The application of human reliability analysis to carpal tunnel decompression.

INTRODUCTION: Many surgical procedures are prone to human error, particularly in the learning phase of skills acquisition. Task standardisation has been suggested as an approach to reducing errors, but it fails to account for the human factors associated with learning. Human reliability analysis (HRA) is a structured approach to assess human error during surgery. This study used HRA methodologies to examine skills acquisition associated with carpal tunnel decompression. METHODS: The individual steps or subtasks required to complete a carpal tunnel decompression were identified using hierarchical task analysis (HTA). The systematic human error reduction and prediction approach (SHERPA) was carried out by consensus of subject matter experts. This identified the potential human errors at each subgoal, the level of risk associated with each task and how these potential errors could be prevented. RESULTS: Carpal tunnel decompression was broken down into 46 subtasks, of which 21 (45%) were medium risk and 25 (55%) were low risk. Of the 46 subtasks, 4 (9%) were assigned high probability and 18 (39%) were assigned medium probability. High probability errors (>1/50 cases) included selecting incorrect tourniquet size, failure to infiltrate local anaesthetic in a proximal-to-distal direction and completion of the World Health Organization (WHO) surgical sign-out. Three (6%) of the subtasks were assigned high criticality, which included failure to aspirate before anaesthetic injection, whereas 21 (45%) were assigned medium criticality. Remedial strategies for each potential error were devised. CONCLUSIONS: The use of HRA techniques provides surgeons with a platform to identify critical steps that are prone to error. This approach may improve surgical training and enhance patient safety.

Bilayer Mucoadhesive Buccal Film for Mucosal Ulcers Treatment: Development, Characterization, and Single Study Case.

The formation of mucosal ulcers is an end result of epithelial damage, and it occurs due to some specific causes, such as trauma, aphthous stomatitis, lichen planus and lichenoid reactions, cytotoxic effects of chemotherapy and radiation, and drug-induced hypersensitivity reactions and malignant settings. This study focused on films for target drug delivery with respect to the treatment of the diseases of the oral mucosa, specifically mucositis. The results of a single clinical study as a pre-experimental design was performed and followed up to the outcome until 30 days. The polymeric film was prepared in a mucoadhesive bilayer structure: the basal layer with lidocaine HCl had a faster release than the apical layer with benzydamine HCl and N-acetyl-cysteine. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and SEM characterized the physical-chemical and morphological properties. The cell viability and cytotoxicity were evaluated in cell line MCF7. The transport mechanism of the solvent (swelling) and the drugs in the basal or apical layer (drug release) was explained with mathematical models. To evaluate the effect of movement inside the mouth, the folding endurance was determined. The mucoadhesive bilayer film is biologically safe and stimulates cellular proliferation. A single study in vivo demonstrated the therapeutic effect of the mucoadhesive bilayer film in buccal mucositis.

Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a standard method for determining the pathologic status of the regional lymph nodes. AIMS: The aim of our study was to determine the incidence and clinicopathologic factors predictive of SLN positivity, and to evaluate the prognostic importance of SLNB in patients with cutaneous melanoma. METHODS: We performed a retrospective analysis of a prospectively maintained database of all patients who underwent SLNB for primary melanoma at our institution from 2005 to 2012. Statistical analysis was performed using χ 2 and Fischer exact test. RESULTS: In total, 318 patients underwent SLNB, of which 65 were for thin melanoma (≤1 mm). There were 36 positive SLNB, 278 negative SLNB and in four cases the SLN was not located. The incidence rate for SLNB was 11.3% overall and 1.5% in thin melanomas alone. Statistical analysis identified Breslow thickness >1 mm (P = 0.006), Clark level ≥ IV (P = 0.004) and age <75 years (P = 0.035) as the strongest predictors of SLN positivity. Our overall false negativity rate was 20% (9/45) with one case of false-negative SLNB in thin melanomas. CONCLUSION: Breslow thickness of the primary tumour remains the strongest predictor of SLN positivity. Our findings point to a possible limited role for SLNB in thin melanoma due to its low positivity rate, associated false-negative rate and related morbidity.

An Analysis of the "Classic" Papers in Aesthetic Surgery.

INTRODUCTION: Over the past 50 years, there has been a significant increase in published articles in the medical literature. The aesthetic surgery literature is vast, consisting of a plethora of diverse articles written by a myriad of illustrious authors. Despite this considerable archive of published material, it remains nebulous as to which precise papers have had the greatest impact on our specialty. The aim of our study was to identify and analyse the characteristics of the top 50 papers in the field of aesthetic surgery in the published literature. METHODS: The 50 most cited papers were identified in several surgical journals through the Web of Science. The articles were ranked in order of the number of citations received. These classic 50 papers were analysed for article type, their journal distribution, level of evidence as well as geographic and institutional origin. RESULTS: Six journals contributed to the top 50 papers in aesthetic surgery with Plastic and Reconstructive Surgery contributing the most with 31 papers.

