Bioetics Issues of Artificial Placenta and Artificial Womb Technology.

Abstract: The worldwide infertility crisis and the increase in mortality and morbidity among infants, due to preterm births and associated complications, have stimulated research into artificial placenta (AP) and artificial womb (AW) technology as novel solutions. These technologies mimic the natural environment provided in the mother's womb, using chambers that ensure the supply of nutrients to the fetus and disposal of waste substances through an appropriate mechanism. This review aims to highlight the background of AP and AW technologies, revisit their historical development and proposed applications, and discuss challenges and bioethical and moral issues. Further research is required to investigate any negative effects of these new technologies, and ethical concerns pertaining to the structure and operation of this newly developed technology must be addressed and resolved prior to its introduction to the public sphere.

Human Cloning: Biology, Ethics, and Social Implications.

Abstract: This scholarly article delves into the multifaceted domains of human cloning, encompassing its biological underpinnings, ethical dimensions, and broader societal implications. The exposition commences with a succinct historical and contextual overview of human cloning, segueing into an in-depth exploration of its biological intri-cacies. Central to this biological scrutiny is a comprehensive analysis of somatic cell nuclear transfer (SCNT) and its assorted iterations. The accomplishments and discoveries in cloning technology, such as successful animal cloning operations and advances in the efficiency and viability of cloned embryos, are reviewed. Future improvements, such as reprogramming procedures and gene editing technology, are also discussed. The discourse extends to ethical quandaries intrinsic to human cloning, entailing an extensive contemplation of values such as human dignity, autonomy, and safety. Furthermore, the ramifications of human cloning on a societal plane are subjected to scrutiny, with a dedicated emphasis on ramifications encompassing personal identity, kinship connections, and the fundamental notion of maternity. Culminating the analysis is a reiteration of the imperative to develop and govern human cloning technology judiciously and conscientiously. Finally, it discusses several ethical and practical issues, such as safety concerns, the possibility of exploitation, and the erosion of human dignity, and emphasizes the significance of carefully considering these issues.

Evidence of Air Trapping During Ex Vivo Lung Perfusion: A Swine Experimental Lung Imaging and Mechanics Study.

Ex vivo lung perfusion (EVLP) allows the ventilation and perfusion of lungs to evaluate their viability for transplantation. The aim of this study is to compare the mechanical, morphologic and functional properties of lungs during EVLP with values obtained in vivo to guide a safe mechanical ventilation strategy. Lungs from 5 healthy pigs were studied in vivo and during 4 hours of EVLP. Lung compliance, airway resistance, gas exchange, and hemodynamic parameters were collected at positive end-expiratory pressure (PEEP) of 5 cm H2O. Computed tomography was performed at PEEP 0, PEEP 5, and total lung capacity (TLC). Lung pressure-volume (PV) curves were performed from PEEP 0 to TLC. Lung compliance decreased during EVLP (53 ± 5 mL/cm H2O vs 29 ± 7 mL/cm H2O, P < .05), and the PV curve showed a lower inflection point. Gas content (528 ± 118 mL vs 892 ± 402 mL at PEEP 0) and airway resistance (25 ± 5 vs 44 ± 9 cmH2O/L∗s-1, P < .05) were higher during EVLP. Alveolar dead space (5% ± 2% vs 17% ± 6%, P < .05) and intrapulmonary shunt (9% ± 2% vs 28% ± 13%, P < .05) increased ex vivo compared to in vivo, while the partial pressure of oxygen to inspired oxygen fraction ratio (PO2/FiO2) did not differ (468 ± 52 mm Hg vs 536 ± 14 mm Hg). In conclusion, during EVLP lungs show signs of air trapping and bronchoconstriction, resulting in low compliance and increased alveolar dead space. Intrapulmonary shunt is high despite oxygenation levels acceptable for transplantation.

Preliminary Experience With Hypothermic Oxygenated Machine Perfusion in an Italian Liver Transplant Center.

