Study aimed to assess long-term bowel function in patients who underwent low anterior resection for cancer five and more years ago. Patients who underwent low anterior resection for rectal cancer from 2010 to 2015 at National Cancer Institute were prospectively included in our study. They were interviewed using low anterior resection syndrome (LARS) score and Wexner questionnaire. We also assessed possible risk factors of postoperative bowel disorder. 150 patients were included in our study. Of them 125 (83.3%) were analysed. The median age at diagnosis was 62 years (40-79), and the average time of follow-up was 7.5 years (5-11). Overall, 58 (46.4%) patients had LARS, of them 33 (26.4%)-major LARS and 25 (20%)-minor LARS and 67 (53.6%) reported no LARS. Wexner score results were: normal in 43 (34.4%) patients, minor faecal incontinence-55 (44%), average faecal incontinence-18 (14.4%), complete faecal incontinence-9 (7.2%). 51 patients (40.8%) had tumour in the upper third rectum, 51 (40.8%)-in the middle and 23 (18.4%)-lower third. Preoperative (chemo) radiotherapy was the only significant risk factors for developing LARS in univariate analysis. Our study showed that only preoperative radiotherapy may be associated with more late problems in defecation after rectal cancer surgery. Trial registration: NCT03920202. Rectal cancer (RC) is a frequent and fatal disease with high incidence rate in developed countries, possibly because of differences in environment and diet 1. The age standardized incidence rate among men and women in Europe, was 15-25/100.000 new cases of RC per year with a range of mortality from four to 10/100.000 2. For the last almost 30 years, the gold standard treatment for RC is low anterior resection (LAR) with total mesorectal excision (TME) as described by Heald 3. Unfortunately, up to 80% of patients undergoing LAR will suffer of bowel dysfunction including faecal urgency, frequent bowel movements, tenesmus or so called Low Anterior Resection Syndrome (LARS) 4. Simply it has been defined as "disordered bowel function after rectal resection, leading to a detriment in quality of life" 4. Same year LARS score was developed 5. This tool is easy to use and has been internationally and in Lithuania validated 6,7. Wexner score is another tool for evaluation of faecal continence 8. Recently Delphi consensus on LARS description was published. To meet the definition, a patient must have had an anterior resection (sphincterpreserving rectal resection) and experience at least 1 of suggested 8 symptoms that result in at least one of suggested 8 consequences 9. The advantaged of the Delphi approach is that unlike most patient-reported outcome measures that were initially produced by expert clinician researchers who then consulted patient populations, the Delphi definition of LARS actively involved all major stakeholders, especially patients, early in the construction to ensure that the resulting tool was fit for purpose. To our knowledge there are only five studies investigating long-term LARS following re...

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1→3)-β-d-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with antimold triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well-established persistently neutropenic New Zealand White (NZW) rabbit model of experimental IPA. Treatment groups included untreated control (UC) rabbits and rabbits receiving ibrexafungerp at 2.5 (SCY2.5) and 7.5 (SCY7.5) mg/kg of body weight/day, isavuconazole at 40 (ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced an in vitro synergistic interaction. There were significant in vivo reductions of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40 treatment groups versus those of the SCY2.5-treated, SCY7.5-treated, and UC (P < 0.01) groups. Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of the SCY2.5-, SCY7.5-, ISA40-treated, or UC (P < 0.05) groups. Serum galactomannan index (GMI) and (1→3)-β-d-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those of animals treated with SCY7.5 or ISA40 (P < 0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, and lower GMI and (1→3)-β-d-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an antimold triazole for treatment of IPA.

The emergence of drug-resistant Staphylococcus aureus is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among S. aureus in the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and toxicity (ADMET) and in vitro antimicrobial activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against drug-resistant S. aureus strains with genetically defined resistance mechanisms. The antimicrobial activity of KTU-286 was determined by CLSI recommendations. The ADMET properties were estimated by using in silico modeling. The activity on biofilm integrity was examined by crystal violet assay. KTU-286 demonstrated low estimated toxicity and low skin permeability. The highest antimicrobial activity was observed among pan-susceptible (Pan-S) S. aureus (minimal inhibitory concentration (MIC) 0.5–2.0 µg/mL, IC50 = 0.460 µg/mL), followed by vancomycin resistant S. aureus (VRSA) (MIC 4.0 µg/mL, IC50 = 1.697 µg/mL) and methicillin-resistant S. aureus (MRSA) (MIC 1.0–16.0 µg/mL, IC50 = 2.282 µg/mL). KTU-286 resulted in significant (p < 0.05) loss of S. aureus biofilm integrity in vitro. Further studies are needed for a better understanding of safety, synergistic relationship, and therapeutic potency of KTU-286.

The p-aminobenzoic acid was applied for the synthesis of substituted 1-phenyl-5-oxopyrrolidine derivatives containing benzimidazole, azole, oxadiazole, triazole, dihydrazone, and dithiosemicarbazide moieties in the structure. All the obtained compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Salmonella enteritidis, Escherichia coli, and Pseudomonas aeruginosa by using MIC and MBC assays. This study showed a good bactericidal activity of γ-amino acid and benzimidazoles derivatives. The antimicrobial activity of the most promising compounds was higher than ampicillin. Furthermore, two benzimidazoles demonstrated good antimicrobial activity against L. monocytogenes (MIC 15.62 µg/mL) that was four times more potent than ampicillin (MIC 65 µg/mL). Further studies are needed to better understand the mechanism of the antimicrobial activity as well as to generate antimicrobial compounds based on the 1-phenyl-5-oxopyrrolidine scaffold.