Open vs. laparoscopic vs. robotic pouch excision: unveiling the best approach for optimal outcomes.

INTRODUCTION: Despite advantages for patients with ulcerative colitis, Crohn's disease, and familial adenomatous polyposis, restorative proctocolectomy with ileal pouch-anal anastomosis carries a risk of pouch failure, necessitating pouch excision. The traditional open approach is associated with potential complications. Robotic and laparoscopic techniques are emerging, but comparative outcome data are limited. METHODS: We conducted a retrospective study of consecutive adult patients undergoing robotic, laparoscopic, and open ileal pouch excision at Mayo Clinic, Rochester, MN, between January 2015 and December 2023. We analyzed data on patient characteristics, perioperative variables, and postoperative outcomes, focusing on short-term complications. Statistical analysis included appropriate tests. RESULTS: The study included 123 patients: 23 underwent robotic-assisted pouch excision, 12 laparoscopic, and 82 open. The robotic approach had the longest median operative time (334 ± 170 min, p = 0.03). However, it demonstrated significantly lower estimated blood loss than open (150 ± 200 ml vs. 350 ± 300 ml, p = 0.002) and laparoscopic surgery (250 ± 250 ml, p = 0.005). Robotic and laparoscopic groups required fewer preoperative ureteral stents than the open group (p = 0.001). Additionally, the robotic approach utilized fewer pelvic drainages (p < 0.0001) and had a lower rate of lysis of adhesions > 60 min compared to open surgery (p = 0.003). Robotic procedures had significantly lower 30-day postoperative complications than the open approach (30.4% vs. 65.9%, p = 0.002) while also demonstrating fewer 30-day reoperations than the laparoscopic group (p = 0.04). CONCLUSIONS: Robotic-assisted pouch excision offered significant benefits, including decreased EBL, reduced need for preoperative ureteral stents, and significantly fewer 30-day postoperative complications compared to open surgery.

Assessing robotic-assisted surgery versus open approach in penetrating Crohn's disease: advantages and outcomes in ileocolic resection.

INTRODUCTION: Penetrating Crohn's disease (CD) often necessitates surgical intervention, with the open approach traditionally favored. Robotic-assisted surgery offers potential benefits but remains understudied in this complex patient population. Additionally, the lack of standardized surgical complexity scoring in CD hinders research and comparisons. METHODS: We retrospectively analyzed adult patients with penetrating CD who underwent either robotic-assisted ileocolic resection (RICR) or open ileocolic resection (OICR) at our institution from January 2007 to December 2021. We assessed endpoints, including length of stay, complications, readmissions, reoperations, and other perioperative outcomes. RESULTS: RICR demonstrated safety outcomes comparable to OICR. Importantly, RICR patients experienced significantly reduced estimated blood loss (p < 0.0001), shorter hospital stays (median 4.5 days versus 6.9 days; p = 0.01), lower surgical site infection rates (0% versus 15.4%; p = 0.01), and decreased 30-day readmission rates (0% versus 15.4%; p = 0.01). Linear regression analysis revealed the need for additional strictureplasties (coefficient: 84.8; p = 0.008), colonic resections (coefficient: 41.7; p = 0.008), and estimated blood loss (coefficient: 0.07; p = 0.002) independently correlated with longer operative times). CONCLUSION: Robotic-assisted surgery appears to be a safe and potentially beneficial alternative for the surgical management of penetrating CD, offering advantages in perioperative outcomes reducing length of stay, blood loss, surgical site infection rates, and readmission rates. Further validation with larger cohorts is warranted.

Understanding the structural details of APOBEC3-DNA interactions using graph-based representations.

Human APOBEC3 (A3; apolipoprotein B mRNA editing catalytic polypeptide-like 3) is a family of seven enzymes involved in generating mutations in nascent reverse transcripts of many retroviruses, as well as the human genome in a range of cancer types. The structural details of the interaction between A3 proteins and DNA molecules are only available for a few family members. Here we use homology modelling techniques to address the difference in structural coverage of human A3 enzymes interacting with different DNA substrates. A3-DNA interfaces are represented as residue networks ("graphs"), based on which features at these interfaces are compared and quantified. We demonstrate that graph-based representations are effective in highlighting structural features of A3-DNA interfaces. By large-scale in silico mutagenesis of the bound DNA chain, we predicted the preference of substrate DNA sequence for multiple A3 domains. These data suggested that computational modelling approaches could contribute in the exploration of the structural basis for sequence specificity in A3 substrate selection, and demonstrated the utility of graph-based approaches in evaluating a large number of structural models generated in silico.

A case of severe actinic prurigo successfully treated with thalidomide.

