Effect of stapled versus layered skin closure on surgical site occurrences after abdominal wall reconstruction.

BACKGROUND: The effect of skin closure technique on surgical site occurrences (SSO) after open abdominal wall reconstruction (AWR) with retromuscular polypropylene mesh placement is largely unknown. We hypothesize that layered subcuticular skin closure with cyanoacrylate skin adhesive is protective of surgical site infection compared to standard stapled closure. METHODS: A retrospective review utilizing the Abdominal Core Health Quality Collaborative (ACHQC) database of all patients at Prisma Health-Upstate. All patients with open abdominal wall reconstruction (AWR) of midline incisional hernia defects with retromuscular polypropylene mesh placement from January 2013 to February 2020 were included. Patient demographics, comorbidities, type of hernia repair with mesh location, method of skin closure, and SSOs were collected. Skin closure method was divided into two groups, reflecting a temporal change in practice: staples (historical control group) versus subcuticular suture with cyanoacrylate skin adhesive with/without polymer mesh tape (study group). Primary endpoint was SSI and SSO. Secondary endpoints were SSO or SSI requiring procedural intervention (SSOPI/SSIPI). Standard statistical methods were utilized. RESULTS: A total of 834 patients were analyzed, with 263 treated with stapled skin closure and 571 with subcuticular and adhesive closure. On univariate analysis, the incidence of SSI was significantly lower in the study group (11.8 vs 6.8%; p = 0.002), as was the need for SSIPI (11.8 vs 6.7%; p = 0.015). Rate of SSO was not significantly different between groups (28.1 vs 27.2%), but the rate of SSO requiring intervention was lower in the study group (14.1 vs 9.3%; p = 0.045). CONCLUSION: Layered skin closure technique, including subcuticular closure and adhesive, may reduce the risk of surgical site infection after open AWR. A prospective randomized trial is planned to confirm these findings.

Computed tomography imaging in ventral hernia repair: can we predict the need for myofascial release?

INTRODUCTION: Currently, the need for additional myofascial release (AMR) in addition to retromuscular dissection during open Rives-Stoppa hernia repair is determined intraoperatively based on the discretion of the surgeon. We developed a novel method to objectively predict the need for AMR preoperatively using computed tomography (CT)-measured rectus width to hernia width ratio (RDR). METHODS: A retrospective chart review of all patients who underwent open retro-muscular mesh repair of midline ventral hernia between August 1, 2007 and February 1, 2018, who had a preoperative CT scan within 1 year prior to their operation. The primary endpoint was the ability of the defect ratio to predict the need for AMR in pursuit of fascial closure. The secondary endpoint was the ability of Component Separation Index (CSI) to predict the need for AMR to obtain fascial closure. RESULTS: Of 342 patients, 208 repaired with rectus abdominis release alone (RM group), while 134 required AMR (RM + group). An RDR of > 1.34 on area under the curve analysis predicted the need for AMR with 77.6% accuracy. There was a linear decrease in the need for AMR with increasing RDR: RDR < 1 required AMR in 78.8% of cases, RDR 1.1-1.49 in 52%, RDR 1.5-1.99 in 32.1%, and RDR > 2 in just 10.8%. Similarly, CSI > 0.146 predicted the need for AMR with 76.3% accuracy on area under the curve analysis. CONCLUSION: The RDR is a practical and reliable tool to predict the ability to close the defect during open Rives-Stoppa ventral hernia repair without AMR. An RDR of > 2 portends fascial closure with rectus abdominis myofascial release alone in 90% of cases.

Prophylactic mesh augmentation using permanent synthetic mesh: outcomes of keyhole and Stapled Ostomy Reinforcement with Retromuscular Mesh techniques.

