Longitudinal monitoring of mRNA levels of regulatory T cell biomarkers by using non-invasive strategies to predict outcome in renal transplantation.

BACKGROUND: Acute T-cell mediated rejection (aTCMR) is still an issue in kidney transplantation, for it is associated with chronic rejection, graft loss, and overall worse outcomes. For these reasons, a standard non-invasive molecular tool to detect is desirable to offer a simpler monitoring of kidney transplant recipients (KTRs). The purpose of our study was to examine, in peripheral blood before and after transplantation, the expression patterns of regulatory T cell (Treg)-related genes: the forkhead box P3 (FOXP3) and the two CTLA-4 isoforms (full-length and soluble) to predict acute rejection onset, de novo donor-specific antibodies (DSA) development and renal dysfunction 1 year after transplantation. METHODS: We profiled by using a relative quantification analysis (qRT-PCR) circulating mRNA levels of these biomarkers in peripheral blood of 89 KTRs within the first post-transplant year (at baseline and 15, 60 and 365 days, and when possible at the acute rejection) and compared also the results with 24 healthy controls. RESULTS: The three mRNA levels drastically reduced 15 days after transplantation and gradually recovered at 1 year in comparison with baseline, with very low levels at the time of aTCMR for FOXP3 (RQ = 0.445, IQR = 0.086-1.264, p = 0.040), maybe for the pro-apoptotic role of FOXP3 during inflammation. A multivariate Cox regression analysis evidenced a significant relation between aTCMR onset and thymoglobuline induction (HR = 6.749 p = 0.041), everolimus use (HR = 7.017, p = 0.007) and an increased risk from the solCTLA-4 expression at 15 days, mainly considering recipients treated with Mycophelolic acid (HR = 13.94 p = 0.038, 95%CI:1.157-167.87). Besides, solCTLA-4 also predisposed to graft dysfunction (eGFR< 60 mL/min/1.73m2) at 1 year (AOR = 3.683, 95%CI = 1.145-11.845, p = 0.029). On the other hand, pre-transplant solCTLA-4 levels showed a protective association with de novo DSAs development (HR = 0.189, 95%CI = 0.078-0.459, p < 0.001). CONCLUSIONS: mRNA levels of Treg-associated genes, mainly for solCTLA-4, in peripheral blood could put forward as candidate non-invasive biomarkers of cellular and humoral alloreactivity in clinical transplantation and might help shape immunosuppression, tailor monitoring and achieve better long-term outcomes of kidney transplantation in the wake of "precision medicine".

Early-Isolated V Lesion in Kidney Allograft: Acute Rejection or Ischemic Injury? A Case Report of Primary Nonfunction and Graft Loss.

Intimal arteritis (v-lesion) is a negative prognostic factor for kidney allograft survival. Early isolated v-lesions do not always represent a pathologic marker of acute T cell- or antibody-mediated rejection. In particular, in the case of transplant negative for C4d and donor-specific antibodies, such a finding can suggest an ischemic-reperfusion injury. There is an intense debate in the literature concerning the origin of this histologic feature. In the present study, we analyze how this argument can have a clinical relevance. Here we report a case of a 61-year-old woman with end-stage renal disease due to autosomal dominant polycystic kidney disease. The patient underwent kidney transplant from expanded criteria donor. Organs from expanded criteria donors are more prone to ischemic-reperfusion injury. Postoperative course was characterized by primary nonfunction of the graft. A first biopsy showed early isolated v-lesion in otherwise normal renal parenchymal. Simultaneously, a computed tomography scan revealed stenosis of the main renal artery. An endovascular stent was placed. Despite improved vascularization of the graft, no clinical response was observed and the patient remained anuric. A second biopsy was performed, showing T-cell mediated rejection (Banff Classification 1A). Despite pulse steroid, the patient lost the graft.

Hepatitis E Outbreak in the Central Part of Italy Sustained by Multiple HEV Genotype 3 Strains, June-December 2019.