Actinic prurigo is an uncommon and usually persistent idiopathic photodermatosis with typical human leukocyte antigen (HLA) associations (HLA-DR4, particularly subtypes DRB1*0407 and DRB1*0401). Although its mechanism of action is not clearly understood, thalidomide has been shown to be particularly efficacious in treating actinic prurigo, among other conditions. A 31-year-old Australian woman who had suffered actinic prurigo for most of her life was treated with two courses of thalidomide (50-100 mg nocte) over consecutive summers. Remission was observed after cessation of the second course of thalidomide and had continued 4 years later. Abnormalities in the cutaneous response to ultraviolet radiation at the time of diagnosis, detected by monochromator phototesting, reverted to normal following treatment.

Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation.

PG490 (triptolide) is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties. PG490 inhibits interleukin(IL)-2 expression by normal human peripheral blood lymphocytes stimulated with phorbol 12-myristate 13-acetate (PMA) and antibody to CD3 (IC50 of 10 ng/ml), and with PMA and ionomycin (Iono, IC50 of 40 ng/ml). In Jurkat T-cells, PG490 inhibits PMA/Iono-stimulated IL-2 transcription. PG490 inhibits the induction of DNA binding activity at the purine-box/antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target sequence but not at the NF-kappaB site. PG490 can completely inhibit transcriptional activation at the purine-box/ARRE/NF-AT and NF-kappaB target DNA sequences triggered by all stimuli examined (PMA, PMA/Iono, tumor necrosis factor-alpha). PG490 also inhibits PMA-stimulated activation of a chimeric transcription factor in which the C-terminal TA1 transactivation domain of NF-kappaB p65 is fused to the DNA binding domain of GAL4. In 16HBE human bronchial epithelial cells, IL-8 expression is regulated predominantly by NF-kappaB, and PG490 but not cyclosporin A can completely inhibit expression of IL-8. The mechanism of PG490 inhibition of cytokine gene expression differs from cyclosporin A and involves nuclear inhibition of transcriptional activation of NF-kappaB and the purine-box regulator operating at the ARRE/NF-AT site at a step after specific DNA binding.

Unique toxic peptides isolated from sawfly larvae in three continents.

D-Amino acid containing peptides have been found to be responsible for sawfly larvae poisoning in many parts of the world. These compounds, unique in the animal kingdom, were isolated from three different species of sawfly indigenous to Australia, Denmark and South America. The octapeptide, lophyrotomin, is the major toxin in the Australian and Danish species and is present in small amounts in the South American sawfly. Pergidin, the main toxin in the South American sawfly, is a heptapeptide containing a phosphoseryl residue. This, as far as we are aware, is the first example of such a peptide to be isolated from an animal source. Small amounts of pergidin have been found in the other two species. All available evidence suggests that both peptides are biosynthesised 'de novo' possibly as a protective device, however it cannot be excluded that microorganisms may be responsible. These compounds are stable to enzymatic breakdown because of their configuration and their strong chemical bonding and lipophilic character provide a potential for residues to remain in the host animal and cause significant changes.

Isolation of a compound from Eupatorium adenophorum (Spreng.) [Ageratina adenophora (Spreng.)] causing hepatotoxicity in mice.

Regular ingestion of Eupatorium adenophorum [Ageratina adenophora (Spreng.)] or Crofton weed causes chronic pulmonary disease in horses mainly in Australia, New Zealand, and the Himalayas. The disease is characterized by pulmonary interstitial fibrosis, emphysema, alveolar epithelisation and reduced tolerance to exercise. Horses apparently are the only animals affected and there are numerous reports of farms losing all their horses. The disorder was produced experimentally in horse feeding trials, and it was shown that characteristic lesions occurred in the lungs. In studies with laboratory animals, mice were shown to be suitable test animals, but in this species lesions occur in the liver rather than the lungs. The hepatic injury in these animals is characterized by multiple areas of focal necrosis of the parenchyma associated with degeneration and loss of the epithelium lining the small bile ducts. The active principle 9-oxo-10,11 dehydroagerophorone responsible for these lesions in mice has been isolated from E. adenophorum. Although the compound has been shown to exhibit toxicity to larvae of invertebrate species, no mammalian toxicity studies have been previously reported involving the isolated toxin. The mechanism of the toxic effect of the compound as well as its possible relevance to the respiratory disease in the horse remain to be investigated.

Concentration of ptaquiloside, a major carcinogen in bracken fern (Pteridium spp.), from eastern Australia and from a cultivated worldwide collection held in Sydney, Australia.