INTRODUCTION: Parastomal hernias (PSH) are the most common complication of stoma creation and can cause significant morbidity. We present a consecutive series of patients receiving prophylactic mesh augmentation (PMA) for prevention of PSH. METHODS: This retrospective review evaluates the efficacy and outcomes of PMA for PSH prevention, and retrospectively compares traditional keyhole PMA (tPMA) (n = 28) with a prophylactic Stapled Ostomy Reinforcement with Retromuscular Mesh technique (pSTORRM) (n = 24). RESULTS: PMA was performed in 52 cases between January 2015 and July 2018. All cases used a large-pore, non-coated, mid-weight polypropylene mesh placed in the retrorectus space. With a median follow-up of 16 mos, parastomal hernia was confirmed in 11.5% (n = 6), 5 of whom were symptomatic. patient-reported outcomes (PRO) indicated 6 additional patients with symptoms associated with PSH without clinical or radiographic confirmation. Patients had similar comorbidities and operative characteristics between tPMA and pSTORRM techniques, and no difference in a median follow-up. pSTORRM patients had fewer surgical site infections (8.3 vs 32.1%; p = 0.046) and occurrences (12.5 vs 46.4%; p = 0.015), and lower rate of PSH, though not statistically significant (4.2 vs 17.9%; p = 0.195). CONCLUSION: Permanent synthetic mesh placed as a sublay in the retromuscular space is safe and appears to decrease the risk of PSH formation after the creation of permanent stomas. A stapled technique may provide advantages over a traditional keyhole technique.

Relative resistance index (RRI) - a scoring system for antibiotic resistance in Pseudomonas aeruginosa.

BACKGROUND: There is a need to measure antibiotic resistance of Pseudomonas aeruginosa (PA) in cystic fibrosis (CF), either qualitatively or quantitatively, to inform patient management. The aim of this study was to develop a simple method by which resistance can be quantified by calculating a relative resistance index (RRI), and to assess correlation of RRIs with clinical variables. METHODS: In our model, RRIs were calculated based on resistance to aztreonam, ceftazidime, ciprofloxacin, colistin, meropenem, tazocin, temicillin and tobramycin. Eighty-five adults with CF and chronic PA colonisation were identified. For each, all PA cultures were allocated a score of 0 for susceptible, 0.5 for intermediate resistance or 1 for resistance for each antibiotic listed above, and the RRI calculated by dividing the sum of these by the number of antibiotics, giving a maximum score of 1. The mean RRIs for all cultures were correlated with key clinical variables monitored in CF patients (including age, FEV1, IV antibiotic days and BMI). RESULTS: RRIs for non-mucoid PA exhibited moderate positive correlation with total number of IV days (r = 0.405; p < 0.001) and moderate negative correlation with FEV1 % predicted (r = -0.437; p < 0.001). RRIs were not significantly correlated with duration of colonisation, typing (clonal vs other strain) or BMI. Median RRIs were significantly higher for females (0.26, IQR 0.13-0.54) than males (0.18, IQR 0.07-0.37) for non-mucoid PA only (p = 0.03). CONCLUSIONS: RRI is an easily calculated measure that correlates with other clinical variables in CF patients and enables quantitative monitoring of resistance.

Toxic epidermal necrolysis and concurrent granulomatosis with polyangiitis (Wegener's granulomatosis). Management of a rare case and review of the literature.

