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1.
BMC Surg ; 24(1): 179, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867261

ABSTRACT

BACKGROUND: Adhesive small bowel obstruction (ASBO) is a leading cause of hospitalization in emergency surgery. The occurrence of bowel ischemia significantly increases the morbidity and mortality rates associated with this condition. Current clinical, biochemical and radiological parameters have poor predictive value for bowel ischemia. This study is designed to ascertain predictive elements for the progression to bowel ischemia in patients diagnosed with non-strangulated ASBO who are initially managed through conservative therapeutic approaches. METHODS: The study was based on the previously collected medical records of 128 patients admitted to the Department of Acute Care Surgery of Padua General Hospital, from August 2020 to April 2023, with a diagnosis of non-strangulated adhesive small bowel obstruction, who were then operated for failure of conservative treatment. The presence or absence of bowel ischemia was used to distinguish the two populations. Clinical, biochemical and radiological data were used to verify whether there is a correlation with the detection of bowel ischemia. RESULTS: We found that a Neutrophil-Lymphocyte ratio (NLR) > 6.8 (OR 2.9; 95% CI 1.41-6.21), the presence of mesenteric haziness (OR 2.56; 95% CI 1.11-5.88), decreased wall enhancement (OR 4.3; 95% CI 3.34-10.9) and free abdominal fluid (OR 2.64; 95% CI 1.08-6.16) were significantly associated with bowel ischemia at univariate analysis. At the multivariate logistic regression analysis, only NLR > 6.8 (OR 5.9; 95% CI 2.2-18.6) remained independent predictive factor for small bowel ischemia in non-strangulated adhesive small bowel obstruction, with 78% sensitivity and 65% specificity. CONCLUSIONS: NLR is a straightforward and reproducible parameter to predict bowel ischemia in cases of non-strangulated adhesive small bowel obstruction. Employing NLR during reevaluation of patients with this condition, who were initially treated conservatively, can help the acute care surgeons in the early prediction of bowel ischemia onset.


Subject(s)
Intestinal Obstruction , Intestine, Small , Lymphocytes , Neutrophils , Humans , Retrospective Studies , Intestinal Obstruction/etiology , Intestinal Obstruction/diagnosis , Intestinal Obstruction/surgery , Male , Female , Aged , Intestine, Small/blood supply , Intestine, Small/pathology , Middle Aged , Lymphocytes/pathology , Tissue Adhesions/diagnosis , Ischemia/diagnosis , Ischemia/etiology , Predictive Value of Tests , Aged, 80 and over , Adult
2.
Front Oncol ; 13: 1268190, 2023.
Article in English | MEDLINE | ID: mdl-38094601

ABSTRACT

Background: Surgical oncological emergencies represent a frequent challenge in acute settings, with postoperative courses characterized by high morbidity and mortality. An accurate selection of patients who could benefit from surgery is essential to avoid unnecessary invasive treatment. In this study, we tried to determine if advanced age (>80 years) represents a risk factor for negative short-term outcome in patients undergoing emergency surgery for acute abdominal oncological illness. Methods: We retrospectively analyzed the records of patients who underwent emergency oncological surgery at the Department of Acute Care Surgery of Padua General Hospital from January 2018 to December 2022. One hundred two cancer patients were included in the study. Among them, 42 were aged ≥80 years (41%). Multiple preoperative and postoperative parameters were recorded, and the follow-up period was at least 90 days. Multivariate logistic regression analyses were used to identify factors associated with short-term postoperative outcomes. Results: In the octogenarian group, 30-day mortality was 11% vs. 9.5% in the younger group [p = not significant (ns)] and 90-day mortality was 17.6% in the octogenarian group vs. 20.5% in the younger group (p = ns). Postoperative morbidity and hospital length of stay were not significantly different in the two groups. Low albumin levels [odds ratio (OR) 30.6, 9.51-87.07] and elevated lactate dehydrogenase (LDH) levels (OR 26.4, 9.18-75.83) were predictive for short-term mortality in surgical oncological emergencies. Conclusion: Advanced age is not a risk factor for negative outcomes in surgical oncological emergencies. Therefore, surgical options should be considered in octogenarians with oncological emergencies and acceptable clinical conditions. Serum albumin levels and LDH can help predict the postoperative outcome after surgery for oncological emergencies.

