Clinical outcomes of triclosan-coated barbed suture in open hernia repair: a retrospective cohort study.

PURPOSE: We assessed clinical outcomes of patients undergoing open hernia repair using STRATAFIX™ Symmetric, a barbed triclosan-coated suture (TCS; Ethicon), versus conventional polydioxanone suture (PDS) for abdominal wall closure. METHODS: This single-center retrospective cohort study identified patients undergoing hernia repair. The site used PDS from 2013 to 2016 and switched exclusively to barbed TCS in 2017. Outcomes were assessed at 30, 60, and 90 days. Multivariate regression analyses and Cox proportional hazards models were used. RESULTS: Of 821 hernia repairs, 446 used barbed TCS and 375 used conventional PDS. Surgical site infections (SSIs) were significantly less frequent with barbed TCS (60 days, 5.9% vs. 11.4%; P = 0.0083; 90 days, 5.9% vs. 11.7%; P = 0.006) and this remained consistent after multivariate adjustment (60 days, OR [95% CI]: 0.5 [0.3-0.9]; 90 days, 0.5 [0.3-0.9]). Among patients with SSI, deep SSIs were less frequent with barbed TCS (60 days, 9.1% vs. 35.7%; P = 0.022; 90 days, 9.1% vs. 34.9%; P = 0.0252). Barbed TCS significantly reduced the risk of perioperative complications (HR [95% CI]: 0.5[0.3-0.8]; P = 0.0058). Hospital length of stay was 2.5 days shorter with barbed TCS (mean [95% CI]: 5.7[4.9-6.6] vs. 8.2[7.3-9.1] days; P < 0.0001). No differences in reoperation rate over time were observed by type of suture (HR[95% CI]:1.3 [0.5-3.4]; P = 0.4793). CONCLUSIONS: This study showed that patients who underwent open hernia repair appeared to recover equally well regardless of the suture type. In addition, the use of barbed TCS was associated with significantly reduced risk of perioperative complications and hospital length of stay.

Increased Perviousness on CT for Acute Ischemic Stroke is Associated with Fibrin/Platelet-Rich Clots.

BACKGROUND AND PURPOSE: Clot perviousness in acute ischemic stroke is a potential CT imaging biomarker for mechanical thrombectomy efficacy. We investigated the association among perviousness, clot cellular composition, and first-pass effect. MATERIALS AND METHODS: In 40 mechanical thrombectomy-treated cases of acute ischemic stroke, we calculated perviousness as the difference in clot density on CT angiography and noncontrast CT. We assessed the proportion of fibrin/platelet aggregates, red blood cells, and white blood cells on clot histopathology. We tested for linear correlation between histologic components and perviousness, differences in components between "high" and "low" pervious clots defined by median perviousness, and differences in perviousness/composition between cases that did and did not achieve a first-pass effect. RESULTS: Perviousness significantly positively and negatively correlated with the percentage of fibrin/platelet aggregates (P = .001) and the percentage of red blood cells (P = .001), respectively. Higher pervious clots had significantly greater fibrin/platelet aggregate content (P = .042). Cases that achieved a first-pass effect (n = 14) had lower perviousness, though not significantly (P = .055). The percentage of red blood cells was significantly higher (P = .028) and the percentage of fibrin/platelet aggregates was significantly lower (P = .016) in cases with a first-pass effect. There was no association between clot density on NCCT and clot composition or first-pass effect. Receiver operating characteristic analysis indicated that clot composition was the best predictor of first-pass effect (area under receiver operating characteristic curve: percentage of fibrin/platelet aggregates = 0.731, percentage of red blood cells = 0.706, perviousness = 0.668). CONCLUSIONS: Clot perviousness on CT is associated with a higher percentage of fibrin/platelet aggregate content. Histologic data and, to a lesser degree, perviousness may have value in predicting first-pass outcome. Imaging metrics that more strongly reflect clot biology than perviousness may be needed to predict a first-pass effect with high accuracy.

Correction to: Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to-severe acute pain after abdominal hysterectomy.