Toxic epidermal necrolysis (TEN) is a rare, acute life-threatening mucocutaneous disorder that is characterised by epidermal loss/exfoliation exceeding 30% total body surface area (TBSA) and is on a spectrum that includes erythema multiforme and Stevens-Johnson syndrome (SJS). It is estimated that 80% of TEN cases are related to medication reactions; the association based on the recognition that TEN usually develops 1-3 weeks following administration of the suspect drug. It is agreed that primary treatment consists of prompt withdrawal of causative drugs and transfer to a regional burn unit. Transfer to a burn unit, no more than 7 days after onset of symptoms, has been acknowledged as reducing the risk of infections, hospital length of stay and infection-related mortality. Due to the uncertainty surrounding TEN pathogenesis, several different modalities have been proposed for the treatment of TEN, including high-dose intravenous immunoglobulins, plasmapheresis, cyclophosphamide, cyclosporine and systemic steroids; however, these therapies are relatively ineffective. The use of systemic corticosteroids for treatment of TEN has in particular been deemed controversial due to associations with increased infections leading to greater length of hospital stay and increased mortality. Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare relapsing-remitting disorder of unknown aetiology, characterised by granulomatosis inflammation and necrotising vasculitis predominantly affecting small- to medium-sized vessels. While a 5-year survival rate of 75-83% is now realised, relapse and associated morbidity is of concern. The established treatment for GPA follows the recommendations of the French National Authority for Health (HAS) for systematic necrotising vasculitis. With induction treatment, it is recommended that GPA be treated with a combination of systemic corticosteroids and immunosuppressants. A review of the literature failed to identify any previous case where both of these conditions coincide. Our search was conducted through databases which included MEDLINE, PubMed, Scopus, AMED, CINAHL and EMBASE, using keywords: toxic epidermal necrolysis, Wegener's granulomatosis, granulomatosis with polyangiitis. We submit the rare case of a 22-year-old woman who presented to our regional burn unit with both GPA and TEN, and we discuss the presentation, investigation and multidisciplinary management of the patient, as well as reviewing the literature regarding these two conditions.

Phenomenological model of interstitial fluid pressure in a solid tumor.

Tumor interstitial fluid pressure (TIFP) has the potential to predict tumor response to nonsurgical cancer treatments, including radiation therapy. At present the only quantitative measures available are of limited use, since they are invasive and yield only point measurements. We present the mathematical framework for a quantitative, noninvasive measure of TIFP. The model describes the distribution of interstitial fluid pressure in three distinct tumor regions: vascularized tumor rim, central tumor region, and normal tissue. A relationship between the TIFP and the fluid flow velocity at the periphery of a tumor is presented. This model suggests that a measure of fluid flow rate from a tumor into normal tissue reflects TIFP. We demonstrate that the acquisition of serial images of a tumor after the injection of a contrast agent can provide a noninvasive and potentially quantitative measure of TIFP.

Does reduced-intensity allogeneic transplantation confer a survival advantage to patients with poor prognosis chronic lymphocytic leukaemia? A case-control retrospective analysis.

BACKGROUND: Reduced-intensity conditioning (RIC) allogeneic haemopoietic cell transplantation (allo-HCT) is increasingly considered as a therapeutic option for younger patients with poor-risk chronic lymphocytic leukaemia (CLL). In this retrospective analysis, we assessed the outcomes of CLL patients undergoing RIC allo-HCT compared with a group of matched controls that were candidates for transplantation but did not have a suitable donor or refused the procedure. PATIENTS AND METHODS: Cases comprised 37 patients who underwent RIC allo-HCT. Haemopoietic cell grafts were harvested from HLA-matched siblings (27) and unrelated donors (7). Controls consisted of 43 patients from the same institutions who received conventional therapy only. Matching variables were age at diagnosis and time to first CLL-specific therapy. RESULTS: Both patient groups were well balanced in terms of cytogenetics by FISH, CD38 and ZAP-70 expression, and immunoglobulin heavy-chain variable region mutational status. Median overall survival was 113 months for HCT patients and 85 months for controls when calculated from time of diagnosis (P = 0.072) and 103 and 67 months, respectively, when calculated from time of first therapy (P = 0.041). CONCLUSION: RIC allo-HCT is a reasonable option for patients with high-risk CLL. However, these results require confirmation before the procedure can be recommended outside clinical trials.

Design and benchtop validation of a handheld integrated dynamic breast imaging system for noninvasive characterization of suspicious breast lesions.

