Development and validation of nomograms predicting postoperative survival in patients with chromophobe renal cell carcinoma.

Objective: The purpose of our study is to construct and validate nomograms that effectively predict postoperative overall survival and cancer-specific survival for patients with chromophobe renal cell carcinoma (chRCC). Method: Clinical, social, and pathological data from 6016 patients with chRCC collected from the SEER database were screened from 2004 to 2015. They were randomly assigned to a training cohort (n = 4212) and a validation cohort (n = 1804) at a 7:3 ratio. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were used to identify the prognostic factors affecting overall survival (OS) and cancer-specific survival (CSS) and establish nomograms. Their performance was validated internally and externally by calculating Harrell's C-indexes, area under the curve (AUC), calibration, and decision curves. For external validation, samples from postoperative patients with chRCC at 3 independent centers in Xuzhou, China, were collected. Risk stratification models were built according to the total scores of each patient. Kaplan-Meier curves were generated for the low-risk, intermediate-risk, and high-risk groups to evaluate survival. Results: The C-indexes, AUC curves, and decision curves revealed the high ability of the nomograms in predicting OS and CSS, overall better than that of AJCC and TNM staging. Moreover, in internal and external validation, the calibration curves of 5-, 8-, and 10-year OS agreed with the actual survival. Kaplan-Meier curves indicated significant differences in survival rates among the 3 risk groups in OS or CSS. Conclusion: The nomograms showed favourable predictive power for OS and CSS. Thus, they should contribute to evaluating the prognosis of patients with chRCC. Furthermore, the risk stratification models established on the nomograms can guide the prognosis of patients and further treatment.

An accidental emamectin benzoate poisoning in child: A case report.

We report a case of accidental Emamectin Benzoate poisoning in a six-year-old child resulting in nausea, vomiting, abdominal pain, and confusion. We did vigorous gastric lavage with saline, activated charcoal, and coconut oil. The other supportive treatment improved the outcome of the patient with complete resolution of symptoms.

[PDE-5i combined with RigiScan-based audiovisual sexual stimulation test versus nocturnal penile tumescence test in evaluation of erectile function].

OBJECTIVE: To explore the clinical value of phosphodiesterase type-5 inhibitors (PDE-5i) combined with RigiScan-based audiovisual sexual stimulation (AVSS) test in comparison with that of nocturnal penile tumescence (NPT) test in evaluation of erectile function. METHODS: A total of 166 ED patients, aged 21－63 (mean 31) years, with a disease course of 3 months to 10 years (mean 14 months), underwent NPT test or PDE-5i + RigiScan-based AVSS test from 2017 to 2018. We compared the results of the diagnostic strategies. Normal NPT patterns were presumed to indicate psychogenic and abnormal ones to indicate organic ED. RESULTS: Compared with the results of NPT test, no statistically significant difference was observed in the accuracy rate between Viagra + AVSS test and Cialis + AVSS test (P > 0.05). PDE-5i + RigiScan-based AVSS test achieved a sensitivity of 78.9% and a specificity of 90.7% in the diagnosis of psychogenic ED and an overall accuracy rate of 81.9%. According to the results of PDE-5i + RigiScan-based AVSS test, the patients fell into a normal and an abnormal erection group, with significant differences between the two groups in age, disease course, IIEF-5 score and maintenance time of penile tip rigidity ≥60% (P < 0.05). ROC curve analysis indicated that PDE-5i + RigiScan-based AVSS test accurately manifested the erectile function of the patients. CONCLUSIONS: Compared with NPT test, PDE -5i combined with RigiScan-based AVSS test is simple, inexpensive, practical and with a high sensitivity and specificity, and therefore can be used as the first-choice strategy for etiological diagnosis of ED.

Direct Oxidative Azo Coupling of Anilines Using a Self-Assembled Flower-like CuCo2O4 Material as a Catalyst under Aerobic Conditions.

Herein, we report the synthesis of a self-assembled flower-like CuCo2O4 material by the oxalate decomposition method. The crystalline structure and morphology of the material have been analyzed by powder X-ray diffraction, Raman spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and energy-dispersive X-ray measurement techniques. The self-assembled flower-like CuCo2O4 material showed remarkable catalytic activity in the direct aerobic oxidative azo coupling of anilines under oxidant and other additive-free reaction conditions. The mechanistic insight of CuCo2O4 in the oxidative azo coupling reaction has been established by density functional theory calculations, which disclosed that the absorption and dissociation of areal oxygen preferentially take place at the Cu site and dissociation of aniline takes place at the Co site. Thus, the Cu and Co sites of CuCo2O4 exert a cooperative effect on the direct oxidative azo coupling reactions through the selective activation of anilines and aerobic oxygen. The CuCo2O4 material was recovered from the reaction mixture and reused for at least eight runs without appreciable loss of catalytic activity.

