[Watch and Wait for Rectal Cancer]. / Surveillance bei Watch-and-Wait nach neoadjuvanter Therapie beim Rektumkarzinom.

About one third of all colorectal carcinomas (CRC) are localised in the rectum. As part of a multimodal therapy concept, neoadjuvant therapy achieves downstaging of the tumour in 50-60% of cases and a so-called complete clinical response (cCR), defined as clinically (and radiologically) undetectable residual tumour after completion of neoadjuvant therapy, in 10-30% of cases.In view of the perioperative morbidity and mortality associated with radical rectal resection, including the occurrence of a symptom complex known as low anterior resection syndrome (LARS) and the need for deviation, at least temporarily, the question of the risk-benefit balance of organ resection in the presence of cCR has been raised. In this context, the therapeutic concept of a "watch-and-wait" approach with omission of immediate organ resection and inclusion in a structured surveillance regime, has emerged.For a safe, oncological implementation of this option, it is necessary to develop standards in the definition of a suitable patient clientele and the implementation of the concept. In addition to the initial correct selection of the patient group that is suitable for a primarily non-surgical procedure, the inherent goal is the early and sufficient detection of tumour recurrence (so-called local regrowth) during the "watch-and-wait" phase (surveillance).In this context, in this paper we address the questions of: 1. the optimal timing of initial re-staging, 2. the criteria for assessing the clinical response and selecting the appropriate patient clientele, 3. the rhythm and design of the surveillance protocol.

The effect of My Health Record use in the emergency department on clinician-assessed patient care: results from a survey.

BACKGROUND: The emergency department has been a major focus for the implementation of Australia's national electronic health record, known as My Health Record. However, the association between use of My Health Record in the emergency department setting and patient care is largely unknown. The aim of this study was to explore the perspectives of emergency department clinicians regarding My Health Record use frequency, the benefits of My Health Record use (with a focus on patient care) and the barriers to use. METHODS: All 393 nursing, pharmacy, physician and allied health staff employed within the emergency department at a tertiary metropolitan public hospital in Melbourne were invited to participate in a web-based survey, between 1 May 2021 and 1 December 2021, during the height of the Delta and Omicron Covid-19 outbreaks in Victoria, Australia. RESULTS: Overall, the survey response rate was 18% (70/393). Approximately half of the sample indicated My Health Record use in the emergency department (n = 39, 56%, confidence interval [CI] 43-68%). The results showed that users typically only engaged with My Health Record less than once per shift (n = 15, 39%, CI 23-55%). Just over half (n = 19/39, 54%, CI 32-65%) of all participants who use My Health Record agreed they could remember a time when My Health Record had been critical to the care of a patient. Overall, clinicians indicated the biggest barrier preventing their use of My Health Record is that they forget to utilise the system. CONCLUSION: The results suggest that My Health Record has not been adopted as routine practice in the emergency department, by the majority of participants. Close to half of self-identified users of My Health Record do not associate use as being critical to patient care. Instead, My Health Record may only be used in scenarios that clinicians perceive will yield the greatest benefit-which clinicians in this paper suggest is patients with chronic and complex conditions. Further research that explores the predictors to use and consumers most likely to benefit from use is recommended-and strategies to socialise this knowledge and educate clinicians is desperately required.

Suppurative thyroiditis caused by ingested fish bone in the thyroid gland: a case report on its diagnostics and surgical therapy.

