Possible association between viral infection and poor survival of the corneal graft after penetrating keratoplasty in patients with congenital corneal opacity: a cohort study

BackgroundCongenital corneal opacity (CCO) is a rare disorder. Penetrating keratoplasty (PK) is the main surgical option for CCO, but many factors affect graft survival. Therefore, this study aimed to perform a virological examination of CCO specimens after PK to explore the relationship between virological factors and graft survival after PK.MethodsThis prospective study included consecutive patients (<6 months of age) diagnosed with CCO and treated with PK at Beijing Tongren Hospital from August 2017 to January 2018. Next-generation sequencing was used to detect viral DNA in the CCO specimens. The survival of the primary graft was analysed using the Kaplan-Meier method.ResultsOverall, 24 eyes of 24 infants were treated with PK during the study period. The mean age at surgery was 4.8±1.1 months. Epstein-Barr virus DNA was detected in two specimens, varicella-zoster virus DNA in one specimen, herpes simplex virus DNA in three specimens and cytomegalovirus DNA in one specimen. In the virus-positive group, only one (14.3%) graft remained clear during follow-up. In contrast, in the virus-negative group (n=17), 13 (76.5%) grafts were still clear at the last follow-up. The mean survival of the grafts in the virus-positive group was significantly shorter than in the virus-negative group (11.0±9.8 months vs 27.1±7.7, p<0.001).ConclusionThe presence of viral DNA in CCO specimens might be associated with poor graft survival after PK.

Clinical and Laboratory Findings of Nosocomial Sepsis in Extremely Low Birth Weight Infants According to Causative Organisms

Background: nosocomial sepsis remains a significant source of morbidity and mortality in extremely low birth weight (ELBW) infants. Early and accurate diagnosis is very important, but it is difficult due to the similarities in clinical manifestation between the causative microorganisms. We tried to identify the differences between causative microorganisms in clinical and laboratory findings and to help choose antibiotics, when sepsis was suspected in ELBW infants. Methods: a retrospective study was conducted on preterm infants, born at less than 28 weeks of gestation, with a birth weight of less than 1000 g between January 2009 and December 2019. Clinical and laboratory findings of suspected sepsis, after the first 72 h of life, were assessed. We classified them into four groups according to blood culture results (gram positive, gram negative, fungal, and negative culture groups) and compared them. Results: a total of 158 patients were included after using the exclusion criteria, with 45 (29%) in the gram positive group, 35 (22%) in the gram negative group, 27 (17%) in the fungal group, and 51 (32%) in the negative culture group. There were no significant differences in mean gestational age, birth weight, and neonatal morbidities, except for the age of onset, which was earlier in the fungal group than other groups. White blood cell (WBC) counts were the highest in the gram negative group and the lowest in the fungal group. The mean platelet counts were the lowest in the fungal group. C-reactive protein (CRP) levels were the highest in the gram negative group, while glucose was the highest in the fungal group. Conclusions: in conclusion, we showed that there are some differences in laboratory findings, according to causative microorganisms in the nosocomial sepsis of ELBW infants. Increased WBC and CRP were associated with gram negative infection, while decreased platelet and glucose level were associated with fungal infection. These data may be helpful for choosing empirical antibiotics when sepsis is suspected.

Microsatellite Instability, Epstein–Barr Virus, and Programmed Cell Death Ligand 1 as Predictive Markers for Immunotherapy in Gastric Cancer

Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers—microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein–Barr encoding region (EBER)—were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy.

Anti-CCP antibody in rheumatoid arthritis patients and its relation with severity of the disease

