Learning from regret.

BACKGROUND: Death after surgery is infrequent but can be devastating for the surgeon. Surgeons may experience intense emotional reactions after a patient's death, reflecting on their part in the death and the patient's loss of life. Excessive rumination or feelings of regret may have lasting negative consequences, but these reactions may also facilitate learning for future decision-making. This qualitative study analysed surgeons' reflections on what might have been done differently before a patient's death and explored non-technical (cognitive and interpersonal) aspects of care as potential targets for improvement. METHODS: In Australia's Queensland Audit of Surgical Mortality, surgeons reflect on factors surrounding the death of patients in their care and respond to the open-ended question: in retrospect, would you have done anything differently? Framework analysis was applied to surgeons' responses to identify themes relating to non-technical aspects of care. RESULTS: Responses from 1214 surgeons were analysed. Two main themes were identified. Dilemmas and difficult decisions confirmed the uncertainty, complexity and situational pressures that often precede a surgical death; regret and empathy for patients featured in some responses. In the second main theme, communication matters, surgeons cited better communication, with patients, families, colleagues and at handover, as a source of reflective change to improve decision-making and reduce regret. CONCLUSION: Surgical decision-making involves uncertainty, and regret may occur after a patient's death. Enhancing the quality of communication with patients and peers in comprehensive assessment of the surgical patient may mitigate postdecision regret among surgeons.

Processes of care in surgical patients who died with hospital-acquired infections in Australian hospitals.

BACKGROUND: Infection may complicate surgical patients' hospital admission. The effect of hospital-acquired infections (HAIs) on processes of care among surgical patients who died is unknown. AIM: To investigate the effect of HAIs on processes of care in surgical patients who died in hospital. METHODS: Surgeon-recorded infection data extracted from a national Australian surgical mortality audit (2012-2016) were grouped into HAIs and no infection. The audit included all-age surgical patients, who died in hospital. Not all patients had surgery. Excluded from analysis were patients with community-acquired infection and those with missing timing of infection. Multivariate logistic regression was used to determine the adjusted effects of HAIs on the processes of care in these patients. Costs associated with HAIs were estimated. FINDINGS: One-fifth of surgical patients who died did so with an HAI (2242 out of 11,681; 19.2%). HAI patients had increased processes of care compared to those who died without infection: postoperative complications [51.0% vs 30.3%; adjusted odds ratio (aOR): 2.20; 95% confidence interval (CI): 1.98-2.45; P < 0.001]; unplanned reoperations (22.6% vs 10.9%; aOR: 2.38; 95% CI: 2.09-2.71; P < 0.001) and unplanned intensive care unit admission (29.3% vs 14.8%; aOR: 2.18; 95% CI: 1.94-2.45; P < 0.001). HAI patients had longer hospital admissions and greater hospital costs than those without infection. CONCLUSION: HAIs were associated with increased processes of care and costs in surgical patients who died; these outcomes need to be investigated in surgical patients who survive.

Predictors of mortality in patients with femoral neck fracture.

PURPOSE: To identify patient and procedural factors associated with in-hospital mortality following a femoral neck fracture. METHODS: Records of 598 female and 259 male consecutive patients aged 29 to 108 (median, 82) years admitted between 2010 and 2014 with femoral neck fracture were retrospectively reviewed to determine patient and procedural factors associated with inhospital mortality. RESULTS: 73% of patients were operated on within 48 hours of admission. The in-hospital mortality was 7.5%, with 2.1% occurring preoperatively and 5.4% postoperatively. Factors associated with increased preoperative mortality included being nonambulant prior to admission (p=0.015), residence in interim care (p=0.001) or low-level care (p=0.049), having synchronous fractures (p=0.001), and having a concurrent acute medical condition (p<0.001). Patient factors associated with increased in-hospital mortality included male gender (p=0.041), age >80 years (p=0.001), non-ambulatory status (p=0.015), residence in high-level care (p=0.031) or low-level care (p=0.018), American Society of Anesthesiologists grade 4 or 5 (p<0.001), weekend admission (p<0.001), and having an acute medical condition on admission (p<0.001). Procedural factors associated with increased in-hospital mortality included >96-hour delay to surgery from admission (p<0.001), surgery over the weekend (p=0.005), and surgical interventions other than total hip arthroplasty (p<0.05). CONCLUSION: Identification of patient and procedural factors can guide changes in best practice to decrease mortality following a femoral neck fracture.

