Blood Chemistry Research Articles

Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage.

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. HS resulted in systemic and local complement activation, cytokine release, hypocoagulopathy, metabolic acidosis, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the animals with hemorrhagic shock treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Hemorrhagic shock triggers early immunopathy and coagulopathy and appears associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

Colic signs caused by an unilateral abdominal seminoma in a Friesian stallion

SummaryThis case report describes the diagnosis and surgical treatment of a 12‐year‐old Friesian stallion that presented with colic and was diagnosed with an unilateral abdominal seminoma. The diagnostic work‐up included haematology, blood chemistry, rectal examination and ultrasonography before the tentative diagnosis of a neoplastic intra‐abdominal testicle was made. The mass was removed surgically and diagnosed as a seminoma via histopathology. Regular follow‐up was performed since suspected metastasis was seen on transrectal ultrasonography and laparoscopy. Unfortunately, the patient was subjected to euthanasia 18 months post‐surgery due to clinical deterioration. Post‐mortem examination was performed and confirmed the cause of clinical deterioration was due to metastasis of the previously removed seminoma. Colic is, to the author's knowledge, rarely seen in stallions with an abdominal testicular neoplasm, in contrast to humans and dogs.

Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Toxicology, pharmacokinetics, and immunogenicity studies of CCR4-IL2 bispecific immunotoxin in rats and minipigs

We have developed a diphtheria toxin-based recombinant human CCR4-IL2 bispecific immunotoxin (CCR4-IL2-IT) for targeted therapy of cutaneous T-cell lymphoma (CTCL). CCR4-IL2-IT demonstrated superior efficacy in an immunodeficient mouse CTCL model. Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model. The comparison demonstrated that CCR4-IL2-IT was significantly more effective than Brentuximab. In this study, we have performed non-GLP (Good Laboratory Practice) toxicology, pharmacokinetics, immunogenicity studies of CCR4-IL2-IT in both rats and minipigs. CCR4-IL2-IT demonstrated excellent safety profiles in both rats and minipigs. The maximum tolerated dose of CCR4-IL2-IT was determined as 0.4 mg/kg in both rats and minipigs. Complete blood count and chemistry analysis did not show significant difference for all measured parameters between the blood samples of pre-injection versus post-injection from the five-day toxicology studies of CCT4-IL2-IT in both rats and minipigs. Histology analysis did not show difference between the PBS treatment group versus CCR4-IL2-IT treatment group at 50 μg/kg in both rats and minipigs. The half-life of CCR4-IL2-IT was determined as about 45 min in rats and 30 min in minipigs. The antibodies against CCR4-IL2-IT were detected in about two weeks after CCR4-IL2-IT treatment. CCR4-IL2-IT did not induce cytokine release syndrome in a peripheral blood mononuclear cell derived humanized mouse model. The depletion of CCR4+ cell and CD25+ cell (two target cell populations of CCR4-IL2-IT) was observed in minipigs. The excellent safety profile promoted us to further develop CCR4-IL2-IT towards clinical trials.

Sotagliflozin attenuates liver-associated disorders in cystic fibrosis rabbits.

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to CF, a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test whether sotagliflozin, a sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver-related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Furthermore, sotagliflozin alleviated nonalcoholic steatohepatitis-like phenotypes, including liver fibrosis. Intriguingly, sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that sotagliflozin attenuates liver disorders in CF rabbits and suggests sotagliflozin as a potential drug to treat CFLD.

Procalcitonin for Early Detection of Pharyngocutaneous Fistula after Total Laryngectomy: A Pilot Study.

The aim of this prospective study was to investigate the role of procalcitonin as an early diagnostic marker of pharyngocutaneous fistula (PCF) in a cohort of head and neck patients treated with total laryngectomy for squamous cell carcinoma. This prospective study was conducted on a sample of patients enrolled from January 2019 to March 2022. All patients were subjected to a "protocol" of blood chemistry investigations, scheduled as follows: complete blood count with formula, ESR dosage, CPR, and PCT. PCT was also dosed by salivary sampling and a pharyngo-cutaneous swab in patients who presented with PCF. The dosage scheme was systematically repeated: the day before the intervention (t0); the 5th day postoperative (t1); the 20th day postoperative (t2); and at time X, the day of the eventual appearance of the pharyngocutaneous fistula. A total of 36 patients met the inclusion criteria. The patients enrolled in the study were subsequently divided into two groups: 27 patients underwent total laryngectomy (TL) for laryngeal cancer without postoperative complications, and 9 patients were undergoing TL with postoperative PCF. Using the Cochran's Q test, statistical significance was found for PCT among T0, T1, Tx, and T2 (p-value < 0.001) between the PCF and non-PCF groups. The Z test demonstrated that there is a difference in PCT levels at T1 and T2 and that this difference is statistically significant (p < 0.001). PCT could be considered an early marker of complications in open laryngeal surgery. According to our results, it could be useful in the precocious detection of pharyngocutaneous fistulas and in the management of antibiotic therapy.