Two surveys of bracken fern for the concentration of the carcinogen ptaquiloside (PT) have been carried out, one of bracken fern from the eastern side of Australia and the other from a worldwide collection of bracken clones held in Sydney Australia. Bracken from eastern Australia contained concentrations of ptaquiloside ranging from 0 to 12,945 micrograms PT/g. From 91 samples 15% contained greater than 5,000 micrograms PT/g and 57% of samples contained more than 1,000 micrograms PT/g bracken on the dry weight basis. Ptaquiloside concentrations were highest in Pteridium revolutum and from P. esculentum from areas where bovine enzootic haematuria was known to occur. Bracken from the cultivated bracken clone collection from world-wide sources tended to have lower concentrations of ptaquiloside ranging from 0 to 9,776 micrograms PT/g. From 77 samples, 8% contained more than 5,000 micrograms PT/g and 35% contained more than 1,000 micrograms PT/g bracken. Samples from both the eastern Australia survey and the Australian representatives in the worldwide collection showed significantly higher concentrations of PT in the P. esculentum collected from the more southern states. In samples from the worldwide collection there were no statistical differences in the concentrations of PT in bracken between taxa.

Specific activation of glucuronide prodrugs by antibody-targeted enzyme conjugates for cancer therapy.

Cancer chemotherapy may be improved by increasing antineoplastic drug specificity for tumor cells. We have synthesized a glucuronide prodrug that can be enzymatically converted to an antineoplastic agent at tumor cells that are able to bind beta-glucuronidase-monoclonal antibody conjugates. The glucuronide prodrug BHAMG, the tetra-n-butyl ammonium salt of (p-di-2-chloroethylaminophenyl-beta-D-glucopyranoside) uronic acid, was 150 times less toxic than the parent drug, N,N-di-(2-chloroethyl)-4-hydroxyaniline, to HepG2 human hepatoma cells and over 1000-fold less toxic than the parent drug to AS-30D rat hepatoma cells in vitro. In the presence of beta-glucuronidase, BHAMG was activated and became as toxic as the parent drug N,N-di-(2-chloroethyl)4-hydroxyaniline. A conjugate (RH1-beta G) was formed by linking beta-glucuronidase to a monoclonal antibody which binds to an antigen expressed on the surface of AS-30D cells. The concentration of BHAMG causing 50% inhibition of AS-30D cellular protein synthesis was reduced over 1000-fold, from greater than 770 microM to less than 0.74 microM after these cells were preincubated with RH1-beta G. Specificity of BHAMG activation at antigen-positive cells was shown by monoclonal antibody RH1 blocking of RH1-beta G conversion of BHAMG to toxic drug and by the inability of BHAMG to be converted to active drug when antigen-negative control cells were preincubated with RH1-beta G. Our results show that the targeted-beta-glucuronidase activation of BHAMG can increase the specificity of chemotherapy for rat hepatoma in vitro and suggest that the targeted activation of glucuronide prodrugs may be useful for cancer therapy.

The nifH gene product is required for the synthesis or stability of the iron-molybdenum cofactor of nitrogenase from Klebsiella pneumoniae.

The MoFe protein of nitrogenase from Klebsiella pneumoniae contains an iron-molybdenum cofactor, FeMoco, the synthesis or processing of which involves the products of at least five genes, nifQ, nifB, nifN, nifE and nifV. We have detected FeMoco activity in extracts of strains which synthesise neither of the MoFe protein subunits, indicating that FeMoco can be synthesised prior to combination with the MoFe protein polypeptides. Expression of the nifH gene (or a large part of it), was essential for FeMoco activity to be observed either in the presence or in the absence of the MoFe protein subunits. The nifH gene product was not involved in the control of the transcription of other nif gene products known to be involved in FeMoco synthesis or processing, nor was it essential for the stability of performed FeMoco before its combination with the MoFe protein polypeptides.

Some effects of chronic mercuric chloride intoxication on renal function in a horse.

Chronic mercuric chloride intoxication in an aged horse given 0.8 mg Hg/kg/day for 14 weeks was manifest by signs of progressive respiratory difficulty and renal disease. The effects were not self-limiting after mercury was withdrawn, and the animal was destroyed six weeks later. Renal function changes included heavy glycosuria, modest proteinuria, phosphaturia, reduced urine osmolality, gradually increasing urine production, reduced glomerular filtration rate, and terminally, azotemia. The condition bore similarities to the Fanconi syndrome in man. Urinary gamma-glutamyl transpeptidase, alkaline phosphatase and amino-aspartate transferase activities were inconsistent indicators of tubular damage in random samples at this dose rate. The pathologic response was characterized by extensive granulomatous infiltration throughout the lungs, in particular, and to a lesser extent in the kidneys, liver and bone marrow. The renal changes included this marked interstitial reaction and proximal tubular degeneration. Mercury levels were negligible in the lungs and highest in the renal cortex. The granulomatous reaction was not encountered in previous mercury toxicity studies in horses and may indicate an individual sensitivity to the agent.