Which factors influence the ED length-of-stay after anterior shoulder dislocations: a retrospective chart review in 716 cases.

BACKGROUND: Anterior shoulder dislocations (ASD) are commonly seen in Emergency Departments (ED). ED overcrowding is increasingly burdening many healthcare systems. Little is known about factors influencing ED length-of-stay (LOS) for ASD. This study defines the factors influencing ED LOS for ASD patients. METHODS: Retrospective chart reviews were performed on all patients ≥12 years admitted with an anterior shoulder dislocation at two regional hospitals in the Netherlands between 2010 and 2016. The electronic patient records were reviewed for baseline patient characteristics, trauma mechanism, reduction methods, medication used, complications and the LOS at the ED. The main objective was determining factors influencing the LOS in patients with an anterior shoulder dislocation at the ED. RESULTS: During the study period, 716 ASD occurred in 574 patients, 374 (65.2%) in males. There were 389 (54.3%) primary ASD; the remainder (327, 45.7%) were recurrent. Median LOS was 92 min (IQR 66 min), with a significantly shorter LOS in those with recurrent dislocations (p < 0.001), younger age group (p < 0.03) and in patients who received no medications in the ED (p < 0.001). Traction-countertraction and leverage techniques were associated with a significant more use of ED medication compared to other techniques. Although the use of more medication might suggest the LOS would be longer for these techniques, we did not find a significant difference between different reduction techniques and LOS. CONCLUSION: To our knowledge this study is the largest of its kind, demonstrating ED LOS in ASD patients is influenced by age, the need for medication and dislocation history, primary versus recurrent. Notably, we found that biomechanical reduction techniques, which are not primarily traction-countertraction or leverage techniques, e.g. scapular manipulation and Cunningham, were associated with less ED medication use. Further research is needed to define how reduction methods influence ED medication use, patient satisfaction and ED throughput times.

An obscure cause of hip pain.

BACKGROUND: We describe the case of a 53-year-old woman with hip pain secondary to an obturator hernia. Obturator hernia is uncommon, and the most lethal of all abdominal hernias. The high mortality rate of this disease requires an acute clinical awareness to facilitate rapid diagnosis and surgical intervention for improved prognosis. OBJECTIVES: This case highlights a vitally important diagnosis that is rarely discussed in the emergency medicine literature. CASE REPORT: Our patient presented without symptoms typical of a bowel obstruction, although a computed tomography scan of her pelvis revealed an incarcerated obturator hernia and a small bowel obstruction. CONCLUSIONS: Early diagnosis and expeditious surgical management resulted in a good outcome.

Targeting choroid plexus epithelia and ventricular ependyma for drug delivery to the central nervous system.

BACKGROUND: Because the choroid plexus (CP) is uniquely suited to control the composition of cerebrospinal fluid (CSF), there may be therapeutic benefits to increasing the levels of biologically active proteins in CSF to modulate central nervous system (CNS) functions. To this end, we sought to identify peptides capable of ligand-mediated targeting to CP epithelial cells reasoning that they could be exploited to deliver drugs, biotherapeutics and genes to the CNS. METHODS: A peptide library displayed on M13 bacteriophage was screened for ligands capable of internalizing into CP epithelial cells by incubating phage with CP explants for 2 hours at 37C and recovering particles with targeting capacity. RESULTS: Three peptides, identified after four rounds of screening, were analyzed for specific and dose dependent binding and internalization. Binding was deemed specific because internalization was prevented by co-incubation with cognate synthetic peptides. Furthermore, after i.c.v. injection into rat brains, each peptide was found to target phage to epithelial cells in CP and to ependyma lining the ventricles. CONCLUSION: These data demonstrate that ligand-mediated targeting can be used as a strategy for drug delivery to the central nervous system and opens the possibility of using the choroid plexus as a portal of entry into the brain.

SDMA is an early marker of change in GFR after living-related kidney donation.