BACKGROUND: Accidental ingestion of fish bone is a common cause of otolaryngological emergency. Migration of the ingested bone into the thyroid gland, however, occurs very rarely. The associated clinical presentation, symptoms and duration of discomfort are also highly variable between patients and can be diagnostically challenging. CASE PRESENTATION: Here, we report the case of a 71-year-old female patient presenting with an ingested fish bone that migrated into the right thyroid lobe as a rare cause of suppurative thyroiditis with the clinical features of sepsis. We outline the diagnostic approach, peri- and intraoperative management as well as complications. It is proposed that besides endoscopy, imaging methods such as ultrasound or computed tomography may be necessary to verify the diagnosis and location of an ingested fish bone. Prompt surgical removal of the foreign body and resection of the infectious focus is recommended to minimize the risk of local inflammation, recurrent nerve lesions and septic complications arising from the spread of infection. CONCLUSION: Fish bone migration into the thyroid gland is an extremely rare event, the successful detection and surgical management of which can be achieved through a careful interdisciplinary approach.

Emergency medicine patient wait time multivariable prediction models: a multicentre derivation and validation study.

OBJECTIVE: Patients, families and community members would like emergency department wait time visibility. This would improve patient journeys through emergency medicine. The study objective was to derive, internally and externally validate machine learning models to predict emergency patient wait times that are applicable to a wide variety of emergency departments. METHODS: Twelve emergency departments provided 3 years of retrospective administrative data from Australia (2017-2019). Descriptive and exploratory analyses were undertaken on the datasets. Statistical and machine learning models were developed to predict wait times at each site and were internally and externally validated. Model performance was tested on COVID-19 period data (January to June 2020). RESULTS: There were 1 930 609 patient episodes analysed and median site wait times varied from 24 to 54 min. Individual site model prediction median absolute errors varied from±22.6 min (95% CI 22.4 to 22.9) to ±44.0 min (95% CI 43.4 to 44.4). Global model prediction median absolute errors varied from ±33.9 min (95% CI 33.4 to 34.0) to ±43.8 min (95% CI 43.7 to 43.9). Random forest and linear regression models performed the best, rolling average models underestimated wait times. Important variables were triage category, last-k patient average wait time and arrival time. Wait time prediction models are not transferable across hospitals. Models performed well during the COVID-19 lockdown period. CONCLUSIONS: Electronic emergency demographic and flow information can be used to approximate emergency patient wait times. A general model is less accurate if applied without site-specific factors.

The novel KIT exon 11 germline mutation K558N is associated with gastrointestinal stromal tumor, mastocytosis, and seminoma development.

Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys-558-Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations.

Predicting Ambulance Patient Wait Times: A Multicenter Derivation and Validation Study.

STUDY OBJECTIVE: To derive and internally and externally validate machine-learning models to predict emergency ambulance patient door-to-off-stretcher wait times that are applicable to a wide variety of emergency departments. METHODS: Nine emergency departments provided 3 years (2017 to 2019) of retrospective administrative data from Australia. Descriptive and exploratory analyses were undertaken on the datasets. Statistical and machine-learning models were developed to predict wait times at each site and were internally and externally validated. RESULTS: There were 421,894 episodes analyzed, and median site off-load times varied from 13 (interquartile range [IQR], 9 to 20) to 29 (IQR, 16 to 48) minutes. The global site prediction model median absolute errors were 11.7 minutes (95% confidence interval [CI], 11.7 to 11.8) using linear regression and 12.8 minutes (95% CI, 12.7 to 12.9) using elastic net. The individual site model prediction median absolute errors varied from the most accurate at 6.3 minutes (95% CI, 6.2 to 6.4) to the least accurate at 16.1 minutes (95% CI, 15.8 to 16.3). The model technique performance was the same for linear regression, random forests, elastic net, and rolling average. The important variables were the last k-patient average waits, triage category, and patient age. The global model performed at the lower end of the accuracy range compared with models for the individual sites but was within tolerable limits. CONCLUSION: Electronic emergency demographic and flow information can be used to estimate emergency ambulance patient off-stretcher times. Models can be built with reasonable accuracy for multiple hospitals using a small number of point-of-care variables.

Intestinal Epithelial Barrier Maturation by Enteric Glial Cells Is GDNF-Dependent.

