Percutaneous nephrolithotomy of a staghorn stone in thoracic ectopic kidney

Congenital thoracic ectopic kidney is a very rare developmental anomaly and the rarest form of all ectopic kidneys. It is usually asymptomatic and discovered incidentally on routine chest radiography. Herein we reported the first case of staghorn stone in a thoracic kidney managed successfully by percutaneous nephrolithotomy.     

Angiosarcomas--clinical profile,pathology and management

Files of 8 patients with primary angiosarcomas treated in the Department of Radiation Oncology at the University of the Witwatersrand from 1982 to 1995 were identified. None of these patients had received prior radiotherapy or chemotherapy which would have predisposed them to the formation of an angiosarcoma. Slides of 6 patients were reviewed. Five of the 6 were confirmed as having angiosarcomas, while 1 patient was found to have a peripheral neuro-epithelial tumour. Four patients had angiosarcomas of the breast, while there was 1 patient each with angiosarcoma of the skin, intestine and brain. Complete excision was the primary modality of management whenever possible. Postoperative radiotherapy was given in cases of incomplete excision, patient refusal of radical surgery or gross tumour. Four patients died within 4 months of diagnosis. Three patients are alive (2 with no evidence of disease) 22-96 months after diagnosis. In 1 patient follow-up details were not available as he did not return for treatment. Angiosarcomas are aggressive malignant tumours arising from the endothelial cells. Complete surgical excision is the treatment of choice in the management of this aggressive disease, which has a poor prognosis.     

Adenoid Cystic Carcinoma of the Salivary Glands: A Review of 10 Years

A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.     

Canakinumab: Promises and Future in Cardiometabolic Diseases and Malignancy

Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1β inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.     

Schweinfurthins A–Q: isolation,synthesis, and biochemical properties

Stilbene analogues have shown remarkable structural diversity constituting simple or tangled structures, which have attracted the synthetic as well as the medicinal chemistry communities. Schweinfurthins are a family of prenylated/geranylated/farnesylated stilbenes that are isolated from an African plant belonging to the Macaranga species. These compounds have displayed potency towards central nervous system, renal and breast cancer cell lines. Specifically, these compounds have been found to be potent and selective inhibitors of cell growth in the National Cancer Institute''s 60 cell-line screen. In this review article, we described the isolation, synthesis, and biochemical properties of schweinfurthins.

An overview of the isolation, synthesis, and biochemical properties of the stilbene-based natural products schweinfurthins A–Q (1999–2017).     

Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project

The objectives of this study were to examine relationships between baseline levels of reproductive hormones in older men and (1) change in bone mineral density (BMD) over 5 years and (2) incident fractures over an average of 6 years' follow‐up. A total of 1705 men aged 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2 years follow‐up (2007–2009), and 5 years follow‐up (2010–2013). At baseline, testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) by immunoassay. Hip BMD was measured by dual X‐ray absorptiometry (DXA) at all three time‐points. Fracture data were collected at 4‐monthly phone calls and verified radiographically. Statistical modeling was by general estimating equations and Cox model regression. Univariate analyses revealed inverse associations for serum SHBG, FSH, and LH and positive association for E1 but not DHT or E2 with BMD loss at the hip across the three time points. Serum levels of SHBG (β = –0.071), FSH (β = –0.085), LH (β = –0.070), and E1 (β = 0.107) remained significantly associated with BMD loss in multivariate‐adjusted models; however, we were unable to identify any thresholds for accelerated BMD loss according to reproductive steroids. Incident fractures (all, n = 171; hip, n = 44; and nonvertebral, n = 139) were all significantly associated with serum SHBG, FSH, and LH levels in univariate models but none remained significantly associated in multivariate‐adjusted model. Serum T, DHT, E2, and E1 levels were not associated with incident fractures in univariate or multivariate‐adjusted analyses. In older men, lower serum SHBG, FSH, and LH and higher E1 levels protected against loss of BMD without increasing fracture rate. This means these reproductive variables may be considered as novel biomarkers of bone health during male aging. © 2015 American Society for Bone and Mineral Research.     

Successful Delivery of RRT in Ebola Virus Disease

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.     

Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans

The emergence of pandemic influenza viruses poses a major public health threat. Therefore, there is a need for a vaccine that can induce broadly cross-reactive antibodies that protect against seasonal as well as pandemic influenza strains. Human broadly neutralizing antibodies directed against highly conserved epitopes in the stem region of influenza virus HA have been recently characterized. However, it remains unknown what the baseline levels are of antibodies and memory B cells that are directed against these conserved epitopes. More importantly, it is also not known to what extent anti-HA stem B-cell responses get boosted in humans after seasonal influenza vaccination. In this study, we have addressed these two outstanding questions. Our data show that: (i) antibodies and memory B cells directed against the conserved HA stem region are prevalent in humans, but their levels are much lower than B-cell responses directed to variable epitopes in the HA head; (ii) current seasonal influenza vaccines are efficient in inducing B-cell responses to the variable HA head region but they fail to boost responses to the conserved HA stem region; and (iii) in striking contrast, immunization of humans with the avian influenza virus H5N1 induced broadly cross-reactive HA stem-specific antibodies. Taken together, our findings provide a potential vaccination strategy where heterologous influenza immunization could be used for increasing the levels of broadly neutralizing antibodies and for priming the human population to respond quickly to emerging pandemic influenza threats.The emergence of novel influenza virus strains poses a continuous public health threat (1, 2). The World Health Organization estimates that influenza viruses infect one-billion people annually, with three- to five-million cases of severe illness, and up to 500,000 deaths worldwide (3). Following influenza virus infection, humoral immune responses against the viral hemagglutinin (HA) protein may persist for decades in humans (4). These anti-HA responses correlate strongly with protection against influenza infection (5). Serological memory is maintained by antibody-secreting long-lived plasma cells and reinforced by memory B cells, which can rapidly differentiate into antibody-secreting cells upon antigen reexposure (6).Influenza vaccine efficacy is constantly undermined by antigenic variation in the circulating viral strains, particularly in the HA and neuraminidase (NA) proteins. Current influenza vaccination strategies rely on changing the HA and NA components of the annual human vaccine to ensure that they antigenically match circulating influenza strains (7, 8). Developing an influenza vaccine that is capable of providing broad and long-lasting protective antibody responses remains the central challenge for influenza virus research.HA is a trimer, with each monomer comprised of two subunits: HA1, which includes the HA globular head, and HA2, whose ectodomain together with the N- and C-terminal parts of HA1 constitute the HA stem region (9). Phylogenetically, the 18 HA subtypes characterized so far are divided into two groups. Among strains that have recently caused disease in humans, H1 and H5 HAs belong to group 1, whereas H3 and H7 HAs belong to group 2 (10). Conventional anti-HA neutralizing antibodies primarily target a few immunodominant epitopes located in proximity to the receptor-binding domain within the globular head region of the molecule (11, 12). Although these antibodies are potentially protective, they are strain-specific because of the high variability of such epitopes, and thus lack, in general, the much-desired broad neutralizing activity. Recently, broadly neutralizing human (13–18) and murine (19) monoclonal antibodies (mAbs) directed against distinct epitopes within the HA stem region have been extensively characterized. These mAbs were shown to interfere with the influenza viruses’ life cycle in different ways (20). By generating monoclonal antibodies from plasmablasts isolated ex vivo, we demonstrated that these broadly neutralizing antibodies could be retrieved from patients infected with or vaccinated against the pandemic H1N1 2009 influenza virus (18, 21). Recent observations that HA stem epitopes are accessible on the majority of HA trimers on intact virions (22), and that a stable HA stem protein that is immunologically intact could be produced (23), provided further hope for the feasibility of a stem-based universal influenza vaccine (24).Notably, HA stem-specific mAbs isolated from humans showed a high degree of affinity maturation, suggesting a memory B-cell origin. These results raised two important questions that we address in the current study. First, what are the baseline levels of broadly cross-reactive stem-binding antibodies and memory B cells? Second, using current influenza vaccines, to what extent can HA stem-specific responses be boosted in comparison with those directed against the HA globular head?Structural studies have clearly demonstrated that the main neutralizing antibody epitopes within the HA stem region are conformation-dependent, and that the integrity of these epitopes requires the presence of the HA1 subunit in addition to the HA2 subunit, which constitute the bulk of the HA stem (16, 17). To be able to directly measure HA stem-reactive antibodies and memory B cells, we used a chimeric HA molecule that expresses the globular head of H9 HA on H1 backbone (25). Our data demonstrate that post-2009 trivalent inactivated vaccines (TIV) induced minimal stem-specific responses in comparison with head-specific responses. On the other hand, immunization with H5N1 generated relatively strong anti-HA stem responses, demonstrating that it is feasible to elicit broadly neutralizing responses in humans given the right immunogen design.