Severe Clinical Symptoms Research Articles

Development and analysis of a comprehensive diagnostic model for aortic valve calcification using machine learning methods and artificial neural networks.

Although advanced surgical and interventional treatments are available for advanced aortic valve calcification (AVC) with severe clinical symptoms, early diagnosis, and intervention is critical in order to reduce calcification progression and improve patient prognosis. The aim of this study was to develop therapeutic targets for improving outcomes for patients with AVC. We used the public expression profiles of individuals with AVC (GSE12644 and GSE51472) to identify potential diagnostic markers. First, the R software was used to identify differentially expressed genes (DEGs) and perform functional enrichment analysis. Next, we combined bioinformatics techniques with machine learning methodologies such as random forest algorithms and support vector machines to screen for and identify diagnostic markers of AVC. Subsequently, artificial neural networks were employed to filter and model the diagnostic characteristics for AVC incidence. The diagnostic values were determined using the receiver operating characteristic (ROC) curves. Furthermore, CIBERSORT immune infiltration analysis was used to determine the expression of different immune cells in the AVC. Finally, the CMap database was used to predict candidate small compounds as prospective AVC therapeutics. A total of 78 strong DEGs were identified. The leukocyte migration and pid integrin 1 pathways were highly enriched for AVC-specific DEGs. CXCL16, GPM6A, BEX2, S100A9, and SCARA5 genes were all regarded diagnostic markers for AVC. The model was effectively constructed using a molecular diagnostic score system with significant diagnostic value (AUC = 0.987) and verified using the independent dataset GSE83453 (AUC = 0.986). Immune cell infiltration research revealed that B cell naive, B cell memory, plasma cells, NK cell activated, monocytes, and macrophage M0 may be involved in the development of AVC. Additionally, all diagnostic characteristics may have varying degrees of correlation with immune cells. The most promising small molecule medicines for reversing AVC gene expression are Doxazosin and Terfenadine. It was identified that CXCL16, GPM6A, BEX2, S100A9, and SCARA5 are potentially beneficial for diagnosing and treating AVC. A diagnostic model was constructed based on a molecular prognostic score system using machine learning. The aforementioned immune cell infiltration may have a significant influence on the development and incidence of AVC.

Epidemiological and Clinical Characteristics of Patients with Dengue Fever in a Recent Outbreak in Oman: A Single Center Retrospective-cohort Study.

Dengue fever (DF) is the most common arthropod-borne viral illness with significant public health implications that can cause severe clinical symptoms and possibly death. We sought to determine the epidemiological and clinical characteristics of patients presented with DF to the Royal Hospital in a recent outbreak in Oman. We conducted a retrospective cohort study between 1 January and 18 April 2022, at the Royal Hospital, Oman, including all patients who presented with febrile illness and laboratory-confirmed DF. Descriptive statistics were used to summarize the results. The cohort included 58 patients with laboratory-confirmed DF, of whom 39 (67.2%) required admission. The overall mean age was 41.0±20.0 years. Over half (55.2%) were females and the majority (86.2%) were Omani citizens. Eighty-one percent of the patients were residents of Bawshar in Muscat governorate. Dengue virus 2 was the isolated serotype. Fever (98.3%), muscular aches and pains (55.2%), and headache (53.4%) were the most common symptoms on presentation. All patients except two had no travel history. The most common comorbidities were hypertension (29.3%) and diabetes mellitus (17.2%). Upon admission, the most prominent hematological and biochemical abnormalities were severe thrombocytopenia (31.0%) with platelet counts of < 50 000/mm3 and hepatic impairment (15.5%). Antibiotics were prescribed to 27.6% of the patients. All patients improved clinically, and no deaths were reported during the study period. Fever and thrombocytopenia were the commonest presentations of DF. Identification of factors linked to increased risk of hospitalization in patients with DF can assist in recognizing individuals who need close monitoring and intensive support.

Clinical and laboratory profile and outcomes of hospitalized COVID-19 patients with type 2 diabetes mellitus in Ghana - Asingle-center study.

