Distinguishing immune checkpoint inhibitor-related pneumonitis from radiation pneumonitis by CT radiomics features in non-small cell lung cancer.

PURPOSE: To develop a CT-based model to classify pneumonitis etiology in patients with non-small cell lung cancer(NSCLC) after radiotherapy(RT) and Immune checkpoint inhibitors(ICIs). METHODS: We retrospectively identified 130 NSCLC patients who developed pneumonitis after receipt of ICIs only (n = 50), thoracic RT only (n = 50) (ICIs only + thoracic RT only, the training cohort, n = 100), and RT + ICIs (the test cohort, n = 30). Clinical and CT radiomics features were described and compared between different groups. We constructed a random forest (RF) classifier and a linear discriminant analysis (LDA) classifier by CT radiomics to discern pneumonitis etiology. RESULTS: The patients in RT + ICIs group have more high grade (grade 3-4) pneumonitis compared to patients in ICIs only or RT only group (p < 0.05). Pneumonitis after the combined therapy was not a simple superposition mode of RT-related pneumonitis(RP) and ICI-related pneumonitis(CIP), resulting in the distinct characteristics of both RT and ICIs-related pneumonitis. The RF classifier showed favorable discrimination between RP and CIP with an area under the receiver operating curve (AUC) of 0.859 (95 %CI: 0.788-0.929) in the training cohort and 0.851 (95 % CI: 0.700-1) in the test cohort. The LDA classifier achieved an AUC of 0.881 (95 %CI: 0.815-0.947) in the training cohort and 0.842 (95 %CI: 0.686-0.997) in the test cohort. Our analysis revealed four principal CT-based features shared across both models:original_glrlm_LongRunLowGrayLevelEmphasis, wavelet-HLL_firstorder_Median, wavelet-LLL_ngtdm_Busyness， and wavelet-LLL_glcm_JointAverage. CONCLUSION: CT radiomics-based classifiers could provide a noninvasive method to identify the predominant etiology in NSCLC patients who developed pneumonitis after RT alone, ICIs alone or RT + ICIs.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Morphologic and molecular alteration during tibia fracture healing in rat.

OBJECTIVE: To monitor morphological feature and related osteogenic and bone metabolic change during healing of tibia fracture in a rat model. MATERIALS AND METHODS: Tibia density and trabecular thickness were evaluated. Histopathology was examined by HE staining. Serous inflammatory factors IL-4, IL-6, TNF-α and metabolic biomarkers ALP, ß-CTX, P1NP, were determined by ELISA. The expression of RUNX2, TGF-ß1, VEGF-α, BMP-2, BMP-4, and BMP-7 in callus tissue were qualified by RT-PCR. RESULTS: Bone density decreased until week 4 and then increased post-operation. Trabeculae in callus were thickened over time with active osteogenesis. ELISA indicated the most severe inflammation at week 2, with the highest level of TNF-α, IL-6, and the lowest level of IL-4. After 4 weeks, the inflammation was alleviated accompanying with the decline of TNF-α and IL-6, while there was the elevation of IL-4. Bone metabolism showed active osteogenesis and resorption at week 6 with high P1NP and ß-CTX. The expression of RUNX2, TGF-ß1, VEGF-α, BMP-2, BMP-4, and BMP-7 increased progressively from week 1 to 6. The major lesions at week 2 in sham were tissue necrosis, periosteal reactive hyperplasia, inflammatory cell infiltration, capillary hyperplasia and slight fibro-blast cytopoiesis. At week 4, proliferation was greatly activated, fibrous callus shaped and chondrogenesis and some osteogenesis occurred at week 8. CONCLUSIONS: In rat model, bone density started to increase at week 6 after fracture, accompanied with trabeculae thickening, serous inflammatory factors decline, and peaked bone morphogenetic protein/growth factors, which indicated active osteogenesis was conforming to the classical phase of secondary fracture healing.

Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy.

