Validation of a risk prediction calculator in Australian patients undergoing head and neck microsurgery reconstruction.

BACKGROUND: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) surgical risk calculator (SRC) is an open access calculator predicting patients' risk of postoperative complications. This study aims to assess the validity of the SRC in patients undergoing microsurgical free flap reconstruction at an Australian tertiary referral centre. METHODS: This is a retrospective cohort study of 200 consecutive patients treated up to November 2020. SRC-predicted rates of postoperative complications and hospital length of stay (LOS) were compared to those observed for the ablative and reconstructive components of the procedure. The performance of the SRC was assessed using Brier scores, area under the receiver operating characteristic (ROC) curve (AUC), and the Hosmer-Lemeshow test. RESULTS: For both ablative and reconstructive components, the SRC discriminates well for pneumonia and urinary tract infection, and it is calibrated well for readmission and sepsis, but it does not discriminate and calibrate well for any single outcome. SRC-predicted hospital LOS and actual LOS did not correlate well for the reconstructive component, but they correlated strongly for the ablative component. CONCLUSIONS: The SRC is a poor predictor of postoperative complication rates and hospital LOS in patients undergoing head and neck microsurgical reconstruction.

Validated specialty-specific models for multi-disciplinary microsurgery training laboratories: a systematic review.

BACKGROUND: Laboratory simulation is increasingly important for teaching microsurgical skills. Training microsurgeons of different specialties within the same simulation laboratory increases efficiency of resource use. For maximal benefit, simulations should be available for trainees to practice specialty-specific, higher-order skills. Selection of appropriate simulations requires knowledge of the efficacy and validity of the numerous described laboratory models. Here we present a systematic review of validated training models that may serve as useful adjuncts to achieving competency in specialty elements of microsurgery, and appraise the evidence behind them. METHODS: In setting up a multi-disciplinary microsurgery training course, we performed a systematic review according to preferred reporting items for systematic reviews and meta-analyses guidelines. EMBASE, MEDLINE, Cochrane and PubMed databases were searched for studies describing validated, microscope-based, specialty-specific simulations, and awarded a level of evidence and level of recommendation based on a modified Oxford Centre for Evidence-Based Medicine classification. RESULTS: A total of 141 papers describing specialty-specific microsimulation models were identified, 49 of which included evidence of validation. Eleven were in the field of neurosurgery, 21 in otolaryngology/head and neck surgery, two in urology/gynaecology and 15 plastic and reconstructive surgery. These papers described synthetic models in 19 cases, cadaveric animals in 10 cases, live animals in 12 cases and human cadaveric material in 10 cases. CONCLUSION: Numerous specialty-specific models for use in the microscope laboratory are available, but the quality of evidence for them is poor. Provision of models that span numerous specialties may encourage use of a microscope lab whilst still enabling more specific skills training over a 'one-size-fits-all' approach.

Rebound of HBV DNA after cessation of nucleos/tide analogues in chronic hepatitis B patients with undetectable covalently closed.

