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Plasmapheresis: Is it a potential alternative treatment for chronic urticaria?

  • Laima Aleksandraviciute EMAIL logo , Laura Malinauskiene , Kestutis Cerniauskas and Anzelika Chomiciene
Published/Copyright: December 23, 2021
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Open Medicine
From the journal Open Medicine Volume 17 Issue 1

Abstract

Background

Chronic urticaria is a common disease. Plasmapheresis is an alternative treatment that can be appropriate for patients who are resistant to treatment with 2nd generation antihistamines or for whom treatment with omalizumab is unsuitable.

Objective

To investigate the effect of plasmapheresis treatment in chronic urticaria.

Methods

A retrospective analysis was performed based on the data of 98 patients suffering from refractory chronic urticaria who received plasmapheresis as an alternative treatment in Vilnius University’s Hospital Santaros Clinics from 2000 to 2020. The efficiency of the treatment was evaluated by clinical judgment.

Results

58.2% of the patients exhibited a complete or significant response; of these, 37.8% had temporary relief of symptoms and 20.4% achieved disease remission; 41.8% showed no response to the plasmapheresis. Men (34.8%) had a tendency to achieve disease remission more often than women (16%) (p < 0.05). One patient did not finish the plasmapheresis treatment due to the symptoms’ exacerbation and treatment with omalizumab was initiated.

Conclusion

Plasmapheresis is a safe and effective alternative treatment when traditional treatment is unavailable or does not relieve symptoms completely. Our data showed that plasmapheresis was effective in more than half of our patients.

Keywords: chronic urticaria; plasmapheresis; omalizumab; antihistamines; urticaria treatment

1 Introduction

Chronic spontaneous urticaria (CSU) defined as the presence of wheals, angioedema, or both, which lasts for at least 6 weeks, affects patients’ quality of life due to recurrent symptoms. Recent studies have shown that CSU prevalence depends on the region and varies between 0.1–1.4% of the general population [1].

Although the main event in CSU is activation and degranulation of dermal mast cells, the pathogenesis of CSU remains mostly unclear. In recent years, more evidence shows that CSU can be an autoimmune disease as up to 40% of the patients have detectable histamine-releasing immunoglobulin G (IgG) autoantibodies directed against immunoglobulin E (IgE) or the high-affinity IgE receptor on mast cells and basophils or IgE autoantibodies to common structures (e.g., thyroid gland) [2].

International guidelines by European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) recommend oral non-sedating antihistamines, the dosage of which can be increased up to four times as a first-line treatment option for CSU. As around half of the CSU patients cannot be controlled on this treatment, biologic omalizumab (anti-IgE) or cyclosporine A are recommended, mainly because the efficacy of these drugs is demonstrated in randomized controlled trials. About 30% of the patients remain symptomatic at licensed doses of omalizumab 150 and 300 mg, even after a treatment period of over 6 months [3]. Patients treated with cyclosporine A achieve remission from 54 to 73% depending on the prescribed dose and treatment duration [4]. Various other treatments have also been used and described for CSU, but are not included in the current international guidelines.

As there is increasing evidence on the possible pathogenetic role for circulating autoantibodies in CSU, we aimed at evaluating the effectiveness of plasmapheresis and to find biomarkers of the effectiveness in our cohort of CSU patients.

2 Methods

In this retrospective study, we analyzed data of 98 CSU patients (75.5% women and 24.5% men) (Table 1) treated between August 2000 and March 2020. The mean age of CSU beginning was 39.8 years. CSU was diagnosed according to EAACI/GA2LEN/EDF/WAO guidelines for the definition, classification, diagnosis, and management of urticaria. All patients suffered from severe refractory to antihistamines CSU, lasting more than 6 weeks, and were treated with 4 times higher dose of 2nd generation antihistamines. Patients with inducible urticaria were excluded from the study. Before receiving plasmapheresis, ten patients were also treated unsuccessfully with omalizumab (available in Lithuania since 2016) and two patients with cyclosporine.

