Approach to Pancytopenia in a Deployed Service Member.

Background: Pancytopenia is a result of increased destruction or decreased production of bone marrow cells and has a broad differential. Pernicious anemia commonly presents as a macrocytic anemia and is typically autoimmune in nature and the result of vitamin B12 deficiency. Pancytopenia is a rare presentation of this disorder especially in the setting of hemolysis. Testing in the deployed setting may be limited and/or challenging. Case Presentation: A 24-year-old female patient with a history of Hashimoto thyroiditis presented during an overseas deployment with a witnessed syncopal episode and was found to be pancytopenic with a mild transaminitis and laboratory tests demonstrating hemolysis. Though initially she was hypotensive, tachycardic, and febrile, her vitals improved after multiple transfusions, but she had persistent cytopenia with transfusion dependence, concerning for aplastic anemia or acute leukemia. Conclusions: Testing for B12 deficiency is crucial in symptomatic, patients with pancytopenic to either diagnose or exclude pernicious anemia and conserve resources by preventing costly workup and transfer/escalation of medical care, especially in the deployed setting. A predeployment screening in those with history of autoimmune disorders may be warranted.

The emerging importance and evolving understanding of clonal hematopoiesis in multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy diagnosed in the United States. With a growing arsenal of novel therapies, patients are living longer and hence are at increased risk of secondary cancers such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). While MDS-associated cytogenetic abnormalities have been described in patients with a diagnosis of for decades, clonal hematopoiesis (CH) has been described only recently. CH has been shown to correlate with inferior survival in MM due to increased risk of disease progression in patients who are treated with high-dose melphalan without lenalidomide maintenance. When involving specific high-risk genes, multiple genes, or when present at high variant allelic frequencies, CH could also potentially elevate the risk of secondary MDS and/or AML, cardiovascular events, and venous thromboembolic events. Despite growing knowledge about CH in patients with MM, many questions remain unanswered. Further studies are needed to better understand the prognostic and therapeutic significance of CH in MM and its precursor conditions, as well as the effect of specific treatments on long-term outcome.

Cavitary Lung Lesion in a Tuberculosis-Negative Patient.

A patient with worsening chronic cough, shortness of breath, and hemoptysis tested negative for tuberculosis; but a chest computed tomography scan showed an upper left lobe cavitary lesion.

Impact of Alcohol Consumption on Snoring and Sleep Apnea: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the international literature for studies evaluating the effect of alcohol consumption on the occurrence and severity of snoring and obstructive sleep apnea and to use the available data to perform a meta-analysis. DATA SOURCES: MEDLINE, Embase, The Cochrane Library, CINAHL/EBASCO, and Scopus. REVIEW METHODS: The protocol was registered in PROSPERO in March 2018. Following PRISMA guidelines, 2 independent researchers conducted a search from their inception through July 2018. Polysomnography (PSG) data were collected for sleep stages, apnea-hypopnea index (AHI), respiratory disturbance index, and/or lowest oxygen saturation (LSAT). Data concerning the frequency and severity of snoring intensity and sleep architecture were also collected. Only studies with PSG data were evaluated, with exclusion of studies with home sleep testing data. A multivariate regression and pooled analysis with forest plot was performed. RESULTS: A total of 1266 manuscripts were screened, and 13 manuscripts with 279 patients met inclusion criteria. Pooled analysis of AHI for control versus alcohol consumption revealed a mean difference (MD) of 3.98 events per hour (95% CI, 3.27 to 4.68; P < .001). Pooled analysis of LSAT for control versus alcohol consumption revealed an MD of -2.72% (95% CI, -3.69 to -1.76; Z score, 5.53; P < .00001). CONCLUSION: Alcohol consumption is associated with worsening severity of snoring, altered sleep architecture, AHI, as well as lowest oxygen saturation among patients susceptible to snoring and obstructive sleep apnea.

Expression of the cytoplasmic nucleolin for post-transcriptional regulation of macrophage colony-stimulating factor mRNA in ovarian and breast cancer cells.

