Efficacy of Cemiplimab as Adjuvant or Neoadjuvant Therapy in the Treatment of Cutaneous Squamous Cell Carcinoma.

INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer in the White population. Unfortunately, the prognosis of advanced cSCC is poor, and management can be challenging. Until recently, the choice of systemic medications was limited, and those that were available had modest efficacy. Cemiplimab is an anti-programmed cell-death protein 1 inhibitor and the first immunotherapeutic agent approved for the treatment of metastatic or locally advanced cSCC. The purpose of this study was to evaluate the efficacy of cemiplimab when used as adjuvant or neoadjuvant therapy in patients treated at our institution. METHODS: A retrospective review of patients with locally advanced or metastatic cSCC who were treated with cemiplimab as adjuvant or neoadjuvant therapy at a single institution between February 2019 and November 2022 was performed. Response to treatment was objectively assessed based on Response Evaluation Criteria in Solid Tumors, version 1.1, criteria. The primary end point was objective response rate. Secondary endpoints included time to observed response, disease-control rate, progression-free survival, overall survival, and adverse effects of therapy. RESULTS: A total of 6 patients were identified with a median age of 79 years (range, 51-90 years). Four patients had locally advanced cSCC, and 2 had distant metastasis. Cemiplimab was used as adjuvant therapy in 3 patients and neoadjuvant therapy in 2 patients. There was 1 patient in which it was used for limb salvage, who would have otherwise required an amputation. Objective response rate, complete response, and partial response were 66% (4 of 6), 33% (2 of 6), and 33% (2 pf 6), respectively. Average time to observed response was 2.9 months. Disease-control rate was 83% (5 of 6), and average progression-free survival was 10 months. Toxicity was reported in 2 patients, both of which were grade 1 severity. CONCLUSIONS: Cemiplimab has established its utility in the treatment of advanced cSCC, demonstrating clinical efficacy while generally having a tolerable adverse effect profile. Our preliminary results suggest that cemiplimab has potential as an adjuvant or neoadjuvant therapy in combination with surgery for treatment of cSCC.

The Severity of Initial Unilateral Cleft Lip and Nasal Deformity Predicts Long-Term Postoperative Esthetic Outcome.

BACKGROUND: Infantile cleft lip and nasal severity influence the final esthetic result of the repair. Although various authors have described methods of cleft lip and nasal repair, there is a paucity of data that correlates cleft severity with esthetic outcomes. The aim of this study was to examine the correlation between presurgical severity of unilateral cleft deformity and long-term postoperative esthetic outcomes. METHODS: This retrospective study, based at a single institution, investigated patients with complete unilateral cleft lip, with or without cleft palate, who underwent repair by a single surgeon, had preoperative infantile facial casts, and had postoperative facial photographs at 6 to 11 years of age (N=31). Preoperative nostril width ratio and columellar angle measurements were taken from facial casts. Postoperative, long-term nasolabial appearance was rated by 5 blinded observers used a modified Kuijpers-Jagtman scale. Linear regression was used to determine the relationship between preoperative cleft severity and postoperative ratings. RESULTS: Preoperative nostril width ratio directly correlated with postoperative nasal form score (r=0.40; P=0.026); likewise, preoperative columellar angle predicted postoperative nasal form score (r=0.37; P=0.040). Preoperative cleft severity was not significantly correlated with vermillion border appearance. Cronbach α values of 0.91 (nasal form) and 0.79 (vermillion border) indicated good inter-rater reliability. Kappa values of 0.87 (nasal form) and 0.70 (vermillion border) indicated good intrarater reliability. CONCLUSIONS: Preoperative unilateral cleft nose severity directly correlates with long-term postoperative nasal appearance in childhood. Outcome studies should present and control for preoperative severity to allow more accurate assessment of repair techniques.

A Longitudinal Investigation of Nasolabial Changes With and Without Revision Surgery in Patients with Non-Syndromic Unilateral Cleft Lip and Palate.