Table 1

Characteristics of 98 CSU patients treated with plasmapheresis

Patients (n = 98)
Female 75 (76.5%)
Male 23 (23.5%)
Median age of CSU manifestation 39.8 years (±15.7)
Sensitivity to NSAIDs by history 17 (17.3%)
Food influence to CSU 7 (7.1%)
Other conditions
 Autoimmune thyroiditis 24 (24.5%)
 Urticarial vasculitis 9 (9.2%)
 Diabetes 6 (6.1%)
 Oncological disease 6 (6.1%)
 Atopic dermatitis 3 (3.1%)
 IgA deficiency 2 (2.0%)

NSAID, non-steroidal anti-inflammatory drugs; CSU, chronic spontaneous urticaria.

One course of plasmapheresis consisted of six procedures which usually were performed every second day. During each procedure, 200–350 mL of plasma was removed and replaced with 750 mL of 0.9% normal saline within 2 h. The volume of removed plasma depended on the patients’ weight, height, and results of laboratory tests. Before procedure, patients underwent a complete blood test, total protein or albumin, creatinine, sodium, potassium, and calcium analyses. During one course of plasmapheresis, approximately 2,000 mL of plasma was removed.

Effectiveness evaluation of the plasmapheresis treatment was based on a modified global evaluation of treatment effectiveness [5]. Physician graded patients depending on how effective treatment had been in controlling the patients’ CSU. Patients were grouped into three groups (Table 2).

Table 2

Patient groups depending on clinical effect

Group Clinical effect
Group 1 Remission: patients had no symptoms for at least 1 month, did not need antihistamines
Group 2 Temporary symptoms relief: patients had no symptoms for less than a month or used lower doses of antihistamines than usual
Group 3 No significant effect: the symptoms remained the same, used the same doses of antihistamines

The autologous serum skin test (ASST) was performed on 47 patients. ASST was performed according to EAACI/GA2LEN guidelines [6].

Anti-TPO antibodies and thyroid-stimulating hormone (TSH) tests were performed on 53 patients. The normal anti-TPO level was considered to be <5.61 kU/L. Normal TSH level was considered to be 0.4–4.0 mU/L.

The statistical program SPSS 20 was used for statistical analysis. Results are presented as mean values and standard deviations. Findings were compared between the groups using the Chi-square test as appropriate. p values < 0.05 were considered statistically significant.

  1. Ethical approval: The study was approved by the Regional Ethics Review Board in Vilnius, Lithuania, and was conducted following ethical standards specified in the Declaration of Helsinki.

3 Results

Plasmapheresis was initiated within 6 months of CSU symptoms appearing in 25.5% (25/98) of the patients (Figure 1). Most of the patients (74.5%), received 1 plasmapheresis course, 1 patient received 6 courses of plasmapheresis within 5 years (Figure 2). We repeated plasmapheresis only in case it was successful and patients were willing to perform it again.

Figure 1 Duration of chronic spontaneous urticaria before plasmapheresis.
Figure 1

Duration of chronic spontaneous urticaria before plasmapheresis.

Figure 2 Number of plasmapheresis courses.
Figure 2

Number of plasmapheresis courses.

The ASST was performed on 47 patients, 22 of them were positive (Table 3). We did not find any statistically significant differences in the plasmapheresis effectiveness in the group of patients with positive ASST (p = 0.065).

Table 3

Plasmapheresis effect in positive and negative ASST groups

Number of patients Clinical effect
Positive autologous serum skin test group
 9 (40.9%) Remission
 9 (40.9%) Temporary symptoms’ relief
 4 (18.2%) No effect
Negative autologous serum skin test group
 3 (12.0%) Remission
 13 (52.0%) Temporary symptoms’ relief
 9 (36.0%) No effect

More than half of the patients were investigated for thyroid dysfunction. Anti-TPO antibodies and TSH tests were performed on 53 patients (Table 4). In a group of patients with increased anti-TPO antibodies, there was a tendency to achieve better disease control results than in patients with normal anti-TPO antibodies level. In a group of patients with increased anti-TPO antibodies, 25% achieved remission and 45.8% felt temporary symptoms’ relief after plasmapheresis. In those with normal anti-TPO antibodies, 24.1% achieved remission and only 27.6% felt temporary symptoms’ relief. However, the results were not statistically significant (p = 0.296).

