Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity.

Inborn errors of immunity (IEIs) are a heterogeneous group of diverse clinical and genetic phenotypes that have an estimated combined prevalence as high as 1/1000. Increased risk of frequent, severe, or opportunistic infections is a common feature of IEIs, but there are also diverse immune-mediated, non-infective complications that are associated with significant morbidity and mortality. As patient survival increases, these are becoming more apparent within the liver. Hepatic involvement of IEIs may not only manifest as infections, but also nodular regenerative hyperplasia, granulomatous disease, autoimmune hepatitis and malignancy. As therapeutic options for patients are expanding, with both pharmaceutical treatments as well as haematopoietic stem cell transplant (HSCT), iatrogenic liver injury is increasingly common and important to identify. This review article summarises the spectrum of hepatic complications seen in IEIs, and highlights the challenges of management within this patient cohort, where immunosuppression is poorly tolerated. Early recognition and prompt diagnosis of potential hepatic complications is therefore crucial in ensuring potentially reversible causes are treated, but significant uncertainty remains regarding best practice for many features of immune dysregulation with limited high-quality evidence.

The Polyol Process and the Synthesis of ζ Intermetallic Compound Ag5Sn0.9.

The present work concerns the intermetallic compound (IMC) existing in the Ag-Sn system and its potential use in electronics as attachment materials allowing the adhesion of the chip to the substrate forming the power module. First, we present the synthesis protocol in polyol medium of a compound with the chemical formula Ag5Sn0.9 belonging to the solid solution of composition located between 9 and 16 at.% Sn, known as solid solution ζ (or ζ-Ag4Sn). This phase corresponds to the peritectic invariant point at 724 °C. Differential thermal analysis and X-ray dispersive analysis confirm the single-phased (monocrystalline) nature of the Ag5Sn0.9 powder issued after synthesis. Scanning electron microscopy shows that Ag5Sn0.9 particles are spherical, and range in submicronic size of around 0.18 µm. X-ray diffraction analysis reveals that the ζ phase mostly exists under the two allotropic varieties (orthorhombic symmetry and hexagonal symmetry) with however a slight excess of the hexagonal variety (60% for the hexagonal variety and 40% for the orthorhombic variety). The lattice parameters resulting from this study for the two allotropic varieties are in good agreement with the Hume-Rothery rules.

Characterization of heterogeneous primary human cartilage-derived cell population using non-invasive live-cell phase-contrast time-lapse imaging.

Reliable and reproducible cell therapy strategies to treat osteoarthritis demand an improved characterization of the cell and heterogeneous cell population resident in native cartilage tissue. Using live-cell phase-contrast time-lapse imaging (PC-TLI), this study investigates the morphological attributes and biological performance of the three primary biological objects enzymatically isolated from primary human cartilage: connective tissue progenitors (CTPs), non-progenitors (NPs) and multi-cellular structures (MCSs). The authors' results demonstrated that CTPs were smaller in size in comparison to NPs (P < 0.001). NPs remained part of the adhered cell population throughout the cell culture period. Both NPs and CTP progeny on day 8 increased in size and decreased in circularity in comparison to their counterparts on day 1, although the percent change was considerably less in CTP progeny (P < 0.001). PC-TLI analyses indicated three colony types: single-CTP-derived (29%), multiple-CTP-derived (26%) and MCS-derived (45%), with large heterogeneity with respect to cell morphology, proliferation rate and cell density. On average, clonal (CL) (P = 0.009) and MCS (P = 0.001) colonies exhibited higher cell density (cells per colony area) than multi-clonal (MC) colonies; however, it is interesting to note that the behavior of CL (less cells per colony and less colony area) and MCS (high cells per colony and high colony area) colonies was quite different. Overall effective proliferation rate (EPR) of the CTPs that formed CL colonies was higher than the EPR of CTPs that formed MC colonies (P = 0.02), most likely due to CTPs with varying EPR that formed the MC colonies. Finally, the authors demonstrated that lag time before first cell division of a CTP (early attribute) could potentially help predict its proliferation rate long-term. Quantitative morphological characterization using non-invasive PC-TLI serves as a reliable and reproducible technique to understand cell heterogeneity. Size and circularity parameters can be used to distinguish CTP from NP populations. Morphological cell and colony features can also be used to reliably and reproducibly identify CTP subpopulations with preferred proliferation and differentiation potentials in an effort to improve cell manufacturing and therapeutic outcomes.

