Orthotopic forelimb transplantation in a Yucatan minipig model: Anatomic and in vivo study.

INTRODUCTION: Above elbow transplants represent 19% of the upper extremity transplants. Previous large-animal models have been too distal or heterotopic, did not use immunosuppression and had short survival. We hypothesize that an orthotopic forelimb transplant model, under standard immunosuppression, is feasible and can be used to address questions on peri-transplant ischemia reperfusion injury, and post-transplantation vascular, immunologic, infectious, and functional outcomes. MATERIALS AND METHODS: Four forelimbs were used for anatomical studies. Four mock transplants were performed to establish technique/level of muscle/tendon repairs. Four donor and four recipient female Yucatan minipigs were utilized for in-vivo transplants (endpoint 90-days). Forelimbs were amputated at the midarm and preserved through ex vivo normothermic perfusion (EVNP) utilizing an RBC-based perfusate. Hourly perfusate fluid-dynamics, gases, electrolytes were recorded. Contractility during EVNLP was graded hourly using the Medical Research Council scale. EVNP termination criteria included systolic arterial pressure ≥115 mmHg, compartment pressure ≥30 mmHg (at EVNP endpoint), oxygen saturation reduction of 20%, and weight change ≥2%. Indocyanine green (ICG) angiography was performed after revascularization. Limb rejection was evaluated clinically (rash, edema, temperature), and histologically (BANFF classification) collecting per cause and protocol biopsies (POD 1, 7, 30, 60 and endpoint). Systemic infections were assessed by blood culture and tissue histology. CT scan was used to confirm bone bridging at endpoint. RESULTS: Animals 2, 4 reached endpoint with grade 0-I rejection. Limbs 1, 3 presented grade III rejection on days 6, 61. CsA troughs averaged 461 ± 189 ng/mL. EVNLP averaged 4.3 ± 0.52 h. Perfusate lactate, PO2 , and pH were 5.6 ± 0.9 mmol/L, 557 ± 72 mmHg and 7.5 ± 0.1, respectively. Muscle contractions were 4 [1] during EVNLP. Transplants 2, 3, 4 showed bone bridging on CT. CONCLUSION: We present preliminary evidence supporting the feasibility of an orthotopic, mid-humeral forelimb allotransplantation model under standard immunosuppression regimen. Further research should validate the immunological, infectious, and functional outcomes of this model.

Long term assessment of antibiotic prophylaxis and biliary microbiome in pancreaticoduodenectomy.

INTRODUCTION: Surgical site infections (SSI) can represent a major complication of pancreaticoduodenectomy (PD). We summarize the outcomes of process improvement efforts to reduce the SSI rates in PD that includes replacing Cefazolin with Ceftriaxone-Metronidazole as antibiotic prophylaxis. Additional efforts included current assessment of biliary microbiome and potential prophylactic failures based on bile cultures and suspected antibiotic allergies. METHOD: A single-center review of PD patients from January-2012 to March-2021. Study groups were divided into Pre and Post May-2015 (Group 1 and 2, respectively) when Ceftriaxone-Metronidazole prophylaxis and routine intraoperative cultures were standardized. Univariate and multivariable analyses were conducted to assess groups' differences and association with SSI. RESULTS: Six hundred ninety patients identified [267(38.7%) and 423(61.3%) in Group 1 and Group2, respectively]. After antibiotic change, SSI rates decreased from 28.1% to 16.5% (incisional: 17.6%-7.5%, organ-space or abscess: 17.2%-13.0%), Group 1 and Group 2, respectively, P<0.001. Ceftriaxone-Metronidazole was used in 75.9% of patients Group 2. When adjusting for other covariates, an SSI-decrease was associated only with Ceftriaxone-Metronidazole (OR 0.34, P<0.001). CONCLUSIONS: Ongoing process improvement has resulted in decreased SSIs with Ceftriaxone-Metronidazole prophylaxis. The benefit of Ceftriaxone-Metronidazole is independent of the biliary microbiome. Improving prophylaxis for those with suspected penicillin allergy is warranted.

Retrobulbar Injection for Hyaluronic Acid Gel Filler-Induced Blindness: A Review of Efficacy and Technique.

While blindness after hyaluronic acid gel filler injection occurs only very rarely, it represents a devastating complication for the patient and the surgeon. Retrobulbar injection with hyaluronidase is the only known potential means of reversing this adverse event. However, positive outcomes remain anecdotal. We have attempted to review the current literature regarding possible efficacy and detail the indications and technique to be utilized, if hyaluronidase retrobulbar injection is to be attempted. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Tumor Size Combined With CA-19 Level Improves Prediction of Survival of Patients With Pancreatic Adenocarcinoma Undergoing Perioperative Chemotherapy and Resection.

