IU Indianapolis ScholarWorks :: Browsing by Author "Timsina, Lava"

Browsing by Author "Timsina, Lava"

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2020 Women in Thoracic Surgery update on the status of women in cardiothoracic surgery
(Elsevier, 2020) Ceppa, DuyKhanh P.; Antonoff, Mara B.; Tong, Betty C.; Timsina, Lava; Ikonomidis, John S.; Worrell, Stephanie G.; Stephens, Elizabeth H.; Gillaspie, Erin A.; Schumacher, Lana; Molena, Daniela; Kane, Lauren C.; Blackmon, Shanda; Donington, Jessica S.; Surgery, School of Medicine
Background Women in Thoracic Surgery (WTS) has previously reported on the status of women in cardiothoracic (CT) surgery. We sought to provide a 10-year update on women in CT. Methods An anonymous REDCap survey link was emailed to female diplomats of the ABTS. Survey questions queried respondents regarding demographics, training, accolades, practice details, and career satisfaction. The survey link was open for 30 days. Results were compared to the 2019 Society of Thoracic Surgeons work force survey. Descriptive analyses were performed using frequency and proportions. Comparisons were performed using Student’s t-tests, Fisher exact and chi-squared tests. Results Of 354 female diplomats, 309 were contacted and 176 (57%) responded. The majority of respondents were age 36-50 (59%), Caucasian (67.4%), and graduated from traditional-track programs (91.4%). Most respondents reported practicing in an urban (64%) and academic setting (73.1%). 36.4% and 23.9% reported a general thoracic and adult cardiac practice (22.7% mixed practice, 9.6% congenital). Fifty percent of respondents reported salaries between $400,000-700,000 annually; 37.7% reported salaries <90% of their male colleagues. 21.6% of respondents in academia are full professor; 53.4% report having a leadership role. While 74.1% would pursue a career in CT again, only 27.3% agreed that CT surgery is a healthy and positive environment for women. Conclusions The number of women in CT surgery has steadily increased. While women are rising in academic rank and into leadership positions, salary disparities and the CT surgery work environment remain important issues in achieving a diverse work force.
Barriers to Upper Extremity Reconstruction for Patients With Cerebral Palsy
(Sage, 2022) Loewenstein, Scott N.; Angulo-Parker, Francisco; Timsina, Lava; Adkinson, Joshua; Surgery, School of Medicine
Background: Reconstructive surgery for upper extremity manifestations of cerebral palsy (CP) has been demonstrated to be safe and effective, yet many potential candidates are never evaluated for surgery. The purpose of this study was to determine barriers to upper extremity reconstruction for patients with CP in a cohort of upper extremity surgeons and nonsurgeons. Methods: We sent a questionnaire to 4167 surgeons and nonsurgeon physicians, aggregated responses, and analyzed for differences in perceptions regarding surgical efficacy, patient candidacy for surgery, compliance with rehabilitation, remuneration, complexity of care, and physician comfort providing care. Results: Surgeons and nonsurgeons did not agree on the literature support of surgical efficacy (73% vs 35% agree or strongly agree, respectively). Both surgeons and nonsurgeons felt that many potential candidates exist, yet there was variability in their confidence in identifying them. Most surgeons (59%) and nonsurgeons (61%) felt comfortable performing surgery and directing the associated rehabilitation, respectively. Neither group reported that patient compliance, access to rehabilitation services, and available financial resources were a major barrier, but surgeons were more likely than nonsurgeons to feel that remuneration for services was inadequate (37% vs 13%). Both groups agreed that surgical treatments are complex and should be performed in the setting of a multidisciplinary team. Conclusions: Surgeons and nonsurgeons differ in their views regarding upper extremity reconstructive surgery for CP. Barriers to reconstruction may be addressed by performing higher level research, implementing multispecialty educational outreach, developing objective referral criteria, increasing surgical remuneration, improving access to trained upper extremity surgeons, and implementing multidisciplinary CP clinics.
