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Background: The outbreak of coronavirus disease 2019 (COVID-19) has posed a huge threat to human health. However, little is known regarding the risk factors associated with COVID-19 severity. We aimed to explore early-stage disease risk factors associated with eventual disease severity. Methods: This study enrolled 486 hospitalized, non-intensive care unit (ICU)-admitted adult patients with COVID-19 (age ≥ 18 years) treated at Wuhan Jinyintan Hospital, who were divided into three groups according to disease severity. The demographic, clinical, and laboratory data at admission and clinical outcomes were compared among severity groups, and the risk factors for disease severity were identified by multiple regression analysis. Results: Of 486 patients with COVID-19, 405 (83.33%) were discharged, 33 (6.71%) died outside of the ICU, and 48 (7.20%) were still being treated in the ICU by the time the study period ended. Significant differences in age, lymphocyte counts, and the levels of procalcitonin, aspartate aminotransferase, and D-dimer (P < 0.001 for all) among the three groups. Further analysis showed that older age, decreased lymphocyte counts, and increased procalcitonin, aspartate aminotransferase, and D-dimer levels were significantly associated with disease progression. Conclusion: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may impair the immune system, the blood coagulation system, and hepatic and cardiac function. Some clinical characteristics and laboratory findings can help identify patients with a high risk of disease severity, which can be significant for appropriate resource allocation during the COVID-19 pandemic.

BACKGROUND A large number of pneumonia cases due to coronavirus disease 2019 (COVID-19) have been first reported in China. Meanwhile, the virus is sweeping all around the world and has infected millions of people. Fever and pulmonary symptoms have been noticed as major and early signs of infection, whereas gastrointestinal symptoms were also observed in a significant portion of patients. The clinical investigation of disease onset was underestimated, especially due to the neglection of cases presenting with gastrointestinal symptoms. AIM To characterize the clinical features of coronavirus-infected patients with gastrointestinal symptoms as initial symptoms. METHODS This is a retrospective, single-center case series of the general consecutive hospitalized patients with confirmed COVID-19 at Wuhan Union Hospital from February 2, 2020 to February 13, 2020. According to their initial symptoms, these patients were classified into two groups. Patients in group one presented with pulmonary symptoms (PS) as initial symptoms, and group two presented with gastrointestinal symptoms (GS). Epidemiological, demographic, clinical, laboratory, and treatment data were collected for analysis. RESULTS Among the 50 patients recruited, no patient has been admitted to intensive care units, and no patient died during the study. The duration of hospitalization was longer in the GS group than in the PS group (12.13 ± 2.44 vs 10.00 ± 2.13, P < 0.01). All of the 50 patients exhibited decreased lymphocytes. However, lymphocytes in the GS group were significantly lower compared to those in the PS group (0.94 ± 0.06 vs 1.04 ± 0.15, P < 0.01). Procalcitonin and hs-CRP were both significantly higher in the GS group than in the PS group. Accordingly, the duration of viral shedding was significantly longer in the GS group compared to the PS group (10.22 ± 1.93 vs 8.15 ± 1.87, P < 0.01). CONCLUSION COVID-19 patients presenting with gastrointestinal symptoms as initial symptoms need more days of viral shedding and hospitalization than the patients presenting with pulmonary symptoms.

Here, we determined whether degree of decreased heart rate due to fingolimod treatment correlates with decreasing degree of lymphocytes in relapse-remitting multiple sclerosis (RRMS). In total, 30 patients with RRMS were treated with 0.5 mg fingolimod and their heart rate recorded every 30 minutes for 24 hours. Time trends of heart rate were characterised as three individual amplitudes and phase angles from three cosine curves using a mixed-effect model. Spearman’s correlation coefficient and regression analysis were used to determine the effect of heart rate information on change in lymphocyte count pre- and post-fingolimod treatment. Moreover, the degree of decreased lymphocytes induced by fingolimod treatment on heart rate was compared between low and high influence groups. Positive correlation between amplitude from the second curve and difference in lymphocyte number (p = 0.006) was observed. Regression analysis was also significant (p = 0.002). Moreover, the second curve derived from the high amplitude group exhibited a greater decrease in lymphocyte number after fingolimod treatment than the low amplitude group (p

