Acute infections in kidney transplant recipients.

Immunosuppressed kidney transplant recipients have a high risk of infectious complications. A variety of infections of viral, bacterial, or mycotic etiology, including opportunistic infections, occur in this group of patients, but bacterial infections are primarily responsible for the high infection-related mortality. Of the bacterial infections, urinary tract infections and pneumonia are the most common, often requiring hospitalization and temporary reduction of immunosuppressive therapy after consultation of the transplant center. In addition to symptoms due to the location of the infection, fever is often present. The differential diagnosis of fever and/or high inflammatory activity is specific to patients after kidney transplantation. In addition to infectious causes, we consider drug-related fever, a rejection episode, a relapse of systemic disease or in patients with graft failure in dialysis treatment graft intolerance syndrome (“symptomatic graft”). Saving the patients life, which often requires a significant reduction in immunosuppressive therapy, always takes precedence over preventing a rejection episode. Infection prevention is an integral part of the care of transplant patients, including the recommendation of vaccination where possible.

Treatment outcomes of MRI-guided adaptive brachytherapy in patients with locally advanced cervical cancer: institutional experiences.

PURPOSE: Image-guided adaptive brachytherapy (IGABT) is currently state of the art in the comprehensive treatment of patients with cervical cancer. Here, we report mature clinical data regarding IGABT of cervical cancer in a large patient sample, examining clinical outcomes, manifestations of late toxicities, and dosimetric findings. METHODS: Between May 2012 and October 2020, we performed a total of 544 uterovaginal IGABT applications in 131 consecutive patients with biopsy-proven cervical carcinoma not suitable for surgery. The median duration of follow-up was 43 months. RESULTS: The estimated 3­, 4­, and 5­year LC rates were 88.3% (95% confidence interval [CI] 81.1-95.5), 86.9% (95% CI 78.5-95.3), and 85.5% (95% CI 76-95%), respectively. The 3­, 4­, and 5­year OS estimates were 72.66% (95% CI 63.64-81.69%), 68.9% (95% CI 59.15-78.66%), and 63.96% (95% CI 52.94-74.97%), respectively. Patients who received ≥ 5 cycles of chemotherapy had statistically significantly better 3­year recurrence-free survival (RFS) compared to patients who completed <5 cycles (79.07% [95% CI 60.81-97.34] vs. 58.10% [95% CI 47.22-68.98]; p = 0.0185). We recorded manifestations of genitourinary and gastrointestinal toxicity grade ≥3 in 6.9% and 5.3%, respectively. CONCLUSION: Our mature long-term data on the treatment patients with locally advanced cervical cancer show that excellent treatment outcomes can be achieved with MRI-based IGABT, as well as acceptable late morbidity.

Inoperable CASTLE of the thyroid gland treated with radical radiotherapy with complete remission.

Carcinoma showing thymus-like elements (CASTLE) is an extremely rare malignant tumor of the thyroid gland and soft tissues of the neck with favorable prognosis. Histological features of the CASTLE are similar to thymic carcinoma, and it is assumed that it arises from the ectopic thymic tissue or the remnants of branchial pouches. The optimal treatment strategy is still uncertain because of the rarity of the tumor. The mainstay of treatment is surgery. The role of other modalities is unclear. We present a case report of a patient with locally advanced CASTLE of the thyroid gland who was not suitable for surgery and underwent radical radiotherapy with subsequent achievement of complete remission. We also present a literature review.

Prediction of treatment response in patients with locally advanced cervical cancer using midtreatment PET/MRI during concurrent chemoradiotherapy.