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic and erosive polyarthritis causing irreversible joint disability. It is the most common persistent inflammatory arthritis, affecting from 0.5 to 1% of the general population worldwide. Antibodies to citrullinated proteins (anti-CCP antibody) have been described in patients with RA and these appear to be the most specific marker of the disease. Methods: This cross-sectional study was carried out at department of medicine, Sher-E-Bangla Medical College Hospital, Barisal Form July’ 2016 to December’ 2016. All rheumatoid arthritis patients attending at OPD and those got admitted under Medicine Dept, who was satisfying the inclusion and exclusion criteria were included consecutively and purposively in this study. Results: Total 70 cases were included; the mean age was found 46.57±13.10 years in anti-CCP antibody positive group and 44.19±11.21 years in anti-CCP antibody negative group. Female were predominant in both groups. Duration of disease was around 8 years in both groups. Mean ESR was 29.0±22.0 mm in anti-CCP antibody positive group and 12.25±10.6 mm in anti-CCP antibody negative group. Mean rheumatoid factor was 189.4±102.1 U/L in anti-CCP antibody positive group and 66.5±36.0 U/L in anti-CCP antibody negative group. Mean DAS 28 score was 4.6±1.4 and 3.6±1.3 in anti-CCP antibody positive and negative group respectively. The mean difference was statistically significant (p<0.05) between the groups. Patients in disease remission had lower anti-CCP antibody titer than those with low, moderate or high disease activity. Significantly positive correlation (r=0.596; p=0.001) between severity of rheumatoid arthritis and anti CCP antibody level was observed. Conclusion: In RA patients’ disease was more severe in anti-CCP antibody positive group and significantly positive correlation between anti-CCP antibody level with disease severity of RA was observed. BIRDEM Med J 2022; 12(1): 36-40

Observation of hyaloid artery remnants in premature infants

AIM: To observe the hyaloid artery remnants in the eyes of premature infants. METHODS: This retrospective study recruited premature infants who consecutively attended the Tongji Hospital for retinopathy of prematurity screening from May 2018 to November 2018. The binocular indirect ophthalmoscope was used for examination. RESULTS: In total, 60 cases were pulled for data analysis. The cases were categorized as having the following condition: hyaloid artery remnants positive or hyaloid artery remnants negative. It was showed that the remnants positive group had significant lower gestational age and birth weight than those of the negative group (P<0.05). There was no significant difference in gender, labor presentation and retinopathy of prematurity between the two groups (P>0.05). The hyaloid artery remnants completely regressed in all the follow-up cases. The range of disappearing time of hyaloid artery remnants was 37-44wk of corrected gestational age. CONCLUSION: The hyaloid artery remnants in preterm infants are most likely to be physiological residues. Younger or lower weight premature infants will have higher positive detection rates of hyaloid artery remnants. It seems like co-existence with retinopathy of prematurity (ROP) has no significant association with the detection of hyaloid artery remnants. When the corrected gestational age extends over 43wk, if the hyaloid artery remnants don’t regress, there is a possibility of pathological changes, and appropriate interventions should be selected according to the severity of the lesions.

Gut Microbiome Profiles in Colonizations with the Enteric Protozoa Blastocystis in Korean Populations

The influence of unicellular eukaryotic microorganisms on human gut health and disease is largely unexplored. Blastocystis species commonly colonize the gut, but their clinical significance and ecological role are unclear. We evaluated the effect of Blastocystis colonization on the fecal microbiota of Koreans. In total, 39 Blastocystis-positive and -negative fecal samples were analyzed. The fecal microbiome was assessed by targeting the V3–V4 region of the bacterial 16S ribosomal gene. Bacterial diversity was greater in the Blastocystis-positive than in the Blastocystis-negative group. The bacterial community structure and phylogenetic diversity differed according to the presence of Blastocystis. The mean proportions of Faecalibacterium species and Ruminococcaceae were larger in the Blastocystis-positive group, and that of Enterococcus species was larger in the Blastocystis-negative group. Linear discriminant analysis showed that Faecalibacterium, Prevotella 9, Ruminococcaceae UCG-002, Muribaculaceae, Rikenellaceae, Acidaminococcaceae, Phascolarctobacterium, and Ruminococcaceae UCG-005 were highly enriched in the Blastocystis-positive group, whereas Enterococcus hirae, Enterococcus faecalis, Enterococcus durans, Enterococcaceae, Lactobacillales, and Bacilli were highly abundant in the Blastocystis-negative group. Overall, our results enlighten the notion that Blastocystis colonization is associated with a healthy gut microbiota.

Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group

PurposeTo analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value.MethodA total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers.ResultsIn total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age &lt;1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P&lt;0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD &lt; 0.1%, and D33 MRD &lt; 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P&lt;0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age &lt;1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P&lt;0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children.ConclusionsETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.

