Background: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). Methods: LT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8-24 h depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity + renal dysfunction, control-2) were analyzed. Results: Fifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 % of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. Conclusion: DPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.

Background: Pneumonia is associated with increased morbidity and costs in the intensive care unit (ICU). Its early identification is key for optimal outcomes, but early biomarkers are lacking. Studies suggest that fibrinolysis resistance (FR) after major abdominal surgery is linked to an increased risk of infection. Patients and Methods: Patients in a randomized controlled trial for hemorrhagic shock were evaluated for FR. Fibrinolysis resistance was quantified by thrombelastography with exogenous tissue plasminogen activator (tPA-TEG) at 24- and 48-hours post-injury and measuring LY30 (%). A receiver-operating characteristics (ROC) curve analysis was used to identify a cutoff for increased risk of pneumonia, which was then validated in ICU patients at risk for venous thromboembolism (VTE). Multivariable logistic regression was used to control for confounders. Results: Forty-nine patients in the hemorrhagic shock cohort had tPA-TEGs at 24- and 48-hours (median ISS, 27; 7% pneumonia). A composite tPA-TEG LY30 of less than 4% at 24 and 48 hours was found to be the optimal cutoff for increased risk of pneumonia. This cohort had a seven-fold increased rate of pneumonia (4% vs. 28%; p = 0.048). Eighty-eight patients in the VTE cohort had tPA-TEGs at 24 and 48 hours post-ICU admission (median ISS, 28; 6% pneumonia). The tPA-TEG LY30 of less than 4% was associated with a 10-fold increased rate of pneumonia (19% vs. 1.5%; p = 0.002). In patients with traumatic brain injury, the same association was found (33% vs. 3.2%; p = 0.006). Adjusting for confounders, the tPA-TEG persisted as a substantial risk factor for pneumonia (adjusted odds ratio [OR], 35.7; 95% confidence interval [CI], 1.9-682; p = 0.018). Conclusions: Fibrinolysis resistance quantified by tPA-TEG within 48 hours of ICU admission is associated with an increased risk of pneumonia in patients in hemorrhagic shock and those at risk for VTE. Prospective validation of the tPA-TEG LY30 optimal cutoff for pneumonia and further investigation into whether endogenous FR is a cause of an altered immunity is warranted.

Background: End stage renal disease (ESRD) is associated with platelet dysfunction but also thrombo-embolic complications. The specific role of increased blood urea nitrogen (BUN) on coagulation is un-clear. We aimed to characterize thromboelastography (TEG) parameters from males and females with ESRD and normal kidney function and evaluate if exogenous urea in vitro reproduced those TEG differences. Methods: We collected blood samples from 20 living kidney donors and 20 kidney recipients. TEG was performed without and with two increasing urea concentrations in vitro. TEG parameters were compared between recipients and donors. Results: Blood from kidney recipients showed baseline increased maximum amplitude (MA) and shortened time to maximum amplitude (TMA) compared to donors. These differences were not confirmed in females. In all patients, BUN was inversely correlated with TMA (r =-0.342; p = 0.031). In males, BUN and creatinine concentrations showed a direct correlation with MA (0.583; p = 0.007) and an inverse correlation with TMA (r =-0.520; p = 0.019). Urea in vitro decreased R-time (p = 0.005) and increased LY30 (p = 0.009) in donors but not recipients. Conclusions: ESRD is associated with increased MA and decreased TMA on TEG. No change in MA was observed with increasing urea concentrations in vitro. Gender-specific variability in TEG parameters were observed. (c) 2023 Elsevier Inc. All rights reserved.

Introduction: Massive bleeding in coagulopathic patients is attributed to tissue injury and ischemia reperfusion. Liver transplantation (LT) is a unique operation in which tissue injury (hepatectomy) is distinctly separated from ischemia reperfusion of the new liver. We hypothesize that massive bleeding during tissue injury has a different coagulation profile than massive bleeding after reperfusion. Methods: LT recipients had serial measurements of coagulation with thrombelastography (TEG). TEG indices included clot formation (R-time= plasma protease, Angle = fibrinogen, MA = platelets) and fibrinolysis (LY30). Subjects were classified by massive transfusion (MT) criteria (>4 RBC units/hour) over the following periods: incision to hepatectomy (tissue injury, TIMT), two hours after liver reperfusion (RMT), continuously (CMT), or none (nMT). Results: 232 LT patients with median age of 55 and MELD-Na of 22 were included. MT occurred in 63% of cases, with TIMT occurring in 10%, RMT in 28%, CMT in 25%. MA was suppressed across all MT cohorts (vs nMT) and was significantly different between groups at all time points. TIMT was associated with early suppressed MA, while RMT was also associated with increased LY30 and a sharp decline in Angle. CMT was associated suppressed MA and Angle throughout surgery. Conclusion: TIMT and RMT have discordant patterns of coagulopathy. Reperfusion bleeding is associated with hyperfibrinolysis with subsequent fibrinogen dysfunction, with tissue injury bleeding appears to be platelet related. These data support a role of early platelets in normotensive bleeding patients and limiting the use of antifibrinolytics and fibrinogen supplementation to those experiencing bleeding after ischemia reperfusion.