3.
Transplant Proc ; 55(3): 554-561, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36948957

ABSTRACT

BACKGROUND: The safety of laparoscopic donor nephrectomy (LDN) has been widely documented, but its challenging learning curve (LC) requires an insightful assessment to expand its application. The aim of this study was to evaluate LC of LDN in a high-volume transplant center. METHODS: Three hundred forty-three LDNs performed from 2001 to 2018 were evaluated. CUSUM analysis based on the operative time was used to assess the number of cases required to reach mastery in the technique for both the entire surgical team and for the 3 main surgeons considered separately. Analysis of association between demographics, perioperative characteristics, and complications within the different LC phases was conducted. RESULTS: Mean operative time was 228.9 minutes. Mean length of stay was 3.8 days and mean warm ischemia time (WIT) was 170.8 seconds. Surgical and medical complication rates were 7.3% and 6.4%, respectively. The CUSUM-LC showed a requirement of 157 cases (for surgical team) and 75 cases (for single surgeons) to reach competence in the procedure. Patient baseline characteristic showed no differences among the LC phases. Compared with the initial LC phase, hospital stay was significantly lower at the end of the LC whereas WIT results were longer in the LC descendent phase. CONCLUSIONS: This study confirms the safety and efficacy of LDN, with a low rate of complications. This analysis suggests that about 75 procedures are required to reach competence and 93 cases to achieve mastery level of skill for a single surgeon. It can be hypothesized that, in a high-volume transplant enter, the time to guarantee training in LDN is compatible with the duration of a clinical fellowship.


Subject(s)
Laparoscopy , Surgeons , Humans , Nephrectomy/methods , Living Donors , Operative Time , Laparoscopy/adverse effects , Laparoscopy/methods , Tissue and Organ Harvesting/adverse effects , Length of Stay , Retrospective Studies
4.
Case Reports Plast Surg Hand Surg ; 10(1): 2285054, 2023.
Article in English | MEDLINE | ID: mdl-38229698

ABSTRACT

In the early 2000s, medical devices based on acellular matrices multiplied in number. Nowadays, the use of porcine ADMs is to be considered a well-established technology, commonly applied in different surgical specialties. In this retrospective analysis of 110 cases, the use of non-crosslinked porcine ADM EGIS® results a safe and effective tool in many procedures and specialties.

5.
BMC Infect Dis ; 21(1): 55, 2021 Jan 12.
Article in English | MEDLINE | ID: mdl-33435866

ABSTRACT

BACKGROUND: Small bowel obstruction is one of the leading reasons for accessing to the Emergency Department. Food poisoning from Clostridium botulinum has emerged as a very rare potential cause of small bowel obstruction. The relevance of this case report regards the subtle onset of pathognomonic neurological symptoms, which can delay diagnosis and subsequent life-saving treatment. CASE PRESENTATION: A 24-year-old man came to our Emergency Department complaining of abdominal pain, fever and sporadic self-limiting episodes of diplopia, starting 4 days earlier. Clinical presentation and radiological imaging suggested a case of small bowel obstruction. Non-operative management was adopted, which was followed by worsening of neurological signs. On specifically questioning the patient, we discovered that his parents had experienced similar, but milder symptoms. The patient also recalled eating home-made preserves some days earlier. A clinical diagnosis of foodborne botulism was established and antitoxin was promptly administered with rapid clinical resolution. CONCLUSIONS: Though very rare, botulism can mimic small bowel obstruction, and could be associated with a rapid clinical deterioration if misdiagnosed. An accurate family history, frequent clinical reassessments and involvement of different specialists can guide to identify this unexpected diagnosis.