A review of sentinel lymph node biopsy for thin melanoma.

INTRODUCTION: Although there is a lack of established survival benefit of sentinel lymph node biopsy (SLNB), this technique has been increasingly applied in the staging of patients with thin (≤1.00 mm) melanoma (T1Nx), without clear supportive evidence. METHODS: We review the guidelines and available literature on the indications and rationale for performing SLNB in thin melanoma. RESULTS: As a consequence of the paucity of evidence of SLNB in thin melanoma, there is considerable variability in the guidelines. It is difficult to define clinicopathologic factors that reliably predict the presence of nodal metastasis. SLNB does not yet inform management in thin melanoma to improve survival outcome. CONCLUSION: Based on available evidence, high risk patients with melanomas between 0.75 and 1.00 mm may be appropriate candidates to be considered for SLN biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy, and the lack of proven survival benefit from any form of surgical nodal staging.

A novel barbed suture tie-over dressing for skin grafts: a comparison with traditional techniques.

INTRODUCTION: Barbed suture devices have a widespread application in plastic surgery. The unidirectional nature of the barbs facilitates a strong grip on tissues and reduces the need to constantly tension the suture manually. We hypothesized that a barbed suture tie-over suture to secure skin grafts would be quicker to perform than traditional tie-overs and would also exert a greater downward pressure on the skin graft. METHODS: Thirty uniform areas of skin were excised from a cadaver. A pressure transducer was placed on the wound bed and covered with the excised skin along with a mineral oil-soaked wool dressing to act as a bolster. Three different sutures were used to secure the graft in place and the pressure was recorded. The tie-over techniques used were the classic silk tie-over, a running Vicryl Rapide™ tie-over and a running barbed tie-over. RESULTS: The barbed tie-over exerted the most downward pressure (82.8 ± 7.3 mmHg) compared to the silk (46 ± 4.85 mmHg) and the Vicryl Rapide™ (18.6 ± 2.4 mmHg). Furthermore, the barbed tie-over was the quickest to perform (1:45 ± 22 s) when compared to the Vicryl Rapide™ (02:57 ± 27 s) and the silk tie-overs (04:26 ± 39 s). CONCLUSION: Barbed sutures are a viable option for securing skin grafts. They are quick to perform and provide significantly improved downward pressure on the skin graft. We feel that this technique would be especially suited to the sole operator as it can be carried out without the need of an assistant.

Role of myosin phosphatase isoforms in cGMP-mediated smooth muscle relaxation.

In vitro experiments showing the activation of the myosin phosphatase via heterophilic leucine zipper interactions between its targeting subunit (MYPT1) and cGMP-dependent protein kinase I suggested a pathway for smooth muscle relaxation (Surks, H. K., Mochizuki, N., Kasai, Y., Georgescu, S. P., Tang, K. M., Ito, M., Lincoln, T. M., and Mendelsohn, M. E. (1999) Science 286, 1583-1587). The relationship between MYPT1 isoform expression and smooth muscle responses to cGMP signaling in vivo has not been explored. MYPT1 isoforms that contain or lack a C-terminal leucine zipper are generated in birds and mammals by cassette-type alternative splicing of a 31-nucleotide exon. The avian and mammalian C-terminal isoforms are highly conserved and expressed in a tissue-specific fashion. In the mature chicken the tonic contracting aorta and phasic contracting gizzard exclusively express the leucine zipper positive and negative MYPT1 isoforms, respectively. Expression of the MYPT1 isoforms is also developmentally regulated in the gizzard, which switches from leucine zipper positive to negative isoforms around the time of hatching. This switch coincides with the development in the gizzard of a cGMP-resistant phenotype, i.e. inability to dephosphorylate myosin and relax in response to 8-bromo-cGMP after calcium activation. Furthermore, association of cGMP-dependent protein kinase I with MYPT1 is detected by immunoprecipitation only in the tissue that expresses the leucine zipper positive isoform of MYPT1. These results suggest that the regulated splicing of MYPT1 is an important determinant of smooth muscle phenotypic diversity and the variability in the response of smooth muscles to the calcium desensitizing effect of cGMP signaling.

Radioadaptation in Indian muntjac fibroblast cells induced by low intensity laser irradiation.

