A specific deficit in spatial memory acquisition in post-traumatic stress disorder and the role of sleep in its consolidation.

Posttraumatic stress disorder (PTSD) is characterized by the presence of anatomo-functional hippocampal alterations. To date, the ability to orient within the environment, which relies on hippocampal integrity, has never been investigated in PTSD. We hypothesized that the ability to form a cognitive map of the environment would be impaired in PTSD. Moreover, spatial memory consolidation benefits from postlearning sleep. Because PTSD individuals often complain about sleep disturbances, we hypothesized that any sleep effect on memory performance would be hampered in these subjects. Twenty-two subjects, all survivors of the L'Aquila 2009 earthquake, were divided into a PTSD and a control group, based on clinical evaluation. After an acquisition phase, they were tested twice ("test" and "retest") on a virtual navigation task. In addition, participants were administered the Digit Span and Task Switching. Subjective sleep quality and sleep disturbances were also assessed. The two testing sessions were on consecutive mornings, interspersed with a night of sleep. During the acquisition phase, the PTSD group took more than twice as long to form a cognitive map of the environment compared to the control group. However, once this phase was successfully completed, the two groups did not differ at test, but they tendentially differed at postsleep retest. Additional analyses comparing performances between groups on test-retest difference scores confirm that sleep-dependent consolidation may be differentially affected in the two groups. Our findings are strictly confined to the navigation performance, excluding a generalized cognitive deficit. PTSD also reported more subjective sleep disturbances and shorter sleep time than controls, which were correlated to worse performance at retest. The specific deficit in the formation of a cognitive map reported in PTSD may be related to hippocampal dysfunctions as well as to the sleep disturbances experienced by these patients. The possible deficiency of sleep-dependent spatial performance improvement should however be confirmed by further studies comprising a wake control group.

Radiofrequency-assisted right hemihepatectomy by using a new incremental bipolar generator combined with liver hanging maneuver.

In order to reduce bleeding, various surgical maneuvers and devices have been used and radiofrequency (RF)-assisted liver resections have been recently advocated by many authors. We performed a right hemihepatectomy for colorectal liver metastases by using new radiofrequency generator (Surtron SB®) combined with hanging maneuver to facilitate the application of the probe and avoid injuries of the interior vena cava (IVC). Operative time was 245 minutes, intraoperative blood loss was 120 ml, transection blood loss was 70 mL. No blood units were administered at any time. After a regular postoperative (PO) course patient was discharged on 11th PO day with normal liver function tests. In conclusion combined use of a RF generator and hanging maneuver in right hemihepatectomy provide bloodless parenchymal transection. The enhanced exposure contributes to better hemostasis and permits the best allocation of the comb with protection of the IVC from injuries.

Switch From Twice-daily Tacrolimus to Once-daily, Prolonged-release Tacrolimus in Kidney Transplantation: Long-term Outcome.

BACKGROUND: One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety. METHODS: The aim of our study was to demonstrate the long-term efficacy and safety of switching from BDT to QDT in KT recipients. Preliminary results have already been published. Forty-one patients (34 men and 7 women), mean age at KT of 43.9 ± 12.7 years, underwent a 1:1 dose switch from BDT to QDT; the mean time from KT to switch was 36.6 ± 16.1 months. In our study population, 4 patients received a living donor KT and 2 received a second allograft. RESULTS: The mean follow-up was 86.8 ± 13 months from the switch and 126.2 ± 22.3 months from KT. Graft and patient survival rates were 90.2% and 95.1%, respectively. All patients maintained stable renal function during follow-up. During the first 3 months after the switch we observed a significant decrease in tacrolimus blood level (P = .0001). No significant differences were observed regarding tacrolimus dose before and after QDT introduction (P = not significant [NS]). Fourteen patients who stopped steroids under BDT treatment and 16 patients who stopped steroids after the switch are currently steroid-free. CONCLUSION: Our study showed safety and efficacy in switching from BDT to QDT. After early (<1 year) dose adjustment, tacrolimus blood levels remained stable throughout follow-up. Moreover, QDT represented a valid alternative for patients showing steroid side effects.

Landmark based navigation in brain-damaged patients with neglect.

