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Mycopathologia Oct 2017Invasive candidiasis is caused mainly by Candida albicans, but other Candida species have increasing etiologies. These species show different virulence and... (Comparative Study)
Comparative Study
Invasive candidiasis is caused mainly by Candida albicans, but other Candida species have increasing etiologies. These species show different virulence and susceptibility levels to antifungal drugs. The aims of this study were to evaluate the usefulness of the non-conventional model Caenorhabditis elegans to assess the in vivo virulence of seven different Candida species and to compare the virulence in vivo with the in vitro production of proteinases and phospholipases, hemolytic activity and biofilm development capacity. One culture collection strain of each of seven Candida species (C. albicans, Candida dubliniensis, Candida glabrata, Candida krusei, Candida metapsilosis, Candida orthopsilosis and Candida parapsilosis) was studied. A double mutant C. elegans AU37 strain (glp-4;sek-1) was infected with Candida by ingestion, and the analysis of nematode survival was performed in liquid medium every 24 h until 120 h. Candida establishes a persistent lethal infection in the C. elegans intestinal tract. C. albicans and C. krusei were the most pathogenic species, whereas C. dubliniensis infection showed the lowest mortality. C. albicans was the only species with phospholipase activity, was the greatest producer of aspartyl proteinase and had a higher hemolytic activity. C. albicans and C. krusei caused higher mortality than the rest of the Candida species studied in the C. elegans model of candidiasis.
Topics: Animals; Aspartic Acid Proteases; Caenorhabditis elegans; Candida; Candidiasis; Disease Models, Animal; Gastrointestinal Tract; Hemolysis; Phospholipases; Survival Analysis; Virulence
PubMed: 28523422
DOI: 10.1007/s11046-017-0142-8 -
Pain and Therapy Jun 2021A previous Delphi survey from the Rational Use of Analgesics (RUA) project involving Italian palliative care specialists revealed some discrepancies between current...
INTRODUCTION
A previous Delphi survey from the Rational Use of Analgesics (RUA) project involving Italian palliative care specialists revealed some discrepancies between current guidelines and clinical practice with a lack of consensus on items regarding the use of strong opioids in treating cancer pain. Those results represented the basis for a new Delphi study addressing a better approach to pain treatment in patients with cancer.
METHODS
The study consisted of a two-round multidisciplinary Delphi study. Specialists rated their agreement with a set of 17 statements using a 5-point Likert scale (0 = totally disagree and 4 = totally agree). Consensus on a statement was achieved if the median consensus score (MCS) (expressed as value at which at least 50% of participants agreed) was at least 4 and the interquartile range (IQR) was 3-4.
RESULTS
This survey included input from 186 palliative care specialists representing all Italian territory. Consensus was reached on seven statements. More than 70% of participants agreed with the use of low dose of strong opioids in moderate pain treatment and valued transdermal route as an effective option when the oral route is not available. There was strong consensus on the importance of knowing opioid pharmacokinetics for therapy personalization and on identifying immediate-release opioids as key for tailoring therapy to patients' needs. Limited agreement was reached on items regarding breakthrough pain and the management of opioid-induced bowel dysfunction.
CONCLUSION
These findings may assist clinicians in applying clinical evidence to routine care settings and call for a reappraisal of current pain treatment recommendations with the final aim of optimizing the clinical use of strong opioids in patients with cancer.
PubMed: 33730338
DOI: 10.1007/s40122-021-00248-x -
Journal of Dual Diagnosis 2015Many individuals receiving methadone maintenance receive their treatment through their primary care provider. As many also drink alcohol excessively, there is a need to...
OBJECTIVE
Many individuals receiving methadone maintenance receive their treatment through their primary care provider. As many also drink alcohol excessively, there is a need to address alcohol use to improve health outcomes for these individuals. We examined problem alcohol use and its treatment among people attending primary care for methadone maintenance treatment, using baseline data from a feasibility study of an evidence-based complex intervention to improve care.
METHODS
Data on addiction care processes were collected by (1) reviewing clinical records (n = 129) of people who attended 16 general practices for methadone maintenance treatment and (2) administering structured questionnaires to both patients (n = 106) and general practitioners (GPs) (n = 15).
RESULTS
Clinical records indicated that 24 patients (19%) were screened for problem alcohol use in the 12 months prior to data collection, with problem alcohol use identified in 14 (58% of those screened, 11% of the full sample). Of those who had positive screening results for problem alcohol use, five received a brief intervention by a GP and none were referred to specialist treatment. Scores on the Alcohol Use Disorders Identification Test (AUDIT) revealed the prevalence of hazardous, harmful, and dependent drinking to be 25% (n = 26), 6% (n = 6), and 16% (n = 17), respectively. The intraclass correlation coefficient (ICC) for the proportion of patients with negative AUDITs was 0.038 (SE = 0.01). The ICCs for screening, brief intervention, and/or referral to treatment (SBIRT) were 0.16 (SE = 0.014), -0.06 (SE = 0.017), and 0.22 (SE = 0.026), respectively. Only 12 (11.3%) AUDIT questionnaires concurred with corresponding clinical records that a patient had any/no problem alcohol use. Regular use of primary care was evident, as 25% had visited their GP more than 12 times during the past 3 months.
