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Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, resulting in immune cell exhaustion, a phenomenon commonly observed in chronic viral infections and cancer. This state of exhaustion involves elevated levels of inhibitory molecules, cells, and cell surface receptors, as opposed to stimulatory counterparts. This review aims to elucidate the expression patterns of various co-inhibitory and co-stimulatory receptors on immune cells isolated from chronic hepatitis B (CHB) patients. By analyzing existing data, the review conducts comparisons between CHB patients and healthy adults, explores the differences between HBV-specific and total T cells in CHB patients, and examines variations between intrahepatic and peripheral immune cells in CHB patients. Understanding the mechanisms underlying immune exhaustion in CHB is crucial for developing novel immunotherapeutic approaches. This detailed analysis sheds light on the immune exhaustion observed in CHB and lays the groundwork for future combined immunotherapy strategies aimed at leveraging checkpoint receptors to restore immune function and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Laminitis is a significant cause of horse mortality and it profoundly impacts the distal locomotor apparatus, causing intense pain primarily in the thoracic limbs. Affected horses exhibit a characteristic arched back and flexed thoracolumbar spinal posture. To the authors' knowledge, there are no studies investigating the relationship between chronic laminitis and thoracolumbar spine injuries. The aim of this study was to investigate the occurrence and severity of injuries in the thoracolumbar spine of horses and the association with (n = 30) or without (n = 30) chronic laminitis. We developed a clinical-assessment method for the equine thoracolumbar spine, along with the equine Grimace Scale for pain assessment and ultrasound scans. The results indicated a significant association between chronic laminitis and thoracolumbar spinal injuries, with affected horses showing higher pain manifestations and increased injury rates based on clinical examination and ultrasound assessments. Horses with laminitis displayed a 14-times higher prevalence of relevant ultrasound injuries in the thoracolumbar spine. These findings emphasize the urgent need for further research to characterize and address these injuries, and an identification of targeted preventive and therapeutic measures to enhance the well-being of horses with chronic laminitis. Postural adaptation is a prominent feature in horses affected by laminitis. Laminitis induces intense pain, especially in the forelimbs, prompting affected horses to assume a caudally displaced trunk posture, resulting in the hyperflexion of the thoracolumbar spine. This study assessed the nature and prevalence of thoracolumbar injuries in horses with chronic laminitis compared to horses without it. Sixty horses were used (thirty laminitic and thirty non-laminitic) of different athletic purposes and ages (2–20 years). The experimental protocol entailed a single assessment of horses' thoracolumbar spines, utilizing physical examination by MACCTORE, a scoring system developed specifically for this study. Additional evaluations included the Grimace Equine Pain Scale (HGS) and ultrasound exams. Statistical tests were used to compare values (Mann–Whitney or t-test) and lesions prevalences (Fisher) between groups (p < 0.05). The results showed a higher pain manifestation (HGS and heart rate, p < 0.0001) and thoracolumbar-spine-injury levels in chronic laminitis horses, both in MACCTORE clinical examinations (11.7 ± 4.8 vs. 4.2 ± 3.3, p < 0.0001) and general ultrasonographic indices (39.6 ± 12.0 vs. 20.7 ± 7.1, p < 0.0001), including specific examination approaches for various spinal elements. Horses with laminitis presented with a 14-fold higher prevalence of ultrasound-relevant lesions in the thoracolumbar spine (CI: 4.4 to 50.6, p < 0.0001) compared to controls. These findings constitute new evidence of an association between chronic laminitis and the presence of thoracolumbar spine injuries in horses, which may be confirmed by more sophisticated study designs. [ABSTRACT FROM AUTHOR]