We tested navigational abilities of brain-damaged patients suffering from representational or perceptual neglect asking them to retrieve a location according to salient spatial cues included in a rectangular empty room. Both groups of patients showed difficulties in learning the spatial definition of the target location in relation to two landmarks. However in a delayed attempt performed after several trials the group of patients with perceptual neglect proved able to easily retrieve the target location. In this condition they performed as controls showing a spared ability to navigate according to a stable representation of the room in long-term memory. In contrast the difficulty of patients with representational neglect remained unchanged across experimental conditions. At variance with clinical assessment, in which patients show asymmetrical performances in describing a well-known environment from memory, this latter result depicts a behavioural counterpart of the disorder, namely the inability to orient in a new environment according to an inner representation. Data are further discussed in order to provide a description of the cognitive mechanisms required for space representation for navigation.

Three-dimensional probabilistic maps of the occipital sulci of the human brain in standardized stereotaxic space.

Developments in functional neuroimaging in normal human subjects, such as functional magnetic resonance imaging (fMRI), have permitted the mapping of several visual areas of the human brain and have already provided provisional identification of some of the visual areas that were first described in nonhuman primates. However, the lack of a detailed description of the sulcal patterns of the human occipital lobe makes it difficult to establish clear relationships between sulcal landmarks and identified visual areas with functional neuroimaging. In the present study we used magnetic resonance images to investigate the morphological variation of the human occipital sulci in both the left and right hemispheres of 40 normal adult human brains. We identified 11 occipital sulci, the parieto-occipital fissure and the temporo-occipital incisure, and their corresponding gray matter voxels were marked in the magnetic resonance volumes which had been transformed into the Montreal Neurological Institute standard proportional stereotaxic space. Probability maps were then constructed for each occipital sulcus. These probability maps provide a quantitative measure of the variability of the occipital sulci in standard stereotaxic space and are a useful tool to identify the location of voxels of other magnetic resonance imaging images transformed in the same stereotaxic space.

The contribution of the fusiform gyrus and superior temporal sulcus in processing facial attractiveness: neuropsychological and neuroimaging evidence.

Current cognitive models suggest that the processing of dynamic facial attributes, including social signals such as gaze direction and facial expression, involves the superior temporal sulcus, whereas the processing of invariant facial structure such as the individuals' identity involves the fusiform face area. Where facial attractiveness, a social signal that may emerge from invariant facial structure, is processed within this dual-route model of face perception is uncertain. Here, we present two studies. First, we investigated the explicit judgments of facial attractiveness and attractiveness-motivated behavior in patients with acquired prosopagnosia, a deficit in familiar face recognition usually associated with damage to medial occipitotemporal cortex. We found that both abilities were impaired in these patients, with some weak residual ability for attractiveness judgments found only in those patients with unilateral right occipitotemporal or bilateral anterior temporal lesions. Importantly, deficits in attractiveness perception correlated with the severity of the face recognition deficit. Second, we performed a functional magnetic resonance imaging study in healthy subjects that included an implicit and explicit processing of facial attractiveness. We found increased neural activity when explicitly judging facial attractiveness within a number of cortical regions including the fusiform face area, but not the superior temporal sulcus, indicating a potential contribution of the fusiform face area to this judgment. Thus, converging neuropsychological and neuroimaging evidence points to a critical role of the inferior occipitotemporal cortex in the processing of facial attractiveness.

Renal allograft immune response is influenced by patient and donor cytokine genotypes.

This study investigated the impact of specific cytokine genotypes on the incidence of acute rejection episodes (ARE), chronic graft dysfunction (CGD), and anti-HLA donor-specific antibody (DS-Ab) production in 86 renal transplant recipients and 70 cadaveric donors. A PCR-SSP method was performed for the analysis of polymorphisms in TNF-alpha, IL-6, TGF-beta, IL-10, and IFN-gamma cytokines. DS-Ab monitoring of sera was performed using a FCXM analysis. Observed cytokine frequencies for patients and donors were not significantly different from the expected frequencies under Hardy-Weinberg equilibrium conditions. The evaluation in recipients revealed a higher frequency of DS-Ab-positive patients among the TNF-alpha high (50.0% vs 25.7%), and for the IL-10 cytokine a greater incidence of ARE-positive patients (35.8% vs 18.2%) with the high + intermediate, compared with the low genotype. The combined effect of these 2 genotypes predisposed to DS-Abs (71.4% vs 25.3%; P = 0.02; odds ratio [OR] = 7.37). As for the TGF-beta1 cytokine, we observed a higher number of CGD-positive patients among high compared with intermediate producers (14.3% vs 0%; P = .050). The analysis of donors revealed a significantly lower incidence of ARE-positive patients among recipients whose donors were carriers of the high IL-6 G/G-genotype compared with the G/C+C/C-genotypes (16.7% vs 41.2%; P = .03), suggesting a protective effect of the G/G genotype on ARE and a predisposing role of donor (-174)allele C. In addition, we noted an association between the IFN-gamma low A/A-genotype and a higher incidence of ARE (42.1% vs 0%; P = .002) and DS-Ab production (47.4% vs 12.5%; P = .02) compared with high producers.

