Chronic spontaneous urticaria after BNT162b2 mRNA (Pfizer-BioNTech) vaccination against SARS-CoV-2

Background: The factors that trigger and exacerbate chronic spontaneous urticaria (CSU) are well known, but it is not unclear whether messenger RNA (mRNA) vaccination against severe acute respiratory syndrome coronavirus 2 can trigger new cases of CSU or a relapse of CSU after long-term remission. Objective: To study the clinical cases of patients with new-onset CSU and CSU in remission who relapsed within 3 months after BNT162b2 mRNA vaccination. Methods: All patients with a CSU diagnosis within 12 weeks of BNT162b2 mRNA vaccination were retrospectively identified and included in the new-onset CSU and the relapsed CSU groups. The first control group (CSU control group) retrospectively consisted of patients diagnosed with CSU in complete clinical remission for ≥ 6 months, with no CSU relapse after vaccination. The second control group (healthy control group) consisted of subjects who were fully vaccinated and without CSU, matched 1:2 for age and sex with patients with CSU. Results: Twenty-seven patients were included in the relapsed CSU group, 32 patients in the new-onset CSU group, 179 patients in the CSU control group, and 476 subjects in the healthy control group. The relapsed CSU and new-onset CSU groups had more allergic comorbidities overall (19 [70.4%] and 13 [40.6%], respectively) than the CSU control group and the healthy control group (50 [27.9%] and 110 [23.1%], respectively; p < 0.001). Multiple logistic regression analysis showed that a positive autologous serum skin test result, overall allergic comorbidities, and basopenia were positively associated with the probability of CSU relapse within 3 months after BNT162b2 mRNA vaccination (odds ratio [OR] 5.54 [95% confidence interval {CI}, 2.36‐13.02], p < 0.001); OR 6.13 [95% CI, 2.52‐14.89], p = 0.001; and OR 2.81 [95% CI, 1.17‐6.72, p = 0.020, respectively). Conclusion: It is possible that BNT162b2 mRNA vaccination serves as a provoking and/or relapsing factor of CSU in individuals with allergic diseases and/or predisposed autoimmunity.

The Quality of Life of People with Solid Cancer is Less Worse than Other Diseases with better Prognosis, Except in the Presence of Depression

Background: Suffering from Solid Cancer (SC) may adversely impact the Health-related Quality of Life (H-QoL). The aims of this study are to measure the H-QoL in a sample of people suffering from SC and to clarify the role of the co-occurrence of depressive episodes. Results were compared with a healthy control group and with groups of other disorders. Methods: In 151 patients with SC (mean±sd age 63.1±11.5; female 54.3%), H-QoL was assessed by SF-12, depressive episodes were identified by PHQ-9. The attributable burden of SC in impairing H-QoL was calculated as the difference between SF-12 score of a community sex and age ¼ matched healthy control group and that of the study sample. The attributable burden of SC was compared with other chronic diseases using specific diagnostic groups drawn from case-control studies that used the same database for selecting control samples. Results: H-QoL in people with SC was significantly worse than in the healthy control group (p<0.0001). The attributable burden in worsening the H-QoL due to SC was similar to those of severe chronic diseases, but lower than Multiple Sclerosis (p<0.0001) or Fibromyalgia (p<0.00001). Having a depressive episode was a strong determinant of decreasing H-QoL, regardless of the severity of cancer. Conclusion: The findings confirm a strong impact of SC but showed that H-QoL in SC was higher than in chronic diseases with better “quoad vitam” outcome. Since depression was a strong determinant, its prevention, early detection and therapy are the main objectives that must be reached in cancer patients.

Humoral Response among Patients with Interstitial Lung Disease Vaccinated with the BNT162b2 SARS-Cov-2 vaccine - A Prospective Cohort Study

Background: Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. We aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy.Methods: We conducted an observational prospective cohort study to evaluate the rate of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement one serology test was drawn from all patients 4-6 months after the second vaccine dose. Two age and sex matched control groups were created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June to August 2021.Results: All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P=1.0). The antifibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [ IQR, 207-811] AU/ml vs 820.75 [IQR, 459-1313] AU/ml; P<0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P<0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [ IQR, 4.25-165] AU/ml vs 970.1 [IQR, 505-1926] AU/ml; P<0.001). Conclusion: IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, maintain a 100% seropositivity rate, 4-6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD, treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose, moreover treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.

CLINICO-HEMATOLOGICAL STUDY OF ACUTE LYMPHOBLASTIC LEUKEMIA AND THEIR CORRELATION WITH INFLAMMATORY MARKERS IN SERUM.