In European countries, autochthonous acute hepatitis E cases are caused by Hepatitis E Virus (HEV) genotype 3 and are usually observed as sporadic cases. In mid/late September 2019, a hepatitis E outbreak caused by HEV genotype 3 was recognized by detection of identical/highly similar HEV sequences in some hepatitis E cases from two Italian regions, Abruzzo and Lazio, with most cases from this latter region showing a link with Abruzzo. Overall, 47 cases of HEV infection were finally observed with onsets from 8 June 2019 to 6 December 2019; they represent a marked increase as compared with just a few cases in the same period of time in the past years and in the same areas. HEV sequencing was successful in 35 cases. The phylogenetic analysis of the viral sequences showed 30 of them grouped in three distinct molecular clusters, termed A, B, and C: strains in cluster A and B were of subtype 3e and strains in cluster C were of subtype 3f. No strains detected in Abruzzo in the past years clustered with the strains involved in the present outbreak. The outbreak curve showed partially overlapped temporal distribution of the three clusters. Analysis of collected epidemiological data identified pork products as the most likely source of the outbreak. Overall, the findings suggest that the outbreak might have been caused by newly and almost simultaneously introduced strains not previously circulating in this area, which are possibly harbored by pork products or live animals imported from outside Abruzzo. This possibility deserves further studies in this area in order to monitor the circulation of HEV in human cases as well as in pigs and wild boars.

Transplant Renal Artery Stenosis: A Case Report of Functional Recovery Six Months After Angioplasty.

Transplant renal artery stenosis (TRAS) is a common vascular complication after kidney transplantation, leading to worsening or refractory hypertension, deterioration in renal function, and possible cause of graft loss. Early diagnosis and an appropriate treatment are crucial for organ preservation. Endovascular treatment, including percutaneous transluminal angioplasty and stent implantation, is considered the first-line therapy for TRAS. Here we report the case of a 69-year-old woman with end-stage renal disease for chronic kidney disease not biopsy proven, who underwent a kidney transplant from expanded criteria donors on December 2018. Postoperative course was characterized by delayed graft function. Doppler ultrasonography (US) showed an increase of peak systolic velocity at the origin of the renal artery, and parvus-tardus waveform in periferic graft arteries and an abdominal computed tomography scan confirmed a stenosis at the origin of the main renal artery (TRAS). The patient underwent a percutaneous transluminal angioplasty. It was not possible to place a stent at the particular location of the stenosis at the anastomosis. Despite the improvement of the graft's perfusion, monitored with Doppler US, the patient showed a very poor improvement in renal function and remained on hemodialysis for months. A percutaneous needle biopsy reported a normal renal parenchyma and excluded acute rejection. During this period, the patient received immunosuppressive therapy. About 6 months after the transplant, the patient had an unexpected and slow renal function recovery until she was weaned completely from hemodialysis.

Follow-up and Management of Kidney Transplant Recipients During the COVID-19 Lockdown: The Experience of an Italian Transplant Center, Including Two Cases of COVID-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new infectious disease that emerged in China in late 2019 and is now spreading around the world. Social distancing measures were needed to reduce transmission, and lockdown included restricted access to health care facilities. The impact of COVID-19 on transplant recipients is unknown, but considering their immunosuppression status and associated comorbidities, they should be considered a high-risk population. METHODS: A kidney transplant center in Central Italy implemented a strategy to maintain follow-up of kidney transplant recipients by phone and e-mail during lockdown. Telephone interviews were used to administer a clinical questionnaire to patients, and e-mail was used to receive the results of diagnostic tests conducted in outpatient settings. RESULTS: From March 17 to April 23, 2020, a total of 143 kidney transplant recipients were contacted. Twenty-eight patients needed in-hospital consultation for problems unrelated to COVID-19, 3 of whom needed hospitalization. Eleven patients were managed at home for mild urinary or respiratory diseases, and 1 was referred to the hematologist. We identified 2 suspected cases of COVID-19 infection, and the patients were referred to hospital care. Immunosuppressive therapy was modulated, and intravenous corticosteroids and potentially effective antiviral therapy were administered with a favorable outcome. CONCLUSIONS: In the context of a lockdown, such as that occurring in response to COVID-19, we suggest implementing remote surveillance programs in kidney transplant recipients with the help of any available technology and offering medical consulting and logistic support as needed.

