Hepatoprotective activity of Balsamodendron mukul extract against Paracetamol-induced liver toxicity in rats: In vivo pharmacological and toxicological evaluation.

Overuse of the antipyretic agent Paracetamol (PCM) is linked to hepatotoxicity, which limits its clinical use. The goal of this investigation was to find out how well Balsamodendron mukul (B. mukul) extract protects the liver from acute PCM poisoning. B. mukul extract was procured from a standard crude drug supplier in the local market. The PCM-induced hepatotoxicity was screened in experimental animals. Animals that were treated only with excessive PCM (2g/kg) had changes in their serum biomarkers (i.e., serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, and serum total bilirubin), oxidative stress, Tumor Necrosis Factor-α (TNF-α), and Interleukin-1 proteins. B. mukul extracts of 245µg and 332µg revealed 50% of hydroxyl radical scavenging and lipid peroxidation inhibiting, respectively, which was found to be more significant when compared to ascorbic acid treatment. The outcomes confirmed that B. mukul extract has strong antioxidant activity, which leads to the inhibition of reactive oxygen species (ROS). Treatment with B. mukul extract at doses of 300 and 600mg/kg produced a dose-dependent reduction in the PCM-induced rise of the biochemical parameters. Silymarin at 100mg/kg body weight significantly prevented such rise in the study. Finally, the findings confirmed that the B. mukul extract has more potent than silymarin and revealed higher antioxidant and hepatoprotective activity, which could consider a novel approach for the reduction of PCM-induced liver toxicity.

Ethnicity in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the commonest gynecological endocrinopathy. Little is known about the exact etiopathogenesis and cardiometabolic mortality and morbidity in women with PCOS. PCOS is beyond the cosmetic concerns of an adolescent and fertility concerns of an adult and can cause serious unhealthy consequences in perimenopausal and postmenopausal age. This area needs to be assessed and addressed since the majority of these patients are lost to follow-up after completion of their families. Good evidence suggests that there are significant racial and ethnic differences in prevalence, insulin resistance, metabolic syndrome, hyperandrogenemia and the related cardiometabolic risk in women with PCOS.

Risk factors and outcome analysis of patients with intraoperative rupture (IOR) of ruptured cerebral aneurysm during microsurgical clipping.

PURPOSE: To analyse baseline characteristics of patients with intraoperative rupture (IOR) or non-IOR who underwent microsurgical clipping for ruptured intracranial aneurysms. Additionally, to asses functional outcome in terms of Glasgow Outcome Scale (GOS) at 6 and 12 months. METHODS: A retrospective analysis of 471 patients who underwent microsurgical clipping for ruptured intracranial aneurysms from 2007 to 2018 in Nepal Mediciti Hospital, Nepal. Patients who underwent surgery for unruptured aneurysm were excluded from the study. The association of the base line characteristic in IOR and non-IOR were analysed. Variables analysed were the Hunt and Hess Scale (HHS) dichotomized as (1-3) and (4-5), Modified Fisher Scale dichotomized as (0-2) and (3-4), type of rupture, use of brain retractor, timing of IOR during surgery, aneurysmal factors (size of the neck, location, lobulation) and time of surgery. Outcome, GOS dichotomized into favourable (4-5) and unfavourable (1-3), assessed at 6 months and 12 months. RESULTS: Out of 471 patients treated for ruptured intracranial aneurysm, IOR occurred in 57 (12.10%) with mean age 49.47 (SD ±12.9), occurred more in smoker than non-smoker (45.6% vs. 18.6%; p=.000) and regular alcohol consumers (36.8% vs. 17.9%; p=.004). Favourable outcome with GOS (4-5) at 6 months was observed among patients with lower HHS (1-3), p=.025 and lower MFS (0-2), p=.04. However, outcome at 12 months was better associated with MFS (p=.013) and aneurysm size (p=.038), with more favourable outcome associated with aneurysm less than 10 mm. CONCLUSIONS: Alcohol consumption and smoking are associated risk factors that may contribute to IOR. HHS and MFS are strong predictors of outcome for IOR patients at 6 months. However, at 12 months, MFS is more predictive of outcome. Aneurysms greater than 10 mm had a strong association with outcome at 12 months than 6 months.

