Improved patient safety with a simplified operating room to pediatric intensive care unit handover tool (PATHQS).

Introduction: Patient handover is a crucial transition requiring a high level of coordination and communication. In the BC Children's Hospital (BCCH) pediatric intensive care unit (PICU), 10 adverse events stemming from issues that should have been addressed at the operating room (OR) to PICU handover were reported into the patient safety learning system (PSLS) within 1 year. We aimed to undertake a quality improvement project to increase adherence to a standardized OR to PICU handover process to 100% within a 6-month time frame. In doing so, the secondary aim was to reduce adverse events by 50% within the same 6-month period. Methods: The model for improvement and a Plan, Do, Study, Act method of quality improvement was used in this project. The adverse events were reviewed to identify root causes. The findings were reviewed by a multidisciplinary inter-departmental group comprised of members from surgery, anesthesia, and intensive care. Issues were batched into themes to address the most problematic parts of handover that were contributing to risk. Intervention: A bedside education campaign was initiated to familiarize the team with an existing handover standard. The project team then formulated a new simplified visual handover tool with the mnemonic "PATHQS" where each letter denoted a step addressing a theme that had been noted in the pre-intervention work as contributing to adverse events. Results: Adherence to standardized handover at 6 months improved from 69% to 92%. This improvement was sustained at 12 months and 3 years after the introduction of PATHQS. In addition, there were zero PSLS events relating to handover at 6 and 12 months, with only one filed by 36 months. Notably, staff self-reporting of safety concerns during handover reduced from 69% to 13% at 6 months and 0% at 3 years. The PATHQS tool created in this work also spread to six other units within the hospital as well as to one adult teaching hospital. Conclusion: A simplified handover tool built collaboratively between departments can improve the quality and adherence of OR to PICU handover and improve patient safety. Simplification makes it adaptable and applicable in many different healthcare settings.

Ultraviolet exposure and risk of melanoma and basal cell carcinoma in Ulm and Dresden, Germany.

BACKGROUND: There is a perpetuating increase in melanoma and basal cell carcinoma (BCC) incidence in Europe. Few studies are evaluating various risk factors for both tumours. OBJECTIVES: This pre-planned additional analysis directly compared occupational and past-time ultraviolet exposure behaviour, and examined the effects of sun sensitivity between melanoma and sporadic BCC, and assessed its importance for the two entities. PATIENTS/METHODS: The study included 503 patients (melanoma, n = 291 and BCC, n = 212), and 329 controls from Germany. In all, 244 (49%) of the cases and 165 (50%) of the controls were male (median age melanoma, 55 years; BCC, 69 years; and controls, 57 years). Selection of important risk factors was performed by backward elimination in a polytomous logistic regression. RESULTS: When directly comparing melanoma and sporadic BCC, actinic elastosis (OR 48.83; 95% CI 17.87, 133.40) and site were associated with a higher risk of melanoma, whereas mountaineering in childhood, sunburn 20 years before diagnosis, farming full time, sunbed use in general, seborrheic keratosis, actinic cheilitis, actinic keratosis and age were associated with a higher risk of sporadic BCC. Gardening 20 years before melanoma, hair colour and solar lentigo were risk factors for both entities. A re-evaluation of the data excluding lentiginous melanoma entities (i.e. acro-lentiginous and lentigo-maligna melanoma) resulted in selection of the same factors. However, compared to controls, atopy evolved as a protective factor for melanoma (OR 0.29; 95% CI 0.15, 0.57) and BCC (OR 0.41; 95% CI 0.17, 0.99), respectively, but was associated with a higher risk of sporadic BCC compared to melanoma. CONCLUSION: The odds for having clinical actinic elastosis was lower in BCC compared to melanoma. In contrast, various factors associated with chronic UV exposure and age had higher odds for sporadic BCC, rather than melanoma. Further research is required to set the context for these findings, especially regarding, atopy in non-lentiginous vs. lentiginous forms of melanoma, and possible molecular pathways involved.

Continuous central venous oxygen saturation monitoring under varying physiological conditions in an animal model.