BACKGROUND: Machine perfusion is increasingly utilized in liver transplantation to face the detrimental consequences of the use of extended-criteria donors. Hypothermic oxygenated machine perfusion (HOPE) appears to be more protective relative to static cold storage. Conversely, normothermic machine perfusion (NMP) allows a better graft evaluation. We describe a pilot prospective study on machine perfusion in selected grafts. METHODS: HOPE was executed for all the grafts procured from donors after cardiac death (DCDs) and for livers from donors after brain death (DBDs) requiring prolonged preservation time. NMP was used when a more precise evaluation was needed. Both HOPE and NMP were performed through the portal vein and hepatic artery. RESULTS: From July 2016 to November 2017, we performed 7 HOPE procedures: 5 for DCD and 2 for DBD grafts. Two livers presented with macrovesicular steatosis >30% (1 DCD and 1 DBD). HOPE lasted 240 minutes (180-320 min) with a total ischemia time of 575 minutes (410-810 min). Six grafts were successfully transplanted. One DCD graft required additional evaluation using NMP. The graft was then discarded due to extensive hepatocellular necrosis. In the post-transplant course, acute and chronic renal failure were the main complications affecting 3 and 2 recipients, respectively. In our series, steatosis was the main risk factor for kidney injury. Patient and graft survival rate was 100% and no ischemic cholangiopathies were observed after 270 days (106-582 days). CONCLUSIONS: Our study confirms HOPE safety and efficacy for DCD and DBD grafts. These data are particularly significant for DCD management in the Italian setting where the mandatory 20-minute hands-off interval before death declaration further prolongs warm ischemia time.

Liver Transplantations and Brain Dead Donors With Alcohol Abuse.

BACKGROUND AND AIM: Liver grafts from donors with chronic and active history of alcohol abuse are usually immediately ruled out for use in liver transplantation (LT). The aim of our study is to evaluate the use of those grafts. METHODS: From 2011 to 2016, a study group (Group 1) composed of 5 adult LT patients transplanted with livers from donors with alcohol abuse, was compared with a control group (Group 2) of 10 randomly matched patients who received liver transplants. Preoperative, intraoperative, and postoperative data were compared. RESULTS: Among donors, serum gamma-glutamyl transferase values were significantly higher in Group 1. In recipients, post-LT laboratory exams showed significantly higher peak values of aspartate transaminase and alanine transaminase in Group 1; higher values of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in Group 1 were also recorded on day 0. Early allograft dysfunction occurred at higher rates in Group 1 (80% vs 20%, P = .025), with no differences in early rejection episodes or early surgical repeat interventions. All patients from both groups were alive after 20 ± 10 (range 6-35) months from LT. CONCLUSION: Despite higher rates of early allograft dysfunction, selected liver grafts from donors with alcohol abuse can be accepted for LT with good clinical results.

Sent Liver Grafts Do Not Have a Detrimental Impact on Post-transplant Outcome.

INTRODUCTION: "Sent livers" (SL) (interregional allocated organs) are considered extended donor criteria grafts. These grafts influence post-transplant outcome. In our donor allocation program, the number of allocated SLs is increasing. The aim of our study is to provide data supporting the possibility to enlarge the use of SLs through adequate donor-to-recipient matching. METHODS: A retrospective analysis was carried out from our prospective-collected database during 2014. RESULTS: Fifty-seven liver transplantations (LTs) were included: 22 SLs and 35 grafts procured by us (nSLs). Only donor risk index among donor characteristics showed a trend toward significant values (SL 1.901 vs nSL 1.726, P = .07). Among LT variables, the number of patients who received interleukin-2 inhibitor induction (SL 7 vs nSL 20, P < .05) and the presence of hepatocellular carcinoma (SL 50% vs nSL 34%, P < .05) reached statistical significance. One case of primary nonfunction occurred in the nSL group. No major retrieval injuries were observed. Retransplantation was performed in 6 cases (2 SLs and 4 nSLs). One patient in the SL group died after retransplantation. Graft survival rates at 1, 3, 6, and 12 months were 100%, 100%, 90%, 86% and 91%, 86%, 86%, 86% (P = .79) in SL and nSL groups, respectively. DISCUSSION: SL performance did not differ from that of nSL. SLs were usually allocated to noncritical candidates, and nSLs were transplanted more frequently in decompensated recipients. Despite this peculiar donor-recipient match, grafts survival was similar in the 2 groups of patients.