Conversion to rapamycin immunosuppression for malignancy after kidney transplantation: case reports.

INTRODUCTION: Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro. METHODS: Eight patients developed the following malignancies after kidney transplantation (mean 102.6 months; range 12 to 252): metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 1), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD) (n = 2). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 2), associated with steroids (n = 4) or mycophenolate mofetil (n = 2). RESULTS: Both patients with metastatic cancer underwent chemotherapy and then succummbed after 6 and 13 months. After a mean follow-up of 20.3 months (range 2 to 47), the remaining six patients are free from cancer disease. Renal graft function was unchanged from diagnosis throughout the follow-up. CONCLUSION: Our observations suggested that rapamycin-based immunosuppression offered the possibility of regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was attributed to Rapamycin treatment or to the reduced immunosuppression.

Transplant surgeon formation: vocation, incentives, between old and new surgeon generations.

The training of the transplant surgeon is one of the most difficult paths in medicine. The transplant surgeon must be trained as a general and a vascular surgeon; he has to be skilled and upgraded in transplant surgical technique; he has to decide the suitability of the donor and of the organs as well as the immunosuppressive therapy for each recipient; he must know the intensive care unit, hepatology, and nephrology. The transplant surgeon has to deal with surgical, infectious, and metabolic complications after organ transplantation. Thus, clinical formation of the transplant surgeon is multifactorial and always upgraded. However, transplants never happen in the morning; retrivals are more likely to be in the night (especially the holidays ones). "Weekend" is a word not frequently used by transplant surgeons. Moreover, when the transplant procedure happens, the normal activity of the ward and of the outpatient clinic were have to be done. The transplant surgeon must have a sort of "vocation" for such a job. Organ harvesting setting is a good proof of adaptability, always during nighttime, often in small hospitals with operating room nurses unfamiliar with the procedure, sometimes waiting for some colleagues or delaying the surgery. This vocation is enhanced by enthusiasm, but incentives are necessary to feed this love. Incentives should be professional and economic; transplant surgeons should be allowed to make clinical decisions, to choose the surgical technique of transplantation, to control the decision process. Lastly, due to the "total on call," the surgeon should profit from a right salary avoiding extramural activities.

Long-term results of kidney transplantation with cyclosporine- and everolimus-based immunosuppression.

The aim of the study was to evaluate safety and efficacy of everolimus with cyclosporine (CsA) in de novo renal transplant recipients. The immunosuppressive regimen, including basiliximab, everolimus (3 mg), and low-dose CsA, was administered to 17 patients, of whom 15 were part of a multicenter randomized study that stipulated cessation of steroids at 7 days posttransplantation in 5 recipients. Five patients underwent dialysis after transplantation for delayed graft function (DGF; 29%), all of whom showed a good recovery within 3 weeks. The mean follow-up was 45.7 months (SD +/- 13). The 1-year graft survival was 100%. We observed one acute rejection episode. No patient experienced a cytomegalovirus infection. Increased cholesterol and triglyceride levels were reported in almost all patients. Severe arthralgia (n = 3) was treated by everolimus dose reduction to maintain trough levels at 3 ng/mL. We noted a high rate of switch to mycophenolate mofetil (MMF) throughout follow-up (n = 7), due to everolimus-induced side effects. However, we did not observe normalization of lipids after the switch: patients always required stain treatment, resulting in slightly lower serum cholesterol and triglycerides. Everolimus plus CsA was effective to prevent acute rejection after kidney transplantation. To manage the induced side effects of the drugs C(2) monitoring is mandatory, targeting 350 ng/mL during 1 year and 200 to 250 ng/mL thereafter. Careful reduction of everolimus trough levels to 3 ng/mL is recommended for patients with arthralgia.

