Macrochimerism and clinical transplant tolerance

Current theory holds that macrochimerism is essential to the development of transplant tolerance. Hematopoietic cell transplantation from the solid organ donor is necessary to achieve macrochimerism. Over the last 10–20?years, trials of tolerance induction with combined kidney and hematopoietic cell transplantation have moved from the preclinical to the clinical arena. The achievement of macrochimerism in the clinical setting is challenging, and potentially toxic due to the conditioning regimen necessary to hematopoietic cell transplantation and due to the risk of graft-versus-host disease. There are differences in chimerism goals and methods of the three major clinical stage tolerance induction strategies in both HLA-matched and HLA-mismatched living donor kidney transplantation, with consequent differences in efficacy and safety. The Stanford protocol has proven efficacious in the induction of tolerance in HLA-matched kidney transplantation, allowing cessation of immunosuppressive drug therapy in 80% of study participants, with the safety profile of conventional transplantation. In HLA-mismatched transplantation, multi-lineage macrochimerism of over a year’s duration can now be consistently achieved with the Stanford protocol, with complete withdrawal of immunosuppressive drug therapy during the second post-transplant year as the next experimental step and test of tolerance.     

A novel suture method to place and adjust peripheral nerve catheters

We have developed a peripheral nerve catheter, attached to a needle, which works like an adjustable suture. We used in‐plane ultrasound guidance to place 45 catheters close to the femoral, saphenous, sciatic and distal tibial nerves in cadaver legs. We displaced catheters after their initial placement and then attempted to return them to their original positions. We used ultrasound to evaluate the initial and secondary catheter placements and the spread of injectate around the nerves. In 10 cases, we confirmed catheter position by magnetic resonance imaging. We judged 43/45 initial placements successful and 42/43 secondary placements successful by ultrasound, confirmed in 10/10 cases by magnetic resonance imaging.     

Incidence of Incisional Hernia Repair After Laparoscopic Compared to Open Resection of Colonic Cancer: A Nationwide Analysis of 17,717 Patients

Background

It remains unknown whether laparoscopic compared to open surgery translates into fewer incisional hernia repairs (IHR). The objectives of the current study were to compare the long-term incidence of IHR and the size of repaired hernias between patients subjected to laparoscopic or open resection of colonic cancer.

Methods

This was a nationwide cohort study comprised of patients undergoing resection for colonic cancer between January 2007 and March 2016 according to the Danish Colorectal Cancer Group database. Patients who subsequently underwent IHR were identified in the Danish Ventral Hernia Database, from which information about the priority of the hernia repair and the size of the fascial defect was retrieved.

Results

The study included 17,717 patients, of whom 482 (2.7%) underwent subsequent IHR during a median follow-up of 4.7 (interquartile range 2.8–6.9) years. There was no significant difference in the 5-year cumulative incidence of hernia repair after laparoscopic compared to open colonic resection (3.9%, CI 3.3–4.4% vs 4.1%, CI 3.5–4.6%). After adjustment for confounders, laparoscopic approach was associated with an increased rate of emergency IHR (HR 2.37, 95% CI 1.03–5.46, P = 0.042) as opposed to elective IHR (HR 0.91, 95% CI 0.73–1.14, P = 0.442). Laparoscopic surgery was significantly associated with a decreased fascial defect area compared to open surgery (mean difference −16.0 cm², 95% CI −29.4 to −2.5, P = 0.020).

Conclusions

There was no difference in the incidence of IHR after open compared to laparoscopic resection. Compared to the open approach, laparoscopic resection increased the rate of subsequent emergency IHR, suggesting that a more aggressive therapeutic approach may be warranted in this patient group upon diagnosis of an incisional hernia.

     

Abdominal wound dehiscence is dangerous: a nationwide study of 14,169 patients undergoing elective open resection for colonic cancer

Hernia - The potential impact of abdominal wound dehiscence on long-term survival after elective abdominal surgery is largely unknown. The aim of this study was to examine the impact of abdominal...     

The impact of a tailored follow-up intervention on comprehensive geriatric assessment in older patients with cancer - a randomised controlled trial

PurposeComprehensive Geriatric Assessment (CGA) can identify health problems in older persons. In addition, CGA includes intervention towards the identified problems. With follow up, more problems may be identified and the interventions can be adjusted. We wanted to compare CGA with or without tailored follow-up in a randomised design.Patients and MethodsPatients 70+ years referred for oncology treatment with four primary tumour sites. Participants were randomised 1:1 to either control group with no follow-up or intervention group with a tailored follow-up by a multidisciplinary team. Primary outcome was adherence to cancer treatment. Secondary outcomes were daily life activities, physical performance and hospitalisation.ResultsIn total, 363 participants were randomised. After randomisation only 301 were planned to receive specific cancer treatment. Median age was 75 years. Among the 301 participants, 52% of control group vs. 61% of intervention group completed treatment. Risk Rate (RR): 1.16 (95% Confidence Interval (CI): 0.95–1.42), p = .14. The impact varied between the included tumour-sites, p < .01. We found no difference in 90 days physical performance or daily life activities between groups. During the study period, 55% of controls vs. 47% in the intervention group were admitted to hospital, RR: 0.86 (95%CI: 0.69–1.07), p = .19.ConclusionIn frail and vulnerable patients with cancer, a tailored follow-up on CGA showed no differences in ability to complete initially planned cancer treatment. The impact varied between the included tumour sites. We did not find any impact of tailored follow-up on daily life activities, physical performance or hospitalisation.     

