IU Indianapolis ScholarWorks :: Browsing by Author "Hassanein, Aladdin H."

Browsing by Author "Hassanein, Aladdin H."

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153. Quantification of Lymphangiogenesis in Murine Lymphedema Tail Model Using Intravital Microscopy
(Wolters Kluwer, 2023-05-19) Mohan, Ganesh; Khan, Imran; Diaz, Stephanie M.; Neumann, Colby R.; Jorge, Miguel D.; Sinha, Mithun; Gordillo, Gayle M.; Sen, Chandan K.; Hassanein, Aladdin H.; Surgery, School of Medicine
PURPOSE: Lymphedema is limb swelling caused by lymphatic dysfunction. It occurs in 30% of patients that undergo axillary lymph node dissection in the treatment of breast cancer. There is no cure for this disease. Understanding the mechanisms of lymphatic growth will play a pivotal role in developing therapeutic strategies against these conditions. Visualization of lymphangiogenesis and functional assessment remains a challenge. Intravital two-photon microscopy (IVM) is a powerful imaging tool for investigating various biological processes in live animals. Tissue nanotransfection technology (TNT) facilitates a direct, transcutaneous non-viral vector gene delivery using a chip with nanochannel poration in a rapid (<100ms) focused electric field. TNT was used in this study to deliver the genetic cargo in the murine tail lymphedema to assess the lymphangiogenesis. The purpose of this study is to experimentally evaluate the applicability of IVM to visualize and quantify lymphatics. METHODS: The murine tail model of lymphedema was utilized. A 3 mm full thickness skin excision and lymphatic vessel disruption was performed 20 mm from the base of the tail in twelve C57BL/6 mice. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: Group I (control) was given pCMV6 (expression vector backbone alone) (n=6); Group II had pCMV6-Prox1 (n=6). Post-TNT (day 10), a 3 cm segment of murine tail was deskinned distal to the site of occlusion to optimize visualization. FITC-Dextran (2000 kD) injected intradermally at the distal tail region for lymphatic uptake. Lymphatic vessels are visualized at the second skin excision site with the Leica SP8 Confocal/Multiphoton Microscope and assessed for number of branching points to determine the newly formed lymphatics. Lymphatic vessel density was also observed by immunostaining with anti-Podoplanin antibody. RESULTS: The experimental group II exhibited increased branching points (3-fold) using filamentation analysis compared to control group I at the site of TNT treatment (n=6, p<0.05). Increased lymphatic vessel density was also observed with Podoplanin immunostaining post-TNT application. Intensity quantification of immunohistochemistry revealed greater expression of Podoplanin in Group II when compared to Group I (n=6, p<0.05). CONCLUSION: This study demonstrates a novel, powerful imaging tool for investigating lymphatic vessels in live murine tail model of lymphedema. Intravital microscopy can be utilized for functional assessment of lymphatics and visualization of lymphangiogenesis following gene-based therapy.
