Tag: pubmed

Lung Cancer. 2021 Jul 20;160:17-27. doi: 10.1016/j.lungcan.2021.07.008. Online ahead of print.

ABSTRACT

OBJECTIVES: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy.

MATERIALS AND METHODS: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern.

RESULTS: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy.

CONCLUSION: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.

PMID:34371299 | DOI:10.1016/j.lungcan.2021.07.008

Microbiol Res. 2021 Jul 31;251:126836. doi: 10.1016/j.micres.2021.126836. Online ahead of print.

ABSTRACT

The concern regarding the emergence of phytopathogens strains which are resistant to conventional agrochemicals has given support to the search for alternatives on the use of chemical pesticides in agriculture. In this context, microorganisms are considered as promising sources of useful natural compounds and actinobacteria are particularly relevant since they are known to produce several bioactive metabolites. The objective of this work was to investigate the production of secondary metabolites with antifungal activity by a strain of the actinobacteria Streptomyces lunalinharesii (A54A) under axenic conditions and in co-cultivation with the phytopathogen Rhizoctonia solani. Tests to evaluate antifungal activity of the extracts indicated the presence of diffusable molecules capable of inhibiting the growth of R. solani produced by S. lunalinharesii, especially when in the presence of the fungus during fermentation. Metabolomic analyzes allowed the putative annotation of the bioactive compounds desferrioxamine E and anisomycin, in addition to the evaluation of the metabolic profile of the isolate when grown in axenic mode and in co-cultivation, while statistical analyzes enabled the comparison of such profiles and the identification of metabolites produced in greater relative quantities in the elicitation condition. Such methodologies provided the selection of unknown features with high bioactive potential for dereplication, and several metabolites of S. lunalinharesii possibly represent novel compounds.

PMID:34371303 | DOI:10.1016/j.micres.2021.126836

Tuberculosis (Edinb). 2021 Aug 5;130:102118. doi: 10.1016/j.tube.2021.102118. Online ahead of print.

ABSTRACT

BACKGROUND: There is an urgent need for new, accurate, rapid, and affordable tuberculosis (TB) diagnostic tests. The aim of the present study was to use mass spectrometry to identify new preliminary candidate TB diagnostic protein biomarkers in saliva obtained from individuals with TB, and patients with other respiratory diseases (ORD).

METHODS: Saliva samples were collected from 22 individuals who self-presented with symptoms suggestive of TB as part of a larger TB biomarker project. Purified salivary proteins were subjected to tryptic digestion peptides were analyzed using a QExactive Orbitrap Mass Spectrometer. Data are available via ProteomeXchange with identifier PXD027294. Identified proteins were subjected to gene ontology and ingenuity pathway analysis for functional enrichment analysis.

RESULTS: 26 of the 652 identified proteins significantly discriminated individuals with TB from those with ORD after Benjamini Hochberg correction (5% FDR), with five of these proteins diagnosing TB with an AUC ≥ 0.80. A 5-protein biosignature comprising of P01011, Q8NCW5, P28072, A0A2Q2TTZ9, and Q99574 diagnosed TB with an AUC of 1.00 (95% CI, 1.00-1.00), sensitivity of 100% (95% CI, 76.2-100%) and specificity of 90.9% (95% CI, 58.7-99.8%) after leave-one-out cross validation.

CONCLUSIONS: We identified novel candidate salivary protein biomarkers and biosignatures with strong potential as TB diagnostic candidates. Our results are preliminary and require validation in larger studies.

PMID:34371310 | DOI:10.1016/j.tube.2021.102118

Mult Scler Relat Disord. 2021 Aug 2;55:103185. doi: 10.1016/j.msard.2021.103185. Online ahead of print.

ABSTRACT

BACKGROUND: We previously reported that the single nucleotide polymorphism (SNP) rs9282860 in serine threonine kinase 11 (STK11) gene which codes for liver kinase B1 (LKB1) has higher prevalence in White relapsing-remitting multiple sclerosis (RRMS) patients than controls. However it is not known if this SNP is a risk factor for MS in other populations.

METHODS: We assessed the prevalence of the STK11 SNP in samples collected from African American (AA) persons with MS (PwMS) and controls at multiple Veterans Affairs (VA) Medical Centers and from a network of academic MS centers. Genotyping was carried out using a specific Taqman assay. Comparisons of SNP frequencies were made using Fisher’s exact test to determine significance and odds ratios. Group means were compared by appropriate t-tests based on normality and variance using SPSS V27.

RESULTS: There were no significant differences in average age at first symptom onset, age at diagnosis, disease duration, or disease severity between RRMS patients recruited from VAMCs versus non-VAMCs. The SNP was more prevalent in AA than White PwMS, however only in secondary progressive MS (SPMS) patients was that difference statistically significant. AA SPMS patients had higher STK11 SNP prevalence than controls; and in that cohort the SNP was associated with older age at symptom onset and at diagnosis.