CONCLUSIONS
Comparing clinical records with patients' experience of SBIRT can shed light on the process of care. Alcohol screening in people who attend primary care for substance use treatment is not routinely conducted. Interventions that enhance the care of problem alcohol use among this high-risk group are a priority.
Topics: Adult; Alcoholism; Feasibility Studies; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Primary Health Care; Substance Abuse Detection
PubMed: 25985200
DOI: 10.1080/15504263.2015.1027630 -
Lancet (London, England) Sep 2019Decreased surgical site infections (SSIs) and morbidity have been reported with mechanical and oral antibiotic bowel preparation (MOABP) compared with no bowel... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Decreased surgical site infections (SSIs) and morbidity have been reported with mechanical and oral antibiotic bowel preparation (MOABP) compared with no bowel preparation (NBP) in colonic surgery. Several societies have recommended routine use of MOABP in patients undergoing colon resection on the basis of these data. Our aim was to investigate this recommendation in a prospective randomised context.
METHODS
In this multicentre, parallel, single-blinded trial, patients undergoing colon resection were randomly assigned (1:1) to either MOABP or NBP in four hospitals in Finland, using a web-based randomisation technique. Randomly varying block sizes (four, six, and eight) were used for randomisation, and stratification was done according to centre. The recruiters, treating physicians, operating surgeons, data collectors, and analysts were masked to the allocated treatment. Key exclusion criteria were need for emergency surgery; bowel obstruction; colonoscopy planned during surgery; allergy to polyethylene glycol, neomycin, or metronidazole; and age younger than 18 years or older than 95 years. Study nurses opened numbered opaque envelopes containing the patient allocated group, and instructed the patients according to the allocation group to either prepare the bowel, or not prepare the bowel. Patients allocated to MOABP prepared their bowel by drinking 2 L of polyethylene glycol and 1 L of clear fluid before 6 pm on the day before surgery and took 2 g of neomycin orally at 7 pm and 2 g of metronidazole orally at 11 pm the day before surgery. The primary outcome was SSI within 30 days after surgery, analysed in the modified intention-to-treat population (all patients who were randomly allocated to and underwent elective colon resection with an anastomosis) along with safety analyses. The trial is registered with ClinicalTrials.gov, NCT02652637, and EudraCT, 2015-004559-38, and is closed to new participants.
FINDINGS
Between March 17, 2016, and Aug 20, 2018, 738 patients were assessed for eligibility. Of the 417 patients who were randomised (209 to MOABP and 208 to NBP), 13 in the MOABP group and eight in the NBP were excluded before undergoing colonic resection; therefore, the modified intention-to-treat analysis included 396 patients (196 for MOABP and 200 for NBP). SSI was detected in 13 (7%) of 196 patients randomised to MOABP, and in 21 (11%) of 200 patients randomised to NBP (odds ratio 1·65, 95% CI 0·80-3·40; p=0·17). Anastomotic dehiscence was reported in 7 (4%) of 196 patients in the MOABP group and in 8 (4%) of 200 in the NBP group, and reoperations were necessary in 16 (8%) of 196 compared with 13 (7%) of 200 patients. Two patients died in the NBP group and none in the MOABP group within 30 days.
INTERPRETATION
MOABP does not reduce SSIs or the overall morbidity of colon surgery compared with NBP. We therefore propose that the current recommendations of using MOABP for colectomies to reduce SSIs or morbidity should be reconsidered.
FUNDING
Vatsatautien Tutkimussäätiö Foundation, Mary and Georg Ehrnrooth's Foundation, and Helsinki University Hospital research funds.
Topics: Administration, Intravenous; Aged; Anti-Bacterial Agents; Cathartics; Cefuroxime; Colectomy; Elective Surgical Procedures; Female; Humans; Male; Metronidazole; Middle Aged; Polyethylene Glycols; Preoperative Care; Prospective Studies; Single-Blind Method; Surgical Wound Infection
PubMed: 31402112
DOI: 10.1016/S0140-6736(19)31269-3 -
Rheumatology (Oxford, England) Dec 2021The Flare Assessment in RA (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between two consultations. This study aimed...
OBJECTIVE
The Flare Assessment in RA (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between two consultations. This study aimed to establish a threshold for FLARE-RA score to identify RA flare.