Subject(s)
Botulinum Antitoxin/administration & dosage , Botulism/diagnosis , Botulism/drug therapy , Clostridium botulinum/genetics , Ileum/physiopathology , Immunologic Factors/administration & dosage , Intestinal Obstruction/diagnostic imaging , Botulism/complications , Botulism/microbiology , Diagnosis, Differential , Diplopia/complications , Emergency Service, Hospital , Feces/microbiology , Food Microbiology , Humans , Ileum/diagnostic imaging , Male , Real-Time Polymerase Chain Reaction , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
6.
Eur J Haematol ; 106(2): 281-289, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33190299

ABSTRACT

OBJECTIVE: Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. METHODS: A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. RESULTS: Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. CONCLUSION: ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic/diagnosis , Spleen/pathology , Adolescent , Adult , Aged , Autoimmunity , Biopsy , Combined Modality Therapy , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/mortality , Purpura, Thrombocytopenic, Idiopathic/therapy , Retrospective Studies , Splenectomy , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Treatment Outcome , Young Adult
7.
J Surg Case Rep ; 2020(3): rjaa016, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32226599

ABSTRACT

Mesenteric vein thrombosis (MVT) is a rare condition, often misdiagnosed due to its vague and misleading clinical presentation. It can cause intestinal infarction, peritonitis, and consequently necessitate bowel resection. CT scanning with intravenous contrast enhancement is the gold standard for its diagnosis. Radiologists have an important role in defining the extent of thrombosis and identifying any signs of intestinal infarction influencing the decision whether or not to operate. In patients with no clinical signs of peritonitis or radiological evidence of intestinal infarction, the treatment can be exclusively medical, based on full anticoagulation (initially with low molecular weight heparin, followed by vitamin K antagonists or direct acting oral-anticoagulants). The duration of medical treatment depends on radiological evidence of resolution of thrombosis and the identification of pro-coagulant risk factors.

8.
Int J Comput Assist Radiol Surg ; 13(1): 73-81, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29101640

ABSTRACT

PURPOSE: Although new techniques and prostheses have been introduced in ventral hernia surgery, abdominal hernia repair still presents complications, such as recurrence, pain, and discomfort. Thus, this work implements a computational method aimed at evaluating biomechanical aspects of the abdominal hernia laparoscopic repair, which can support clinical research tailored to hernia surgery. METHODS: A virtual solid model of the abdominal wall is obtained from MRI scans of a healthy subject. The mechanical behavior of muscular and fascial tissues is described by constitutive formulations with specific parameters. A defect is introduced to reproduce an incisional hernia. Laparoscopic repair is mimicked via intraperitoneal positioning of a surgical mesh. Numerical analyses are performed to evaluate the mechanical response of the abdominal wall in healthy, herniated and post-surgery configurations, considering physiological intra-abdominal pressures. RESULTS: During the deformation of the abdominal wall at increasing pressures, a percentage displacement increment up to 6% is found in the herniated condition, while the mechanical behavior of the repaired abdomen is similar to the healthy one. In the pressure range between 8 mmHg and 55 mmHg, the herniated abdomen shows an incremental stiffness differing of 7% with respect to the healthy condition, while the post-surgery condition shows an increase of the incremental stiffness up to 58%. CONCLUSIONS: This computational approach may be exploited to investigate different aspects of abdominal wall surgical repair, including mesh mechanical characteristics and positioning. Numerical modeling offers a helpful support for selecting the best-fitting prosthesis for customize pre-surgery planning.


