Interpretation of Kidney Biopsy in Indian Patients Older than 60 Years: A Tertiary Care Experience.

The adult population above the age of 60 years has significantly increased in India, with a life expectancy of 68.4 years in 2016. Data regarding the renal histopathology in these patients are scarce though the number of native kidney biopsies done in this subset of population is increasing. The present study is a retrospective analysis of 231 biopsies from a total of 700 biopsies, from patients above 60 years of age (M = 65.8%; F = 34.2%) with a mean age of 64 ± 6.03 years. The indications for kidney biopsy included nephrotic syndrome (NS) (30.4%), nephritic syndrome (19.1%), rapidly progressive renal failure (11.7%), acute kidney injury (AKI) (15.7%), and acute worsening of preexisting chronic kidney disease (CKD) (23%). The median percentage of glomerulosclerosis was 22% (5%-45%), and interstitial fibrosis and tubular atrophy was 30% (10%-50%). The most common cause for nephrotic syndrome was membranous nephropathy (31.4%) and for nephritic syndrome was benign arterionephrosclerosis (22.7%). Postinfectious glomerulonephritis (29.6%) was the leading cause for rapidly progressive renal failure. Acute injury on CKD was notable in patients with diabetic nephropathy (30.2%). The predominant causes for AKI were acute tubulointerstitial nephritis (33.3%), acute tubular necrosis (22.2%), and acute pyelonephritis (19.4%). The biopsy proven histopathological features enabled us in tailoring the therapy. None of the patients developed life-threatening complications following ultrasonography-guided biopsy.

Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution.

INTRODUCTION: Noxafil® (posaconazole; POS) is a potent, selective triazole antifungal approved for use in adults as an oral suspension, oral tablet and intravenous (IV) Solution. In support of pediatric administration of POS IV Solution to childrentwo years of age, two studies were undertaken using magnetic resonance imaging (MRI) to monitor brain ventricle size longitudinally during three months administration of POS IV in adult and juvenile dogs. Necropsy was performed on all animals at the end of the studies. From the baseline MRI images, great variability in ventricle size was noted in both the adult and juvenile dogs; these images were used to distribute differently sized ventricles between treatment and vehicle groups as to not skew group means during the course of the study. RESULTS: POS IV Solution had no effect on ventricle volume at any timepoint during dosing in either the adult or the juvenile dogs. Further, no gross or histomorphologic differences between groups were observed in either study. Compared to juvenile dogs, MRI analysis showed that adult dogs had larger ventricles, lower variability in all ventricle volumes, and a greater rate of increase in total ventricle volume. DISCUSSION: Information on growth and development of brains is one of the few areas in which more detailed information is available about humans than about the standard laboratory animals used to model disease and predict toxicities. The use of MRI helped elucidate large natural variabilities in the dog brain, which could have altered the interpretation of this de-risking study, and provided a valuable noninvasive means to monitor the brain ventricles longitudinally.

Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review.

INTRODUCTION: This systematic review addresses the use of epidermal growth factor receptor (egfr) inhibitors in three populations of advanced non-small-cell lung cancer (nsclc) patients-unselected, selected, and molecularly selected-in three treatment settings: first line, second line, and maintenance. METHODS: Ninety-six randomized controlled trials found using the medline and embase databases form the basis of this review. RESULTS: In the first-line setting, data about the efficacy of egfr tyrosine kinase inhibitors (tkis) compared with platinum-based chemotherapy are inconsistent. Results from studies that selected patients based on clinical characteristics are also mixed. There is high-quality evidence that an egfrtki is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene. The egfrtkis are associated with a higher likelihood of response, longer progression-free survival, and improved quality of life. Multiple trials of second-line therapy have compared an egfrtki with chemotherapy. Meta-analysis of those data demonstrates similar progression-free and overall survival. There is consequently no preferred sequence for second-line egfrtki or second-line chemotherapy. The egfrtkis have also been evaluated as switch-maintenance therapy. No molecular marker could identify patients in whom a survival benefit was not observed; however, the magnitude of the benefit was modest. CONCLUSIONS: Determination of EGFR mutation status is essential to making appropriate treatment decisions in patients with nsclc. Patients who are EGFR mutation-positive should be treated with an egfrtki as first-line therapy. An egfrtki is still appropriate therapy in patients who are EGFR wild-type, but the selected agent should be administered as second- or third-line therapy.

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population.

BACKGROUND: Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada. METHODS: Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993-1999, 2000-2005, and 2006-2011. RESULTS: Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993-1999 to 2006-2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993-1999 vs. 84% in 2006-2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome. INTERPRETATION: The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.

Design and validation of an error capture tool for quality evaluation in the vascular and endovascular surgical theatre.