We compared saturations from a paediatric central venous oximetry catheter with co-oximetry values with changes in drug infusions, intravascular blood volume and hypoxia in an animal model. Piglets (large white) were anaesthetised, intubated and mechanically ventilated. PediaSat oximetry catheters were placed in the superior vena cava via jugular vein cut-down and in the inferior vena cava percutaneously via the femoral vein. A carotid arterial catheter was placed via cut-down for blood sampling and pressure monitoring. Anaesthesia was maintained with continuous thiopentone and supplemental morphine. Haemodynamics (heart rate, mean arterial blood, central venous pressure), fibreoptic ScvO2 (ScvO2-inferior) from inferior vena cava, fibreoptic ScvO2 (ScvO2-superior) from superior vena cava and blood gas oximetry (ScvO2-co-ox) were measured simultaneously at predetermined intervals during increasing adrenaline and sodium nitroprusside infusions and during increasing hypoxia and hypovolaemia. There was good agreement of both superior vena cava and inferior vena cava ScvO2 catheters with co-oximetry during adrenaline and sodium nitroprusside infusions. During the hypoxia study there was good agreement between the co-oximeter to ScvO2-superior catheter but poor agreement with to the inferior vena cava catheter samples. In the hypovolaemic phase of the experiment there was good agreement between the measured co-oximetry value and ScvO2-superior catheter until the mean blood pressure reached 43 mmHg. The oximetry catheter is capable of identifying changes in ScvO2 under physiological conditions usually encountered in clinical medicine but was less accurate at the extremes of physiology and when placed in the inferior vena cava catheter especially during hypovolaemia and hypoxia.

Acute renal failure in children undergoing cardiopulmonary bypass.

OBJECTIVE: To investigate the incidence, implicating factors and outcome of acute renal failure after cardiopulmonary bypass in patients admitted to a paediatric intensive care unit. DESIGN: Prospective observational pilot study. SETTING: A 14 bed paediatric intensive care unit in a university affiliated, tertiary care referral children's hospital. PATIENTS: One hundred and one children (less than sixteen years of age) admitted to the Pediatric Intensive Care Unit following cardiopulmonary bypass between June 2003 and May 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PRISM-III score was calculated on admission. Baseline admission urea (mmol/L) and creatinine (micromol/L) serum levels and highest urea and creatinine levels were measured. Urine output (mL/kg/hour) and frusemide dose (mg/kg/day) were also noted. A baseline inotrope score was calculated on admission and the highest inotrope score was noted based on maximum infused doses of inotrope in the first 36 hours. The surgical procedure was used to determine a Jenkins score. Eleven (11%) children developed acute renal injury (doubling of creatinine), one child (1%) developed acute renal failure (tripling of creatinine) and one child died (1%). No child required dialysis for acute renal failure and none developed chronic renal impairment. Low cardiac output was the only significant risk factor identified for developing acute renal injury or failure. CONCLUSIONS: Acute renal injury is common and occurred in 11% of our children following congenital cardiac surgery, but acute renal failure requiring dialysis is uncommon.

Risk and protective factors for sporadic basal cell carcinoma: results of a two-centre case-control study in southern Germany. Clinical actinic elastosis may be a protective factor.

BACKGROUND: There are very few data regarding sun exposure behaviour of patients with basal cell carcinoma (BCC) in central Europe. OBJECTIVES: A case-control study of patients with sporadic BCC was conducted to assess the risk of occupational and leisure-time sun exposure behaviour, precursor lesions for skin cancer and phenotypic factors on the development of sporadic BCC in Ulm and Dresden, Germany. METHODS: A comparison was made of 213 patients with BCC (128 from Ulm, 85 from Dresden; 103 men and 110 women; median age at diagnosis 69 years) and 411 controls (237 from Ulm, 174 from Dresden; 197 men and 214 women; median age 58 years). Crude odds ratios (ORs) and corresponding 95% confidence intervals for all of 64 possible risk factors revealed strong associations in 33 items. Selection of important risk factors was performed in a multiple logistic regression. RESULTS: For sporadic BCC, an increased risk was shown for persons with actinic cheilitis (OR 7.1), actinic keratosis (OR 2.7) and solar lentigo (OR 2.5). The only phenotypic factor indicating risk of sporadic BCC was hair colour, with a higher risk for red/fair than brown/black hair (OR 4.3). There was an increased risk for persons with BCC in first-degree relatives (OR 5.1) and those with sunburn 20 years before sporadic BCC was diagnosed (OR 3.6). Additionally, occupational ultraviolet (UV) exposure appeared to be a risk factor (OR 2.4). In contrast, clinical actinic elastosis showed a protective effect (OR 0.1). CONCLUSIONS: In contrast to earlier reports, clinical actinic elastosis turned out to be the only protective factor for sporadic BCC. A special relationship between wrinkling and BCC risk could not be shown. For basic research, future work should be aimed at elucidating further the different forms of collagen repair processes after intermittent and/or chronic UV exposure. The data strongly support the recommendation that a change in recreational UV exposure habits in individuals, and sunburn avoidance in particular, are necessary not only because of the increased long-term risk of melanoma, but also because of the risk of other skin cancers such as sporadic BCC.