PURPOSE: We aimed to find metabolic, functional or morphological characteristics of the tumor predicting failure to achieve complete metabolic remission (CMR) by the midtreatment PET/MRI (positron emission tomography/magnetic resonance imaging) in cervical cancer patients. METHODS: We evaluated 66 patients treated between August 2015 and November 2019 who underwent pretreatment staging, subsequent midtreatment evaluation, and definitive restaging 3 months after completing the whole treatment, all using PET/MRI. The pretreatment parameters (pre-SUVmax, pre-SUVmean, pre-MTV, pre-MTV­S, pre-TLG, pre-TLG­S [SUV: standard uptake value, MTV: metabolic tumor volume, TLG: total lesion glycolysis]), and the midtreatment parameters at week 5 during chemoradiotherapy (mid-SUVmax, mid-SUVmean, mid-MTV, mid-MTV­S, mid-TLG and mid-TLG-S) were recorded. The value of ADC (apparent diffusion coefficient) was also measured. Furthermore, we recorded absolute and relative changes in all parameters-∆ and ∆%. We divided the whole group of patients into "responders" (CMR) and "non-responders" (non-CMR), and compared them on the basis of the parameters from pre-PET/MRI and mid-PET/MRI. RESULTS: A statistically significant difference in the evaluated parameters between responders and non-responders was found for the following parameters: mid-MTV, mid-TLG, mid-TLG­S, mid-MTV­S, mid-tumor size, and ∆%SUVmax. According to the ROC (receiver operating characteristic) analysis, mid-MTV­S showed the best albeit moderate discrimination ability for the prediction of non-CMR. Significant mutual correlations of all variables, in particular between mid-MTV­S and mid-TLG­S and between mid-MTV and mid-TLG, were found (all p < 0.05). CONCLUSION: Our study confirmed that when using the midtreatment PET/MRI we are able to identify metabolic parameters having the discrimination ability for the prediction of non-CMR. In particular mid-MTV­S, mid-MTV, mid-tumor size, mid-TLG­S, mid-TLG and ∆%SUVmax.

Late side effects of 3T MRI-guided 3D high-dose rate brachytherapy of cervical cancer : Institutional experiences.

PURPOSE: This article reports experiences with 3T magnetic resonance imaging(MRI)-guided brachytherapy (BT) for cervical cancer focusing on late side effects. METHODS: Between June 2012 and March 2017 a total of 257 uterovaginal BT administrations were performed in 61 consecutive patients with inoperable cervical cancer. All patients were treated with BT combined with external beam radiotherapy. RESULTS: The mean HR-CTV (high risk-clinical target volume) D90 was 87 ± 5.1 Gy equivalent dose corresponding to the conventional fractionation using 2 Gy per fraction (EQD2, range 70.7-97.9 Gy). The mean doses in OAR (organs at risk), namely rectum, sigmoid and bladder were D2 cm3rectum = 62.6 ± 6.9 Gy EQD2 (range 38.2-77.2 Gy), D2 cm3sigmoid = 66.2 ± 6.8 Gy EQD2 (43.2-78.6 Gy) and D2 cm3bladder = 75.1 ± 8.3 Gy EQD2 (58.2-92.6 Gy). There were no signs of late gastrointestinal (GI) toxicity in 49 patients, grade 3 toxicity was seen in 2 patients and grade 4 toxicity in 3 patients. There were no signs of late genitourinary (GU) toxicity in 41 patients, grade 3 toxicity was seen in 4 patients and no signs of grade 4 toxicity were seen. After the treatment, 60 patients (98.4%) achieved locoregional remission. In 54 patients (88.5%) the remission was complete, whereas in 6 patients (9.8%) remission was partial. CONCLUSION: The use of 3T MRI-guided BT leads to achievement of high rates of local control with limited late morbidity as demonstrated in this series of patients.

ADAMTS13 kinetics after therapeutic plasma exchange and plasma infusion in patients with Upshaw-Schulman syndrome.

BACKGROUND: Hereditary thrombotic thrombocytopenic purpura, also called Upshaw-Schulman syndrome (USS), is a rare disease caused by genetic mutations in the ADAMTS13 gene, which severely decrease the activity of ADAMTS13, a metalloprotease that cleaves von Willebrand factor multimers (VWF). Genotypically identical patients can show great phenotypic diversity. OBJECTIVES: Comparison of selected laboratory parameters and ADAMTS13 pharmacokinetics among patients with USS was performed. PATIENTS/METHODS: Six patients with USS on prophylactic plasma therapy have been reviewed, retrospectively. Blood counts, lactate dehydrogenase (LDH), and ADAMTS13 activity at various time-points before and after different treatment cycles were evaluated. RESULTS: ADAMTS13 recovery and pharmacokinetics were affected by treatment modality, and also reflected the patients' comorbidities and their current physiological and clinical condition. CONCLUSIONS: Our present findings support a multifactorial contribution to treatment efficacy, and confirm the importance of adaptability and individualization of USS therapy. Therapeutic plasma exchange even in hereditary TTP is an option that can in some patients prolong intervals between plasma administration.