SUMMARY: Acute lymphoblastic leukemia (ALL) is early childhood hematological malignancies. In present scenario immunophenotyping became an important tool for subtyping of ALL into B-ALL and TALL. In order to understand the mechanism of development of leukemia it is important to study the cytokine environment of malignant cells. OBJECTIVE: Aim of the present study was to evaluate clinical and hematological features in ALL and correlate serum levels of IL6 and IL-10 expression in ALL patients and their subtypes. MATERIALS & METHODS: A total of 68 ALL cases along with 20 healthy controls were included in the study between periods of 2015 to 2017. About 4 mL blood samples were collected from all cases for immunophenotyping and serum studies. Levels of IL6 and IL10 were determined in all cases by ELISA. RESULT: In the present study immunphenotyping was done in all cases of ALL, which showed 52 cases (76.5%) of B-ALL and 16 cases (23.5%) of T-ALL. T-ALL was mostly found in higher aged children than B-ALL. A male predominance was seen in all cases. No signicant differences in hemoglobin levels and platelet counts were found between T-ALL and B-ALL. A signicantly high percentage of T-ALL cases were having more than 50000 cells per microliter than B-ALL (56.2% vs. 23.1%). Almost similar clinical features were found in both subgroups, only bleeding manifestation was found signicantly higher in T-ALL than B-ALL (31.2% vs.11.5%). Acute lymphoblastic leukemia (ALL) patients were associated with signicantly elevated serum IL6 and IL10 level than the healthy control group. Mean levels of serum IL6 were 167.9±306.46 pg/mL in ALL, and 6.51 ± 2.27 pg/mL in healthy control group. Mean IL10 levels were 70.56±111.48 pg/mL in ALL and 29.39 ± 4.27 pg/mL in control group. There were no signicant differences found in IL-6 and IL-10 serum levels between T-ALL and B-ALL. CONCLUSION: Present study found elevated level of IL-6 and IL-10 in ALL patients which suggest possible role of these cytokines in disease transformation. Detection of IL-6 and IL-10 in newly diagnosed patient may predict disease outcome and possibly poor prognosis in patients

Role of Glutathione S-transferase Mu 1 and Glutathione S-transferases Theta 1 Polymorphism in the Risk of Developing Type 2 Diabetes Mellitus at Universitas Sumatera Utara Hospital, Medan

BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. Glutathione S-transferases (GSTs) is group of multifunction antioxidant enzyme can be used as important biomarkers for DM.. GSTM1, T1 genes variant polymorphism result in decreased or loss of enzyme activity. AIM: The study aimed to evaluate the role of GSTM1 and GSTT1 gene polymorphism in the risk of developing T2DM. METHODS: GSTM1 and GSTT1 polymorphisms were genotyped in 87 T2DM patients and 87 healthy control group to analyze their association with T2DM susceptibility by using multiplex Polymerase Chain Reaction (PCR). PCR products were electrophoresed using agarose 2%. Odds ratio (OR) with 95% confidence interval (CI) and P value were calculated using SPSS software (version 21.0). RESULTS: The genotype distribution of GSTM1 and GSTT1 were not different between T2DM patients and healthy control group (p = 0.542, OR= 0.780, CI 95%=0.350-1.737 and p=0.879, OR=1.047, CI 95%=0.577-1.903). The genotype distribution of combination of GSTM1 and GSTT1 were also not not different between T2DM patients and healthy control group (p = 0.640, OR= 0.640, CI 95%=0.224-1.83 and p=0.551, OR=0.721, CI 95%=0.245-2.120. CONCLUSION: In summary, this study showed that GSTT1 null, GSTM1 null, the combination of GSTM1 null and GSTT1 null genotype or combination of GSTM1 null and GSTT1 positive (or contrary) did not have any risk of developing T2DM at Universitas Sumatera Utara Hospital, Medan.

Composition and Diversity of the Ocular Surface Microbiota in Patients With Blepharitis in Northwestern China