Metastasis of squamous cell carcinoma of the head and neck to the thyroid: a single institution's experience with a review of relevant publications.

The thyroid gland is a rare site of metastasis, and in particular of those of squamous cell carcinoma (SCC) from the head and neck region. We have reviewed the aetiology, pathogenesis, clinical characteristics, radiological features, immunohistochemical profile, prognosis, and management of metastatic SCC from the head and neck region to the thyroid, and searched current publications on the Medline, Embase, and Cochrane databases using the following keywords: "SCC of thyroid", "secondary SCC of thyroid", and "metastasis to the thyroid", for papers published during the last 33 years (April 1984 to October 2017).We found a total of 19 papers that reported a total of 32 cases that were relevant. Four further cases were discovered as an incidental finding on follow-up positron emission tomographic/computed tomographic scans with magnetic resonance imaging of the head and neck at our hospital, which were confirmed with an ultrasound-guided core needle biopsy followed by immunohistochemical examination. For patients who are doing well, whose disease is controlled at the primary site, and who have no evidence of distant metastatic disease, total thyroidectomy could be considered followed by adjuvant radiation or chemoradiotherapy, depending on the presence of intermediate or high-risk features on pathological examination and previous history of radiation. This may help to control the disease and avoid local morbidity.

Ocular manifestations in tuberculosis cases with HIV in Nepal.

INTRODUCTION: TB has seen resurgence associated with HIV. Tuberculosis can affect any ocular tissue. The association of HIV with TB is supposed to increase the incidence and plethora of ocular manifestations in tuberculosis. OBJECTIVES: To study the various ocular manifestations seen in tuberculosis patients with associated HIV infection. MATERIAL AND METHODS: This hospital based, cross sectional descriptive study was conducted in Tribhuvan University, Teaching Hospital, Maharajgunj, Nepal and Geta Eye Hospital, Kailali from 2010 to 2015. Diagnosed cases of pulmonary and extra pulmonary tuberculosis with HIV co infection were evaluated for ocular manifestations after excluding other opportunistic infections. RESULTS: Of 70 cases eligible for the study, extra pulmonary tuberculosis was seen in60% of the cases. 5 patients (7.1 %) had ocular manifestations. CD4 counts were <50/mm3 in 3 cases. Ocular involvement was seen in the form of choroidal granulomas, papillitis, cranial nerve palsy, retinal vasculitis and central serous chorioretinopathy. CONCLUSION: This study demonstrated that ocular involvement is a frequent finding in cases with tuberculosis and HIV. Ocular findings are more common in cases with lesser CD4 counts. As ocular tuberculosis can be visually devastating, we recommend regular ocular evaluation of all patients with HIV and systemic tuberculosis.

Minimally invasive and targeted therapeutic cell delivery to the skin using microneedle devices.

BACKGROUND: Translation of cell therapies to the clinic is accompanied by numerous challenges, including controlled and targeted delivery of the cells to their site of action, without compromising cell viability and functionality. OBJECTIVES: To explore the use of hollow microneedle devices (to date only used for the delivery of drugs and vaccines into the skin and for the extraction of biological fluids) to deliver cells into skin in a minimally invasive, user-friendly and targeted fashion. METHODS: Melanocyte, keratinocyte and mixed epidermal cell suspensions were passed through various types of microneedles and subsequently delivered into the skin. RESULTS: Cell viability and functionality are maintained after injection through hollow microneedles with a bore size ≥ 75 µm. Healthy cells are delivered into the skin at clinically relevant depths. CONCLUSIONS: Hollow microneedles provide an innovative and minimally invasive method for delivering functional cells into the skin. Microneedle cell delivery represents a potential new treatment option for cell therapy approaches including skin repigmentation, wound repair, scar and burn remodelling, immune therapies and cancer vaccines.