Background: Infection is a leading cause of morbidity in liver transplant (LT). Considering that the fibrinolytic system is altered in sepsis, we investigated the relationship between fibrinolysis resistance (FR) and post-transplant infection. Methods: Fibrinolysis was quantified using thmmbelastography (TEG) with the addition of tPA to quantify FR. FR was defined as LY30 = 0% and stratified as transient if present on POD1 or PODS (tFR), persistent (pFR) if present on both, or no FR (nFR) if absent. Results: 180 LT recipients were prospectively enrolled. 52 (29%) recipients developed infection. 72 had tFR; 37 had pFR; and 71 had nFR. Recipients with pFR had significantly greater incidence of infections (51% vs. 26% tFR vs. 20% nFR, p = 0.002). pFR was independently associated with increased odds of post-transplant infection (adjusted OR 3.39, p = 0.009). Conclusions: Persistent fibrinolysis resistance is associated with increased risk of post-transplant infection.

A thiol protease inhibitor was purified from rat liver by a rapid procedure involving heat treatment of the post-lysosomal fraction, affinity chromatography on papain-Sepharose 4B and Sephadex G-75. The purified inhibitor appeared homogeneous on sodium dodecyl sulfate electrophoresis. The inhibitor had a molecular weight of about 11,500 and consisted of three forms (pI 4.9, 5.2 and 5.6). The preparation inhibited thiol proteases, such as papain, cathepsin H, cathepsin B and cathepsin L, but not serine proteases (trypsin, chymotrypsin, mast cell protease and cathepsin A) or cathepsin D.

Electronic cigarette (e-cigarette) usage in the USA has drastically increased in the past 5 years due to age restrictions on conventional cigarettes, aggressive marketing and a perception that e-cigarettes are a healthy alternative. E-cigarettes contain nicotine, water, glycerol, propylene glycol and optional flavouring. On inhalation, the device heats the ingredients into a vapour [1]. While tobacco cigarette smoke is known to cause deleterious effects on the cardiovascular system, angiogenesis and skin capillary perfusion by causing direct injury to blood vessel walls, increased platelet aggregation, microvascular thrombosis [2–4] and inflammation [5], the consequences of e-cigarette vapour exposure on the lung are still largely unexplored [6, 7]. Recently, Lerner et al. [8] reported that vapours produced by e-cigarettes and e-cigarette fluids with flavourings induced toxicity, oxidative stress and inflammatory response in human bronchial airway epithelial cells (H292) and fetal lung fibroblasts (HFL1) as well as mouse lung. Garcia-Arcos et al. [9] showed that the aerosolised nicotine-containing e-cigarette fluid increased airway hyperreactivity, distal airspace enlargement, mucin production, and cytokine and protease expression in mice, implying potential dangers of nicotine inhalation during e-cigarette use. The inflammatory response to e-cigarette use involved increased neutrophil activation and mucus production [10], and decreased mucociliary clearance [11]. In human embryonic and mouse neural stem cells, human pulmonary fibroblasts [12], and skin and lung cells [13], cytotoxicity of e-cigarette vapour was correlated with the number and concentration of chemicals used to flavour the fluids. We recently showed in the skin flap survival model in vivo that nicotine-containing e-cigarette vapour is just as harmful to the microcirculation as tobacco cigarette smoke [4]. Electronic cigarettes are as toxic as tobacco cigarettes and can cause significant lung damage http://ow.ly/qT1l30ig1oR

Objective: The present report describes an alternative technique of using a flow- through, double-paddle, fibular, osteocutaneous free flap based on one perforator from the peroneal system and one perforator from the anterior tibial system for a through-and-through mandibular defect. Methods: The patient was a 65-year-old man who underwent a composite resection of the floor of the mouth, mandible, and chin pad due to recurrent oral cavity squamous cell carcinoma. The fibula was harvested with one posterior-lateral septal perforator from the peroneal system and with a second skin perforator from the anterior tibial system to perfuse a 15 × 14 cm skin island. The anterior tibial perforator was anastomosed to the distal end of the peroneal artery in a flow-through technique, and the area between the peroneal and tibial perforators was de-epithelialized to reconstruct separately the floor of mouth and cutaneous defects. Results: Good inflow and outflow of both skin islands were noted at the end of the procedure, and the patient recovered successfully without any fistulas or donor site morbidity. Conclusions: Perforators from the anterior tibial system should be considered for large, through-and-through mandibular defects when using 2 perforators from the peroneal system is not possible. In addition, we believe the flow-through technique can be useful in patients with vessel-depleted necks and provides a suitable match for vessel size between an anterior tibial perforator and the distal end of the peroneal system.

