Bilateral adrenal cryptococcosis causing adrenal insufficiency in an immunocompetent patient.

ABSTRACT: Cryptococcosis usually occurs in immunocompromised patients and presents as meningitis and lung disease. Adrenal gland involvement may be observed, yet primary adrenal insufficiency by cryptococcal infection is infrequent. We present a case of a middle-aged immunocompetent man with primary adrenal insufficiency and bilateral adrenal lesions, splenomegaly, and miliary mottling in the lungs on imaging. No evidence of meningitis was witnessed. The clinico-radiological findings led toward the differential diagnosis of disseminated tuberculosis or fungal infection. Detection of cryptococcus organism was done on fine-needle aspiration cytology and biopsy on periodic acid-Schiff stain and Gomori`s methenamine silver stain. Thus, it is recommended to keep the possibility of cryptococcosis in mind while dealing with instances that have a tuberculosis-like clinico-radiological presentation. The detection of the causal organism on Fine needle aspiration (FNA)/biopsy examination may be useful in confirming the diagnosis and determining the appropriate medical treatment.

Post-hepatectomy venous thromboembolism: a systematic review with meta-analysis exploring the role of pharmacological thromboprophylaxis.

PURPOSE: Patients undergoing hepatectomy are at moderate-to-high risk of venous thromboembolism (VTE). This study critically examines the efficacy of combining pharmacological (PTP) and mechanical thromboprophylaxis (MTP) versus only MTP in reducing VTE events against the risk of hemorrhagic complications. METHODS: A systematic review of major reference databases was undertaken, and a meta-analysis was performed using common-effects model. Risk of bias assessment was performed using Newcastle-Ottawa scale. Trial sequential analysis (TSA) was used to assess the precision and conclusiveness of the results. RESULTS: 8 studies (n = 4238 patients) meeting inclusion criteria were included in the analysis. Use of PTP + MTP was found to be associated with significantly lower VTE rates compared to only MTP (2.5% vs 5.3%; pooled RR 0.50, p = 0.03, I2 = 46%) with minimal type I error. PTP + MTP was not associated with an increased risk of hemorrhagic complications (3.04% vs 1.9%; pooled RR 1.54, p = 0.11, I2 = 0%) and had no significant impact on post-operative length of stay (12.1 vs 10.8 days; pooled MD - 0.66, p = 0.98, I2 = 0%) and mortality (2.9% vs 3.7%; pooled RR 0.73, p = 0.33, I2 = 0%). CONCLUSION: Despite differences in the baseline patient characteristics, extent of hepatectomy, PTP regimens, and heterogeneity in the pooled analysis, the current study supports the use of PTP in post-hepatectomy patients (grade of recommendation: strong) as the combination of PTP + MTP is associated with a significantly lower incidence of VTE (level of evidence, moderate), without an increased risk of post-hepatectomy hemorrhage (level of evidence, low).

Classification of paediatric brain tumours by diffusion weighted imaging and machine learning.

To determine if apparent diffusion coefficients (ADC) can discriminate between posterior fossa brain tumours on a multicentre basis. A total of 124 paediatric patients with posterior fossa tumours (including 55 Medulloblastomas, 36 Pilocytic Astrocytomas and 26 Ependymomas) were scanned using diffusion weighted imaging across 12 different hospitals using a total of 18 different scanners. Apparent diffusion coefficient maps were produced and histogram data was extracted from tumour regions of interest. Total histograms and histogram metrics (mean, variance, skew, kurtosis and 10th, 20th and 50th quantiles) were used as data input for classifiers with accuracy determined by tenfold cross validation. Mean ADC values from the tumour regions of interest differed between tumour types, (ANOVA P < 0.001). A cut off value for mean ADC between Ependymomas and Medulloblastomas was found to be of 0.984 × 10-3 mm2 s-1 with sensitivity 80.8% and specificity 80.0%. Overall classification for the ADC histogram metrics were 85% using Naïve Bayes and 84% for Random Forest classifiers. The most commonly occurring posterior fossa paediatric brain tumours can be classified using Apparent Diffusion Coefficient histogram values to a high accuracy on a multicentre basis.