The Role of von Willebrand Factor, ADAMTS13, and Cerebral Artery Thrombus Composition in Patient Outcome Following Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND The aim of the study was to investigate the role of von Willebrand factor (vWF), the vWF-cleaving protease, ADAMTS13, the composition of thrombus, and patient outcome following mechanical cerebral artery thrombectomy in patients with acute ischemic stroke. MATERIAL AND METHODS A prospective cohort study included 131 patients with ischemic stroke (<6 hours) with or without intravenous thrombolysis. Interventional procedure parameters, hemocoagulation markers, vWF, ADAMTS13, and histological examination of the extracted thrombi were performed. The National Institutes of Health Stroke Scale (NIHSS) score was used on hospital admission, after 24 hours, at day 7; the three-month modified Rankin Scale score was used. RESULTS Mechanical thrombectomy resulted in a Treatment in Cerebral Ischemia (TICI) score of 2-3, with recanalization in 89% of patients. Intravenous thrombolysis was used in 101 (78%). Patients with and without intravenous thrombolysis therapy had a good clinical outcome (score 0-2) in 47% of cases (P=0.459) using the three-month modified Rankin Scale. Patients with a National Institutes of Health Stroke Scale (NIHSS) score ≥15 had significantly increased vWF levels (P=0.003), and a significantly increased vWF: ADAMTS13 ratio (P=0.038) on hospital admission. Significant correlation coefficients were found for plasma vWF and thrombo-embolus vWF (r=0.32), platelet (r=0.24), and fibrin (r=0.26) levels. In the removed thrombus, vWF levels were significantly correlated with platelet count (r=0.53), CD31-positive cells (r=0.38), and fibrin (r=0.48). CONCLUSIONS In patients with acute ischemic stroke, mechanical cerebral artery thrombectomy resulted in a good clinical outcome in 47% of cases, with and without intravenous thrombolysis therapy.

Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency.

AIMS: We sought to identify biochemical predictors that indicate susceptibility to in-stent restenosis (ISR) after coronary artery bare-metal stenting. METHODS: A total of 111 consecutive patients with post-percutaneous coronary intervention (PCI) in-stent restenosis of a target lesion within 12 months were matched for age, sex, vessel diameter, and diabetes with 111 controls without post-PCI ISR. Plasma or serum levels of biochemical markers were measured: matrix metalloproteinases (MMP) 2, 3, 9; myeloperoxidase (MPO); asymmetric dimethylarginine (ADMA); lipoprotein (a) (Lp[a]); apolipoproteins E and D (ApoE and D); and lecitin-cholesterol acyltransferase (LCAT). Multivariable logistic regression association tests were performed. RESULTS: Increased plasma MMP-3 (OR: 1.013; 95% CI: 1.004-1.023; P = 0.005), MMP-9 (OR: 1.014; 95% CI: 1.008-1.020; P < 0.0001) or MPO (OR: 1,003; 95% CI: 1.001-1.005; P = 0.002) was significantly associated with increased risk of ISR. Increased levels of ADMA (OR: 0.212; 95% CI: 0.054-0.827; P = 0.026), ApoE (OR: 0.924; 95% CI: 0.899-0.951; P < 0.0001), ApoD (OR: 0.919; 95% CI: 0.880-0.959; P = 0.0001), or LCAT (OR: 0.927; 95% CI: 0.902-0.952; P < 0.0001) was associated with risk reduction. No correlation was found between plasma MMP-2 or Lp (a) and ISR risk. CONCLUSIONS: Increased levels of MMP-3, MMP-9, and MPO represent predictors of ISR after bare-metal stent implantation. In contrast, increased ADMA, LCAT, and Apo E and D indicate a decreased in-stent restenosis occurrence.