METHODS
The Tocilizumab SubCutAneous study evaluated the efficacy and safety of s.c. tocilizumab (TCZ) to patients with active RA. Disease activity was assessed with the DAS28ESR at baseline and at week 2 (W2), W4, W12 and W24. The FLARE-RA questionnaire was administered at W12 and W24. Patient satisfaction, assessed at baseline and W24 with the Patient Acceptable Symptom State (PASS), was used as a surrogate marker of no flare. A correlation was sought between the FLARE-RA score at W12 and W24 and the area under the receiver operating characteristic (ROC) curve (AUC) for monthly DAS28ESR. The optimal FLARE-RA cut-off below which patient satisfaction reached the PASS was explored with an ROC curve.
RESULTS
A total of 139 patients were included (mean age 57.3 ± 13.8 years, 74.1% women, mean RA duration 10.8 ± 9.2 years, mean DAS28ESR 5.8 ± 1.1). The correlation between the FLARE-RA score and DAS28ESR AUC was moderate at all times: ρ = 0.41 at W12 (P < 0.0001) and 0.51 at W24 (P < 0.0001). The optimal cut-off for the FLARE-RA score to identify absence of flare (i.e. an acceptable situation based on the PASS) was 2.3 with an AUC of 0.81.
CONCLUSION
FLARE-RA and DAS28ESR assessment differ; we propose a FLARE-RA cut-off of 2.3, below which the situation (i.e. without flare) is acceptable for patients.
Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Severity of Illness Index; Symptom Flare Up
PubMed: 33788913
DOI: 10.1093/rheumatology/keab261 -
Omics : a Journal of Integrative Biology Sep 2021Radiology and radiotherapy are currently undergoing radical transformation with use of biomarkers and digital technologies such as artificial intelligence. These current...
Radiology and radiotherapy are currently undergoing radical transformation with use of biomarkers and digital technologies such as artificial intelligence. These current and upcoming changes in radiology speak of an overarching new vision for personalized medicine. This is particularly evident in the case of radiotherapy of cancers, and of liver cancer in particular. The development of modern radiotherapy with stereotactic body radiotherapy allows targeted treatments to be delivered to the tumor site, limiting the dose to surrounding healthy organs, thus becoming a new therapeutic alternative for hepatocellular carcinoma and other liver tumors. However, not all patients have the same response to radiotherapy or display the same side-effect profile. Biomarkers of response and toxicity in liver radiotherapy would facilitate the vision and practice of personalized medicine. This expert review examines the available molecular, radiomic, and radiogenomic biomarker candidates for acute liver toxicity with potential use for prediction of radiotherapy-induced liver toxicity. To this end, I highlight for oncologists and life scientists that radiomics allows diagnostic images to be analyzed using computer algorithms to extract information imperceptible to the human eye and of relevance to forecasting clinical outcomes. This article underscores particularly (1) the microRNA-based biomarker candidates as among the most promising predictors of radiation-induced liver toxicity and (2) the texture features in radiomic analyses for response prediction. Radiotherapy of hepatocellular carcinoma is edging toward personalized medicine with emerging radiomic biomarker candidates. Future large-scale biomarker studies are called for to enable personalized medicine in liver cancers.
Topics: Artificial Intelligence; Biomarkers; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Precision Medicine
PubMed: 34448625
DOI: 10.1089/omi.2021.0065 -
PLoS Neglected Tropical Diseases 2015Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares....
BACKGROUND
Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14), 4 T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), 1 T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPLC) were examined with respect to the presence of nucleotide intrastrain heterogeneous sites.
METHODOLOGY/PRINCIPAL FINDINGS
The number of identified intrastrain heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23 intrastrain heterogeneous sites (in 17 genes) were found in 5 out of 10 investigated treponemal genomes including TPA strains Nichols (n = 5), DAL-1 (n = 4), and SS14 (n = 7), TPE strain Samoa D (n = 1), and TEN strain Bosnia A (n = 5). Although only one heterogeneous site was identified among 4 tested TPE strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites were mostly strain-specific and were identified in four tpr genes (tprC, GI, I, K), in genes involved in bacterial motility and chemotaxis (fliI, cheC-fliY), in genes involved in cell structure (murC), translation (prfA), general and DNA metabolism (putative SAM dependent methyltransferase, topA), and in seven hypothetical genes.
CONCLUSIONS/SIGNIFICANCE
Heterogeneous sites likely represent both the selection of adaptive changes during infection of the host as well as an ongoing diversifying evolutionary process.
Topics: Bacterial Outer Membrane Proteins; Genome, Bacterial; Humans; Retrospective Studies; Treponema
PubMed: 26436423
DOI: 10.1371/journal.pntd.0004110 -
Breast Cancer (Dove Medical Press) 2017Pleomorphic invasive lobular carcinoma (P-ILC) is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the...
