A systematic review of pre, peri and postoperative factors and their implications for the lengths of resected bowel segments in patients with Crohn's disease

Aim: Several pre, peri and postoperative factors may have implications for the lengths of resected small bowel segments in Crohn's disease patients. It might also affect patient outcome. We reviewed the current literature on factors and their implications for the lengths of resected small bowel segments and possible correlations with postoperative outcome. Method: Searches were independently engineered by the authors and a research-librarian in MEDLINE and OVID databases using PubMed and EMBASE engines in compliance with PRISMA recommendations. All original articles, reviews and guidelines published in the period of 1985–2016 with last search date 13th of February 2016 on bowel resection in Crohn's disease patients were assessed for inclusion. Results: We identified 52 studies for synthesis. Preoperative: Perforation as indication for surgery and increased visceral obesity may be factors resulting in longer lengths of resected small bowel segments. Administration of total parenteral nutrition might reduce resection lengths. Perioperative: No difference in resection lengths in elective versus acute surgery, laparoscopic versus open approaches or in case of intra-operative blood transfusions. Stapled anastomoses might conserve more bowel than sutured ones. Postoperative: The lengths of the resected small bowel segments most likely have no impact on recurrence rates. Conclusion: No pre, peri or postoperative factors were found to have definitive implications for the lengths of resected small bowel segments. Correlation between the lengths of resection and recurrence is weak

Assessments of Thioridazine as a Helper Compound to Dicloxacillin against Methicillin-Resistant Staphylococcus aureus: In Vivo Trials in a Mouse Peritonitis Model

The rise in antimicrobial resistance is a major global concern and requires new treatment strategies. The use of helper compounds, such as thioridazine (TDZ), an antipsychotic drug, in combination with traditional antibiotics must be investigated.The aim of this study was to investigate the efficacy of TDZ as a helper compound for dicloxacillin (DCX) against methicillin-resistant Staphylococcus aureus (MRSA) in vivo, and compare the combination treatment of DCX+TDZ with vancomycin (VAN).Mice were inoculated with an intraperitoneal (IP) injection of MRSA (108 CFU) and treated in a 12-hour cycle for 48 hours. By termination, bacterial quantities in a peritoneal flush, spleen and kidneys were obtained. In the main trial the drugs were administered subcutaneously in five treatment groups: 1) DCX, 2) TDZ, 3) DCX+TDZ, 4) VAN, 5) SALINE. Additional smaller studies with IP administration and higher subcutaneous dosages (×1.5 and ×4) of the drugs were subsequently performed.In the main trial no significant differences were found between DCX+TDZ and DCX or TDZ alone (p≥0.121-0.999). VAN performed significantly better than DCX+TDZ on all bacteriological endpoints (p<0.001). Higher subcutaneous dosages of DCX and TDZ improved the antibacterial efficacy, but the combination treatment was still not significantly better than monotherapy. IP drug administration of DCX+TDZ revealed a significantly better antibacterial effect than DCX or TDZ alone (p<0.001) but not significantly different from VAN (p>0.999).In conclusion, TDZ did not prove to be a viable helper compound for dicloxacillin against MRSA in subcutaneous systemic treatment. However, IP-administration of DCX+TDZ, directly at the infection site resulted in a synergetic effect, with efficacy comparable to that of VAN

Fractional laser-assisted topical delivery of bleomycin quantified by LC-MS and visualized by MALDI mass spectrometry imaging

Bleomycin exhibits antiproliferative effects desirable for use in dermato-oncology but topical use is limited by its 1415 Da molar mass. Ablative fractional laser (AFL)-assisted drug delivery has been shown to enhance drug uptake in skin. The aim of this study was with AFL to deliver bleomycin into skin, quantify uptake, and visualize biodistribution with mass spectrometry. In a Franz diffusion cell study, pig skin samples (n = 66) were treated with AFL (λ = 10,600 nm), 5% density, and 0, 5, 20, or 80 mJ/microbeam (mb) pulse energies before exposure to bleomycin for 0.5, 4, or 24 h. Bleomycin was quantified in biopsy cryosections at depths of 100, 500, and 1500 µm using high-performance liquid chromatography-mass spectrometry (LC-MS), and drug biodistribution was visualized for 80 mJ/mb samples by matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The pulse energies 5, 20, and 80 mJ/mb resulted in microscopic ablation zones (MAZs) reaching superficial, mid, and deep dermis respectively. Bleomycin was successfully delivered into the skin and deeper MAZs and longer exposure time resulted in higher skin concentrations. After 24 h, AFL exposure resulted in significant amounts of bleomycin throughout all skin layers (≥510 µg/cm3, p ≤ .002). In comparison, concentrations in intact skin exposed to bleomycin remained below limit of quantification. MALDI-MSI supported the quantitative LC-MS results by visualizing bleomycin biodistribution and revealing high uptake around MAZs with delivery into surrounding skin tissue. In conclusion, topical drug delivery of the large and hydrophilic molecule bleomycin is feasible, promising, and should be explored in an in vivo setting

In vivo dermal delivery of bleomycin with electronic pneumatic injection:drug visualization and quantification with mass spectrometry

Background: Intralesional bleomycin (BLM) administration by needle injection is effective for keloids and warts but has significant drawbacks, including treatment-related pain and operator-depended success rates. Electronic pneumatic injection (EPI) is a promising, less painful, needle-free method that potentially enables precise and controlled dermal drug delivery. Here, we aimed to explore the cutaneous pharmacokinetics, biodistribution patterns, and tolerability of BLM administered by EPI in vivo. Research Design and Methods: In a pig model, EPI with BLM or saline (SAL) were evaluated after 1, 48 and 216 hours. Mass spectrometry quantification and imaging were used to assess BLM concentrations and biodistribution patterns in skin biopsies. Tolerability was assessed by scoring local skin reactions (LSR) and measuring transepidermal water loss (TEWL). Results: Directly after BLM injection a peak concentration of 109.2 µg/cm3 (43.9–175.2) was measured in skin biopsies. After 9 days BLM was undetectable. EPI resulted in a focal BLM biodistribution in the mid-dermal delivery zone resembling a triangular shape. Mild LSRs were resolved spontaneously and TEWL was unaffected. Conclusions: BLM administered by EPI resulted in quantifiable and focal mid-dermal distribution of BLM. The high skin bioavailability holds a great potential for clinical effects and warrants further evaluation in future human studies

A-D: Main trial: Box-whisker plots of bacterial quantities displayed as ln(CFU/mL) in all treatments groups sorted by bacteriological endpoints–(A) P-flush, (B) Spleen, (C) Kidney, and (D) Total.

<p>The filled dots indicate outliers. DCX: Dicloxacillin; TDZ: Thioridazine; VAN: Vancomycin; SALINE: Isotonic saline.</p

A + B: Main trial: (A) Development in mean weight displayed as a percentage of baseline weight (100%) within each treatment group during the 48-hour trial period. DCX: Dicloxacillin; TDZ: Thioridazine; VAN: Vancomycin; SALINE: Isotonic saline.

<p><b>(B)</b> Scatter plot with a predicted linear regression line and a 95% CI (grey zone) of the predicted mean showing the correlation between the total quantity of bacteria and total change in weight during the entire trial period displayed as a percentage of baseline weight (100%).</p