Rapid ex vivo examination of Mohs specimens using optical coherence tomography.

BACKGROUND: Mohs micrographic surgery (MMS) is an effective treatment for certain non-melanoma skin cancers. Optical coherence tomography (OCT) is a biomedical imaging modality that permits high-resolution imaging of the epidermis and dermis with the potential to detect both healthy tissue and tumour. OCT may also provide a means of detecting and differentiating between the various histological subtypes of basal cell carcinomas (BCC) in vivo. OBJECTIVE: The aim of this prospective ex vivo study was to evaluate the efficacy of OCT in recognising healthy and pathological margins of excised BCC lesions and detecting different BCC subtypes. METHODS: Seventy-three subjects with biopsy-proven BCCs on the facial region undergoing MMS were recruited. Narrow clinically healthy margins of the skin surrounding the tumour were included in the excisional biopsy. Biopsies were scanned with the OCT instrument immediately ex vivo and processed to obtain horizontal Mohs frozen sections and compared with their corresponding OCT images. RESULTS: Histopathological analysis of 280 margins showed 232 tumour free margins and 48 tumour-involved margins. OCT showed very good sensitivity (81.2%) and specificity (94.3%) in detecting healthy from tumour-involved margins. OCT accuracy was 93.4%, and the intra- and inter-observer reliability was substantial (Kappa value ranged between 0.63-0.76). CONCLUSION: This study shows the accuracy of ex vivo OCT in identifying the margin status of BCCs of the head and neck region. Moreover, this modality has demonstrated good capability in distinguishing different BCC subtypes and the potential for in vivo in situ diagnostics.

Differentiating recurrent tumours from post-treatment changes in head and neck cancers: does diffusion-weighted MRI solve the eternal dilemma?

AIM: To evaluate the utility of diffusion-weighted imaging (DWI) in differentiating post-treatment changes from tumour recurrence in head and neck cancers and to establish a threshold apparent diffusion coefficient (ADC) value to differentiate the two conditions. MATERIALS AND METHODS: This was a prospective study of 80 treated head and neck cancer patients. The patient cohort consisted of a wide spectrum of head and neck sites, including the oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses, orbits, salivary glands, and infra-temporal fossa. Qualitative analysis of the diffusion images and quantitative analysis of the corresponding ADC maps was performed and the data were correlated with histopathological findings and clinical examinations. RESULTS: The mean ADC value of recurrent tumours in the present cohort was 0. 932±0.19×10-3 mm2/s and the mean ADC value of lesions representing post-treatment changes was 1.394±0.32×10-3 mm2/s. A threshold ADC value of 1.2×10-3mm2/s used to differentiate post-treatment changes from recurrent head and neck cancers showed the highest combined sensitivity of 90.13%, specificity of 82.5%, accuracy of 86.4%, positive predictive value of 84.4%, negative predictive value of 88.9%, and mean kappa measurement of agreement of 72.8. CONCLUSION: Combined qualitative and quantitative analysis of DWI is a useful non-invasive technique to differentiate recurrent head and neck malignancies from post-treatment changes using a threshold ADC value.

Scleritis and Takayasu's disease - rare combined presentation.

INTRODUCTION: Takayasu's disease (TD) (pulseless disease, aortic arch syndrome) is a rare but potentially life-threatening chronic giant cell vasculitis. The major complications attributed to the disease include Takayasu's retinopathy, secondary hypertension, aortic regurgitation, and arterial aneurysm. The aim of this study is to describe a patient with Takayasu's disease and scleritis and to show its association. CASE REPORT: We describe a 44-year-old female patient with Takayasu's disease who presented with bilateral anterior scleritis in the form of painful red eye. Patient did not have any associated autoimmune diseases. Patient was diagnosed to have TD and was treated with immunosuppressant. CONCLUSION: Scleritis though rare can be a vasculitic feature of TD. This is a first report of Takayasu's disease with scleritis, which has been documented in Nepal.