Deterioration of Lung Function in a Pig Model of Uncontrolled Cardiac Death.

INTRODUCTION: Uncontrolled donors after circulatory determination of death (uDCDD) represent a yet unexplored pool of organs potentially available for transplantation. The aims of this study were to validate a protocol of cardiac death in the pig and to investigate lung function during the process. MATERIALS AND METHODS: Cardiac death was induced in preanesthetized animals with an injection of 600 mg propofol; once systolic blood pressure was <50 mm Hg (Agonal Phase), a 20 mEq bolus of KCl was given and, after asystolia was documented, cardiopulmonary resuscitation (CPR) started, followed by 5 minutes no touch (end-CPR). Invasive blood pressure (BP) and heart rate (HR) were recorded; blood samples taken at baseline, 15 minutes after CPR, and after the no touch period (end-CPR). Computed tomography (CT) scans were taken at baseline and at end-CPR. RESULTS: Agonal phase was reached in 6 ± 1 minutes and lasted 3 ± 1 minutes; average HR was 49 ± 16 beats/min, and BP was 41 ± 12 mm Hg. CPR lasted 35 ± 3 minutes; average HR and BP were 113 ± 32 beats/min and 86 ± 63 mm Hg, respectively. PaO2/FiO2 decreased from 442 ± 31 mm Hg at baseline to 63 ± 36 at end-CPR (P < .001). pH decreased from 7.378 ± 0.045 to 6.931 ± 0.042 (P < .001), with a corresponding increase of lactate from 0.9 ± 0.2 to mmol/L to 12.8 ± 2.1 (P < .001). As assessed using CT scan, total lung volume decreased (baseline vs end-CPR 1107 ± 106 mL vs 617 ± 95; P < .001), whereas noninflated tissue (ie, atelectasis) significantly increased (46 ± 10 g vs 131 ± 89; P = .008). CONCLUSIONS: Lung function greatly deteriorated after cardiac death. The model we set may constitute a reproducible platform for future investigations on lung uDCDD.

Negative Pressure Wound Treatment of Infections Caused By Extensively Drug-Resistant Gram-Negative Bacteria After Liver Transplantation: Two Case Reports.

Although survival after liver transplantation (LT) has progressively improved over the last years, an increased prevalence of clinically relevant infections in LT patients is well documented. In particular, the spread of infections sustained by extensively drug-resistant bacteria (XDR) produced an increase in the incidence of wound infections. Implementation of treatments for these life-threatening events is mandatory. This study describes 2 LT patients in whom XDR wound infection was effectively treated using negative pressure wound treatment (NPWT) combined with targeted local and systemic antibiotic therapy. Over the last 3 years, 2 of 8 patients with XDR infection admitted to our unit developed wound infection caused by XDR Klebsiella pneumoniae (KP-XDR). Positive results of the abdominal fluid culture and of the wound swab for KP-XDR were followed by sepsis. In both cases wound debridement was required and deep fascial layer dehiscence was detected. Combination antibiotic therapy was administered for sepsis treatment and, after failure of conventional NPWT, a NPWT with local instillation (NPWTi; V.A.C.-Ulta/VeraFlo-Instillation Therapy-KCI USA, Inc., San Antonio, TX, USA) of colistin-rifampicin was applied. After NPWTi application a reduction in bacterial load and exudate was observed with reduction in inflammatory markers. A complete healing of wound was achieved and both patients are currently alive. Instillation and NPWT are widely discussed in the literature. Results of the present study indicate beneficial effects of NPWT combined with targeted local and systemic antibiotic therapy; in both cases a life-threatening complication was cured. We consider local instillation of selected antibiotics applied to NPWTi a valuable tool for deep wound infection sustained by XDR bacteria.

Arterial anastomosis in liver transplantation for Rendu-Osler-Weber disease: two case reports.