Quantitative MRI demonstrates abnormalities of the third ventricle subventricular zone in neurofibromatosis type-1 and sporadic paediatric optic pathway glioma.

BACKGROUND: The subventricular zone of the third ventricle (TVZ) is a germinal stem cell niche, identified as the possible location of optic pathway glioma (OPG) cell origin. Paediatric OPGs are predominantly diagnosed as low-grade astrocytomas, which are either sporadic or are associated with neurofibromatosis type-1 (NF1). These tumours often cause a significant impairment to visual acuity (VA). Infiltrative/invasive tumour activity is associated with increased apparent diffusion coefficient (ADC) and cerebral blood flow (CBF). This study aimed to determine whether TVZ imaging features differed between sporadic-OPG, NF1-OPG and controls, and whether the ADC and CBF profile at the germinal stem cell niche (the TVZ) correlated with the primary outcome of VA. METHODS: ADC and CBF MRI data were acquired from 30 paediatric OPG patients (median age 6 years; range 8 months-17 years), along with VA measurements, during clinical surveillance of their tumour. Values for mean ADC and maximum CBF were measured at the TVZ, and normalized to normal-appearing grey matter. These values were compared between the two OPG groups and the healthy control subjects, and multivariate linear regression was used to test the linear association between these values and patient's VA. RESULTS: In the TVZ, normalized mean ADC was higher in NF1-associated OPG patients (N = 15), compared to both sporadic OPG patients (N = 15; p = 0.010) and healthy controls (N = 14; p < 0.001). In the same region, normalized maximum CBF was higher in sporadic OPG patients compared to both NF1-OPG patients (p = 0.016) and healthy controls (p < 0.001). In sporadic OPG patients only, normalized mean ADC in the TVZ was significantly correlated with visual acuity (R2 = 0.41, p = 0.019). No significant correlations were found between TVZ CBF and ADC values and visual acuity in the NF1-associated OPG patients. CONCLUSION: Quantitative MRI detects TVZ abnormalities in both sporadic and NF1-OPG patients, and identifies TVZ features that differentiate the two. TVZ features may be useful MRI markers of interest in future predictive studies involving sporadic OPG.

Cytotoxicity of Graphene Oxide (GO) and Graphene Oxide Conjugated Losartan Potassium (GO-LP) on Neuroblastoma (NB41A3) Cells.

Despite several advancements in the biomedical sciences, an efficient cancer therapy still remains a challenge. Nanomedicines have shown potential to overcome certain roadblocks faced in the existing treatment modalities. Losartan potassium (LP) which is a known vasodilator also exhibits anti fibrolytic and anti-metastatic properties altogether. Further, also being a potential angiotensin II type 1 receptor antagonist, it has been well explored for down regulating tumourogenic biomarkers like VEGF-A (Vascular endothelial growth factor A) and suppression of neovascularization, making it a suitable drug to target for cancer treatment. Besides this, it too reflected the stimulation of pro apoptotic signaling pathways. But due to its lower bioavailability and extensive hepatic metabolism its therapeutic index reduces down. Thus, the present study is focused on designing a nano-delivery system using graphene oxide (GO) as a nano-vehicle and conjugated the LP with it. Then, the successful synthesis of GO and GO-LP nano conjugates were characterized by high-resolution transmission electron microscopy, X-ray diffraction, FTIR and UV visible spectroscopy, confirming the formation of nanosheets. The qualitative morphological evaluation of NB41A3 neuroblastoma cell line treated with bare GO, LP and GO-LP using microscopy and DAPI staining revealed the inhibitory action of GO-LP nano conjugate on cell proliferation. Additionally, the cytotoxicity was also estimated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), Nitric oxide (NO) and Lactate dehydrogenase (LDH) assays. The results show that GO-LP significantly suppresses the cell viability in comparison to control and bare GO suggesting that the designed system may express its potential to be used with existing chemo drugs for the treatment of neural cancers.

Delineation of the visual pathway in paediatric optic pathway glioma patients using probabilistic tractography, and correlations with visual acuity.