BACKGROUND: Early detection of changes in the glomerular filtration rate (GFR) is crucial in detecting acute kidney injury. There is burgeoning evidence from preclinical and clinical studies that symmetrical dimethylarginine (SDMA) correlates well with different parameters of renal function. In some studies, SDMA even outperformed creatinine as a marker of GFR. It is however unknown how fast SDMA is increasing after reduction in GFR. The aim of our study was therefore to determine the temporal change of SDMA in comparison with cystatin C after a defined reduction in GFR. METHODS: Blood samples from 24 healthy living-related kidney donors (19 F/5 M), mean age 55.2 ± 8.3 years, were collected prior to donation of the kidney as well as 1, 6, 12, 24, 72 and 168 h after unilateral nephrectomy. SDMA levels were measured using a liquid chromatography-mass spectrometry-based method. RESULTS: Within 6 h after unilateral nephrectomy, i.e. reduction of GFR by 50%, SDMA rose from 0.571 ± 0.120 to 0.659 ± 0.135 µmol/L (P < 0.001). Baseline cystatin C levels increased from 0.87 ± 0.16 to 1.07 ± 0.15 mg/L (P < 0.001). Also, serum creatinine rose significantly within 6 h after removal of one kidney from 65.4 ± 8.4 to 88.8 ± 10.2 µmol/L (P < 0.001). DISCUSSION: SDMA might be a valuable and early marker of change in GFR in the clinical and experimental setting. Future studies will have to clarify whether sensitivity, specificity and temporal resolution of SDMA make it an attractive candidate for the assessment of renal function in both the experimental and clinical setting.

Improved outcome with immunosuppressive monotherapy after renal transplantation in Schimke-immuno-osseous dysplasia.

SIOD is a multisystem disorder caused by a mutant chromatin remodelling protein. The main clinical findings are spondyloepiphyseal dysplasia with disproportionate growth restriction, defective cellular immunity, and steroid-resistant nephrotic syndrome secondary to biopsy proven FSGS leading to ESRF. Concerning ESRF, kidney transplantation is the therapy of choice since FSGS does not recur in the graft. However, with respect to the underlying immune disorder and the increased susceptibility to life threatening infections, the question of the optimal immunosuppressive therapy after renal transplantation remains unresolved. Under conventional immunosuppressive regimens some SIOD patients have developed severe disseminated cutaneous papilloma virus infections or EBV associated lymphoproliferative disease. We present several cases of children with SIOD (four of five had SMARCAL1 mutations) and monotherapy maintenance immunosuppression after renal transplantation and compare them with 13 patients from the SIOD registry. We have found that post-renal transplantation immunosuppressive monotherapy results in a good outcome with a reduced number of severe infections. Due to the underlying immunodeficiency in SIOD, limited immunosuppression may be possible without increasing the risk of acute or chronic rejection.

Cola therapy for oesophageal food bolus impactions a case series.

INTRODUCTION: This retrospective case series describes the use of cola to immediately treat complete oesophageal food bolus obstructions in the emergency centre. Short of emergent endoscopy - which is invasive, expensive, not without adverse events, and often unavailable in low-resource settings - no other proven therapies exist to relieve oesophageal food impactions. METHODS: We performed a chart review of adults with complete oesophageal food bolus obstructions presenting to two Dutch emergency centres. Our primary outcome was cola's success rate in resolving the obstruction. Our secondary outcome was adverse event occurrence. RESULTS: We identified 22 cola interventions in 19 patients, the majority of whom (77.3%) were male. The median age was 59 years (IQR 29-73). All presentations were due to meat impaction. Endoscopy revealed relevant upper gastrointestinal pathology in 54.5%. When initiated in the emergency centre, cola successfully resolved 59% of complete oesophageal obstructions. No adverse events were reported in patients successfully treated with cola. DISCUSSION: While keenly aware of our retrospective study's limitations, we found a promising success rate for cola as an acute intervention for oesophageal food bolus impactions. We registered no adverse events attributable to cola. Also, given that cola is cheap, widely available and seemingly safe we believe it can be considered in patients with oesophageal obstructions due to food, either as pre-endoscopy treatment or in case endoscopy is not available at all. We think our findings provide an impetus for prospective research on this intervention.

The renal arterial resistance index and renal allograft survival.