ImportanceHeart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated.ObjectiveTo explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later.Design, Setting, and ParticipantsA single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020.ExposuresHigh levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; α-HBDH).Main Outcomes and MeasuresMortality in hospital and days from admission to mortality (survival days).ResultsOf 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21∼83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission (≥ 6.126 pg/mL), even within the clinical normal range (0∼28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4+ and CD8+ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and α-HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and α-HBDH on admission were associated with higher mortality. Both high LDH and α-HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days (r= -0.42, 95% CI= -0.64∼-0.12, P=0.005). LDH level on admission was negatively correlated with survival days (r= -0.35, 95% CI= -0.59∼-0.05, P=0.022).Conclusions and RelevanceHeart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury.Key pointsQuestionDoes coronavirus disease 2019 (COVID-19) cause heart injury and hereby impact mortality?FindingsIn this retrospective cohort study including 188 patients with COVID-19, patients with high levels of high-sensitivity cardiac troponin I (hs-TNI) on admission had significantly higher mortality (50.0%) than patients with moderate or low levels of hs-TNI (10.0% or 9.1%). hs-TNI level on admission was significantly negatively correlated with survival days (r= -0.42, 95% CI= -0.64∼-0.12, P=0.005).MeaningCOVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, in order to maximally prevent or rescue heart injury-related mortality in COVID-19.

Background: A new virus broke out in Wuhan, Hubei, China, that was later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical characteristics of severe pneumonia caused by SARS-CoV-2 are still not clear. Objectives: The aim of this study was to explore the clinical characteristics and risk factors of severe pneumonia caused by the SARS-CoV-2 in Wuhan, China. Methods: The study included patients hospitalized at the Central Hospital of Wuhan who were diagnosed with COVID-19. Clinical features, chronic comorbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of patients with severe pneumonia caused by SARS-CoV-2. Results: A total of 110 patients diagnosed with COVID-19 were included in the study, including 38 with severe pneumonia and 72 with nonsevere pneumonia. Statistical analysis showed that advanced age, increased D-Dimer, and decreased lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with severe pneumonia showed that the illness can progress rapidly. Conclusions: Advanced age, decreased lymphocytes, and D-Dimer elevation are important characteristics of patients with severe COVID-19. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.

Cancer-related inflammation may play an important role in disease progression and patient outcome, and could be easily monitored through indirect parameters routinely evaluated at diagnosis. Here, we investigated if peripheral blood cells and the ratios of neutrophils to lymphocytes (NLR) and of lymphocytes to monocytes (LMR) as surrogate markers of cancer related inflammation are associated with disease progression and survival of melanoma patients at any stage of the disease. Records of 1,182 melanoma patients included in an Institutional tumor registry in the period 2000-2010, were reviewed. Among them, 584 patients with a cutaneous or unknown primary melanoma and available pre-operative blood tests were analyzed. Survival was estimated with the Kaplan-Meier method, and analyzed using Log-rank test, Cox regression and multivariate Cox proportional hazard models. We found that patients presenting with distant metastases had higher leukocytes, neutrophils and monocytes, and lower lymphocytes compared to Stage I-III patients. Furthermore, at a single-patient level, hematological profiles changed on disease progression from regional to distant metastatic, with significantly increased circulating leukocytes, neutrophils and monocytes, and decreased lymphocytes. Peripheral blood cell counts were not associated with survival of patients with a localized or regionally metastasized melanoma. Instead, in Stage IV patients, leukocytes (p = 0.001), neutrophils (p = 0.0002), monocytes (p = 0.002), NLR (p