BACKGROUND: Only limited evidence is available regarding the cytokine repertoire of effector T cells associated with peanut allergy, and how these responses relate to IgE antibodies to peanut components. OBJECTIVE: To interrogate T cell effector cytokine populations induced by Ara h 1 and Ara h 2 among peanut allergic (PA) children in the context of IgE and to evaluate their modulation during oral immunotherapy (OIT). METHODS: Peanut-reactive effector T cells were analysed in conjunction with specific IgE profiles in PA children using intracellular staining and multiplex assay. Cytokine-expressing T cell subpopulations were visualized using SPICE. RESULTS: Ara h 2 dominated the antibody response to peanut as judged by prevalence and quantity among a cohort of children with IgE to peanut. High IgE (> 15 kU(A)/L) was almost exclusively associated with dual sensitization to Ara h 1 and Ara h 2 and was age independent. Among PA children, IL-4-biased responses to both major allergens were induced, regardless of whether IgE antibodies to Ara h 1 were present. Among subjects receiving OIT in whom high IgE was maintained, Th2 reactivity to peanut components persisted despite clinical desensitization and modulation of allergen-specific immune parameters including augmented specific IgG4 antibodies, Th1 skewing and enhanced IL-10. The complexity of cytokine-positive subpopulations within peanut-reactive IL-4(+) and IFN-γ(+) T cells was similar to that observed in those who received no OIT, but was modified with extended therapy. Nonetheless, high Foxp3 expression was a distinguishing feature of peanut-reactive IL-4(+) T cells irrespective of OIT, and a correlate of their ability to secrete type 2 cytokines. CONCLUSION: Although total numbers of peanut-reactive IL-4(+) and IFN-γ(+) T cells are modulated by OIT in highly allergic children, complex T cell populations with pathogenic potential persist in the presence of recognized immune markers of successful immunotherapy.

Infection with human rhinovirus 16 promotes enhanced IgE responsiveness in basophils of atopic asthmatics.

BACKGROUND: Rhinovirus and IgE act in concert to promote asthma exacerbations. While basophils are the principal cell type in the blood that is activated by IgE, their role in virus-induced asthma episodes remains elusive. OBJECTIVE: To monitor IgE responsiveness in circulating basophils of rhinovirus-infected atopic asthmatics during acute infection and convalescence. METHODS: The capacity for basophils to respond to IgE was assessed by testing the effects of allergen, or cross-linking anti-FcεRI and anti-IgE antibodies, on surface TSLP receptor in 24-hour PBMC cultures. Activation profiles of basophils from atopic asthmatics challenged intranasally with human rhinovirus 16 were monitored directly ex vivo or else in 24-hour cultures, at baseline (day 0), and then at days 4 and 21 post-challenge. RESULTS: Basophils in atopic asthmatics, but not in non-atopic controls, upregulated TSLP receptor upon IgE receptor ligation. The magnitude of this response was correlated with the proportion of serum total IgE that was allergen-specific (r = 0.615, P < 0.05). Following rhinovirus infection, all subjects developed nasal symptoms that peaked 3-5 days after viral challenge. Basophils displayed maximal IgE responsiveness 3 weeks post-challenge as judged by TSLP receptor levels in 24-hour cultures. No significant change in total IgE or specific IgE antibodies was detected during rhinovirus infection. By contrast, levels of IgE receptor-associated spleen tyrosine kinase, Syk, were increased on day 4 (P < 0.05), and elevated levels were also detected three weeks post-challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating basophils display increased IgE responsiveness 3 weeks after rhinovirus infection in atopic asthmatics. This observation, coupled with increased expression of Syk, implicates basophils in promoting, or else prolonging, rhinovirus-induced inflammation in atopic asthmatics.

The effect of formulation on radioiodide thyroid uptake in the hyperthyroid cat.

This investigation was designed to compare in vitro dissolution profiles from sodium iodide capsules with radioiodide thyroid uptake in hyperthyroid cats using sodium iodide capsules prepared with a formulation exhibiting a complete release of radioiodide (I-123) in vitro and a formulation with an incomplete release of radioiodide. In vitro dissolution profiles for I-123 sodium iodide capsules with two different formulations were determined using the USP XXIII dissolution test. The two formulations studied in vitro were sodium phosphate dibasic powder with 1% magnesium stearate and calcium phosphate dibasic powder with 3% magnesium stearate. By 20 min after initiation of the dissolution test, over 95% of the I-123 was released from capsules of sodium phosphate dibasic powder. The capsules of calcium phosphate dibasic powder reached 75% at 65 min, with no further release occurring thereafter. There was a statistically significant difference in the dissolution profiles of the two formulations. The thyroid uptake of I-123 from capsules exhibiting complete release and incomplete release of radioiodide was determined in hyperthyroid cats. At 4 hr, the mean percentage thyroid uptake value for sodium phosphate dibasic powder with 1% magnesium stearate (complete release formulation) was 12.0% compared to 9.4% for calcium phosphate dibasic powder with 3% magnesium stearate (incomplete release formulation); at 24 hr, the values were 34.4% compared to 23.7%. The data suggest that the incomplete dissolution profile observed in vitro may correlate with a reduction in the bioavailability of the radioiodide in vivo. However, using the Wilcoxon signed rank test, statistically significant differences did not occur between the complete release formulation and incomplete release formulation at either 4 hr or 24 hr (p > .05). The results of the in vivo study with five hyperthyroid cats were not conclusive due to the variability in response between individual cats.