Subject(s)
Abdominal Wall/surgery , Computer Simulation , Hernia, Ventral/surgery , Herniorrhaphy/methods , Laparoscopy/methods , Surgical Mesh , Humans
9.
Clin Transplant ; 28(12): 1433-40, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25297945

ABSTRACT

This study reports on a large series of 200 dual kidney transplantations (DKTs) from expanded criteria donors (ECDs) and proposes specific ways to optimize outcomes. Data concerning 200 DKTs performed in the last 14 yr were retrospectively analyzed. Kidneys from high-risk ECD were allocated for use in DKTs on an old-for-old basis after histological assessment. Different surgical techniques and immunosuppressant regimens were used over time, and the outcomes are discussed. Donors and recipients were a median 73 (70-77) and a 62 (58-67) yr old, respectively. Delayed graft function occurred in 31.5% of cases, and acute rejection in 13.5%. Patient and graft survival at five yr were 90.4% and 85.8%, respectively. Unilateral kidney placement was preferred for 75% of patients, and was associated with a low rate of surgical complications. Our current standard therapy comprising low-dose calcineurin inhibitors (CNIs) associated with mammalian target of rapamycin inhibitors (mTOR) and steroids appears to offer the best risk/benefit profile for elderly patients undergoing DKT. In our experience, outcomes after DKT can be improved by: (i) kidney clinical-histological assessment; (ii) unilateral kidney placement; (iii) minimal use of CNI associated with mTOR.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Postoperative Complications , Tissue Donors/statistics & numerical data , Tissue and Organ Harvesting/methods , Aged , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Kidney Function Tests , Kidney Transplantation/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
10.
Transplantation ; 91(2): 161-8, 2011 Jan 27.
Article in English | MEDLINE | ID: mdl-21088649

ABSTRACT

BACKGROUND: The role potential of recombinant human activated protein C (rhaPC), a recently developed molecule with anticoagulant and antiinflammatory properties, in prolonging survival in immunosuppressed primate recipients of porcine renal xenografts has been evaluated. METHODS: rhaPC was administered daily for 5 days (24 µg/kg/hr; group A; n = 3) or throughout the postoperative period (8-24 µg/kg/hr; group B; n = 2; or 24-48 µg/kg/hr; group C; n = 4). Animals in group D (n = 2) received rhaPC daily (24 µg/kg/hr) combined with recombinant human antithrombin (84 U/kg every 8 hr). Two animals served as control (group E). RESULTS: The results indicate that rhaPC is protective against fibrin deposition early after transplantation but does not prevent fibrin deposition and the occurrence of acute humoral xenograft rejection (AHXR) later on. Animals in the study survived between 8 and 55 days. At the dose used, rhaPC is able to prevent fibrin deposition in the graft in the first 2 weeks after xenotransplantation, except when it is administered in conjunction with antithrombin. However, rhaPC did not prevent the eventual occurrence of AHXR in primate recipients of porcine xenografts. CONCLUSIONS: In this pig to primate model, rhaPC confers a short advantage in the prevention of early perioperative xenograft damage but does not represent an effective strategy for preventing AHXR.


Subject(s)
Graft Survival/drug effects , Protein C/administration & dosage , Animals , Animals, Genetically Modified , Antithrombins/administration & dosage , Blood Coagulation/drug effects , Fibrin/metabolism , Graft Survival/immunology , Graft Survival/physiology , Humans , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Kidney Transplantation/physiology , Macaca fascicularis , Recombinant Proteins/administration & dosage , Sus scrofa , Transplantation, Heterologous
12.
Clin Transplant ; 23(1): 124-8, 2009.
Article in English | MEDLINE | ID: mdl-19200224

ABSTRACT

Chronic renal failure (CRF) due to calcineurin inhibitor (CNI) nephrotoxicity is one of the most serious side effects influencing mortality and morbidity after liver transplantation (LTx). One way to offer a longer survival and better quality of life to LTx recipients who develop CRF is kidney transplantation, though this is not feasible for all candidates due to the shortage of organs. With changes in the characteristics of the global donor pool, which includes increasing number of elderly donors, both kidneys from one older donor are transplanted into the same adult recipient (dual kidney transplantation, DKT) to offset the lower nephron mass. DKT might be an option after LTx to rescue a patient from dialysis, with consequent survival benefits. We report on two cases of DKT after LTx in patients with CRF who were on dialysis due to CNI nephrotoxicity.