A behavioral rating system predicts weight loss and quality of life after bariatric surgery
(Elsevier, 2018-08) Hilgendorf, William; Butler, Annabelle; Timsina, Lava; Choi, Jennifer; Banerjee, Ambar; Selzer, Don; Stefanidis, Dimitrios; Pediatrics, School of Medicine
Background Bariatric surgery represents the most effective intervention for severe obesity available today; however, significant variability in postoperative outcomes exists. Effective tools that predict postoperative outcomes are needed for decision-making and patient counseling. Objectives We hypothesized that a validated behavioral assessment tool, the Cleveland Clinic Behavioral Rating Scale (CCBRS), would predict excess weight loss, health-related quality of life, depression, anxiety, and alcohol use after bariatric surgery. Setting Hospital in the United States. Methods A prospective observational study with 2-year planned follow-up was conducted with patients who completed a psychological clinical interview, the Short Form 36 (SF-36) v.2 Health Survey and brief self-report questionnaires measuring depression (PHQ-9), anxiety (GAD-7), and alcohol use (AUDIT) preoperatively. At the conclusion of the preoperative psychological evaluation, the psychologist completed the CCBRS. All questionnaires were readministered at 6, 12, 18, and 24 months after surgery. Generalized estimating equations were used to assess whether any CCBRS ratings predicted surgery outcomes. Results One hundred seventy-nine patients (113 Roux-en-Y gastric bypass and 66 sleeve gastrectomy) were included in the analyses. SF-36 scores, PHQ-9 scores, and the AUDIT total scores improved significantly after surgery, while GAD-7 scores did not change appreciably. Higher preoperative CCBRS ratings predicted higher SF-36 scores, and lower PHQ-9, GAD-7 and AUDIT scores. The CCBRS social support rating predicted higher postoperative percent excess weight loss. Conclusion A behavioral rating scale (CCBRS) completed before bariatric surgery predicted postoperative weight loss, quality of life, depression, and anxiety. Therefore, this tool may prove useful in patient counseling and expectation management before surgery.
Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
(The American Society for Clinical Investigation, 2023-11-30) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Singh, Kanhaiya; Timsina, Lava; Suh, Lily J.; Rinne, Ethan; Van Natta, Bruce W.; Neumann, Colby R.; Mohan, Ganesh; Lester, Mary; VonDerHaar, R. Jason; German, Rana; Marino, Natascia; Hassanein, Aladdin H.; Gordillo, Gayle M.; Kaplan, Mark H.; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Surgery, School of Medicine
This study investigates a mechanistic link of bacterial biofilm–mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.
Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
(ASCI, 2024-02) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Singh, Kanhaiya; Timsina, Lava; Suh, Lily J.; Rinne, Ethan; Van Natta, Bruce W.; Neumann, Colby R.; Mohan, Ganesh; Lester, Mary; VonDerHaar, R. Jason; German, Rana; Marino, Natascia; Hassanein, Aladdin H.; Gordillo, Gayle M.; Kaplan, Mark H.; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Chemistry, School of Science
This study investigates a mechanistic link of bacterial biofilm–mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.
Case Volume-to-Outcome Relationship in Minimally-Invasive Esophagogastrectomy
(Elsevier, 2019) Salfity, Hai; Timsina, Lava; Su, Katherine; Ceppa, DuyKhanh; Birdas, Thomas; Surgery, School of Medicine
Background Outcomes after open esophagectomy (OE) have been shown to depend on institution case volume. We aim to determine whether a similar relationship exists for minimally-invasive esophagogastrectomy (MIE). Methods Patients who had OE or MIE (excluding robotic procdures) between 2010 and 2013 in the National Cancer Database were included. Outcomes included 30- and 90-day mortality, length-of-stay, hospital readmission, margin positivity, and number of lymph nodes harvested. Logistic and linear regression were used to adjust for possible confounders including age, gender, tumor size, Charlson score, induction therapy, and type of institution (academic vs. community-based). Results We identified 2371 patients in the MIE group and 6285 patients in the OE group. In multivariate analysis, high case volume was an independent predictor for lower 30-day, 90-day mortality, shorter length-of-stay, and higher rate of negative-margin resection in OE (P<0.001) but not MIE. After quartile ranking of institutions based on volume, MIE outcomes were found to be better in institutions in the highest volume quartile compared to those in the lowest (p< 0.0001). Conclusions In this dataset, MIE postoperative outcomes, unlike OE, did not correlate with hospital case volume. Volume-outcome relationships may be affected by surgical approach. The effect of case volume on long-term outcomes after MIE warrants further study.
