The impact of age on prognosis in patients with gastric cancer: experience in a tertiary care centre

BackgroundGastric cancer (GC) is a leading cause of cancer-related death in the world and most patients have advanced disease upon presentation. The effect of age on prognosis in GC is controversial. We aimed to determine the impact of age on survival in patients with GC.MethodsThis was a retrospective study of the medical records of Lebanese patients diagnosed with GC at the American University of Beirut Medical Center (AUBMC) between 2005 and 2014. Patients were divided into young (<65 years) and older groups (≥65 years). A multivariate analysis was done to determine the independent predictors of survival. Kaplan-Meier method was used for analysis of long-term survival outcomes.ResultsThe sample consisted of 156 patients. The mean age was 62.15 (SD 13.54). Most patients presented with stage 4 disease (62.2%) and poorly differentiated histology (66.4%). The most common symptoms were abdominal pain and weight loss. On bivariate analysis, advanced stage (P=0.02) and higher grade (P=0.04) were associated with increased mortality. Patients <65 years of age were significantly more likely to have poorly differentiated tumours, while patients ≥65 years had more comorbidities (P=0.001). The 5-year DFS were 35% and 37% for patients <65 years of age and ≥65 years of age, respectively (P=0.15).ConclusionsHigher grade and advanced stage are associated with worse survival in patients with GC, but age did not seem to have an impact. Screening high risk patients and early diagnosis are necessary to improve survival.     

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study

BACKGROUND AND PURPOSE:Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up.MATERIALS AND METHODS:We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis.RESULTS:At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR  = 12.1; 95% CI, 3.5–42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3–2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3–2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7–6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm³ [IQR, 0.97–1.16 cm³] versus 0.86 cm³ [IQR, 0.73–1.00 cm³]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13–31%] versus 2% [IQR, 0–14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8–24%] versus 0% [IQR, 0–5%]; P < .001).CONCLUSIONS:Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Atherosclerosis in the carotid arteries is one of the leading causes of ischemic stroke with arterio-arterial embolism as the main mechanism.^1,2 The degree of lumen stenosis and the symptomatic status of the patient are currently used for risk assessment and treatment decision-making.^3,4 Patients with severe (≥70%) and moderate (50%–69%) carotid artery stenosis benefit from carotid endarterectomy; however, the number needed to treat to prevent recurrent stroke is relatively high.⁵ Moreover, almost half of neurologic events occur in patients with a low degree of stenosis.^6,7 This finding has triggered investigations into other markers that may help to identify patients with a high risk of recurrent stroke. Much attention has been paid to markers of atherosclerosis, like plaque composition and plaque ulceration, with the aim of identifying vulnerable plaques.⁸ These vulnerable plaques have a high risk of rupture, which results in thrombus formation and embolization of plaque material and/or thrombus migrating into the intracranial circulation, thereby causing vascular occlusion and a subsequent ischemic stroke.²Plaque composition is predictive of future cerebrovascular events.^9-12 Atherosclerotic plaque ulceration, visible as plaque-surface disruption, which is a marker of previous plaque rupture, is also correlated with recurrent symptoms and associated with a higher risk of ischemic stroke.^13,14 However, the relation between vulnerable plaque components and plaque rupture is rarely investigated. Both plaque composition and ulceration can be assessed in vivo with different imaging modalities, but MR imaging is the best technique to assess plaque composition due to its superior soft-tissue contrast,¹⁵ whereas MDCTA exceeds MR imaging in the detection of plaque ulcerations due to its excellent spatial resolution with the possibility of multiplanar reconstruction.^16,17Most previous studies investigated the relation between plaque ulcerations and plaque features using a cross-sectional study design. Generally, it was found that intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), and thinning or ruptured fibrous cap were associated with the presence of ulcerations,^18-21 while the presence of calcifications was inversely related to ulcerations.¹⁹ A prospective study in asymptomatic patients with severe carotid artery stenosis revealed that LRNC volume was a predictor of new surface disruption.^22,23 The aim of the current study was to investigate, in symptomatic patients with mild-to-moderate (30%–69%) carotid artery stenosis, which plaque components at baseline are predictive of plaque rupture at follow-up.     

Ocular pressure waveform reflects ventricular bigeminy and aortic insufficiency

Ocular pulse amplitude (OPA) is defined as the difference between maximum and minimum intraocular pressure (IOP) during a cardiac cycle. Average values of OPA range from 1 to 4 mmHg. The purpose of this investigation is to determine the source of an irregular IOP waveform with elevated OPA in a 48-year-old male. Ocular pressure waveforms had an unusual shape consistent with early ventricular contraction. With a normal IOP, OPA was 9 mmHg, which is extraordinarily high. The subject was examined by a cardiologist and was determined to be in ventricular bigeminy. In addition, he had bounding carotid pulses and echocardiogram confirmed aortic insufficiency. After replacement of the aortic valve, the bigeminy resolved and the ocular pulse waveform became regular in appearance with an OPA of 1.6–2.0 mmHg. The ocular pressure waveform is a direct reflection of hemodynamics. Evaluating this waveform may provide an additional opportunity for screening subjects for cardiovascular anomalies and arrhythmias.     