PURPOSE: The anterolateral thigh (ALT) free flap is one of the most commonly used flaps for head and neck reconstruction. Given that perforators of an ALT flap routinely arise sequentially from the descending branch of the lateral circumflex artery as it descends down the thigh, a long ALT flap can be more reliably harvested than a wide ALT flap. The purpose of this study is to demonstrate indications and outcomes for single-pedicle ALT free flaps compared to double-pedicle ALT flaps as well as multiple simultaneous thigh (MST) flaps. METHODS: Our series of 81 consecutive patients undergoing head and neck reconstruction with an ALT flap was retrospectively reviewed. Patients with a composite mandibular defect who underwent reconstruction with both a fibular free flap and an ALT free flap were excluded. Receiver operating characteristics curve analysis was performed to determine our cut-off values for width and length of single-pedicle versus double-pedicle ALT flaps. RESULTS: Fifty-seven and 18 patients were reconstructed with an ALT flap with one or two pedicles, respectively. Six patients underwent MST flaps. Defect size (width ≥12 cm, length ≥17 cm) for cutaneous defects (p<0.05), the presence of divergent mucosal defects, and through-and-through oral cavity or pharyngeal defects were associated with the use of two pedicles. There was one flap failure of a single-pedicle ALT flap. While operative time was increased for the groups of double-pedicle ALT flaps and MST flaps, there were no flap complications including partial flap loss, venous congestion, or wound healing issues from poor flap perfusion. CONCLUSION: Harvesting an ALT flap with two pedicles has the potential to reduce flap complications and should be considered for divergent and extremely wide (>12 cm) or extremely long (>17 cm) defects. Our proposed algorithms will help guide flap choice when designing an ALT free flap for a cutaneous and/or mucosal defect of the head and neck. B.B. Trinh: None. I.E. Rodriguez: None. F.W. Deleyiannis: None.

Importance Flap choice and design are crucial to the success of free flap reconstruction of the head and neck. These are dependent on donor and recipient site characteristics. Objective To demonstrate indications and outcomes of a single-pedicle anterolateral thigh flap (standard ALT flap) vs a thigh free flap with 2 pedicles in head and neck reconstruction. Design, Setting, and Participants A retrospective case series of consecutive patients treated in a tertiary academic care center between October 2011 and June 2017 by a single reconstructive microsurgeon was carried out. Eighty-one patients underwent reconstruction of a cutaneous and/or mucosal defect of the head and neck. Patients with a composite mandibular defect who received both a fibular flap and a thigh flap were excluded. Those with less than 6 months of follow-up were excluded. Main Outcomes and Measures Patient characteristics and clinical variables, including age, sex, primary diagnosis/indication for reconstruction, type of flap, dimensions of flap, and number of perforators in the flap, were collected. Optimal cutoff values to quantitate the differences in length and width between the standard ALT and 2-pedicle thigh flaps were determined using receiver operating characteristic (ROC) curve analysis and the Youden Index. The types of flap were compared to determine any difference in flap complications including flap loss, venous congestion, and poor wound healing. Results Of the 81 patients (mean [SD] age, 58.2 [15.9] years; 62 [76.5%] men), 57 and 18 patients were reconstructed with a standard ALT flap and a thigh flap with 2 pedicles, respectively. Six patients underwent multiple simultaneous thigh (MST) flaps. Defect size (width ≥12 cm, standard ALT: 95% CI, 7.6-9.7; thigh flap with 2 pedicles: 95% CI, 7.0-17.4; P = .02; length ≥17 cm, standard ALT: 95% CI, 11.9-15.2; thigh flap with 2 pedicles: 95% CI, 13.6-30.0; P = .001), the presence of divergent mucosal defects, and through-and-through oral cavity/pharyngeal defects were associated with the use of 2 pedicles. Within groups of thigh flaps with 2 pedicles and MST flaps, there were no flap complications (ie, partial loss, venous congestion, or wound healing issues from poor perfusion). Conclusions and Relevance Harvesting a thigh flap with 2 pedicles has the potential to reduce flap complications and should be considered for divergent and wide or long defects. Width and length measurements respectively of 12 cm and 17 cm are reasonable numbers to initially consider when deciding whether to include a second pedicle. Level of Evidence 3.