BACKGROUND: The unique and complex vascular and endovascular theatre environment is associated with significant risks of patient harm and procedural inefficiency. Accurate evaluation is crucial to improve quality. This pilot study attempted to design a valid, reproducible tool for observers and teams to identify and categorise errors. METHODS: Relevant published literature and previously collected ethnographic field notes from over 250 h of arterial surgery were analysed. A comprehensive log of vascular procedural errors was compiled and twelve vascular experts graded each error for the potential to disrupt procedural flow and cause harm. Using this multimodal approach, the Imperial College Error CAPture (ICECAP) tool was developed. The tool was validated during 21 consecutive arterial cases (52 h operating-time) as an observer-led error capture record and as a prompt for surgical teams to determine the feasibility of error self-reporting. RESULTS: Six primary categories (communication, equipment, procedure independent pressures, technical, safety awareness and patient related) and 20 error sub-categories were determined as the most frequent and important vascular procedural errors. Using the ICECAP, the number of errors detected correlated well between two observers (Spearman rho = 0.984, p < 0.001). Both observers identified all moderate or severe errors similarly and categorised all but 4/139 (2.9%) of the total errors in an identical fashion. Self-reporting of errors without prompting identified a mean of 24.4% (range 0-50%) of all recorded errors, whereas surgical teams reported a mean of 69.7% (range 50-100%) of errors when ICECAP error-category prompts were used. CONCLUSION: The ICECAP tool may be useful for capturing and categorising errors that occur during vascular/endovascular procedures. ICECAP may also have a role as an error recall prompt for self-reporting purposes by vascular surgical teams.

Development of novel approach to diagnostic imaging of lung cancer with 18F-Nifene PET/CT using A/J mice treated with NNK.

Development of novel methods of early diagnosis of lung cancer is one of the major tasks of contemporary clinical and experimental oncology. In this study, we utilized the tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice as an animal model for development of a new imaging technique for early diagnosis of lung cancer. Lung cancer cells in A/J mice overexpress nicotinic acetylcholine receptors. Longitudinal CT scans were carried out over a period of 8 months after NNK treatment, followed by PET/CT scans with 18F-Nifene that binds to α4-made nicotinic receptors with high affinity. PET/CT scans of lungs were also obtained ex vivo. CT revealed the presence of lung nodules in 8-month NNK-treated mice, while control mice had no tumors. Imaging of live animals prior to necropsy allowed correlation of results of tumor load via PET/CT and histopathological findings. Significant amount of 18F-Nifene was seen in the lungs of NNK-treated mice, whereas lungs of control mice showed only minor uptake of 18F-Nifene. Quantitative analysis of the extent and amount of 18F-Nifene binding in lung in vivo and ex vivo demonstrated a higher tumor/nontumor ratio due to selective labeling of tumor nodules expressing abundant α4 nicotinic receptor subunits. For comparison, we performed PET/CT studies with 18F-FDG, which is used for the imaging diagnosis of lung cancer. The tumor/nontumor ratios for 18F-FDG were lower than for 18F-Nifene. Thus, we have developed a novel diagnostic imaging approach to early diagnosis of lung cancer using 18F-Nifene PET/CT. This technique allows quantitative assessment of lung tumors in live mice, which is critical for establishing tumor size and location, and also has salient clinical implications.

Site specific bone adaptation response to mechanical loading.

Over 25 million Americans suffer from osteoporosis. Bone size and strength depends both upon the level of adaptation due to physical activity (applied load), and genetics. We hypothesized that bone adaptation to loads differs among mice breeds and bone sites. Forty-five adult female mice from three inbred strains (C57BL/6 [B6], C3H/HeJ [C3], and DBA/2J [D2]) were loaded at the right tibia and ulna in vivo with non-invasive loading devices. Each loading session consisted of 99 cycles at a force range that induced approximately 2000 microstrain (microepsilon) at the mid-shaft of the tibia (2.5 to 3.5 N force) and ulna (1.5 to 2 N force). The right and left ulnae and tibiae were collected and processed using protocols for histological undecalcified cortical bone slides. Standard histomorphometry techniques were used to quantify new bone formation. The histomorphometric variables include percentage mineralizing surface (%MS), mineral apposition rate (MAR), and bone formation rate (BFR). Net loading response [right-left limb] was compared between different breeds at tibial and ulnar sites using two-way ANOVA with repeated measures (p<0.05). Significant site differences in bone adaptation response were present within each breed (p<0.005). In all the three breeds, the tibiae showed greater percentage MS, MAR and BFR than the ulna at similar in vivo load or mechanical stimulus (strain). These data suggest that the bone formation due to loading is greater in the tibiae than the ulnae. Although, no significant breed-related differences were found in response to loading, the data show greater trends in tibial bone response in B6 mice as compared to D2 and C3 mice. Our data indicate that there are site-specific skeletal differences in bone adaptation response to similar mechanical stimulus.

Recurrent respiratory papillomatosis complicated by aspergillosis: a case report with review of literature.