Disease-modifying immune-modulatory effects of the N-163 strain of Aureobasidium pullulans-produced 1,3-1,6 Beta glucans in young boys with Duchenne muscular dystrophy: Results of an open-label, prospective, randomized, comparative clinical study

Background: Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder causing progressive muscle weakness and premature death. Steroids remain the mainstream approach for supportive care but have side effects; other targeted therapies and gene therapies are also being developed. As there is limited evidence on the use of disease modifying nutritional supplement adjuncts in DMD, this pilot trial is to evaluate the effects of supplementation of Aureobasidium pullulans-derived 1,3 1,6 beta glucan from the N163 strain in young patients with DMD. Methods: Twenty-seven patients with Duchenne muscular dystrophy (DMD), nine in the control arm (undergoing conventional therapies) participated. The patients were divided into groups: those not administered steroids (Steroid negative) (n = 5), those administered steroids (Steroid positive) (n = 4), and 18 in the treatment arm (N163 beta glucan supplement along with conventional therapies; N-163 Steroid negative and N-163 Steroid positive); they participated in the study for 45 days. Assessments of muscle function, disease status, and levels of IL6, IL13, TGF beta;, creatinine kinase (CK), titin, TNF Alpha;, haptoglobin, and dystrophin in the blood and myoglobin in the urine were performed at baseline and at the end of the study. Results: IL6 showed a significant decrease in the N163 Steroid negative group, from a baseline value of 7.2 pg/ml to 2.7 pg/ml. IL13 decreased in both treatment groups, from 157.76 pg/ml to 114.08 pg/ml (N-163 Steroid negative) and from 289.56 pg/ml to 255.56 pg/ml (N-163 Steroid positive). TGF beta levels showed a significant decrease in the N163 Steroid negative group, from a baseline value of 3302 ng/ml to 1325.66 ng/ml post intervention. Dystrophin levels increased by up to 32% in both Steroid positive and negative groups. Medical research council (MRC) grading showed muscle strength improvement in 12 out of 18 patients (67%) in the treatment group and four out of nine (44%) subjects in the control group. Conclusion: Supplementation with the N163 beta glucan food supplement produced disease-modifying beneficial effects: a significant decrease in inflammation and fibrosis markers, increase in dystrophin and improvement in muscle strength in DMD subjects over 45 days, thus making this a potential adjunct treatment for DMD after validation. A longer duration of follow up and further research on the mechanism of action and commonalities with other diseases provoked by hyperactive inflammation and/or fibrosis may pave the way for their extended applications in other dystrophinopathies and neuroinflammatory diseases.

Negative partisanship is not more prevalent than positive partisanship

The dominant narrative among scholars and political pundits characterizes American partisanship as overwhelmingly negative --- portraying citizens as more repelled by the opposing party than attached to their own party. To assess the valence of partisan identity, we use novel measures, several new and existing nationally representative surveys, and behavioral outcomes obtained from two experiments. Our findings consistently depart from the negative partisanship narrative. For the majority of Americans, partisanship is either equally positive and negative or more positive than negative. Only partisan leaners stand out as negative partisans. We pair these observational findings with experimental data that differentiate between positive group behavior and negative group behavior in the partisan context. We find that the behavioral manifestations of party identity similarly include both positive and negative biases in balance, reinforcing our conclusion that descriptions of partisanship as primarily negative are exaggerated.

Immunogenicity after Second ChAdOx1 nCoV-19 (AZD1222) Vaccination According to the Individual Reactogenicity, Health Status and Lifestyle

The immune-acquired responses after vaccination vary depending on the type of vaccine and the individual. The purpose of this study was to investigate the relationship between the acquisition of immunity and the side effects, health status, and lifestyle after completion of the second dose of AZD1222. Blood samples were collected after a second dose of AZD1222. The Euroimmun Anti-SARS-CoV-2 ELISA (IgG) for anti-S1 antibody, the cPASS SARS-CoV-2 neutralizing antibody detection kit for the surrogate virus neutralization test, and the T-spot Discovery SARS-CoV-2 kit were used to identify cellular immunogenicity. Patient experience of adverse effects was investigated using questionnaires. Information on health status and lifestyle were collected from the most recent health checkup data. Generally, females experience more reactogenicity in both intensity and duration. The rash of the first shot and chills of the second shot were associated with humoral immunity. However, comprehensive adverse effects had no correlation with humoral and cellular immunity. The T-spot-positive group had a higher creatinine level, which reflects muscle mass, than the T-spot-negative group. Males presented a higher level of T-spot assays. Body mass index and age were negatively correlated with the T-spot assay and anti-S1 antibody, respectively. Immune acquisition after the second AZD1222 shot was not associated with reactogenicity. However, individuals’ sex, age, and BMI were found to be associated with immunogenicity after vaccination.