Effects of Croton sonderianus essential oil in tambaqui (Colossoma macropomum) feeds on growth, hematology, blood chemistry, and resistance of the fish to infection with Aeromonas hydrophila

Effects of Croton sonderianus essential oil in tambaqui (Colossoma macropomum) feeds on growth, hematology, blood chemistry, and resistance of the fish to infection with Aeromonas hydrophila

Diagnostic benefits of platelet-to-lymphocyte, neutrophil-to-lymphocyte, and albumin-to-globulin ratios in dogs with nasal cavity diseases

BackgroundA multimodal approach for diagnostic tests under anesthesia is required to diagnose nasal cavity pathology (NP) reliably in dogs. Blood test results may provide clues to the suspected NP.MethodsThis prospective blinded study assessed 72 dogs with chronic nasal discharge due to NPs, and 10 healthy dogs as the control group (CG). NPs were diagnosed using whole-body computed tomography (CT), upper airway endoscopy, examination of nasal mucosal swabs by bacterial and fungal culture, and histopathological examination of nasal mucosa biopsies. The exclusion criteria were the presence of any additional diseases or corticosteroid pre-treatment. In consideration of these exclusion criteria, 55 dogs entered the study. Dogs were classified into benign (benign tumors, idiopathic rhinitis (IR), and others) and malignant (carcinomas and sarcomas) NP groups. Blood count and blood chemistry tests were performed. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin-to-globulin ratio (AGR) were calculated and compared.Results25 dogs with malignant NP (13 and 12 with carcinomas and sarcomas, respectively) and 30 dogs with benign NP (seven with benign tumors,13 with IR, and 10 others) were included. In general, in dogs with NP there were only slight abnormalities in complete blood count. However, PLR was significantly higher in dogs with malignant NP (carcinoma and sarcoma) than in those with benign NP and in the CG. Compared with the CG, the NLR was significantly increased in all dogs with NP, and the AGR was mild but significantly lower, except in dogs with sarcomas and benign tumors.ConclusionsIn dogs with nasal disease alone, there are usually no marked abnormalities in blood count. However, while mildly increased NLR and decreased AGR can be observed in almost all NPs, an increased PLR may indicate a malignant NP and can be used as an additional screening tool in dogs with nasal discharge due to nasal cavity pathology.

Physiological response to fetal intravenous lipid emulsion.

In preterm neonates unable to obtain sufficient oral nutrition, intravenous lipid emulsion is life-saving. The contribution of post-conceptional level of maturation to pathology that some neonates experience is difficult to untangle from the global pathophysiology of premature birth. In the present study, we determined fetal physiological responses to intravenous lipid emulsion. Fetal sheep were given intravenous Intralipid 20® (n = 4 females, 7 males) or Lactated Ringer's Solution (n = 7 females, 4 males) between 125 ± 1 and 133 ± 1 d of gestation (term = 147 d). Manufacturer's recommendation for premature human infants was followed: 0.5-1 g/kg/d initial rate, increased by 0.5-1 to 3 g/kg/d. Hemodynamic parameters and arterial blood chemistry were measured, and organs were studied postmortem. Red blood cell lipidomics were analyzed by LC-MS. Intravenous Intralipid did not alter hemodynamic or most blood parameters. Compared with controls, Intralipid infusion increased final day plasma protein (P=0.004; 3.5 ± 0.3 vs. 3.9 ± 0.2 g/dL), albumin (P = 0.031; 2.2 ± 0.1 vs. 2.4 ± 0.2 g/dL), and bilirubin (P<0.001; conjugated: 0.2 ± 0.1 vs. 0.6 ± 0.2 mg/dL; unconjugated: 0.2 ± 0.1 vs. 1.1 ± 0.4 mg/dL). Circulating IGF-1 decreased following Intralipid infusion (P<0.001; 66 ± 24 vs. 46 ± 24 ng/mL). Compared with control Oil Red O liver stains (median score 0), Intralipid-infused fetuses scored 108 (P=0.0009). Lipidomic analysis revealed uptake and processing of infused lipids into red blood cells, increasing abundance of saturated fatty acids. The near-term fetal sheep tolerates intravenous lipid emulsion well, although lipid accumulates in the liver. Increased levels of unconjugated bilirubin may reflect increased red blood cell turnover or impaired placental clearance. Whether Intralipid is less well tolerated earlier in gestation remains to be determined.

