Saba Radhi

Proton Pump Inhibitors and Risk of Fracture: A Systematic Review and Meta-Analysis of Observational Studies

OBJECTIVES:Proton pump inhibitors (PPIs) are widely used in several acid-related gastrointestinal disorders. In vivo studies have suggested that gastric suppression by PPIs could result in decreased intestinal calcium absorption. Subsequently, there have been concerns that the chronic use of a PPI is associated with an increased risk of bone fracture. However, the results of clinical studies are conflicting.METHODS:We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risks of PPI use on fracture outcome. All controlled observational studies that compared fracture outcome in patients with PPI therapy with a control group were included. We calculated pooled odds ratios (ORs) using a random-effects model.RESULTS:Of 1,668 identified studies, 10 (4 cohort and 6 case–control) with 223,210 fracture cases were included in our analysis. In PPI users, compared with non/past users, the OR for hip fracture (n=9) was 1.25 (95% confidence interval (CI)=1.14–1.37). The OR for vertebral fracture (n=4) was 1.50 (95% CI=1.32–1.72) and for wrist/forearm fracture (n=3) was 1.09 (95% CI=0.95–1.24). In subgroup analysis of hip fracture, this association was observed in both high-dose and low-dose PPI exposure. When stratified by duration of exposure, the short duration of PPI use was associated with increased risk of developing hip fracture (OR=1.24; 95% CI=1.19–1.28), whereas there was no significant increase in risk of hip fracture in long-term PPI users (OR=1.30; 95% CI=0.98–1.70). There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the subgroup analyses.CONCLUSIONS:Our results should be interpreted with caution. We found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding. Thus, randomized controlled studies are required to confirm or refute these results.

Aging, cancer, and cancer vaccines.

World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people [1]. Most cancers are age-related diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be diagnosed in elderly patients by 2020 [2]. Further, cancer-related mortality increases with age: 70% of all malignancy-related deaths are registered in people aged 65 years or older [3]. Here we introduce the microscopic aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence. Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present be recommended in association to a stronger cancer prevention and conventional therapies (surgery, chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality associated to cancer progression.

Hyperthyroidism and Pulmonary Hypertension: An Important Association

Pulmonary hypertension is a complex disorder with multiple etiologies. The World Health Organization Group 5 (unclear multifactorial mechanisms) includes patients with thyroid disorders. The authors reviewed the literature on the association between hyperthyroidism and pulmonary hypertension and identified 20 publications reporting 164 patients with treatment outcomes. The systolic pulmonary artery (PA) pressures in these patients ranged from 28 to 78 mm Hg. They were treated with antithyroid medications, radioactive iodine and surgery. The mean pretherapy PA systolic pressure was 39 mm Hg; the mean posttreatment pressure was 30 mm Hg. Pulmonary hypertension should be considered in hyperthyroid patients with dyspnea. All patients with pulmonary hypertension should be screened for hyperthyroidism, because the treatment of hyperthyroidism can reduce PA pressures, potentially avoid the side-effects and costs with current therapies for pulmonary hypertension and limit the consequences of untreated hyperthyroidism. However, the long-term outcome in these patients is uncertain, and this issue needs more study. Changes in the pulmonary circulation and molecular regulators of vascular remodeling likely explain this association.

Chimeric Antigen Receptor Engineering: A Right Step in the Evolution of Adoptive Cellular Immunotherapy

Cancer immunotherapy comprises different therapeutic strategies that exploit the use of distinct components of the immune system, with the common goal of specifically targeting and eradicating neoplastic cells. These varied approaches include the use of specific monoclonal antibodies, checkpoint inhibitors, cytokines, therapeutic cancer vaccines and cellular anticancer strategies such as activated dendritic cell (DC) vaccines, tumor-infiltrating lymphocytes (TILs) and, more recently, genetically engineered T cells. Each one of these approaches has demonstrated promise, but their generalized success has been hindered by the paucity of specific tumor targets resulting in suboptimal tumor responses and unpredictable toxicities. This review will concentrate on recent advances on the use of engineered T cells for adoptive cellular immunotherapy (ACI) in cancer.

Mast cells and the liver aging process

It has now ascertained that the clinical manifestations of liver disease in the elderly population reflect both the cumulative effects of longevity on the liver and the generalized senescence of the organism ability to adjust to metabolic, infectious, and immunologic insults. Although liver tests are not significantly affected by age, the presentation of liver diseases such as viral hepatitis may be subtler in the elderly population than that of younger patients.Human immunosenescence is a situation in which the immune system, particularly T lymphocyte function, deteriorates with age, while innate immunity is negligibly affected and in some cases almost up-regulated.We here briefly review the relationships between the liver aging process and mast cells, the key effectors in a more complex range of innate immune responses than originally though.