Vitamin D,autoimmunity and recurrent pregnancy loss: More than an association

Recurrent pregnancy loss (RPL) affects close to 1% of couples; however, the etiology is known in only about 50% of the cases. Recent studies show that autoimmune dysregulation is a probable cause of RPL, which in some cases may be overlooked. In order for a pregnancy to proceed to term, early modulation of immunologic response is required to induce tolerance to the semi‐allogenic fetus. Certain subsets of both the innate and adaptive immune responses play a role in the induction of fetomaternal tolerance. A relatively predominant T‐cell helper (Th) 2 and T regulatory (Treg) cell population seem to favor a better pregnancy outcome, whereas Th1 and Th17 cell populations appear to have an opposite effect. Lately, the role of vitamin D in the modulation of immune response was established. Vitamin D has been shown to promote a more favorable environment for pregnancy through various mechanisms, such as enhancement of the shift toward Th2 cells and regulation of immune cell differentiation and cytokine secretion. Therefore, it seems that vitamin D deficiency sways the balance toward a worse outcome and may play a part in recurrent pregnancy loss. This review sheds light on the immunologic changes, which occur in early pregnancy and the regulatory role vitamin D has in the maintenance of this delicate balance.     

Breastfeeding and autoimmunity: Programing health from the beginning

Breast milk is not only a completely adapted nutrition source for the newborn but also an impressive array of immune‐active molecules that afford protection against infections and shape mucosal immune responses. Decisive imprinting events might be modulated during the first months of life with potential health long‐term effects, enhancing the importance of breastfeeding as a major influence on the immune system correct development and modifying disease susceptibility. The aim of this review was to clarify the link between breastfeeding and autoimmune diseases, inquiring the related mechanisms, based on data available in the literature. Being breastfed was associated with a lower incidence of diabetes, celiac disease, multiple sclerosis and asthma, explained by the protection against early infections, anti‐inflammatory properties, antigen‐specific tolerance induction, and regulation of infant's microbiome. The protective role of human milk in idiopathic juvenile arthritis, rheumatoid arthritis, and inflammatory bowel diseases remains controversial. On the other hand, the breastfeeding mother faces a health‐challenging period in life. High levels of prolactin may lead either to the development of autoimmune diseases in susceptible mothers or exacerbations of current immune‐mediated disorders. These features raise the question if mothers with autoimmune diseases, mainly systemic lupus erythematosus, should avoid breastfeeding.     

Inflammation and Metabolic Complications in HIV

Purpose of Review

We aim to provide an in-depth review of recent literature highlighting the role of inflammation involving the adipose tissue, liver, skeletal muscles, and gastrointestinal tract in the development of metabolic complications among persons living with HIV (PLWH).

Recent Findings

Recent studies in PLWH have demonstrated a significant association between circulating inflammatory markers and development of insulin resistance and metabolic complications. In adipose tissue, pro-inflammatory cytokine expression inhibits adipocyte insulin signaling, which alters lipid and glucose homeostasis. Increased lipolysis and lipogenesis elevate levels of circulating free fatty acids and promote ectopic fat deposition in liver and skeletal muscles. This leads to lipotoxicity characterized by a pro-inflammatory response with worsening insulin resistance. Finally, HIV is associated with gastrointestinal tract inflammation and changes in the gut microbiome resulting in reduced diversity, which is an additional risk factor for diabetes.

Summary

Metabolic complications in PLWH are in part due to chronic, multisite tissue inflammation resulting in dysregulation of glucose and lipid trafficking, utilization, and storage.

     

The role of stress in the mosaic of autoimmunity: An overlooked association

Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (T_h2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (T_h1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.     

Personalized treatment in metastatic triple‐negative breast cancer: The outlook in 2020

Compared with other breast cancer subtypes, patients with triple‐negative breast cancer (TNBC), and irrespective to their disease stage, were always recognized to have the worst overall survival data. Although this does not seem different at the present time, yet the last few years have witnessed many breakthrough genomic and molecular findings, that could dramatically improve our understanding of the biological complexity of TNBC. Based on genomic analyses, it was consistently evident that TNBC comprises a heterogeneous group of cancers, which have numerous diverse molecular aberrations. This—in return—has provided a platform for a new generation of clinical trials using many innovative therapies, directed against such novel targets. At the present time, two PARP inhibitors and one anti‐PD‐L1 monoclonal antibody (in combination with chemotherapy) have been approved in certain subpopulations of metastatic TNBC (mTNBC) patients, which have finally brought this disease into the era of personalized medicine. In the current review, we will explore the genomic landscape of TNBC, through which many actionable targets were graduated. We will also discuss the results of the key—practice changing—clinical studies, and some upcoming personalized treatment options for patients with mTNBC, that may be clinically adopted in the near future.