Enteric glial cells (EGCs) of the enteric nervous system are critically involved in the maintenance of intestinal epithelial barrier function (IEB). The underlying mechanisms remain undefined. Glial cell line-derived neurotrophic factor (GDNF) contributes to IEB maturation and may therefore be the predominant mediator of this process by EGCs. Using GFAPcre x Ai14floxed mice to isolate EGCs by Fluorescence-activated cell sorting (FACS), we confirmed that they synthesize GDNF in vivo as well as in primary cultures demonstrating that EGCs are a rich source of GDNF in vivo and in vitro. Co-culture of EGCs with Caco2 cells resulted in IEB maturation which was abrogated when GDNF was either depleted from EGC supernatants, or knocked down in EGCs or when the GDNF receptor RET was blocked. Further, TNFα-induced loss of IEB function in Caco2 cells and in organoids was attenuated by EGC supernatants or by recombinant GDNF. These barrier-protective effects were blunted when using supernatants from GDNF-deficient EGCs or by RET receptor blockade. Together, our data show that EGCs produce GDNF to maintain IEB function in vitro through the RET receptor.

Correction to: Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion.

In the published article, the legend for figure 3 was incorrect. The correct legend is given below.

Health Outcomes and Healthcare Efficiencies Associated with the Use of Electronic Health Records in Hospital Emergency Departments: a Systematic Review.

Healthcare organisations and governments have invested heavily in electronic health records in anticipation that they will deliver improved health outcomes for consumers and efficiencies across emergency departments. Despite such investment, electronic health records designed to support emergency care have been poorly evaluated. Given the accelerated development and adoption of information technology across healthcare, it is timely that a systematic review of this evidence base is updated in order to drive improvements to design, interoperability and overall clinical utility of electronic health record systems implemented in emergency departments. To assess the impact of electronic health records on healthcare outcomes and efficiencies in the emergency department we carried out a systematic review of published studies on this topic. This is the first review to summarise the cost efficiencies associated with electronic health record use outside of just the United States of America. A systematic search was performed in three scientific databases (MEDLINE, EMcare and EMBASE), of literature published between January 2000 and September 2019. Studies were included in this review if they evaluated electronic health records or health information exchanges (and synonyms for these terms), reported patient outcome and/or healthcare efficiency benefits, were peer-reviewed and published in English. Out of 6635 articles, 23 studies met our inclusion criteria. Wide variation regarding electronic health record access in the emergency department was reported (1.46-56.6%), yet was most frequently reported as less than 20%. Seven different types of health outcomes and three different types of efficiency improvements associated with electronic health record use in the emergency department were identified. The most frequently reported findings were efficiencies, including reductions in diagnostic tests, imaging and costs. This review is the first to report moderate to significant increases in admission rates are associated with electronic health record use in the emergency department, contrasting the findings of previous reviews. Diversity in the methodology employed across the included studies emphasises the need for further research to examine the impact of electronic health record implementation and system design on the findings reported, in order to ensure return on investment for stakeholders and optimised consumer care.

Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion.

Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell-cell contacts. EGFR is critical for cell adhesion and barrier recovery. In line with this, Dsg2-deficient enterocytes display impaired barrier properties and increased cell proliferation. Mechanistically, Dsg2 directly interacts with EGFR and undergoes heterotypic-binding events on the surface of living enterocytes via its extracellular domain as revealed by atomic force microscopy. Thus, our study reveals a new mechanism by which Dsg2 via Src shapes EGFR function towards cell adhesion.

Emergency consultants value medical scribes and most prefer to work with them, a few would rather not: a qualitative Australian study.