Although the external conformation of wild horse hooves has been proposed as an ideal model for domesticated modern horses, histological signs of laminitis have been reported among them. With the hypothesis that the lamellar tissue of horses of Iberian origin raised in semi-feral is healthier than those raised in an intensive management system (stall confinement and high-calorie diet intake), the objective was to compare their lamellar tissues. Lamellar tissue samples were taken from the forelimb hoof of eight domesticated Mangalarga Marchador (MM) horses and from six semi-feral Marajoara (MJ) and Puruca (MP) horses. Primary epidermal lamella (PEL) and secondary epidermal lamella (SEL) were measured (length and width) in several regions, and their shapes were morphologically classified into different types. Breed groups were compared using analysis of variance, followed by Tukey or Dunn tests (P<0.05). Early signs of laminitis such as abnormal keratinization of the abaxial primary dermal lamella, tapered tips of the axial PELs, pointed tips of the SEL, nuclei condensation, and abnormal spatial orientation of the secondary epidermal basal cells (SELBC), were seen only in MM horses. MP horses had a greater interface of epidermis/dermis contact than MJ horses and more rounded nuclei in the round SELBC than MM horses. In agreement with the study hypothesis, semi-feral MJ and MP horses' lamellae were classified as healthier than MM horses, which showed early signs of endocrinopathic laminitis. [ABSTRACT FROM AUTHOR]

The analgesic specificity of navicular bursa (NB) anesthetic infiltration is still questionable. The study aimed to determine the mechanical nociceptive threshold of non-specific analgesia in the dorsal lamellar stratum, as well as in the sole, coronary band, and heel bulbs of the hoof, after navicular bursa anesthetic infiltration. Six healthy horses with no clinical or radiographic changes of the digits and no communication between the NB and the distal interphalangeal joint, were used. After random selection, the NB of one of the forelimbs was infiltrated with 2% lidocaine and the contralateral one with lactated ringer's solution. Contrast was added to confirm radiographic infiltration. The mechanical nociceptive threshold was determined using a portable pressure dynamometer, before and at various times after the infiltration, in 10 points of the hoof. The effects of time and treatment were verified by ANOVA (P<0.05). There was no statistical difference in the values of the mechanical nociceptive threshold (P>0.05) in all regions evaluated. However, in one of the six hooves that receives lidocaine, complete absence of response to the painful stimulus (maximum force of 6 Kg over an area of 38.46 mm2, for a maximum of 4 seconds) was observed in the dorsal lamellae between 30 and 60 min after infiltration. In conclusion, lidocaine infiltration of NB did not promote significant increases in the nociceptive threshold of the sole, coronary band, bulbs of the heel and dorsal lamellae clinically healthy horses. However, the occurrence of analgesia in one of the six hooves subjected to NB anesthesia indicates that the technique may not be fully specific in few horses. [ABSTRACT FROM AUTHOR]

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Summary: Background: Obeticholic acid (OCA) was recently approved as the only on‐label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. Aim: To assess the effectiveness and safety of OCA in a real‐world cohort of patients with non‐effective UDCA therapy. Methods: Open‐label, prospective, real‐world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK‐PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA. Liver fibrosis was evaluated by FIB‐4 and AST to platelet ratio index (APRI). Results: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0‐13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy‐eight patients completed at least 1 year of OCA. The Globe‐PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK‐PBC score decreased to 0.81 (95% CI −0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB‐4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). Conclusions: This study supports data from phase III trials with significant improvement of PBC‐Globe continuous prognostic marker score among OCA‐treated patients with good tolerability. [ABSTRACT FROM AUTHOR]

Purpose: Nursing home-acquired pneumonia (NHAP) patients are at higher risk of multidrug resistant infection (MDR) than those with community-acquired pneumonia (CAP). Recent evidence suggests a single risk factor for MDR does not accurately predict the need for broadspectrum antibiotics. The goal of this study was to compare the rate antibiotic failure between NHAP and CAP patients. Methods: Demographic characteristics, co-morbidities, clinical and laboratory variables, antibiotic therapy, and mortality data were collected retrospectively for all patients with pneumonia admitted to an Internal Medicine Service between April 2017 and April 2018. Results: In total, 313 of 556 patients had CAP and 243 had NHAP. NHAP patients were older, and were more likely to be dependent, to have recent antibiotic use, and to experience treatment failure (odds ratio (OR) 1.583; 95% CI 1.102-2.276; p = 0.013). In multivariate analysis, patient's origin did not predict treatment failure (OR 1.083; 95% CI 0.726-1.616; p = 0.696). Discussion: Higher rates of antibiotic failure and mortality in NHAP patients were explained by the presence of other risk factors such as comorbidities, more severe presentation, and age. Admission from a nursing home is not a sufficient condition to start broader-spectrum antibiotics. [ABSTRACT FROM AUTHOR]