In sub-Saharan Africa and particularly in Ghana, there is scarcity of published literature specifically on the impact of DM on outcomes in COVID-19 patients. Based on the difference in genetic makeup and demographic patterns in Africans compared to the Western world and with the rising burden of DM and other non-communicable diseases in Ghana there is a need to define the impact DM has on persons with COVID-19. This would ensure adequate risk stratification and surveillance for such patients as well as appropriate scale up of therapeutic management if needed. This single-center study describes the clinical and laboratory profile and outcomes of COVID-19 in-patients with type 2 diabetes mellitus (DM) in Ghana. Retrospective analysis was undertaken of the medical records of adults with COVID-19 hospitalized at a facility in Ghana from March to October 2020. Clinical, laboratory and radiological data and outcomes were analysed. Comparisons between COVID-19 patients with DM and non-diabetics were done with an independent t-test or a Mann-Whitney test when normality was not attained. Odds ratios (95% CI) were calculated using univariate logistic regression. Out of 175 COVID-19 patients, 64 (36.6%) had DM. Overall mean age was 55.9 ± 18.3 years; DM patients were older compared to non-diabetics (61.1 ± 12.8 vs. 53.0 ± 20.2 years, p=.049). Compared to non-diabetics, diabetics were more likely to have higher blood glucose at presentation, have hypertension, be on angiotensin 2 receptor blockers [OR, 95% CI 3.3 (1.6-6.7)] and angiotensin converting enzyme inhibitors [OR, 95% CI 3.1 (1.3-7.4)]; and be HIV negative (p < .05). Although the values were normal, diabetics had a higher platelet count but decreased lymphocytes, aspartate transaminase and alkaline phosphatase compared to non-diabetics (p < .05). There was no difference in clinical symptoms, severity or mortality between the two groups. The clinical profile of patients studied are similar to prior studies. However the outcome of this study showed that DM was not associated with worse clinical severity and in-hospital mortality. This could have been due to majority of DM patients in this study having relatively good blood glucose control on admission. Secondly, DM alone may not be a risk factor for mortality. Rather its concurrent existence with multiple co-morbidities (especially cardiovascular co-morbidities which may predispose to pro-inflammatory and pro-thrombotic states) may be driving the rise in severity and mortality risks reported in other studies. Furthermore, this study was conducted among an African population and Africa has been shown to be generally less severely hit by the COVID-19 pandemic compared to other regions outside the continent. This has been postulated to be due, among other factors, to inherent protective mechanisms in Africans due to early and repeated exposure to parasitic and other organisms resulting in a robust innate immunity. This study suggested that DM was not associated with more severe clinical symptoms or worse outcomes among hospitalized COVID-19 patients. Despite this, it is important that DM patients adhere to their therapy, observe the COVID-19 containment protocols and are prioritized in the administration of the COVID-19 vaccines. In this retrospective, single-centre study on the clinical and laboratory profile and outcome of hospitalized DM patients with COVID-19, patients with DM did not have a more severe clinical profile or worse outcomes. They were, however, significantly older, more likely to have higher admission blood glucose, have hypertension, be on angiotensin 2 receptor blockers and angiotensin converting enzyme inhibitors; and be HIV negative compared to the cohort without DM. DM patients should be a priority group for the COVID-19 vaccines.

Inflammation in COVID-19: A Risk for Superinfections

The worldwide coronavirus pandemic has been one of the most significant health crisis threats in recent years. COVID-19 has not been the only cause of mortality in this pandemic. A dangerous but frequent complication of viral infections is secondary superinfection or superimposed bacterial infection. Despite lacking data on the prevalence, microbiology, and outcomes of co-infection and superinfection, limited publications have reported the high incidence of severe infection in COVID-19 patients and its effect on mortality. Those who have severe clinical symptoms of the disease, and others requiring prolonged stay in intensive care units (ICU), are more susceptible to developing superinfections by nosocomial pathogens. Ventilator-acquired pneumonia (VAP) is the most common type of infection observed among COVID-19 patients, followed by bacteraemia with sepsis, and urinary tract infections (UTI). There is an urgent need for prospective studies to provide epidemiological, clinical, and microbiological data on superinfections, which can be used to form effective antimicrobial guidelines that could have an important role in disease outcomes.