We have developed a portable, handheld, integrated, dynamic breast imaging system that integrates a near infrared tissue oximeter, clinical ultrasound, and two pressure sensors for noninvasive detection of pressure-induced structural and functional dynamics of suspicious breast lesions. A series of benchtop tests were conducted to validate multiple performance characteristics of the integrated dynamic near infrared/ultrasound breast imaging system (idNIRUS), including the reconstruction of the absorptive heterogeneities and the generation of the dynamic compression stimuli. In absorptive heterogeneity testing, we reconstructed the absorption coefficients of transparent polypropylene tubing circulated with a skim milk-India ink mixture and embedded in a gel wax tissue simulating phantom. High linear correlations (R(2) greater than 0.989) were observed between the reconstructed and the measured absorption coefficients of the embedded tubing. In dynamic compression testing, five volunteer operators generated ten successive compression sessions by compressing the idNIRUS imager on a breast self examination wearable model following the computer simulated pressure profile. The manually generated pressure profiles demonstrated an accuracy of 95.7% and operator-dependent variation of less than 5%. The results of the current benchtop tests will help to optimize the most appropriate testing conditions for our future planned clinical trial.

Quantitative estimation of permeability surface-area product in astroglial brain tumors using perfusion CT and correlation with histopathologic grade.

BACKGROUND AND PURPOSE: Glioma angiogenesis and its different hemodynamic features, which can be evaluated by using perfusion CT (PCT) imaging of the brain, have been correlated with the grade and the aggressiveness of gliomas. Our hypothesis was that quantitative estimation of permeability surface area product (PS), cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in astroglial brain tumors by using PCT will correlate with glioma grade. High-grade gliomas will show higher PS and CBV as compared with low-grade gliomas. MATERIALS AND METHODS: PCT was performed in 32 patients with previously untreated astroglial tumors (24 high-grade gliomas and 8 low-grade gliomas) by using a total acquisition time of 170 seconds. World Health Organization (WHO) glioma grades were compared with PCT parameter absolute values by using Student or nonparametric Wilcoxon 2-sample tests. Receiver operating characteristic (ROC) analyses were also done for each of the parameters. RESULTS: The differences in PS, CBV, and CBF between the low- and high-grade tumor groups were statistically significant, with the low-grade group showing lower mean values than the high-grade group. ROC analyses showed that both CBV (C-statistic 0.930) and PS (C-statistic 0.927) were very similar to each other in differentiating low- and high-grade gliomas and had higher predictability compared with CBF and MTT. Within the high-grade group, differentiation of WHO grade III and IV gliomas was also possible by using PCT parameters, and PS showed the highest C-statistic value (0.926) for the ROC analyses in this regard. CONCLUSIONS: Both PS and CBV showed strong association with glioma grading, high-grade gliomas showing higher PS and CBV as compared with low-grade gliomas. Perfusion parameters, especially PS, can also be used to differentiate WHO grade III from grade IV in the high-grade tumor group.

Donor CD31 genotype and its association with acute graft-versus-host disease in HLA identical sibling stem cell transplantation.

CD31 gene polymorphisms are implicated in the pathogenesis of graft-versus-host disease (GvHD) following haematopoietic stem cell transplantation (HST). We investigated the influence of CD31 genotype on the incidence of GvHD following HST from an human leukocyte antigen (HLA)-identical sibling donor. Donor and recipient CD31 codons 125, 563 and 670 DNA polymorphisms were determined in 85 cases of HLA identical sibling HST from two transplant centres. A correlation between CD31 genotype and acute GvHD was considered significant if observed in patients from both transplant centres independently. A strong correlation was identified between donor CD31 codon 125 genotype and the incidence of acute GvHD. Acute GvHD grades II-IV occurred in 27 of 46 (59%) recipients with a CD31 codon 125 leucine / valine heterozygous donor compared to nine of 39 (23%) recipients with a CD31 codon 125 homozygous donor (P=0.0019, relative-risk 2.45, 95% confidence interval 1.3-4.5). This correlation was significant in patients from both transplant centres (P=0.015 and P=0.019). We suggest that CD31 genotype may influence the function of donor-derived leukocytes and may be informative when there is a choice of comparable donors.

Effect of intravascular-to-extravascular water exchange on the determination of blood-to-tissue transfer constant by magnetic resonance imaging.