Table 4

Thyroid dysfunction and plasmapheresis effect

Number of patients Thyroid stimulating hormone level
36 (67.9%) Normal
16 (30.2%) Hypothyroidism
1 (1.9%) Hyperthyroidism
Number of patients Clinical effect
Patient with increased anti-TPO antibodies
 6 (25.0%) Remission
 11 (45.8%) Temporary symptoms’ relief
 7 (29.2%) No effect
Patient with normal anti-TPO antibodies
 7 (24.1%) Remission
 8 (27.6%) Temporary symptoms’ relief
 14 (48.3%) No effect

58.2% of the patients exhibited a complete or significant response; of these, 37.8% had temporary symptoms’ relief and 20.4% achieved disease remission; 41.8% showed no response to plasmapheresis (Figure 3). The study showed that men (34.8%) tended to achieve disease remission more often than women (16%) (p < 0.05).

Figure 3 Effect of plasmapheresis.
Figure 3

Effect of plasmapheresis.

4 Discussion

In most cases, CSU is treated based on EAACI/GA2LEN/EDF/WAO recommended algorithm. Although, in clinical practice a bunch of different alternative treatment options are used. One of them is plasmapheresis.

Plasmapheresis can be performed by centrifugation or filtration [7]. During filtration plasmapheresis, whole blood passes through a filter and plasma components are separated from the larger cellular components of red blood cells, white blood cells, and platelets. Double–filtration plasmapheresis removes medium to large molecules, including various antibodies [8]. Centrifugation is usually performed by blood bankers. Although in our clinic, centrifugal plasmapheresis was performed on patients with CSU. Only a few case reports with positive outcomes of the plasmapheresis treatment in severe CSU have been published. Patients with CSU often have circulating IgG autoantibodies against high-affinity IgE receptors or IgE. Recently there is some evidence of IgE antibodies against self-antigens (e.g., TPO) [9]. It is presumed that CSU is caused by autoantibodies activating mast cells. We can expect the plasmapheresis treatment to be effective because through this treatment medium and large molecular substances such as IgG and IgE are removed from circulation.

If there is a suspicion of autoimmune or autoreactive urticaria, a screening test such as ASST can be performed. Basophil activation assays and basophil mast cell histamine release tests are used to detect functional autoantibodies against IgE and FcεRIα [10]. Antibody specificity is confirmed by immunoassay. In clinical practice, laboratory tests are not performed routinely [11]. Our study results showed that the plasmapheresis treatment was more effective in patients with positive ASST than in those with negative ASST, but the data were not statistically significant (p = 0.065). Some studies have also shown that reduction of functional auto-antibodies via plasmapheresis had a temporary benefit in some, severely affected patients [12,13].

There is little information about the effect of plasmapheresis in patients with CSU and thyroid dysfunction. A case report of successful resistant CSU treatment with plasmapheresis in a patient who also had thyroid gland disorder was published in Poland [13]. We found that in a group of patients with increased anti-TPO antibodies, there was a tendency to achieve better treatment results (p = 0.296). Even though plasmapheresis seems to be more effective for patients with increased anti-TPO antibodies, further investigation needs to be done.

CSU may develop in children and adults, but it mostly affects adults between the age of 20 and 40 years [14]. In our study, the average age of disease manifestation was 39.8 years (±15.7). Since the disease affects young, working-age people, and has a negative impact on life quality, it is very important to start effective treatment as soon as possible. Based on our data there was no correlation between the duration of urticaria and the plasmapheresis effect (Table 5).

Table 5

Plasmapheresis effect depending on duration of CSU

Clinical effect Duration of CSU
<6 months 6 months–1 year 1–5 years 5–10 years >10 years
Remission 3 (12%) 2 (11.1%) 5 (22.7%) 4 (30.8%) 6 (30.0%)
Temporary symptoms’ relief 9 (36.0%) 9 (50.0%) 9 (40.9%) 3 (23.1%) 7 (35.0%)
No effect 13 (52.0%) 7 (38.9%) 8 (36.4%) 6 (46.1%) 7 (35.0%)

Omalizumab is available in Lithuania as a treatment for CSU since 2016, that is why we used plasmapheresis quite often in antihistamines-resistant CSU. Nowadays, CSU patients are treated with plasmapheresis only when omalizumab is ineffective or the patient refuses to be treated with it. Patients for whom plasmapheresis was effective were willing to repeat it when CSU reoccurred. One patient received even six courses of plasmapheresis. The initial four courses of plasmapheresis were successful, but after the fifth ineffective course, she was treated with omalizumab, which was partially effective. The patient underwent a sixth course of plasmapheresis but it did not have a significant effect. Since then, the patient is being treated with omalizumab. The patient’s symptoms are less severe but full remission has not been reached.