Hypoxia in A Patient with Anti-p200 Pemphigoid under Combined Dapsone and Pantoprazole Treatment

A 70-year-old male patient was admitted to our dermatology outpatient clinic with newly developed personality changes and signs of hypoxemia. His anti-p200 Pemphigoid was treated with Dapsone for a few weeks. Due to generalized tonic-clonic seizure with a subsequent Glasgow Coma Scale of 5 points and a peripheral oxygen saturation not exceeding 88% under conditions of high-flow nasal cannula, he was intubated by the emergency team and transferred to the intensive care unit. Comprehensive tests were performed, but Dapsone-induced methemoglobinemia remained the exclusive explanation for the observed scenario, although arterial MetHb analysis showed a peak value of only 6%. The patient recovered shortly after repeated infusions of Methylene blue and Ascorbate, and cessation of Dapsone. We provide an overview of the pathophysiology, diagnostic procedures, and possible explanations for this case of Dapsone-induced methaemoglobinaemia. In conclusion, our case report provides evidence that even mild chronic methemglobinemia can induce severe clinical symptoms.

Inborn Errors of Metabolism Screening in Neonates: Current Perspective with Diagnosis and Therapy.

Inborn errors of metabolism (IEMs) are rare hereditary or acquired disorders resulting from an enzymatic deformity in biochemical and metabolic pathways influencing proteins, fats, carbohydrate metabolism, or hampered some organelle function. Even though individual IEMs are uncommon, together, they represent a diverse class of genetic diseases, with new issues and disease mechanisms being portrayed consistently. IEM includes the extraordinary multifaceted nature of the fundamental pathophysiology, biochemical diagnosis, molecular level investigation, and complex therapeutic choices. However, due to the molecular, biochemical, and clinical heterogeneity of IEM, screening alone will not detect and diagnose all illnesses included in newborn screening programs. Early diagnosis prevents the emergence of severe clinical symptoms in the majority of IEM cases, lowering morbidity and death. The appearance of IEM disease can vary from neonates to adult people, with the more serious conditions showing up in juvenile stages along with significant morbidity as well as mortality. Advances in understanding the physiological, biochemical, and molecular etiologies of numerous IEMs by means of modalities, for instance, the latest molecular-genetic technologies, genome engineering knowledge, entire exome sequencing, and metabolomics, have prompted remarkable advancement in detection and treatment in modern times. In this review, we analyze the biochemical basis of IEMs, clinical manifestations, the present status of screening, ongoing advances, and efficiency of diagnosis in treatment for IEMs, along with prospects for further exploration as well as innovation.

Association of cortical thickness and cognition with schizophrenia treatment resistance.

Approximately a third of patients with schizophrenia fail to adequately respond to antipsychotic medications, a condition known as treatment resistance (TR). We aimed to assess cognitive and cortical thickness deficits and their relationship to TR in schizophrenia. We recruited patients with schizophrenia (n = 127), including patients at treatment initiation (n = 45), treatment-responsive patients (n = 40) and TR patients (n = 42), and healthy controls (n = 83). Clinical symptoms, neurocognitive function, and structural images were assessed. We performed group comparisons, and explored association of cortical thickness and cognition with TR. The TR patients showed significantly more severe clinical symptoms and cognitive impairment relative to the treatment-responsive group. Compared to healthy controls, 56 of 68 brain regions showed significantly reduced cortical thickness in patients with schizophrenia. Reductions in five regions were significantly associated with TR (reduction in TR relative to treatment-responsive patients), i.e. in the right caudal middle frontal gyrus, superior frontal cortex, fusiform gyrus, pars opercularis of the inferior frontal cortex, and supramarginal cortex. Cognition deficits were also significantly correlated with cortical thickness in these five regions in patients with schizophrenia. Cortical thickness of the right caudal middle frontal gyrus, superior frontal cortex and pars opercularis of the inferior frontal cortex also significantly mediated effects of cognitive deficits on TR. Treatment resistance in schizophrenia was associated with reduced thickness in the right caudal middle frontal gyrus, superior frontal cortex, fusiform gyrus, pars opercularis of the inferior frontal cortex, and supramarginal cortex. Cortical abnormalities further mediate cognitive deficits known to be associated with TR.

