Successful kidney transplant in a patient with IgG anti HLA Class-I auto-antibodies: A case report

Donor specific antibodies (DSA) play a significant role in graft rejection. Many laboratory methods, varied in sensitivity and specificity, are used to detect them. We report a case of a 38-year-old man presented with end stage renal disease considered for kidney transplantation. He had no history of blood transfusions nor transplantation procedures. Dilemma rose when he got multiple positive crossmatches with matching donors and a positive autologous crossmatch due to IgG anti HLA auto-antibodies, which are at the same time against matched donors. Since positive crossmatch is a contraindication for transplant, we couldn’t perform transplant from any matched donor. Therefore, we considered a total mismatched donor then transplantation was performed. Observation after surgery showed normalization of creatinine, blood pressure and a good function of the planted allograft for two years of follow up.     

Systems Medicine: from molecular features and models to the clinic in COPD

Background and hypothesis

Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice.

Objective and method

Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework.

Results

In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice.

Conclusions

The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models. Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them.

     

Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats

The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague–Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.     

Stage IIB carcinoma of the cervix that is associated with pelvic kidney: A therapeutic dilemma

Locally advanced cervical cancer with congenital pelvic kidney is reported uncommonly. A 50-year-old patient with stage IIB cervical cancer and pelvic kidney was treated with irradiation and concurrent chemotherapy. Follow-up evaluation for 2 years revealed normal renal function and no evidence of recurrent disease.     

F-FDG18PET/CT incidental detection of tumor-to-tumor metastasis in patients investigated for squamous cell lung cancer

Tumor-to-tumor metastasis (TTM) is a well-known entity, although this is still an extremely rare phenomenon. The lung cancers are considered the most frequent metastatic donors while kidney cancers are the most common recipient. The finding of TTM is often incidental during a biopsy of metastases or on surgical specimens but never suspected on radiological assessment of tumor extension. The finding of an unexpected region of Fluorodeoxyglucose (FDG) uptake can occur when performing whole body Positron Emission Tomography/computed tomography (PET/CT) scan and potentially raises the possibility of a second primary tumor. However, PET/CT scan incidental detection of tumor-to-tumor metastasis has never been reported in English literature. We report here a case of clear cell renal carcinoma, receptor of metastases originating from an oligometastatic squamous cell lung cancer detected on the PET/CT scan performed as part of the extension workup. Morphological and immunohistochemical analysis of a percutaneous biopsy of the renal mass were consistent with the diagnosis of a metastasis of lung cancer into renal cell carcinoma. This is the first case of oligometastatic lung cancer with the occurrence of TTM suspected in PET/CT scan. Although this is a rare setting, it should be considered in daily practice, as it could potentially modify the oncological management offered to the patients.     

Intramyocardial Injection of Autologous Bone Marrow-Derived Ex Vivo Expanded Mesenchymal Stem Cells in Acute Myocardial Infarction Patients is Feasible and Safe up to 5 Years of Follow-up

In experimental studies, mesenchymal stem cell (MSC) transplantation in acute myocardial infarction (AMI) models has been associated with enhanced neovascularization and myogenesis. Clinical data however, are scarce. Therefore, the present study evaluates the safety and feasibility of intramyocardial MSC injection in nine patients, shortly after AMI during short-term and 5-year follow-up. Periprocedural safety analysis demonstrated one transient ischemic attack. No other adverse events related to MSC treatment were observed during 5-year follow-up. Clinical events were compared to a nonrandomized control group comprising 45 matched controls. A 5-year event-free survival after MSC-treatment was comparable to controls (89 vs. 91 %, P?=?0.87). Echocardiographic imaging for evaluation of left ventricular function demonstrated improvements up to 5 years after MSC treatment. These findings were not significantly different when compared to controls. The present safety and feasibility study suggest that intramyocardial injection of MSC in patients shortly after AMI is feasible and safe up to 5-year follow-up.     

Power-Dependent Investigation of Photo-Response from GeSn-Based p-i-n Photodetector Operating at High Power Density

We report an investigation on the photo-response from a GeSn-based photodetector using a tunable laser with a range of incident light power. An exponential increase in photocurrent and an exponential decay of responsivity with increase in incident optical power intensity were observed at higher optical power range. Time-resolved measurement provided evidence that indicated monomolecular and bimolecular recombination mechanisms for the photo-generated carriers for different incident optical power intensities. This investigation establishes the appropriate range of optical power intensity for GeSn-based photodetector operation.     

Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes

The complexes: [CoL₂](ClO₄)₂ (1), [FeL₂](ClO₄)₂ (2), [NiL₂](ClO₄)₂ (3) and [MnLCl₂] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized. Structural analysis revealed two distinct patterns influenced by the counter ions where L acts as a tridentate chelating ligand. The in vitro antitumor activity of L and L′ (diethyl 2,2′-(pyridine-2,6-diylbis(5-methyl-1H-pyrazole-3,1-diyl)) diacetate) as well as their metal complexes, was tested by the measurement of their cytostatic and cytotoxic properties towards the blood cancer mastocytoma cell line P815. We have also investigated their interactions with the antioxidant enzyme system. As a result, [MnL′Cl₂] (1′) exhibited the strongest activity compared to reference cis-platin with no cytotoxicity towards normal cells PBMCs (Peripheral Blood Mononuclear Cells). On the other hand, the antioxidant enzyme activity showed that the efficiency of metal complex 1′ against P815 tumor cells was via the rise in the SOD activity and inhibition of CAT enzyme activity. This proof of concept study allows disclosure of a new class of molecules in cancer therapeutics.

The complexes: [CoL₂](ClO₄)₂ (1), [FeL₂](ClO₄)₂ (2), [NiL₂](ClO₄)₂ (3) and [MnLCl₂] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized.     

Bridging the gap in epilepsy care: A single-center experience of 3700 outpatient tele-epilepsy visits

We describe the largest-to-date single-center implementation of tele-epilepsy. Beginning in 2017, all patients at a single tertiary care academic epilepsy center were offered the option to complete outpatient follow-up visits via video-conferencing using personal devices. A retrospective review of all patients who self-selected virtual visits over nearly 3 years showed 2140 patients completed 3698 tele-epilepsy visits, with 41% completing more than one visit during the study period. Based on the distance from the center to the home address, 26.7% of patients were local (≤50 miles), 30.5% were near regional (51-150 miles), 20.1% were far regional (151-270 miles), and 22.7% were remote (>270 miles), from 43 different states. An estimated 928 696 miles of travel was prevented, with a median travel distance saved of 124.5 miles (interquartile range = 45.0-253.0). The mean visit time was 15.7 (±10.4) minutes. More than 90% of patients gave the visit and provider experience the maximum rating, with a nearly 60% response rate on the post-visit survey. Virtual outpatient follow-up care provides a convenient way to connect with epilepsy specialists and reduce the burden of care by cutting travel time. Our experience demonstrates that outpatient tele-epilepsy is feasible, sustainable, and scalable.