CORRECTION: Following publication of the original article [1], the authors reported that additional file 10 contained a typing error in the table "Percentage of responders (≥50% max TOTPAR) over two, four, six and eight hours (single-dose phase) (ITT Population)". The table is to be read as follows.

Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to-severe acute pain after abdominal hysterectomy.

BACKGROUND: Dexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics, which have different mechanisms of action for the treatment of moderate to severe acute pain. METHODS: Randomised, double-blind, parallel, placebo and active-controlled, single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents (dexketoprofen 25 mg and tramadol 100 mg) in moderate to severe acute pain after abdominal hysterectomy. Patients received seven consecutive doses of study drug within a 3-day period, each dose separated by an 8-hour interval. A placebo arm was included during the single-dose phase to validate the pain model. Efficacy assessments included pain intensity, pain relief, patient global evaluation and use of rescue medication. The primary endpoint was the mean sum of pain intensity differences over the first 8 h (SPID8). RESULTS: The efficacy analysis included 606 patients, with a mean age of 48 years (range 25-73). The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint (p <0.001). Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses. Most common adverse drug reactions (ADRs) were nausea (4.6%) and vomiting (2.3%). All other ADRs were experienced by less than 2% of patients. CONCLUSIONS: The study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain, as confirmed by the single-dose efficacy, repeated-dose sustained effect and good safety profile observed. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT number 2012-004545-32, registered 04 October 2012); Clinicaltrials.gov ( NCT01904149, registered 17 July 2013).

MicroRNA expression profiles of seminoma from paraffin-embedded formalin-fixed tissue.

In this study, we used microRNA (miRNA) microarrays in an unbiased screen for aberrantly expressed miRNAs in seminoma, a primitive type of germ cell tumor. Formalin-fixed and paraffin-embedded (FFPE) surgical samples from 11 cases of normal testicular tissue resected for nonneoplastic causes and from 11 cases of seminoma were assessed for miRNA expression. Normal testicular tissue and seminoma were paired by race. We found 112 miRNAs to be differentially expressed between seminoma and normal testicular tissue; 52 miRNAs were overexpressed, and 60, downregulated in seminoma. We did not observe significant differences between black and white populations in our race-paired study. The upregulation of the expression of hsa-mir-21, hsa-mir-372, hsa-mir-373, has-mir-221, and hsa-mir-222 was validated by reverse transcription and real-time PCR. Hsa-mir-372 was upregulated around 1,270-fold (95 % confidence interval (CI) 525.2-3,064.8; p = 8.1e-5 by Mann-Whitney U test). Hsa-mir-373 was upregulated around 1,530-fold (95 % CI 620.5-3,785.6; p = 8.0e-5 by Mann-Whitney U test), consistent with previous reports, indicating that the miRNAs in FFPE are well preserved, and FFPE can be a valuable source for the miRNA study of seminoma. In addition, expression of hsa-mir-21 (12.2-fold, 0.0095), hsa-mir-221 (3.8-fold, 0.014) and hsa-mir-222 (3.8-fold, 0.019) was found elevated in seminoma compared to normal testicular tissue.

Association of HLA polymorphisms with post-transplant lymphoproliferative disorder in solid-organ transplant recipients.

The association between HLA polymorphisms and PTLD was investigated in a case-control study, comparing 110 predominantly adult solid-organ transplant recipients who developed PTLD to 5601 who did not. Donor and recipient HLA were analyzed. We detected a significant association between recipient HLA-A26 and the development of PTLD (OR 2.74; p = 0.0007). In Caucasian recipients, both recipient and donor HLA-A26 were independently associated with development of PTLD (recipient A26 OR 2.99; p = 0.0004, donor A26 OR 2.81; p = 0.002). Analysis of HLA-A and -B haplotypes revealed that recipient HLA-A26, B38 haplotype was strongly correlated with a higher incidence of EBV-positive PTLD (OR 3.99; p = 0.001). The common ancestral haplotype HLA-A1, B8, DR3, when carried by the donor, was protective against PTLD (OR 0.41; p = 0.05). Several other HLA specificities demonstrated associations with clinical and pathological characteristics as well as survival. These findings demonstrate the importance of HLA polymorphisms in modulating the risk for PTLD, and may be useful in risk stratification and development of monitoring and prophylaxis strategies.