Graft failure due to hemolytic uremic syndrome recurrence.

The hemolytic uremic syndrome (HUS) is a severe disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. We herein report our experience with a 43-year-old female patient who underwent a second cadaveric kidney transplantation in February 2005, for adult-onset HUS. The first renal transplantation, which was performed in 1996, required removal after 3 weeks for probable recurrence of HUS. The immunosuppressive regimen for the second transplant included basiliximab, tacrolimus, mycophenolate mofetil, and steroids. On postoperative day (POD) 7, she received steroid treatment for an acute rejection episode with improved renal function. On POD 19 due to worsening renal function, a graft biopsy showed HUS recurrence, thus we instituted hemodialysis and then plasmapheresis treatments. At two months after transplantation, the patient continued under plasmapheresis treatment due to clinical evidence of HUS. On POD 80, cytomegalovirus infection was diagnosed and intravenous gancyclovir treatment started for 3 weeks. After 110 days from transplant, a deterioration in renal function was evident: the graft was swollen and painful with Doppler ultrasound showing patency of both the renal artery and vein but, low blood flow. After 2 weeks of hemodialysis, the patient underwent transplantectomy. In adult-onset HUS the recurrence rate reduces graft survival, particularly among patients undergoing second transplantation.

Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154.

Clinical islet cell transplantation has resulted in insulin independence in a limited number of cases. Rejection, recurrence of autoimmunity, and impairment of normal islet function by conventional immunosuppressive drugs, e.g., steroids, tacrolimus, and cyclosporin A, may all contribute to islet allograft loss. Furthermore, intraportal infusion of allogeneic islets results in the activation of intrahepatic macrophages and endothelial cells, followed by production of proinflammatory mediators that can contribute to islet primary nonfunction. We reasoned that the beneficial effects of anti-CD154 treatment on autoimmunity, alloreactivity, and proinflammatory events mediated by macrophages and endothelial cells made it an ideal agent for the prevention of islet allograft failure. In this study, a nonhuman primate model (Papio hamadryas) was used to assess the effect of humanized anti-CD154 (hu5c8) on allogeneic islet engraftment and function. Nonimmunosuppressed and tacrolimus-treated recipients were insulin independent posttransplant, but rejected their islet allografts in 8 days. Engraftment and insulin independence were achieved in seven of seven baboon recipients of anti-CD154 induction therapy administered on days -1, 3, and 10 relative to the islet transplant. Three of three baboons treated with 20 mg/kg anti-CD154 induction therapy experienced delayed rejection episodes, first detected by elevations in postprandial blood glucose levels, on postoperative day (POD) 31 for one and on POD 58 for the other two. Re-treatment with three doses of anti-CD154 resulted in reversal of rejection in all three animals and in a return to normoglycemia and insulin independence in two of three baboons. It was possible to reverse multiple episodes of rejection with this approach. A loss of functional islet mass, as detected by reduced first-phase insulin release in response to intravenous glucose tolerance testing, was observed after each episode of rejection. One of two baboons treated with 10 mg/kg induction therapy became insulin independent post-transplant but rejected the islet graft on POD 10; the other animal experienced a reversible rejection episode on POD 58 and remained insulin independent and normoglycemic until POD 264. Two additional baboon recipients of allogeneic islets and donor bone marrow (infused on PODs 5 and 11) were treated with induction therapy (PODs -1, 3, 10), followed by initiation of monthly maintenance therapy (for a period of 6 months) on POD 28. Rejection-free graft survival and insulin independence was maintained for 114 and 238 days, with preservation of functional islet mass observed in the absence of rejection. Prevention and reversal of rejection, in the absence of the deleterious effects associated with the use of conventional immunosuppressive drugs, make anti-CD154 a unique agent for further study in islet cell transplantation.

Infectious complications in the renal transplant recipient.