Comparison of clinical severity, genotype and toxin gene expression of binary toxin-producing Clostridioides difficile clinical isolates in Japan.

The emerging Clostridioides difficile strain BI/NAP1/027 has been reported to be associated with more severe clinical symptoms and higher mortality rates, thought in part due to production of a novel binary toxin alongside conventional A and B toxins. However, recent studies suggest that this may not always be the case. Therefore, the purpose of this report was to investigate the correlation between clinical severity and microbiological characteristics of CDT-producing C. difficile isolates in Japan. Eight Japanese isolates of CDT producing C. difficile were investigated using genotyping, cytotoxic activity assays and toxin gene expression. Correlation with clinical severity was performed retrospectively using the patient record. Three of eight patients were assessed as having severe C. difficile infection (CDI). PCR ribotyping resolved six ribotypes including ribotype 027. No specific genes were identified determining severe compared with non-severe cases. Positive correlation of expression levels of tcdA, tcdB and cdtB were observed although these expression levels were not correlated with cytotoxicity. CDI severity index neither correlated with toxin gene expression level nor cytotoxicity. These data indicate that the possession of the CDT gene and toxin gene expression levels may not relate to C. difficile cytotoxicity or clinical severity.

Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts.

Purpose of reviewThis review aims to describe clinical and histological features, treatment, and prognosis in patients with anti-signal recognition particle (SRP) autoantibodies positive immune-mediated necrotizing myopathy (SRP-IMNM) based on previous findings.Previous findingsAnti-SRP autoantibodies are specific in IMNM. Humoral autoimmune and inflammatory responses are the main autoimmune characteristics of SRP-IMNM. SRP-IMNM is clinically characterized by acute or subacute, moderately severe, symmetrical proximal weakness. Younger patients with SRP-IMNM tend to have more severe clinical symptoms. Patients with SRP-IMNM may be vulnerable to cardiac involvement, which ought to be regularly monitored and cardiac magnetic resonance imaging is the recommended detection method. The pathological features of SRP-IMNM are patchy or diffuse myonecrosis and myoregeneration accompanied by a paucity of inflammatory infiltrates. Endoplasmic reticulum stress-induced autophagy pathway and necroptosis are activated in skeletal muscle of SRP-IMNM. Treatment of refractory SRP-IMNM encounters resistance and warrants further investigation.SummaryAnti-SRP autoantibodies define a unique population of IMNM patients. The immune and non-immune pathophysiological mechanisms are involved in SRP-IMNM.

Does the Augmentation of Trauma Informed Hatha Yoga Increase the Effect of Dialectical Behavior Therapy for Substance Use Disorders on Psychopathological Strain of Patients with Borderline Personality Disorder and Comorbid Substance Use Disorder? Results of a Quasi-Experimental Study

Background: Borderline personality disorder (BPD) is one of the most common personality disorders among persons with substance use disorders (SUDs) and is characterized by severe clinical symptoms. The aim of this study was to investigate if the effect of dialectical behavior therapy for substance use disorders (DBT-S) inpatient treatment on psychopathological symptom load in patients suffering from both BPD and SUD can be augmented by weekly 60-min “Trauma Informed Hatha Yoga” sessions. Materials and Methods: Thirty-nine patients suffering from comorbid BPD and SUD were consecutively in time included in this quasi-experimental pilot study (first intervention then control group). In the intervention group, weekly Trauma Informed Hatha Yoga sessions were added to standard DBT-S for 8 weeks. The participants of the control group received standard DBT-S. All participants completed several self-report questionnaires to assess symptoms of depression, anxiety, symptoms of BPD, and their subjective stress perception at three points in time during the study course. Results: A repeated measures analysis of variance with patients’ psychopharmacological medication as covariate revealed a significant main effect of time for each of the psychometric scales (State and Trait Anxiety Inventory subscale for state anxiety [STAI-S] p = 0.001, Beck Depression Inventory [BDI] p < 0.001; Borderline Symptom List 23 [BSL] p = 0.036) indicating that the psychopathological symptom load of the patients was significantly lower at the end of the DBT-S therapy compared to the beginning in both study groups. Moreover, there was a significant interaction effect of group*time on the psychometric scales STAI-T (subscale for trait anxiety) sum score (p = 0.010) and the sum score of the Perceived Stress Scale (PSS) (p = 0.043). This was expressed by the fact that the participants of the intervention group showed a significant reduction of the STAI-T sum score as well as the sum score of the Perceived Stress Scale (PSS), while the control group did not. Due to the exploratory nature of this study, correction for multiple testing was omitted. Conclusion: Although they are very preliminary, our results suggest that practicing Trauma Informed Hatha Yoga on a regular basis in addition to DBT-S inpatient treatment seems to reduce the level of trait anxiety and perceived stress significantly more than DBT-S inpatient treatment alone. Nevertheless, the effectiveness of Trauma Informed Hatha Yoga in reducing trait anxiety and perceived stress in patients suffering from SUD und BPD must be tested in large randomized controlled trials.