Randomized single-blind clinical trial of intradermal methylene blue on pain reduction after open diathermy haemorrhoidectomy.

BACKGROUND: Open haemorrhoidectomy has been associated with considerable postoperative pain and discomfort. Perianal intradermal injection of methylene blue has been shown to ablate perianal nerve endings and may bring about temporary pain relief after haemorrhoidectomy. We hypothesized that the administration of intradermal methylene blue would reduce postoperative pain during the initial period after surgery. METHOD: A randomized, prospective, single-blind placebo-controlled trial was conducted. Patients were randomized to intradermal injection at haemorrhoidectomy of either 4 ml 1% methylene blue and 16 ml 0.5% marcaine or of 16 ml 0.5% marcaine and 4 ml saline prior to surgical dissection. Patients were asked to fill in a pain diary with a visual analogue scale. The primary outcome measure was pain score and analgesic use. Secondary outcomes were complications. RESULTS: There were 37 patients in the methylene blue arm and 30 patients in the placebo arm. There were no statistically significant differences in the sex, type of haemorrhoid, number of haemorrhoids excised, duration of surgery or hospital stay. The mean pain scores were significantly lower and the use of paracetamol was also significantly less in the methylene blue group during the first three postoperative days. The risk ratio of acute urinary retention occurring when methylene blue was not used was 2.320 (95% CI 1.754-3.067). Other complication rates were not significantly different. CONCLUSION: Perianal intradermal injection of methylene blue was useful in reducing the initial postoperative pain of open haemorrhoidectomy.

Proximal bowel necrosis after high ligation of the inferior mesenteric artery in colorectal surgery.

BACKGROUND AND AIMS: High ligation of the inferior mesenteric artery may jeopardize blood supply to the proximal bowel. We undertook this study to review the clinical features and outcomes of patients who developed proximal bowel necrosis after high ligation of the inferior mesenteric artery, and to assess the incidence and the risk factors for this complication. MATERIALS AND METHODS: A retrospective analysis of patients undergoing high or low ligation for sigmoid colon and rectal cancer with a primary anastomosis between April 2004 and March 2009 was performed. Patient and tumor characteristics and the incidence of bowel necrosis were reviewed. RESULTS: Four hundred and nine patients were included to the analysis. Six out of 302 patients (2.0%) with high ligation developed proximal bowel necrosis, while the remaining 107 patients with low ligation did not suffer from this complication. All patients who developed proximal bowel necrosis underwent secondary surgery with resection of necrotic bowel. The pathological examination of the resected specimen revealed mucosal to transmural ischemic necrosis without the evidence of vascular thrombosis or embolic occlusion. Univariate analysis revealed that advanced age, cerebrovascular disease, and hypertension were significantly associated with proximal bowel necrosis. Multivariate analysis demonstrated that cerebrovascular disease was an independent predictor of this complication. Of these six patients, two died from associated complications. CONCLUSIONS: Proximal bowel necrosis after high ligation is potentially fatal, and this report provides a warning in clinical settings where high ligation is indicated. Further studies are warranted to evaluate its distinct relationship with high ligation and to clarify whether low ligation would be a safeguard.

Multimedia article. Transanal endoscopic resection of the rectum with high ligation on a swine model--a novel type of natural orifice endoscopic surgery.

We present the video of a transanal radical resection of the rectum on a swine model (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A4). The equipment used included simple instruments used in perianal surgery and a flexible endoscope with diathermy. The equipment and skill set required for this technique is easily accessible and reproduced. The potential exists to further develop this procedure with the ultimate aim of performing an incisionless and painless radical resection of the rectum in humans.

Sushi-roll wrap of Seprafilm for ileostomy limbs facilitates ileostomy closure.