Earlier reports have indicated that an adaptive, protective response to ionizing radiation is inducible by pre-treatment with low intensity laser irradiation (LILI). We have investigated the potential of LILI to induce an adaptive response against the damaging effects of ionizing radiation in Indian muntjac fibroblasts. LILI at 660, but not 820 nm, at 11.5 and 23.0 J/cm2, induced an apparent adaptive response in the form of a reduction in the frequency of radiation-induced chromosome aberrations, but not in cell survival. There was also a trend towards a reduction in the level of single-stranded and double-stranded DNA breaks induced by ionizing radiation when cells were preconditioned with LILI. However, this did not contribute to the reduced chromosome aberration frequency. Further analysis revealed that the reduced aberration frequency was caused by a laser-induced extension of G2 delay. The adaptive response was therefore the result of cell cycle modulation by LILI, at a wavelength where there is no known DNA damaging effect to induce the checkpoint mechanisms that are normally responsible for altering cell cycle progression.

Cell-cycle delay is induced in cells of a U937 promonocytic cell line by low-intensity light irradiation at 660 nm.

Visible-light irradiation (VLI) at 660 nm and 11.5 J/cm2 inhibits proliferation of cells of the U937 promonocytic cell line, as monitored by autoradiographical analysis. The S-phase cell population is reduced at 6 h post-radiation treatment. Flow cytometric analysis confirms this, and also shows that light irradiation of cells induces a statistically significant increase in G2/M cells at 6 h post-radiation treatment. It has been postulated that VLI at 660 nm can alter cell-cycle progression by affecting intracellular concentrations of ions, in particular pH and calcium. However, no significant effects of light irradiation on these intracellular ions have been observed. These effects of VLI are not a consequence of radiation-induced DNA strand breaks, therefore events other than direct DNA damage are involved. These findings demonstrate a direct photobiological effect of VLI at 660 nm on the cell cycle, and indicate a previously unsuspected mechanism for the induction of cell-cycle delay that is neither a result of changes in the concentration of intracellular ions nor initiated by DNA strand breaks.

Isolation of gene fusions (soi::lacZ) inducible by oxidative stress in Escherichia coli.

Mu dX phage was used to isolate three gene fusions to the lacZ gene (soi::lacZ; soi for superoxide radical inducible) that were induced by treatment with superoxide radical anion generators such as paraquat and plumbagin. The induction of beta-galactosidase in these fusion strains with the superoxide radical generating agents required aerobic metabolism. Hyperoxygenation (i.e., bubbling of cultures with oxygen gas) also induced the fusions. On the other hand, hydrogen peroxide did not induce the fusions at concentrations that are known to invoke an adaptive response. Introduction of oxyR, htpR, or recA mutations did not affect the induction. Two of the fusion strains exhibited increased sensitivity to paraquat but not to hydrogen peroxide. The third fusion strain showed no increased sensitivity to either agent. All three fusions were located in the 45- to 61-min region of the Escherichia coli chromosome.

Reduced systemic drug exposure by combining intraarterial cis-diamminedichloroplatinum(II) with hemodialysis of regional venous drainage.

During cancer chemotherapy toxicity to normal tissues often limits the tolerable dose. To increase drug delivery to tumor while maintaining tolerable systemic exposure, regional treatments, such as intraarterial drug delivery, have been used. Despite intraarterial delivery, systemic toxicity often remains the dose-limiting sensitivity. If systemic drug exposure could be reduced after intraarterial infusion, the intraarterial dose could be increased, which should increase the therapeutic response. We compared the pharmacokinetic advantage after cisplatin infusion into the internal carotid artery to that obtained after infusing cisplatin into the internal carotid artery during extracorporeal removal of cisplatin from the jugular blood by hemodialysis. Four patients with malignant gliomas received intracarotid cisplatin, 100 mg/m2 over 60 min, every 4 weeks. During one treatment, while cisplatin was infused into the internal carotid artery, the jugular blood was dialyzed extracorporeally at 300 ml/min and returned to the inferior vena cava. Seventy to 96% of the free platinum that entered the dialyzer was removed. By aspirating blood from the jugular vein at 300 ml/min, 30-79% of the ipsilateral carotid blood was collected for extracorporeal circulation. Hemodialysis of the cerebral venous drainage during intracarotid infusion reduced the systemic exposure to cisplatin by 51-61% when compared to the exposure from internal carotid artery infusion without hemodialysis. The pharmacokinetic advantage (brain/body exposure ratio) was increased from 3 to 5/1 during internal carotid artery infusion alone to as much as 15/1 during treatment combining intracarotid infusion with hemodialysis of the jugular blood. Systemic toxicity now limits the dose of cisplatin that can be administered safely. Increased tumor exposure without increased systemic toxicity may be possible with the technique described and greater doses of cisplatin. Assuming no associated local toxicities, the results of the current study indicate that the dose of intracarotid cisplatin can be increased while maintaining tolerable systemic exposure.

Cardiac arrest and resuscitation: brain iron delocalization during reperfusion.