BACKGROUND: Most renal transplants fail because of chronic allograft nephropathy or because the recipient dies, but no reliable factor predicting long-term outcome has been identified. We tested whether a renal arterial resistance index of less than 80 was predictive of long-term allograft survival. METHODS: The renal segmental arterial resistance index (the percentage reduction of the end-diastolic flow as compared with the systolic flow) was measured by Doppler ultrasonography in 601 patients at least three months after transplantation between August 1997 and November 1998. All patients were followed for three or more years. The combined end point was a decrease of 50 percent or more in the creatinine clearance rate, allograft failure (indicated by the need for dialysis), or death. RESULTS: A total of 122 patients (20 percent) had a resistance index of 80 or higher. Eighty-four of these patients (69 percent) had a decrease of 50 percent or more in creatinine clearance, as compared with 56 of the 479 patients with a resistance index of less than 80 (12 percent); 57 patients with a higher resistance index (47 percent) required dialysis, as compared with 43 patients with a lower resistance index (9 percent); and 36 patients with a higher resistance index (30 percent) died, as compared with 33 patients with a lower resistance index (7 percent) (P<0.001 for all comparisons). A total of 107 patients with a higher resistance index (88 percent) reached the combined end point, as compared with 83 of those with a lower resistance index (17 percent, P<0.001). The multivariate relative risk of graft loss among patients with a higher resistance index was 9.1 (95 percent confidence interval, 6.6 to 12.7). Proteinuria (protein excretion, 1 g per day or more), symptomatic cytomegalovirus infection, and a creatinine clearance rate of less than 30 ml per minute per 1.73 m2 of body-surface area after transplantation also increased the risk. CONCLUSIONS: A renal arterial resistance index of 80 or higher measured at least three months after transplantation is associated with poor subsequent allograft performance and death.

Management of inflammatory bowel disease flares in the emergency department

Because of the chronic relapsing nature of inflammatory bowel disease (IBD), emergency clinicians frequently manage patients with acute flares and complications. IBD patients present with an often-broad range of nonspecific signs and symptoms, and it is essential to differentiate a mild flare from a life-threatening intra-abdominal process. Recognizing extraintestinal manifestations and the presence of infection are critical. This issue reviews the literature on management of IBD flares in the emergency department, including laboratory testing, imaging, and identification of surgical emergencies, emphasizing the importance of coordination of care with specialists on treatment plans and offering patients resources for ongoing support.

Knee Dislocation: A Case Report, Diagnostic Vascular Work-Up, and Literature Review.

Knee dislocation is an uncommon, potentially limb-threatening, knee injury. Most often caused by high-velocity trauma, it can also result from low- or even ultra-low-velocity trauma. Rapid identification of the injury, reduction, and definitive management are necessary to minimize neurovascular damage. We present a case of rotatory anterolateral knee dislocation sustained during a twisting sports-related event. Special emphasis is placed on diagnosing vascular injuries associated with knee dislocations.

Management of inflammatory bowel disease flares in the emergency department [digest].

Because of the chronic relapsing nature of inflammatory bowel disease (IBD), emergency clinicians frequently manage patients with acute flares and complications. IBD patients present with an often-broad range of nonspecific signs and symptoms, and it is essential to differentiate a mild flare from a life-threatening intra-abdominal process. Recognizing extraintestinal manifestations and the presence of infection are critical. This issue reviews the literature on management of IBD flares in the emergency department, including laboratory testing, imaging, and identification of surgical emergencies, emphasizing the importance of coordination of care with specialists on treatment plans and offering patients resources for ongoing support. [Points & Pearls is a digest of Emergency Medicine Practice.].

Majocchi's granuloma after kidney transplantation.

Mycosis may follow an atypical course in an individual undergoing immunosuppressive therapy. We describe a patient with a fungal infection that was manifested as a bilateral inguinal granuloma. Owing to suspected inguinal lymphadenopathy characterized by distinct subcutaneous swellings in the groin, a 39-year-old man who had undergone kidney transplantation 14 years earlier was admitted to the Nephrologisches Zentrum in Hann. Muenden, Germany. The results of a clinical examination revealed bilateral, soft, partly fluctuant, indolent swellings in the groin as well as onychomycosis of the right great toe. An ultrasonographic scan showed bilateral hypoechogenic lesions (

Enhanced phagemid particle gene transfer in camptothecin-treated carcinoma cells.