BACKGROUND: Sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm) reduced postoperative intraabdominal adhesion. In this study, we examined whether Seprafilm reduces operative difficulties in ileostomy closure. PATIENTS AND METHODS: During the creation of the ileostomy, Seprafilm was cut in half and used to wrap both the ileum and mesentery. Patients who underwent ileostomy closure before February 2008 (without Seprafilm, Group T, n = 18) and after March (with Seprafilm, Group S, n = 18) were enrolled in this study. All operations were performed by surgical residents. Operative time and perioperative complications were analyzed. RESULTS: The mean operative time of Group S (106.88 min) was significantly less than that of Group T (120.6 min). The amount of intraoperative bleeding in Groups S and T was not significantly different and there were no major complications. CONCLUSION: Seprafilm applied to the two limbs of the ileostomy and mesentery facilitate ileostomy closure done by non-expert surgeons.

The use of a wound protector to prevent port site recurrence may not be totally logical.

The wound protector has been used widely to prevent port site metastases (PSM). Although port site metastases ties in with poor survival, it is not because of PSM itself, but rather because PSM is a sign of more widespread metastatic disease. Whilst being touted as a method of preventing PSM, it fails to address the bigger issue of preventing intra-abdominal recurrence. Proper surgical technique in tumour handling following rigorous oncological principles, and not just putting in a wound protector is the key to good surgery with low recurrences and excellent survival rates.

Randomized clinical trial comparing LigaSure haemorrhoidectomy with open diathermy haemorrhoidectomy.

BACKGROUND: Milligan-Morgan excision haem-orrhoidectomy remains a very popular treatment modality for third and fourth degree haemorrhoids due to its cost effectiveness and good long-term results. The LigaSure tissue-sealing device is an alternative technique used in haemorrhoidectomy that has been shown to produce favourable results. The aim of this study was to assess the effectiveness of the LigaSure tissue sealing device in comparison with conventional diathermy haemorrhoidectomy. METHODS: A prospective clinical trial was conducted. Patients with newly diagnosed haemorrhoids requiring haemorrhoidectomy were randomized to either LigaSure haemorrhoidectomy or diathermy haemorrhoidectomy. Surgical technique and postoperative care was standardized. Outcome measures were operative time and bleeding, postoperative pain (measured on a visual analogue scale) and rate of wound healing. RESULTS: We randomized 44 patients, 22 to LigaSure and 22 to diathermy; 43 patients were evaluated. They were aged between 19 and 71 years. There were no differences in patient demographics or type of haemorrhoid being operated on. LigaSure haemorrhoidectomy had a significantly lower mean operative time and intraoperative bleeding. At 3 weeks after surgery, haemorrhoidectomy performed with LigaSure had an odds ratio for complete epithelialization of 3.1 over diathermy (95% CI 1.2-8.2). There was no difference in postoperative pain. CONCLUSION: LigaSure haemorrhoidectomy is superior to diathermy for open haemorrhoidectomy.

Randomized clinical trial of 0.2 per cent glyceryl trinitrate ointment for wound healing and pain reduction after open diathermy haemorrhoidectomy.

BACKGROUND: Open haemorrhoidectomy is associated with considerable postoperative pain and discomfort. This study assessed whether glyceryl trinitrate (GTN) ointment promotes wound healing and reduces pain after open haemorrhoidectomy. METHODS: A randomized prospective double-blind placebo-controlled trial was conducted. Patients were randomized to either 0.2 per cent GTN ointment or placebo ointment (petroleum jelly). Patients were asked to fill in a pain diary. Complete healing was defined as complete epithelialization. RESULTS: There were 40 patients in the GTN group and 42 in the placebo group. There were no statistically significant differences in sex, weight, type of haemorrhoid, type of surgery (emergency or elective), number of haemorrhoids excised, duration of surgery, hospital stay and complication rate between the groups. Pain scores and analgesic use were not significantly different. By week 3, however, 17 patients in the GTN group had completely epithelialized wounds compared with eight patients in the placebo group (P = 0.021). Only one patient who received GTN experienced headache requiring discontinuation of the ointment. CONCLUSION: TGN 0.2 per cent ointment improved wound healing rates, but did not reduce pain in this study.