Accumulation of Cytochrome b558 at the Plasma Membrane: Hallmark of Oxidative Stress in Phagocytic Cells.

Neutrophils play a very key role in the human immune defense against pathogenic infections. The predominant players in this role during the activation of neutrophils are the release of cytotoxic agents stored in the granules and secretory vesicles and the massive production of reactive oxygen species (ROS) initiated by the enzyme NADPH oxidase. In addition, in living organisms, cells are continuously exposed to endogenous (inflammations, elevated neutrophil presence in the vicinity) and exogenous ROS at low and moderate levels (travels by plane, radiotherapy, space irradiation, blood banking, etc.). To study these effects, we used ROS induced by gamma radiation from low (0.2 Gy) to high (25 Gy) dose levels on PLB-985 cells from a myeloid cell line differentiated to neutrophil-like cells that are considered a good alternative to neutrophils. We determined a much longer lifetime of PLB-985 cells than that of neutrophils, which, as expected, decreased by increasing the irradiation dose. In the absence of any secondary stimulus, a very low production of ROS is detected with no significant difference between irradiated and non-irradiated cells. However, in phagocytosing cells, irradiation doses above 2 Gy enhanced oxidative burst in PLB-985 cells. Whatever the irradiation dose, NADPH oxidase devoid of its cytosolic regulatory units is observed at the plasma membrane in irradiated PLB-985 cells. This result is different from that observed for irradiated neutrophils in which irradiation also induced a translocation of regulatory subunits suggesting that the signal transduction mechanism or pathway operate differently in both cells.

Outcomes of primary and recurrent inguinal hernia repair with prosthetic mesh in a single region over 15 years.

BACKGROUND: Sutured inguinal hernia repairs are now uncommon, with evidence suggesting that those augmented with mesh are associated with a lower recurrence rate. We aimed to explore the suggestion that the established use of mesh does indeed lower the rate of operation for recurrence in a single National Health Service region. METHOD: We collected retrospective Office of Population Censuses and Surveys coded data across one region of all primary and recurrent inguinal hernia repairs over 15 years (2004-2019). Electronic records of recurrent repairs were scrutinised to identify year and type of previous primary repair. RESULTS: In total, 7,234 repairs were performed during this time, of which 289 (4%) were for symptomatic recurrence. Operations for primary repair increased year on year (111 in 2004 to 402 in 2019). Frequency of operation for recurrent herniation declined with increasing use of mesh (8.8% in 2004 to 3.5% in 2019). The majority of repairs (73%) for recurrence were by an open approach. As opposed to an open mesh repair, a primary laparoscopic repair was associated with an earlier recurrence. CONCLUSIONS: Inguinal hernia repairs are increasing in frequency but operations for later symptomatic recurrence following an open primary prosthetic mesh repair are not.

Radiation-induced reactive oxygen species partially assemble neutrophil NADPH oxidase.

Neutrophils are key cells from the innate immune system that destroy invading bacteria or viruses, thanks mainly to the non-mitochondrial reactive oxygen species (ROS) generated by the enzyme NADPH oxidase. Our aim was to study the response of neutrophils to situations of oxidative stress with emphasis on the impact on the NADPH oxidase complex. To mimic oxidative stress, we used gamma irradiation that generated ROS (OH•, O2•- and H2O2) in a quantitative controlled manner. We showed that, although irradiation induces shorter half-lives of neutrophil (reduced by at least a factor of 2), it triggers a pre-activation of surviving neutrophils. This is detectable by the production of a small but significant amount of superoxide anions, proportional to the dose (about 3 times that of sham). Investigations at the molecular level showed that this ROS increase was generated by the NADPH oxidase enzyme after neutrophils irradiation. The NADPH oxidase complex undergoes an incomplete assembly which includes p47phox and p67phox but excludes the G-protein Rac. Importantly, this irradiation-induced pre-activation is capable of considerably improving neutrophil reactivity. Indeed, we have observed that this leads to an increase in the production of ROS and the capacity of phagocytosis, leading to the conclusion that radiation induced ROS clearly behave as neutrophil primers.