Outdoor activities in childhood: a protective factor for cutaneous melanoma? Results of a case-control study in 271 matched pairs.

BACKGROUND: A matched case-control study was performed in Munich, Germany, in 1996-97 to evaluate the risk of cutaneous melanoma due to ultraviolet (UV) exposure behaviour in Southern Bavaria, Germany. OBJECTIVES: Patients with cutaneous melanoma and controls were investigated by two physicians using a standardized questionnaire to identify risk factors for the development of melanoma, such as professional and leisure sun exposure behaviour. In each person, a total body examination was performed to detect benign skin alterations, phenotypic characteristics and precursor lesions for skin cancer. PATIENTS/METHODS: A total of 271 melanoma patients and 271 controls were individually matched for residence, age and gender. A multiple conditional logistic regression analysis was performed. RESULTS: Of 56 factors, those risk factors with a strong effect on the development of melanoma were: the existence of melanoma in first degree relatives, solar lentigo, actinic keratosis, actinic cheilitis, skin phototype, immediate skin reaction to UV light at the start of the outdoor season, sunburn in childhood and sun exposure during holidays in sunny areas 20 years before melanoma was diagnosed; outdoor activities in childhood were found to be protective. CONCLUSIONS: Sunburn in childhood and increased sun exposure during annual holidays in sunny areas should be avoided. In contrast, outdoor activities in childhood, including soccer and gardening, should be encouraged because they are associated with a lower risk of melanoma formation.

Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.

In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway activated in response to infections is based on degradation of IkappaB inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show that IKKalpha is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-kappaB target genes, and processing of the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF-kappaB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation.

Chromosome 7 aneusomy. A marker for metastatic melanoma? Expression of the epidermal growth factor receptor gene and chromosome 7 aneusomy in nevi, primary malignant melanomas and metastases.

Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) play an important role in a variety of malignant neoplasias, making the search for aberrations in the relevant chromosomes an important issue. Differential expression of the EGFR gene was investigated by reverse transcriptase (RT)-PCR on tissue samples of normal skin, nevi, primary melanomas, and melanoma metastases. The EGFR gene is located on chromosome 7p12.3-p12.1. To determine the number of chromosomes 7 in cell nuclei of the mentioned tissue samples we performed fluorescence in situ hybridization (FISH) on touch preparations, using a DNA probe that hybridizes specifically to the centromeric region of chromosome 7. Additionally, chromosome 7 number in interphase nuclei was determined in short-term primary cell cultures of nevi, primary melanomas, and metastases. The highest EGFR gene expression frequency was found in melanoma metastases. By FISH we detected the highest fraction of cell nuclei with more than two chromosomes 7 in the group of metastases. Our results suggest that overexpression of the EGFR gene might play an important role in metastasis of malignant melanoma. This is well reflected by polysomy 7, possibly accounting for an increased EGFR gene copy number.

UVB-induced decrease of p16/CDKN2A expression in skin cancer patients.

The lack of p16 expression has been shown in cultured melanoma cells, however contradictory evidence for p16 expression in melanoma tissues exist. Ultraviolet (UV) C and UVB have been shown to affect p16 expression, which impairs cell cycle regulation in vitro and in vivo. In this study, p16/CDKN2A gene expression was determined by reverse transcription polymerase chain reaction in seven skin cancer patients, in one dysplastic nevus patient and in seven healthy individuals, prior to UVB exposure and at various times after application of one minimal erythema dose (MED). Five of the seven skin cancer patients showed a down-regulation of p16/CDKN2A expression after UVB exposure, while controls remained unaltered. The UVB-induced decline of p16/CDKN2A in skin cancer patients might offer new insights into photocarcinogenesis. The putative sequence of events could start with a down-regulation of p16/CDKN2A expression, which would lead to impaired cell cycle regulation. Altered expression patterns of p16/CDKN2A following UVB exposure could be of value for identifying people with an increased risk of UV-induced skin cancer.

S100 beta is a more reliable tumor marker in peripheral blood for patients with newly occurred melanoma metastases compared with MIA, albumin and lactate-dehydrogenase.

