Association of biomarkers for human papillomavirus with survival among adults with Barrett high-grade dysplasia and esophageal adenocarcinoma

Importance: The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. Objective: To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. Design, Setting, and Participants: This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017. Main Outcomes and Measures: Disease-free survival and overall survival. Results: Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04). Conclusions and Relevance: This study's findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status

A pilot randomized controlled trial of WeiNaoKang (SaiLuoTong) in treating vascular dementia

Abstract Objective WeiNaoKang (or SaiLuoTong) is an herbal formula consisting of ginkgo, ginseng, and saffron. Our objective was to investigate if WeiNaoKang could improve cognitive function and cerebral perfusion in patients suffering from vascular dementia. Methods A 16‐week randomized double‐blind, placebo‐controlled trial was carried out in the setting of a memory disorder clinic at a single center. Patients with vascular dementia diagnosed clinically but supported by imaging and other investigations were invited to participate. The diagnoses were based on the National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS‐AIREN) criteria. An independent blinded assessor evaluated the effects of the formula. Intervention group was compared to the control group. A subgroup of participants was randomly chosen for further evaluation of cerebral perfusion by single photon emission computed tomography scans post‐treatment. Results Both groups were comparable in age (mean = 74 ± 7.2 years in the placebo group and 75 ± 7.4 in the intervention group) and in other demographics. Sixty‐two participants were included in final analysis. Alzheimer's Disease Assessment Scale – Cognitive Portion (ADAS‐cog) was the primary outcome. By week 16, the mean ADAS‐cog reduced from 24.48 to 20.30 (mean reduction = 4.18) for those in the treatment group, and from 18.98 to 17.81 (mean reduction = 1.18) for those in the placebo group. The difference in mean reduction of ADAS‐cog was −3.00 (95% confidence interval [CI] = −4.910 to −1.100) in favor of the treatment group. Secondary outcomes of activities of daily living and quality of life measures also showed significant difference. In the perfusion scan analysis, the difference in the change in cerebral blood flow (t‐scores) pre‐ and post‐treatment between the intervention group (n = 7) and the placebo group (n = 11) was statistically significant (P < 0.001). Conclusion In this randomized, double‐blind placebo‐controlled trial, we demonstrated significant differences in improvement in cognitive function and activities of daily living. The clinical improvement is corroborated with improvement in cerebral perfusion in a subset of participants

Role of endoscopic ultrasound in pancreatic cancer

Pancreatic cancer (PC) is the fourth most common cause of cancer deaths in Western societies. It is an aggressive tumor with an overall 5-year survival rate of less than 5%. Surgical resection offers the only possibility of cure and long-term survival for patients suffering from PC; however, unfortunately, fewer than 20% of patients suffering from PC have disease that is amendable to surgical resection. Therefore, it is important to accurately diagnose and stage these patients to enable optimal treatment of their disease. The imaging modalities involved in the diagnosis and staging of PC include multidetector CT scanning, endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreaticography and MRI. The roles and relative importance of these imaging modalities have changed over the last few decades and continue to change owing to the rapid technological advances in medical imaging, but these investigations continue to be complementary. EUS was first introduced in the mid-1980s in Japan and Germany and has quickly gained acceptance. Its widespread use in the last decade has revolutionized the management of pancreatic disease as it simultaneously provides primary diagnostic and staging information, as well as enabling tissue biopsy. This article discusses the potential benefits and drawbacks of EUS in the primary diagnosis, staging and assessment of resectability, and EUS-guided fine-needle aspiration in PC. Difficult diagnostic scenarios and pitfalls are also discussed. A suggested management algorithm for patients with suspected PC is also presented

Is bigger better? : a retrospective analysis of native renal biopsies with 16 Gauge versus 18 Gauge automatic needles

Aim Percutaneous renal biopsy (PRB) remains the gold standard for the diagnosis of renal disease; however, the tissue yield which relates to the optimal needle size used for native-kidney biopsies has not been clearly established. Our study compares the sample adequacy and complication rates using 16 gauge (G) and 18 gauge (G) automatic needles on native kidney PRB. Methods A retrospective analysis was performed of native-kidney biopsies at two centres, one exclusively using 16G and the other exclusively using 18G needles. All samples were assessed by a single centralized pathology service. We compared patient characteristics, indications, diagnoses, adequacy of tissue samples, and complications. Results A total of 934 native-kidney biopsies were performed with real time ultrasound guidance: 753 with Bard Max Core 16G x 16 cm needles, and 181 with Bard Magnum 18G x 20 cm needles. The median (range) of total glomeruli count per biopsy was higher in the 16G group compared with the 18G group (19 (0-66) vs 12 (0-35), P < 0.001), despite having fewer cores per biopsy (2 (0-4) vs 3 (1-4), P < 0.001). The 16G group provided a greater proportion of adequate biopsy samples (94.7% vs 89.4%, P = 0.001). There was no significant difference in the frequency of total complications between the 16G and 18G groups (3.7% vs 2.2%, P = 0.49). Conclusion This retrospective study demonstrates 16G needles provide more glomeruli, more diagnostically adequate renal tissue, with fewer cores without a significant increase in complications compared with 18G needles. Based on these observations, 16G needles should be considered as the first line option in native-kidney PRB

Association of Biomarkers for Human Papillomavirus With Survival Among Adults With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma

Importance: The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. Objective: To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. Design, Setting, and Participants: This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017. Main Outcomes and Measures: Disease-free survival and overall survival. Results: Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04). Conclusions and Relevance: This study\u27s findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status

Contribution of climate change to degradation and loss of critical fish habitats in Australian marine and freshwater environments

Australia's aquatic ecosystems are unique, supporting a high diversity of species and high levels of endemism; however, they are also extremely vulnerable to climate change. The present review assesses climate-induced changes to structural habitats that have occurred in different aquatic ecosystems. Climatic impacts are often difficult to discern against the background of habitat degradation caused by more direct anthropogenic impacts. However, climate impacts will become more pronounced with ongoing changes in temperature, water chemistry, sea level, rainfall patterns and ocean currents. Each of these factors is likely to have specific effects on ecosystems, communities or species, and their relative importance varies across different marine and freshwater habitats. In the Murray–Darling Basin, the greatest concern relates to declines in surface water availability and riverine flow, owing to declining rainfall and increased evaporative loss. On the Great Barrier Reef, increasing temperatures and ocean acidification contribute to sustained and ongoing loss of habitat-forming corals. Despite the marked differences in major drivers and consequences of climate change, the solution is always the same. Greenhouse-gas emissions need to be reduced as a matter of urgency, while also minimising non-climatic disturbances. Together, these actions will maximise opportunities for adaptation by species and increase ecosystem resilience