The Role of Human Papilloma Virus (HPV) Infection in Non-Anogenital Cancer and the Promise of Immunotherapy: A Review

Over the past 30 years, human papilloma virus (HPV) has been shown to play a role in the development of various cancers. Most notably, HPV has been linked to malignant progression in neoplasms of the anogenital region. However, high-risk HPV has also been suggested to play a significant role in the development of cancers in other anatomic locations, such as the head and neck, lung, breast and bladder. In 2006, the first vaccine for HPV, Gardasil, was approved for the prevention of subtypes 6, 11, 16 and 18. A few years later, Cevarix was approved for the prevention of subtypes 16 and 18, the HPV subtypes most frequently implicated in malignant progression. Although increased awareness and vaccination could drastically decrease the incidence of HPV-positive cancers, these approaches do not benefit patients who have already contracted HPV and developed cancer as a result. For this reason, researchers need to continue developing treatment modalities, such as targeted immunotherapies, for HPV-positive lesions. Here, we review the potential evidence linking HPV infection with the development of non-anogenital cancers and the potential role of immunotherapy in the prevention and eradication of HPV infection and its oncogenic sequela.

Cancer Testes Antigens in Breast Cancer: Biological Role, Regulation, and Therapeutic Applicability

Breast cancer remains one of the leading causes of death among women across the world. The last few decades have seen significant reduction in mortality owing to earlier detection and better adjuvant treatments that were developed based on clinical staging and morphological features. As these treatments have evolved, the heterogeneity of breast cancer poses a new challenge, since there is no standard gold-therapy suitable for all tumors of the mammary gland. Therefore, contemporary management and research efforts are directed toward specific prognostic and predictive molecular signatures that can guide targeted individualized therapy. The goal of ongoing research in this field is to identify specific molecular targets for developing novel therapeutic approaches. These targets can also serve to improve screening of breast cancer. This review focuses on the role of cancer testis antigens (CTAs) in breast carcinogenesis and explores the potential for development of targeted screening and therapeutic approaches. Normally found in the testes, these antigens are highly correlative with cancers of the breast, skin, and ovaries. These implications have been further corroborated through uncovering the interaction of CTAs with genes and proteins involved in tumor suppression and homeostasis like p53. There is some evidence that these genes can be targeted for early detection in addition to being candidates for cancer immunotherapy.

Pheochromocytoma Presenting as Systemic Inflammatory Response Syndrome and Lactic Acidosis

Pheochromocytomas can secrete catecholamines, hormones, and cytokines, and the patterns of secretion strongly influence the complexity of the clinical presentation. We now report a patient who presented with abdominal pain, fever, leukocytosis, and tachycardia. In addition, he had lactic acidosis without shock. Our review of the literature indicates that this patient had systemic inflammatory response syndrome most likely secondary to high levels of IL-6 and that he had type B lactic acidosis secondary to high circulating levels of epinephrine. The combined presentation is unique and resolved with successful surgery. Pheochromocytoma should be included in the differential diagnosis of SIRS and of lactic acidosis.

Treatment of Metastatic Colorectal Cancer in a Pregnant Woman with Lynch Syndrome- A Case Report

Colorectal carcinoma is the third most common cancer diagnosed in females in the United States [1]. It accounts for 8% of the new cancers diagnosed in women and an estimated 63,700 new cases of CRC expected in 2015. CRC diagnosed in pregnancy is not common with an incidence of 1 in 13,000 pregnancies [2-4]. Management of a pregnant woman with CRC is challenging due to various unknowns to guide the antineoplastic treatment decision. CRC cases during pregnancy and use of chemotherapy agents have reported in the past decade [5-12]. Reporting of management of such situations is helpful in assisting clinicians to further investigating the use of chemotherapy agents in pregnancy. We report an unusual, but the challenging case of 24-year-old pregnant women diagnosed with metastatic colon cancer as a consequence of lunch syndrome treated with FOLFOX chemo regimen with no apparent fetal harm.

Cuff Leak Tests at the Time of Extubation Correlate With Voice Quality Assessment

Background. Endotracheal intubation frequently causes laryngeal injury, including edema, ulceration, and vocal cord immobility. These problems can complicate the immediate postextubation course. Methods. The authors measured the cuff leak and made bedside assessment of the voice in 51 patients requiring mechanical ventilation for acute respiratory failure. Results. The median tidal volume was 450 mL (range = 300-600 mL). The median duration of ventilation was 3 days (range = 0-19 days). The median cuff leak was 180 mL (range = −33 to 460 mL); the median percentage cuff leak was 40.9% (range = −7.75% to 99.2%). Women had significantly smaller cuff leaks (18.6% of tidal volume vs 50.3% in men, P = .01). Patients with hoarseness frequently had smaller cuff leaks (median 24.1% vs. 46.7% in nonhoarse patients). Eleven patients (84.6%, 11/13) with a cuff leak 15% had hoarseness (P = .01). Four patients had stridor, and all had a cuff leak >15% of the ti...