Lactate-dehydroxynase (LDH) has been described as a leading blood parameter in patients with melanoma metastases. However, recent data indicates that levels of S100 as well as melanoma inhibiting activity (MIA) in peripheral blood, correlate with melanoma progression. The aim of this study was to evaluate tumor markers S100, MIA, LDH and albumin in peripheral blood of 373 melanoma patients. 284 patients presented with in-situ or UICC stage I/II, and 89 with stage III/IV (54 tumor-free, 29 with newly occurred metastases). For newly occurred metastases, sensitivity was highest for S100 in peripheral blood (0.86), followed by MIA (0.80), LDH (0.48), and albumin (0.15). Specificity for albumin (0.99) and LDH (0.98) was higher than for S100 (0.91) and MIA (0.62). This data indicate that S100 in peripheral blood as compared to MIA, LDH and albumin appears to be the most appropriate tumor marker for newly occurred melanoma metastases.

Increased blood levels of human S100 in melanoma chick embryo xenografts' circulation.

The chorioallantoic membrane (CAM) of the fertilized egg allows grafting of human melanomas for short-term investigations and offers the opportunity to investigate the behavior of metastasizing cells and the release of S100beta into peripheral blood. Tissue from one primary melanoma as well as cutaneous and subcutaneous metastases of 10 melanoma patients with elevated levels of S100 in the peripheral blood before surgery were transplanted onto the CAM of chick embryos at day 5/6 of development. Grafts were nourished by the host blood supply 2 days after transplantation. Histologically, 3 days after grafting, metastasizing melanoma cells could be found near the vessels of the host membrane, penetrating the endothelial layer and entering the blood system. Growth conditions remained stable for 6 days after transplantation. Blood samples were taken from a larger CAM vessel before collecting the xenografts 5 days after grafting. Measurement of human S100 in peripheral blood was performed in a blinded manner. No negative control showed elevated levels of human S100 protein. Samples deriving from melanoma xenografts contained highly elevated levels of S100 protein in 80% of cases. The data strongly support the concept of graft-host interaction concerning adherence of tumors and extravasation of human melanoma cells.

Interlaboratory evaluation of a new reverse transcriptase polymerase chain reaction-based enzyme-linked immunosorbent assay for the detection of circulating melanoma cells: a multicenter study of the Dermatologic Cooperative Oncology Group.

PURPOSE: Reverse transcription-polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is the most frequently used laboratory method for the detection of circulating tumor cells in melanoma patients. However, previously published results showed considerable variability in the PCR positivity rates. MATERIALS AND METHODS: We designed a collaborative study to assess the sensitivity, specificity, and clinical relevance of a new standardized RT-PCR-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating melanoma cells. Blood samples of healthy donors mixed with cells of a melanoma cell line were prepared in a blinded fashion, and aliquots were sent to seven participating laboratories experienced in RT-PCR. RESULTS: The results demonstrate a high sensitivity (1 melanoma cell/mL blood) and specificity (no false-negatives and 7.4% [2 of 28] false-positives) of the assay and a satisfactory rate of interlaboratory reproducibility. The analysis of aliquots of blinded samples derived from 60 melanoma patients identified tyrosinase mRNA in 17 of 60 (28.3%): three (20%) of 15 stage I patients, two (13.3%) of 15 stage II patients, five (35.7%) of 14 stage III patients, and seven (43.8%) of 16 stage IV patients. The interlaboratory reproducibility of positive samples, however, was extremely low and indicates the presence of low amounts of target mRNA. CONCLUSION: Reverse transcriptase-PCR ELISA has a high sensitivity and specificity for the detection of tyrosinase mRNA in peripheral blood cells. The low interlaboratory reproducibility for the detection of tumor cells in blood samples of melanoma patients, however, raises the question of relevance of this assay for clinical use.

Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer.

The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), HER2, HER3 and HER4 are involved in the pathogenesis of multiple human malignant neoplasias. However, their role in the carcinogenesis of basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) remains to be elucidated. In order to further define the role of these RTKs, 56 human skin tissue samples of normal skin, BCC and SCC were studied by conventional and differential and quantitative reverse transcriptase-polymerase chain reaction (rtPCR). EGFR and HER3 were predominantly expressed in the BCCs and SCCs, while HER2 was ubiquitously expressed. HER4 was not expressed in any sample. Since in vitro studies have provided compelling evidence that heterodimer formation of these receptors are associated with different signal transduction processes, coexpression patterns might be decisive for the induction and maintenance of a malignant phenotype. These results confirm this concept: isolated HER2 expression and EGFR/HER2 were predominantly found in normal skin, while HER2/HER3 and the triple expression of EGFR/HER2/HER3 were seen more frequently in the BCCs and SCCs compared with normal skin (50% and 40% compared with 26%, respectively). The activation of HER3, in addition to EGFR and HER2, might therefore be associated with the malignant phenotype. However, due to the small numbers in this study, further confirmation of the patterns is needed.