We hypothesize that brain injury from cardiac arrest occurs during reperfusion and is in part mediated by iron-dependent lipid peroxidation. We conducted a study to examine the time course of brain iron delocalization and lipid peroxidation in an animal model of cardiac arrest and resuscitation. Assays for brain tissue iron in low-molecular-weight species (LMWS iron) used the o-phenanthroline test on an ultrafiltered (molecular weight less than 30,000) tissue sample; malondialdehyde (MDA), a product of lipid peroxidation, in brain tissue was assayed by the thiobarbituric acid test (TBA). Samples of the parietal cortex from 11 nonischemic control dogs (Group 1) had LMWS iron levels of 9.6 +/- 4.9 nmol/100 mg tissue and MDA levels of 7.7 +/- 2.0 nmol/100 mg tissue. Samples from the parietal cortex taken from five dogs after 15 minutes of cardiac arrest (Group 2) had LMWS iron levels of 9.3 +/- 3.1 nmol/100 mg tissue and MDA levels of 6.1 +/- 1.0 nmol/100 mg tissue. Samples from the parietal cortex taken from five dogs after 45 minutes of cardiac arrest (Group 3) had LMWS iron levels of 6.7 +/- 3.3 nmol/100 mg tissue and MDA levels of 5.6 +/- 0.4 nmol/100 mg tissue. There was no significant difference among the three groups for either LMWS iron or MDA. Five dogs were subjected to 15 minutes of cardiac arrest and definitive resuscitation by internal cardiac massage and defibrillation (Group 4). Following resuscitation the chest was closed and the dogs were given intensive care for two hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of treatment on the evolution of renal abnormalities in lupus nephritis.

We retrospectively studied the evolution of histopathologic features in successive renal biopsies in patients with lupus nephritis, to evaluate the effects of various treatment regimens. Repeat renal biopsies had been performed in 62 patients after more than 18 months of observation (median interval, 44 months) in randomized therapeutic trials comparing prednisone with cytotoxic drugs. Renal histopathologic features were graded individually, and a composite score reflecting the number and severity of irreversible lesions was defined as a chronicity index. The chronicity index for patients treated with conventional high-dose prednisone increased linearly with the interval between biopsies, whereas the index in the group receiving cytotoxic-drug treatments did not increase over time. After statistical adjustment for important prognostic factors (age and initial chronicity index) identified by multiple linear regression, the difference in the slopes between the group receiving prednisone and the group receiving cytotoxic drugs was significant (P less than 0.0001). We conclude that cytotoxic-drug treatment reduces the likelihood of progressive renal scarring in lupus nephritis.

Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome.

Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic factors in lupus nephritis. Contribution of renal histologic data.

The predictive value of laboratory results and renal histologic data was examined in 102 patients upon entry into prospective, randomized, therapeutic trials of lupus nephritis. Three clinical features at the time of entry into the study were individually associated with increased rates of renal failure: age less than 24 years, male gender, and an elevated serum creatinine level. Subjects with diffuse proliferative or membranoproliferative glomerulonephritis were at a modest but significantly increased risk for the development of end-stage renal disease compared with patients with other classes of lupus nephritis. Semiquantitative scores of histologic features (specified by activity and chronicity indexes) identified subgroups of patients with comparatively high renal failure rates. To address the controversial issue of whether renal histologic data significantly improve the outcome predictions in patients with lupus nephritis, multivariate survival models were generated, permitting simultaneous consideration of multiple prognostic factors. Outcome predictions based on the strongest clinical predictors (age, sex, and serum creatinine level) were significantly enhanced by the addition of activity and chronicity indexes. Only age and chronicity index contributed significantly to the five-variable model and together constituted a two-variable model, the predictions of which were similar to observed outcomes. In the context of the highly significant prognostic indicators (age and chronicity index), immunosuppressive agents appeared to provide a slight therapeutic advantage over oral corticosteroids alone.

Cerebral cortical perfusion during and following resuscitation from cardiac arrest in dogs.

Perfusion of the cerebral cortex during closed chest CPR in dogs, generating systolic pressures of 60 to 70 mmHg, is only 10% of pre-arrest blood flow. In contrast, internal cardiac massage produces normal cortical perfusion rates. Following a 20-min perfusion arrest, during pressure controlled reperfusion, cortical flow rates decay to less than 20% normal after 90 min of reperfusion. This appears to be due to increasing cerebral vascular resistance, and is not due to rising intracranial pressure. The post-arrest cortical hypoperfusion syndrome is prolonged with cortical flow remaining below 20% normal up to 18 hr post arrest. The use of a variety of calcium antagonists, including flunarizine, lidoflazine, verapamil, and Mg2+, immediately post-resuscitation maintains cerebral vascular resistance and cortical perfusion at normal levels. A prospective blind trial of the calcium antagonist lidoflazine following a 15-min cardiac arrest in dogs and resuscitation by internal massage, demonstrates amelioration of neurologic deficit in the early postresuscitation period.