The aim of this study was to estimate the incidence of infectious diseases in a group of patients who underwent kidney transplantation from January 1, 2004 to September 30, 2004, including 121 operations, with 119 from cadaveric and 2 from living donors. The protocol sought herpes viruses (CMV, VZV, and EBV), hepatitis viruses, human immunodeficiency virus, T. gondii, M. tubercolosis, and T. pallidum. Therapy for CMV was used both as prophylaxis in immunoglobulin (Ig)G-negative recipients from IgG-positive donors and preemptive therapy, that is, before the appearance of clinical symptoms, but after viremia reached borderline levels. For VZV infections, the treatment started after the appearance of papulo-vesicular cutaneous eruptions and antibody positivity. The treatment for pneumonia consisted of empirical therapy after radiography; for pyelonephritis, antibiotic therapy was based on the results of kidney echography, blood culture, and urine culture. Infectious complications appeared in 25 patients (20.7%), 3 of the which were polymicrobic: 12 CMV infections, 9 VZV infections, 3 pneumoniae, 4 pyelonephritis, and 1 salmonellosis. The most frequent infection was CMV, which occurred in the first 3 months after transplantation in 9 of 12 cases. This study showed that a knowledge of infection prevalence can help the physician to establish a more specific, efficacious antimicrobial therapy, despite the laboratory response not being available in a short time.

Urologic complications in kidney transplantation.

Urologic complications in kidney transplantation have an incidence ranging from 3% to 20%, representing an important cause of organ loss. From January 2001 to September 2004, 123 renal transplantations were performed using an immunosuppressive protocol including basiliximab, mycophenolate mofetil, calcineurin inhibitors, and steroids. The surgical technique was vascular anastomoses to external iliac vessels, and ureteral anastomosis according to Lich Gregoire technique using a JJ ureteral stent. We report 5 renal complications (4.2%) and 4 extrarenal complications (3.5%), the majority of which required corrective surgery. The surgical strategy uses the clinical condition of the donor and the recipient; the anatomic anomalies of the graft, and a reduced cold ischemia time. Moreover, a reduction in acute rejection episodes and immediate renal function has been fundamental to reduce urologic complications. In fact, the main cause of urologic complications is ureteral ischemia, linked both to backtable surgery and to rejection episodes. Another important factor in the reduction of early urologic complications has been the routine use of a JJ stent, which allowed us a conservative approach in this setting.

Malignancies after kidney transplantation.

The most effective treatment of end-stage renal disease is renal transplantation; its superiority to prolong the longevity of patients is well established. Patient and graft survivals have improved with more potent immunosuppression but this advance has been associated with an increased incidence of cancer. The aim of this study was to assess the prevalence of cancer among 265 kidney transplant recipients engrafted between 1968 and October 2004. The overall prevalence of de novo malignancies was 3%. The mean age at diagnosis was 53.3 years (range, 28-63 years) and the duration of the transplant was 11.6 years (range, 0.3-33 years). One patient among 127 (0.8%) who had a history of less than 3 years under immunosuppression, developed a posttransplantation lymphoproliferative disorder (PTLD). Among the 138 patients who had more than 3 years immunosuppression, 7 (5%) developed neoplasms of vulva, colon, native kidneys, prostatic gland, and ovary. One patient was affected by de novo carcinoma in the transplanted kidney. Compared with other published studies, our early cancer prevalence is low, possibly due to a careful history before grafting, good HLA matching, and abstinence from anti-T-cell therapy for treatment of acute rejection episodes. The low level of immunosuppression may account for the low prevalence of neoplasia. The risk of developing a malignancy increases with long-term immunosuppression, comparable with most reports.

Switch to tacrolimus for cyclosporine-induced gynecomastia in liver transplant recipients.

We report herein on two male liver transplant (LT) recipients who presented with cyclosporine (CsA)-related gynecomastia 6 and 10 months after transplantation. The clinical workup showed increased luteinizing hormone (LH), associated with a slight reduction in testosterone blood levels in one patient and increased prolactin levels in the other. After excluding concomitant primary endocrine and/or malignant disease, conversion to tacrolimus (TAC) was performed resulting in clinical improvement of gynecomastia and return of hormone blood levels to normal range within 3 months. Our report confirms a putative role of CsA in post-LT gynecomastia, reversible however upon conversion to TAC.

Current indications and limits of pancreatic islet transplantation in diabetic nephropathy.