Background: Radiological biomarkers which correlate with visual function are needed to improve the clinical management of optic pathway glioma (OPG) patients. Currently, these are not available using conventional magnetic resonance imaging (MRI) sequences. The aim of this study was to determine whether diffusion MRI could be used to delineate the entire optic pathway in OPG patients, and provide imaging biomarkers within this pathway which correlate with a patient's visual acuity (VA). Methods: Multi-shell diffusion MRI data were acquired in a cohort of paediatric OPG patients, along with VA measurements in each eye. Diffusion MRI data were processed using constrained spherical deconvolution and probabilistic fibre tractography, to delineate the white matter bundles forming the optic pathway in each patient. Median fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in the optic nerves, tracts, and radiations, and correlated against each patient's VA. Results: In the optic nerves, median FA significantly correlated with VA (R2adj = 0.31, p = 0.0082), with lower FA associated with poorer vision. In the optic radiations, both lower FA and higher ADC were significantly associated with poorer vision (R2adj = 0.52, p = 0.00075 and R2adj = 0.50, p = 0.0012 respectively). No significant correlations between VA and either FA or ADC were found in the optic tracts. Conclusions: Multi-shell diffusion MRI provides in vivo delineation of the optic pathway in OPG patients, despite the presence of tumour invasion. This technique provides imaging biomarkers which are sensitive to microstructural damage to the underlying white matter in this pathway, which is not always visible on conventional MRI.

Molecular Characterization of Pro-Inflammatory Cytokines Interleukin-1ß and Interleukin-8 in Asian Elephant (Elephas maximus).

Interleukin (IL)-1ß and IL-8 are pro-inflammatory cytokines produced primarily by monocytes and macrophages in response to a variety of microbial and nonmicrobial agents. As yet, no molecular data have been reported for IL-1ß and IL-8 of the Asian elephant. In the present study, we have cloned and sequenced the cDNA encoding IL-1ß and IL-8 of the Asian elephant. The open reading frame (ORF) of Asian elephant IL-1ß is 789 bp in length, encoded a propeptide of 263 amino acid polypeptide. The predicted protein revealed the presence of IL-1 family signature motif and an ICE cut site. Whereas, IL-8 contained 321 bp of open reading frame. Interestingly, the predicted protein sequence of 106 aa, contains an ELR motif immediately upstream of the CQC residues, common in all vertebrate IL-8 molecules. Identity levels of the nucleic acid and deduced amino acid sequences of Asian elephant IL-1ß ranged from 68.48 (Squirrel monkey) to 98.57% (African elephant), and 57.78 (Sheep) to 98.47% (African elephant), respectively, whereas that of IL-8 ranged from 72.9% (Human) to 87.8% (African elephant), and 63.2 (human, gorilla, chimpanzee) to 74.5% (African elephant, buffalo), respectively. The phylogenetic analysis based on deduced amino acid sequenced showed that the Asian elephant IL-1ß and IL-8 were most closely related to African elephant. Molecular characterization of these two cytokines, IL-1ß and IL-8, in Asian elephant provides fundamental information necessary to progress the study of functional immune responses in this animal and gives the potential to use them to manipulate the immune response as recombinant proteins.

Challenges for the functional diffusion map in pediatric brain tumors.

BACKGROUND: The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. METHODS: Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. RESULTS: Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. CONCLUSIONS: Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size.

A two-stage model for in vivo assessment of brain tumor perfusion and abnormal vascular structure using arterial spin labeling.

The ability to assess brain tumor perfusion and abnormalities in the vascular structure in vivo could provide significant benefits in terms of lesion diagnosis and assessment of treatment response. Arterial spin labeling (ASL) has emerged as an increasingly viable methodology for non-invasive assessment of perfusion. Although kinetic models have been developed to describe perfusion in healthy tissue, the dynamic behaviour of the ASL signal in the brain tumor environment has not been extensively studied. We show here that dynamic ASL data acquired in brain tumors displays an increased level of 'biphasic' behaviour, compared to that seen in healthy tissue. A new two-stage model is presented which more accurately describes this behaviour, and provides measurements of perfusion, pre-capillary blood volume fraction and transit time, and capillary bolus arrival time. These biomarkers offer a novel contrast in the tumor and surrounding tissue, and provide a means for measuring tumor perfusion and vascular structural abnormalities in a fully non-invasive manner.