The lateral rectus abdominis positioned stoma (LRAPS) in the construction of end colostomies, loop ileostomies and ileal conduits.

BACKGROUND: Stomas are traditionally constructed through the belly of the rectus muscle. Parastomal herniation is common with the use of mesh prophylaxis still deliberated. METHODS: A novel trephine, the lateral rectus abdominis positioned stoma or LRAPS, that minimises damage to the musculature of the anterior abdominal wall, has been used in the construction of end colostomies, loop ileostomies and ileal conduits. RESULTS: In a cohort of 106 patients with end colostomy, the cumulative rate of parastomal herniation at 1, 2 and 3 years were 6, 10 and 17%, respectively. In 56 patients in whom an ileal conduit was performed, there was no clinical or radiological evidence of parastomal herniation at 1 year. CONCLUSION: In contrast to a traditional trephine through the belly of the muscle, this technique avoids damage to the rectus abdominis muscle. Early symptomatic parastomal herniation is unusual after LRAPS.

Ipsilateral Spigelian hernia: just an infrequent variant?

Spigelian hernias are generally considered to occur through solitary defects in the fascial layers of the anterior abdominal wall in the 'Spigelian hernia belt' but can be found anywhere along the line of the linea semilunaris. They are uncommon in children and in adults thought to be acquired and associated with obesity. We describe an unusual case of Spigelian herniation previously unreported and possibly previously unrecognised.

Management of the uncomplicated primary inguinal hernia in 2019: the practice amongst members of the British Hernia Society.

INTRODUCTION: The aim of this study was to survey the current practice of UK-based hernia surgeons in elective inguinal hernia repair. MATERIALS AND METHODS: A questionnaire was created using SurveyMonkey™ and sent electronically to registered members of the British Hernia Society. RESULTS: A total of 368 responses were obtained (a response rate of 55%); 83% were consultant surgeons, 91% were male and 91% stated that they had an interest in laparoscopic surgery. For an uncomplicated inguinal hernia in a male patient, 60% would perform an open Lichtenstein repair, 20% trans-abdominal pre-peritoneal repair and 20% totally extra-peritoneal repair. In a female patient, 54% would perform an open Lichtenstein repair, 25% trans-abdominal pre-peritoneal repair and 21% totally extra-peritoneal repair. 90% always use mesh in inguinal hernia repair. 93% of surgeons rarely or never perform a tissue repair. CONCLUSIONS: Despite recent controversy, UK surgeons support the use of mesh in the repair of inguinal hernias with an open Lichtenstein repair being the most common choice. There has only been a modest increase in the use of laparoscopic surgery over the past 20 years.

Benefits of pre-emptive analgesia by local infiltration at day-case general anaesthetic open inguinal hernioplasty.

Introduction The open prosthetic repair of inguinal hernias under local anaesthesia (LA) is well established, with the concept of intraoperative 'pre-emptive analgesia' evolving so that patients are as comfortable as possible. We used a peri-incisional LA solution in patients undergoing day-case inguinal hernioplasty under general anaesthesia (GA) and recorded use of analgesia in the immediate postoperative period. Methods In this observational cohort study, 100 consecutive unselected men underwent open inguinal hernia repair as a day case. Of these, 75 underwent repair under GA and 25 with peri-incisional LA solution (equal mixture of 0.5% bupivacaine and 1% lignocaine with 1:200,000 adrenaline). Analgesia prescribed at induction, for maintenance and after cessation of anaesthesia was scored in accordance with the World Health Organization (WHO) analgesic ladder. Results The median age in the GA group was 59 years (range: 25-89 years) and in the GA+LA group, it was 62 years (range: 27-88 years). Of the 100 patients, 82 underwent a mesh plug repair by seven surgeons whereas 18 underwent a flat (Lichtenstein) mesh repair by two surgeons. WHO analgesic induction and postoperative scores were significantly lower in the GA+LA group (p=0.034 and p<0.001 respectively). There was also a significant difference in use of postoperative antiemetics (23% vs 0% in the GA only and GA+LA cohorts respectively, p=0.020). Six patients (8%) in the GA group failed day-case discharge criteria. Conclusions Patients undergoing contemporary day-case GA inguinal hernioplasty with pre-emptive LA solution infiltration require lower levels of postoperative opioid analgesia and antiemetics. These cases are less likely to fail discharge criteria for planned day surgery.