ANALYSIS OF FELINE AORTIC THROMBOEMBOLISM CASES: A LITERATURE REVIEW FROM 2014 TO 2023

Feline Aortic Thromboembolism (FATE) is a condition with a poor prognosis. This case is also commonly called 'saddle thrombus', occurs when a thrombus forms in one part of the circulation which becomes embolized (aortic trifurcation), which is an area where the aorta branches in the pelvis to the right and left iliac arteries. This case study aims to elaborate on the etiology, clinical symptoms, treatment and prevention of Feline Aortic Thromboembolism cases. This research is a literature review using descriptive and systematic methods on 21 cases of Feline Aortic Thromboembolism obtained from 20 journals during the 2014-2023 period. The diagnosis of Feline Aortic Thromboembolism (FATE) can be determined from the dominan clinical symptoms that appear including paralysis/paresis (24%) unilaterally and (67%) bilaterally, cold paw (38%) and paw discoloration/cyanosis (29%). The results of supporting examinations that can be used to confirm the diagnosis of FATE include Echocardiography examination which was carried out in 15 of 21 cases (72%), Hematology examination (43%) which was carried out in 9 of 21 FATE cases, and Blood Chemistry (57%). Treatment for cats in cases of Feline Aortic Thromboembolism (FATE) includes administration of antiplatelets (57%), administration of anticoagulants (52%), as well as administration of analgesics and heart treatment (33%). The results of this paper provide a good understanding of the clinical symptoms, diagnosis and appropriate therapy regarding one of the rare cases in cats, namely Feline Aortic Thromboembolism.

Hematological and blood biochemistry parameters as prognostic indicators of survival in canine multicentric lymphoma treated with COP and L-COP protocols.

Hematological and blood chemistry parameters are crucial for evaluating and monitoring canine multicentric lymphoma during chemotherapy. Pre-treatment hematological and blood chemistry parameters can be used as prognostic survival outcomes for this disease. Therefore, this study aimed to investigate the effect of hematological and blood chemistry parameters pre-treatment and 4 weeks post-treatment on the survival outcomes of dogs treated with either a combination of cyclophosphamide, vincristine, and prednisolone (COP) or a combination of COP with L-asparaginase (L-COP) protocols. We conducted a retrospective study. Medical records and hematological and blood chemistry parameters of 41 dogs with multicentric lymphoma treated with L-COP (n = 26) and the COP protocols (n = 15) were obtained from the hospital information system. Most cases were classified as high-grade lymphoma based on the Kiel cytological classification. The effects of hematological and blood chemistry parameters on survival outcomes were investigated using the Cox proportional hazard regression model. The median survival time (MST) for each hematological and blood chemistry parameter affecting survival outcome was established and compared using the Kaplan-Meier product limit method with the log-rank test. Dogs with high-grade multicentric lymphoma that were treated with the COP protocol and had monocytosis at pre-treatment had a significantly shorter MST than dogs with normal monocyte counts (p = 0.033). In addition, dogs with azotemia, both pre-treatment and 4 weeks post-treatment, had a significantly shorter MST than dogs with normal serum creatinine levels (p = 0.012). Dogs with high-grade multicentric lymphoma treated with the L-COP protocol who had hypoalbuminemia (serum albumin concentration <2.5 mg/dL) at both pre-treatment and 4 weeks post-treatment had a significantly shorter MST than dogs with normal serum albumin levels (p < 0.001). Furthermore, dogs with leukocytosis at 4 weeks post-treatment had a significantly shorter MST than those with a normal total white blood cell count (p = 0.024). Serum albumin level can serve as a simple negative prognostic indicator of survival outcomes in dogs with high-grade multicentric lymphoma treated with the L-COP protocol. Dogs with hypoalbuminemia pre-treatment and 4 weeks post-treatment tended to have a shorter MST than those with normal serum albumin concentrations.

Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N=2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N=1098 (48%)] were identified to create longitudinal data for N=204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

High variability in short and long-term recovery kinetic of blood cell count and blood chemistry in a partial body irradiation mouse model

Purpose In the aftermath of a nuclear disaster or accident, survivors will suffer from radiation-induced normal tissue damage. Recovery after radiation exposure is dictated by several factors, one of which is degree of shielding at time of exposure. This study aims to characterize the short and late term changes in kinetics and magnitude of pancytopenia and blood chemistry in a model of heterogeneous radiation exposure, or partial body irradiation (PBI), compared to whole body irradiation (WBI). Materials and methods Male C57BL/6 mice, 8-10 weeks of age, were WBI at 6 different doses (6, 6.1. 6.15, 6.2, 6.5, and 7.5 Gy) to establish the LD50. To determine the effect of shielding on blood cell counts and chemistry, animals were either WBI at 6 Gy (LD2230) or 6 Gy PBI with one leg shielding (LD030). Complete blood counts and chemistry were measured at 1, 5-, 10-, 20-, 30- and 120-days post-irradiation. Results and conclusions Irradiated animals had significant depletion of white blood cells, red blood cells and platelets up to 10 days post-irradiation. Separation between PBI and WBI were observed at 10- and 20-days post-irradiation at which point PBI animals showed sign of recovery while overall cell count remains depleted in WBI animals up to 30 days post-irradiation. In addition, significant changes were found in parameters indicative of hematopoietic injury including hemoglobin count, hematocrit count and white blood cell population. Significant changes were observed in kidney function with changes to blood urea nitrogen and calcium concentration at 5-days post-irradiation. At 10-days post-irradiation. liver function changes differentiated WBI from PBI animals. Long-term, irradiated animal’s chemistry values and many blood counts were not significantly different from Sham. In conclusion, partial shielding ensured complete survival and demonstrated a different recovery kinetics of blood and chemistry parameters after irradiation compared to survivors of whole body irradiation and no single hemopoietic parameter was able to consistently differentiate irradiated from Sham animals. This seems to indicate that there is no single robust hemopoietic parameter to differentiate those exposed from those who were not due to the inherent variability in individual responses. Furthermore, there were no significant long-term effects on these blood parameters between survivors of WBI and PBI except that shielding accelerated recovery.

Penyuluhan Pengaruh Minyak Jelantah dan Pelatihan Pemeriksaan Kadar Kimia Darah di Desa Keutapang, Syamtalira Aron

Waste cooking oil is oil derived from plants such as corn oil, vegetable oil, and ghee which has been used as cooking oil and is usually reused for economic reasons. However, when viewed from its chemical composition, used cooking oil contains carcinogenic compounds which occurs during the frying process. The use of used cooking oil can disrupt the body's hemostasis, it can cause many disorders, can increase cholesterol, blood sugar, and uric acid, and can even damage organs. Knowledge about the effects of used cooking oil is expected to be able to change people's lifestyles so that they no longer use used cooking oil. Training on blood chemistry examinations related to cholesterol, uric acid, and blood sugar levels by Cadres in Keutapang Village can help the community and health workers in Keutapang Village as an initial screening to prevent systemic diseases. This activity aims to increase public knowledge regarding the influence of used cooking oil and cadres in Keutapang Village to be able to independently carry out blood chemistry checks for cholesterol, uric acid, and blood sugar levels.

Pre-disease detection of stress-associated disorders in combatants depending on professional activity profile

Relevance. Combat stress and other forms of stress-associated mental disorders, as well as their consequences currently remain a most urgent issue in military personnel directly or indirectly involved in armed conflicts. Active deployment of weapons for remote destruction of manpower and infrastructure has caused qualitative transformations in the profile of medical casualties, thus becoming a powerful stress factor of intense psychological pressure on personnel. The fundamentally new nature of armed confrontations, which in many ways is incompatible with domestic experience acquired over the recent decades during local hostilities in the "hot zones", is gaining relevance, as well as effective prevention and treatment of health disorders associated with combat mental trauma in the personnel deployed in the special military operation. The objective is to identify pre-disease characteristics of stress-associated disorders in combatants, depending on their professional activity profile.Methods. We examined 209 males earlier deployed in combat zones. All the examined combatants were divided in three groups according to professional criteria: group 1 – employees of the Ministry of Internal Affairs of Russia (n = 71); group 2 – soldiers of the National Guard of Russia (the Rosgvardiya) (n = 70); group 3 – employees of the EMERCOM of Russia (n = 68). Clinical and psychopathological examination with prior blood chemistry and toxicological screening were conducted to identify metabolites of psychoactive substances.Results and discussion. Although the research showed an elevated risk of post-traumatic stress disorder in the combatants across all the three groups, employees of the EMERCOM of Russia and the Ministry of Internal Affairs of Russia demonstrated average stress coping ability, whereas soldiers of the National Guard of Russia showed higher levels of maladaptation and greater susceptibility to subclinical anxiety and depressive disorders. Combatants directly involved in combat operations often resort to alcohol or sedatives.Conclusion. Programs for medical and psychological rehabilitation implemented as part of psychological and psychiatric prevention efforts shall be adjusted to the combatants’ professional profile with a specific focus on the type of combat service duties.