OBJECTIVE: To determine a baseline of anticipated change in nasolabial appearance following primary repair of unilateral cleft lip/palate and evaluate the degree to which revision surgery improves nasolabial appearance. DESIGN: Retrospective chart review. SETTING: Patients treated at the Lancaster Cleft Palate Clinic interdisciplinary clinic. PATIENTS: Twenty-three patients with complete unilateral cleft lip and palate who underwent primary surgical repair and 19 additional patients who underwent subsequent revision surgery were included. INTERVENTIONS: Patients in the non-revision group underwent a Tennison-Randall triangular flap lip repair at 3mo. Patients in the revision group underwent a modification of the Nakajima straight-line repair after primary Tennison-Randall triangular flap lip repair at an average age of 141mo. MAIN OUTCOME MEASURES: A modification of the Asher-McDade Aesthetic Index was utilized to evaluate Nasolabial Frontal (NLF), Nasolabial Profile (NLP), Vermillion Border (VB), and total change in appearance. Scores for patients in the revision group were evaluated before and after revision while appearance for patients without revision was evaluated at 3 distinct ages. Scores were averaged across time-points and inter-rater reliability was assessed. RESULTS: Nasolabial appearance in the non-revision sample did not change significantly over time, except for nasal profile. Scores improved after revision surgery - NLP: 3.48 to 2.97, (p = 0.001); NLF: 3.50 to 2.95 (p = 0.001); and Total Nasolabial Score: 3.29 to 3.01 (p = 0.004), with no significant change in VB. CONCLUSION: Decisions regarding need for nasolabial revision surgery may be made as early as 5yo with successful outcomes following secondary surgery improving appearance except for vermillion border appearance.

Evolving swaps in transplantation: global exchange, vouchers, liver, and trans-organ paired exchange.

PURPOSE OF REVIEW: With the ongoing organ shortage, several mechanisms to facilitate organ exchanges and expand the scope of living kidney or liver donation have been proposed. Although each addresses at least one barrier to transplantation, these innovative programs raise important ethical, logistical, and regulatory considerations. RECENT FINDINGS: This review addresses four recent proposals to expand living donor transplantation. For kidney transplantation, we discuss global paired exchange and advanced donation programs ('vouchers') and for liver transplantation, liver paired exchange. Lastly, this review considers trans-organ exchange. We explore the conceptual framework of the exchange, current status, benefits, and concerns for implementation among each of these evolving pathways. SUMMARY: Through highlighting novel mechanisms in organ exchange, greater awareness, discussion, or support can occur to create more avenues for transplantation. These innovative mechanisms require regulations and safeguards for donors to ensure informed consent, and proper follow-up is maintained.

Liver paired exchange: Can the liver emulate the kidney?

Kidney paired exchange (KPE) constitutes 12% of all living donor kidney transplantations (LDKTs) in the United States. The success of KPE programs has prompted many in the liver transplant community to consider the possibility of liver paired exchange (LPE). Though the idea seems promising, the application has been limited to a handful of centers in Asia. In this article, we consider the indications, logistical issues, and ethics for establishing a LPE program in the United States with reference to the principles and advances developed from experience with KPE. Liver Transplantation 24 677-686 2018 AASLD.

Use of Thromboprophylaxis after Autologous Breast Reconstruction: A Cost-Effective Break-Even Analysis.

PURPOSE: Post-operative venous thromboembolism (VTE) is a major source of morbidity and mortality. The use of thromboprophylaxis amongst surgeons is not well studied in autologous breast reconstruction. The purpose of this study was to determine the rate of VTE in breast cancer patients undergoing autologous breast reconstruction and to compare the cost-effectiveness of postoperative chemoprophylactic agents. METHODS: The TriNetX LLC. National Health Research Network database was used to identify patients with breast cancer who underwent autologous breast reconstruction surgery between 2002-2022. The incidence of occurrence of VTE within the first 30 days of surgery was calculated. Then a break-even analysis was performed to determine the break-even rate of VTE at which the chemoprophylactic agent would be cost effective. RESULTS: A cohort of 8,221 patients was identified in this study. The rate of VTE was significantly higher in those without anticoagulation (4.0%) compared to those who received anticoagulation (2.6%) (*p=0.0008). The break-even analysis for heparin and enoxaparin's cost-effectiveness yielded ARRs of 0.73% and 1.63% for high risk patients requiring 30 days of therapy and 0.20% and 0.43% for moderate risk patients requiring 7 days of therapy, respectively. CONCLUSION: The use of thromboprophylaxis significantly lowered the risk of VTE within 30 days after autologous breast reconstruction. Heparin appeared to be more cost-effective at preventing VTE compared to enoxaparin for both high and moderate risk patients. The presented model holds potential for other institution-specific variables that can be easily applied by plastic surgeons to determine the cost-effectiveness of any therapy of their choice.