Background. With the hypothesis that equine dorsal lamellar tissue can be desensitized by anesthesia injection into distal interphalangeal joint (DIPJ), the objective was to assess the mechanical nociceptive threshold of hoof dorsal lamellae following intra-articular (IA) administration of lidocaine into this joint. Methods. The DIPJ of the forelimbs of six adult healthy horses were injected with either 5 mL of lidocaine, or 5 mL of lactated Ringer's solution. Treatments were randomly distributed, with each forelimb undergoing a single treatment. The hooves were evaluated pre- and post-injection at pre-selected times over 4 h, using a pressure algometry model. Mechanical nociceptive thresholds (MNTs)were recorded for the sole (dorsal, palmarolateral, and palmaromedial regions), coronary band (medial, lateral, and dorsal regions), heel bulbs (medial and lateral), and dorsal lamellar region (2 cm and 4 cmdistal to the coronary band). The MNT means were compared over time using the Friedman test and between treatments using the Wilcoxon signed-rank test, with values of P <0:05 considered statistically significant. Results. There were no differences between treatments for any region of the hoof during the evaluation period. However, MNT values indicating analgesia were recorded in the dorsal lamellar region in 50% of hooves following administration of lidocaine into the DIPJ. Conclusion. The administration of 5 mL of lidocaine into the DIPJ does not significantly increase the mechanical nociceptive threshold of the equine hoof. [ABSTRACT FROM AUTHOR]

The 3‐DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including >2300 HCV genotype 1–infected patients. Real‐world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ‐I and TOPAZ‐II are ongoing phase 3b trials, assessing safety, efficacy and long‐term progression of liver disease and clinical outcomes for up to 5 years post‐treatment in patients treated with OBV/PTV/r + DSV ± RBV. High rates of sustained virologic response (SVR) were achieved regardless of presence or absence of cirrhosis.In this report, we assessed the long‐term progression of liver disease and incidence of clinical outcomes up to 3 years of post‐treatment follow‐up in patients with chronic HCV GT1 infection who were treated with (OBV/PTV/r + DSV) ± RBV in the TOPAZ‐I and TOPAZ‐II studies. Improvements were observed in liver disease markers including FIB‐4, METAVIR and Child‐Pugh scores as well as platelet counts. Clinical outcomes related to long‐term progression of liver disease such as liver decompensation were infrequent (<1%). Hepatocellular carcinoma (HCC) occurred in 1.4% of cirrhotic patients. [ABSTRACT FROM AUTHOR]

The use of photobiomodulation therapy (PBMT) has shown promising results for the inflammatory modulation of tissue repair. This study aimed to evaluate the antiinflammatory potential of gallium arsenide (GaAs) PBMT in skin wound healing via (1) measurement of the temperature on the surface of the skin wound; (2) white blood cell count; and (3) histopathological examination. Skin lesions were induced on the dorsum of 20 Wistar rats, after which the animals were divided into two groups: a treatment group, subjected to GaAs PBMT, and a control group. Thermography was performed daily in all of the study animals until the end of the experiment. On the fourth day after lesion induction, whole blood was collected (white blood cell count), animals were euthanized, and skin lesions were biopsied (histopathological examination). There were no differences in the number of leukocytes and in the histopathological evaluations between the groups; however, the thermography analysis indicated an increase in temperature in the treated group. The antiinflammatory activity of GaAs PBMT was not confirmed. The increase in temperature on the surface of the skin lesions after LLLT requires further elucidation because this result could not be justified by the direct action of PBMT. [ABSTRACT FROM AUTHOR]

Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. Results. We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence. [ABSTRACT FROM AUTHOR]