Impact of SARS-CoV-2 infection on the profiles and responses of innate immune cells after recovery.

BackgroundsSARS-CoV-2 infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic to severe symptoms and death. Most COVID-19 pathogenesis is associated with hyperinflammatory conditions driven primarily by myeloid cell lineages. The long-term effects of SARS-CoV-2 infection post recovery include various symptoms.MethodsWe performed a longitudinal study of the innate immune profiles 1 and 3 months after recovery in the Thai cohort by comparing patients with mild, moderate, and severe clinical symptoms using peripheral blood mononuclear cells (n = 62).ResultsSignificant increases in the frequencies of monocytes compared to controls and NK cells compared to mild and moderate patients were observed in severe patients 1–3 months post recovery. Increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were observed in all recovered patients, even after 3 months. Increased IL-6 and TNFα levels in monocytes were observed 1 month after recovery in response to lipopolysaccharide (LPS) stimulation, while decreased CD86 and HLA-DR levels were observed regardless of stimulation. A multiplex analysis of serum cytokines performed at 1 month revealed that most innate cytokines, except for TNFα, IL4/IL-13 (Th2) and IFNγ (Th1), were elevated in recovered patients in a severity-dependent manner. Finally, the myelopoiesis cytokines G-CSF and GM-CSF were higher in all patient groups. Increased monocytes and IL-6- and TNFα-producing cells were significantly associated with long COVID-19 symptoms.ConclusionsThese results reveal that COVID-19 infection influences the frequencies and functions of innate immune cells for up to 3 months after recovery, which may potentially lead to some of the long COVID symptoms.

Synergistic pathogenicity by coinfection and sequential infection with JXA1-like HP-PRRSV and PCV2d in PCV2 antibody-positive post-weaned pigs

Porcine reproductive and respiratory syndrome virus (PRRSV) and Porcine circovirus (PCV) are two important pathogens, which caused respiratory disease in pigs. PRRSV and PCV2 had caused great economic losses to the pig industry. Pigs coinfection with PCV2 and PRRSV were common in the clinic, PCV2 antibodies can be detected in most of the pigs. PCV2d and HP-PRRSV(JXA1-like) were two major viruses circulating in the pigs in China. In this study, HP-PRRSV (JXA1-like) and PCV2d were used to coinfect and (or) sequential infect 5-week-old weaned PCV2-antibody positive pigs and the clinical indications, pathological, virus load, and specific antibodies of the challenged post-weaned piglets were evaluated. Thirty 5-week-old post-weaned pigs were divided into six groups infected with PBS, PCV2, PRRSV, PCV2-PRRSV, PRRSV-PCV2, and Co-PRRSV-PCV2 according to the PCV2 specific antibodies. Pigs infected with PRRSV can experience diarrhea, increased body temperature, weight loss, and even death. The pigs in the PRRSV infected group and PRRSV-PCV2 infected group showed severe clinical symptoms, high mortality, and low average daily gain. The main pathological changes were widening of the lung interstitium, lung adhesion, and so on. The PRRSV-PCV2 infected group showed high levels of TNF-α and IL-2. In conclusion, PRRSV and PRRSV-PCV2 sequential infected pigs showed most pathogenic signs, and PCV2-PRRSV sequential infected pigs showed less pathogenicity than pigs of PCV2 and PRRSV coinfection and PRRSV monoinfection from day 10–14, partially suppressing the cytokine storm produced by PRRSV.