BACKGROUND AND OBJECTIVE: Five-year survival in pancreatic adenocarcinoma is less than 20%. While previous studies have postulated that a carbohydrate antigen 19-9 (CA19-9) threshold could predict outcome of resection, the role for CA19-9 in decision-making remains unclear. This study aims to assess whether CA19-9 levels combined with tumor size improve prediction of post-resection survival. METHOD: A retrospective analysis was conducted on 109 patients with pancreatic adenocarcinoma who underwent perioperative chemotherapy followed by resection. The primary outcome of mortality was, divided into short (<1 year) or prolonged (>2 years). Univariate and multivariable analyses compared the tumor size-adjusted CA19-9 between the outcome groups. RESULTS: Twenty-seven (24.78%) and eighty-two (75.23%) patients were in the short survival and prolonged-survival groups, respectively. The mean CA19-9 was significantly greater in the short vs prolonged group (P < .001). Analyzing CA19-9 level by tumor size, the association of high CA19-9 and short survival was significant for small (≤2 cm) and large tumor (>4 cm), but not for intermediate-size tumors (2-4 cm). Adjusting for preoperative variable did not change this association. CONCLUSION: CA 19-9 in combination with tumor size better identifies patients with prolonged post-resection survival. This prediction is most accurate in patients with either small (≤2 cms) or large (>4 cms) tumors compared to intermediate-size tumors.

How much narcotics are really needed after bariatric surgery: results of a prospective study.

BACKGROUND: To mitigate the opioid crisis, physicians are reevaluating opioid prescribing patterns. OBJECTIVES: To evaluate outcomes of maximal opioid reduction on top of an existing Enhanced Recovery after Surgery (ERAS) pathway in our The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited bariatric surgery program. SETTING: Academic tertiary care hospital, United States. METHODS: Patients undergoing primary bariatric operation were studied from July 2017 to April 2019, (standard ERAS cohort), and compared to patients from April 2019 to February 2021 (standard ERAS with Sparing Opioid Use Postoperatively protocol) (SOUP cohort). The primary endpoint was reduction of perioperative opioid use. RESULTS: Of 367 patients, 212 (57.8%) and 155 (42.2%) were in the ERAS and SOUP cohorts, respectively. Roux-en-Y gastric bypass was 48.6% (n = 103) versus 54.2% (n = 84) and sleeve gastrectomy was 51.4% (n = 109) versus 45.8% (n = 71) for ERAS versus SOUP, respectively (P = .29). The SOUP cohort of patients required a low median inpatient morphine equivalent dose of 4 mg [0-6.2]. The ERAS cohort was discharged on a higher morphine equivalent dose than the SOUP cohort at 186.7 mg ± 92.9 versus 37.6 ± 32.3 (P < .05), and median consumption of the standard 5 mg oxycodone tablet was 1.5 tablets [0-4]. The SOUP cohort patients rated their pain satisfaction score on a scale of 1 to 10 at 9.1 points (standard deviation ± 1.8). The SOUP cohort had a shorter length of stay (P < .05), with comparable readmission rates. CONCLUSIONS: An opioid-sparing protocol can be implemented after bariatric surgery with high overall satisfaction with pain control.

Ex vivo normothermic preservation of amputated limbs with a hemoglobin-based oxygen carrier perfusate.