Quantification of diffusion and anisotropy in intracranial epidermoids using diffusion tensor metrics and p: q tensor decomposition.

PURPOSE: To quantitatively evaluate the diffusion tensor metrics p, q, L and fractional anisotropy in intracranial epidermoids in comparison with normal white matter in the splenium of the corpus callosum. METHODS: This retrospective study included 20 consecutive patients referred to our institute. All patients had a magnetic resonance imaging (MRI) study on a 1.5-Tesla MR system. A spin-echo echo-planar DTI sequence with diffusion gradients along 30 non-collinear directions was performed. The eigen values (λ1, λ2, λ3) were computed for each voxel and, using p: q tensor decomposition, the DTI metrics p, q and L-values and fractional anositropy (FA) were calculated. The region of interest (ROI) (6 pixels each) was placed within the lesion in all the cases and in the splenium of the corpus callosum. RESULTS: The mean FA in the lesion and splenium were 0.50 and 0.88 respectively, with a statistically significant difference between them (P<0.01). On p: q tensor decomposition, the mean p-value in the epidermoid was 1.55±0.24 and 1.35±0.20 in the splenium; the mean q-values in the epidermoid was 0.67±0.13 and 1.27±0.17 in the splenium; the differences were statistically significant (P=0.01 and <0.01 respectively). The significant difference between p- and q-values in epidermoids compared with the splenium of callosum was probably due to structural and orientation differences in the keratin flakes in epidermoids and white matter bundles in the callosum. However, no significant statistical difference in L-values was noted (P=0.44). CONCLUSION: DTI metrics p and q have the potential to quantify the diffusion and anisotropy in various tissues thereby gaining information about their internal architecture. The results also suggest that significant differences of DTI metrics p and q between epidermoid and the splenium of the corpus callosum are due to the difference in structural organization within them.

Use of Doppler ultrasound in the management of uteroplacental perfusion during cardiopulmonary bypass in pregnancy.

Cardiopulmonary bypass, the extreme of non-obstetric surgery during pregnancy, presents unique challenges to minimize maternal and fetal risk. We present our experience with a woman who was diagnosed with a left atrial myxoma following an ischemic cerebrovascular accident. We discuss clinical management specific to cardiopulmonary bypass during pregnancy and delivery in the context of a multidisciplinary team approach. We recommend using intermittent Doppler ultrasound as a non-invasive real-time assessment of uteroplacental perfusion during non-obstetric surgery in pregnancy. Monitoring of perfusion facilitates active feedback for appropriate in utero resuscitation in these cases.

Polycystic ovary syndrome and metabolic syndrome: the worrisome twosome?

By virtue of insulin resistance being the common etiology for polycystic ovary syndrome (PCOS) and metabolic syndrome, the cardiometabolic risks of these two syndromes are shared. The usual concerns of a PCOS patient are cosmetic or reproductive. However, there are more serious concerns past the reproductive age. Early treatment of insulin resistance, hypertension and hyperlipidemia reduces the long-term risk. This review highlights the unhealthy association of metabolic syndrome with PCOS and emphasizes the importance of early diagnosis, patient education and long-term follow-up beyond the reproductive age into menopause to prevent the long-term serious co-morbidities.

Carotid interventions (CEA and CAS) in acute stroke patients: which procedure on which patient.