Previous studies showed contradictory results of static magnetic field (SMF) influence on behavior, hematological parameters and organ damage. The aim of this study was to investigate influence of subchronic continuous exposure to upward and downward oriented SMF of moderate intensity on behavior, hematological characteristics, heart and kidney tissue of spontaneously hypertensive rats. SH rats exposed to downward oriented SMF demonstrated lack of anxious-like behavior. SMF of either orientation caused decrease in the number of platelets in peripheral blood, granulocytes in the spleen and bone marrow and increase in the number of erythrocytes in the spleen, in both exposed groups. We also demonstrated that spontaneously hypertensive rats exposed to upward oriented SMF exhibited decreased lymphocytes count in blood, decreased bone marrow erythrocytes count and rats exposed to downward oriented SMF had increased lymphocytes count in bone marrow. The results showed adverse effect of differently oriented SMF on hematological parameters of spontaneously hypertensive rats. Also, exposure to different oriented SMF didn't affect their heart and kidney morphological characteristics.

Tuberculosis is one of the top ten death’s causes in the world and even cause more deaths than HIV in 2015. In the same years, there are 10.4 million new TB case incidences with case notification rate is 142/100,000 population globally. Monocytes and lymphocytes play an important role in the body’s defense mechanism against tuberculosis. Tuberculosis can induce increased monocytes and decreased lymphocytes. The ratio of Monocytes to lymphocytes is expected to be used as predictors of tuberculosis. Therefore, this study was conducted to determine the ratio of monocytes to lymphocytes accuracy as tuberculosis predictor. This diagnostic study was done at dr. Mohammad Hoesin General Hospital Palembang. Samples of this study had been taken from medical records which fulfilled the inclusion and exclusion criteria. The study was analyzed using SPSS version 22.0. The sample of the study was 101 tuberculosis subjects. Most of the subjects were men (70,3%) and were 36-45 years old group (25,7%). The cut-off value of 0,476 allowed the discrimination of tuberculosis with positive bacterial culture from negative bacterial culture, with a sensitivity of 95,1% and a specificity of 70%. Therefore, we concluded that the ratio of monocytes to lymphocytes can be considered as an early predictor marker of tuberculosis.

The effect of antioxidant rich diet supplements of Spirulina and tamarind fruit pulp at 230 mg kg−1 body weight, separately as well as in combination, on various hematological parameters of Swiss albino mice exposed to fluoride for seven days at daily doses of 190 mg kg−1 body weight and for 90 days at daily doses of 94 mg kg−1 body weight is reported. Compared with controls, fluoride exposure decreased erythrocyte (12%–18%), leukocyte (16%) and platelet counts (7%, only for short-term exposure), hemoglobin (2%–17%) and packed cell volume (2%–14%) in Swiss albino mice reared on standard feed but these were altered little in the diet supplement groups. Fluoride exposure decreased lymphocytes in both standard feed (16%–21%) and diet supplement groups (5%–19%, but only after long-term exposure). Fluoride withdrawal led to recovery of the post-treated mice from long-term exposure. Spirulina alone and also in combination with tamarind fruit pulp was found more effective than tamarind alone in reducing hematolo...

Terminal body weights (TBWs), thymus weight parameters, and thymus morphology were retrospectively evaluated in 453 cynomolgus monkeys assigned to control groups on nonclinical toxicity studies. Morphology of bone, ovary, and testis/epididymis were used to determine maturity status of individual animals. There was no correlation between TBW and thymus weight (absolute and/or relative to TBW or brain weight). Thymus weight parameters and grades of decreased lymphocytes in the thymus were highly variable in immature animals compared to mature animals. There was also high (up to 11-fold) variability of thymus weight parameters within a given control group on the same study (generally 3 or 4 animals per sex). Several parameters evaluated had more pronounced age-related changes in males when compared to females. Our results demonstrate the inherent variability of thymus weight parameters and morphologic observations for cynomolgus monkeys on toxicology studies. Changes in thymus parameters in cynomolgus monkeys are unreliable indicators of immunomodulation or immunotoxicity in the absence of other relevant findings. Therefore, the thymus parameters commonly evaluated in preclinical safety assessments should not be the primary data set used to determine the presence of a direct test article–related effect on the immune system.