The formation of the mRNP complex is a critical component of translational regulation and mRNA decay. Both the 5' and 3'UTRs of CSF-1 mRNA are involved in post-transcriptional regulation. In CSF-1 mRNA, a small hairpin loop structure is predicted to form at the extreme 5' end (2-21nt) of the 5'UTR. Nucleolin binds the hairpin loop structure in the 5'UTR of CSF-1 mRNA and enhances translation, while removal of this hairpin loop nucleolin binding element dramatically represses translation. Thus in CSF-1 mRNA, the hairpin loop nucleolin binding element is critical for translational regulation. In addition, nucleolin interacts with the 3'UTR of CSF-1 mRNA and facilitates the miRISC formation which results in poly (A) tail shortening. The overexpression of nucleolin increases the association of CSF-1 mRNA containing short poly (A)n≤26, with polyribosomes. Nucleolin both forms an mRNP complex with the eIF4G and CSF-1 mRNA, and is co-localized with the eIF4G in the cytoplasm further supporting nucleolin's role in translational regulation. The distinct foci formation of nucleolin in the cytoplasm of ovarian and breast cancer cells implicates the translational promoting role of nucleolin in these cancers.

The Application and Outcome of Standard of Care Treatment in Elderly Women with Ovarian Cancer: A Literature Review over the Last 10 Years.

The rising number and increasing longevity of the elderly population calls for improvements and potentially a more personalized approach to the treatment of cancer in this group. Elderly patients frequently present with a number of comorbidities, complicating surgery and chemotherapy tolerability. In the case of ovarian cancer, elderly women present with more advanced disease, making the issue of providing adequate treatment without significant morbidity critical. Most studies support the application of standard of care treatment to elderly women with ovarian cancer, yet it seems to be offered less frequently in the elderly. The objective of this review is to examine the application and outcome of standard of care treatment in elderly women with ovarian cancer. The aim is to ultimately improve the approach to treatment in this group.

Contraceptive Use and Uptake of HIV-Testing among Sub-Saharan African Women.

Despite improved availability of simple, relatively inexpensive, and highly effective antiretroviral treatment for HIV/AIDS, the disease remains a major public health challenge for women in sub-Saharan Africa (SSA). Given the numerous barriers in access to care for women in this region, every health issue that brings them into contact with the health system should be optimized as an opportunity to integrate HIV/AIDS prevention. Because most non-condom forms of modern contraception require a clinical appointment for use, contraception appointments could provide a confidential opportunity for access to HIV counseling, testing, and referral to care. This study sought to investigate the relationship between contraceptive methods and HIV testing among women in SSA. Data from the Demographic and Health Survey from four African countries-Congo, Mozambique, Nigeria, and Uganda-was used to examine whether modern (e.g., pills, condom) or traditional (e.g., periodic abstinence, withdrawal) forms of contraception were associated with uptake of HIV testing. Data for the current analyses were restricted to 35,748 women with complete information on the variables of interest. Chi-square tests and logistic regression models were used to assess the relationship between uptake of HIV testing and respondents' baseline characteristics and contraceptive methods. In the total sample and in Mozambique, women who used modern forms of contraception were more likely to be tested for HIV compared to those who did not use contraception. This positive association was not demonstrated in Congo, Nigeria, or Uganda. That many women who access modern contraception are not tested for HIV in high HIV burden areas highlights a missed opportunity to deliver an important intervention to promote maternal and child health. Given the increasing popularity of hormonal contraception methods in low-income countries, there is an urgent need to integrate HIV counseling, testing, and treatment into family planning programs. Women on hormonal contraceptives should be encouraged to continue to use condoms for HIV-prevention.

Antenatal care and uptake of HIV testing among pregnant women in sub-Saharan Africa: a cross-sectional study.