Insulin-dependent diabetes mellitus (IDDM) is a disease caused by a progressive autoimmune destruction of the insulin-producing beta-cells within the pancreas. A major task of diabetes research consists in developing new forms of treatment to delay or prevent the development of the chronic complications associated with the disease. Islet transplantation could become an attractive alternative to whole organ transplantation, since it is a simpler and safer procedure. However, the requirement for long-term immunosuppression has limited the indication of islet transplantation to patients receiving a simultaneous kidney transplant or already bearing one. While the majority of recipients of islet allografts did not become insulin independent, the field has witnessed significant progress and the long-term results in patients with even partial graft function are comparable or better than those achievable with intensive insulin therapy. Recent trials of donor bone marrow infusions combined with solid organ transplants are in progress to determine whether donor-specific tolerance can be achieved with the potential to expand the future indications of islet transplantation in diabetes.

Sirolimus in kidney transplantation from marginal donors.

Nephrotoxicity caused by calcineurin inhibitors can lead to either delayed graft function or long-term decline of renal function after kidney transplantation. Therefore, recipients of renal transplants from marginal donors require non-nephrotoxic immunosuppression. Eighteen patients received kidney transplants from marginal donors, with a calcineurin inhibitor-free immunosuppressive regimen, based on basiliximab, mycophenolate mofetil, steroids, and sirolimus. Renal graft biopsy was performed in all cases before surgery. Mean follow-up was 11.8 months. We report immediate renal function in 9 patients, delayed graft function in 5 and acute tubular necrosis in 4 patients. One patient was successfully treated for biopsy-proven acute rejection. Hypercholesterolemia and hypertriglyceridemia were the most common adverse effects (n = 13) associated with arthralgia (n = 2) and thrombocytopenia (n = 2). Five patients underwent a switch to tacrolimus, due to sirolimus-induced side effects. Immunosuppression without the use of calcineurin inhibitors is a safe and effective regimen in kidney transplantation, although sirolimus-related side effects still represent a morbidity factor in these patients.

[Plastic surgery of the abdominal wall in laparocele in a patient with previous kidney transplant]. / Plastica della parete addominale per laparocele in paziente con pregresso trapianto renale.

The authors report the case of a patient undergoing kidney transplant from a non-related but compatible living donor who subsequently developed a voluminous incisional hernia affecting almost the entire small intestine in the right iliac fossa, the site of earlier surgery. After having analysed the problems involved when a transplant patient requires further surgery owing to the chronic administration of drugs, the authors describe the case. The patient was treated using the insertion of a prolene graft and remodelling the abdominal wall in correspondence with the lower quadrants using abdominoplasty without repositioning the umbilicus.

Placental, lipid, and glucidic effects of mammalian target of rapamycin inhibitors: impact on fetal growth and metabolic disorders during pregnancy after solid organ transplantation.

BACKGROUND: Mammalian target of rapamycin inhibitors (mTORi) are a promising new family of immunosuppressive drugs. No teratogenic effects have been reported to date. Their lipid and glucidic effects should not be underestimated, however, especially during pregnancy. Moreover, mTORi may affect fetal growth by mTOR placental activity. OBJECTIVE: Our purpose was to highlight mTORi placental impact and metabolic implications to detect possible maternal or fetal effects and define management guidelines in pregnant women after solid organ transplantation. METHODS: A literature search was performed for articles from the Medline and Pubmed databases with the use of the following keywords: mTOR inhibitors, pregnancy, placental transport, lipid metabolism, glucose metabolism. RESULTS: mTOR works as a positive regulator of system A, system L, and taurine placental amino acid transporter activity, which are critical for the transport of amino acids to the fetus. Exposing trophoblast cells to rapamycin reduces system L activity; therefore, treatment with rapamycin in human pregnancies could alter fetal growth with intrauterine growth restriction (IUGR). Regarding the metabolic effects mTORi increase lipolysis, impair insulin's antilipolytic effect and reduce lipid storage, which may potentially contribute to dyslipidemia. Chronic rapamycin treatment reduces adipose tissue size and ß-cell mass/function, causes hyperlipidemia, severe insulin resistance, and glucose intolerance, and promotes hepatic gluconeogenesis. CONCLUSIONS: The studies on mTORi treatment in transplanted pregnant women have not focused to date on the potential metabolic and placental effects. Selection of women at high risk for metabolic disorders could be needed and consideration of switching to another immunosuppressive drug required if diabetes and abnormal blood lipids have been diagnosed in prepregnancy counseling. It seems to be mandatory to encourage prompt reporting of any additional cases of pregnancy during mTORi exposure to provide a better understanding of the placental effects and safety profile of these immunosuppressive drugs.