Jack W. Rostas

Long-term outcomes with the use of bioprosthetic plugs for the management of complex anal fistulas.

PURPOSE: This study was undertaken to determine the long-term outcomes of patients whose anal fistulas were managed by use of bioprosthetic plugs. METHOD: A retrospective analysis was performed of all patients whose anal fistula was managed by use of a bioprosthetic plug between May 2005 and September 2006, who had a minimum of 1 year of follow-up since their last treatment. Patients whose fistulas were clinically healed were offered MRI to confirm healing of the fistula. RESULTS: The bioprosthetic fistula plug was used to treat an anal fistula in 63 patients with clinical healing of the fistula in 51 (81%). Multivariate analysis showed that tobacco smoking, posterior fistula, and history of previous failure of the bioprosthetic plug was predictive of failure of the bioprosthetic plug. Eight patients with clinical healing after a minimum of 1 year since their last treatment underwent MRI. No evidence of residual fistula tract or fluid in the area of the previous fistula was found in 6 (75%) of these patients. CONCLUSION: Bioprosthetic plugs are effective for the long-term closure of complex fistulas-in-ano. Randomized clinical trials comparing bioprosthetic plugs with other sphincter-preserving methods for fistula management need to be conducted to further determine the role of bioprosthetics in the management of anal fistulas.

microRNA-29 negatively regulates EMT regulator N-myc interactor in breast cancer

BackgroundN-Myc Interactor is an inducible protein whose expression is compromised in advanced stage breast cancer. Downregulation of NMI, a gatekeeper of epithelial phenotype, in breast tumors promotes mesenchymal, invasive and metastatic phenotype of the cancer cells. Thus the mechanisms that regulate expression of NMI are of potential interest for understanding the etiology of breast tumor progression and metastasis.MethodWeb based prediction algorithms were used to identify miRNAs that potentially target the NMI transcript. Luciferase reporter assays and western blot analysis were used to confirm the ability of miR-29 to target NMI. Quantitive-RT-PCRs were used to examine levels of miR29 and NMI from cell line and patient specimen derived RNA. The functional impact of miR-29 on EMT phenotype was evaluated using transwell migration as well as monitoring 3D matrigel growth morphology. Anti-miRs were used to examine effects of reducing miR-29 levels from cells. Western blots were used to examine changes in GSK3β phosphorylation status. The impact on molecular attributes of EMT was evaluated using immunocytochemistry, qRT-PCRs as well as Western blot analyses.ResultsInvasive, mesenchymal-like breast cancer cell lines showed increased levels of miR-29. Introduction of miR-29 into breast cancer cells (with robust level of NMI) resulted in decreased NMI expression and increased invasion, whereas treatment of cells with high miR-29 and low NMI levels with miR-29 antagonists increased NMI expression and decreased invasion. Assessment of 2D and 3D growth morphologies revealed an EMT promoting effect of miR-29. Analysis of mRNA of NMI and miR-29 from patient derived breast cancer tumors showed a strong, inverse relationship between the expression of NMI and the miR-29. Our studies also revealed that in the absence of NMI, miR-29 expression is upregulated due to unrestricted Wnt/β-catenin signaling resulting from inactivation of GSK3β.ConclusionAberrant miR-29 expression may account for reduced NMI expression in breast tumors and mesenchymal phenotype of cancer cells that promotes invasive growth. Reduction in NMI levels has a feed-forward impact on miR-29 levels.

Clinical clearance of the cervical spine in patients with distracting injuries: It is time to dispel the myth

