In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin-based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3-palmitate (EV-P), an ester lipidic prodrug for entecavir (EV), was employed. The EV-P-loaded TS was prepared by ultra-sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 μm), crystallinity (melting point of 160-165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS-injected site, drug aggregates of up to 500 μm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS-injected site, with >4 weeks remaining of the oily vehicle in micro-computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long-acting delivery, with improved local tolerability.

Tail docking in lambs is associated with an acute inflammatory and ischemic response correlated to pain. The present study sought to quantify these responses by utilizing infrared thermographic imaging (IRT) after tail docking lambs. Images were taken for each lamb before tail docking (T0), within a minute after the band was placed (T1), at 5 minutes (T5), and 15 minutes (T15) respectively and analyzed for pixel intensity in areas on the lamb\'s rump, tail base, and two locations below the docking band. The pixel intensity at 2 cm below the docking band did significantly decrease (p < 0.05) over the course of the study at 15 minutes, indicating the presence of ischemia, and a significant decrease in the pixel intensity of the rump and tail base was observed. The closest location to the rubber ring showed the presence of inflammation as an indirect indicator of acute pain . IRT is a valuable tool in the detection of inflammation and ischemic areas and has the potential to be used to quantify and measure the experience of inflammation and pain after tail docking.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31-7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22-4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis.

The purpose of this work was to determine the viscoelastic behavior of porcine and human oral mucosa under physiological conditions of temperature, hydration and chewing. The linear elastic and viscous shear moduli of these soft tissues were determined by small-amplitude oscillatory shear (SAOS) tests at masticatory frequency using a stress-controlled rheometer equipped with an immersion cell on punched biopsies 8 mm in diameter. Non physiological conditions of temperature were also used to access other parameters such as the denaturation temperature of collagen. First, the different parameters such as normal force, frequency and maximal strain were adjusted to obtain reliable data on porcine mucosa. The optimal normal force was 0.1N and the linear viscoelastic limit was found for a strain amplitude of 0.5% for both 0.1 and 1 Hz. The storage moduli of porcine mucosa, ranging from 5 to 16 kPa, were in the same range as cutaneous tissues determined by SAOS at equivalent frequencies. The storage modulus, superior to the loss modulus G″, indicates a predominant elastic contribution to shear stress in chewing conditions. Second, this protocol evidenced an influence of the anatomic site of the mouth on the viscoelastic behavior of porcine mucosa, mandibular biopsies having higher storage moduli than maxillary biopsies. Temperature scans showed the mechanical manifestation of collagen denaturation in the 60-70 °C range as previous calorimetric analyses. Finally, this mechanical protocol was successfully adapted to characterize human mucosa in an elderly population. It was shown that the elastic modulus is impacted by local inflammation (gingivitis), decreasing significantly from 6 ± 1.4 kPa to 2.5 ± 0.3 kPa.

Introduction The genesis of chronic rhinosinusitis is always a topic of debate. A polyp is a pale, edematous tissue emerging mostly from the middle meatus. An epithelial injury caused by continuous inflammation of the nasal mucosa is considered to be a possible cause of the genesis of nasosinusal polyps. Objective To understand the link between serum albumin levels and nasal polyposis. Methods A retrospective study of 180 consecutive patients between January 2016 and January 2020 at our center. We then divided the patients into three age- and gender-matched groups: 60 patients with chronic rhinosinusitis with nasal polyposis, 60 patients with chronic rhinosinusitis without nasal polyposis, and a control group with 60 patients. No patient had a history of any pathology that could alter serum albumin. We then compared the level of serum albumin between the three groups. Results The group of patients with rhinosinusitis and nasal polyposis consisted of 60 patients with a serum albumin value of 4.49 ± 0.29 g/dL, whereas in the control group, the serum albumin value was 4.67 ± 0.2 g/dL. We found a significant difference between the group with nasal polyposis and the other two groups evaluated: chronic rhinosinusitis without nasal polyposis (p<0.001) and the control group (p<0.001). Conclusions Lower levels of serum albumin can be seen in patients with chronic rhinosinusitis with nasal polyposis. Further studies should aim to apply its value since it is a non-expensive marker, to the follow-up of those patients or even to stratify them according to their endotype.

In recent years, the interplay between oral microbiota and systemic disease has gained attention as poor oral health is associated with several pathologies. The oral microbiota plays a role in the maintenance of overall health, and its dysbiosis influences chronic inflammation and the pathogenesis of gum diseases. Periodontitis has also been associated with other diseases and health complications such as cancer, neurogenerative and autoimmune disorders, chronic kidney disease, cardiovascular diseases, rheumatic arthritis, respiratory health, and adverse pregnancy outcomes. The host microbiota can influence immune cell development and immune responses, and recent evidence suggests that changes in oral microbiota composition may also contribute to sensitization and the development of allergic reactions, including asthma and peanut allergies. Conversely, there is also evidence that allergic reactions within the gut may contribute to alterations in oral microbiota composition. Here we review the current evidence of the role of the oral microbiota in inflammatory diseases and health complications, as well as its future relevance in improving health and ameliorating allergic disease.