Treatment of carotid bifurcation disease in patients presenting with acute stroke has been a controversial issue over the past four decades. Classically, patients were asked to wait four to six weeks before intervention was entertained in order for the brain to stabilize and the risks of intervention to be minimized. Unfortunately, up to 20% of patients will have a secondary event after their index event and the window of opportunity to save, potentially salvageable ischemic tissue will be missed. Early reports had demonstrated poor results with intervention. However, more recently, institutions such as ours have demonstrated excellent result in early intervention in patients who present with stable mild to moderate stroke with an NIH stroke scale less than 15 and preferably less than 10, present with stroke and ipsilateral carotid artery lesion of 50% or greater. Also more recently, we have been aggressively treating patients with larger ulcerative plaques even if the stenosis approaches 50%. In our and others experiences, patients who are treated at institutions that have comprehensive stroke centers (CSCs) where they have a multidisciplinary system that consists of vascular surgeons, neuro interventionalists, stroke neurologists, specifically trained stroke nursing staff and a neuro intensive ICU have had optimal results. Early assessment, diagnosis of stroke with recognition of cause of embolization is mandatory but patient selection is extremely important; finding those patients who will benefit the most from urgent intervention. Most studies have demonstrated the benefit of carotid endarterectomy in these patients. More recent studies have demonstrated acceptable results with carotid stenting, especially in smaller lesions, those less than 1.2 centimeters. Early intervention should be avoided in most patients who are obtunded or with an NIH stroke scale greater than 15 or who do not have any "brain at risk" to salvage. These patients may be better served by being treated medically than those small group of patients that do have some improvement may benefit from interval intervention.

Remote surveillance after colorectal cancer surgery: an effective alternative to standard clinic-based follow-up.

AIM: Most colorectal cancer recurrences are asymptomatic and are detected through routine postoperative clinic surveillance programmes with associated investigations. However, attendance at these clinics has a financial cost and may be associated with an increase in patient anxiety and dissatisfaction. The results of a remote follow-up system developed for selected patients are reported. METHOD: A remote surveillance programme has been in place in our institution for over 9 years. Patients having elective and emergency treatment for colorectal cancer were enrolled. The timeliness of the investigation, detection of local recurrence and distant metastases and overall 5-year survival rates were determined. A cost review and patient satisfaction survey were performed. RESULTS: The programme was suitable for over 900 patients who had received surgery for colorectal cancer between 2004 and 2012, representing some 50% of the total number of patients treated in this period. Of these, 811 (90%) had investigations carried out on time. Five-year survival rates were comparable with national data. Cost-minimization analysis demonstrated a financial saving of 63% and a 75% reduction in clinic appointments. High levels of overall patient satisfaction (97%) were noted with the programme. CONCLUSION: A remote surveillance system after colorectal cancer surgery is a safe and cost-effective alternative to traditional clinic-based follow up and has high patient satisfaction.

Discrepancy in fetal sex assignment between cell free fetal DNA and ultrasound.

Noninvasive prenatal testing utilizing free fetal DNA is commonly used in pregnancy to screen for trisomy 13, 18, 21 and also fetal sex aneuploidy. We report on two cases of discrepancy between phenotypic and genotypic sex and potential medical implications. In our first case, a patient with known male gender via cell free fetal DNA (cffDNA) testing had an ultrasound at 18 weeks' gestation, which identified Dandy-Walker malformation and female-appearing ambiguous genitalia. As Dandy-Walker malformation could not be considered isolated in the presence of ambiguous genitalia, this finding allowed for more complete counseling of the parents as well as extensive genetic workup. Our second case involved a fetus with intrauterine growth restriction diagnosed by ultrasound and normal-appearing female genitalia. After birth, adrenal insufficiency was diagnosed and chromosome analysis identified normal male chromosomes. These two cases showed that fetal sex determination by cffDNA can be used as a tool for earlier identification of affected pregnancies, allowing for parental decision-making, genetic testing and earlier intervention.