OBJECTIVE: The utilisation of medical scribes in the USA has enabled productivity gains for emergency consultants, though their personal experiences have not been widely documented. We aimed to evaluate the consultant experience of working with scribes in an Australian ED. METHODS: Emergency consultants working with scribes and those who declined to work with scribes were invited to participate in individual interviews (structured and semistructured questions) about scribes, scribe work and the scribe program in October 2016. RESULTS: Of 16 consultants, 13 participated in interviews, that is, 11 worked with scribes and 2 did not and 3 left Cabrini prior to the interviews. Consultants working with scribes found them most useful for capturing initial patient encounters, for finding information and completing discharge tasks. Scribes captured more details than consultants usually did. Editing was required for omissions, misunderstandings and rearranging information order, but this improved with increasing scribe experience. Consultants described changing their style to give more information to the patient in the room. Consultants felt more productive and able to meet demands. They also described enjoyment, less stress, less cognitive loading, improved ability to multitask, see complex patients and less fatigue.In interviews with the two consultants declining scribes, theme saturation was not achieved. Consultants declining scribes preferred to work independently. They did not like templated notes and felt that consultation nuances were lost. They valued their notes write-up time as time for cognitive processing of the presentation. They thought the scribe and computer impacted negatively on communication with the patient. CONCLUSION: Medical scribes were seen to improve physician productivity, enjoyment at work, ability to multitask and to lower stress levels. Those who declined scribes were concerned about losing important nuances and cognitive processing time for the case.

Feasibility evaluation of a pilot scribe-training program in an Australian emergency department.

Objective Medical scribes have an emerging and expanding role in health, particularly in Emergency Medicine in the US. Scribes assist physicians with documentation and clerical tasks at the bedside while the physician consults with his or her patient. Scribes increase medical productivity. The aim of the present study was to examine the feasibility of a pilot hospital-administered scribe-training program in Australia and to evaluate the ability of an American training course (Medical Scribe Training Systems) to prepare trainee scribes for clinical training in an emergency department in Australia. Methods The present study was a pilot, prospective, observational cohort study from September 2015 to February 2016 at Cabrini Emergency Department, Melbourne. Scribe trainees were enrolled in the pre-work course and then trained clinically. Feasibility of training scribes and limited efficacy testing of the course was undertaken. Results The course was acceptable to users and demand for training exists. There were many implementation tasks and issues experienced and resources were required to prepare the site for scribe implementation. Ten trainees were enrolled for preclinical training. Six candidates undertook clinical training, five achieved competency (required seven to 16 clinical shifts after the preclinical course). The training course was helpful and provided a good introduction to the scribe role. The course required adaptation to a non-US setting and the specific hospital setting. In addition, it needed more detail in some common emergency department topics. Conclusion Training scribes at a hospital in Australia is feasible. The US training course used can assist with preclinical training. Course modification is required. What is known about the topic? Scribes increase emergency physician productivity in Australia. There is no previous work on how to train scribes in Australia. What does this paper add? We show that implementing a scribe-training program is feasible and that a training package can be purchased from the US to train scribes in Australia and that it is useful. We also show the adaptation that the course may require to meet Australian emergency department needs. What are the implications for practitioners? Scribes could become an additional member of the emergency department team in Australia and can be trained locally.

Acupuncture for analgesia in the emergency department: a multicentre, randomised, equivalence and non-inferiority trial.

OBJECTIVES: This study aimed to assess analgesia provided by acupuncture, alone or in combination with pharmacotherapy, to patients presenting to emergency departments with acute low back pain, migraine or ankle sprain. DESIGN: A pragmatic, multicentre, randomised, assessor-blinded, equivalence and non-inferiority trial of analgesia, comparing acupuncture alone, acupuncture plus pharmacotherapy, and pharmacotherapy alone for alleviating pain in the emergency department. Setting, participants: Patients presenting to emergency departments in one of four tertiary hospitals in Melbourne with acute low back pain, migraine, or ankle sprain, and with a pain score on a 10-point verbal numerical rating scale (VNRS) of at least 4. MAIN OUTCOME MEASURES: The primary outcome measure was pain at one hour (T1). Clinically relevant pain relief was defined as achieving a VNRS score below 4, and statistically relevant pain relief as a reduction in VNRS score of greater than 2 units. RESULTS: 1964 patients were assessed between January 2010 and December 2011; 528 patients with acute low back pain (270 patients), migraine (92) or ankle sprain (166) were randomised to acupuncture alone (177 patients), acupuncture plus pharmacotherapy (178) or pharmacotherapy alone (173). Equivalence and non-inferiority of treatment groups was found overall and for the low back pain and ankle sprain groups in both intention-to-treat and per protocol (PP) analyses, except in the PP equivalence testing of the ankle sprain group. 15.6% of patients had clinically relevant pain relief and 36.9% had statistically relevant pain relief at T1; there were no between-group differences. CONCLUSION: The effectiveness of acupuncture in providing acute analgesia for patients with back pain and ankle sprain was comparable with that of pharmacotherapy. Acupuncture is a safe and acceptable form of analgesia, but none of the examined therapies provided optimal acute analgesia. More effective options are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12609000989246.