Water exchange across capillary walls couples intra- and extravascular (IV-EV) protons and their magnetization. A bolus i.v. injection of an extracellular MRI contrast agent (MRCA) causes a large increase in the spin-lattice relaxation rate, R1, of water protons in the plasma and blood cells within the capillaries and changes the effective relaxation rate R1eff in tissue via IV-EV water exchange. An analysis of the effect of plasma-red cell and IV-EV water exchange on the MRI-measured influx and permeability of capillaries to the MRCA is presented and focused on the brain and the blood-brain barrier. The effect of arrival of a bolus of an MRCA in the capillary on the relaxation rate R1eff in tissue via IV-EV water exchange occurs more rapidly than the MRCA uptake in tissue and can dominate the initial time curve of the R1eff change before the MRCA uptake in tissue becomes significant. This raises the possibility that (tissue dependent) IV-EV rate of exchange of water molecules can affect estimates of MRCA transfer constant. We demonstrate that an approach that considers IV-EV water exchange and uses the theoretical model of blood-brain tracer distribution developed by Patlak et al. (J Cereb Blood Flow Metab 1983;3:1-7) can lead to an accurate estimate of the MRI-determined influx rate constant of the MRCA and to an underestimation of the tissue blood volume.

Sickle red blood cells accumulate in tumor.

The preferential accumulation of sickle blood cells in tumor vasculature is demonstrated noninvasively using MRI and sickle red blood cells loaded with Gd-DTPA and invasively by two other techniques. The distribution of red blood cells in rat brain tumors relative to normal brains were measured using three separate techniques: MRI of Gd-DTPA loaded cells, fluorescent microscopy detection of Oregon Green 488 fluorescence conjugated to a streptavidin-biotin complex that binds to red blood cell surface proteins, and autoradiography using a technetium (99m)Tc-labeling kit. Labeled red cells were infused intravenously in rats with brain tumors. Sickle cells preferentially accumulated in tumor relative to normal brain, with highest concentrations near the tumor / normal tissue boundary, whereas control normal red cells did not preferentially aggregate at the tumor periphery. This demonstrates the potential of sickle red blood cells to accumulate in the abnormal tumor vessel network, and the ability to detect their aggregation noninvasively and at high spatial resolution using MRI. The application of the noninvasive measurement of sickle cells for imaging tumor neovasculature, or as a delivery tool for therapy, requires further study.

Total registration of non-Hodgkin's lymphoma and Hodgkin's disease in Scotland: effect of deprivation and caseload on outcome.

All cases S16 years of age with a histological diagnosis of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) presented in Scotland between 1 January 1994 and 31 December 1996 were registered prospectively in the Scotland and Newcastle Lymphoma Group database by a process of total registration. The census population of Scotland in 1996-1997 was 5.1 million. One thousand seven hundred and sixty three patients were registered with NHL and 350 patients with HD. These patients have been followed up for a median of 47 months in the case of NHL and 51 months for HD cases. Actuarial 5-year survival for adult NHL was 35% and for HD, 75%. Outcome for both NHL and HD was particularly poor in the population over 60 years with median survival of 18 months for NHL and 27 months for HD. When analysis of survival was related to degree of material deprivation using the Carstairs score a significantly poorer survival was seen for NHL with increasing deprivation that could not be explained by a different pattern of age or stage at presentation. Deprivation had no impact on incidence or survival in HD. Analysis of impact of caseload of the physician initiating therapy showed no significant difference in 5-year survival.

Autologous peripheral blood stem cell transplantation in first remission adult acute myeloid leukaemia--an intention to treat analysis and comparison of outcome using a predictive model based on the MRC AML10 cohort.

The role of autologous peripheral blood stem cell transplantation (APBSCT) in acute myeloid leukaemia (AML) remains controversial. The current study evaluated the application of APBSCT in a large consecutive series of patients with untreated AML, and compared outcome with a predictive model based on MRC AML10 data. Of 148 evaluable patients, 118 patients entered complete remission (CR) after induction therapy comprising three cycles of daunorubicin, cytosine arabinoside and oral 6-thioguanine. Of these patients, 68 (57%) proceeded to consolidation therapy with two courses of intermediate dose cytosine arabinoside, and stem cell mobilisation, and 40 of these patients (34%) underwent the APBSCT procedure after high dose busulphan conditioning. Harvest quality was the main factor precluding APBSCT. Five-year event-free survival (EFS) in patients who achieved CR was 38% and in APBSCT patients was 57%. There were no transplant-related deaths. No significant differences were demonstrated between observed and expected outcomes at 1 and 2 years, based on the predictive model derived from the MRC AML10 study. These data therefore indicate that only a third of eligible adult patients will undergo APBSCT. However, the results demonstrate favourable survival in such patients, with no transplant-related mortality.