Influence of iodine-131 solution volume and storage time on in vitro dissolution.

OBJECTIVE: This investigation was conducted to determine the influence of 131I solution volume and storage time on the in vitro release of radioiodide from capsules. METHODS: In vitro dissolution profiles for 131I sodium iodide capsules compounded in a centralized nuclear pharmacy were determined using the USP XXIII Dissolution Test. Iodine-131 solution volumes of 0.05, 0.15 and 0.25 ml and storage times of 2, 5, 7 and 9 days were considered. RESULTS: By 80 min after initiation of the dissolution test, more than 95% of the 131I was released from capsules prepared with 0.15 and 0.25 ml of the 131I solution. The 0.05-ml capsules reached 95% at 55 min. Capsules prepared with 0.05 ml of solution and stored 2, 5, 7 or 9 days released over 95% of the radioactivity within 65 min. Capsules prepared with 0.25 ml of solution and stored for 2, 5, 7 or 9 days released over 95% of the 131I by 55 min after initiation of the dissolution test. CONCLUSION: Neither the different volume of radioactive sodium iodide solution used in the preparation of capsules nor the time of storage greatly influenced the release of 131I from the capsules. Based on dissolution profiles, it appears that the bioavailability of 131I would not be influenced by factors studied in this investigation.

[Enteral nutrition in the severely head injured patients].

This study evaluated the effect of modified element diet as early nutritional support in 20 severe head-injured patients. The study group (20 cases) was fed gastrically with the element diet of dextrin as glycogen by a nasal feeding tube, and the control group (20 cases) was nutritional supported with common method. The enteral nutrition (EN) was started within 5.0 +/- 2. 1 days post injury for study group versus 9.1 #+/- 4.6 days for control group (P < 0.05). The serum albumin levels of the study group rose in the third week post injury, the data of the forth week was slightly higher than that of the first week. In control group, the serum albumin levels reduced continuously within four weeks post injury. The serum glucose levels of the study group was significantly lower than that of the control group on the fifth day post injury (P < 0.05). 45% patients in the study group had diarrhea. This study showed that the modified element diet can be helpful for the early enteral nutrition and beneficial to improve the nutritional condition of the severe head-injured patients.

Therapeutic drug monitoring can avoid iatrogenic alterations caused by 99mTc-methylene diphosphonate (MDP)-gentamicin interaction.

Gentamicin is an aminoglycoside antibiotic used to treat a wide variety of infections caused by gram-negative organisms, but it is potentially toxic to the kidneys. Due to its nephrotoxicity, gentamicin may cause abnormal renal uptake to be seen on 99mTc-MDP bone scintigraphy. The presence of the radiopharmaceutical in the kidneys, along with an increase in renal retention, tend to produce scintigraphic results that falsely identify characteristics related to diseases such as renal vascular, or urinary tract obstruction, and even renal cancer. An altered biodistribution may provide misleading information that can either mask or mimic certain disease symptoms. A method to maximize the therapeutic benefit of gentamicin while minimizing the risk of nephrotoxicity and the appearance of a hot kidney on scintigraphy is desirable. Serial pharmacokinetic dosing has been proposed as a method to accomplish this goal. Therapeutic drug monitoring (TDM) of gentamicin therapy, and bone scintigraphy employing 99mTc-MDP as the radiopharmaceutical was carried out in 22 patients. The data presented here demonstrate that with serial pharmacokinetic dosing of gentamicin, the iatrogenic alteration caused by gentamicin therapy can be avoided.

[Urinary tract infection caused by Corynebacterium sp.--a case report and an experimental study].

We repose of chronic cystitis associated with alkali urine, struvite stones and a subsequent vesicorectal fistula caused by Corynebacterium sp, probably Corynebacterium group D2. We also studied in vitro and in vivo stone formation caused by Corynebacterium renale isolated clinically. C. renale inoculated into normal human urine increased urine pH and formed struvite crystals after a 24-hr incubation. Bladder stones were also formed in rats experimentally infected by C. renale as well as P. mirabilis. Some urea splitting species of Corynebacterium such as C. group D2 and C. renale may play a role in the formation of human struvite stone.