Transplant Patients' Isolation and Social Distancing Because of COVID-19: Analysis of the Resilient Capacities of the Transplant in the Management of the Coronavirus Emergency.

BACKGROUND: One of the peculiar aspects of the transplant patient's life is that, in the post-surgery phase, the patient lives in an "isolation" condition, having to pay particular attention to the living environment and preferring a limited social life given that the immunosuppressive treatment entails immunodepression in the patient. With coronavirus disease 2019 (COVID)-19, as in a post-surgery situation, social isolation is being implemented. MATERIALS AND METHODS: The study started on March 17, 2020, and ended on April 24, 2020. Consulting/phone interviews were made. The phone questionnaire, submitted to 71 patients, consisted of a set of 15 questions that investigated structure and psychological resistance. Eight patients have been monitored exclusively for the psychological aspect through a more articulate supporting path. RESULTS: In essence, from the overall analysis of the data derived from the study of the positioning of patients based on the stage of renal function, the bands related to the development of psychopathological aspects, and the use of positive personal resources, it emerges that patients in stage V kidney failure are in the first bracket as regards the development of psychopathological aspects (absence of these experiences) and in the third bracket as regards the good use of positive resources to deal with isolation. Therefore, it can be deduced that, although with data that can be expanded, a serious or medium-serious situation from an organic point of view in this socio-health emergency situation is well addressed by the transplanted patient. CONCLUSION: Transplant patients have faced the measure of social distancing adequately and in adherence to the treatment thanks to the phone assistance of all the medical-surgical and psychological team.

Analysis of Psychopathologic Elements as a Compliance Limitation: Team Work as a Therapeutic Response.

INTRODUCTION: The psychological evaluation of the patient, carried out through psychodiagnostic tests, clinical interviews, and a joint work with the medical-surgical team, provided useful information to assess the compliance of the kidney transplant recipient. METHODOLOGY: Two hundred and forty-five visits were carried out between September 2018 and May 2019 in the General Surgery and Organ Transplant Department of the San Salvatore Hospital, L'Aquila. The visits consisted of clinical interviews, targeted psychodiagnostic evaluations, graphic-projective tests, and personality and cognitive structure evaluation tests. These assessments were key not only to defining the patient's personality picture but also to offering suitable psychological support to patients on waiting lists for transplantation, during hospitalization, and during follow-up visits from transplantation phases. RESULTS: From the analysis of the tests and from the clinical and support interviews, some of the patients presented forms of psycho-emotional immaturity that impaired the predisposition to compliance and ultimately the establishment of the therapeutic alliance. During 8 months, 18 compliance limit cases were observed, 5 patients were sent to mental health centers, and 13 psychological support courses were activated within the Regional Transplant Center-Abruzzo Region Molise Region. No structured psychological support courses were deemed necessary for 9 of these 13 cases, whereas 4 were sent to the mental health centers. CONCLUSIONS: By assessing the complexity of each patient from a medical and a psychological point of view and by considering the high number of transplant surgeries currently occurring, it can be noted that compliance to therapy is strongly linked to the reliability of the relationships between patients and caregivers.

Psychodiagnostic Examination of a Living Kidney Donor. Correlation Between the Scales Referred to the Paranoia of the Minnesota Multiphasic Personality Inventory-2: A Case Report.