OBJECTIVE The purpose of this study was to prospectively assess the sensitivity and efficacy of clinical examination for screening of cervical spine (c-spine) injury in awake and alert blunt trauma patients with concomitant “distracting injuries.” METHODS During the 24-month period from December 2009 to December 2011, all blunt trauma patients older than 13 years were prospectively evaluated with a standard cervical spine examination protocol by the trauma surgery team at a Level 1 trauma center. Awake and alert patients with a Glasgow Coma Score (GCS) ≥14 underwent clinical examination of the cervical spine. Clinical examination was performed regardless of “distracting injuries.” Patients without complaints of pain or tenderness on physical exam had their cervical collar removed, and the c-spine was considered clinically cleared of injury. All awake and alert patients with “distracting injuries,” including those clinically cleared and those with complaints of c-spine pain or tenderness underwent computerized tomographic (CT) scanning of the entire c-spine. “Distracting injuries” were categorized into three anatomic regions: head injuries, torso injuries and long bone fractures. Patients with minor distracting injuries were not considered to have a “distracting injury.” RESULTS During the 24-month study period, 761 blunt trauma patients with GCS ≥14 and at least one “distracting injury” had been entered into the study protocol. Two-hundred ninety-six (39%) of the patients with “distracting injuries” had a positive c-spine clinical examination, 85 (29%) of whom were diagnosed with c-spine injury. Four hundred sixty-four (61%) of the patients with “distracting injuries” were initially clinically cleared, with one patient (0.2%) diagnosed with a c-spine injury. This yielded an overall sensitivity of 99% (85/86) and negative predictive value greater than 99% (463/464) for cervical spine clinical examination in awake and alert blunt trauma patients with “distracting injuries.” CONCLUSIONS In the awake and alert blunt trauma patient with “distracting injuries,” clinical examination is a sensitive screening method for cervical spine injury. Radiological assessment is unnecessary for safe clearance of the asymptomatic cervical spine in awake and alert blunt trauma patients with “distracting injuries.” These findings suggest the concept of “distracting injury” in the context of cervical spine clinical examination is invalid. Expanding the utility of cervical spine clinical examination to patients with “distracting injuries” allows for significant reduction of both healthcare cost and radiation exposure. LEVEL OF EVIDENCE Diagnostic study, level I.

Outcomes using a bioprosthetic mesh at the time of permanent stoma creation in preventing a parastomal hernia: a value analysis

PURPOSE/METHODS A retrospective review of the medical records of all patients who had a prosthetic placed at the time of stoma creation for the prevention of a parastomal hernia was performed. The purpose of this study was to evaluate the safety, efficacy, and cost-effectiveness of bioprosthetics. RESULTS A bioprosthetic was used in 16 patients to prevent the occurrence of a parastomal hernia. The median follow-up was 38 months. There were no mesh-related complications, and no parastomal hernias occurred. On value analysis, to be cost-effective, the percentage of patients who would have subsequently needed surgical repair of a parastomal hernia would have to be in excess of 39% or the bioprosthetic would have to cost less than

Loss of N-Myc interactor promotes epithelial-mesenchymal transition by activation of TGF-β/SMAD signaling.

2,267 to

Helmet use is associated with a decrease in intracranial hemorrhage following all-terrain vehicle crashes

4,312. CONCLUSIONS These data show the safety and efficacy of using a bioprosthetic at the time of permanent stoma creation in preventing a parastomal hernia and defines the parameters for this approach to be cost-effective.

Micro-RNA-632 downregulates DNAJB6 in breast cancer

Epithelial–mesenchymal transition is one of the critical cellular programs that facilitate the progression of breast cancer to an invasive disease. We have observed that the expression of N-myc interactor (NMI) decreases significantly during progression of breast cancer, specifically in invasive and metastatic stages. Recapitulation of this loss in breast cell lines with epithelial morphology (MCF10A (non-tumorigenic) and T47D (tumorigenic)) by silencing NMI expression causes mesenchymal-like morphological changes in 3D growth, accompanied by upregulation of SLUG and ZEB2 and increased invasive properties. Conversely, we found that restoring NMI expression attenuated the mesenchymal attributes of metastatic breast cancer cells, accompanied by distinctly circumscribed 3D growth with basement membrane deposition and decreased invasion. Further investigations into the downstream signaling modulated by NMI revealed that NMI expression negatively regulates SMAD signaling, which is a key regulator of cellular plasticity. We demonstrate that NMI blocks TGF-β/SMAD signaling via upregulation of SMAD7, a negative feedback regulator of the pathway. We also provide evidence that NMI activates STAT signaling, which negatively modulates TGF-β/SMAD signaling. Taken together, our findings suggest that loss of NMI during breast cancer progression could be one of the driving factors that enhance the invasive ability of breast cancer by aberrant activation of TGF-β/SMAD signaling.