UNASSIGNED: Telangiectatic osteosarcoma (TOS) is a rare but highly malignant subtype of osteosarcoma. Although surgical treatment is the primary treatment modality for osteosarcoma, evidence on the benefits of different surgical methods in patients with TOS is lacking. This study aimed to compare the effects of different surgical and adjuvant treatments on overall survival of TOS, and the association of patient demographics, oncological characteristics, and socioeconomic status on treatment outcomes.
UNASSIGNED: This retrospective study selected the most common TOS cases of the extremities registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1989 to 2019. Univariate and multivariate Cox regression models were used to analyze all prognostic factors, and Kaplan-Meier analyses were performed for disease-specific treatment factors of survival.
UNASSIGNED: A total of 127 patients were included in the analysis. The average age at initial diagnosis was 20.09 years. In univariate analyses, the absence of metastasis at initial diagnosis, limb-salvage surgery, adjuvant chemotherapy, and no regional lymph node dissection were associated with a lower risk of death. Multivariate analysis further showed that the presence or absence of distant metastasis and regional lymph node dissection, implementation of adjuvant chemotherapy, and choice of surgical method were independent predictors of prognosis.
UNASSIGNED: Distant metastasis and regional lymph node dissection are associated with poorer outcomes in TOS, and amputation has no better prognosis than limb salvage surgery. Compared with conventional chemotherapy, neoadjuvant chemotherapy did not significantly improve the prognosis of TOS.

Rotigotine (RTG) is prescribed as a once-daily transdermal patch for managing early Parkinson’s disease (PD), which presents issues such as skin irritation and poor patient adherence. Therefore, the aims of the present study were to formulate aqueous and oily vehicle-based RTG crystalline suspensions for prolonged delivery and to compare their pharmacokinetic profiles and the local behaviors of RTG crystals. RTG-loaded aqueous (AS) and oil suspensions (OS) were fabricated using bead-milling technology (100 mg/mL as RTG), employing carboxymethyl cellulose and sesame oil as suspending agent and oily vehicle, respectively. RTG AS and OS exhibited comparable physical properties in terms of particle size (about 800−900 nm), crystallinity, and dissolution profile, despite higher drug solubility in OS than AS (19.6 and 0.07 mg/mL, respectively). However, AS and OS exhibited markedly distinctive local distribution and inflammatory responses at the injection site, which further promoted different pharmacokinetic patterns following subcutaneous injection in rats. With OS, no drug aggregates were observed with prolonged persistence of the Sudan III-stained oily vehicle at the injection site. In contrast, with AS injection, drug clusters > 7 mm were formed, followed by an enclosure with macrophages and a fibroblastic band. Accordingly, AS exhibited a protracted pharmacokinetic profile over 3 weeks, with prolonged elimination half-life. The local inflammatory response caused by AS injection was almost alleviated after 3 weeks post-dosing. Based on these findings, we conclude that RTG AS system can be a platform to design sophisticated long-acting delivery systems with extended dosing intervals to manage PD.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical disease with an increasing incidence. The absorption route of CSDH is not clear. Whether inflammatory factors enter the peripheral blood and cause systemic reactions is unknown.
METHODS: We screened 105 CSDH patients and 105 control individuals. Their clinical characteristics and blood routine results were collected and compared. The blood routine changes of CSDH patients before and after treatment were compared. Age-stratified analysis was performed due to age may affect the inflammatory markers.
RESULTS: The white blood cell count, absolute neutrophil count, neutrophil percentage, neutrophil-lymphocyte count ratio (NLR), and platelet to lymphocyte count ratio (PLR) of CSDH patients before treatment were within the normal range, while were significantly higher than the control individuals (p < 0.001). The absolute lymphocyte count and lymphocyte percentage of control individuals were higher than those of patients (p < 0.001). The inflammatory cells in patients of different age groups were similar. After the patient was cured, the white blood cell count, the absolute value and percentage of neutrophils decreased (p < 0.05), while the number of monocytes increased.
CONCLUSIONS: CSDH caused slight systemic inflammatory responses in the peripheral blood, implying that there is a non-hematologic route for the absorption of hematoma.

Occult hypoperfusion (OH) is defined as persistent lactic acidosis despite normalization of vital parameters following trauma. The aim of this study was to analyze the association of occult hypoperfusion with local circulation and inflammation of injured soft tissue in a porcine polytrauma model.
This experimental study was performed with male landrace pigs who suffered a standardized polytrauma, including a femoral fracture, blunt chest trauma, liver laceration and a mean arterial pressure (MAP) controlled hemorrhagic shock. One hour after induction of trauma, the animals were resuscitated with retrograde femoral nailing, liver packing and volume replacement. Animals were stratified into Group Norm (normalizing lactate levels after resuscitation) and Group occult hypoperfusion (OH) (persistent lactate levels above 2 mmol/l with normalizing vital parameters after resuscitation). Local circulation (oxygen saturation, hemoglobin amount, blood flow) was measured with optical sensors at the subcutaneous soft tissue at the fractured extremity as well as at the stomach and colon. Local inflammatory parameters [interleukin (IL) 6, 8, 10, and heat shock protein (HSP)] were analyzed in the subcutaneous tissue of the fractured extremity.
Group Norm (n = 19) and Group OH (n = 5) were comparable in baseline vital and laboratory parameters. The shock severity and total amount of blood loss were comparable among Group Norm and Group OH. Following resuscitation Group OH had significantly lower local relative hemoglobin amount at the injured soft tissue of the fractured extremity when compared with Group Norm (39.4, SD 5.3 vs. 63.9, SD 27.6 A.U., p = 0.031). The local oxygenation was significantly lower in Group OH compared to Group Norm (60.4, SD 4.6 vs. 75.8, SD 12.8, p = 0.049). Local IL-6 in the fatty tissue was significantly higher in Group OH (318.3, SD 326.6 [pg/ml]) when compared with Group Norm (73.9,SD 96.3[pg/ml], p = 0.03). The local circulation at the abdominal organs was comparable in both groups.
OH is associated with decreased local circulation and increased local inflammation at the injured soft tissue of the extremity in polytrauma. OH might reflect the severity of local soft tissue injuries, and guide treatment strategies.