INTRODUCTION: The study involves the psychodiagnostic evaluation of a 53-year-old female living kidney donor. The donation is in favor of the 56-year-old sister. The potential donor is separated, is currently unemployed, and holds a lower secondary education diploma. METHODOLOGY: The psychodiagnostic evaluation of the donor was carried out by means of clinical-anamnestic interviews, followed by Graphic-Projective Tests. The MMPI-2 Personality Test was administered at a later stage. RESULTS: It was noted that the patient showed: an initial lack of collaboration to undergo the psychodiagnostic evaluation; limited cognitive aspects of flexibility, criticism, and judgment; a distinct emotive response, which manifested as closure, anxiety, and dependence on the other; and elements that resulted from MMPI-2. The analysis of the clinical interviews, of the tests and their correlations, shows the existence of a simple personality framework characterized by concrete thinking that seldom performs functions exceeding the limits by a tendency toward closure and introversion and by consistent mood tone. No elements of psychopathology were identified. CONCLUSIONS: The psychodiagnostic evaluation resulted in excluding the subsistence of psychopathologies and allowed for a positive judgment of the suitability for donation. The evaluation also provided significant information on the limited capacity for therapeutic alliance and on the general attitude of closure and rejection of inputs coming from the external world. Patient monitoring is recommended in case of actual donation.

Evaluation of Plasma Levels of Soluble HLA-G and HLA-G Genotypes in Kidney Transplant Recipients.

In the field of transplantation, expression of HLA-G, a nonclassical HLA molecule with immunosuppressive functions and limited gene polymorphism, is considered beneficial for graft acceptance; various studies have aimed to demonstrate this role in transplantation. Recently, in other clinical conditions, it has been observed that insulin resistance was associated with HLA-G14bpins/del polymorphism, the most studied regulatory polymorphism of this molecule. In the present study, plasma levels of the soluble form of HLA-G (sHLA-G) were analyzed in kidney transplant recipients (n = 103) with different HLA-G14bpins/del genotypes. In a group of 26 recipients, sHLA-G was detected before and after transplantation (1 year) to evaluate early variations. In 77 recipients, sHLA-G was detected after transplantation (3-24 years) and correlated with occurrence of long-term post-transplant morbidity (diabetes mellitus, hyperlipidemia, hypertension, obesity, etc.). METHODS: Levels of sHLA-G were measured in plasma with an enzyme-linked immunosorbent assay; HLA-G14bpins/del and HLA-G+3142C>G genotypes were assessed using direct polymerase chain reaction. RESULTS: Plasma levels of sHLA-G significantly decreased during the first year after transplantation (P = .019); no significant correlations were found with genotypes or early post-transplant events. Lower levels of sHLA-G were found in recipients with post-transplant diabetes mellitus or obesity carrying the HLA-G14bpins/ins (P = .006 and P = .003, respectively) or HLA-G+3142G/G genotypes. CONCLUSIONS: A complex modulation of HLA-G, which includes both immunologic and metabolic effects, could affect the risk for long-term post-transplant morbidity in kidney transplant recipients. Associations of HLA-G, diabetes, and obesity deserve to be investigated by deeply exploring HLA-G regulatory variants.

Viremia Negativization After BK Virus Infection in Kidney Transplantation: A National Bicentric Study.

BACKGROUND: BK virus (BKV) infection represents a potentially dreadful complication after kidney transplantation (KT). When BK viremia is detected, the best therapeutic approach remains not entirely clarified. Critical elements of BK viremia treatment are immunosuppression minimization and introduction of drugs like leflunomide, everolimus, and fluoroquinolones. The study aimed to analyze the results of the BK viremia management in 2 collaborative Italian centers. METHODS: Ten patients undergoing KT in the 2 collaborative Italian centers of Sapienza University of Rome and University of L'Aquila from January 2013 to December 2017 and showing a post-KT diagnosis of BK viremia were retrospectively investigated. RESULTS: Mean time from KT to BKV positivity was 7 months (range: 1-19 months). At diagnosis, the mean viral load was 683,842 copies/mL (range: 5800-4,052,415 copies/mL), with an average zenith of 2,428,410 copies/mL (range: 6762-18,022,500 copies/mL). In the 5 patients with BKV nephropathy, we observed a switch from antimetabolite to leflunomide (n = 5), a switch from tacrolimus to everolimus (n = 3), or an introduction of fluoroquinolones (n = 3). BKV clearance was achieved in 3 patients. CONCLUSIONS: Early BKV diagnosis and stepwise minimization of immunosuppression remain the first-line approach in patients with BK viremia. In the presence of BKV nephropathy, a combination of antiviral drugs like leflunomide and fluoroquinolones/everolimus should favor viremia clearance.