BACKGROUND
Pleomorphic invasive lobular carcinoma (P-ILC) is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.
MATERIALS AND METHODS
We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC) and 574 cases of high-grade invasive ductal carcinoma (HG-IDC). We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.
RESULTS
P-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway), its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.
CONCLUSION
This is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field.
PubMed: 29263698
DOI: 10.2147/BCTT.S145570 -
BMC Genomics Jan 2020Spirochetal organisms of the Treponema genus are responsible for causing Treponematoses. Pathogenic treponemes is a Gram-negative, motile, spirochete pathogen that...
BACKGROUND
Spirochetal organisms of the Treponema genus are responsible for causing Treponematoses. Pathogenic treponemes is a Gram-negative, motile, spirochete pathogen that causes syphilis in human. Treponema pallidum subsp. endemicum (TEN) causes endemic syphilis (bejel); T. pallidum subsp. pallidum (TPA) causes venereal syphilis; T. pallidum subsp. pertenue (TPE) causes yaws; and T. pallidum subsp. Ccarateum causes pinta. Out of these four high morbidity diseases, venereal syphilis is mediated by sexual contact; the other three diseases are transmitted by close personal contact. The global distribution of syphilis is alarming and there is an increasing need of proper treatment and preventive measures. Unfortunately, effective measures are limited.
RESULTS
Here, the genome sequences of 53 T. pallidum strains isolated from different parts of the world and a diverse range of hosts were comparatively analysed using pan-genomic strategy. Phylogenomic, pan-genomic, core genomic and singleton analysis disclosed the close connection among all strains of the pathogen T. pallidum, its clonal behaviour and showed increases in the sizes of the pan-genome. Based on the genome plasticity analysis of the subsets containing the subspecies T pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue, we found differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) on subsp.-based study.
CONCLUSIONS
In summary, we identified four pathogenicity islands (PAIs), eight genomic islands (GIs) in subsp. pallidum, whereas subsp. endemicum has three PAIs and seven GIs and subsp. pertenue harbours three PAIs and eight GIs. Concerning the presence of genes in PAIs and GIs, we found some genes related to lipid and amino acid biosynthesis that were only present in the subsp. of T. pallidum, compared to T. pallidum subsp. endemicum and T. pallidum subsp. pertenue.
Topics: Genome, Bacterial; Genomic Islands; Humans; Phylogeny; Syphilis; Treponema pallidum
PubMed: 31924165
DOI: 10.1186/s12864-019-6430-6 -
International Journal of Radiation... Mar 2021We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after...
PURPOSE
We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after breast conservative surgery.
METHODS AND MATERIALS
From December 2010 to December 2018, we treated 338 women with APBI-tomotherapy: 38.5 Gy in 10 once-daily fractions. Patients selected were age ≥50 years old, with ≤3 cm in size unifocal tumor and at least 2 mm of clear margins. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes, and American Society for Radiation Oncology (ASTRO) 2017 updated consensus groupings.
RESULTS
The median age was 65 years (range, 50-86). The invasive ductal (87.5%) and the luminal A-like molecular phenotype (70%) were the most common tumors. Overall 242 patients (71.6%) were considered "suitable" for enrollment in APBI according to the eligibility criteria of the ASTRO-2017 consensus statement. With a median follow-up of 76 months (range, 17-113), 2 patients (0.6%) had an invasive ipsilateral breast tumor recurrence (IBTR), and 2 patients (0.6%) had an axillary ipsilateral failure. The rate of local control in terms of free of IBTR was 99.4% and locoregional control (no recurrence in ipsilateral breast as well as in regional nodes) was 98.8%. Progression-free survival was 98.4% and 92% at 5 and 10 years, respectively. Acute and late skin toxicity, graded according to the Common Terminology Criteria for Adverse Events, were 7.7% (G1) and 0.6% (G2) and 4.4% (G1) and 1.1% (G2), respectively. There were no grade 3/4 toxicities, however. Very few patients (2%) or physicians (2%) assessed cosmetic outcome as fair or poor at the 2-year follow-up.
CONCLUSIONS
This phase 2 trial on APBI-tomotherapy shows excellent long-term results. Once-daily fractionation schedule was well tolerated with a low rate of adverse events and worse cosmetic outcome. In this series, even among those deemed cautionary or unsuitable for APBI by ASTRO criteria, we demonstrated a low rate of IBTR.
Topics: Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Consensus; Dose Fractionation, Radiation; Esthetics; Female; Humans; Kaplan-Meier Estimate; Margins of Excision; Mastectomy, Segmental; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Radiotherapy; Radiotherapy, Intensity-Modulated; Time Factors; Treatment Outcome
PubMed: 33098960
DOI: 10.1016/j.ijrobp.2020.10.009