Invasive bacillary angiomatosis in a kidney transplant recipient: A challenging case on belatacept immunosuppression.

Bacillary angiomatosis is a disseminated vascular proliferative disease caused by aerobic gram-negative bacilli Bartonella henselae or Bartonella quintana. Bacillary angiomatosis is mostly described in immunosuppressed patients with HIV infection and organ transplant recipients. We describe the case of a female aged 75 years who is a kidney transplant recipient who was admitted for a 3-month history of intermittent fever, chills, vomiting, and a 12-kg weight loss. The maintenance immunosuppression was based on prednisone, mycophenolate, and monthly infusions of belatacept. Physical examination was unremarkable. Laboratory investigations revealed elevated blood acute phase proteins but all blood cultures were negative. Serological tests for Bartonella were negative. Thoracoabdominal computed tomography scan and transesophageal echocardiography were normal. A Positron Emission Tomography scan showed a hypermetabolic mass in the duodenopancreatic region, with multiple hepatic and splenic lesions. Histological findings of spleen and pancreatic biopsies were not conclusive. The histopathological examination of a celiac lymph node biopsy finally demonstrated bacillary angiomatosis. The diagnosis of bacillary angiomatosis in immunocompromised patients is most often delayed in the absence of skin involvement. A high index of clinical suspicion is needed when interpreting negative results.

Comparison of artificial intelligence and human-based prediction and stratification of the risk of long-term kidney allograft failure.

BACKGROUND: Clinical decisions are mainly driven by the ability of physicians to apply risk stratification to patients. However, this task is difficult as it requires complex integration of numerous parameters and is impacted by patient heterogeneity. We sought to evaluate the ability of transplant physicians to predict the risk of long-term allograft failure and compare them to a validated artificial intelligence (AI) prediction algorithm. METHODS: We randomly selected 400 kidney transplant recipients from a qualified dataset of 4000 patients. For each patient, 44 features routinely collected during the first-year post-transplant were compiled in an electronic health record (EHR). We enrolled 9 transplant physicians at various career stages. At 1-year post-transplant, they blindly predicted the long-term graft survival with probabilities for each patient. Their predictions were compared with those of a validated prediction system (iBox). We assessed the determinants of each physician's prediction using a random forest survival model. RESULTS: Among the 400 patients included, 84 graft failures occurred at 7 years post-evaluation. The iBox system demonstrates the best predictive performance with a discrimination of 0.79 and a median calibration error of 5.79%, while physicians tend to overestimate the risk of graft failure. Physicians' risk predictions show wide heterogeneity with a moderate intraclass correlation of 0.58. The determinants of physicians' prediction are disparate, with poor agreement regardless of their clinical experience. CONCLUSIONS: This study shows the overall limited performance and consistency of physicians to predict the risk of long-term graft failure, demonstrated by the superior performances of the iBox. This study supports the use of a companion tool to help physicians in their prognostic judgement and decision-making in clinical care.

The ability to predict the risk of a particular event is key to clinical decision-making, for example when predicting the risk of a poor outcome to help decide which patients should receive an organ transplant. Computer-based systems may help to improve risk prediction, particularly with the increasing volume and complexity of patient data available to clinicians. Here, we compare predictions of the risk of long-term kidney transplant failure made by clinicians with those made by our computer-based system (the iBox system). We observe that clinicians' overall performance in predicting individual long-term outcomes is limited compared to the iBox system, and demonstrate wide variability in clinicians' predictions, regardless of level of experience. Our findings support the use of the iBox system in the clinic to help clinicians predict outcomes and make decisions surrounding kidney transplants.

Relative Change of Protidemia Level Predicts Intradialytic Hypotension.

Background Hemodialysis patients are at risk of intradialytic hypotension (IDH), which is associated with mortality and cardiovascular and neurological events. The use of biomarkers of volemia such as relative change in protidemia and BNP (B-natriuretic peptide) levels to predict IDH remains unknown. Methods and Results We conducted a prospective observational study, which enrolled 170 chronic hemodialysis patients in a single center from September 2015 to March 2016. BNP and the relative change of protidemia level (Δprotidemia=postdialysis protidemia-predialysis protidemia) were measured monthly over 6 months. A logistic mixed regression model was used to define the best biomarkers that predict the 30-day risk of IDH. Receiver operating characteristic analysis area under the curve was used to define the cutoff values of Δprotidemia that predict IDH A logistic mixed model reveals that Δprotidemia predicts the 30-day risk of IDH but not BNP or age; odds ratio=1.12, 95% CI 1.08-1.17), odds ratio=0.81, 95% CI (0.64; 1.07) and odds ratio =0.015 95% CI (0.99; 1.03), respectively. Adding the ultrafiltration rate did not improve the model. A receiver operating characteristic curve analysis showed that Δprotidemia of 10 g/L allowed for discrimination of the patients with IDH (area under the curve= 0.67; 95% CI 0.62-0.72, P<0.05). There was an increase in area under the curve to 0.71 (95% CI 0.63-0.76) in a subgroup of hemodialysis with BNP <300 ng/L, for a cutoff value of 11 g/L, especially for the nondiabetic patients. Conclusions Relative change in protidemia level (Δprotidemia) outperforms BNP and ultrafiltration rate as a predictor for 30-day risk of IDH. These results should be confirmed by a prospective study.

HLA-DQ alloantibodies directly activate the endothelium and compromise differentiation of FoxP3high regulatory T lymphocytes.