Pulmonary extension of recurrent invasive papillomatosis often poses a diagnostic challenge to the examining bronchoscopist, pathologist, radiologist and surgeon, in distinguishing it as a benign lesion that is confined to the mucosa and extending along the branches of the tracheobronchial tree from true invasion of a malignant tumor. We document here a case of recurrent invasive respiratory papillomatosis which initially presented as a laryngeal papilloma. After multiple recurrences, the patient presented with bronchopulmonary involvement, complicated by invasive aspergillosis in a non-immunocompromised setting.

Idiopathic arterial calcification of infancy - a case report.

Idiopathic arterial calcification of infancy is a rare condition characterized by extensive calcification and stenosis of large and medium sized arteries. A ten day old female baby developed sudden shortness of breath and was treated with oxygen and antibiotics. Antenatal echocardiography showed calcification of the aorta and pulmonary arteries. Autopsy examination revealed extensive calcification in the walls of major arteries and vessels of several organs. The baby was found to have a karyotype of 47 chromosomes.

Right ventricular myocardium in Fallot's tetralogy: a light microscopic, morphometric and ultrastructural study.

AIMS: To analyze peroperative biopsies of RV myocardium in Tetralogy of Fallot by light microscopy, morphometry and electron microscopy in order to determine the degree of hypertrophy and degenerative changes and to correlate these changes with clinical and haemodynamic parameters. MATERIALS AND METHODS: Right ventricular myocardium obtained peroperatively during surgical correction of Tetralogy of Fallot along with age-matched control samples were processed for routine light and electron microscopy using standard processing techniques. Mean cell diameter was analyzed using manual morphometric methods and ultrastructural study was carried out using a Philips transmission electron microscope. RESULTS: The most consistent features of hypertrophy were the mitochondrial changes and increased nuclear convolutions. Majority of the patients had hypertrophy with mild to moderate degenerative changes. Severe degeneration was associated with irreversibility and was related to the severity and chronicity of the disease. There was a significant correlation of the morphological changes with clinical and haemodynamic parameters. CONCLUSIONS: Peroperative histomorphometric and ultrastructural evaluation of the RV myocardium in Tetralogy of Fallot reflects the effect of haemodynamic stresses on the right ventricular muscle and correlates with clinical cardiac dysfunction. It may be a useful adjunct in determining the time for surgical intervention and in predicting clinical outcome.

Chronic lower limb ulcer? No--chloroma!

Extra medullary deposits are often associated with myeloproliferative disorders, especially with myeloid neoplasia. These are called granulocytic sarcoma, aleukemic leukemia cutis, myeloblastoma, chloroleukemia, extra-medullary myeloid tumor, and chloroma. They commonly present in the bone, periosteum, soft tissue, lymph nodes, and the skin but can occur anywhere. The authors present their experience with a patient with no history of neoplasm presented with a nonhealing ulcer of the lower limb that was a chloroma associated with chronic myeloid leukemia.

Idiopathic pulmonary haemosiderosis.

Idiopathic pulmonary haemosiderosis (IPH) is a rare disorder characterized by recurrent bouts of haemoptysis, iron deficiency anaemia, and pulmonary infiltrates on chest radiograph. We present such a case and believe that it is the first report from the Middle East.

Recurrent haematuria in coexisting IgA nephropathy and interstitial nephritis.

We report here a case of recurrent hematuria in a young man who presented with deteriorating renal function due to interstitial nephritis, secondary to, probably enteric fever. Immunofluorescence studies showed IgA nephropathy and ultrastructural studies revealed thin basement membrane nephropathy.

Identifying disability: comparing house-to-house survey and rapid rural appraisal.

This study compared house-to-house survey and rapid rural appraisal as methods used to identify people with disabilities in a sample rural population in South India. The research showed that by using these methods, two distinctly different populations were identified. The factors that influenced the identification processes were: local perceptions and definitions of disability; social dynamics, particularly those of gender and age; relationships within the rapid rural appraisal groups and between the health auxiliary and the respondents in the house-to-house survey; and the type of disability and the associated social implications and stigma of that disability. While a few more people were identified through the house-to-house survey, the rapid rural appraisal was a better approach for identifying disability in the community because of the greater community participation. The researchers believe that this community participation provided a greater understanding of the complex contextual dynamics influencing the identification of disability, thereby increasing the validity of the study findings. Another advantage of the rapid rural appraisal was the methodological and analytical simplicity. Both methods, however, failed to identify some individuals with disabilities who were later identified on the follow-up verification visits. Taking into account the factors discussed above, the researchers conclude that no single method could be used to comprehensively identify people with disability in a community. They suggest that a judicious combination of methods which takes into account local perceptions and priorities, includes more specific screening techniques, and facilitates informed voluntary referrals, would be the most effective approach.

Primary intracardiac yolk sac tumor.

A 2-year-old male child presented with fever, complete heart block, and congestive cardiac failure. Echocardiography showed a dumbbell-shaped mass in the right ventricle and right atrium. He was operated on with a provisional diagnosis of rhabdomyoma. Histopathology and immunohistochemistry of the resected tumor revealed a malignant germ cell tumor with predominant yolk sac differentiation.