Purpose: To investigate the composition and diversity of the microbiota on the ocular surface of patients with blepharitis in northwestern China via 16S rDNA amplicon sequencing.Methods: Thirty-seven patients with blepharitis divided into groups of anterior, posterior and mixed blepharitis and twenty healthy controls from northwestern China were enrolled in the study. Samples were collected from the eyelid margin and conjunctival sac of each participant. The V3–V4 region of bacterial 16S rDNA in each sample was amplified and sequenced on the Illumina HiSeq 2500 sequencing platform, and the differences in taxonomy and diversity among different groups were compared.Results: The composition of the ocular surface microbiota of patients with blepharitis was similar to that of healthy subjects, but there were differences in the relative abundance of each bacterium. At the phylum level, the abundances of Actinobacteria, Cyanobacteria, Verrucomicrobia, Acidobacteria, Chloroflexi, and Atribacteria were significantly higher in the blepharitis group than in the healthy control group, while the relative abundance of Firmicutes was significantly lower (p &lt; 0.05, Mann-Whitney U). At the genus level, the abundances of Lactobacillus, Ralstonia, Bacteroides, Akkermansia, Bifidobacterium, Escherichia-Shigella, Faecalibacterium, and Brevibacterium were significantly higher in the blepharitis group than in the healthy control group, while the relative abundances of Bacillus, Staphylococcus, Streptococcus, and Acinetobacter were significantly lower in the blepharitis group (p &lt; 0.05, Mann-Whitney U). The microbiota of anterior blepharitis was similar to that of mixed blepharitis but different from that of posterior blepharitis. Lactobacillus and Bifidobacterium are biomarkers of posterior blepharitis, and Ralstonia is a biomarker of mixed blepharitis. There was no significant difference in the ocular surface microbiota between the eyelid margin and conjunctival sac with or without blepharitis.Conclusion: The ocular surface microbiota of patients with blepharitis varied among different study groups, according to 16S rDNA amplicon sequencing analysis. The reason might be due to the participants being from different environments and having different lifestyles. Lactobacillus, Bifidobacterium, Akkermansia, Ralstonia, and Bacteroides may play important roles in the pathogenesis of blepharitis.

Effect of an Anterior Cruciate Ligament Rupture on Knee Proprioception Within 2 Years After Conservative and Operative Treatment: A Systematic Review with Meta-Analysis

Background The anterior cruciate ligament (ACL) plays a major role in knee proprioception and is thus responsible for maintaining knee joint stability and functionality. The available evidence suggests that ACL reconstruction diminishes somatosensory feedback and proprioceptive functioning, which are vital for adequate joint positioning and movement control. Objective The aim of this systematic review and meta-analysis was to investigate the effect of an ACL rupture on knee proprioception after arthroscopic ACL repair surgery or conservative treatment. Methods A systematic review with meta-analysis was conducted according to the Preferred Reporting Guidelines for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was performed in the following databases from inception to 10th October 2020: PubMed, Web of Science, SPORTDiscus, Cochrane Library and Scopus. Randomized and non-randomized studies that evaluated proprioception using the joint position sense (JPS) and threshold to detection of passive motion (TTDPM) techniques at 15°–30° knee flexion with an external healthy control group in a time period between 6 and 24 months post injury or operation were included in the analysis. Results In total, 4857 studies were identified, from which 11 were included in the final quantitative analysis. The results demonstrated that proprioception after arthroscopic ACL repair surgery was significantly lower than in the healthy control group (JPS: standardized mean difference [SMD] 0.57, 95% confidence interval [CI] 0.27–0.87, p < 0.01, n = 6 studies; TTDPM: SMD 0.77, 95% CI 0.20–1.34, p < 0.01, n = 4 studies). There were no significant differences in proprioception between the conservative treatment group and the healthy control group (JPS: SMD 0.57, 95% CI − 0.69 to 1.84, p = 0.37, n = 4 studies; TTDPM: SMD 0.82, 95% CI − 0.02 to 1.65, p = 0.05, n = 2 studies), although measures for TTDPM were close to statistical significance. Conclusion The findings of the present systematic review and meta-analysis revealed that knee proprioception is persistently compromised 6–24 months following surgical treatment of ACL tears compared with healthy controls. The reduced kinesthetic awareness after ACL surgery is of high relevance for optimizing individual treatment plans in these patients. As the current literature is still scarce about the exact underlying mechanisms, further research is needed. Trial Registration The present systematic review was registered in PROSPERO (CRD42021198617).

Can the Imbalance Between Neurotrophic and Apoptotic Proteins be the "Beware the Ides of March" for Unaffected Relatives of Schizophrenia Patients?

Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that the siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which is tpa-BDNF pathways proteins and thought to play a role in synaptic pruning as a possible endophenotype of schizophrenia. Forty drug-naïve patients with first-episode psychosis (FEP) matched for age, gender and level of education, 40 unaffected siblings (UAS) of patients with FEP and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway, pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiateFEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the healthy control group with statistically significant differences between all 3 groups. The plasma levels of pro-BDNF in the healthy control group were similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data Support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ, and this imbalance could be an endophenotype of the disease.