Pain Control after Reduction Mammaplasty with Combination Bupivacaine and Dexamethasone Regional Block: A Randomized Controlled Trial.

BACKGROUND: There are many approaches to pain control in reduction mammaplasty. Preoperative bupivacaine regional blocks control pain relatively inexpensively ($0.07/mL), but last only 8 hours. A liposomal bupivacaine formulation lasts 72 hours but can be costly ($17.21/mL). Orthopedic and thoracic operations have demonstrated that dexamethasone ($0.44/mL) plus bupivacaine can prolong analgesia. The authors conducted a double-blind, randomized, controlled trial to determine whether dexamethasone plus bupivacaine regional block improves postoperative pain control, reduces inpatient narcotic use, and improves patient satisfaction. METHODS: Female patients were randomized into control and experimental groups. Both groups received preoperative modified block of the pectoral nerves: bupivacaine plus saline (control group) or bupivacaine plus dexamethasone (experimental group). Postoperative pain regimens were standardized. Vital signs, pain scores, narcotic consumption, and antiemetic use were recorded throughout the hospitalization. Quality-of-life surveys were distributed at the first postoperative visit. RESULTS: Fifty-one patients completed the study: 25 control and 26 experimental group patients. The experimental group averaged lower pain scores, although there was no statistically significant difference overall or at each 4-hour interval. Postoperative narcotic use was significantly lower in the experimental group (mean, 23.2 oral morphine equivalents versus 36.6 oral morphine equivalents per patient; P = 0.026). There were no differences in 4-hour interval vital signs, antiemetic use, or length of stay. Survey results showed enhanced quality of life in the experimental group, but this was not statistically significant. CONCLUSIONS: The addition of dexamethasone to bupivacaine in the preoperative modified block of the pectoral nerves block before bilateral reduction mammaplasty resulted in significantly less narcotic consumption in the hospital. This can be a cost-effective adjunct for postoperative pain control. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Therapeutic Use and in Bioengineering Applications.

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation. MSC-produced EVs are less immunogenic and can serve as an alternative to cellular therapies by transmitting signaling or delivering biomaterials to diseased areas of the body. This review article is focused on understanding the properties of EVs derived from different types of MSCs and MSC-EV-based therapeutic options. The potential of modern technologies such as 3D bioprinting to advance EV-based therapies is also discussed.

Ultrasound-guided Hydro-dissection Facilitates Tissue Expander Placement and Components Separation in Complex Ventral Hernia Repair.

Tissue expanders are known adjuncts in ventral hernia repair, used in a staged approach where tissue closure or coverage of the defect is preferred but inadequate. Placement of tissue expanders in the correct tissue plane can be difficult, especially in thin patients or with loss of domain. This case series describes a technique in which tissue expander placement is facilitated by ultrasound-guided hydro-dissection, following the placement of a transversus abdominis plane (TAP) block. In short, after induction of anesthesia, the same needle used for the ultrasound-guided TAP block can be repositioned by the anesthesiologist to instill tumescent solution into the fascial plane between the internal and external oblique muscles. This allows for identification of the fascial planes in the ensuing operation. Our technique may prove to be an alternative tool in the placement of tissue expanders for ventral hernia repair, or in other procedures requiring device placement.

Reducing Wound Hemorrhage: Use of Bilayer Collagen Matrix in Chronic Myelogenous Leukemia.

Donor site preparation is a critical step before the application of an autologous split-thickness skin graft (STSG). Comorbidities can lead to complications and graft loss, including that due to hematoma. In this case, a bilayer collagen matrix was used as a temporary wound dressing in a 25-year-old woman with active chronic myelogenous leukemia. She presented with a bleeding diathesis and spontaneous intramuscular and intracompartmental hematomas of the right leg. She experienced ongoing high-volume blood loss from her fasciotomy wounds, requiring wound care to be performed in the operating room under general anesthesia, and requiring multiple blood and platelet transfusions. Instead of immediate STSG, a bilayer collagen matrix was placed to reduce the bleeding and further prepare the wound bed over a 9-week period while she underwent medical optimization. Once stabilized from a hematologic standpoint, STSG was performed with total graft take. Both uncontrolled chronic myelogenous leukemia and its therapy, tyrosine kinase inhibitors, have a risk of hemorrhagic and thrombotic complications. Bilayer collagen matrix serves as an adjunct in the limb salvage algorithm that can reduce transfusion needs whereas a temporary bleeding diathesis is medically corrected before the application of an autologous skin graft.