BACKGROUND & AIMS: Nucleos(t)ide analogues (NUCs) effectively suppress serum HBV DNA. Previously, we have identified 21 patients with undetectable covalently closed circular DNA (cccDNA) upon long-term NUC therapy. This study investigated the effect of NUC withdrawal in patients with undetectable cccDNA. METHODS: Nineteen patients on long term NUCs (median 13.4 years) were recruited: 13 were randomized to discontinue NUCs; 6 to continue taking NUCs. All had undetectable cccDNA at the time of last liver biopsy (median time 2.9 years prior to randomization). Serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), liver biochemistry, and serum HBV RNA were monitored. RESULTS: At the time of randomization, all patients had undetectable serum HBV DNA and HBV RNA. Twelve of the 13 patients had HBV DNA rebound to 100 IU/ml within 20 weeks of NUC discontinuation. The thirteenth patient had HBV DNA rebound at week 70. Three patients experienced biochemical flares after re-treatment which subsequently resolved. There was no significant association between the time of HBV DNA rebound and baseline HBsAg, HBcrAg and alanine aminotransferase, duration of treatment, and age at which treatment was stopped (all p >0.05). At the time of HBV DNA rebound, HBV DNA levels correlated with HBcrAg levels (p = 0.003), but not with HBsAg levels (p = 0.262). CONCLUSIONS: In patients with undetectable intrahepatic cccDNA, virologic rebound still occurred after NUC cessation. At the rebound of HBV DNA, the kinetics of HBsAg production were independent of those of viral DNA replication. Additional studies are required to determine the factors that may predict virologic rebound and when NUCs can be discontinued in HBsAg-positive patients with chronic hepatitis B. LAY SUMMARY: It has been shown that following long-term nucleos(t)ide analogue treatment for chronic hepatitis B, some patients have undetectable levels of viral DNA in their livers. We tested the results of withdrawing nucleos(t)ide analogue treatment in these patients and found that viral relapse could occur in patients with undetectable viral DNA. Further research is required to determine whether nucleos(t)ide analogue treatment can be discontinued in specific patients with chronic hepatitis B.

Mesenchymal stem cells promote healing of nonsteroidal anti-inflammatory drug-related peptic ulcer through paracrine actions in pigs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most important causes of peptic ulcer disease in high-income countries. Proton pump inhibitors are the current standard treatment; however, safety and long-term adverse effects of using these drugs are attracting more and more concerns in recent years. Using a porcine model of NSAID-related gastric ulcer, we herein show that adipose-derived mesenchymal stem cells (ADMSCs) delivered by endoscopic submucosal injection promoted ulcer healing with less inflammatory infiltration and enhanced reepithelization and neovascularization at day 7 and day 21 when compared with the controls (saline injection). However, only few engrafted ADMSCs showed myofibroblast and epithelial cell phenotype in vivo, suggesting the ulcer healing process might be much less dependent on the stem cell transdifferentiation. Further experiment with submucosal injection of MSC-derived secretome revealed a therapeutic efficacy comparable to that of stem cell transplantation. Profiling analysis showed up-regulation of genes associated with inflammation, granulation formation, and extracellular matrix remodeling at day 7 after injection of MSC-derived secretome. In addition, the extracellular signal-regulated kinase/mitogen-activated protein kinase and the phosphoinositide-3-kinase/protein kinase B pathways were activated after injection of ADMSCs or MSC-derived secretome. Both signaling pathways were involved in mediating the major events critical to gastric ulcer healing, including cell survival, migration, and angiogenesis. Our data suggest that endoscopic submucosal injection of ADMSCs serves as a promising approach to promote healing of NSAID-related peptic ulcer, and the paracrine effectors released from stem cells play a crucial role in this process.

Reconstruction of the trachea.

This article reviews established methods of autologous tracheal reconstruction, the various synthetic prostheses that have been used in clinical practice, and briefly describes the latest developments in stem cell tracheal bioengineering and allogeneic tracheal transplantation. Reconstruction of the trachea is challenging due to its part cervical part thoracic location, proximity to major vessels, variable blood supply, and its constant colonization with bacteria. In cases of limited resection, primary anastomosis, autologous patch grafts, local advancement rotation flaps, and locoregional cutaneous and muscle flaps will often suffice. In more extensive resections, complex composite microsurgical reconstruction with a radial forearm free flap with cartilage grafts for skeletal support has proven to be viable and reliable. Synthetic tracheal prostheses, solid as well as porous, have been trialed with disappointing results. Infection, dislodgement, migration, and obstruction are not uncommon. Reconstruction with the cadaveric tracheal allografts and aortic allografts continue to be fraught with complications, specifically graft infections. Tracheal bioengineering and tracheal allotransplantation have emerged relatively recently. Despite early promising results, long-term outcome data on these new techniques are still lacking.

Reconstruction of the (Crico)trachea for malignancy in the virgin and irradiated neck.