BACKGROUND: Ex vivo normothermic limb perfusion (EVNLP) preserves amputated limbs under near-physiologic conditions. Perfusates containing red blood cells (RBCs) have shown to improve outcomes during ex vivo normothermic organ perfusion, when compared with acellular perfusates. To avoid limitations associated with the use of blood-based products, we evaluated the feasibility of EVNLP using a polymerized hemoglobin-based oxygen carrier-201 (HBOC-201). METHODS: Twenty-four porcine forelimbs were procured from Yorkshire pigs. Six forelimbs underwent EVNLP with an HBOC-201-based perfusate, six with an RBC-based perfusate, and 12 served as static cold storage (SCS) controls. Ex vivo normothermic limb perfusion was terminated in the presence of systolic arterial pressure of 115 mm Hg or greater, fullness of compartments, or drop of tissue oxygen saturation by 20%. Limb contractility, weight change, compartment pressure, tissue oxygen saturation, oxygen uptake rates (OURs) were assessed. Perfusate fluid-dynamics, gases, electrolytes, metabolites, methemoglobin, creatine kinase, and myoglobin concentration were measured. Uniformity of skin perfusion was assessed with indocyanine green angiography and infrared thermography. RESULTS: Warm ischemia time before EVNLP was 35.50 ± 8.62 minutes (HBOC-201), 30.17 ± 8.03 minutes (RBC) and 37.82 ± 10.45 (SCS) (p = 0.09). Ex vivo normothermic limb perfusion duration was 22.5 ± 1.7 hours (HBOC-201) and 28.2 ± 7.3 hours (RBC) (p = 0.04). Vascular flow (325 ± 25 mL·min-1 vs. 444.7 ± 50.6 mL·min-1; p = 0.39), OUR (2.0 ± 1.45 mL O2·min-1·g-1 vs. 1.3 ± 0.92 mL O2·min-1·g-1 of tissue; p = 0.80), lactate (14.66 ± 4.26 mmol·L-1 vs. 13.11 ± 6.68 mmol·L-1; p = 0.32), perfusate pH (7.53 ± 0.25 HBOC-201; 7.50 ± 0.23 RBC; p = 0.82), flexor (28.3 ± 22.0 vs. 27.5 ± 10.6; p = 0.99), and extensor (31.5 ± 22.9 vs. 28.8 ± 14.5; p = 0.82) compartment pressures, and weight changes (23.1 ± 3.0% vs. 13.2 ± 22.7; p = 0.07) were not significantly different between HBOC-201 and RBC groups, respectively. In HBOC-201 perfused limbs, methemoglobin levels increased, reaching 47.8 ± 12.1% at endpoint. Methemoglobin saturation did not affect OUR (ρ = -0.15, r2 = 0.022; p = 0.45). A significantly greater number of necrotic myocytes was found in the SCS group at endpoint (SCS, 127 ± 17 cells; HBOC-201, 72 ± 30 cells; RBC-based, 56 ± 40 cells; vs. p = 0.003). CONCLUSION: HBOC-201- and RBC-based perfusates similarly support isolated limb physiology, metabolism, and function.

Clinical significance of donor lung weight at procurement and during ex vivo lung perfusion.

BACKGROUND: Elevated donor lung weight may adversely affect donor lung transplant suitability and post-transplant outcomes. The objective of this study is to investigate the impact of lung weight after procurement and ex vivo lung perfusion (EVLP) on transplant suitability, post-transplant graft dysfunction, and clinical outcomes and define the donor lung weight range most relevant to clinical outcomes. METHODS: From February 2016 to August 2020, 365 human lung donors to a single transplant center were retrospectively reviewed. 239 were transplanted without EVLP, 74 treated with EVLP (50 went on to transplant), and 52 declined for transplant without EVLP consideration. Donor lung weights were measured immediately after procurement and, when performed, after EVLP. Lung weights were adjusted by donor height and divided into 4 quartiles. RESULTS: Donor lungs in the highest weight quartile at donor hospital had a significantly lower transplant suitability rate after EVLP, higher rates of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay. For lungs treated with lung perfusion, the highest lung weight quartile at the end of lung perfusion was associated with a significantly lower transplant suitability rate, higher incidence of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay, compared to the other categories. CONCLUSIONS: Donor lung weight stratified by quartile categories can assist decision-making regarding need for EVLP at the donor hospital as well as during EVLP evaluation. Caution should be used when considering donor lungs in the highest weight quartile for transplantation.

Ex Vivo Normothermic Perfusion of Human Upper Limbs.

BACKGROUND: Ischemia-reperfusion injury remains a primary concern in upper extremity transplantation. Ex vivo normothermic perfusion (EVNP) enables near-physiological organ preservation, avoiding the deleterious effects of hypoxia and cooling. We investigated the effectiveness of human limb EVNP compared with static cold storage (SCS). METHODS: Twenty human upper extremities were procured. Ten were perfused at 38 °C with an oxygenated red blood cell-based solution, and contralateral limbs served as SCS control (4 °C). EVNP was terminated with systolic arterial pressure ≥115 mm Hg, compartment fullness, or a 20% decline in oxygen saturation. Weight, contractility, compartment pressure, tissue oxygen saturation, and uptake rates were assessed. Perfusate fluid dynamics, gases, electrolytes, and metabolites were measured. Myocyte injury scores and liquid chromatography-mass spectrometry analysis were performed. RESULTS: EVNP duration was 41.6 ± 9.4 h. Vascular resistance averaged 173.0 ± 29.4 mm Hg × min/L. Weight change and compartment pressures were 0.4 ± 12.2% ( P = 0.21) and 21.7 ± 15.58 mm Hg ( P = 0.003), respectively. Arterial and venous carbon dioxide partial pressure, oxygen saturation, and pH were 509.5 ± 91.4 mm Hg, 15.7 ± 30.2 mm Hg, 87.4 ± 11.4%, and 7.3 ± 0.2, respectively. Oxygen uptake rates averaged 5.7 ± 2.8 mL/min/g. Lactate reached 20 mmol/L after 15 (interquartile range = 6) h. Limb contractility was preserved for 30.5 (interquartile range = 15.8) h ( P < 0.001) and negatively correlated with perfusate potassium (ρ = -0.7, P < 0.001). Endpoint myocyte injury scores were 28.9 ± 11.5% (EVNP) and 90.2 ± 11.8% (SCS) ( P < 0.001). A significant increase in taurine ( P = 0.002) and decrease in tryptophan ( P = 0.002) were detected. Infrared thermography and indocyanine green angiography confirmed the presence of peripheral perfusion. CONCLUSIONS: EVNP can overcome the limitations of cold preservation by extending preservation times, enabling limb quality assessment, and allowing limb reconditioning before transplantation.