177. Prophylactic Absorbable Antibiotic Beads For High Risk Implant-based Reconstruction: A Single Institution Pilot Study
(Wolters Kluwer, 2023-05-19) Ahmed, Shahnur; Lee, Jason T. C.; Roth, Dylan D.; Liu, Steven; Fisher, Carla S.; Fan, Betty; Imeokparia, Folasade; Ludwig, Kandice; Lester, Mary E.; Hassanein, Aladdin H.; Surgery, School of Medicine
PURPOSE: Infections are problematic in implant-based reconstruction after mastectomies. Infection rates have been reported to be as high as 31%. Strategies to reduce the risk of infection include various antibiotic irrigation solutions, “no-touch” techniques, optimizing sterility, and empiric antibiotic use for skin flora coverage. Absorbable antibiotic beads have been well described for other indications, including orthopedic and pressure sore reconstruction. The purpose of this study is to evaluate the use of prophylactic biodegradable antibiotic beads during pre-pectoral and sub-pectoral implant-based breast reconstruction following mastectomy. METHODS: A single-center retrospective review of patients who underwent implant-based breast reconstruction post-mastectomy between 2019 to 2022. Patients were divided into two groups: Group I were deemed “high risk” by the senior author and received biodegradable antibiotic beads (1 gram vancomycin, 240 mg gentamicin) during tissue expander or implant reconstruction (pre-pectoral or subpectoral) while Group II (control) had no antibiotic beads. Demographic data, diabetes, body mass index (BMI), implant plane (pre-pectoral or sub-pectoral), smoking and use of mesh were recorded. Outcome variables included postoperative cellulitis or infection requiring oral or intravenous antibiotics and tissue expander loss at 90 days. RESULTS: In our study period, 19 patients (36 total implants/expanders) received biodegradable antibiotic beads during implant-based breast reconstruction (Group I). There were 174 patients (290 total expanders) who did not receive antibiotic beads (Group II). Patients in Group I had a history of previous expander/implant infection in 73.6%. Pre-pectoral placement of implants occurred in 84.2% of patients in Group I and 74.1% in Group II. Diabetes was prevalent in 15.8% of Group I compared to 5.7% seen in Group II patients. The mean BMI in Group I was 30.5 kg/m2 compared to 27.8 kg/m2 in Group II (p-value 0.88). Implant infection rate of Group I at 90 days was 8.3% (3/36 total expanders) compared to 8.6% (25/290 total expanders) in Group II. Implant loss in Group I was 5.5% (2/26 total expanders) compared to 7.6% (22/290) in Group II. CONCLUSION: The incidence of infection in high risk patients who have absorbable antibiotic beads placed during the time of reconstruction appears to be normalized to the control group in this pilot study, suggesting that absorbable antibiotic beads may decrease postoperative infection complications. Future studies may further clarify its benefit in selected groups.
80. Lymphatic Preconditioning: Novel Investigation Of A “Lymphatic Delay Phenomenon”
(Wolters Kluwer, 2024-04-19) Hulsman, Luci; Mohan, Ganesh; Ahmed, Shahnur; Jorge, Miguel D.; Sullivan, Steven J.; Mohammed, Imran; Sinha, Mithun; Hassanein, Aladdin H.; Surgery, School of Medicine
Background: The vascular delay phenomenon is a well-described concept of flap physiology with many clinical applications used to increase flap viability. The approach employs a staged surgical procedure with selective partial disruption of the flap’s blood supply to increase the robustness of the remaining blood supply, followed by interval flap transfer 7-10 days later. While this vascular delay phenomenon has been thoroughly studied, no investigation has been performed to determine if a similar “delay phenomenon” exists for lymphatic vessels. Lymphedema frequently occurs following injury of lymphatics during lymph node dissection. The purpose of this study was to evaluate whether lymphatic preconditioning with staged disruption of lymphatics can be protective against lymphedema. Methods: The standard murine tail lymphedema model was utilized which involves creating a 3 mm circumferential skin excision by the base of the tail and surgically clipping two lymphatics. This standard model was used for a control (Group 1, Control A, n=6). A second control (Group 2, Control B, n=5) had 3 mm circumferential skin excision, one tail lymphatic clipped at that level, and an immediate second hemi-circumferential skin excision on the more proximal tail with disruption of the other remaining lymphatic. Group 3 (experimental lymphatic preconditioning, n=6), had a 3 mm full thickness skin excision by the base of the tail, disruption of one tail lymphatic at that level (leaving one lymphatic vessel intact) followed by staged hemi-circumferential skin excision with disruption of the remaining lymphatic vessel 7 days later. Tail volume was assessed with tail measurements using the truncated cone equation. Immunohistochemistry and histology was sent. Results: Group 3 (experimental lymphatic preconditioning) had a change in tail volume of 79.1 mm3 compared to Group 1 (Control A) 154.6 mm3 (p=0.03) and Group 2 (Control B) 126.6 mm3 (p=0.05) at 28 days post-lymphatic injury. Conclusion: Mice that underwent lymphatic preconditioning with partial lymphatic injury followed by staged completion of lymphatic disruption 7 days later exhibited less tail swelling. This study demonstrates evidence for a novel concept of “lymphatic delay phenomenon” parallel to the well-known vascular delay phenomenon. Lymphatic preconditioning has potential translational clinical applications for protective effects to minimize lymphatic dysfunction.