Single-coil arterial spin-tagging for estimating cerebral blood flow as viewed from the capillary: relative contributions of intra- and extravascular signal.

The single-capillary model was applied to the exchange microvessels for water in the cerebral parenchyma and used to calculate blood-to-brain flux of water; the theory of the steady-state arterial spin-tagging (AST) technique for estimating cerebral blood flow (CBF) was revised to incorporate the presence of both extravascular (tissue) and capillary signal. A crucial element of the single-coil AST experiment is that magnetization transfer (MT) shortens the effective T1 of the extravascular water, making it one-quarter that of the T1 of capillary blood. Furthermore, the mean capillary transit time is on the order of the T1 of the extravascular water. The single-coil AST experiment is distinguished from other methods which use water as an indicator for measurement of CBF in that the (flow-dependent) populations of inverted protons in the intra- and extravascular compartments can be nearly equal for normal physiological conditions. The following questions are considered: Is single-coil AST contrast linear in resting CBF? Is contrast in the single-coil AST technique likely to be linear under changes in CBF in normal tissue? Is the contrast likely to be linear in such common pathologies as stroke and cerebral tumor? We demonstrate that, if the population of inverted protons in the microvessels is included in the experiment, the voxel population of inverted protons will be approximately linear with flow across a broad range of flow values. We predict that the single-coil AST experiment will systematically overestimate resting CBF for flows in the normal range, that changes in CBF in normal tissue will produce an approximately linear response in AST measurement, and, finally, we predict the operating characteristics of the measurement in common cerebral pathologies.

Interregional variation of longitudinal relaxation rates in human brain at 3.0 T: relation to estimated iron and water contents.

In a study of interregional variation of the longitudinal relaxation rate (R(1)) in human brain at 3 T, R(1) maps were acquired from 12 healthy adults using a multi-slice implementation of the T one by multiple readout pulses (TOMROP) sequence. Mean R(1) values were obtained from the prefrontal cortex (0.567 +/- 0.020 sec(-1)), caudate head (0.675 +/- 0.019 sec(-1)), putamen (0.749 +/- 0.023 sec(-1)), substantia nigra (0.873 +/- 0.037 sec(-1)), globus pallidus (0.960 +/- 0.034 sec(-1)), thalamus (0.822 +/- 0.027 sec(-1)), and frontal white matter (1.184 +/- 0.057 sec(-1)). For gray matter regions other than the thalamus, R(1) showed a strong correlation (r = 0.984, P < 0.0001) with estimated regional nonheme iron concentrations ([Fe]). These R(1) values also showed a strong correlation (r = 0.976, P < 0.0001) with estimates of 1/f(w) obtained from MRI relative proton density measurements, where f(w) represents tissue water content. When white matter is included in the consideration, 1/f(w) is a better predictor of R(1) than is [Fe]. An analysis based on the fast-exchange two-state model of longitudinal relaxation suggests that interregional differences in f(w) account for the majority of the variation of R(1) across gray matter regions. Magn Reson Med 45:71-79, 2001.

Prospects for gene therapy using haemopoietic stem cells.

Gene therapy has thus far promised much and delivered little. Much of this has been due to deficiencies in the reagents and methodologies employed in early clinical trials. Recent technological advances in vectors and haemopoietic stem cell manipulation, coupled with improved pre-clinical assays of gene transfer and expression in re-populating stem cells give cause for greater optimism. Here we review these advances and indicate areas requiring further development before clinical gene therapy in the haemopoietic system becomes a widely applicable treatment modality.