CONCLUSIONS: The results suggest that the STK11 SNP represents a risk factor for SPMS in AA patients, and can influence both early (onset) and later (conversion to SPMSS) events.

PMID:34371271 | DOI:10.1016/j.msard.2021.103185

Am J Dent. 2021 Aug;34(4):222-227.

ABSTRACT

PURPOSE: To evaluate the effect of a stannous-containing fluoride dentifrice on gingival health and on the composition of the oral microbiome versus a positive control dentifrice over 2 weeks, in a population of healthy adults with self-reported sub-optimal oral health at baseline.

METHODS: This was a randomized, controlled, double-blind clinical study. 87 subjects with self-reported sub-optimal oral health at enrollment were randomized to brush twice daily with either an experimental dentifrice (n= 43) or a marketed positive control dentifrice (n= 43), both containing stannous chloride and 0.321% sodium fluoride. All subjects used a soft, manual toothbrush that was provided. The Mazza modification of gingival papillary bleeding Index (Mazza GI) was used to assess gingivitis at baseline and at Week 2. Supragingival plaque was collected for microbiome composition analyses at baseline, Week 1, and Week 2.

RESULTS: 83 subjects completed the study. Baseline means were balanced between the treatment groups (P> 0.34). At Week 2, the positive control dentifrice demonstrated a 63.8% statistically significant (P< 0.0001) reduction relative to baseline for Mazza number of gingival bleeding sites. The experimental stannous containing dentifrice provided a comparable 63.5% gingival bleeding reduction versus baseline. There was no significant (P= 0.96) difference between the two dentifrices for either Mazza GI score or number of bleeding sites measured. The microbiome composition analysis at Week 1 found that 28 gingivitis-associated bacterial genera, including Porphyromonas, Tannerella, and Fusobacterium, were significantly inhibited in both dentifrice groups when compared to baseline, while the relative abundance of genera associated with oral health, such as Rothia, Streptococcus, Haemophilus, and Lautropia, was significantly elevated after treatment. These improvements in the oral ecosystem were sustained at Week 2.

CLINICAL SIGNIFICANCE: An experimental stannous-containing sodium fluoride dentifrice significantly reduced gingival bleeding comparable to a positive control, and both dentifrices promoted a shift in the oral microbiome towards those genera associated with oral health in a subject population with self-reported sub-optimal oral health at baseline.

PMID:34370916

G Ital Med Lav Ergon. 2021 Jun;43(2):118-125.

ABSTRACT

Background. Spondylodiscopathies are usually counted among the “work-related diseases” that are those chronic-degenerative diseases with multifactorial etiology where the work environment can sometimes assume the role of direct and efficient contributing cause. Low back pain is the main cause of functional limitation and absence from work in the western world, resulting in a huge individually and socially economic burden. Objective. This work was designed to provide an overview of the impact that lumbar rachipathies have on health surveillance, highlighting the correlations between the pathology severity, characterization of professional risk and issue of elegibility for the specific task. Methods. Was analyzed a case studies of lumbar rachipathies reports received by INAIL in the entire Abruzzo region in 2017, the last year available in the INAIL database at the time of data extrapolation dating back to May 2019. For each dossier were collected data extrapolated from: DVR, medical record and risk, instrumental examinations and specialist visits. The software “Epi Info” version 7 was used for the statistical analysis of the sample, provided by the CDC (Centers for Disease Control and Prevention) in Atlanta. Results. The expression of work elegibility with limitations and/or prescriptions by the phisicians is related only to clinical symptoms and not to the presence of a herniated disc on CT or MRI tests. The exposure to risk from MMH and WBV, documented in the DVR, was not found to be related to the presence of a herniated disc on instrumental examinations. There was no significant difference in the average age between workers recognized as technopathic from non-technopathic. Conclusions. Although biomechanical overload has always been considered as an important wear element of the intervertebral disc, genetic influences and constitutional factors seem to be elements more implicated in the development of hernial disc disease.

PMID:34370921

G Ital Med Lav Ergon. 2021 Jun;43(2):156-166.

ABSTRACT

Haemophilia in its most severe clinical form can lead to alterations in the physical and psychosocial state with important repercussions on the quality of life. Purpose. A retrospective study was conducted to highlight the impact of haemophilic arthropathy on quality of life. Materials. We considered 25 patients, with a mean age of 42 years (min 17 – max 71) with haemophilia A, 18 had the severe clinical form (72%). The WFH Physical Examination Score, specific for haemophilia, was used for joint function; the joints examined were: knee, ankle, hip and elbow. To assess the quality of life, two generic self-filling questionnaires were used, SF-36 and the EQ 5D. Results. Significant statistical values have shown that arthropathy affects the SF-36 domain of general health and the subjective well-being EQ-VAS. Conclusions. In the treatment of haemophilic arthropathy, prevention is essential, understood both as a prophylactic medical therapy and as a physiotherapeutic treatment in order to maintain or improve joint function and at the same time play a fundamental role in improving the quality of life of patients.