Perineal Richter's herniation following proctectomy.

In a Richter's hernia, only part of the anti-mesenteric border of the bowel is incarcerated within the underlying defect. We report three cases presenting between 18 days and 11 years following proctectomy. As all patients had functioning stomas a high index of suspicion is necessary to avoid a delay in diagnosis.

Pre-existing diabetes is a risk factor for increased rates of cellular rejection after kidney transplantation: an observational cohort study.

AIM: To investigate whether people with diabetes have an elevated risk of kidney allograft rejection in a well characterized clinical cohort in the setting of contemporary immunosuppression. METHODS: We conducted a retrospective cohort study including all kidney allograft recipients at a single centre between 2007 and 2015, linking clinical, biochemical and histopathological data from electronic patient records. RESULTS: Data were analysed for 1140 kidney transplant recipients. The median follow-up was 4.4 years post-transplantation, and 117 of the kidney transplant recipients (10.2%) had diabetes at time of transplantation. Kidney allograft recipients with vs without diabetes were older (53 vs 45 years; P<0.001) and more likely to be non-white (41.0% vs 26.4%; P=0.001). Kidney allograft recipients with vs without diabetes had a higher risk of cellular rejection (19.7% vs 12.4%; P=0.024), but not of antibody-mediated rejection (3.4% vs 3.7%; P=0.564). Graft function and risk of death-censored graft loss were similar in the two groups, but kidney allograft recipients with diabetes had a higher risk of death and overall graft loss than those without diabetes. In a Cox regression model of non-modifiable risk factors at time of transplantation, diabetes was found to be an independent risk factor for cellular rejection (hazard ratio 1.445, 95% CI 1.023-1.945; P=0.042). CONCLUSIONS: Kidney allograft recipients with diabetes at transplantation should be counselled regarding their increased risk of cellular rejection but reassured regarding the lack of any adverse impact on short-to-medium term allograft function or survival.

Gallstone ileus in an 'asymptomatic' parastomal hernia.

Parastomal hernias are common and often asymptomatic. We report the first known case in which later, acute symptoms developed owing to gallstone ileus in a sac containing both omentum and small bowel. Urgent computed tomography established the diagnosis.

Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation.

The demand for liver transplantation (LT) exceeds supply, with rising waiting list mortality. Utilization of high-risk organs is low and a substantial number of procured livers are discarded. We report the first series of five transplants with rejected livers following viability assessment by normothermic machine perfusion of the liver (NMP-L). The evaluation protocol consisted of perfusate lactate, bile production, vascular flows, and liver appearance. All livers were exposed to a variable period of static cold storage prior to commencing NMP-L. Four organs were recovered from donors after circulatory death and rejected due to prolonged donor warm ischemic times; one liver from a brain-death donor was declined for high liver function tests (LFTs). The median (range) total graft preservation time was 798 (range 724-951) min. The transplant procedure was uneventful in every recipient, with immediate function in all grafts. The median in-hospital stay was 10 (range 6-14) days. At present, all recipients are well, with normalized LFTs at median follow-up of 7 (range 6-19) months. Viability assessment of high-risk grafts using NMP-L provides specific information on liver function and can permit their transplantation while minimizing the recipient risk of primary graft nonfunction. This novel approach may increase organ availability for LT.