Trauma and melanoma formation: a true association?

BACKGROUND: Little is known about the role of mechanical trauma in the pathogenesis of malignant melanoma. In individual patients, traumatic events have been discussed as a causative factor for the induction of melanoma and diagnosis of melanoma following trauma may raise medico-legal questions. OBJECTIVES: To evaluate the relationship between traumatic single or recurrent events and melanoma characteristics. METHODS: Retrospective questionnaire in 369 melanoma patients. RESULTS: A large number of patients (337 of 369; 91.3%) denied an association between a possible traumatic event and melanoma formation. Thirty-two of 369 patients (8.7%) considered an association of trauma and melanoma formation likely. Of these 32 patients, 22 patients (13 men, nine women) reported a single event, and 10 patients (four men, six women) a persisting irritation. An irritation of a pre-existing melanocytic naevus was reported by two patients with histologically confirmed melanoma on acquired or congenital naevus. CONCLUSIONS: As most of the patients who mentioned a trauma in this study suffered from acral melanoma, or melanoma located on the extremities, a history of trauma should be expected more frequently at these body sites. A review of epidemiological, clinical and scientific research indicates that there seems to be no evidence for single or persistent traumatic events as a causative factor for melanoma formation.

[Cutaneous radiation syndrome: clinical features, diagnosis and therapy]. / Das kutane Strahlensyndrom. Klinik, Diagnostik und Therapie.

Accidental exposure to ionizing radiation may occur during such catastrophic events as the Chernobyl accident in 1986 or over days to weeks as in Goiania in 1987 and in the military camp during the training of soldiers in Lilo/Georgia in 1997, as well as in medical institutions. The cutaneous symptoms after radiation exposure are based on a combination of inflammatory processes and alteration of cellular proliferation as a result of a specific pattern of transcriptionally activated proinflammatory cytokines and growth factors. They follow a time course consisting of prodromal erythema, latency period, acute stage, chronic stage and late stage. The entire complex is referred to as cutaneous radiation syndrome. The time course depends on several factors such as the radiation dose, radiation quality, individual radiation sensitivity, the extent of contamination and absorption and amount of skin exposed. For the diagnosis of the cutaneous radiation syndrome the following procedures are used: 7.5 MHz to 20 MHz-B-scan sonography, thermography, capillary microscopy, profilometry, nuclear magnetic resonance imaging, bone scintigraphy and histology. Based on the results of experimental and clinical research, today treatment may include topical or systemic corticosteroids, gamma-interferon, pentoxifylline, vitamin E and superoxide dismutase. The treatment depends on the stage of the cutaneous radiation syndrome. Due to the complexity of the clinical manifestations of radiation disease, most patients require interdisciplinary treatment in specialized centres. Dermatologists are essential partners in the life-long follow-up and therapy of such patients.

Lymph node dissection in cutaneous melanoma: surgical and oncological implications.

The concept of Sentinel Lymph Node Dissection (SLND) has strongly influenced the surgical approach towards primary melanoma in the last decade. Initiated by the disappointing results of elective lymph node dissection (ELND) in this malignancy, the concept of analyzing the first draining lymph node (Sentinel) of a regional basin was developed as a diagnostic means to avoid unnecessary ELND in case of negative SLNs. According to recent standards detection of the SLN should be performed by a triple approach: injection of 90 nm Technetium and patent blue in the periphery of the primary melanoma, and intraoperative tracing of radioactivity with the aid of a hand-held gamma probe. Histopathological examination of alternating series sections of the whole lymph node appears to be the best analytic approach. Molecular biologic procedures such as tyrosinase RT-PCR are time-consuming to perform and produce contradictory results. SLND for cutaneous melanoma is an interdisciplinary diagnostic approach involving surgery, dermatology, pathology, and nuclear medicine. In spite of a variety of published promising results derived from clinical trials ranging from a few dozens to several hundred included patients the diagnostic and prognostic value of SLND remains to be confirmed by ongoing controlled prospective clinical trials. At this stage, SLND can by no means be considered a therapeutic procedure. These aspects have to be kept in mind when informed consent is obtained from patients as well as in the individual determination of the risk-benefit ratio.