Correlation of Duplex Ultrasonographic Parameters with Glomerular Filtration Rate in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease encompasses a spectrum of different pathophysiological processes associated with abnormal renal function and a progressive decline in glomerular filtration rate. Duplex ultrasonography is widely available and important imaging investigation required in the work?up of chronic kidney disease. The objective of the study was to assess correlation of renal duplex ultrasonographic parameters with decreased glomerular filtration rate in patients with chronic kidney disease. METHODS: This was a crosssectional hospital-based study. A total of sixty-two patients with chronic kidney disease referred for ultrasonography were included in the study. Patients were evaluated by duplex ultrasonography. Correlation of renal length, parenchymal thickness, cortical thickness, cortical echogenicity, peak systolic velocity, end diastolic velocity pulsatility index and resistive index with glomerular filtration rate was evaluated by using Pearson's correlation coefficient. RESULTS: Chronic kidney disease was seen more prevalent in 41-50 years of age group. The major risk factors associated with Chronic kidney disease was Hypertension and Diabetes Mellitus. A significant positive correlation of renal length, parenchymal thickness, cortical thickness (p value < 0.01) and end diastolic velocity (p value < 0.05) with eGFR and significant negative correlation of cortical echogenicity, resistive index and pulsatility index (p value < 0.01) with eGFR was derived. CONCLUSIONS: Duplex sonographic findings of renal length, parenchymal thickness, cortical thickness, cortical echogenicity, end diastolic velocity, pulsatility index and resistive index are found to be useful parameters in evaluation of chronic kidney disease.

Clinical Patterns and Computed Tomography Findings in Patients with Cranio-Cerebral Trauma in Tertiary Hospital in Eastern Nepal.

BACKGROUND: Head injury is a common problem encountered in emergency department. Among various neurological diseases, cranio-cerebral trauma ranks high in order of frequency and gravity. In acute setting, computed tomography is modality of choice because of its high accuracy in detecting intracranial lesions. The study was done to analyze computed tomography findings in cerebral trauma in regards to sociodemographic characteristics and find out associations of Computed tomography findings with mechanism of injury and clinical manifestations. METHODS: The study was carried in Department of Radiology, BPKIHS, over a period of one year from Aug. 2015 to Aug. 2016. 450 patients were included in our study and findings noted on structured pro forma. Analysis was done using SPSS version 20 applying simple descriptive statistical methods. RESULTS: Among 450 patients, 220 patients (48.9%) had various cranio-cerebral injuries. Most were in age group of 20-29 years (49.5%) and most common mode was road traffic accident (44.6%).Most patients presented with altered sensorium (39.2%) and Glasgow Coma Scale score of ?13 (70.9%). Scalp lesion was the most common finding (24%) followed by bone fractures (19.8 %). Patients with road traffic accident (59.7%) and fall from height (46.7%) had more positive computed tomography findings than from physical assault (28.2%). Glasgow Coma Scale showed significant statistical association with computed tomography findings (p<0.001). CONCLUSIONS: Road traffic accident is the most common mode of head injury in young adults patients presenting in our hospital. Glasgow Coma Scale can be considered as an important clinical marker for predicting positive computed tomography findings. Also computed tomography is an important initial investigation to evaluate the various craniocerebral injury in trauma patients.

Visible Light-Emitting Diode Light-Driven Cu0.9Fe0.1@RCAC-Catalyzed Highly Selective Aerobic Oxidation of Alcohols and Oxidative Azo-Coupling of Anilines: Tandem One Pot Oxidation-Condensation to Imidazoles and Imines.

