Endovascular Repair of Bilateral Internal Mammary Artery Aneurysms in a Patient with Marfan Syndrome.

BACKGROUND: True internal mammary artery aneurysms are rare but rupture has been described. CASE REPORT: A 39-year-old male patient with Marfan syndrome was diagnosed with large asymptomatic bilateral internal mammary artery aneurysms (IMAAs) on contrast-enhanced CT scan, without other arterial lesions. Both aneurysms were coil embolized, a stent graft was deployed in the left subclavian artery to cover a wide neck that precluded complete and safe embolization of the left IMAA. Reintervention on the right side was performed 5 years later due to recanalization. Eight years after the initial procedure, the patient presented with a type A aortic dissection that was successfully repaired. CONCLUSIONS: Although extremely rare, endovascular treatment should be considered to prevent rupture of internal mammary artery aneurysms.

[Endovascular management of chronic limb ischemia. Experience in 48 procedures]. / Manejo endovascular de la isquemia crítica distal: análisis de una serie contemporánea.

BACKGROUND: Chronic limb ischemia can lead to high rates of limb loss and mortality. Open surgery is the gold standard for treatment of distal disease. Endovascular surgery should have less complications with similar outcomes. AIM: To report a cohort of patients with distal arterial disease treated with endovascular surgery at our institution. MATERIAL AND METHODS: Review of angioplasty records of patients undergoing distal lower extremity endovascular procedures between 2016 and 2019. Demographics, comorbidities, form of presentation, type of intervention, perioperative complications, and length of stay were analyzed. The primary outcomes were wound healing, reinterventions and freedom from major amputation. Secondary outcomes were overall survival and amputation-free survival. RESULTS: Forty-eight limbs of 41 patients with a mean age 75 years (78% males) were treated. Ninety-three percent had hypertension, 88% diabetes, 30% chronic kidney disease. 73% presented with major wounds. Plain balloon and drug coated balloon angioplasties were carried out in 65 and 31% of procedures respectively, with no difference in results. In 46% of the cases, only chronic total occlusions were treated. Wound healing was achieved in 85% of procedures and 90% of patients were free from amputation at one year of follow up. Complications were observed in 18% of procedures, perioperative mortality was 2% and one-year survival was 76%. CONCLUSIONS: Endovascular therapy achieves high rates of wound healing and freedom from amputation with low perioperative mortality and moderate complication rates.

Acute cellular and antibody-mediated rejection of the pancreas allograft: incidence, risk factors and outcomes.

Antibody-mediated rejection (AMR) after pancreas transplantation is a recently identified entity. We describe the incidence of, risk factors for, and outcomes after AMR, and the correlation of C4d immunostaining and donor-specific antibody (DSA) in the diagnosis of AMR. We retrospectively analyzed 162 pancreas transplants in 159 patients who underwent 94 pancreas allograft biopsies between 2006 and 2009. Univariate and multivariate analyses were performed to evaluate risk factors for pancreas graft AMR. One-year rejection rates and survival after rejection were calculated by Kaplan-Meier methods. AMR occurred in 10% of patients by 1-year posttransplant. Multivariate risk factors identified for AMR include nonprimary simultaneous pancreas-kidney (SPK) transplant, primary solitary pancreas (PAN) transplant and race mismatch. After pancreas rejection, patient survival was 100% but 20% (8 of 41) of pancreas grafts failed within 1 year. Graft survival after acute cellular rejection (ACR), AMR and mixed rejection was similar. Of biopsies that stained >5% C4d, 80% were associated with increased Class I DSA. In summary, AMR occurs at a measurable rate after pancreas transplantation, and the diagnosis should be actively sought using C4d staining and DSA levels in patients with graft dysfunction, especially after nonprimary SPK and primary PAN transplantation.

Nox2 is a mediator of chronic CsA nephrotoxicity.

We hypothesized that Nox2, the classical phagocytic NADPH oxidase, plays an important role in calcineurin inhibitor (CNI)-induced renal fibrosis. We tested this hypothesis in vitro, in animal and in human studies. Cyclosporine A (CsA) and tacrolimus (TAC) were associated with greater levels of Nox2 mRNA and epithelial to mesenchymal transition (EMT) in NRK52E cells. CsA increased Nox2, α-SMA and phosphorylated-p38MAPK, Smad3 and NFκB proteins. Nox2 upregulation and EMT were inhibited in TGF-ß1 knockout cells suggesting that TGF-ß1 is required for Nox2 activation. Fisher344 rats treated with high dose CsA showed increased Nox2 in the tubulointerstitium and greater Nox2, α-SMA, phosphorylated Smad3 and nitrotyrosine by immunoblot analyses. Inhibition of Nox2 by coadministration of apocynin or diphenyleneiodonium was associated with reduced fibrogenesis. We validated these findings by treating wild type and Nox2 null (B6.129S-Cybb(Tm1Din)/J) mice with high dose CsA. Western blot analyses confirmed the absence of Nox2 and significantly lower levels of α-SMA and 4-hydroxynonenal (HNE) in CsA-treated knockout mice. These findings were clinically relevant since Nox2 and α-SMA were increased in the tubulointerstitium of kidneys from 15 liver transplant recipients with biopsy-confirmed chronic CsA or TAC nephrotoxicity. In conclusion, specific Nox2 inhibition strategies may improve chronic CNI nephrotoxicity in solid organ transplantation.