Subject(s)
Graft Rejection/prevention & control , Graft Survival/immunology , Kidney Transplantation , Liver Transplantation , Renal Dialysis , Adult , Humans , Liver Cirrhosis/surgery , Male
13.
Am J Gastroenterol ; 103(7): 1598-609, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18557707

ABSTRACT

OBJECTIVE: The loss of myenteric neurons in the lower esophageal sphincter (LES) characterizes achalasia, an esophageal motor disorder. Because the presence of lymphocytic infiltrates suggests an immuno-mediated mechanism ongoing at the sites of disease, we investigated the T-cell receptor (TCR) repertoire and the ability to recognize human herpes virus type 1 (HSV-1) antigens of LES-infiltrating T lymphocytes in achalasia patients. METHODS: Fifty-nine patients with idiopathic achalasia and 38 heart-beating cadaveric multiorgan donors (controls) were studied. By flow cytometry evaluation and CDR3 length spectratyping analysis, the lymphocytes of 18 patients and 15 controls were analyzed, whereas 41 patients and 23 controls were employed for functional assays. RESULTS: Achalasia patients were characterized by a significantly higher esophagus lymphocytic infiltrate than controls (24.71%+/- 3.11 and 9.54%+/- 1.34, respectively; P < 0.05), mainly represented by CD3+CD8+ T cells. The characterization of TCR beta chain repertoire of CD3+ cells showed the expression of a limited number of TCR beta variable (BV) gene families (from two to five out of 26), with highly restricted spectratypes, suggesting a disease-associated oligoclonal selection of T cells. Furthermore, lymphocytes from achalasia LES specifically responded to exposure to HSV-1 antigens in vitro as showed by increased proliferation and Th-1 type cytokines release. CONCLUSIONS: These data suggest that the oligoclonal lymphocytic infiltrate within the LES of achalasia patients may represent the trace of an immune-inflammatory reaction triggered by HSV-1 antigens and that the Th1-type cytokines released by the activated lymphocytes may contribute to establish the neuronal damage accounting for the clinical features of idiopathic achalasia.


Subject(s)
Antigens, Viral/immunology , Esophageal Achalasia/immunology , Herpesvirus 1, Human/immunology , Myenteric Plexus/immunology , Receptors, Antigen, T-Cell/analysis , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Cadaver , Esophageal Sphincter, Lower/innervation , Female , Flow Cytometry , Humans , Male , Middle Aged , Polymerase Chain Reaction
14.
Clin Transplant ; 21(1): 57-62, 2007.
Article in English | MEDLINE | ID: mdl-17302592

ABSTRACT

BACKGROUND: Kidneys from expanded-criteria donors may be particularly susceptible to calcineurin inhibitor (CI)-mediated vasoconstriction and nephrotoxicity. In the early post-transplant phase, using CI may prolong ischemic injury and, in the long term, chronic CI nephrotoxicity is an even greater concern. To avoid the acute and chronic consequences of CI in kidneys from marginal donors, CI-free protocols have been introduced for maintenance immunosuppressive therapy. A CI-free protocol of anti-thymocyte globulin (ATG) induction, sirolimus, mycophenolate mofetil (MMF) and steroids has been adopted at our center in recipients of dual kidney transplantation (DKT) from elderly donors (EDs). METHODS: Dual kidney transplantations performed since April 2003 on CI-free immunosuppression (group 1 = 31) were compared with earlier DKTs in recipients treated with CI-based therapy (group 2 = 25), retrospectively analyzing patient and graft survival, surgical and medical complications, rejection episodes and renal function. RESULTS: No deaths occurred after a mean follow-up of 10.1 +/- 7.6 (group 1) and 48.2 +/- 17.4 months (group 2). Graft loss occurred in one patient in group 1 (bilateral renal vein thrombosis) and in three patients in group 2 (one primary non-function [PNF], one chronic rejection, one Kaposi's sarcoma). The incidence of acute rejection was 19% in group 1 and 16% in group 2. Delayed graft function (DGF) was recorded in 16% and 48%, respectively. Renal function was better in group 1, with a mean S-Cr of 135 +/- 48 vs. 210 +/- 141 micromol/L at one month and 116 +/- 30 vs. 149 +/- 49 micromol/L at six months. CONCLUSIONS: After DKT from EDs, a CI-free immunosuppressive regimen including ATG induction, sirolimus, MMF and steroids affords excellent results, with a lower DGF rate and a better renal function.


