two groups would be the independent samples t-test. If the variances are not equal, the Welch’s t-test should be used instead. If the data of at least one group is not normally distributed, non-parametric tests such as the Mann–Whitney U-test or Wilcoxon rank-sum test can be used to compare the difference between the two groups. For categorical variables, Fisher’s exact test was used.

  1. Ethical considerations: To maintain patient privacy and confidentiality, all patient information was de-identified and kept secure throughout the study. Only authorized personnel had access to the data, and all electronic medical records were stored on a secure server that was password-protected. Moreover, patient data were analyzed in aggregate form to ensure that individual patients could not be identified.

3 Results

All patients in this study had no important organ bleeding except skin or mucosal bleeding, such as gastrointestinal bleeding, intracranial bleeding, etc., so we focused on evaluating the platelet response during treatment. Demographics are presented in Table 1.

Table 1

Demographics and presenting features of patients in Group 1 and Group 2

Characteristics Group 1 Group 2
No. (%) Range [IQR] No. (%) Range [IQR]
Female 16 (64) 17 (68)
Age in median, years 56 26–81 [45.5–72.0] 53 20–83 [41.0–67.0]
Platelets (×10 9 /L)
Day 1 5 0–27 [2.0–13.0] 9 1–23 [3.5–12.0]
Day 3 22 1–98 [3.5–48.5] 49 1–138 [13.0–95.5]
Day 7 74 2–304 [25.0–151.0] 159 1–520 [91.5–241.5]
Day 14 184 2–515 [40.5–337.0] 266 8–572 [129.0–353.0]
Treatment
1 8 (32) 15 (60)
2 8 (32) 7 (28)
3 5 (20) 2 (8)
4 4 (16) 1 (4)

Treatment 1: glucocorticoids alone; Treatment 2: glucocorticoids in combination with IVIG; Treatment 3: sequential treatment with glucocorticoids, IVIG, and thrombopoietin receptor agonists (TPO-RA); Treatment 4: sequential treatment with glucocorticoids, IVIG, TPO-RA, and rituximab.

We can observe that both groups of patients are predominantly female with similar proportions, with median ages of 56 and 53 years, and platelets at Day 1 were 5 and 9 × 109/L, respectively. In summary, the two groups of patients have similar baseline characteristics. However, only 32% of patients in Group 1 received glucocorticoids alone during hospitalization, while the proportion of such patients in Group 2 was 60%. In Group 1, a higher proportion of patients required combination therapy with other drugs including IVIG, thrombopoietin receptor agonists (TPO-RA), and even rituximab. Among those, eight patients (32%) received IVIG, five patients (20%) received both IVIG and TPO-RA, and four patients (16%) received IVIG, TPO-RA, and rituximab. In contrast, in Group 2, seven patients (28%) received IVIG, two patients (8%) received both IVIG and TPO-RA, and one patient (4%) received IVIG, TPO-RA, and rituximab.

Due to the small sample size, we assessed the normality of the data using the Shapiro–Wilk test (Table 2). As the platelet data for at least one of the groups was found to have a skewed distribution, we opted to use the Mann–Whitney U-test or Wilcoxon rank-sum test to compare differences between the groups for all days (Table 3 and Figure 1). On Day 1, the median platelet counts were 5 and 9 × 109/L, and on Day 14, they were 184 and 266 × 109/L, respectively, with no statistically significant differences observed. However, on Day 3, the median counts were 22 and 49 × 109/L, and on Day 7, they were 74 and 159 × 109/L, respectively, with statistically significant differences observed between the two groups (P < 0.05).

Table 2

Assessment of normality using Shapiro–Wilk test for platelet data in two groups

Shapiro–Wilk Day 1 Day 3 Day 7 Day 14
1 2 1 2 1 2 1 2
Statistic 0.872 0.940 0.877 0.907 0.888 0.885 0.905 0.968
df 25 25 25 25 25 25 25 25
P value 0.005 0.148 0.006 0.026 0.010 0.009 0.023 0.596

1: Group 1; 2: Group 2.

Table 3

Comparison of platelets between two groups using Mann–Whitney U-test and Wilcoxon rank-sum test on different days

Day 1 Day 3 Day 7 Day 14
Mann–Whitney U 276.000 198.500 170.000 238.000
Wilcoxon W 601.000 523.500 495.000 563.000
Z –0.710 –2.214 –2.765 –1.446
P value 0.478 0.027 0.006 0.148
Figure 1 
               Comparison of platelets between two groups using independent-samples Mann–Whitney U-test.
Figure 1

Comparison of platelets between two groups using independent-samples Mann–Whitney U-test.

After conducting subgroup analysis using Fisher’s exact test (Table 4), it was observed that the gender distribution did not significantly differ between the two groups. However, a greater proportion of patients in Group 1 had platelet counts less than 30 × 109/L on Day 3 than in Group 2, although this difference was not statistically significant. Furthermore, there was a significant difference between the two groups with respect to the proportion of patients having platelet counts less than 100 × 109/L on Day 7, as well as requiring second-line therapy, with a higher proportion observed in Group 1 (P < 0.05).