Analysis of deficiencies in care following cholecystectomy.

INTRODUCTION: Failure To Rescue was first defined in patients who died due to a complication following (open) cholecystectomy but research into the relevant factors has been scarce. This study was designed to determine a chronological sequence of deficiencies in care. METHODS: Adult patients who died under the care of a surgeon following cholecystectomy in Queensland were identified from the Australian and New Zealand Audit of Surgical Mortality (ANZASM) database. RESULTS: Not unexpectedly, this is a high-risk patient population: median age of the 48 patients was 74.5 years and the median number of comorbidities and American Society of Anesthesiologists class was 4. Death occurred on postoperative day 6. Most deaths occurred at the end of the week. Over 80% of deaths followed emergency cholecystectomy. In almost half the patients, there were no deficiencies in care. Most common deficiency was during postoperative management (i.e. Failure To Rescue), however, significant deficiencies also arose prior to surgical admission; choice and timing of intervention as well as intraoperative decision-making. CONCLUSION: Surgeons who perform cholecystectomy need to be aware of the levels at which deficiencies arise given that many may be preventable.

Analysis of the causes and effects of delay before diagnosis using surgical mortality data.

BACKGROUND: The aim of the study was to assess the causes and effects of delay in diagnosis in surgical patients who died in 20 public hospitals participating in the Queensland Audit of Surgical Mortality (QASM) in Australia. METHODS: This was a retrospective cross-sectional analysis (June 2007 to December 2011) of deaths reported to QASM. Deaths were assigned to one of two groups (no delay or delay in diagnosis). Logistic regression was used to compare the association of delay with surgical complications, both overall and by surgical specialty. RESULTS: A total of 3139 deaths were reported. Diagnostic delay was reported in 293 (9·3 per cent). The primary cause of delay was attributed to diagnostic support services (41·7 per cent). Some 174 (13·8 per cent) of 1259 general (gastrointestinal) surgery patients experienced delayed diagnosis. Delay across all surgical specialties was associated with an increased risk of unplanned return to theatre (odds ratio (OR) 1·77, 95 per cent confidence interval 1·24 to 2·52), of being treated in intensive care (OR 1·71, 1·15 to 2·54) and of postoperative complications (OR 1·39, 1·05 to 1·85). CONCLUSION: General (gastrointestinal) surgery patients who experienced delayed diagnosis were at increased risk of postoperative complications.

Fentanyl buccal soluble film (FBSF) for breakthrough pain in patients with cancer: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Fentanyl buccal soluble film (FBSF) has been developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. The objective of this study was to evaluate the efficacy of FBSF at doses of 200-1200 microg in the management of breakthrough pain in patients with cancer receiving ongoing opioid therapy. PATIENTS AND METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, multiple-crossover study that included opioid-tolerant adult patients with chronic cancer pain who experienced one to four daily episodes of breakthrough pain. The primary efficacy assessment was the sum of pain intensity differences at 30 min (SPID30) postdose. RESULTS: The intent-to-treat population consisted of 80 patients with > or =1 post-baseline efficacy assessment. The least-squares mean (LSM +/- SEM) of the SPID30 was significantly greater for FBSF-treated episodes of breakthrough pain than for placebo-treated episodes (47.9 +/- 3.9 versus 38.1 +/- 4.3; P = 0.004). There was statistical separation from placebo starting at 15 min up through 60 min (last time point assessed). There were no unexpected adverse events (AEs) or clinically significant safety findings. CONCLUSIONS: FBSF is an effective option for control of breakthrough pain in patients receiving ongoing opioid therapy. In this study, FBSF was well tolerated in the oral cavity, with no reports of treatment-related oral AEs.

Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis.