A Novel Framework for Optimizing Efficiency and Education in Microsurgical Breast Reconstruction
(Wolters Kluwer, 2023-11-27) Lester, Mary E.; Berns, Jessica; Dawson, Steven; Newsom, Keeley; Hartman, Brett; Hassanein, Aladdin H.; Surgery, School of Medicine
Deep inferior epigastric perforator (DIEP) flaps are becoming the most frequent choice for autologous breast reconstruction. There are many benefits to DIEP flaps, but the procedures can be lengthy and have a steep learning curve. The balance of efficiency and education can be difficult to achieve. A framework was implemented to focus on both efficiency and education at each stage of the DIEP flap procedure. The author's methods to improve efficiency include a two-team approach with assigned roles for faculty and residents. The roles are consistent across the institution. Methods to enhance education include practice in a laboratory-based microsurgical training course and assigning goals for the rotation. Trainees include independent and integrated plastic surgery residents without microsurgical fellows. Bilateral DIEPs are performed with two attendings, and unilateral DIEPs, with one attending. A retrospective review identified patients undergoing DIEP flap reconstruction from 2017 to 2020. Outcome measures include operative time and complications, which are comparable to previously published data. Focusing on education allows residents to learn each stage of the case. The authors present a framework for training residents in DIEP flap reconstruction to optimize efficiency and education.
Abstract 68: The False Positive Rate Of Transcutaneous Tissue Oximetry Alarms In Microvascular Breast Reconstruction Rises After 24 Hours
(Wolters Kluwer, 2020-05-13) Tran, Phu C.; DeBrock, Will; Lester, Mary E.; Hartman, Brett C.; Socas, Juan; Hassanein, Aladdin H.; Medicine, School of Medicine
Purpose: Transcutaneous tissue oximetry is widely used as an adjunct for postoperative monitoring after microvascular breast reconstruction and has been shown to improve flap salvage rates. Despite a high sensitivity at detection of postoperative vascular issues, alarms from probe malfunctions/ and or positioning can generate unnecessary nursing calls, concerns, and evaluations. The purpose of this study is to analyze the false positive rate of transcutaneous tissue oximetry monitoring over the postoperative period and assess changes in its utility over time. Methods: Consecutive patients undergoing microvascular breast reconstruction out our institution were assessed between 2017-2019. Inclusion criteria included use of transcutaneous tissue oximetry for monitoring. Variables of interest were transcutaneous tissue oximetry alarms that triggered nursing calls, flap loss, re-exploration, and salvage rates. Results: The study included 175 patients (286 flaps). The flap loss rate was 1.0% (3/175). A total of twelve patients (6.8%) required re-exploration, with a 67.0% flap salvage rate. Nine of these patients required exploration within 24 hours. The 3 takebacks after 24 hours were not for vascular compromise but were for abdominal wall hematoma, increasingly sanguineous drain output, and exam concerning for hematoma. Within the 24-hour postoperative period, 43 tissue oximetry alarms triggered nursing calls; 7 alarms (16.2%) were confirmed to be for flap issues secondary to vascular compromise. After 24 hours, 44 alarms were triggered, none of which were associated with flap compromise. The false positive rate of the alarm within 24 hours was 83.7% (36/43) compared to 100% (44/44) after 24 hours (p= 0.01). Conclusions: Transcutaneous tissue oximetry is a helpful adjunct to the clinical exam in the postoperative monitoring of flaps in microsurgical breast reconstruction. The false positive rate significantly rises after 24 hours. The benefit may not outweigh the concerns, labor, and effort that results from alarms after postoperative day 1. We recommend considering discontinuing transcutaneous tissue oximetry monitoring after 24 hours.