Here, we have demonstrated visible light-emitting diode light-driven selective and efficient aerobic oxidation of primary/secondary alcohols to aldehydes/ketones and oxidative azo-coupling of anilines using biomass rice husk-derived chemically activated carbon sheet-supported copper-iron bimetallic hybrid nanomaterials (Cu x Fe1-x @RCAC) under oxidant and additive-free conditions. The catalytic activity of the Cu x Fe1-x @RCAC materials has been investigated for the oxidation of alcohols and anilines, and Cu0.9Fe0.1@RCAC was established as the best catalyst. Moreover, a tandem one-pot protocol has been developed for the sequential oxidation of alcohols followed by condensation to functionalized imidazole and imine derivatives in high isolated yields. The hybrid materials were highly robust and stable under the reaction conditions and were recovered simply by filtration and recycled up to 12th run without considerable loss in catalytic activity.

Prevalence of Dangerous Ethmoid in a Tertiary Center in Eastern Nepal.

INTRODUCTION: Endoscopic sinus surgery is a well-known approach for sino-nasal pathologies. Due to close proximity to the brain and orbit, the surgeon should be aware of the sino-nasal anatomy and its associated variations. Detailed preoperative assessment of the sinus computed tomography scans reduces the frequency of severe complications in patients undergoing an endoscopic sinus surgery. So, the aim of this study is to find the prevalence of dangerous ethmoid in a tertiary center in eastern Nepal. METHODS: A descriptive cross-sectional study was performed in a Computed tomography scan of 50 patients with chronic sinusitis undergoing endoscopic sinus surgery from February 2018 to August 2018 in the department of Otolaryngology and Radiology of BP Koirala institute of health sciences after taking ethical approval from Institutional Review Committee of the institute. Measurements are taken in the coronal plane. The depth of the lateral lamella of the cribriform plate was defined according to the Keros classification which defines the dangerous ethmoid. and side. Data entered in MS excel. Statistical analysis was performed in SPSS version 11.5. RESULTS: Keros type I, II, and III were noted in 17 (17%), 54 (54%) and 29 (29%) of cases respectively. The mean width of the olfactory fossa, medial orbital wall distance and distance from medial nasal concha were 3.57mm, 8.77mm & 17.78mm respectively. CONCLUSIONS: The most common type of dangerous ethmoid was keros type II. CONCLUSIONS: The most common type of dangerous ethmoid was keros type II.

Effective use of simple computer programmes and clay models to demonstrate the planning and operative steps for teaching and presentations.

BACKGROUND: Presenting and demonstrating a surgical procedure in the current era is difficult without good intraoperative pictures and videos. A long, complex, multi-staged surgery is better illustrated by detailed intraoperative images at various stages. Although desirable, it may be difficult due to various reasons. MATERIAL AND METHODS: A simple method of preparing illustrations with pictures/diagrams created on PowerPoint and clay models to recreate the missing links in clinical photographs has been proposed. RESULTS: It is a simple technique with a moderate learning curve. Once familiar with technique, one can effectively use the technique to convey the details in much more clear manner. CONCLUSION: It is a simple and effective way of communicating through digital images, and gives the audience a 3 dimensional idea about the concept.

Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials.

Fostamatinib is a selective inhibitor of spleen tyrosine kinase which has a role in the pathogenesis of RA. Multiple RCTs have been performed to study the effects of fostamatinib. The objective of this study was to perform a meta-analysis to analyze the efficacy and safety of fostamatinib in the management of RA. We searched PubMed, EMBASE and Cochrane CENTRAL through 11/9/15. Random effect model was used to estimate odds ratio (OR) and 95 % confidence interval. We measured outcomes with efficacy analysis using ACR20/50/70 response criteria and safety with adverse events. Five studies were included in the meta-analysis with total of 2105 patients including 1419 in fostamatinib group and 686 in placebo. Fostamatinib was effective in achieving ACR20, ACR50 and ACR70 responses compared to placebo (48 vs. 32.8 %, OR 1.86, 95 % CI 1.32-2.62, P = 0.0004, I (2) 63 %; 26.4 vs. 12.5 %, OR 2.50, 95 % CI 1.93-3.23, P < 0.00001, I (2) 0 % and 12.7 vs. 4.4 %, OR 3.00, 95 % CI 1.99-4.51, P < 0.00001, I (2) 0 %, respectively). Response to fostamatinib was rapid and significant effect on ACR20 response was seen by week 1 (OR 3.70, 95 % CI 2.33-5.87, P < 0.00001, I (2) 42 %). Safety analysis showed an increased risk of infection (OR 1.59, 95 % CI 1.2-2.11; P = 0.001; I (2) 0 %), diarrhea (OR 3.54; 95 % CI 2.43-5.16; P < 0.00001; I (2) 2 %), hypertension (OR 2.55, 95 % CI 1.54-4.22, P = 0.0003; I (2) 42 %) and neutropenia (OR 5.68, 95 % CI 1.97-16.42, P = 0.001, I (2) 35 %) and showed a trend toward the increase in ALT ≥3 times ULN (OR 1.76, 95 % CI 0.99-3.13; P = 0.05; I (2) 0 %). This meta-analysis concludes that fostamatinib has moderate effect in the treatment of RA with mostly mild-to-moderate adverse events and dose-dependent, transient neutropenia and hypertransaminasemia.

Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge.

Avian influenza A H7N7/NL/219/03 virus creates a serious pandemic threat to human health because it can transmit directly from domestic poultry to humans and from human to human. Our previous vaccine study reported that mice when immunized intranasally (i.n) with live Bac-HA were protected from lethal H7N7/NL/219/03 challenge, whereas incomplete protection was obtained when administered subcutaneously (s.c) due to the fact that H7N7 is a poor inducer of neutralizing antibodies. Interestingly, our recent vaccine studies reported that mice when vaccinated subcutaneously with Bac-HA (H7N9) was protected against both H7N9 (A/Sh2/2013) and H7N7 virus challenge. HA1 region of both H7N7 and H7N9 viruses are differ at 15 amino acid positions. Among those, we selected three amino acid positions (T143, T198 and I211) in HA1 region of H7N7. These amino acids are located within or near the receptor binding site. Following the selection, we substituted the amino acid at these three positions with amino acids found on H7N9HA wild-type. In this study, we evaluate the impact of amino acid substitutions in the H7N7 HA-protein on the immunogenicity. We generated six mutant constructs from wild-type influenza H7N7HA cDNA by site directed mutagenesis, and individually expressed mutant HA protein on the surface of baculovirus (Bac-HAm) and compared their protective efficacy of the vaccines with Bac-H7N7HA wild-type (Bac-HA) by lethal H7N7 viral challenge in a mouse model. We found that mice immunized subcutaneously with Bac-HAm constructs T143A or T198A-I211V or I211V-T143A serum showed significantly higher hemagglutination inhibition and neutralization titer against H7N7 and H7N9 viruses when compared to Bac-HA vaccinated mice groups. We also observed low level of lung viral titer, negligible weight loss and complete protection against lethal H7N7 viral challenge. Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA vaccine against H7N7/NL/219/03 virus.

Concentration and purification of enterovirus 71 using a weak anion-exchange monolithic column.

BACKGROUND: Enterovirus 71 (EV-71) is a neurotropic virus causing Hand, Foot and Mouth Disease (HFMD) in infants and children under the age of five. It is a major concern for public health issues across Asia-Pacific region. The most effective way to control the disease caused by EV-71 is by vaccination thus a novel vaccine is urgently needed. Inactivated EV-71 induces a strong, virus-neutralizing antibody response in animal models, protecting them against a lethal EV-71 challenge and it has been shown to elicit cross-neutralizing antibodies in human trials. Hence, the large-scale production of purified EV-71 is required for vaccine development, diagnosis and clinical trials. METHODS: CIM® Monolith columns are single-piece columns made up of poly(glycidyl methacrylate co-ethylene dimethacrylate) as support matrix. They are designed as porous channels rather than beads with different chemistries for different requirements. As monolithic columns have a high binding capacity, flow rate and resolution, a CIM® DEAE-8f tube monolithic column was selected for purification in this study. The EV-71 infected Rhabdomyosarcoma (RD) cell supernatant was concentrated using 8% PEG 8000 in the presence of 400 mM sodium chloride. The concentrated virus was purified by weak anion exchange column using 50 mM HEPES + 1 M sodium chloride as elution buffer. RESULTS: Highly pure viral particles were obtained at a concentration of 350 mM sodium chloride as confirmed by SDS-PAGE and electron microscopy. Presence of viral proteins VP1, VP2 and VP3 was validated by western blotting. The overall process achieved a recovery of 55%. CONCLUSIONS: EV-71 viral particles of up to 95% purity can be recovered by a single step ion-exchange chromatography using CIM-DEAE monolithic columns and 1 M sodium chloride as elution buffer. Moreover, this method is scalable to purify several litres of virus-containing supernatant, using industrial monolithic columns with a capacity of up to 8 L such as CIM® cGMP tube monolithic columns.