Omalizumab is a third-line add-on therapy to second-generation H1-antihistamines. It is an effective and well-tolerated treatment option for CSU patients who remain symptomatic despite second-generation H1-antihistamines treatment. In our study, ten patients received unsuccessful treatment with omalizumab before plasmapheresis. For half of them, plasmapheresis was effective; 4 felt temporary symptoms’ relief and 1 achieved disease remission after 4 years of CSU. Some patients who received plasmapheresis initially did not need further treatment with omalizumab. 25 of our analyzed patients did not receive omalizumab after plasmapheresis. For the majority of these 25 patients, plasmapheresis was effective; 12 felt the relief of symptoms, and 9 achieved disease remission (Table 6).

Table 6

Plasmapheresis effect in group of patients for whom omalizumab was ineffective

Clinical effect Duration of CSU
<6 months 6 months–1year 1–5 years 5–10 years >10 years
Remission 2 (28.6%) 2 (40.0%) 2 (40.0%) 1 (50.0%) 2 (33.3%)
Temporary symptoms’ relief 5 (71.4%) 1 (20.0%) 2 (40.0%) 1 (50.0%) 3 (50.0%)
No effect 0 (0.0%) 2 (40.0%) 1 (20.0%) 0 (0.0%) 1 (16.7%)

Plasmapheresis is an alternative treatment that is effective in some cases, as shown by available data [8,12,13,15]. Grattan et al. published an analysis on eight patients with severe, unremitting, CSU who underwent plasmapheresis. Urticarial activity score was evaluated by wheal numbers, duration, frequency, and itchiness (each symptom scored from 0 to 4, the maximum total score being 16). Six of eight patients had a positive response to the treatment [12]. In our study, a large group of patients were analyzed. 58.2% of all patients exhibited a complete or significant response after one course of plasmapheresis, of which 37.8% had temporary symptoms relief and 20.4% achieved disease remission. 41.8% showed no response to plasmapheresis.

Plasmapheresis is a safe treatment option. The procedure is contraindicated for patients who do not tolerate central line placement, are hemodynamically unstable, or have hypocalcemia. Major possible adverse events of plasmapheresis are hypothermia, numbness, hypotension, and puncture site hematoma. In rare cases arrhythmia, convulsions, or loss of consciousness can occur. There were no severe adverse events in our analyzed group of patients. Only one patient discontinued plasmapheresis due to the exacerbation of the symptoms.

There are numerous gaps in the knowledge about the pathogenesis of CSU. Large, controlled, well-designed, and randomized trials have not been conducted for most of the alternative agents including plasmapheresis. Despite very effective biological treatment, a rational, patient-based approach can still be used that is based on evidence, the potential for adverse effects, costs, and patient preferences.

Our study has some limitations. The retrospective single-center analysis was performed without objective evaluation criteria (e.g., Urticaria Activity Score summed over 7 days, Dermatology Life Quality Index, and disease-specific Chronic Urticaria Quality of Life Questionnaire).

5 Conclusion

In our study, more than half of all patients exhibited a complete or significant response to the treatment. Based on our data, plasmapheresis is a safe, effective alternative treatment. Although there was a tendency of better results in patients with positive ASST and increased anti-TPO antibodies, more studies are needed to evaluate the effect of plasmapheresis for patients with autoimmune thyroid disease and autoreactive urticaria.

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  1. Funding information: No external funding source for this study.