Subject(s)
Calcineurin/adverse effects , Immunosuppression Therapy/methods , Kidney Transplantation/immunology , Tissue Donors/statistics & numerical data , Aged , Follow-Up Studies , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Kidney Transplantation/mortality , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Renal Replacement Therapy , Reoperation/statistics & numerical data , Survival Analysis , Treatment Outcome , Uremia
15.
Transpl Int ; 19(6): 485-91, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16771870

ABSTRACT

Dual kidney transplantation (DKT) from marginal donors is increasingly used at many centers to help cope with the organ shortage problem. The disadvantages of DKT consist in longer operating times and the risk of surgical complications. DKT can be performed in two ways, i.e. using monolateral or bilateral procedures. From October 1999 to June 2005, 58 DKTs were performed at our unit. In 29 cases (group I), the kidneys were extraperitoneally placed bilaterally in the iliac fossae via two separate incisions; as of June 2003, monolateral kidney placement was preferred in 29 cases, whenever compatible with the recipient's morphological status (group II). After a mean follow-up of 51 +/- 19 months for group I and 15 +/- 7 months for group II, all patients are alive with 1-year graft survival rates of 93% and 96%, respectively. Mean operating times were 351 +/- 76 min in group I and 261 +/- 31 min in group II (P = 0.0001). The mean S-creatinine levels in groups I and II were 132 +/- 47 and 119 +/- 36 mumol/l, respectively, at 1 year. We observed eight surgical complications in group I and seven in group II. Both techniques proved safe, with no differences in surgical complication rates. The monolateral procedure has the advantage of a shorter operating time and the contralateral iliac fossa remains available for further retransplantation procedures.


Subject(s)
Kidney Transplantation/methods , Kidney/pathology , Aged , Aged, 80 and over , Female , Follow-Up Studies , Graft Survival , Humans , Immunosuppressive Agents/pharmacology , Kidney/metabolism , Kidney Transplantation/adverse effects , Male , Middle Aged , Models, Anatomic , Time Factors , Treatment Outcome
16.
Pharmacol Res ; 54(3): 181-5, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16750634

ABSTRACT

A combination of tacrolimus (TAC) and sirolimus (SIR) has recently proved to be a very effective immunosuppressive regimen in organ transplantation. In pediatric transplant recipients, co-administration of these two drugs has been shown to result in a significant decrease of exposure to TAC, whereas conflicting data have been obtained regarding this pharmacokinetic interaction in adults. The aim of this study was to investigate the effect of SIR on TAC pharmacokinetics in adult transplant recipients. Sixteen adult patients (mean age 38+/-8 years), who had been on standard TAC plus low-dose SIR immunosuppressive treatment for 6 months after renal transplantation, were enrolled for a TAC pharmacokinetic study before and 15 days after discontinuing SIR. Eight patients had received SIR 0.5 mg day(-1) and eight patients 2 mg day(-1). TAC doses remained the same in all patients after SIR withdrawal. After discontinuing SIR, statistically significant, dose-dependent increases were observed in area under the curve (AUC), peak (C(max)) and trough (C(min)) TAC concentrations (+15-20% and +27-32%, after discontinuing the 0.5 and the 2 mg day(-1) doses, respectively). Proportional decreases were consistently observed in apparent oral clearance (-13% and -23%). Very good correlations were found between TAC AUC and C(min), both before and after SIR withdrawal (R(2)=0.94, P<0.0001 and R(2)=0.97, P<0.0001, respectively). Our findings clearly demonstrate that the SIR-induced reduction in TAC exposure also takes place in adults and is, therefore, a general, age-independent phenomenon. Hence, TAC levels need to be carefully monitored in transplant recipients of any age, in order to avoid possible TAC overexposure upon SIR discontinuation.