PMID:34370927

Am J Dent. 2021 Aug;34(4):191-194.

ABSTRACT

PURPOSE: To evaluate the in vitro protective effect of a mint formulation containing (-)-epigallocatechin-3-gallate (EGCg-mint) on root dentin exposed to a highly erosive environment in the presence and absence of proteolytic challenge.

METHODS: Root dentin specimens were subjected to an erosion-remineralization cycling model (6×/day; 5 days) that included 5-minute immersion in 1% citric acid and 60-minute immersion in remineralization solution (RS). At the remineralization half-time, the specimens were treated (n= 20) with EGCg-mint, RS (negative control) or sodium fluoride (1,000 ppm of NaF; positive control). Half of the specimens were kept overnight in RS (pH cycling) and the other half in RS with Clostridium histolyticum collagenase (pH-proteolytic cycling). Erosion depth was measured using optical profilometry and data analyzed by two-way ANOVA and Tukey tests (α= 0.05).

RESULTS: Under pH-cycling, NaF resulted in statistically lower erosion depth compared to EGCg-mint (P= 0.020) and RS (P= 0.005). Under pH-proteolytic cycling, EGCg-mint and NaF significantly decreased the tissue loss (erosion depth, P< 0.001) compared to the RS. The EGCg-mint exhibited an anti-erosion property on root dentin under a proteolytic challenge. NaF presented an anti-erosion property regardless of the erosive cycling model.

CLINICAL SIGNIFICANCE: The anti-erosive action of an over-the-counter mint, containing active ingredients, including epigallocatechin-3-gallate, is likely by the protective mechanisms of the dentin extracellular matrix.

PMID:34370910

Am J Dent. 2021 Aug;34(4):211-214.

ABSTRACT

PURPOSE: To assess the prevalence of periapical abscesses in patients with rheumatoid arthritis, and to evaluate the effect of commonly used antirheumatic medications on such prevalence.

METHODS: Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for rheumatoid arthritis and periapical abscess was retrieved by searching the appropriate query in the database. The odd ratio (OR) of periapical abscesses, its association with rheumatoid arthritis and intake of three commonly prescribed antirheumatic medications were calculated and analyzed statistically.

RESULTS: The prevalence of periapical abscesses in patients with rheumatoid arthritis was 1.53% as compared to 0.51% in the general patient population of the hospital. The OR was 2.60 and the difference was statistically significant (P< 0.0001). In patients treated with either Methotrexate, Sulfasalazine, or Etanercept, the ORs were 2.88, 3.1, and 1.07, respectively. The differences between Methotrexate and Sulfasalazine were statistically significant (P< 0.0001). The OR for prevalence of periapical abscesses in patients treated with Etanercept was significantly lower than that of patients treated with either Methotrexate or Sulfasalazine (P< 0.005).

CLINICAL SIGNIFICANCE: Oral healthcare providers should be aware of the possible association between rheumatoid arthritis and occurrence of periapical abscesses. Patients with rheumatoid arthritis, mainly women, may exhibit higher prevalence of periapical abscesses. Treatment with TNF alpha inhibitors may lower the prevalence of periapical abscesses in such patients.

PMID:34370914

Dig Endosc. 2021 Aug 9. doi: 10.1111/den.14103. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Underwater endoscopic mucosal resection (UEMR) have been reported as effective endoscopic treatment for superficial duodenal tumors (SDETs). However, it has been reported that a notable problem of UEMR for SDETs is that en bloc resection rate is relatively low. Therefore, we proposed a novel technique to improve en bloc resection rate: UEMR combining partial submucosal injection (PI-UEMR). The aim of this study is to evaluate efficacy and safety of PI-UEMR for SDETs by comparing to UEMR.

METHODS: This is a retrospective observational study in a single-center. The patients who underwent UEMR or PI-UEMR from June 2010 to August 2020 ware included in this study. Eligible patients were selected from included patients in a 1 :1 ratio using propensity score matching. The clinical outcomes of endoscopic resection [procedure time, En bloc resection rate, complication rate (immediate perforation, delayed bleeding, delayed perforation)], and histopathological diagnosis (Adenoma/Cancer) were compared between each group.

RESULTS: Two-hundred twenty-eight patients were included in this study. Of included patients, 47 patients were selected in each group by propensity score matching. There were no statistical differences in procedure time (11±1.2min vs 9±1.2min, p=0.30), complication rate [immediate perforation (0% vs 2%, p=0.12), delayed bleeding(0% vs 2%, p=0.12),and no delayed perforation] and histopathological diagnosis (Adenoma; 100% vs 96%, p=0.14) in each group. However, en bloc resection rate of PI-UEMR was significantly higher than UEMR (96% vs 83%, p <0.05).

CONCLUSION: PI-UEMR might be superior procedure for en bloc resection in SDETs compare to UEMR.

PMID:34370891 | DOI:10.1111/den.14103