OBJECTIVE: The identification of novel autoantibodies in juvenile dermatomyositis (DM) may have etiologic and clinical implications. The aim of this study was to describe autoantibodies to a 140-kd protein in children recruited to the Juvenile DM National Registry and Repository for UK and Ireland. METHODS: Clinical data and sera were collected from children with juvenile myositis. Sera that recognized a 140-kd protein by immunoprecipitation were identified. The identity of the p140 autoantigen was investigated by immunoprecipitation/immunodepletion, using commercial monoclonal antibodies to NXP-2, reference anti-p140, and anti-p155/140, the other autoantibody recently described in juvenile DM. DNA samples from 100 Caucasian children with myositis were genotyped for HLA class II haplotype associations and compared with those from 864 randomly selected UK Caucasian control subjects. RESULTS: Sera from 37 (23%) of 162 patients with juvenile myositis were positive for anti-p140 autoantibodies, which were detected exclusively in patients with juvenile DM and not in patients with juvenile DM-overlap syndrome or control subjects. No anti-p140 antibody-positive patients were positive for other recognized autoantibodies. Immunodepletion suggested that the identity of p140 was consistent with NXP-2 (the previously identified MJ autoantigen). In children with anti-p140 antibodies, the association with calcinosis was significant compared with the rest of the cohort (corrected P < 0.005, odds ratio 7.0, 95% confidence interval 3.0-16.1). The clinical features of patients with anti-p140 autoantibodies were different from those of children with anti-p155/140 autoantibodies. The presence of HLA-DRB1*08 was a possible risk factor for anti-p140 autoantibody positivity. CONCLUSION: This study has established that anti-p140 autoantibodies represent a major autoantibody subset in juvenile DM. This specificity may identify a further immunogenetic and clinical phenotype within the juvenile myositis spectrum that includes an association with calcinosis.

The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro.

We have studied the in vitro actions of the sesquiterpene lactone parthenolide (PTL) on cells isolated from patients with chronic lymphocytic leukemia (CLL). Dye reduction viability assays showed that the median LD(50) for PTL was 6.2 muM (n=78). Fifteen of these isolates were relatively resistant to the conventional agent chlorambucil but retained sensitivity to PTL. Brief exposures to PTL (1-3 h) were sufficient to induce caspase activation and commitment to cell death. Chronic lymphocytic leukemia cells were more sensitive towards PTL than were normal T lymphocytes or CD34(+) haematopoietic progenitor cells. The mechanism of cell killing was via PTL-induced generation of reactive oxygen species, resulting in turn in a proapoptotic Bax conformational change, release of mitochondrial cytochrome c and caspase activation. Parthenolide also decreased nuclear levels of the antiapoptotic transcription factor nuclear factor-kappa B and diminished phosphorylation of its negative regulator IkappaB. Killing of CLL cells by PTL was apparently independent of p53 induction. This is the first report showing the relative selectivity of PTL towards CLL cells. The data here warrant further investigation of this class of natural product as potential therapeutic agents for CLL.

Solitary testicular myofibroma: a case report and review of the literature.

Myofibromas are benign mesenchymal neoplasms of myofibroblastic origin. Most present as solitary lesions at any age, but the presentation of multiple lesions in newborns and infants is known as infantile myofibromatosis. Multicentric lesions commonly involve soft tissues and bone and may involve internal organs, where they are associated with an unfavorable prognosis. Solitary lesions involving the viscera are rare. We report a case of a 3-month-old male infant with a left testicular mass detected during an evaluation for suspected torsion. The patient underwent orchiectomy, revealing a nodular mass with grossly evident foci of necrosis. Histologically, the lesion exhibited small fascicles of plump eosinophilic, smooth muscle actin-positive spindle cells, alternating with larger areas of primitive cells with vesicular nuclei and scant cytoplasm arranged around a hemangiopericytoma-like vasculature. To our knowledge, this is the first report of a myofibroma localized within the testis.

The pre-operative identification of low-risk endometrialcancer: an audit of women treated in the South Island of New Zealand 1998-2000.

OBJECTIVE: To determine whether pre-operative investigations identify a group of patients with low-risk endometrial cancer, who do not require tertiary referral for surgical staging or pelvic radiotherapy. DESIGN: Retrospective chart review. SETTING: South Island of New Zealand gynaecological oncology services. SAMPLE: One hundred and forty consecutive patients with newly diagnosed endometrial cancer from 1988 to 2000. METHODS: The results of preoperative investigations were compared with the final pathology. MAIN OUTCOME MEASURES: Correlation of preoperative investigations with low risk disease. For the purpose of the study, women with grade 1 or 2 endometrioid tumours confined to the uterine body and less than 50% myometrial invasion were considered to have low risk disease. RESULTS: In total, 50 women had low risk disease. Only 53% of patients with grade 1 tumours on initial biopsy had low risk disease. Women who had a grade 1 tumour at biopsy and, an ultrasound report with an endometrial thickness of less than 20 mm, and no evidence of myometrial invasion, cervical involvement or adnexal metastasis had a 76% chance of having low risk disease. CONCLUSION: We were unable to accurately define the low risk group from pre-operative assessment.