Correlation of antigen-specific immune response with disease severity among COVID-19 patients in Bangladesh.

Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM+ (both OX40+CD137+ and OX40+CD40L+) CD4+ T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIMs (CD137+CD69+), which indicates the exhaustion of CD8+ T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2.

Dynamic magnetic resonance imaging findings in the early stages of neonatal hypoglycemic brain injury.

Neonatal hypoglycemic brain injury was most common in the occipital lobes. Severe clinical symptoms were significantly associated with extensive brain injury involving the internal capsule, basal ganglia, and thalamus, which could be attributed to hypoxia-ischemia and lead to a poor prognosis. •There is no clear neurological safe threshold for hypoglycemia in neonates. Studies suggest that symptomatic hypoglycemia can be related tobrain injury. •Severe clinical symptoms are significantly associated with extensive brain injury on MRI scans. Extensive brain injuries involving the internal capsule, basal ganglia, and thalamus, which could be due to associated hypoxia-ischemia and lead to a poor prognosis.

Isolated adrenocorticotropic hormone deficiency associated with sintilimab therapy in a patient with advanced lung adenocarcinoma: a case report and literature review

BackgroundSeveral immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy.Case presentationA 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level.ConclusionsOur patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.

(NZW × BXSB) F1 male mice: An unusual, severe and fatal mouse model of lupus erythematosus.

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune/inflammatory disease. The heterogeneity and complexity of clinical presentation has made it challenging to study or treat this syndrome. The (NZW×BXSB) F1 lupus-prone male mouse model of this disease is potentially useful to study mechanism and treatment modalities, but there is a lack of information about this model’s characterization and disease progression. Therefore, the aim was to examine this lupus model’s physical/clinical disease presentation and its immunological status.Materials and methodsClinical and physical status were observed in 8- and 16-week-old male and female (± 1 week) (NZW/LacJ x BXSB/MpJ) F1 mice (n = 8 per group). Young males (8 ± 1 week) without disease and female (16 ± 1 week) mice served as controls. Physical changes, quantitative values of autoantibodies, and blood cell parameters were determined. Necropsy and post-mortem histopathology were also performed.ResultsWith aging (≥ 12 weeks), significant increases in severe abdominal distension/swelling, inability to walk, paleness of paws and significant weight increase were observed compared to controls (p < 0.05). The necropsy examination showed abdominal distension associated with serous effusion and histological examination identified severe edema and multi-organ abnormalities (spleen, lymph nodes, and kidney). Significant increases in anti-double-stranded DNA antibody (anti-dsDNA) was seen in old/sick compared to female (p = 0.0002) or young male (p = 0.0036) mice. Old mice developed immune thrombocytopenia compared to female (p = 0.0056) and young male (p = 0.0007) mice. Anti-platelet was detectable in old, sick mice. The mortality rate increased with aging; more than 35% of male mice died during this study between the ages of 13-18 weeks.ConclusionWe found that the (NZW/LacJ x BXSB/MpJ) F1 male mice spontaneously exhibit, over varying lengths of time, extremely severe and fatal clinical disease symptoms. This model may be too severe to be helpful in investigating SLE and testing potential treatment modalities.

A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (β=-0.521, P=0.036); patients aged ≥64 years had lower PCS than those aged<55 years (β=-0.636, P=0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (β=1.063, P<0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (β=-0.860, P=0.002), while the PCS of those with severe clinical symptoms was much lower (β=-1.126, P<0.001). Patients treated with combination therapy had higher PCS than untreated patients (β=0.731, P=0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (β=-0.712, P=0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (β=-1.183, P=0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

Does potential antibody-dependent enhancement occur during SARS-CoV-2 infection after natural infection or vaccination? A meta-analysis