The safety of Aquaflor® (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2× the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5× the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

This study describes a canine lymphosarcoma with a rapid proliferation and recurrence. A 4-year-old, male, Shih Tzu dog was examined for acute swelling mass. The mass had been identified since 3 months ago and enlarged 10×7 cm and located in the right axillary region. The surgical removal was recommended when patient visited veterinarian and the operation was conducted. The removed tumor was 11×8×7 cm and firm, lobulated and white cut surface. Routine screening laboratory test was as-sessed with blood and radiological analysis. The metastasis sign was not detected on thoracic and ab-dominal radiography. Blood test revealed decreased lymphocytes. After surgical removal of the mass, microscopic histopathological examination was performed to determine the final diagnosis. Histopathologically, the tumors are characterized by the same histological features, including the pres-ence of neoplastic cellular populations, and lymphocytes infiltration in varying proportions. Also, DNA was extracted and PCR analysis was employed to analyze the origin of tumor cells. T-cell specific nu-cleic acid fragments were specifically amplified by PCR. On the basis of the laboratory results, the tu-mor was diagnosed with canine T-cell lymphosarcoma. On the basis of our knowledge, this is the first report of canine T-cell lymphosarcoma in a Shih Tzu dog.

OBJECTIVE CC chemokines are mainly chemotactic for monocytes and lymphocytes. The aim of this study was to evaluate the involvement of the CC chemokines, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, in the pathogenesis of bronchiolitis obliterans organizing pneumonia (BOOP). METHODOLOGY The concentrations of MIP-1alpha and MIP-1beta in BAL fluid (BALF) obtained from patients with BOOP (n = 13) and control patients (CP, n= 18) were measured by enzyme-linked immunosorbent assay. RESULTS MIP-1alpha in BALF was significantly higher in patients with BOOP (mean +/- SD; 123.8 +/- 98.0 pg/mL) than in CP (62.5 +/- 46.1 pg/mL). Significantly higher MIP-1beta was also detected in patients with BOOP (51.6 +/- 72.5 pg/mL) than in CP (6.4 +/- 3.7 pg/mL). The concentration of MIP-1alpha significantly correlated with the percentage of lymphocytes in BALF, and the concentration of MIP-1beta significantly correlated with the numbers of lymphocytes, neutrophils and eosinophils in BALF. Both MIP-1alpha and MIP-1beta in BALF were decreased after corticosteroid therapy and this was accompanied by decreased lymphocytes in BALF. CONCLUSION This study suggests that MIP-1alpha and MIP-1beta may play important roles in the recruitment of immuno-inflammatory cells into the lungs, and may contribute to the pathogenesis of BOOP.