INTRODUCTION: Current guidelines recommend inclusion of HIV testing in routine screening tests for all pregnant women. For this reason, antenatal care (ANC) represents a vital component of efforts to prevent mother-to-child transmission (PMTCT) of HIV. To elucidate the relationship between ANC services and HIV testing among pregnant women in sub-Saharan Africa, we undertook an analysis of data from four countries. METHODS: Four countries (Congo, Mozambique, Nigeria and Uganda) were purposively selected to represent unique geographical regions of sub-Saharan Africa. Using Demographic and Health Survey datasets, weighted crude and adjusted logistic regression models were used to explore factors that influenced HIV testing as part of ANC services. The study was approved by the Institutional Review Board of the University of Arizona. RESULTS: Pooled results showed that 60.7% of women received HIV testing as part of ANC. Ugandan women had the highest rate of HIV testing as part of ANC (81.5%) compared with women in Mozambique (69.4%), Nigeria (54.4%) and Congo (45.4%). Difficulty reaching a health facility was a barrier in Congo and Mozambique but not Nigeria or Uganda. HIV testing rates were lower in rural areas, among the poorest women, the least educated and those with limited knowledge of HIV. In every country, crude regression analyses showed higher odds of being tested for HIV if women received their ANC services from a skilled attendant compared with an unskilled attendant. After adjusting for confounders, women in the total sample had 1.78 (99% CI: 1.45-2.18) times the odds of having an HIV test as part of their ANC if they went to a skilled attendant compared with an unskilled attendant. CONCLUSIONS: There is a need for integration of HIV testing into routine ANC service to increase opportunities for PMTCT programmes to reach HIV-positive pregnant women. Attention should be paid to the expansion of outreach services for women in rural settings, and to the training, supervision and integration of unskilled attendants into formal maternal and child health programmes. Education of pregnant women and their communities is needed to increase HIV knowledge and reduce HIV stigma.

The effects of prenatal cannabis exposure on fetal development and pregnancy outcomes: a protocol.

INTRODUCTION: The effects of exposure to marijuana in utero on fetal development are not clear. Given that the recent legislation on cannabis in the US is likely to result in increased use, there is a need to assess the effects of prenatal cannabis exposure on fetal development and pregnancy outcomes. The objective of this review is to assess the effects of prenatal exposure to cannabis on pregnancy outcomes (including maternal and child outcomes). METHODS AND ANALYSES: Major databases will be searched from inception to the latest issue, with the aim of identifying studies that reported the effects of prenatal exposure to cannabis on fetal development and pregnancy outcomes. Two investigators will independently review all titles and abstracts to identify potential articles. Discrepancies will be resolved by repeated review, discussion and consensus. Study quality assessment will be undertaken, using standard protocols. To qualify for inclusion, studies must report at least one maternal or neonatal outcome post partum. Cross-sectional, case-control, cohort and randomised controlled trials published in English will be included. In order to rule out the effects of other drugs that may affect fetal development and pregnancy outcomes, studies will only be included if they report outcomes of prenatal exposure to cannabis while excluding other illicit substances. Data from eligible studies will be extracted, and data analysis will include a systematic review and critical appraisal of evidence, and meta-analysis if data permit. Meta-analysis will be conducted if three or more studies report comparable statistics on the same outcome. ETHICS AND DISSEMINATION: The review which will result from this protocol has not already been conducted. Preparation of the review will follow the procedures stated in this protocol, and will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ethical approval of data will not be required since the review will use data that are already available in the public domain through published articles and other reports.

Appropriate use of complementary and alternative medicine approaches in gynecologic cancers.

OPINION STATEMENT: Gynecologic cancer patients frequently desire alternative and/or complementary interventions or medicines to aid in relief of both cancer-related and treatment-related side effects. Furthermore, women also seek treatment to aid in superior outcomes and cure rates. Unfortunately, evidence suggests that the use of complementary and/or alternative medicine (CAM) is underreported or not discussed with physicians providing cancer care. In gynecologic cancer literature, there is a lack of scientific evidence either supporting or negating CAM. Because of the lack of information available, health care providers do not have good information regarding safety, efficacy, and dose of CAM. This leads to miscommunication or absence of communication between providers and patients. Because patients do use CAM to improve quality of life (QOL) during and after treatment, it would be educational for providers to know the specific QOL deficits among patients that require attention. Thus, with the ultimate goal of improving QOL for gynecologic cancer patients, providers should be pushed to investigate CAM and determine an honest support or rejection of these therapies.

Updates on drug discovery in ovarian cancer.

Drug discovery in the ovarian cancer arena continues to launch important new clinical trials. Many biologic agents are being studied in phase II and phase III clinical trials for recurrent disease. These agents include compounds that disrupt angiogenesis through a variety of mechanisms. Other oncogenic pathways are also specifically targeted such as PARP, MEK, and topoisomerase inhibitors which are currently being studied in phase III trials. Various cytotoxic agents, as well as therapeutic vaccines, are also under investigation, and continue to demonstrate promising new data. The relevant agents in the treatment of ovarian cancer which have demonstrated positive phase II activity will be discussed.