Mechanisms of T cell peptide epitope-dependent late asthmatic reactions.

Short peptide sequences corresponding to T cell epitopes have been identified in the major cat allergen Fel d 1. In order to directly activate allergen-specific T cells in cat-allergic asthmatic individuals, peptides were administered by intradermal injection. Subsequently, a proportion of subjects experienced a delayed reduction of airway calibre manifested as a decrease in FEV(1). Changes in lung function occurred approximately 3 h after peptide injection, peaked at 6 h and resembled an isolated late asthmatic reaction (LAR). Using molecular tissue typing techniques, it was determined that many of the individuals experiencing isolated LAR expressed particular HLA-DR molecules. These molecules were shown in subsequent experiments to bind individual peptides within the preparation and thus to activate T cells in a major histocompatibility complex (MHC)-restricted fashion. The precise mechanisms whereby MHC-restricted activation of allergen-specific T cells gives rise to bronchoconstriction are currently under investigation.

Photodynamic therapy targeted to tumor-induced angiogenic vessels.

Cancer photodynamic therapy (PDT) with benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) may be effective not only by being directly cytotoxic to tumor cells, but also by being cytotoxic to the endothelium of tumor neovasculature. In the present study, we investigated the effect of PDT with an experimental liposomal formulation of BPD-MA on tumor-induced angiogenic vessels using a murine dorsal air sac model. First, hemostasis of neovasculature was examined by varying the regimen of PDT. Laser irradiation at 15 min after injection of 2 mg/kg liposomal BPD-MA (15 min PDT) caused complete blocking of blood flow in neovasculature. In contrast, PDT did not inhibit blood flow when the irradiation occurred 3 h after the injection of liposomal BPD-MA (3 h PDT). Next, the antitumor effect of PDT on Meth A sarcoma-bearing mice was investigated by using the hemostasis-inducing regimen. Tumor growth was strongly inhibited after the 15 min PDT with BPD-MA at a dose of 0.5-2 mg/kg. In contrast, 3 h PDT with BPD-MA at a dose of 2 mg/kg suppressed tumor growth only partially. The current study indicates that 15 min PDT causes strong suppression of tumor growth, perhaps through damaging endothelial cells in the tumor neovasculature rather than through a direct cytotoxic effect on tumor cells.

Grit-blasted titanium femoral stem in cementless primary total hip arthroplasty: a 5- to 10-year multicenter study.

A total of 133 cementless primary total hip arthroplasties using the Zweymuller-Alloclassic grit-blasted titanium tapered stem were performed in 3 institutions. The patient cohort was divided into 2 subgroups, nonselected and selected, on the basis of excellent bone stock and age (<65 years old at surgery). Acetabular components were all cementless, and bearing surfaces were all alumina-ceramic on polyethylene. After a 7.3-year average follow-up period (range, 5-10 years), 118 primary femoral replacements in 109 patients could be reviewed fully. Mean age at surgery was 55.7 years (range, 27-84 years). According to the Merle d'Aubigne and Charnley rating system, clinical results were graded excellent and good in 89% of hips and fair in 11%. Radiologically, early subsidence >2 mm could be detected in 4 hips (3.4%). Calcar atrophy and spot welds were noted in 77% and 82% of hips. Femoral osteolysis granuloma was noted in 4 hips (3.4%). There has been no stem fracture and no ceramic head breakage. The survivorship at 10 years with definite femoral aseptic loosening (radiographic failure) as the endpoint was 100% (95% Wilson confidence interval, 78.4%-100%; worst scenario, 95.4%). A significant difference between the nonselected and selected patient subgroups was observed only for early reoperation (P =.03) and proximal stress shielding (P =.01). Press-fitting but not filling the femoral canal with a rough titanium, straight, tapered femoral component represents, at intermediate follow-up, a promising cementless option in primary total hip arthroplasty.

Diaphragmatic hernia after Ivor-Lewis esophagectomy manifested as lower gastrointestinal bleeding.

Diaphragmatic hernia after esophageal resection is a recognized but rare complication. Parahiatal hernias may result from manipulation and extension of the crura during surgery. This can lead to a wide array of symptoms depending on the extent and organ that is herniated. A high index of suspicion is required because there is no one symptom that is specific for herniation. This report represents the first case of a patient presenting with lower gastrointestinal bleed from a parahiatal hernia after esophageal resection.