The Effect of Blood Transfusion in Lung Donors on Recipient Survival.

BACKGROUND: Blood transfusion can have detrimental effects on the pulmonary system, leading to lung injury and respiratory decompensation with subsequent increased morbidity and mortality in surgical and critically ill patients. How much of this effect is carried from a lung donor to transplant recipient is not fully understood, raising questions regarding transplant suitability of lungs from transfused donors. METHODS: United Network for Organ Sharing data were reviewed. Lung transplants from adult donors and known donor transfusion status were included; multiorgan transplants and retransplants were excluded. Recipient mortality was evaluated based on donor and recipient characteristics using a Kaplan-Meier survival estimate, Cox proportional hazards, and logistic regression models. We further assessed whether recipient mortality risk modified the donor transfusion effect. RESULTS: From March 1996 to June 2017, 20,294 transplants were identified. Outcome analysis based on transfusion status showed nonsignificant difference in 1-year mortality (P = .214). Ninety-day recipient mortality was significantly higher with transfusion of >10 units (U) vs 1-10 U or no transfusion (8.5%, 6.1%, and 6.0%, respectively, P = .005). Multivariable analysis showed increased 90-day mortality with transfusion of >10 U compared to no transfusion (odds ratio 1.62, P < .001), whereas 1-10 U showed no difference (odds ratio 1.07, P = .390). When stratified by recipient transplant risk, transfusion of >10 U was associated with increased mortality even with the lowest-risk recipients, while transfusion of 1-10 U showed no mortality increase even in the highest-risk recipients. CONCLUSIONS: Donor transfusion of >10 U of blood was associated with increased 90-day recipient mortality even in low-risk transplants. This risk should be considered when evaluating donor lungs.

Ex-Vivo Normothermic Limb Perfusion With a Hemoglobin-Based Oxygen Carrier Perfusate.

INTRODUCTION: Ex-vivo normothermic limb perfusion (EVNLP) has been proven to preserve limb viability better than standard cold storage. Perfusates containing packed red blood cells (pRBC) improve outcomes when compared to acellular perfusates. Limitations of pRBC-based perfusion include limited availability, need for cross match, mechanical hemolysis, and activation of pro-inflammatory proteins. Hemoglobin-based oxygen carrier (HBOC)-201 (Hemopure) is a solution of polymerized bovine hemoglobin, characterized by low immunogenicity, no risk of hemolytic reaction, and enhanced convective and diffusive oxygen delivery. This is a preliminary study on the feasibility of EVNLP using HBOC-201 as an oxygen carrier. MATERIALS AND METHODS: Three porcine forelimb perfusions were performed using an established EVNLP model and an HBOC-201-based perfusate. The perfusion circuit included a roller pump, oxygenator, heat exchanger, and reservoir. Electrolytes, limb temperature, weight, compartment pressure, nerve conduction, and perfusion indicated by indocyanine green angiography and infra-red thermography were monitored. Histological evaluation was performed with hematoxylin and eosin and electron microscopy. RESULTS: Three limbs were perfused for 21.3 ± 2.1 hours. Muscle contractility was preserved for 10.6 ± 2.4 hours. Better preservation of the mitochondrial ultrastructure was evident at 12 hours in contrast to crystallization and destruction features in the cold-storage controls. CONCLUSIONS: An HBOC-201-EVNLP produced outcomes similar to RBC-EVNLP with preservation of muscle contractility and mitochondrial structure.

Lung Transplant for Patient With Idiopathic Pneumonia Syndrome.

Idiopathic pneumonia syndrome (IPS) is a serious complication after hematopoietic stem cell transplantation. Despite the high mortality rate with medical management, there have been no reported cases of lung transplants for patients with IPS. We report a case involving a 44-year-old woman who developed IPS 5 months after hematopoietic stem cell transplantation for myelodysplastic syndrome. Despite aggressive medical management, the patient required intubation and was administered extracorporeal membrane oxygenation while awaiting recovery. However, her condition continued to deteriorate, and she subsequently underwent a double lung transplant with uneventful recovery. With the high mortality of medically managed IPS, lung transplant could prove to be lifesaving.