P906 The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease. A retrospective observational study

Abstract Background Thiopurines are commonly used to treat inflammatory bowel disease but withdrawal due to side-effects are common. Thioguanine has been suggested to be better tolerated than conventional thiopuries. We aimed to study drug-survival of low-dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines. Methods All patients born in the year 1956 and later, and who at least once started thiopurine treatment between the years 2006-2022 were included. A medical chart review was performed that noted drug-survival for every thiopurine treatment attempt. Mantel-Cox rank test was used to test differences in drug-survival for different thiopurines. Blood chemistry analysis and faecal calprotectin levels was registered the first five years of treatment. Results In the study population there was 379 initiated thiopurine treatments (210 for Crohns disease and 169 for ulcerative colitis) in 307 patients with IBD. Low-dose thioguanine (median dose 11 mg; 25-75th percentile 7-19 mg) had been initiated in 31 patients. Overall, when including all thiopurine attempts, the median time on treatment for the different thiopurine treatments were for azathioprine 24 months (25th-75th percentile 3-59 months), for 6-mercaptopurine 15 months (3-59 months), for azathioprine/allopurinol 22 months (1-25 months) and for thioguanine 33 months (11-64 months). Thioguanine had longest drug-survival (Mantel-cox rank test: thioguanine versus azathioprine p=0.014; thioguanine versus 6-mercaptopurine (6-MP) p&amp;lt;0.001). For second line thiopurine treatment, the median time on treatment for 6-mercaptopurine were 13 months (2-69) and for thioguanine 33 months (11-64). Thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: p=0.006) (Figure). At 60 months, 86% of the patients who started low dose thioguanine was still on treatment compared to 42% of the patients who started 6-MP (p=0.022). The median 6-TGN levels in patients treated with thioguanine was 364 pmol/8x108. Patients on thioguanine treatment showed significantly lower values of median mean corpuscular volume at follow-up than patients treated with azathioprine and 6-MP. Patients treated with 6-MP had signficantly lower levels of F-calprotectin at year three and year four compared to patients treated with azathioprine. Overall there was a similar response on inflammatory markers the first five years from starting treatment with thioguanines compared to conventional thiopurines. Conclusion Treatment with a low-dose of thioguanine is well tolerated in patients with IBD and have a significantly higher drug survival than conventional thiopurines.

Identification of phenomic data in the pathogenesis of cancers of the gastrointestinal (GI) tract in the UK biobank

Gastrointestinal (GI) cancers account for a significant incidence and mortality rates of cancers globally. Utilization of a phenomic data approach allows researchers to reveal the mechanisms and molecular pathogenesis of these conditions. We aimed to investigate the association between the phenomic features and GI cancers in a large cohort study. We included 502,369 subjects aged 37–73 years in the UK Biobank recruited since 2006, followed until the date of the first cancer diagnosis, date of death, or the end of follow-up on December 31st, 2016, whichever occurred first. Socio-demographic factors, blood chemistry, anthropometric measurements and lifestyle factors of participants collected at baseline assessment were analysed. Unvariable and multivariable logistic regression were conducted to determine the significant risk factors for the outcomes of interest, based on the odds ratio (OR) and 95% confidence intervals (CI). The analysis included a total of 441,141 participants, of which 7952 (1.8%) were incident GI cancer cases and 433,189 were healthy controls. A marker, cystatin C was associated with total and each gastrointestinal cancer (adjusted OR 2.43; 95% CI 2.23–2.64). In this cohort, compared to Asians, the Whites appeared to have a higher risk of developing gastrointestinal cancers. Several other factors were associated with distinct GI cancers. Cystatin C and race appear to be important features in GI cancers, suggesting some overlap in the molecular pathogenesis of GI cancers. Given the small proportion of Asians within the UK Biobank, the association between race and GI cancers requires further confirmation.