Fecal colonization and infection with Pseudomonas aeruginosa in recipients of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Pseudomonas aeruginosa, especially multidrug-resistant (MDR) isolates, is an important pathogen in allogeneic hematopoietic stem cell transplant (HCT) recipients. The ability to identify patients at risk for these infections and administer appropriate empiric therapy, particularly during episodes of neutropenia, may improve outcomes and also direct infection control and antimicrobial stewardship efforts. Many transplant centers obtain routine surveillance stool cultures (SSCs) from HCT recipients to test for colonization with vancomycin-resistant enterococci, and extended-spectrum beta lactamase-producing Enterobacteriaceae. Our center initiated the performance of SSCs for P. aeruginosa, because of a perceived increase in the frequency of infection with MDR strains. The aim of this study was to determine the utility of this practice. METHODS: We conducted a 2-year (2010-2011) retrospective review of the medical records of all patients who underwent allogeneic HCT at our cancer center to (a) determine the frequency of fecal colonization with P. aeruginosa, including MDR strains; (b) to determine the overall frequency of subsequent P. aeruginosa infection, as well as the frequency of infection with MDR strains; (c) to ascertain the proportion of subsequent infections likely arising from the intestinal tract; and (d) to determine risk factors for progression from colonization to infection. RESULTS: Of 794 study patients, 58 (7.3%) had at least 1 positive SSC for P. aeruginosa; 19/58 (32.8%) developed a subsequent pseudomonal infection (11 with matching antimicrobial resistance patterns). On the other hand, 37/736 (5%) of the patients who were not colonized, developed a pseudomonal infection. The type of infection observed was pneumonia in 26 (46%) patients, bloodstream infection in 20 (36%), urinary tract infection in 8 (14%), and infections at other sites in 2 (4%). The incidence of MDR P. aeruginosa in the entire cohort was 2.2% (18 of 794): 12 had positive SSCs and 7 of these patients later developed MDR P. aeruginosa infections. Patients with acute myelogenous leukemia were more likely to be colonized and to develop subsequent infection. No infection-related deaths were observed during the first 30 days after infection. CONCLUSIONS: The incidence of P. aeruginosa colonization and subsequent infection was low. Patients who were not colonized had a low chance of developing P. aeruginosa infection. Most patients who developed infection did not have fecal colonization, suggesting a different source of infection. SSCs for P. aeruginosa provide incomplete information regarding the source of infection.

Vaccination guidelines after hematopoietic stem cell transplantation: practitioners' knowledge, attitudes, and gap between guidelines and clinical practice.

BACKGROUND: Hematopoietic stem cell transplant (HCT) recipients are more susceptible to infections from vaccine-preventable diseases than the general population. Despite the development of international consensus guidelines addressing immunization after HCT, studies have shown that deviations from recommended immunization practices commonly occur. METHODS: An anonymous survey aimed at determining awareness of the guidelines and attitudes toward vaccination was distributed to our HCT clinicians. In parallel, we retrospectively evaluated patients' characteristics and post-HCT vaccine administration practices from 2010 to 2013. RESULTS: The majority of survey respondents (96%) were familiar with post-HCT vaccination protocols. Seventy-four percent of respondents reported that influenza vaccines were given to >70% of their patients, and 41% stated that they prescribed live vaccines to eligible patients. However, our pharmacy database review revealed that 38% of patients received the first series of vaccinations by the recommended 6 months post HCT, and 60% received them by 1 year after HCT. Most patients who had their vaccines withheld had relapsed disease or were undergoing treatment for graft-versus-host disease. Furthermore, we identified lower immunization rates in non-English speaking individuals, African-Americans, and Hispanic patients. CONCLUSIONS: Survey respondents reported being aware of current guidelines; however, adherence to the recommendations varied, likely connected to conflicting data on vaccine effectiveness and a lack of clear recommendations in complex clinical scenarios. Similar to the general population, patient barriers also could have contributed to lower vaccination rates in some cases. To decrease the large gap between the post-HCT vaccination guidelines and clinical practice, further studies on vaccine effectiveness and specific populations are warranted.

Unilateral closed lip schizencephaly with septo-optic dysplasia.

Schizencephaly is a rare malformation of the central nervous system. Both genetic and non-genetic etiologies like prenatal infections or ischemia have been postulated. Clinical manifestations most often include varying degrees of developmental delay, motor impairment and seizures. It can be associated with septo-optic dysplasia (SOD), optic nerve hypoplasia and absence of septum pellucidum, pachygyria, polymicrogyria, heterotopia and arachnoid cysts. We report a case of unilateral closed lip schizencephaly with SOD.