Strategies to enhance the efficacy of intravescical therapy for non-muscle invasive bladder cancer.

Transitional cell carcinoma (TCC) is the second most common urologic malignancy, and 70% of patients present with superficial, or non-muscle invasive disease (NMIBC). Bacillus Calmette-Guerin (BCG), currently the most effective intravesical agent at preventing disease recurrence, is the only therapy shown to inhibit disease progression. Unfortunately, approximately 20% of patients discontinue BCG due to local and systemic toxicity and more than 30% show evidence of recurrence; this has led to increased interest in alternate chemotherapeutic agents. Induction intravesical chemotherapy has shown comparable efficacy to BCG in select patients and the immediate perioperative instillation of chemotherapeutic agents has become standard of care. Clinical trial evidence demonstrating the efficacy of BCG plus interferon 2B, gemcitabine and anthracyclines (doxorubicin, epirubicin, valrubicin) in patients refractory or intolerant to BCG is accumulating. Phase I trials investigating alternative agents such as apaziquone, taxanes (docetaxel, paclitaxel), and suramin are reporting promising data. Current efforts are also being directed towards optimizing the administration of existing chemotherapeutic regimens, including the use of novel modalities including hyperthermia, photodynamic therapy, magnetically targeted carriers, and liposomes. Despite recent enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and select patients with naive T1 tumors and aggressive features. Our aim in this report is to provide a comprehensive review of contemporary intravesical therapy options for NMIBC with an emphasis on emerging agents and novel treatment modalities.

Resolution of nephrotic syndrome after successful bariatric surgery in patient with biopsy-proven FSGS.

The incidence of obesity-related nephropathy (ORG) is increasing with the growing incidence of obesity. ORG is associated with morbid obesity, proteinuria and renal biopsy findings of focal global and segmental glomerulosclerosis (FSGS), which can be associated with significant renal impairment. Weight reduction is associated with improvement of ORG, however, conservative measures aiming at long-term weight reduction are difficult to achieve. Bariatric surgery is the most effective way of achieving long-term weight reduction. We present a case of ORG with nephrotic-range proteinuria and FSGS on renal biopsy. Following bariatric surgery, patient achieved successful weight reduction with significant decrease in proteinuria and stabilization of renal function.

Activity of N-acetyl-beta-D-hexosaminidase (HEX) and its isoenzymes A and B in human milk during the first 3 months of breastfeeding.

PURPOSE: Milk contains free and bound oligo- and heteropolisaccharides, which protect newborns against pathogens and have nutritional value. N-acetyl-beta-D-hexosaminidase (HEX), the most active lysosomal exoglycosidase, modify and degrade oligo- and heteropolysaccharides. The objective of our study was to determine HEX activity and isoenzymes A and B in the progression of lactation. MATERIAL AND METHODS: Human milk samples were collected from 51 women on the 3rd, 21st and 100th day postpartum. Enzymatic activity was determined the Zwierz et al method modified by Marciniak et al. Protein and lactose concentrations were determined by a MilkoScan 4000 apparatus. RESULTS: The total HEX activity decreased by the 21st day in comparison to the 3rd day, and increased by the 100th day as compared to the 21st day. HEX A activity decreased by the 21st and the 100th day as compared to the 3rd day. HEX B activity decreased by 21st day and has the tendency to decrease by the 100th day as compared to the 3rd day. Protein concentration decreased and the lactose concentration increased in milk taken on the 21st day in comparison to concentration of protein and lactose on the 3rd day. HEX and its isoenzymes' activity significantly correlate with the progression of lactation. At the beginning of lactation, HEX A activity, which releases hexosamines from acidic oligosaccharides, dominates; later, HEX B releases hexosamines from neutral oligosaccharides. CONCLUSIONS: To better understand the degradation of human milk oligosaccharides, it would be useful to investigate and document their detailed structures and evaluate the activity of other exoglycosidases' activity in human breast milk over the course of lactation.

Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells.

Prolactin (PRL) stimulates the cytoskeletal re-organization and motility of breast cancer cells. During PRL receptor signaling, Vav2 becomes phosphorylated and activated, an event regulated by the serine/threonine kinase Nek3. Given the regulatory role of Vav2, the function of Nek3 in PRL-mediated motility and invasion was examined. Overexpression of Nek3 in Chinese hamster ovary transfectants potentiated cytoskeletal re-organization in response to PRL. In contrast, downregulation of Nek3 expression by small-interfering RNA (siRNA) attenuated PRL-mediated cytoskeletal reorganization, activation of GTPase Rac1, cell migration and invasion of T47D cells. In addition, PRL stimulation induced an interaction between Nek3 and paxillin and significantly increased paxillin serine phosphorylation, whereas Nek3 siRNA-transfected cells showed a marked reduction in paxillin phosphorylation. Analysis of breast tissue microarrays also demonstrated a significant up-regulation of Nek3 expression in malignant versus normal specimens. These data suggest that Nek3 contributes to PRL-mediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation.

Stabilization of prolactin receptor in breast cancer cells.

The role of the hormone prolactin (PRL) in the pathogenesis of breast cancer is mediated by its cognate receptor (PRLr). Ubiquitin-dependent degradation of the PRLr that negatively regulates PRL signaling is triggered by PRL-mediated phosphorylation of PRLr on Ser349 followed by the recruitment of the beta-transducin repeats-containing protein (beta-TrCP) ubiquitin-protein isopeptide ligase. We report here for the first time that interaction between PRLr and beta-TrCP is less efficient in human breast cancer cells than in non-tumorigenic human mammary epithelial cells. Furthermore, we demonstrate that both PRLr degradation and PRLr phosphorylation on Ser349 are impaired in breast tumor cells and tissues, an observation that directly correlates with enhanced expression of the PRLr in malignant breast epithelium. These findings represent a novel mechanism through which altered PRLr stability may directly influence the pathogenesis of breast cancer.

Annexin-V imaging for noninvasive detection of cardiac allograft rejection.

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

Predicting prostate specific antigen outcome preoperatively in the prostate specific antigen era.

PURPOSE: We evaluated the ability of previously defined risk groups to predict prostate specific antigen (PSA) outcome 10 years after radical prostatectomy in patients diagnosed with clinically localized prostate cancer during the PSA era. MATERIALS AND METHODS: Between 1989 and 2000, 2,127 men with clinically localized prostate cancer underwent radical prostatectomy, including 1,027 at Hospital of the University of Pennsylvania (study cohort) and 1,100 at Brigham and Women's Hospital (validation cohort). Cox regression analysis was done to calculate the relative risk of PSA failure with the 95% confidence interval (CI) in patients at intermediate and high versus low risk. The Kaplan-Meier actuarial method was used to estimate PSA outcome 10 years after radical prostatectomy. RESULTS: Compared with low risk patients (stages T1c to 2a disease, PSA 10 ng./ml. or less and Gleason score 6 or less) the relative risk of PSA failure in those at intermediate (stage T2b disease or PSA greater than 10 to 20 ng./ml. or less, or Gleason score 7) and high (stage T2c disease, or PSA greater than 20 ng./ml. or Gleason score 8 or greater) risk was 3.8 (95% CI 2.6 to 5.7) and 9.6 (95% CI 6.6 to 13.9) in the study cohort, and 3.3 (95% CI 2.3 to 4.8) and 6.3 (95% CI 4.3 to 9.4) in the validation cohort. The 10-year PSA failure-free survival rate in the 1,020 patients in the low, 693 in the intermediate and 414 in the high risk groups was 83%, 46% and 29%, respectively (p <0.0001). CONCLUSIONS: Based on 10-year actuarial estimates of PSA outcome after radical prostatectomy 3 groups of patients were identified using preoperative PSA, biopsy Gleason score and 1992 clinical T category.