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease.

Regulation of the intestinal epithelial barrier is a differentiated process, which is profoundly deranged in inflammatory bowel diseases. Recent data provide evidence that the glial cell line-derived neurotrophic factor (GDNF) is critically involved in intestinal epithelial wound healing and barrier maturation and exerts antiapoptotic effects under certain conditions. Furthermore, not only the enteric nervous system, but also enterocytes synthesize GDNF in significant amounts, which points to a potential para- or autocrine signaling loop between enterocytes. Apart from direct effects of GDNF on enterocytes, an immunomodulatory role of this protein has been previously assumed because of a significant reduction of inflammation in a model of chronic inflammatory bowel disease after application of GDNF. In this review we summarize the current knowledge of GDNF on intestinal epithelial barrier regulation and discuss the novel role for GDNF as a regulator of intestinal barrier functions in health and disease.

An economic evaluation of the costs of training a medical scribe to work in Emergency Medicine.

OBJECTIVE: To undertake a cost analysis of training medical scribes in an ED. METHODS: This was a pilot, observational, single-centre study at Cabrini ED, Melbourne, Australia, studying the costs of initiating a scribe programme from the perspective of the hospital and Australian Health sector. Recruitment and training occurred between August 2015 and February 2016 and comprised of a prework course (1 month), prework training sessions and clinical training shifts for scribe trainees (2-4 months, one shift per week) who were trained by emergency physicians. Costs of start-up, recruitment, administration, preclinical training, clinical training shifts and productivity changes for trainers were calculated. RESULTS: 10 trainees were recruited to the prework course, 9 finished, 6 were offered clinical training after simulation assessment, 5 achieved competency. Scribes required clinical training ranging from 68 to 118 hours to become competent after initial classroom training. Medical students (2) required 7 shifts to become competent, premedical students (3) 8-16 shifts, while a trainee from an alternative background did not achieve competency. Based on a scribe salary of US$15.91/hour (including 25% on-costs) plus shift loadings, costs were: recruitment and start-up US$3111, education US$1257, administration US$866 and clinical shift costs US$1137 (overall cost US$6317 per competent scribe). Physicians who trained the clinical trainee scribes during shifts did not lose productivity. CONCLUSIONS: Training scribes outside the USA is feasible using an on-line training course and local physicians. It makes economic sense to hire individuals who can work over a long period of time to recoup training costs. TRIAL REGISTRATION NUMBER: ACTRN12615000607572.

Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro.