Pretransplant immune-regulation predicts allograft tolerance.

CD4⁺ Tregs specific for noninherited maternal antigens (NIMA(d) ) are detectable in some but not all B6 × BDF1 backcross, H-2(b) homozygous offspring, and their presence is strongly correlated with extent of maternal (BDF1) microchimerism. We hypothesized that the level of pretransplant donor antigen-specific Tregs could predict allograft tolerance. To test this idea, mice were screened for bystander suppression in a DTH assay, followed 1 week later by DBA/2 heterotopic heart transplantation. NIMA(d) -exposed, H-2(b) offspring that failed to suppress DTH uniformly rejected heart allografts (12/12) by d15. In contrast, 5/6 NIMA(d) -exposed DTH 'regulators' accepted their allografts >100 days. The defect in 'nonregulator" offspring could be corrected by transfer of CD4⁺CD25⁺, but not CD4⁺ CD25(neg) or CD8⁺ T cells from transplant acceptor mice. In conclusion, donor-specific T reg screening of F1 backcross offspring correctly predicted which recipients would accept a heart allograft. If translated to the clinic, similar pretransplant Treg screening could greatly enhance the effectiveness of tolerance as a clinical strategy in transplantation between family members.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

Early and limited use of tacrolimus to avoid rejection in an alemtuzumab and sirolimus regimen for kidney transplantation: clinical results and immune monitoring.

Alemtuzumab induction with 60 days of tacrolimus treatment and continuous sirolimus treatment prevented acute rejection in nine of 10 consecutive renal allograft recipients. All patients are alive with a functioning kidney graft at 27-39 months of follow-up. Extensive immune monitoring was performed in all patients. Alloantibody detection, cytokine kinetics assay (CKA), and trans vivo delayed-type hypersensitivity (DTH) assay were performed every 6 months showing correlation with clinical evolution. Despite alloantibody presence in five patients, eight patients remain without the need for specific treatment and only sirolimus monotherapy in decreasing dosage. Four patients take only 1 mg sirolimus daily with levels of 3-4 ng/mL. One patient showed clinical signs of rejection at month 9 post-transplant, with slow increase in serum creatinine and histological signs of mixed cellular (endarteritis) and humoral rejection (C4d positivity in peritubular capillaries and donor-specific antibody (DSA)). In summary, the addition of tacrolimus therapy for 2 months to a steroid-free, alemtuzumab induction and sirolimus maintenance protocol limited the previously shown acute rejection development. Nevertheless, alloantibody was present in serum and/or C4d present on 1-year biopsy in half the patients. The combination of CKA and DSA monitoring or the performance of transvivo DTH correlated with immune status of the patients.

Calcineurin inhibitor withdrawal after renal transplantation with alemtuzumab: clinical outcomes and effect on T-regulatory cells.

To address the results of calcineurin inhibitor (CNI) withdrawal after alemtuzumab induction relative to CNI continuation, we performed a pilot randomized clinical trial in renal allograft recipients on CNI, a mycophenolic acid derivative and steroids after the first 2 months posttransplantation. Forty patients were randomized to taper off CNI or to maintain it, and followed for at least 1 year. Four patients in the withdrawal group were treated for acute rejection while no patient received antirejection treatment in the control group. Two control patients withdrew CNI due to nephrotoxicity. Estimated GFR was similar in both groups after 1 year. Flow cytometry of CD4(+)CD25(+)CTLA-4(+)FoxP3(+) regulatory T cells (Treg) demonstrated a significant increase in Treg percentages in the peripheral blood of alemtuzumab-treated patients on CNI early postransplant. Furthermore, the increased Treg percentages in the withdrawal cohort were unchanged at month 6 postenrollment, whereas they decreased significantly in those patients maintained on CNI. Patients withdrawn from CNI after alemtuzumab trend toward a higher rejection rate, but most patients can be weaned from a CNI using this regimen. With the exception of maintaining increased Treg levels, the benefits are not appreciable in this short follow-up, and a larger randomized trial is justified.

Unaltered graft survival and intragraft lymphocytes infiltration in the cardiac allograft of Cxcr3-/- mouse recipients.

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3(-/-) mice. Interestingly, in our hands, neither of the independently derived Cxcr3(-/-) lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-gamma production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3(-/-) recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.

Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

Manejo endovascular de la isquemia crítica distal: análisis de una serie contemporánea

Background: Chronic limb ischemia can lead to high rates of limb loss and mortality. Open surgery is the gold standard for treatment of distal disease. Endovascular surgery should have less complications with similar outcomes. Aim: To report a cohort of patients with distal arterial disease treated with endovascular surgery at our institution. Material and Methods: Review of angioplasty records of patients undergoing distal lower extremity endovascular procedures between 2016 and 2019. Demographics, comorbidities, form of presentation, type of intervention, perioperative complications, and length of stay were analyzed. The primary outcomes were wound healing, reinterventions and freedom from major amputation. Secondary outcomes were overall survival and amputation-free survival. Results: Forty-eight limbs of 41 patients with a mean age 75 years (78% males) were treated. Ninety-three percent had hypertension, 88% diabetes, 30% chronic kidney disease. 73% presented with major wounds. Plain balloon and drug coated balloon angioplasties were carried out in 65 and 31% of procedures respectively, with no difference in results. In 46% of the cases, only chronic total occlusions were treated. Wound healing was achieved in 85% of procedures and 90% of patients were free from amputation at one year of follow up. Complications were observed in 18% of procedures, perioperative mortality was 2% and one-year survival was 76%. Conclusions: Endovascular therapy achieves high rates of wound healing and freedom from amputation with low perioperative mortality and moderate complication rates.

[Peritoneal csf pseudocysts. Rare complication of ventriculo-peritoneal shunts]. / Pseudo-kystes péritonéaux de L.C.R.. Complication rare des dérivations ventriculo-péritonéales.

The authors report 6 cases of abdominal CSF pseudo-cysts as a complication of ventriculo-peritoneal shunts. The clinical picture and diagnosis confirmation by radiology and echography are reviewed. Histogenesis and pathogenesis are discussed.

Acute pulmonary injury: high-resolution CT and histopathological spectrum.

Acute lung injury usually causes hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS). Although diffuse alveolar damage is the hallmark of ARDS, other histopathological patterns of injury, such as acute and fibrinoid organising pneumonia, can be associated with acute respiratory failure. Acute eosinophilic pneumonia can also cause acute hypoxaemic respiratory failure and mimic ARDS. This pictorial essay reviews the high-resolution CT findings of acute lung injury and the correlative histopathological findings.

Enfermedades respiratorias laborales en Chile: Ley 16.744 / Work related respiratory diseases in Chile – Law 16.744

Since 1968 Chile has two separate systems to manage the health problems of Chileans. One is devoted to prevent and care for all kind of diseases, from gestation to death, and the other one is devoted exclusively to work-related diseases and accidents. The last one has been very successful in lowering the work related accidents below 5 percent, rate that is similar to those of developed countries. The system has been replicated in other Latin-American countries. Occupational diseases, on the other hand, had been neglected by the system (although not in its design). The current article visit the most relevant aspects of the system and focus on the role of respiratory diseases specialists in the diagnosis and management of work related respiratory diseases.

Desde 1968 Chile cuenta con dos sistemas paralelos para manejar los problemas de salud de la población. Uno está orientado a prevenir y curar todo tipo de enfermedades, desde la gestación hasta la muerte; el otro está diseñado para preocuparse de las enfermedades y accidentes relacionados con la actividad laboral. Este último sistema ha sido muy exitoso en disminuir la accidentabilidad laboral, la que se ubica actualmente bajo el 5 por ciento, frecuencia similar a la observada en países desarrollados. Este sistema ha sido copiado en otros países de Latinoamérica. Las enfermedades ocupacionales han sido descuidadas por el sistema, aun cuando fueron adecuadamente consideradas en el cuerpo legal. El presente artículo presenta los aspectos más relevantes de este sistema y destaca el papel de los especialistas en enfermedades respiratorias en el diagnóstico y manejo de las enfermedades respiratorias ocupacionales.

Inhalación masiva de amoniaco: reporte de dos casos / Massive ammonia inhalation: report of two cases

Ammonia (NH3) is an irritant and corrosive gas whose inhalation at high concentrations mainly occurs during agricultural and industrial activities, as occupational accidents. The extent and severity of the damage depends on the concentration and time of exposure to the toxic, which can cause skin, eye, respiratory and life-threatening injuries. We present two cases of patients acutely exposed to high concentrations of NH3. Both patients survived to the acute phase of the respiratory injury, but developed chronic lung derangements.

El amoniaco (NH3) es un gas irritante y corrosivo cuya inhalación aguda en altas concentraciones se produce principalmente durante accidentes laborales en el sector agrícola e industrial. La extensión y severidad del daño depende de la concentración y tiempo de exposición al tóxico, el cual puede causar lesiones a nivel cutáneo, ocular, respiratorio y riesgo vital. Presentamos dos casos de pacientes expuestos en forma aguda a NH3 en altas concentraciones. Ambos pacientes sobrevivieron a la fase aguda y evolucionaron con lesiones respiratorias crónicas.