O46 SUTURABLE MESH IMPROVES OUTCOMES FOR LAPAROTOMY CLOSURE IN COMPARISON TO POLYPROPYLENE SUTURE IN A REALISTIC PORCINE MODEL

Abstract Aim Laparotomy closures fail due to suture pull-through. We hypothesize that a novel suturable mesh device may limit pull-through via mechanisms of force distribution at the suture-tissue interface and fibrous encapsulation of the device filaments. This new tissue approximation device may lead to improved outcomes for laparotomy closure. Material and Methods Fifteen domestic swine 74 kg in size were randomly allocated to three groups for epigastric laparotomy closure with either size 0 suturable mesh, number 1 suturable mesh, or number 1 polypropylene. All three devices were placed in running fashion with 1 cm bites and 1 cm travels. Primary endpoints were hernia formation at 13 weeks and a semiquantitative analysis of the histological tissue response. Secondary endpoints included adhesions, surgical site occurrence (SSO), and documentation of “loose sutures”. Results There were numerically fewer hernias in the number 1 suturable mesh group. Nine of the 10 suturable mesh devices were well encapsulated within the tissues and could not be pulled away, while 4 of the 5 polypropylene sutures were loose. Adhesions were least for number 1 suturable mesh. Histologically, the suturable mesh implanted devices showed good fibrovascular ingrowth and were judged to be “non-irritants”. The soft tissue response was statistically greater (p = .006) for the number 1 suturable mesh than for the number 1 polypropylene. Conclusions The mechanism of how meshes support closure sites is clearly demonstrated with this model. Suturable mesh has the potential to change surgical algorithms for abdominal wall closure.

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A phase Ib study of atezolizumab (atezo) alone or in combination with lenalidomide or pomalidomide and/or daratumumab in patients (pts) with multiple myeloma (MM).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.tps8053 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. TPS8053-TPS8053 ◽

Cited By ~ 1

Author(s):

Hearn J. Cho ◽

Craig Cole ◽

Thomas G. Martin ◽

Jeffrey A. Zonder ◽

Joseph W. Fay ◽

...

Keyword(s):

Immune Escape ◽

Treatment Options ◽

Single Agent ◽

Proteasome Inhibitors ◽

Additional Treatment ◽

Immunomodulatory Activity ◽

Primary Endpoints ◽

Improved Outcomes ◽

Secondary Endpoints ◽

Ecog Ps

TPS8053 Background: The advent of proteasome inhibitors and immunomodulatory drugs (IMiDs) have significantly improved outcomes in MM, and the first monoclonal antibodies for MM have been recently approved (daratumumab, elotuzumab). Despite novel therapies and improved disease management, MM is still considered incurable and most pts relapse, confirming the need for additional treatment options. MM cells express PD-L1, with higher levels observed after relapse and with advanced disease. Additionally, PD-L1–expressing immune cells in the microenvironment promote MM cell survival and potential immune escape. However, anti–PD-1 monotherapy did not result in objective responses in the MM cohort of a Ph I study, suggesting that MM pts need combination therapy. Daratumumab has activity as a single agent, as well as in combination with IMiDs plus dexamethasone and bortezomib plus dexamethasone in R/R MM. Immunomodulatory activity for daratumumab has also been reported. Thus, disruption of the PD-L1/PD-1 pathway may be additive or synergistic. The safety and efficacy of atezo (anti–PD-L1) alone or with lenalidomide or pomalidomide and/or daratumumab will be evaluated in a Ph Ib study of MM pts. NCT02431208. Methods: R/R MM pts with ≤ 3 prior therapies will be enrolled in Cohorts A (atezo), B (atezo + lenalidomide), D (atezo + daratumumab) and E (atezo + daratumumab + lenalidomide); MM pts with measurable disease after ASCT (Cohort C: atezo) or ≥ 3 prior therapies (Cohort F: atezo + daratumumab + pomalidomide) will also be enrolled. Cohorts B, D, E and F include a safety run-in (D) or dose escalation phase (B, E, F) and an expansion. Lenalidomide and pomalidomide will be dose escalated and the MTD evaluated in expansion phases. Atezo will be given at 1200 mg IV (A, B, C) or 840 mg IV (D, E, F); pts will get daratumumab at 16 mg/kg IV (D, E, F). All pts will be ECOG PS ≤ 2. Primary endpoints are ORR and the RP2D of lenalidomide and pomalidomide with atezo and daratumumab and the RP2D of lenalidomide with atezo. DOR and PFS are secondary endpoints; safety, PK and the relationship between biomarkers and other endpoints, including efficacy, will be assessed. Pts will be enrolled at 19 US sites. Clinical trial information: NCT02431208.