Liver transplantation (LT) in patients with hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber, disease is a problematic procedure. In patients with hepatic involvement due to clinically significant arterovenous malformations, there is high risk of intraoperative bleeding and intra- or perioperative complications. Some surgical corrections have been proposed for venous problems, concerning the vena caval anastomosis. A common finding in HHT is arterial enlargement of the celiac trunk and of the common hepatic artery. We report 2 cases of LT in HHT where the arterial anastomosis was successfully performed using the splenic artery of the recipient, which shows less tendency for enlargement than the celiac trunk.

In vivo conditioning of acid-base equilibrium by crystalloid solutions: an experimental study on pigs.

PURPOSE: Large infusion of crystalloids may induce acid-base alterations according to their strong ion difference ([SID]). We wanted to prove in vivo, at constant PCO(2), that if the [SID] of the infused crystalloid is equal to baseline plasma bicarbonate, the arterial pH remains unchanged, if lower it decreases, and if higher it increases. METHODS: In 12 pigs, anesthetized and mechanically ventilated at PCO(2) ≈40 mmHg, 2.2 l of crystalloids with a [SID] similar to (lactated Ringer's 28.3 mEq/l), lower than (normal saline 0 mEq/l), and greater than (rehydrating III 55 mEq/l) baseline bicarbonate (29.22 ± 2.72 mEq/l) were infused for 120 min in randomized sequence. Four hours of wash-out were allowed between the infusions. Every 30 min up to minute 120 we measured blood gases, plasma electrolytes, urinary volume, pH, and electrolytes. Albumin, hemoglobin, and phosphates were measured at time 0 and 120 min. RESULTS: Lactated Ringer's maintained arterial pH unchanged (from 7.47 ± 0.06 to 7.47 ± 0.03) despite a plasma dilution around 12%. Normal saline caused a reduction in pH (from 7.49 ± 0.03 to 7.42 ± 0.04) and rehydrating III induced an increase in pH (from 7.46 ± 0.05 to 7.49 ± 0.04). The kidney reacted to the infusion, minimizing the acid-base alterations, by increasing/decreasing the urinary anion gap, primarily by changing sodium and chloride concentrations. Lower urine volume after normal saline infusion was possibly due to its greater osmolarity and chloride concentration as compared to the other solutions. CONCLUSIONS: Results support the hypothesis that at constant PCO(2), pH changes are predictable from the difference between the [SID] of the infused solution and baseline plasma bicarbonate concentration.

Fulminant multiorgan failure due to varicella zoster virus and HHV6 in an immunocompetent adult patient, and anhepatia.

Varicella is a well-known contagious disease of childhood that can also affect both immunodepressed and immunocompetent adults. The present observations concern a previously healthy adult patient who presented with a fulminant hepatitis evolving in multiorgan failure (MOF), associated with an atypical papulo-ethemateous cutaneous rash without fever. An hepatic biopsy showed massive necrosis. Because of the persistent MOF and severe hemodynamic instability, total hepatectomy was performed as a bridge to urgent liver transplantation (OLT). Despite temporary improvement, the patients condition progressively deteriorated and he died 11 hours after the hepatectomy, i.e. 7 days after admission to the intensive care unit. High viral loads of varicella zoster virus (VZV) and human herpes virus 6 (HHV6) were demonstrated in the blood and in DNA at post mortem examination of the liver, kidneys, lung, and heart. We hypothesize that VZV infection may occasionally occur in immunocompetent patients due to extremely virulent strains that can be rapidly fatal. The clinical influence of simultaneous infection with HHV6 is not clear. Moreover, the role of a previous steroid treatment as a trigger for a temporary immunodepressed state must be considered. The diagnosis of liver disease from VZV should always be clinically suspected in the presence of concurrent atypical skin lesions and a temporarily immunocompromised state. Therapy with acyclovir was ineffective in our patient. Based on the wide spectrum of VZV infections, fulminant MOF in immunocompetent adults must raise the possibility of VZV with simultaneous HHV6 infection with early listing of the patient for a urgent OLT, possibly with a total hepatectomy as a bridge, due to the therapeutic uncertainty of medical treatments.