Comparison of a Trauma Comorbidity Index with Other Measures of Comorbidities to Estimate Risk of Trauma Mortality
(Wiley Online Library, 2021-04-29) Jenkins, Peter C.; Dixon, Brian E.; Savage, Stephanie A.; Carroll, Aaron E.; Newgard, Craig D.; Tignanelli, Christopher J.; Hemmila, Mark R.; Timsina, Lava; Surgery, School of Medicine
Background Comorbidities influence the outcomes of injured patients, yet a lack of consensus exists regarding how to quantify that association. This study details the development and internal validation of a trauma comorbidity index (TCI) designed for use with trauma registry data and compares its performance to other existing measures to estimate the association between comorbidities and mortality. Methods Indiana state trauma registry data (2013-2015) was used to compare the TCI with the Charlson and Elixhauser comorbidity indices, a count of comorbidities, and comorbidities as separate variables. The TCI approach utilized a randomly selected training cohort and was internally validated in a distinct testing cohort. The C-statistic of the adjusted models was tested using each comorbidity measure in the testing cohort to assess model discrimination. C-statistics were compared using a Wald test, and stratified analyses were performed based on predicted risk of mortality. Multiple imputation was used to address missing data. Results The study included 84,903 patients (50% each in training and testing cohorts). The Indiana TCI model demonstrated no significant difference between testing and training cohorts (p = 0.33). It produced a C-statistic of 0.924 in the testing cohort, which was significantly greater than that of models using the other indices (p < 0.05). The C-statistics of models using the Indiana TCI and the inclusion of comorbidities as separate variables – the method used by the American College of Surgeons Trauma Quality Improvement Program – were comparable (p = 0.11) but use of the TCI approach reduced the number of comorbidity-related variables in the mortality model from 19 to one. Conclusions When examining trauma mortality, the TCI approach using Indiana state trauma registry data demonstrated superior model discrimination and/or parsimony compared to other measures of comorbidities.
The EGS Grading Scale For Skin And Soft Tissue Infections Is Predictive Of Poor Outcomes : A Multicenter Validation Study
(Lippincott, Williams & Wilkins, 2020-04-01) Savage, Stephanie A.; Li, Shi Wen; Utter, Garth H.; Cox, Jessica A.; Wydo, Salina M.; Cahill, Kevin; Sarani, Babak; Holzmacher, Jeremy; Duane, Therese M.; Gandhi, Rajesh R.; Zielinski, Martin D.; Ray-Zack, Mohamed; Tierney, Joshua; Chapin, Trinette; Murphy, Patrick B.; Vogt, Kelly N.; Schroeppel, Thomas J.; Callaghan, Emma; Kobayashi, Leslie; Coimbra, Raul; Schuster, Kevin M.; Gillaspie, Devin; Timsina, Lava; Louis, Alvancin; Crandall, Marie; Medicine, School of Medicine
Introduction: Over the last five years, the American Association for the Surgery of Trauma (AAST) has developed grading scales for Emergency General Surgery (EGS) diseases. In a prior validation study using diverticulitis, the grading scales were predictive of complications and length of stay. As EGS encompasses diverse diseases, the purpose of this study was to validate the grading scale concept against a different disease process with a higher associated mortality. We hypothesized that the grading scale would be predictive of complications, length of stay and mortality in skin and soft tissue infections (STI). Methods: This multi-institutional trial encompassed 12 centers. Data collected included demographic variables, disease characteristics and outcomes such as mortality, overall complications, hospital and ICU length of stay. The EGS scale for STI was used to grade each infection and two surgeons graded each case to evaluate inter-rater reliability. Results: 1170 patients were included in this study. Inter-rater reliability was moderate (kappa coefficient 0.472-0.642, with 64-76% agreement). Higher grades (IV and V) corresponded to significantly higher LRINEC scores when compared with lower EGS grades. Patients with grade IV and V STI had significantly increased odds of all complications, as well as ICU and overall length of stay. These associations remained significant in logistic regression controlling for age, gender, comorbidities, mental status and hospital-level volume. Grade V disease was significantly associated with mortality as well. Conclusion: This validation effort demonstrates that Grade IV and V STI are significantly predictive of complications, hospital length of stay and mortality. Though predictive ability does not improve linearly with STI grade, this is consistent with the clinical disease process, in which lower grades represent cellulitis and abscess and higher grades are invasive infections. This second validation study confirms the EGS grading scale as predictive, and easily used, in disparate disease processes.