Detection of different strains of Potato virus Y and their mixed infections using competitive fluorescent RT-PCR.

A competitive fluorescent RT-PCR assay (CF RT-PCR) was developed for the rapid and reliable detection and discrimination of the two most common strains of Potato virus Y (PVY) found in potato (necrotic and ordinary). The assay incorporates two strain specific primers labelled with fluorescent labels, used in conjunction with a universal PVY primer. The strain specific primers compete for the same annealing site which further increases specificity. Discrimination is conferred by the fluorescent labels; green PCR products for PVY(O) and red for PVY(N), whilst mixed infections are detected as orange PCR products without the need for staining agarose gels. The assay can be scaled up for the processing of 96 samples simultaneously, with the detection of PCR products directly using a fluorescent microtitre plate reader. The assay successfully discriminated between 20 isolates of PVY tested, and could be used for the direct detection of PVY in potato tubers.

Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils.

Interleukin-9 (IL-9) has been implicated in the pathogenesis of allergic disorders. To examine the interaction between IL-9 and eosinophils, we evaluated mature peripheral blood eosinophils for their expression of the specific alpha-subunit of the IL-9 receptor (IL-9R-alpha). The expression of IL-9R-alpha by human eosinophils was detected at the messenger RNA (mRNA) and protein levels by reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, and immunocytochemical analysis, respectively. Functional analyses demonstrated that recombinant human (rh)IL-9 inhibited in vitro peripheral blood human eosinophil apoptosis in a concentration-dependent manner. We then examined the role of IL-9 in eosinophil differentiation using the human cord blood CD34(+) cells and human promyelocytic leukemia cells (HL-60). The addition of IL-9 to CD34(+) cells cultured in IL-3 and IL-5 enhanced eosinophil development, and IL-9 alone induced the expression of IL-5R-alpha. IL-9 also up-regulated the IL-5R-alpha chain cell surface expression during terminal eosinophil differentiation of the HL-60 cell line. Our findings suggest that IL-9 may potentiate in vivo eosinophil function by increasing their survival and IL-5-mediated differentiation and maturation. Taken together, these results suggest a mechanism by which IL-9 potentiates airway and tissue eosinophilia.

Basic skin flaps for the general surgeon: a teaching method.

BACKGROUND: Teaching residents the design and creation of skin flaps is challenging because the use of skin flaps is not common enough during the course of a typical residency to provide a broad experience base. METHODS: A 12 x 12-inch board with a 1/8-inch foam rubber covering was designed to provide for the creation of four flaps and one Z-plasty. A lecture and practical exercise were used to teach basic techniques. Performance was measured by preexamination and postexamination, as well as by a resident satisfaction survey. RESULTS: Mean scores improved by 45%. The resident survey revealed an average subjective rating was 4.7 on a scale of 1 to 5. All residents rated this format superior to traditional lecture instruction. Total cost to provide laboratory experience for 16 residents was $50. Materials can be recovered and reused at a cost of $0.40 each. CONCLUSIONS: The materials developed provided an effective, inexpensive nonbiologic model for teaching preoperative skills.

Malignant peripheral nerve sheath tumors of the head and neck: analysis of prognostic factors.

Malignant peripheral nerve sheath tumors of the head and neck region are uncommon and may be associated with neurofibromatosis or occur in a sporadic manner. This is a retrospective review of 17 patients with these tumors who were treated at a single institution. Analysis of clinical and pathologic factors that influenced outcome was performed. There were 9 men and 8 women. Seven patients had a history of neurofibromatosis. Radiotherapy was implicated as a possible etiologic factor in 4 patients. The neck was the most frequently involved site. Overall survival at 5 years was 52%. Survival was improved for women and for patients with low-grade tumors. Age, tumor site, and size had no impact on survival. Survival was worse for patients with neurofibromatosis than for those with the sporadic form of the disease (P = 0.02). Survival was calculated by the method of Kaplan and Meier. The significance of such results was based on results of the log rank test. Local recurrence correlated with tumor size and resection margin status. No local recurrences occurred in those patients who had negative margins of resection and received adjuvant radiotherapy. Tumor grade was predictive of the development of distant metastases. Negative margins of resection are essential for obtaining local control, and the addition of adjuvant radiotherapy may be beneficial in this group. Salvage surgery for local recurrence is possible in some patients.