Recent data suggest that neurotrophic factors from the enteric nervous system are involved in intestinal epithelial barrier regulation. In this context the glial cell line-derived neurotrophic factor (GDNF) was shown to affect gut barrier properties in vivo directly or indirectly by largely undefined processes in a model of inflammatory bowel disease (IBD). We further investigated the potential role and mechanisms of GDNF in the regulation of intestinal barrier functions. Immunostaining of human gut specimen showed positive GDNF staining in enteric neuronal plexus and in enterocytes. In Western blots of the intestinal epithelial cell lines Caco2 and HT29B6, significant amounts of GDNF were detected, suggesting that enterocytes represent an additional source of GDNF. Application of recombinant GDNF on Caco2 and HT29B6 cells for 24 h resulted in significant epithelial barrier stabilization in monolayers with immature barrier functions. Wound-healing assays showed a significantly faster closure of the wounded areas after GDNF application. GDNF augmented cAMP levels and led to significant inactivation of p38 MAPK in immature cells. Activation of p38 MAPK signaling by SB-202190 mimicked GDNF-induced barrier maturation, whereas the p38 MAPK activator anisomycin blocked GDNF-induced effects. Increasing cAMP levels had adverse effects on barrier maturation, as revealed by permeability measurements. However, increased cAMP augmented the proliferation rate in Caco2 cells, and GDNF-induced proliferation of epithelial cells was abrogated by the PKA inhibitor H89. Our data show that enterocytes represent an additional source of GDNF synthesis. GDNF contributes to wound healing in a cAMP/PKA-dependent manner and promotes barrier maturation in immature enterocytes cells by inactivation of p38 MAPK signaling.

[Incisional hernias: minimally invasive surgical procedures]. / Narbenhernien: minimalinvasive Operationsverfahren.

BACKGROUND: In recent years many new surgical techniques for minimally invasive treatment of ventral hernias have been developed and introduced. This review article presents these new minimally invasive surgical techniques, such as extended totally extraperitoneal (eTEP) repair, mini or less open sublay (MILOS), endoscopic-assisted linea alba reconstruction (ELAR), the ventral transabdominal preperitoneal patch (TAPP) technique, intraperitoneal onlay mesh (IPOM) plus and laparoscopic intracorporeal rectus aponeuroplasty (LIRA) and discusses recently published results. RESULTS: Modern minimally invasive techniques for the treatment of ventral hernias have the potential to reduce surgical site infections, lower postoperative pain and lead to a shorter duration of hospital stay compared to the classical open hernia repair; however, especially techniques with a retromuscular mesh position are technically challenging due to the preparation in a limited space and difficult to perform endoscopic sutures and necessitate detailed knowledge of the anatomy of the abdominal wall. The treatment of larger hernias in particular should therefore only be carried out under the prerequisite of extensive experience and case numbers. CONCLUSION: The new endoscopic and endoscopically assisted techniques for treatment of ventral hernias enable the experienced laparoscopic surgeon to primarily and secondarily treat ventral hernias with minimally invasive techniques.

[Personalized treatment of pheochromocytoma]. / Personalisierte Therapie des Phäochromozytoms.

BACKGROUND: Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment of pheochromocytoma. MATERIAL AND METHODS: A narrative review article based on the most recent literature is presented. RESULTS AND DISCUSSION: The proportion of pheochromocytomas as tumors of adrenal origin is about 5% of incidentally discovered adrenal tumors. The classical symptomatic triad of headaches, sweating, and palpitations occurs in only about 20% of patients, while almost all patients show at least 1 of these symptoms. To diagnose pheochromocytoma, levels of free plasma metanephrines or alternatively, fractionated metanephrines in a 24­h urine collection is required in a first step. In the second step an imaging procedure, computed tomography (CT) or magnetic resonance imaging (MRI), is performed to localize the adrenal tumor. Functional imaging is also recommended to preoperatively detect potential metastases. Genetic testing should always be offered during the course of treatment as 30-40% of pheochromocytomas are associated with genetic mutations. The dogma of preoperative alpha blockade is increasingly being questioned and has been controversially discussed in recent years. Minimally invasive removal of the adrenal tumor is the standard surgical procedure to cure patients with pheochromocytoma. The transabdominal and retroperitoneal laparoscopic approaches are considered equivalent. The choice of the minimally invasive procedure depends on the expertise and experience of the surgeon and should be tailored accordingly. Individualized and regular follow-up care is important after surgery.