Exosome-Mediated Crosstalk between Keratinocytes and Macrophages in Cutaneous Wound Healing
(ACS, 2020-09) Zhou, Xiaoju; Brown, Brooke A.; Siegel, Amanda P.; El Masry, Mohamed S.; Zeng, Xuyao; Song, Woran; Das, Amitava; Khandelwal, Puneet; Clark, Andrew; Singh, Kanhaiya; Guda, Poornachander R.; Gorain, Mahadeo; Timsina, Lava; Xuan, Yi; Jacobson, Stephen C.; Novotny, Milos V.; Roy, Sashwati; Agarwal, Mangilal; Lee, Robert J.; Sen, Chandan K.; Clemmer, David E.; Ghatak, Subhadip; Surgery, School of Medicine
Bidirectional cell–cell communication involving exosome-borne cargo such as miRNA has emerged as a critical mechanism for wound healing. Unlike other shedding vesicles, exosomes selectively package miRNA by SUMOylation of heterogeneous nuclear ribonucleoproteinA2B1 (hnRNPA2B1). In this work, we elucidate the significance of exosome in keratinocyte–macrophage crosstalk following injury. Keratinocyte-derived exosomes were genetically labeled with GFP-reporter (Exoκ-GFP) using tissue nanotransfection (TNT), and they were isolated from dorsal murine skin and wound-edge tissue by affinity selection using magnetic beads. Surface N-glycans of Exoκ-GFP were also characterized. Unlike skin exosome, wound-edge Exoκ-GFP demonstrated characteristic N-glycan ions with abundance of low-base-pair RNA and was selectively engulfed by wound macrophages (ωmϕ) in granulation tissue. In vitro addition of wound-edge Exoκ-GFP to proinflammatory ωmϕ resulted in conversion to a proresolution phenotype. To selectively inhibit miRNA packaging within Exoκ-GFPin vivo, pH-responsive keratinocyte-targeted siRNA-hnRNPA2B1 functionalized lipid nanoparticles (TLNPκ) were designed with 94.3% encapsulation efficiency. Application of TLNPκ/si-hnRNPA2B1 to the murine dorsal wound-edge significantly inhibited expression of hnRNPA2B1 by 80% in epidermis compared to the TLNPκ/si-control group. Although no significant difference in wound closure or re-epithelialization was observed, the TLNPκ/si-hnRNPA2B1 treated group showed a significant increase in ωmϕ displaying proinflammatory markers in the granulation tissue at day 10 post-wounding compared to the TLNPκ/si-control group. Furthermore, TLNPκ/si-hnRNPA2B1 treated mice showed impaired barrier function with diminished expression of epithelial junctional proteins, lending credence to the notion that unresolved inflammation results in leaky skin. This work provides insight wherein Exoκ-GFP is recognized as a major contributor that regulates macrophage trafficking and epithelial barrier properties postinjury.
Expanding the Donor Pool with Utilization of Extended Criteria DCD Livers
(AASLD, 2019) Mihaylov, Plamen; Mangus, Richard; Ekser, Burcin; Cabrales, Arianna; Timsina, Lava; Fridell, Jonathan; Lacerda, Marco; Ghabril, Marwan; Nephew, Lauren; Chalasani, Naga; Kubal, Chandrashekhar A.; Pediatrics, School of Medicine
Utilization of donation after circulatory death donor (DCD) livers for transplantation has remained cautious in the U.S. The aim of this study was to demonstrate the expansion of DCD liver transplant (LT) program with the use of extended criteria DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with one of the followings: 1) donor age >50 years, 2) donor BMI >35 kg/m2, 3) donor functional warm ischemia time (fWIT) >30 minutes, and 4) donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush, and efforts to minimize ischemic times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC) and change in DCD LT volume. Of 135 consecutive DCD LT, 62 were ECD DCDs. 24 ECD DCD LT were performed before (Era I) and 38 after the institution of optimization protocol (Era II), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in Era II, with a significantly lower incidence of IC (5% vs. 17% in Era I; P = 0.03) and better 1‐year graft survival (93% vs. 75% in Era I, P = 0.07). Survival outcomes for ECD DCD LT in Era II were comparable to matched deceased donor (DBD) LT. With the expansion of the DCD donor pool, the number of DCD LT performed at our center gradually increased in Era II to account for > 20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT.

Browsing by Author "Timsina, Lava"

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