BACKGROUND: Reconstruction of the trachea following resection for malignancy is challenging. We present our experience over a 5-year period, and a reconstruction algorithm with particular emphasis on minimising complications associated with radiotherapy. METHODS: A maximum of six tracheal rings can be resected and anastomosed primarily with acceptable tension. A more conservative approach is required in an irradiated trachea. For a limited defect localised anteriorly or laterally, a tracheal flap can be fashioned. As for more eccentric defects, an option is to convert the defect into an asymmetrical segmental defect, and to primarily anastomose the trachea with rotation of the distal stump. Our workhorse loco-regional flaps for patch reconstruction or suture line reinforcement include the sternocleidomastoid, internal mammary artery perforator and pectoralis major myocutaneous flaps. For extensive defects, a radial forearm free flap (RFFF) with rib cartilage struts for rigidity provides a good solution. RESULTS: Fifteen patients (M:F = 4:11, median age 69 years) were identified. Six cases were locally aggressive papillary thyroid cancer. Mean follow-up was 17 months. Five and two patients had had radiotherapy prior to and following tracheal resection, respectively. Nine patients were extubated at the end of surgery, two were successfully decannulated from their T tube subsequently, and one from his tracheostomy. The two surgical complications included a partial RFFF dehiscence causing minor air leak, and major haemorrhage that warranted urgent operation and pectoralis major flap reconstruction. CONCLUSION: Reconstruction of the trachea requires individualised techniques suited to the patient's body habitus, co-morbidity, previous treatment and the configuration of the defect.

Randomized double-blind crossover study to determine the effects of erythromycin on small intestinal nutrient absorption and transit in the critically ill.

BACKGROUND: The gastrokinetic drug erythromycin is commonly administered to critically ill patients during intragastric feeding to augment small intestinal nutrient delivery. However, erythromycin has been reported to increase the prevalence of diarrhea, which may reflect reduced absorption and/or accelerated small intestinal transit. OBJECTIVE: The objective was to evaluate the effects of intravenous erythromycin on small intestinal nutrient absorption and transit in the critically ill. DESIGN: On consecutive days, erythromycin (200 mg in 20 mL 0.9% saline) or placebo (20 mL 0.9% saline) were infused intravenously between -20 and 0 min in a randomized, blinded, crossover fashion. Between 0 and 30 min, a liquid nutrient containing 3-O-methylglucose (3-OMG), [13C]triolein, and [(99m)Tc]sulfur colloid was administered directly into the small intestine at 2 kcal/min. Serum 3-OMG concentrations and exhaled (13)CO2 (indices of glucose and lipid absorption, respectively) were measured. Cecal arrival of the infused nutrient was determined by scintigraphy. Data are medians (ranges) and were analyzed by using Wilcoxon's signed-rank test. RESULTS: Thirty-two mechanically ventilated patients were studied. Erythromycin increased small intestinal glucose absorption [3-OMG AUC360: 105.2 (28.9-157.0) for erythromycin compared with 91.8 (51.4-147.9) mmol/L · min for placebo; P = 0.029] but tended to reduce lipid absorption [cumulative percentage dose (13)CO2 recovered: 10.4 (0-90.6) compared with 22.6 (0-100) %; P = 0.06]. A trend to slower transit was observed after erythromycin [300 (39-360) compared with 228 (33-360) min; P = 0.07]. CONCLUSIONS: Acute administration of erythromycin increases small intestinal glucose absorption in the critically ill, but there was a tendency for the drug to reduce small intestinal lipid absorption and slow transit. These observations have implications for the use of erythromycin as a gastrokinetic drug in the critically ill. This trial was registered in the Australian New Zealand Clinical Trials Registry as ACTRN 12610000615088.

Achromatization of Wollaston polarizing beam splitters.

We describe the achromatization of Wollaston prisms to reduce the angular dispersion in the splitting angle. Analytical theory and ray-tracing modeling is presented. In an example application, a sixfold reduction in dispersion is achieved for wavelengths in the region 400 nm to 1.7 µm. Experimental proof of concept is demonstrated, and in an example application, the spectral dispersion of extended images recorded through cascaded Wollaston prisms is shown to be reduced by an order of magnitude.