Unfavourable results in free tissue transfer.

With recent advances in the instrumentation and with increased expertise the results of microvascular surgery are getting better. Complications though, cannot be completely avoided. This paper gives a brief introduction to the possible complications at various stages of free tissue transfer. With careful planning and execution and vigilant postoperative care the overall success rate can be improved.

Pilot study of granulocyte-colony stimulating factor for treatment of Alzheimer's disease.

Human granulocyte colony-stimulating-factor (G-CSF) is widely used for treatment of neutropenia and to mobilize stem/progenitor cells for bone marrow transplantation. In studies of thousands of healthy donor subjects treated with G-CSF to mobilize stem/progenitor cells, the side-effect profile has been reported to be mild and reversible. In pre-clinical studies, G-CSF was reported to improve spatial learning performance and to markedly reduce amyloid deposition in hippocampus and entorhinal cortex in a murine model of Alzheimer's disease (AD). The present study investigated the effects of a five day schedule of G-CSF administration on tolerability, safety, and cognition in eight patients with mild to moderate stage AD. A double-blind placebo control, cross-over design was implemented. Treatment with G-CSF did not result in serious adverse events. The most common and expected side effects were transient increases in white blood cell count, myalgias and diffuse aching that improved with non-steroidal anti-inflammatory medications. Of a battery of cognitive tests administered using the CANTAB computerized system, only the mean paired associate learning (PAL total trials adjusted) was significantly improved at the final visit of the study compared to baseline values (p < 0.05). There were no significant differences in amyloid-ß1-42 levels in cerebrospinal fluid measured two weeks after G-CSF and two weeks after placebo treatments. In conclusion, administration of G-CSF in a dosage regimen commonly used for bone marrow donors was well tolerated and safe, and provided a signal of positive change in a hippocampal-dependent task of cognitive performance.

High Blood caffeine levels in MCI linked to lack of progression to dementia.

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer's disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65-88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2-4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (-51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2-4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI.

An effective technique of helical cartilage scoring for correction of prominent ear deformity.

Otoplasty has a long history starting from 1948, when Dieffenbach described it first. Multiple technical modifications have been reported since. We propose a technique of scoring the helical cartilage without a visible incision on the lateral aspect of pinna for easier remolding of cartilage through posterior approach. The results have been excellent.

Traction splints: effective nonsurgical way of managing proximal phalanx fractures.

BACKGROUND: Treating proximal phalanx fracture without compromising the mobility is difficult. METHODS: Clinical and radiologic results of 30 patients with proximal phalangeal fracture of the hand treated conservatively from January 2004 to December 2006 were evaluated. Application of traction splint was followed by supervised rehabilitation. Patients were followed for 6 months. Results were evaluated using "Total Active Motion Scores" and grip strength. RESULTS: The results were excellent in 72% of the patients, good in 22%, and poor in 6%. For long-term assessment patients were contacted and reviewed in October 2007. Eighty percent patient responded to call and the results achieved were found to be stable in most of the patients. CONCLUSIONS: Proximal phalangeal fractures can be effectively treated by closed methods, using the stabilizing effect of soft tissues (zancolli complex-metacarpophalangeal retention apparatus) and external devices (traction splints), thus enabling bone healing and movement recovery at the same time.

Extensor digitorum brevis muscle flap: modified approach preserving extensor retinaculum.

BACKGROUND: Although numerous reconstructive options for covering defects over distal third of leg and dorsum of foot have been suggested, obtaining satisfactory cover remains difficult problem. Extensor digitorum brevis muscle flap as proximally or distally based island flap has been well described to be a promising alternative. METHODS: Between 2004 and 2005, 10 defects over dorsum of foot and around malleoli were reconstructed with extensor digitorum brevis muscle flap. Six were proximally based and four were distally based flaps. Retrospectively, data were collected from these patients records like age, gender, type of injury, flap used, flap survival, complications, hospital stay, return to work. RESULTS: Mean follow-up period was 17.5 months (26-12 months). Of 10 flaps, one flap had failed (approximately 10%). Minor donor site problem presented in one case (10%). All patients returned to work after variable periods of rest (average 1(1/2) month). First web hypoesthesia was present only in two patients. CONCLUSIONS: This flap provides an excellent local option for small defects around ankle and over dorsum of foot. The advantages of this flap are its easy dissection, reliable blood supply. Disadvantages related to donor site can be minimized with careful technique.