Table 4

Subgroup analysis using Fisher’s exact test: gender distribution and platelets in two groups

Group 1 Group 2 P value
Male 9 8 0.500
Female 16 17
Platelets <30 × 109/L on Day 3 15 10 0.129
Platelets ≥30 × 109/L on Day 3 10 15
Platelets <100 × 109/L on Day 7 15 8 0.044
Platelets ≥100 × 109/L on Day 7 10 17
Need for second-line therapy 9 3 0.048
No need for second-line therapy 16 22

4 Discussion

This study aimed to evaluate the platelet response to first-line treatment in patients with de novo ITP after COVID-19 vaccination. We compared the platelet counts and treatment outcomes of two groups of patients: Group 1 (de novo ITP patients who received COVID-19 vaccination) and Group 2 (historical de novo ITP patients). We found that Group 1 had a lower response rate to first-line treatment, with a higher proportion of patients requiring combination therapy and lower platelet counts on Days 3 and 7. The difference in platelet counts on Day 14 was not significant and may be related to early combination therapy improving platelet counts. The baseline characteristics of the two groups of patients were similar, indicating that the differences observed in treatment response were likely due to the effect of COVID-19 vaccination on the disease course.

In our study, 36% of patients in Group 1 required second-line therapy, consistent with Choi et al.’s report that 39% of COVID-19 vaccine-related ITP patients needed additional treatment due to poor response to first-line therapy [10]. In contrast, Saluja et al. reported that most similar cases responded well to first-line therapy [11]. The sample sizes of these three studies were all less than 100, and the differences in their results may be due to factors such as limited sample size and different types of COVID-19 vaccines administered. Further research with larger sample sizes and standardized protocols is necessary to better understand the relationship between COVID-19 vaccine administration and the treatment response of ITP.

Some studies have raised concerns about using rituximab for ITP patients during the COVID-19 pandemic due to the potential risk of infection from decreased humoral immunity after treatment [12,13]. However, thanks to the Chinese government’s strict measures for epidemic prevention and control until December 2022, we were not overly concerned about this side effect and decided to administer rituximab to four vaccinated patients with refractory ITP. The average platelets of these four patients on Day 7 and Day 14 remained low at 52 and 23.5 × 109/L, respectively. Therefore, we initiated rituximab 100 mg/week for them. On Day 28, one patient was lost to follow-up, but the remaining three patients demonstrated platelet counts of 46, 123, and 237 × 109/L, respectively. These results suggest that clinicians may need to be aware of the potential for poor treatment response in de novo ITP patients who have received COVID-19 vaccination and adjust treatment plans accordingly. Rituximab may be a useful treatment option for vaccinated ITP patients who are refractory to conventional therapies, even during the COVID-19 pandemic, with proper measures for infection control in place.

Further studies exploring the immune mechanisms involved in vaccine-related ITP may shed light on the underlying mechanisms of the observed treatment response differences. For example, it is worth investigating whether differences in antibody titers after COVID-19 vaccination may affect the response of ITP patients to first-line treatment, and whether the vaccine may induce persistent pathogenic antibody secretion in some patients through a germinal center response [14,15]. These issues warrant further basic research. In addition, some studies have suggested that COVID-19 vaccination induces a strong T-cell response, and therefore, the possibility of the involvement of cell-mediated immunity in the development of ITP in these patients also deserves exploration [16].

Although the study provides valuable insights into the treatment response of de novo ITP patients following COVID-19 vaccination, there are several limitations to consider. In light of constraints within our medical institution, platelet antibody testing is currently unfeasible. Due to the lack of an assessment of the concentration and specificity of antiplatelet antibodies, interference with treatment response cannot be ruled out. The lack of a prospective cohort control study design prevents us from determining whether first-line treatment can improve platelet counts in patients with poor short-term responses at Day 14 or beyond. Additionally, the local government’s promotion of COVID-19 vaccination has resulted in a lack of ITP patient data without vaccination during the same period. To address these limitations, future studies should incorporate larger sample sizes, more comprehensive assays, and prospective controlled designs, as well as data from unvaccinated ITP patients during the same period through multi-center research.

Overall, despite the limitations related to the data and study design, the study provides a useful starting point to further investigate the potential long-term effects of COVID-19 vaccination on ITP, exploring alternative treatment options for refractory cases, and conducting larger prospective controlled studies to confirm the observed treatment response differences.

5 Conclusion

Our study suggests that de novo ITP patients who received COVID-19 vaccination had a lower response rate to first-line treatment compared to those prior to the pandemic. A higher proportion of vaccinated patients required combination therapy and had lower platelet counts on Day 3 and Day 7. This highlights the importance of close monitoring and tailored treatment for vaccinated de novo ITP patients. However, our study still has certain limitations, including the absence of platelet antibody testing and a lack of a prospective cohort control study, which precludes the exclusion of potential confounding factors, including the possible interference of different vaccines with treatment outcomes. Larger studies are needed to confirm our findings and explore the potential impact of COVID-19 vaccination on ITP development and progression.

Acknowledgments

The authors would like to express their sincere gratitude to Dr. Ting Yang for her enduring guidance throughout this work.

  1. Author contributions: Hp.X. and Bb.Z. collected, sorted, analyzed the data, prepared figures and/or tables, and drafted the manuscript. Lj.X. conceived and designed the experiments, reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.

  2. Conflict of interest: The authors declare that they have no competing interests.

  3. Data availability statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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Received: 2023-06-10
Revised: 2024-02-16
Accepted: 2024-03-05
Published Online: 2024-03-23

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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