  2. Conflict of interest: The authors have no conflict of interest to declare.

  3. Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Received: 2021-05-04
Revised: 2021-10-17
Accepted: 2021-10-28
Published Online: 2021-12-23

© 2022 Laima Aleksandraviciute et al., published by De Gruyter

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

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  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
https://doi.org/10.1515/med-2021-0399
Keywords for this article
chronic urticaria; plasmapheresis; omalizumab; antihistamines; urticaria treatment
Creative Commons
BY 4.0

Articles in the same Issue

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  2. AMBRA1 attenuates the proliferation of uveal melanoma cells
  3. A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma
  4. Differences in complications between hepatitis B-related cirrhosis and alcohol-related cirrhosis
  5. Effect of gestational diabetes mellitus on lipid profile: A systematic review and meta-analysis
  6. Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4
  7. Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data
  8. Plasmapheresis: Is it a potential alternative treatment for chronic urticaria?
  9. The biomarkers of key miRNAs and gene targets associated with extranodal NK/T-cell lymphoma
  10. Gene signature to predict prognostic survival of hepatocellular carcinoma
  11. Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12
  12. Does diabetes affect paraneoplastic thrombocytosis in colorectal cancer?
  13. Is there any effect on imprinted genes H19, PEG3, and SNRPN during AOA?
  14. Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease
  15. Pericentric inversion of chromosome 6 and male fertility problems
  16. Staple line reinforcement with nebulized cyanoacrylate glue in laparoscopic sleeve gastrectomy: A propensity score-matched study
  17. Retrospective analysis of crescent score in clinical prognosis of IgA nephropathy
  18. Expression of DNM3 is associated with good outcome in colorectal cancer
  19. Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation
  20. CRRT influences PICCO measurements in febrile critically ill patients
  21. SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis
  22. lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells
  23. circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer
  24. Prognostic value of nicotinamide N-methyltransferase in human cancers: Evidence from a meta-analysis and database validation
  25. GPC2 deficiency inhibits cell growth and metastasis in colon adenocarcinoma
  26. A pan-cancer analysis of the oncogenic role of Holliday junction recognition protein in human tumors
  27. Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer
  28. Association between preventable risk factors and metabolic syndrome
  29. miR-29c-5p knockdown reduces inflammation and blood–brain barrier disruption by upregulating LRP6
  30. Cardiac contractility modulation ameliorates myocardial metabolic remodeling in a rabbit model of chronic heart failure through activation of AMPK and PPAR-α pathway
  31. Quercitrin protects human bronchial epithelial cells from oxidative damage
  32. Smurf2 suppresses the metastasis of hepatocellular carcinoma via ubiquitin degradation of Smad2
  33. circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury
  34. Sonoclot’s usefulness in prediction of cardiopulmonary arrest prognosis: A proof of concept study
  35. Four drug metabolism-related subgroups of pancreatic adenocarcinoma in prognosis, immune infiltration, and gene mutation
  36. Decreased expression of miR-195 mediated by hypermethylation promotes osteosarcoma
  37. LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the β-catenin pathway
  38. Cx43 upregulation in HUVECs under stretch via TGF-β1 and cytoskeletal network
  39. Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey
  40. Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?
  41. Analysis of the expression and prognostic value of MT1-MMP, β1-integrin and YAP1 in glioma
  42. Optimal diagnosis of the skin cancer using a hybrid deep neural network and grasshopper optimization algorithm
  43. miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells
  44. Clinical value of SIRT1 as a prognostic biomarker in esophageal squamous cell carcinoma, a systematic meta-analysis
  45. circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8
  46. miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2
  47. hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling
  48. circ_0085296 inhibits the biological functions of trophoblast cells to promote the progression of preeclampsia via the miR-942-5p/THBS2 network
  49. TCD hemodynamics findings in the subacute phase of anterior circulation stroke patients treated with mechanical thrombectomy
  50. Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid
  51. Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway
  52. circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis
  53. Human amniotic fluid as a source of stem cells
  54. lncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox
  55. NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
  56. Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak
  57. Risk factors for adverse drug reactions associated with clopidogrel therapy
  58. Serum zinc associated with immunity and inflammatory markers in Covid-19
  59. The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies
  60. LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis
  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
  68. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis
  69. miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1
  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
  78. circRNF20 aggravates the malignancy of retinoblastoma depending on the regulation of miR-132-3p/PAX6 axis
  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
  80. Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy
  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
  88. A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia
  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
  92. Value of ultrasonography parameters in diagnosing polycystic ovary syndrome
  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
  99. Identification of osteoporosis based on gene biomarkers using support vector machine
  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
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