Canine diabetes mellitus demonstrates multiple markers of chronic inflammation including Th40 cell increases and elevated systemic-immune inflammation index, consistent with autoimmune dysregulation.

Canine diabetes mellitus (CDM) is a relatively common endocrine disease in dogs. Many CDM clinical features resemble human type 1 diabetes mellitus (T1DM), but lack of autoimmune biomarkers makes calling the disease autoimmune controversial. Autoimmune biomarkers linking CDM and T1DM would create an alternative model for drug development impacting both human and canine disease. We examined peripheral blood of diagnosed CDM dog patients comparing it to healthy control (HC) dogs. Dogs were recruited to a study at the Colorado State University Veterinary Teaching Hospital and blood samples collected for blood chemistry panels, complete blood counts (CBC), and immunologic analysis. Markers of disease progression such as glycated albumin (fructosamine, the canine equivalent of human HbA1c) and c-peptide were addressed. Significant differences in adaptive immune lymphocytes, innate immune macrophages/monocytes and neutrophils and differences in platelets were detected between CDM and HC based on CBC. Significant differences in serum glucose, cholesterol and the liver function enzyme alkaline phosphatase were also detected. A systemic immune inflammation index (SII) and chronic inflammation index (CII) as measures of dynamic changes in adaptive and innate cells between inflammatory and non-inflammatory conditions were created with highly significant differences between CDM and HC. Th40 cells (CD4+CD40+ T cells) that are demonstrably pathogenic in mouse T1DM and able to differentiate diabetic from non-diabetic subjects in human T1DM were significantly expanded in peripheral blood mononuclear cells. Based on each clinical finding, CDM can be categorized as an autoimmune condition. The association of significantly elevated Th40 cells in CDM when compared to HC or to osteoarthritis, a chronic but non-autoimmune disease, suggests peripheral blood Th40 cell numbers as a biomarker that reflects CDM chronic inflammation. The differences in SII and CII further underscore those findings.

Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). This cross-sectional study included 50 healthy adolescents, aged 14-18years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. The mean age of all participants was 15.9years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53±0.04mm vs 0.47±0.02mm, p=0.001). Among adolescents with a parental history of PCAD, those with ≥3 CRFs had significantly higher IMT values (0.56mm) than those with <3 CRFs (0.52mm) and controls (0.48mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Effect of brooding conditions on the blood chemistry and performance of turkey poults

Hematologic parameters and the levels of certain plasma metabolites offer an objective measure, and real-time insight into the physiological status of an animal. We hypothesized that blood chemistry analysis in brooding poults varies with even minor differences of temperature and can affect poult performance. A total of 2240 1-d-old turkey hens were assigned randomly to one of 4 treatments [Control (C) = 32C and 60%RH; Cold stress (CS) = 29C and 60%RH; Heat stress (HS) = 35C and 60%RH; and Heat stress plus Humidity (HHS) = 35C and 75%RH]. In all the treatments, the temperatures were lowered 2 degrees Celsius the first week, and 1.5 degrees Celsius each week thereafter. The relative humidity was maintained constant, as much as possible, throughout the 35 d duration of the experiment. Brooding treatment affected pH, partial carbon dioxide (pCO2), potassium (K), and sodium (Na). The treatments HS and HHS had higher pH and K, and lower pCO2 and K in the blood. These changes suggest an attempt by the poults to cool down by increased water intake and panting. Furthermore, by the end of the experiment more birds in these two treatment groups had distended crops, possible to increased water intake also. The increase of ketone in the plasma, at 3 d of age, of poults from the two warmest brooding conditions (HS and HHS) suggests that these birds were consuming less feed and using more fat as its main fuel source. Furthermore, at 28 d of age significantly more poults from HS and HHS had reduced ventricular contractility of their hearts. However, no significant differences in the concentration of creatinine kinase (CK) or cardiac troponin I (cTnI) were found between treatments. In conclusion, this research revealed that blood parameters were influenced by minor temperature and humidity changes. Warmer brooding temperatures resulted in a higher incidence of pendulous crop. Overall, there were no significant differences in the estimated BW between the treatments. Further research is needed to optimize the number of samples needed and the time of sampling to optimize brooding conditions. We also need to investigate blood parameters that can reveal reduced contractility of the heart and if the reduced myocardial contractility from birds kept at a higher temperature and relative humidity predisposes them to dilated cardiomyopathy or other metabolic diseases.