ASO Author Reflections: Immediate Lymphatic Reconstruction: A Proactive Approach to Breast Cancer-Related Lymphedema
(Springer, 2021-03) Cook, Julia A.; Hassanein, Aladdin H.; Surgery, School of Medicine
Biofilm Derived Oxylipin Mediated Autoimmune Response in Breast Implant Subjects
(medRxiv, 2020-11-20) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Natta, Bruce W. Van; Neumann, Colby R.; Suh, Lily J.; Singh, Kanhaiya; Lester, Mary; VonDerHaar, R. Jason; Gordillo, Gayle M.; Hassanein, Aladdin H.; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Chemistry and Chemical Biology, School of Science
Over 10 million women worldwide have breast implants for breast cancer/prophylactic reconstruction or cosmetic augmentation. In recent years, a number of patients have described a constellation of symptoms that are believed to be related to their breast implants. This constellation of symptoms has been named Breast Implant Illness (BII). The symptoms described include chronic fatigue, joint pain, muscle pain and a host of other manifestations often associated with autoimmune illnesses. In this work, we report that bacterial biofilm is associated with BII. We postulate that the pathogenesis of BII is mediated via a host-pathogen interaction whereby the biofilm bacteria Staphylococcus epidermidis interacts with breast lipids to form the oxylipin 10-HOME. The oxylipin 10-HOME was found to activate CD4+ T cells to Th1 subtype. An increased abundance of CD4+Th1 was observed in the breast tissue of BII subjects. The identification of a mechanism of immune activation associated with BII via a biofilm enabled pathway provides insight into the pathogenesis for implant-associated autoimmune symptoms.
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.
Breast Implant Reconstruction in the Ptotic Patient: Evaluation of Wise and Vertical Skin Sparing Mastectomy
(Sage, 2024-03-12) Holohan, M. Margaret; Diaz, Stephanie M.; Newsom, Keeley; Smith, Alex; Fan, Betty; Imeokparia, Folasade O.; Fisher, Carla S.; Ludwig, Kandice K.; Lester, Mary E.; Hassanein, Aladdin H.; Surgery, School of Medicine
Introduction: Post-mastectomy reconstruction in patients with severe breast ptosis can be challenging. Traditionally, a skin sparing mastectomy (SSM) with a circumareolar incision or a horizontal elliptical extension results in a long, horizontally-oriented scar in the central breast. The Wise pattern SSM with an inferiorly-based dermal flap addresses skin redundancy and provides added vascularized implant coverage in ptotic patients with macromastia. The purpose of this study is to compare outcomes in ptotic patients undergoing SSM with Wise pattern and a modified vertical technique which also uses de-epithelialized excess skin under the incision. Methods: A retrospective chart review was performed on patients that underwent SSM using a Wise or vertical skin reducing technique. The Wise pattern was performed using an inferiorly-based dermal flap and the vertical method used a laterally-based dermal flap covering the implant/tissue expander (TE). Results: SSM with the use of autoderm was performed in 42 patients (67 breasts) using either the Wise (n = 49 breasts) or vertical (n = 18 breasts) method. Both groups had similar BMI (35.4). The prepectoral plane was used in 93.5% of Wise pattern patients and all vertical patients. All cases of seroma and hematoma occurred in the Wise pattern group (10.2%). Mastectomy skin necrosis requiring unplanned return to surgery for debridement occurred in 20.4% of those undergoing Wise pattern SSM and 11.1% undergoing the vertical pattern (p = 0.49). Conclusion: Severely ptotic patients undergoing SSM have a high risk of skin necrosis. A dermal flap under the closure has the advantage of vascularized tissue reinforcing the wound in implant based reconstruction. The vertical pattern SSM using a laterally-based dermal flap may be a safe, simple alternative to the Wise pattern in select patients.

Browsing by Author "Hassanein, Aladdin H."

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