Subject(s)
Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation , Sirolimus/pharmacology , Tacrolimus/pharmacokinetics , Adult , Drug Interactions , Female , Humans , Kidney/metabolism , Male , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Sirolimus/blood , Tacrolimus/blood
17.
Transplantation ; 81(8): 1125-32, 2006 Apr 27.
Article in English | MEDLINE | ID: mdl-16641597

ABSTRACT

BACKGROUND: The Perforin-Granzyme B and Fas/Fas Ligand apoptotic mechanisms are involved in the development of acute renal rejection (AR). We describe our experience of analyzing the expression of cytotoxic T-lymphotoxins (CTL) in biopsies and peripheral blood leukocytes (PBL) for the diagnosis of AR. METHODS: We analyzed Perforin (P), Granzyme B (GB) and Fas Ligand (FL) expression in 68 renal biopsies and 64 PBL using comparative kinetic RT-PCR and, for GAPDH and FL, we also replicated with real-time RT-PCR. The levels of expression were measured in different groups, such as T0 (biopsies before reperfusion and PBL in recipient before the transplant [Tx]), Td (biopsies and PBL collected for clinical purposes) and Tp (biopsies and PBL two months after Tx). RESULTS: A higher CTL expression was seen in non-rejecting (NR) biopsies in the first 2 months after Tx. P and FL were significantly more expressed during AR in all biopsies and in Td, while P remained upregulated in Tp. In PBL, there was no significant increase in CTL transcription during AR. A variable expression of CTL emerged in all T0 biopsies. CONCLUSIONS: Two lytic pathways are activated in biopsies when AR occurs shortly after Tx, whereas the P/GB mechanism prevails if it occurs later on. Only P and FL in biopsies might be able to predict AR diagnosis, but with a considerable variability in each sample, possibly due to the small portion of tissue core, which may be inadequate for molecular diagnosis. CTL expression in PBL does not correlate with histological AR.


Subject(s)
Graft Rejection/diagnosis , Kidney Transplantation/immunology , Membrane Glycoproteins/genetics , Serine Endopeptidases/genetics , T-Lymphocytes, Cytotoxic/immunology , Tumor Necrosis Factors/genetics , Acute Disease , Adult , Aged , Biopsy , Fas Ligand Protein , Female , Granzymes , Humans , Kidney/pathology , Male , Middle Aged , Perforin , Pore Forming Cytotoxic Proteins , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, Homologous
18.
N Engl J Med ; 354(4): 343-52, 2006 Jan 26.
Article in English | MEDLINE | ID: mdl-16436766

ABSTRACT

BACKGROUND: Long-term survival of kidney grafts from older donors is inferior to that of grafts from younger donors. We sought to determine whether selecting older kidneys according to their histologic characteristics before implantation would positively influence long-term outcome. METHODS: In a prospective cohort study, we assessed outcomes among 62 patients who received one or two histologically evaluated kidneys from donors older than 60 years of age. These outcomes were compared with outcomes among 248 matched recipients of single kidney grafts that had not been histologically evaluated and were either from donors 60 years of age or younger (124 positive-reference recipients who, according to available data, were expected to have an optimal outcome) or from those older than 60 years (124 negative-reference recipients, expected to have a worse outcome). The primary end point was graft survival. RESULTS: During a median period of 23 months, 4 recipients (6 percent) of histologically evaluated kidneys progressed to dialysis, as compared with 7 positive-reference recipients (6 percent) and 29 negative-reference recipients (23 percent). Graft survival in recipients of histologically evaluated kidneys did not differ significantly from that of grafts in positive-reference recipients but was superior to that of grafts in negative-reference recipients (hazard ratio for graft failure in the negative-reference recipients relative to the recipients of histologically evaluated kidneys, 3.68; 95 percent confidence interval, 1.29 to 10.52; P=0.02). The performance of preimplantation histologic evaluation predicted better survival both in the whole study group (P=0.02) and among recipients of kidneys from older donors (P=0.01). CONCLUSIONS: The long-term survival of single or dual kidney grafts from donors older than 60 years of age is excellent, provided that the grafts are evaluated histologically before implantation. This approach may help to expand the donor-organ pool for kidney transplantation.