Sarcopenia Diagnosis: Reliability of the Ultrasound Assessment of the Tibialis Anterior Muscle as an Alternative Evaluation Tool

Sarcopenia is a skeletal muscle disorder characterized by reduced muscle mass, strength, and performance. Muscle ultrasound can be helpful in assessing muscle mass, quality, and architecture, and thus possibly useful for diagnosing or screening sarcopenia. The objective of this study was to evaluate the reliability of ultrasound assessment of tibialis anterior muscle in sarcopenia diagnosis. We included subjects undergoing total or partial hip replacement, comparing measures with a healthy control group. We measured the following parameters: tibialis anterior muscle thickness, echogenicity, architecture, stiffness, skeletal muscle index (SMI), hand grip strength, and sarcopenia related quality of life evaluated through the SarQoL questionnaire. We included 33 participants with a mean age of 54.97 ± 23.91 years. In the study group we found reduced tibialis anterior muscle thickness compared to the healthy control group (19.49 ± 4.92 vs. 28.94 ± 3.63 mm, p < 0.05) with significant correlation with SarQoL values (r = 0.80, p < 0.05), dynamometer hand strength (r = 0.72, p < 0.05) and SMI (r = 0.76, p < 0.05). Moreover, we found reduced stiffness (32.21 ± 12.31 vs. 27.07 ± 8.04 Kpa, p < 0.05). AUC measures of ROC curves were 0.89 predicting reduced muscle strength, and 0.97 predicting reduced SMI for tibialis anterior muscle thickness, while they were 0.73 and 0.85, respectively, for muscle stiffness. Our findings showed that ultrasound assessment of tibialis anterior muscle might be considered a reliable measurement tool to evaluate sarcopenia.

The Long-term Chondroprotective Effect of Meniscal Allograft Transplant: A 10- to 14-Year Follow-up Study

Background: The long-term chondroprotective effect of meniscal allograft transplant (MAT) and its superiority over meniscectomy have rarely been reported. Hypothesis: MAT would reduce osteoarthritis (OA) progression when compared with the meniscus-deficient knee. Graft extrusion distance would strongly affect the chondroprotective effect of the MAT. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 17 knees receiving MAT were followed up as the MAT group. The MAT group was further divided into the nonextrusion subgroup (n = 9) and the extrusion subgroup (n = 8) according to 3-mm extrusion on the magnetic resonance imaging (MRI) coronal section. A further 26 consecutive patients receiving meniscectomy in the same period were followed up as the ME group. The healthy control group consisted of healthy contralateral legs chosen from the MAT and ME groups (n = 27). Joint space width (JSW) narrowing was measured on radiographs. Three-dimensional MRI with a T2 mapping sequence was used to quantitatively analyze cartilage degeneration and meniscal allograft extrusion in 5 directions (0°, 45°, 90°, 135°, and 180°). The cartilage degeneration index (CDI) was calculated according to the size and degree of the chondral lesions on MRI scans. The correlation between the CDI increase and the extrusion distance was analyzed. Results: The mean follow-up time was 11.3 years (range, 10-14 years). The MAT group had moderate superiority in chondral protection with less JSW narrowing (0.58 ± 0.66 mm) and CDI increase (1132 ± 1589) compared with the ME group (JSW narrowing: 1.26 ± 1.13 mm, P = .025; CDI increase: 2182 ± 1958, P = .079). The JSW narrowing (0.71 ± 0.80 mm; P = .186) and CDI increase (2004 ± 1965; P = .830) of the extrusion subgroup were close to those of the ME group, demonstrating that a 3-mm extrusion led to complete loss of the meniscal chondroprotective effect. The nonextrusion group had significantly less JSW narrowing (0.48 ± 0.48 mm; P = .042) and CDI increase (358 ± 249; P = .011) than the ME group. The JSW narrowing of the healthy control group was 0.22 ± 0.27 mm. The cartilage T2 values of the extrusion subgroup were similar to those of the ME group, with more OA features, whereas the T2 values of the nonextrusion subgroup were closer to those of the healthy control group. The extrusion distance in the 90° direction ( P = .002) and the follow-up time ( P = .019) significantly affected the CDI increase in the multivariate regression model. The average extrusion distance in the 45°, 90°, and 135° directions better predicted chondroprotection compared with the other individual directions. Conclusion: MAT had moderate advantages in chondroprotection compared with meniscectomy in the long term. Graft extrusion distance strongly affected the chondroprotective effect of MAT. The chondroprotective effect of the nonextruded meniscal allograft was close to that of the native meniscus, whereas the allografts with an extrusion >3 mm completely lost their function after meniscectomy.