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Comparing the Responses of Osseous Versus Soft-Tissue Metastases of Renal Cell Carcinoma to Receptor Tyrosine Kinase Inhibitors and Immunotherapy

Kidney Cancer ◽

10.3233/kca-200094 ◽

2020 ◽

Vol 4 (3) ◽

pp. 151-158

Author(s):

Katherine Yuxi Tai ◽

Jad M. El Abiad ◽

Carol D. Morris ◽

Mark Christopher Markowski ◽

Adam S. Levin

Keyword(s):

Renal Cell Carcinoma ◽

Soft Tissue ◽

Cell Carcinoma ◽

Receptor Tyrosine Kinase ◽

Renal Cell ◽

Kinase Inhibitors ◽

Tissue Response ◽

Bone Response ◽

Soft Tissue Response ◽

Receptor Tyrosine Kinase Inhibitors

BACKGROUND: Checkpoint inhibitors and receptor tyrosine kinase inhibitors (RTKIs) have changed the standard of care for metastatic renal cell carcinoma (mRCC). Anecdotal evidence suggests these therapies may be less effective for treating bone than soft-tissue metastases. PURPOSE: We performed a retrospective review evaluating the relative clinical responses in soft-tissue and bone metastases in patients undergoing therapy using RTKIs and anti-programmed death-1 (PD-1) agents for mRCC. METHODS: Of the 2,212 patients in our institutional cancer registry with renal cell carcinoma (1997–2017), 68 (82 disease courses) were identified with measurable bone and soft-tissue metastases treated with RTKIs and/or PD-1s. Extent of metastasis was quantified at the time of therapy initiation (baseline) and at 3 months, 6 months, and 1 year. Changes in disease status were categorized as complete response, partial response, stable, mixed, or progression of disease according to RECIST v1.1 and MD Anderson criteria. These categories were further organized into “response to treatment” or “evidence of progression” to generate a generalized linear effects model with soft-tissue response as the independent variable and bone response as the dependent variable. Alpha = 0.05. RESULTS: Soft-tissue response correlated with bone response at 3 months (76 disease courses, p = 0.005) and 6 months (48 disease courses, p = 0.017). Of the patients with controlled soft-tissue disease, only 14 (19%) and 15 (32%) had progression in bone at 3 and 6 months, respectively. CONCLUSION: Contrary to anecdotal reports, osseous metastases do not appear to respond worse than soft-tissue metastases to treatment with these agents.

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Activity Tracking After Surgery: Does It Correlate With Postoperative Complications?

The American Surgeon ◽

10.1177/0003134820988818 ◽

2021 ◽

pp. 000313482098881

Author(s):

Yehonatan Nevo ◽

Tali Shaltiel ◽

Naama Constantini ◽

Danny Rosin ◽

Mordechai Gutman ◽

...

Keyword(s):

Postoperative Complications ◽

Enhanced Recovery ◽

Length Of Hospital Stay ◽

Inverse Correlation ◽

Complication Rates ◽

Activity Tracking ◽

Primary Endpoints ◽

Specific Complication ◽

Secondary Endpoints ◽

Enhanced Recovery Programs

Background Postoperative ambulation is an important tenet in enhanced recovery programs. We quantitatively assessed the correlation of decreased postoperative ambulation with postoperative complications and delays in gastrointestinal function. Methods Patients undergoing major abdominal surgery were fitted with digital ankle pedometers yielding continuous measurements of their ambulation. Primary endpoints were the overall and system-specific complication rates, with secondary endpoints being the time to first passage of flatus and stool, the length of hospital stay, and the rate of readmission. Results 100 patients were enrolled. We found a significant, independent inverse correlation between the number of steps on the first and second postoperative days (POD1/2) and the incidence of complications as well as the recovery of GI function and the likelihood of readmission ( P < .05). POD2 step count was an independent risk factor for severe complications ( P = .026). Discussion Digitally quantified ambulation data may be a prognostic biomarker for the likelihood of severe postoperative complications.