Subject(s)
Graft Survival , Kidney Transplantation , Tissue Donors , Age Factors , Aged , Biopsy , Female , Humans , Kidney/anatomy & histology , Male , Middle Aged , Patient Selection , Preoperative Care , Proportional Hazards Models , Prospective Studies , Survival Analysis , Treatment Outcome
19.
Transplantation ; 80(10): 1501-10, 2005 Nov 27.
Article in English | MEDLINE | ID: mdl-16340797

ABSTRACT

BACKGROUND: Fibrin deposition is central to the acute humoral rejection process occurring in the presence of consumptive coagulopathy when pig organs are transplanted into primates. METHODS: To assess whether strategies aimed at preventing fibrin formation may extend xenograft survival, we administered high daily doses of recombinant human antithrombin (rhAT) (500 U/kg twice daily) to obtain both anticoagulant and anti-inflammatory effects in immunosuppressed primate recipients of porcine kidneys. RESULTS: Some degree of consumptive coagulopathy developed in both rhAT-treated (n=3) and untreated (n=3) primates. No major differences in the coagulation parameters analyzed were observed between the 2 groups. Similarly, no difference in survival was seen between rhAT-treated (20.6+/-4 days; range: 15-23 days) and untreated animals (17.3+/-11.6 days; range: 7-30 days), although the rhAT-treated primates had a higher bleeding tendency. Despite the high daily dose of rhAT, considerable fibrin deposition was observed in the graft as early as 2 weeks after transplantation. CONCLUSIONS: These results suggest that a high daily dose of rhAT fails to influence survival or prevent fibrin formation and deposition in the graft in our pig-to-primate model. However, the potential role of rhAT administered in combination with heparins or other clotting inhibitor concentrates in this model remains to be determined.


Subject(s)
Antithrombins/therapeutic use , Kidney Transplantation/methods , Recombinant Proteins/therapeutic use , Transplantation, Heterologous/immunology , Animals , Animals, Genetically Modified , Antithrombins/administration & dosage , Antithrombins/pharmacokinetics , Fibrin/antagonists & inhibitors , Humans , Immunosuppression Therapy/methods , Kidney Transplantation/pathology , Macaca fascicularis , Partial Thromboplastin Time , Protein C/analysis , Protein S/analysis , Recombinant Proteins/administration & dosage , Swine , Transplantation, Heterologous/pathology
20.
Microsurgery ; 25(3): 227-34, 2005.
Article in English | MEDLINE | ID: mdl-15744724

ABSTRACT

Hamster-to-rat heterotopic cardiac xenotransplantation is widely used as an experimental model to study xenograft rejection, accommodation, and tolerance, as well as in studies aimed at developing immunosuppressive strategies in xenotransplantation. Despite its widespread application, no detailed description of a surgical technique for this model has been provided in the literature. Indeed, all publications so far on the use of this species combination refer to the rat allotransplantation technique. Hence the present paper provides a detailed, up-to-date description of the surgical method adopted at our center for the hamster-to-rat heterotopic cardiac xenotransplantation model. Considerable effort went into developing a reliable, reproducible experimental model in rodents, and the description given here is enriched with "tips" that we learned in the process. The discussion of the technique also addresses several significant related issues, e.g., the anesthesia and organ preservation solution used (aspects that, in our experience, are crucial to a good surgical outcome).


Subject(s)
Heart Transplantation/methods , Animals , Cricetinae , Female , Male , Models, Animal , Rats , Transplantation, Heterologous
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