Successful reversal of severe refractory cardiac allograft rejection by photopheresis.

We treated 4 patients with refractory International Society of Heart and Lung Transplantation Grades IIIA to IV cardiac allograft rejection with extracorporeal photopheresis. Following treatment on 2 consecutive days, 3 patients demonstrated complete histologic reversal of rejection. The remaining patient improved more gradually, but manifested complete cessation of rejection following three 2-day treatments. We conclude that photopheresis is a safe and effective modality for the treatment of severe refractory cardiac allograft rejection and that these results support the use of photopheresis in this clinical setting.

Estimating the impact on prostate cancer mortality of incorporating prostate-specific antigen testing into screening.

OBJECTIVES: Whether early detection using prostate-specific antigen (PSA) and digital rectal examination (DRE) compared with DRE alone will reduce prostate cancer mortality awaits the results of ongoing prospective randomized trials. However, the impact that early detection could have on prostate cancer-specific survival can be estimated by assuming that PSA failure after radical prostatectomy (RP) will translate into death from prostate cancer. METHODS: The study population consisted of 1274 men with clinically localized prostate cancer who underwent RP in Boston, Massachusetts or Philadelphia, Pennsylvania between 1989 and 2000 and had a preoperative PSA level greater than 4 but not more than 10 ng/mL. The primary endpoint was actuarial freedom from PSA failure (defined as PSA outcome). RESULTS: The relative risk of PSA failure after RP for patients diagnosed with a PSA of greater than 4 to 5, 5 to 6, 6 to 7, or 7 to 8 ng/mL compared with greater than 8 up to 10 ng/mL was 0.3 (95% confidence interval [CI] 0.2 to 0.5), 0.5 (95% CI 0.4 to 0.8), 0.6 (95% CI 0.4 to 0.9), or 0.9 (95% CI 0.6 to 1.3), respectively. On the basis of the estimates of the 5-year PSA outcome, patients with a biopsy Gleason score of 5 or 6 (781 of 1274; 61%) consistently benefited from RP performed when the PSA at diagnosis was greater than 4 to 7 ng/mL compared with greater than 8 to 10 ng/mL (93% versus 78%, P <0.0001). A benefit to early detection was not found for the vast majority (266 of 312; 88%) of patients who had a biopsy Gleason score of 7 or higher. CONCLUSIONS: Early detection using both PSA and DRE-based screening may benefit men who present with biopsy Gleason score 5 or 6 prostate cancer and a PSA level greater than 4 to 7 ng/mL compared with greater than 8 up to 10 ng/mL. This finding awaits validation from ongoing prospective randomized trials.

Metachronous Epstein-Barr virus-related smooth muscle tumors in a child after heart transplantation: case report and review of the literature.

Soft tissue tumors are uncommon manifestations of Epstein-Barr virus (EBV) infection in patients who have had transplants. The authors report 2 metachronous EBV-containing smooth muscle tumors in a child who had a heart transplant, and review the literature on posttransplant soft tissue tumors.

Emergent lung retransplantation after discovery of two primary malignancies in the donor.

A 50-year-old woman underwent single lung transplantation for advanced chronic obstructive pulmonary disease. Shortly after the procedure, it was discovered that the donor suffered from both a renal cell carcinoma and a spindle-cell sarcoma of the ascending aorta, which had metastasized to the spleen. The patient was emergently listed for a retransplantation and underwent bilateral lung transplantation after a new donor became available 4 days after the initial transplantation procedure. After 24 months, the patient is without evidence of malignancy. This case illustrates the role of immediate retransplantation for patients who have inadvertently received thoracic organs from donors harboring occult malignancies.

Post-transplant lymphoproliferative disease in children.

Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue-proven PTLD 1-60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease > or = 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV-related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B-cell PTLD, including those with negative serology.