Rib fractures and their association With solid organ injury: higher rib fractures have greater significance for solid organ injury screening

BACKGROUND With the recent increase in size and horsepower of all-terrain vehicles (ATVs), it is imperative that preventable injuries be identified to protect the large population using ATVs. Currently, many states have no laws regulating ATV or helmet use. By identifying preventable injuries, the legislature can design appropriate laws to protect both children and adults. METHODS A retrospective review of all patients with ATV injuries presenting between the years 2005 and 2010 was conducted. The data were grouped in several ways for analysis. This included age less than 9 years, weight less than 30 kg, crash at night, substance abuse, and presence of a helmet. RESULTS There were 481 patients included in the study. Only 28 (8%) were using a helmet at the time of the crash. Helmet use was associated with less intracranial hemorrhage (3% vs. 22%, p = 0.01) and a decreased incidence of loss of consciousness (14% vs. 35%, p = 0.01). Patients testing positive for alcohol intoxication with or without drugs were significantly more likely to have intracranial hemorrhage, to crash at night, to have facial fracture, to have rib fracture, to arrive intubated, and to have a higher Injury Severity Score (ISS) (p < 0.01 for all). CONCLUSION With the recent increase in size and horsepower of ATVs, it is imperative that preventable injuries be identified to help protect a growing population of ATV operators. This study reveals a high rate of intracranial hemorrhage following an ATV crash in operators who do not use a helmet. Legislative efforts to implement strict helmet laws for ATV operators may be warranted. LEVEL OF EVIDENCE Prognostic study, level III.

The validity of abdominal examination in blunt trauma patients with distracting injuries.

DNAJB6 is a constitutively expressed member of the HSP40 family. It has been described as a negative regulator of breast tumor progression and a regulator of epithelial phenotype. Expression of DNAJB6 is reported to be compromised with tumor progression. However, factors responsible for its downregulation are still undefined. We used a knowledge-based screen for identifying miRNAs capable of targeting DNAJB6. In this work, we present our findings that hsa-miR-632 (miR-632) targets the coding region of DNAJB6. Invasive and metastatic breast cancer cells express high levels of miR-632 compared with mammary epithelial cells. Analysis of RNA from breast tumor specimens reveals inverse expression patterns of DNAJB6 transcript and miR-632. In response to exogenous miR-632 expression, DNAJB6 protein levels are downregulated and the resultant cell population shows significantly increased invasive ability. Silencing endogenous miR-632 abrogates invasive ability of breast cancer cells and promotes epithelial like characteristics noted by E-cadherin expression with concomitant decrease in mesenchymal markers such as Zeb2 and Slug. Thus, miR-632 is a potentially important epigenetic regulator of DNAJB6, which contributes to the downregulation of DNAJB6 and plays a supportive role in malignant progression.

Improved rate of pancreatic fistula after distal pancreatectomy: parenchymal division with the use of saline-coupled radiofrequency ablation

BACKGROUND The purpose of this study was to identify patients with rib injuries who were at risk for solid organ injury. METHODS A retrospective chart review was performed of all blunt trauma patients with rib fractures during the period from July 2007 to July 2012. Data were analyzed for association of rib fractures and solid organ injury. RESULTS In all, 1,103 rib fracture patients were identified; 142 patients had liver injuries with 109 (77%) associated right rib fractures. Right-sided rib fractures with highest sensitivity for liver injury were middle rib segment (5 to 8) and lower segment (9 to 12) with liver injury sensitivities of 68% and 43%, respectively (P < .001); 151 patients had spleen injuries with 119 (79%) associated left rib fractures. Left middle segment rib fractures and lower segment rib fractures had sensitivities of 80% and 63% for splenic injury, respectively (P < .003). CONCLUSIONS Rib fractures higher in the thoracic cage have significant association with solid organ injury. Using rib fractures from middle plus lower segments as indication for abdominal screening will significantly improve rib fracture sensitivity for identification of solid organ injury.