Background Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a relatively rare but well known complication among patients under MTX treatment. Spontaneous regression of LPD after MTX withdrawal is regarded as a distinct character of MTX-LPD. Although detection of Epstein-Barr virus encoded small RNAs (EBER) in the pathological tissue is reported as a predictor of regression, although it is not necessarily specific 1) . Objectives To investigate the factors involved in spontaneous regression of LPD following MTX withdrawal. Methods We retrospectively reviewed 43 rheumatoid arthritis (RA) patients complicated with MTX-LPD from January 2000 to October 2015 in our institution. Age, sex, RA duration matched 76 control MTX-treated patients were selected. MTX-LPD patients were divided into two groups regarding to the status of LPD after MTX cessation; regressive LPD (R group) and persistent LPD (P group), and clinical parameters were compared. Flowcytometric analysis of the whole blood was underwent in a part of the MTX-LPD patients (N=10, 7 regressive, and 3 persistent LPD) and controls (N=10). The time of MTX cessation (= time of LPD diagnosis) was defined as week 0, and whole blood sample was collected at week 0, 4 and 12. Epstein Barr Virus antigen specific CD8+ T cells (EBV specific CD8+) was defined as MHC/EBV peptide tetramer positive CD8+ T cells. Results At the time of MTX cessation (week 0), number of peripheral lymphocytes was significantly decreased in LPD group, compared to control group. Among the LPD group, significant increase of lymphocyte number following MTX withdrawal was observed only in the R group, but not in P group while MTX dose, EBER positivity rate and pathological phenotypes did not show significant difference. Flowcytometric analysis revealed significant decrease in proportion of effector memory CD8+ T cells (EM CD8+), EBV specific CD8+ and T helpler 1 (Th1) subset in R group compared to control group. Following MTX cessation, significant increase in proportion of these subsets were observed only in the R group, but not in P group. On the other hand, proportion of CD14-CD15+ cells in lymphocyte fraction, which include myeloid derived suppressor cells 2) (MDSC) was significantly increased in LPD group at week 0, and significantly decreased following MTX cessation only in the R group, but not in P group. Proportion of CD14-CD15+ cells negatively and significantly correlated with the proportion of EM CD8+T cells. Conclusions Our study suggested that decreased lymphocytes at the time of LPD diagnosis and restoration following MTX withdrawal are associated with pathogenesis and clinical course of “regressive” MTX-LPD. Proportion of Th1 cells, EM CD 8+, EBV specific CD8+ and CD14-CD15+ cells was restored following MTX cessation, indicating their involvement in regression of MTX-LPD. References Ichikawa A, et al. Eur J Haematol 2013;91:20–8. Austin D, etal. Cancer Immunol Immunother 2013;62:299–307. Acknowledgement none Disclosure of Interest S. Saito: None declared, K. Suzuki Grant/research support from: Eisai Co.,Ltd., Bristol–Myers K.K., K. Yamaoka Paid instructor for: Pfizer, Chugai Pharma, Mitsubishi-Tanabe Pharma, Takeda Industrial Pharma, GlaxoSmithKline, Nippon Shinyaku, Eli Lilly, Janssen Pharma, Eisai Pharma, Astellas Pharma and Actelion Pharmaceuticals, T. Shimizu: None declared, T. Mori Paid instructor for: Astellas Pharma,Chugai Pharma,Eisai Co.,Ltd.,Janssen Pharmaceutical K.K., S. Okamoto Grant/research support from: Astellas Pharma,Chugai Pharma,Eisai Co.,Ltd.,Bristol–Myers K.K., Takeda Pharmaceutical Co.,Pfizer, Paid instructor for: Astellas Pharma,Chugai Pharma,Eisai Co.,Ltd.,Bristol–Myers K.K.,Takeda Pharmaceutical Co., Pfizer, K. Amano: None declared, M. Tokuhira: None declared, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co.,Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Teijin Pharma Ltd., AbbVie GK, 2,Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Paid instructor for: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co.,Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Teijin Pharma Ltd., AbbVie GK, 2,Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K.

Crossbred weanling gilts were fed a standard ration containing 0, 1, 10, or 100 ppm purified hexachlorobenzene (HCB) for 13 wk. No mortalities, ill health, neurological disorders, or significant depressions in weight gain were observed. Postmortem examination revealed brightly fluorescent livers at all levels of HCB. The group receiving 100 ppm had a tendency for smaller spleens, larger livers with swollen hepatocytes, and decreased lymphocytes. HCB accumulated in the dissectable fat of growing swine to concentrations five- to sevenfold higher than the dietary concentration; residues in 11 other tissues examined were below the dietary concentration.

Objective: To compare the efficacy of 0.03% tacrolimus eye drops diluted in two different vehicles (linseed oil and olive oil) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: This study included 60 dogs. Of this group, 20 were healthy and allocated to the control group, and 40 were diagnosed with bilateral KCS and randomly allocated to either the TO (tacrolimus in olive oil) or the TL (tacrolimus in linseed oil) groups. Ophthalmic examinations, Schirmer Tear Test-1 (STT-1), Tear Film Break-up Time (TBUT) and Fluorescein Test (FT) were carried out monthly, along with cytological and histopathological examinations at the beginning and end of the study. Results: The clinical signs, corneal ulcers, Schirmer Tear Test-1 values, and Tear Film Break-up Time values improved in both groups after one month of treatment. Cytological examination at the end of the study showed decreased lymphocytes, neutrophil, metaplastic, and squamous cell counts in both groups, while the histopathological analysis showed decreases in lymphocytes and neutrophils and an increase in goblet cell density (cells/mm2). The decreases in neutrophil count were more significant (p