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Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study

Cephalalgia ◽

10.1177/0333102421989232 ◽

2021 ◽

Vol 41 (3) ◽

pp. 294-304 ◽

Cited By ~ 2

Author(s):

Messoud Ashina ◽

Uwe Reuter ◽

Timothy Smith ◽

Judith Krikke-Workel ◽

Suzanne R Klise ◽

...

Keyword(s):

Controlled Trial ◽

Study Drug ◽

Statistical Testing ◽

Control Group ◽

Double Blind ◽

Treatment Groups ◽

Primary Endpoints ◽

Registration Number ◽

Secondary Endpoints ◽

Common Teaes

Background We present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks. Methods Patients were randomized 1:1:1 to one of three treatment groups – lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack. The primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in ≥2/3 attacks. Secondary endpoints included pain relief, sustained pain freedom and disability freedom. Statistical testing used a logistic regression model and graphical methodology to control for multiplicity. Results Overall, 1471 patients treated ≥1 migraine attack with the study drug. Both primary endpoints were met for lasmiditan 100 mg and 200 mg ( p < 0.001). All gated secondary endpoints were met. The incidence of treatment-emergent adverse events (TEAEs) was highest during the first attack. The most common TEAEs with lasmiditan were dizziness, paresthesia, fatigue, and nausea; these were generally mild or moderate in severity. Conclusions These results confirm the early and sustained efficacy of lasmiditan 100 mg and 200 mg and demonstrate consistency of response across multiple attacks. Trial Registration Number: NCT03670810

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Soft Tissue Response After Chin Advancement Using Two Different Genioplasty Techniques

Journal of Craniofacial Surgery ◽

10.1097/scs.0000000000000863 ◽

2014 ◽

Vol 25 (4) ◽

pp. 1383-1388 ◽

Cited By ~ 6

Author(s):

Sameh Ahemd Seifeldin ◽

Maha Shawky ◽

Saleem M. Hicham Nouman

Keyword(s):

Soft Tissue ◽

Tissue Response ◽

Soft Tissue Response

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SARS-COV-2 colonizes coronary thrombus and impairs heart microcirculation bed in asymptomatic SARS-CoV-2 positive subjects with acute myocardial infarction

Critical Care ◽

10.1186/s13054-021-03643-0 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Raffaele Marfella ◽

Pasquale Paolisso ◽

Celestino Sardu ◽

Luciana Palomba ◽

Nunzia D’Onofrio ◽

...

Keyword(s):

Myocardial Infarction ◽

Viral Load ◽

Coronary Intervention ◽

Cardiovascular Death ◽

Left Ventricular ◽

Major Adverse Cardiovascular Events ◽

Grade 5 ◽

Primary Endpoints ◽

Load Effects ◽

Secondary Endpoints

Abstract Background The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons has been equal to that of symptomatic patients. On the other hand, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. Therefore, we evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial blush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. Methods This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization. Results In the study population, ASAP vs. SANE showed a significant greater use of GP IIb/IIIa inhibitors and of heparin (p < 0.05), and a higher thrombus grade 5 and thrombus dimensions (p < 0.05). Interestingly, ASAP vs. SANE patients had lower MBG and left ventricular function (p < 0.001), and 39 (84.9%) of ASAP patients had thrombus specimens positive for SARS-COV-2. After PPCI, a MBG 2–3 was present in only 26.1% of ASAP vs. 97.7% of SANE STEMI patients (p < 0.001). Notably, death and nonfatal AMI were higher in ASAP vs. SANE patients (p < 0.05). Finally, in ASAP STEMI patients the thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (p < 0.005). Thus, multiple logistic regression analyses evidenced that thrombus SARS-CoV-2 infection and dimension were significant predictors of poorer MBG in STEMI patients. Intriguingly, in ASAP patients the female vs. male had higher thrombus viral load (15.53 ± 4.5 vs. 30.25 ± 5.51 CT; p < 0.001), and thrombus dimension (4.62 ± 0.44 vs 4.00 ± 1.28 mm2; p < 0.001). ASAP vs. SANE patients had a significantly lower in-hospital survival for MACE following PPCI (p < 0.001). Conclusions In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG. These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.