Students' perspective of the effectiveness of an asynchronous on-line seminar.

This study was conducted to understand students' perceptions of the usefulness of on-line discussion for a nursing seminar. The interpretative approach was selected to explore the students' perceptions of the effectiveness of the on-line discussion. The participants were recruited from maternity nursing courses on two rural campuses in Nebraska. A convenience sample of 31 participated in the study with a purposive sample of 10 representing extreme views selected for in-depth interviews. Eight patterns emerged as a plausible interpretation of the on-line experience. These patterns were exemplified by the themes of engagement theory (relate, create, and donate). The pattern that was identified as relational was learner-to-learner learning without face-to-face communication. However, isolation was found to inhibit relating. Creating, the second theme, was exemplified by multiperspective opinions, however, frustration with the technology and anxiety/information overload inhibited the creative aspects. Finally, the third theme, donate, was represented by having time for critical thinking/reflection while participating in the on-line discussions. The findings of this research support the need for more studies to explore students' perception of the usefulness of on-line discussion.     

Antibacterial activity of norfloxacin in the gastrointestinal tracts of rats.

The capacities of norfloxacin (MK-0366) and neomycin to reduce the numbers of bacteria in the gastrointestinal tracts of rats were evaluated. Results of a 3-day treatment with norfloxacin were compared with those of a 3-day treatment with neomycin. Both drugs significantly decreased gram-negative and gram-positive bacteria. Norfloxacin effected a significantly greater reduction in numbers of gram-negative bacteria than did neomycin. Norfloxacin also significantly increased the number of anaerobic bacteria. Although neomycin reduced gram-positive bacteria more effectively than did norfloxacin, this difference between the two drugs was not significant. Norfloxacin merits further study for potential as a bowel sterilant.     

Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation

The incidence and clinical picture of non-painful and painful phantom limb sensations as well as stump pain was studied in 58 patients 8 days and 6 months after limb amputation. The incidence of non-painful phantom limb, phantom pain and stump pain 8 days after surgery was 84, 72 and 57%, respectively. Six months after amputation the corresponding figures were 90, 67 and 22%, respectively. Kinaesthetic sensations (feeling of length, volume or other spatial sensation of the affected limb) were present in 85% of the patients with phantom limb both immediately after surgery and 6 months later. However, 30% noticed a clear shortening of the phantom during the follow-up period; this was usually among patients with no phantom pain. Phantom pain was significantly more frequent in patients with pain in the limb the day before amputation than in those without preoperative limb pain. Of the 67% having some phantom pain at the latest interview 50% reported that pains were decreasing. Four patients (8%), however, reported that phantom pains were worse 6 months after amputation than originally. During the follow-up period the localization of phantom pains shifted from a proximal and distal distribution to a more distal localization. While knifelike, sticking phantom pains were most common immediately after surgery, squeezing or burning types of phantom pain were usually reported later in the course. Possible mechanisms for the present findings either in periphery, spinal cord or in the brain are discussed.     

A versatile flow phantom for intravoxel incoherent motion MRI

Although there have been many advancements in cancer research, much is still unknown about the heterogeneous tumor microenvironment. Diffusion-weighted MRI has proven to be a viable and versatile microstructural probe. Diffusion-weighted sequences specifically sensitive to intravoxel incoherent motion (IVIM) have seen a recent resurgence of interest as they promise to provide a valuable window on the vascular microenvironment. To understand, test, and optimize IVIM-sensitive approaches, a complex flow phantom was constructed to mimic certain characteristics of the tumor microenvironment such as tortuous microvasculature, heterogeneous vascular permeability, and interstitial fluid pressure buildup. Results using this phantom on a clinical scanner platform confirmed IVIM sensitivity to microscopic flow effects. Biexponential fitting of signal decay curves enabled quantitative extraction of perfusion fraction, IVIM-related pseudodiffusivity, and tissue diffusivity. Parametric maps were also generated, illustrating the potential utility of IVIM-sensitive imaging in clinical settings. The flow phantom proved to be an effective test-bed for validating and optimizing the IVIM-MRI technique to provide surrogate markers for microvascular properties.