Engineered phage-based vectors are an attractive alternative strategy for gene delivery because they possess no natural mammalian cell tropism and can be genetically modified for specific applications. Genotoxic treatments that increase the transduction efficiency of single-stranded adeno-associated virus were tested on cells transfected by single-stranded phage. Indeed, green fluorescent protein transgene expression by epidermal growth factor-targeted phagemid particles increased with heat shock, UV irradiation, and camptothecin (CPT) treatment. CPT resulted in transduction efficiencies of 30-45% in certain human carcinoma cell lines and reduced the minimal dose needed to detect green fluorescent protein-expressing cells to as low as 1-10 particles/cell. Targeted phage transduction was effective in many tumor cell lines and in prostate tumor xenografts with CPT treatment. Taken together, these data suggest the feasibility of using phage-based vectors for therapeutic gene delivery to cancer cells.

Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection.

Phage display technologies are powerful tools for selecting binding ligands against purified molecular targets, live cells, and organ vasculature. However, the selection of natural ligands using phage display has been limited because of significant problems associated with the display of complex cDNA repertoires. Here we describe the use of cDNA fragmentation and open reading frame (ORF) selection to display a human placental cDNA library on the pIII coat protein of filamentous phage. The library was enriched for ORFs by selecting cDNA-beta-lactamase fusion proteins on ampicillin, resulting in a cDNA population having 97% ORFs. The ORF-selected cDNAs were fused to pIII in the phagemid vector, pUCMG4CT-198, and the library was rescued with a pIII-deleted helper phage for multivalent display. The resulting phagemid particle library consisted of 87% ORFs, compared to only 6% ORFs when prepared without ORF selection. Western blot analysis indicated cDNA-pIII fusion protein expression in eight out of nine ORF clones tested, and seven of the ORF encoded peptides were displayed multivalently. The high level of cDNA expression obtained by ORF selection suggests that ORF-enriched phage cDNA libraries prepared by these methods will be useful as functional genomics tools for identifying natural ligands from various source tissues.

Evolving phage vectors for cell targeted gene delivery.

We adapted filamentous phage vectors for targeted gene delivery to mammalian cells by inserting a mammalian reporter gene expression cassette (GFP) into the vector backbone and fusing the pIII coat protein to a cell targeting ligand (i.e. FGF2, EGF). Like transfection with animal viral vectors, targeted phage gene delivery is concentration, time, and ligand dependent. Importantly, targeted phage particles are specific for the appropriate target cell surface receptor. Phage have distinct advantages over existing gene therapy vectors because they are simple, economical to produce at high titer, have no intrinsic tropism for mammalian cells, and are relatively simple to genetically modify and evolve. Initially transduction by targeted phage particles was low resulting in foreign gene expression in 1-2% of transfected cells. We increased transduction efficiency by modifying both the transfection protocol and vector design. For example, we stabilized the display of the targeting ligand to create multivalent phagemid-based vectors with transduction efficiencies of up to 45% in certain cell lines when combined with genotoxic treatment. Taken together, these studies establish that the efficiency of phage-mediated gene transfer can be significantly improved through genetic modification. We are currently evolving phage vectors with enhanced cell targeting, increased stability, reduced immunogenicity and other properties suitable for gene therapy.

Selection of internalizing ligand-display phage using rolling circle amplification for phage recovery.

Selection of phage libraries against complex living targets such as whole cells or organs can yield valuable targeting ligands without prior knowledge of the targeted receptor. Our previous studies have shown that noninfective multivalent ligand display phagemids internalize into mammalian cells more efficiently than their monovalent counterparts suggesting that cell-based selection of internalizing ligands might be improved using multivalently displayed peptides, antibodies or cDNAs. However, alternative methods of phage recovery are needed to select phage from noninfective libraries. To this end, we reasoned that rolling circle amplification (RCA) of phage DNA could be used to recover noninfective phage. In feasibility studies, we obtained up to 1.5 million-fold enrichment of internalizing EGF-targeted phage using RCA. When RCA was applied to a large random peptide library, eight distinct human prostate carcinoma cell-internalizing peptides were isolated within three selection rounds. These data establish RCA as an alternative to infection for phage recovery that can be used to identify peptides from noninfective phage display libraries or infective libraries under conditions where there is the potential for loss of phage infectivity.