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Abstract 15116: The Prognostic Value of Left Ventricular Mechanical Dyssynchrony in Patients With Idiopathic Dilated Cardiomyopathy

Circulation ◽

10.1161/circ.142.suppl_3.15116 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Yangjie Li ◽

Yuanwei Xu ◽

Siqi Tang ◽

Xiaoyue Zhou ◽

Yucheng Chen

Keyword(s):

Dilated Cardiomyopathy ◽

Primary Endpoint ◽

Prognostic Value ◽

Mechanical Dyssynchrony ◽

Idiopathic Dilated Cardiomyopathy ◽

Ratio Estimate ◽

Apical Level ◽

Primary Endpoints ◽

Secondary Endpoints ◽

Cmr Imaging

Backgrounds: The mechanical dyssynchrony has been commonly observed in idiopathic dilated cardiomyopathy (DCM) patients, and several cardiac magnetic resonance (CMR) imaging techniques were used to evaluate the mechanical dyssynchrony. Standard deviation of time-to-peak (T2Psd) and uniformity ratio estimate (URE) indices are two widely used parameters to reflect the incoordinate movement of the left ventricle. However, the prognostic value of mechanical dyssynchrony in DCM patients is not clear. Methods and Results: We prospectively enrolled 402 DCM patients undergoing CMR imaging between Jun 2012 to Sep 2018. Mechanical dyssynchrony was measured as T2Psd and URE indices by CMR deformable registration algorithm (DRA) analysis. The primary endpoint was defined as all-cause mortality and heart transplantation, and the secondary endpoint was a combination of primary endpoint, aborted sudden cardiac death, and heart failure readmission. Univariate and multivariate Cox regression analyses were performed to identify the association between variables and outcome. Survival curves were obtained by Kaplan-Meier survival analysis and compared by log-rank test. During a median follow-up of 25.1 months (IQR: 16.2-41.6), there were 57 patients reached primary endpoints, and secondary endpoints occurred in 132 patients. Circumferential uniformity ratio estimate (CURE) at basal, mid and apical level, radial uniformity ratio estimate (RURE)at mid and apical level and longitudinal uniformity ratio estimate (LURE) were significantly worse in patients with primary endpoint compared to patients without primary endpoint. While no significant differences were observed regarding the T2Psd value between patients with and without primary endpoints. In multivariate analysis, CURE at apical level was independently associated with primary endpoints (HR 0.214, P=0.005) and secondary endpoints (HR 0.402, P=0.018). Furthermore, among patients with LVEF <35% or presence of LGE, those with decreased CURE at apical level (<0.917) showed a significantly higher rate of adverse outcome. Conclusion: The CURE at apical level is an independent predictor of adverse cardiac events in DCM patients. Compared with T2Psd, URE index is a better predictor of adverse events.

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Procalcitonin and Interleukin-6 Levels: Are They Useful Biomarkers in Cardiac Surgery Patients?

Blood Purification ◽

10.1159/000454672 ◽

2017 ◽

Vol 43 (4) ◽

pp. 290-297 ◽

Cited By ~ 4

Author(s):

Anna Clementi ◽

Alessandra Brocca ◽

Grazia Maria Virzì ◽

Massimo de Cal ◽

Davide Giavarina ◽

...

Keyword(s):

Intensive Care Unit ◽

Cardiac Surgery ◽

Interleukin 6 ◽

Independent Predictor ◽

Chronic Renal Disease ◽

Kidney Injury ◽

Renal Outcome ◽

Primary Endpoints ◽

Secondary Endpoints ◽

Overall Mortality

Background/Aim: Cardiac surgery-associated acute kidney injury is an independent predictor of chronic renal disease and mortality. The scope of this study was to determine the utility of procalcitonin (PCT) and plasma interleukin-6 (IL-6) levels in predicting renal outcome and mortality in these patients. Methods: PCT and plasma IL-6 levels of 122 cardiac surgery patients were measured at 48 h after the surgical procedure. Primary endpoints were adverse renal outcome and mortality. Secondary endpoints were length of stay, bleeding, and number of transfusions. Results: PCT was found to be a better predictor of adverse renal outcome than IL-6. IL-6 seemed to be a better predictor of both 30-day and overall mortality than PCT. Neither PCT nor IL-6 levels were found to be good predictors of intensive care unit stay and bleeding. Conclusion: PCT may be considered a good predictor of adverse renal outcome in cardiac surgery patients, whereas IL-6 seems to possess a good predictive value for mortality in this population of patients.

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