Coronavirus disease 2019 (COVID-19) continues to constitute an international public health emergency. Vaccination is a prospective approach to control this pandemic. However, apprehension about the safety of vaccines is a major obstacle to vaccination. Amongst health professionals, one evident concern is the risk of antibody-dependent enhancement (ADE), which may increase the severity of COVID-19. To explore whether ADE occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and increase confidence in the safety of vaccination, we conducted a meta-analysis to investigate the relationship between post-immune infection and disease severity from a population perspective. Databases, including PubMed, EMBASE, Chinese National Knowledge Infrastructure, SinoMed, Scopus, Science Direct, and Cochrane Library, were searched for articles on SARS-CoV-2 reinfection published until 25 October 2021. The papers were reviewed for methodological quality, and a random effects model was used to analyse the results. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated using a funnel plot and Egger’s test. Eleven studies were included in the final meta-analysis. The pooled results indicated that initial infection and vaccination were protective factors against severe COVID-19 during post-immune infection (OR = 0.55, 95%CI = 0.31–0.98). A subgroup (post-immune infection after natural infection or vaccination) analysis showed similar results. Primary SARS-CoV-2 infection and vaccination provide adequate protection against severe clinical symptoms after post-immune infection. This finding demonstrates that SARS-CoV-2 may not trigger ADE at the population level.

Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis.

Infectious mononucleosis (IM) is an acute syndrome mostly associated with primary Epstein-Barr virus (EBV) infection. The main clinical symptoms include irregular fever, lymphadenopathy, and significantly increased lymphocytes in peripheral blood. The pathogenic mechanism of IM is still unclear; there is no effective treatment method for it, with mainly symptomatic therapies being available. The main question in EBV immunobiology is why only a small subset of infected individuals shows severe clinical symptoms and even develop EBV-associated malignancies, whilemost individuals are asymptomatic for life with the virus. B cells are first involved in IM because EBV receptors are presented on their surface. Natural killer (NK) cells are cytotoxic innate lymphocytes that are important for killing EBV-infected cells. The proportion of CD4+ T cells decreases while that of CD8+ T cells expands dramatically during acute EBV infection, and the persistence of CD8+ T cells is important for lifelong control of IM. Those immune cells play important roles in IM, and their functions need to be identified separately. For this purpose, monocytes are separated first from peripheral blood mononuclear cells (PBMCs) of IM individuals using CD14 microbeads, a column, and a magnetic separator. The remaining PBMCs are stained with peridinin-chlorophyll-protein (PerCP)/Cyanine 5.5 anti-CD3, allophycocyanin (APC)/Cyanine 7 anti-CD4, phycoerythrin (PE) anti-CD8, fluorescein isothiocyanate (FITC) anti-CD19, APC anti-CD56, and APC anti-CD16 antibodies to sort CD4+ T cells, CD8+ T cells, B cells, and NK cells using a flow cytometer. Furthermore, transcriptome sequencing of five subpopulations was performed to explore their functions and pathogenic mechanisms in IM.

Presence of Varicella Zoster Virus DNA in Saliva May Be Associated with the Severity of Ramsay Hunt Syndrome.

Background: The relationship between varicella zoster virus (VZV) collected from saliva and Ramsay Hunt syndrome (RHS) remains unclear. Therefore, this study aimed to investigate whether VZV DNA in saliva alters the clinical symptoms and prognosis of RHS. Methods: To measure the severity of clinical symptoms of 100 RHS patients, the initial House–Brackmann (HB) grade and associated symptoms were evaluated. The final HB grade at the end of treatment was measured to determine the prognosis. Electroneurography (ENoG) was performed on four facial muscles, including the frontalis, oculi, nasalis, and oris. Results: Salivary VZV DNA was isolated from 72 patients with RHS. The VZV DNA-positive group was 34.023 times more likely to have severe initial HB grade than the control group (95% CI, 3.21–359.68; p = 0.003). There were no significant differences in final HB grade. All ENoG values of the VZV DNA-positive group were significantly higher than those of the control group (frontalis, p = 0.003; oculi, p = 0.001; nasalis, p < 0.001; oris, p = 0.037). Conclusions: RHS patients with salivary VZV DNA have more severe clinical symptoms than the control group. There were no differences in prognosis and associated symptoms. A VZV DNA test using saliva samples of patients with RHS can evaluate the clinical symptoms and provide early confirmation of VZV infection, enabling timely treatment in a non-invasive way.