Standard laparoscopic versus single-incision laparoscopic colectomy for cancer: early results of a randomized prospective study.

BACKGROUND: Standard laparoscopic colectomy (SLC) for cancer is a safe, feasible, and oncologically effective procedure with better short-term and similar long-term results of open colectomy. Conversely, owing to technical difficulties in colonic resection and full mesenteric dissection, single-incision laparoscopic colectomy (SILC) has been considered unsuitable for oncologic purposes. We compared the technical feasibility and early clinical outcomes of SLC and SILC for cancer. METHODS: In this prospective randomized clinical trial, 16 (50%) patients underwent SLC (10 left and 6 right) and 16 (50%) patients underwent SILC (8 left and 8 right). RESULTS: Demographics, preoperative data, and characteristics of the tumor were similar. The mean number of resected lymph nodes was 16 ± 5 in the SLC and 18 ± 6 in the SILC group (P = NS). Surgical time was 124 ± 8 minutes and 147 ± 5 minutes, respectively (P = NS). Surgical mortality was nil and the major morbidity rate was 6.3% in both groups. CONCLUSIONS: SILC for cancer is a technically feasible and safe oncologic procedure with short-term results similar to those obtained with a traditional laparoscopic approach.

Laparoscopic transperitoneal decortication of a giant peripelvic renal cyst.

Laparoscopic decortication is currently considered the standard treatment of peripelvic renal cysts, in spite of the technical challenge due to the close contiguity with renal hilar structures. However, to date, few small series or single cases of laparoscopic decortication for symptomatic peripelvic cyst have been reported. In this paper, we report the first case of a giant peripelvic cyst (25 x 18 x 9 cm) treated by transperitoneal laparoscopic decortication in a young adult female. Pain relief and hypertension control were obtained early after surgery, and the patient is symptom free at a 30-month follow-up.

Totally laparoscopic total and subtotal gastrectomy with extended lymph node dissection for early and advanced gastric cancer: early and long-term results of a 100-patient series.

BACKGROUND: Controversies exist about feasibility and oncologic effectiveness of laparoscopic gastrectomies with extended lymphadenectomy for advanced gastric cancer. The aim of our study was to determine if long-term results of these laparoscopic procedures may justify their use as an alternative to open surgery also in advanced gastric cancer. METHODS: We performed a retrospective review of 100 patients after laparoscopic surgery for gastric cancer. RESULTS: Tumor stage (S) was SIA in 21 patients, SIB in 20, SII in 17, SIIIA in 17, SIIIB in 5, and SIV in 20. Eleven total and 89 subtotal R0 gastrectomies were performed. The mean number of dissected lymph nodes was 35 +/- 18. The conversion rate was 3%. Surgical mortality and major morbidity were 6% and 13%, respectively. Overall and disease-free 5-year survival rates were 59% and 57%, respectively. CONCLUSIONS: Laparoscopic gastrectomy with extended lymphadenectomy for early and advanced gastric cancer is feasible, safe, and oncologically effective. Long-term survival rates are similar to those observed after open surgery.

[Thyroid surgery: total and partial resection. Analysis of complications and a review of the literature]. / La chirurgia tiroidea: exeresi totale ed exeresi parziale. Analisi in termini di complicanze e revisione della letteratura.

The authors review the recent international literature relating to approximately 36,800 cases of thyroid surgery, analysing the complications associated with total thyroidectomy versus partial resection of the thyroid, with a view to drawing up lines of conduct in terms of indications for surgery of benign disease and suggestions on surgical technique to reduce complications such as recurrent laryngeal nerve injuries (transient and definitive), hypocalcaemia (transient and definitive) and superior laryngeal nerve injuries.