Development of donor-specific antibodies is associated with reduced allograft survival in renal transplantation. Recent clinical studies highlight the prevalence of human leukocyte antigen (HLA)-DQ antibodies amongst de novo donor-specific antibodies (DSAs), yet the specific contribution of these DSAs to rejection has not been examined. Antibody-mediated rejection primarily targets the microvasculature, so this study explored how patient HLA-DQ alloantibodies can modulate endothelial activation and so immunoregulation. HLA-DQ antibodies phosphorylated Akt and S6 kinase in microvascular endothelial cells. This activation prior to culture with alloreactive lymphocytes increased IL-6 and RANTES secretion. The antibody-mediated upregulation of IL-6 was indeed Akt-dependent. The binding of HLA-DQ antibodies to endothelial cells selectively reduced T cell alloproliferation and FoxP3high Treg differentiation. In clinical studies, detection of HLA-DQ DSAs with other DSAs is associated with worse graft survival than either alone. Endothelial cells stimulated with HLA-DR and HLA-DQ antibodies showed a synergistic increase in pro-inflammatory cytokine secretion and a decrease in Treg expansion. HLA-DQ antibodies strongly promote pro-inflammatory responses in isolation and in combination with other HLA antibodies. Thus, our data give new insights into the pathogenicity of HLA-DQ DSAs.

Renal failure during chemotherapy: renal biopsy for assessing subacute nephrotoxicity of pemetrexed.

BACKGROUND: Pemetrexed, a multitargeted antifolate cytotoxic agent, is currently used primarily in combination with cisplatin for metastatic non-small cell lung cancer and for malignant mesothelioma. Acute renal toxicity of pemetrexed has been recently described with polychemotherapy, in which the individual responsibility of each drug is difficult to establish. Only one recent report documents renal involvement in long-term exposed patients. CASE PRESENTATION: We report on a case of rapidly progressive nephropathy leading to the cessation of platinum salts and the secondary interruption of pemetrexed and bevacizumab. Acute tubular necrosis shown on the renal biopsy could potentially be due to pemetrexed. Persistent severe renal failure after the resumption of all drugs led to new treatment lines with gemcitabine (while the glomerular filtration rate was below 30 ml/min/1.73m2), then followed by Taxol. CONCLUSIONS: The optimal strategy with regard to renal complications in cancer patients is not clear. Acute or chronic loss in renal function generally leads to a new treatment line, possibly impairing the overall success of the treatment. The use of chemotherapy in patients with a glomerular filtration rate below 30 ml/min/1.73m2 is usually associated with an increased risk of side effects when not contraindicated by renal elimination of the drug.

Diagnosis of systemic inflammatory diseases among patients admitted for acute pericarditis with pericardial effusion.

AIMS: Acute pericarditis may be the heralding manifestation of various systemic inflammatory diseases (SIDs). The aim of this study was to identify clinical indicators for SIDs in patients admitted for acute pericarditis with pericardial effusion. METHODS: All consecutive adult patients hospitalized in a Department of Internal Medicine over a 10-year period for acute pericarditis with pericardial effusion were retrospectively reviewed. Patients with cancer and tuberculosis were excluded. A structured clinical panel for extra-cardiac symptoms of SIDs was applied. SIDs were classified using current international criteria. RESULTS: Ninety-nine patients were admitted for acute pericarditis with pericardial effusion. After exclusion, 74 (49.7 ±â€Š19.7 years, 56.7% women) patients were analyzed. Among them, 23 (23.2%) patients had a SID that was revealed by pericarditis in 12 cases. Systemic lupus erythematosus, undifferentiated connective-tissue disease, and Sjogren's syndrome accounted for 75% of the SID. Patients with SIDs were younger (P < 0.001), more frequently of female sex (P = 0.025), and had a higher frequency of extra-cardiac symptoms (P < 0.001) including arthralgia, myalgia, Raynaud phenomenon, and skin rash, as compared with patients with idiopathic pericarditis (n = 51). Overall, after exclusion of neoplasm and tuberculosis, the probability of SIDs in patients admitted with an acute pericarditis with pericardial effusion was 89.7% in patients younger than 50 who had extra-cardiac symptoms. Conversely, the probability fell to 8.4% in patients older than 50 with no extra-cardiac symptoms. CONCLUSION: Both age and extra-cardiac symptoms suggest an underlying SID as a possible cause of acute pericarditis.

Kidney allograft fibrosis after transplantation from uncontrolled circulatory death donors.

BACKGROUND: Existing data suggest that increased interstitial fibrosis may occur abnormally in renal transplants from donations after uncontrolled circulatory death (uDCD). METHODS: To evaluate the factors that are associated with the progression of fibrosis and its functional impact on renal grafts, we compared 76 uDCD recipients with 86 recipients of kidney donations after brain death at 1-year after transplantation. Groups were matched for donor age, rank of transplantation, and absence of human leukocyte antigen sensitization. Histology was performed on sequential biopsies in uDCD recipients. Associations between variables were analyzed using linear mixed models and univariate analyses. RESULTS: In the uDCD group, increased fibrosis was detected 3 months after transplantation compared to before implantation. After 1 year, interstitial fibrosis and tubular atrophy score was significantly greater (1.5±0.7 vs. 1.0±0.9; P=0.003) and estimated glomerular filtration rate (49.5±17.4 vs. 60.6±19.1 mL/min/1.73 m2; P=0.0003) was significantly lower in the uDCD group than in the donations after brain death group. No flow duration and donor age were significantly associated with accelerated fibrosis. Interstitial fibrosis and tubular atrophy score, interstitial inflammation score, and estimated glomerular filtration rate were significantly worse in uDCD patients with no flow longer than 10 min. CONCLUSION: Donations after uncontrolled circulatory death grafts show more fibrosis after transplantation. No flow duration is associated with accelerated fibrosis and should be considered during uDCD graft allocation.