Arteriovenous malformations (AVMs) are a type of high-flow vascular malformation that are characterized by abnormal capillary communications between the arterial and venous systems. While they are most commonly located in the head and neck region, their appearance in the nose is considerably rare, resulting in a paucity of literature regarding the surgical management of these lesions. We present the case of a 13-year-old male with a 6.5 × 6 cm AVM of the nose with a history of frequent nosebleeds since early childhood, often requiring aggressive measures, such as silver nitrate cauterization for control. Use of nasal decongestants and aminocaproic acid provided only transient improvement. After determination of arterial supply, AVM was approached with a combination of preoperative selective embolization and surgical excision with subsequent forehead flap defect coverage. Due to the size and complexity of this AVM, extra precautions were taken to avoid severe intraoperative bleeding, and femoral sheaths were placed prior to excision. The patient tolerated the procedure well, and with subsequent debulking surgery and Laser Hair Removal achieved an acceptable cosmetic outcome.

Hypercalcemia is often an incidental finding accompanying a nonspecific clinical presentation. Depending on the level of calcium overload, symptoms can range from muscle weakness, polyuria, and thirst, to cognitive dysfunction, renal impairment, and pancreatitis. Life-threatening conditions, such as dysrhythmias and cardiomyopathies, can be seen in severe cases. Although related to several underlying entities, as much as 90% of cases are due to primary hyperparathyroidism or malignancy.1 After actively managing the elevated calcium levels, and if hyperparathyroidism and malignancy have been ruled out, attention should be directed toward identifying less common causes of this electrolyte disturbance. A rare and scarcely documented cause of hypercalcemia is the ectopic production of 1,25-dihydroxy vitamin D (or calcitriol), originating from macrophage-driven granulomatous reactions to foreign bodies, such as silicone or (poly)methyl methacrylate. Hypercalcemia results from calcitriol-induced increase in calcium absorption from the gut and increased bone reabsorption.2 Visnyei et al.3 and Agrawal et al.4 presented separate cases where 2 patients with extensive silicone injections, as part of male-to-female gender reassignment procedures, presented with symptoms and laboratory results consistent with calcitriol-mediated hypercalcemia. In both cases, diagnosis was confirmed by regional lymph node biopsy. We present a case of a 74-year-old female with a history of hypertension, transient ischemic attacks, diabetes, and coronary artery disease. She presented to the emergency department with polyuria, fatigue, mild confusion, malaise, and a recent episode of syncope. She was found to have a serum calcium level of 14.0 mg/dL (normal, 8.8–10.3 mg/dL), initially managed with fluid resuscitation and calcitonin. Besides her persistently elevated calcium levels, more thorough laboratory studies showed low parathyroid hormone levels and elevated 1,25-dihydroxy vitamin D, as well as high creatinine, suggestive of acute kidney injury secondary to hypercalcemia. Given these findings, and her previous history of breast implants, focus was directed to ruling out vitamin D–producing granulomatous disease. Ultrasound and computed tomography scans were ordered, revealing marked calcifications, as well as silicone-consistent densities beyond capsules, suggesting bilateral implant rupture (Fig. 1). After consulting with the Plastic Surgery department, a decision to remove implants was made (Fig. 2).Fig. 1.: Bilateral silicone gel implants, with calcification of shells and rupture.Fig. 2.: Implants at the time of explantation.Following successful explantation, patient continued to recover and was discharged on postoperative day 2. On subsequent follow-ups, her calcium levels have consistently remained within normal range. Even though this is still a rare and not well-documented entity, the increasing demand of silicone injections, fillers, and implants for body contouring procedures, especially in the transgender community, could result in an increased incidence of granuloma-induced, vitamin D–dependent hypercalcemia. In our opinion, this diagnosis should be considered in patients with a history of cosmetic surgery presenting with idiopathic persistent hypercalcemia.

Summary: This report describes a new method for the surgical repair of the chest wall deformity encountered in complex Poland's syndrome. In this report, we describe the use of a customized titanium implant that was used to replace the missing second through fifth ribs and to provide chest wall stabilization before breast reconstruction. This approach might be considered an alternative to autologous rib grafting in patients who have reached skeletal maturity. It avoids the morbidity and risk associated with rib grafts and improves chest wall symmetry.