Oral iron replacement vs. IV iron treatment in bariatric surgery patients with anemia.

ABSTRACT: Bariatric surgery has become a recognized tool to reduce weight and resolve or improve comorbid conditions associated with obesity. Patients with obesity are at risk for nutritional deficiencies because of poor-quality diets and the chronic inflammatory state of obesity. Iron deficiency is common in these patients, with incidence rates as high as 21.5% preoperatively and 49% postoperatively. Iron deficiency is often overlooked and not treated, leading to increased complications. This article reviews the risk factors for developing iron-deficiency anemia, diagnosis, and treatment considerations for oral versus IV iron replacement for patients undergoing bariatric surgery.

Traveler's diarrhea.

ABSTRACT: Traveler's diarrhea (TD) is one of the most common illnesses afflicting the modern traveler. TD refers to a watery diarrhea that varies in severity from tolerable to incapacitating and that develops in individuals during or within 10 days of returning from travel to developing or low-/middle-income countries. Most cases of TD are self-limiting, but in consideration of the ease of international travel, it is important for providers to diagnose and manage TD with the best available evidence.

Resilience of T cell-intrinsic dysfunction in transplantation tolerance.

Following antigen stimulation, naïve T cells differentiate into memory cells that mediate antigen clearance more efficiently upon repeat encounter. Donor-specific tolerance can be achieved in a subset of transplant recipients, but some of these grafts are rejected after years of stability, often following infections. Whether T cell memory can develop from a tolerant state and whether these formerly tolerant patients develop antidonor memory is not known. Using a mouse model of cardiac transplantation in which donor-specific tolerance is induced with costimulation blockade (CoB) plus donor-specific transfusion (DST), we have previously shown that systemic infection with Listeria monocytogenes (Lm) months after transplantation can erode or transiently abrogate established tolerance. In this study, we tracked donor-reactive T cells to investigate whether memory can be induced when alloreactive T cells are activated in the setting of tolerance. We show alloreactive T cells persist after induction of cardiac transplantation tolerance, but fail to acquire a memory phenotype despite becoming antigen experienced. Instead, donor-reactive T cells develop T cell-intrinsic dysfunction evidenced when removed from the tolerant environment. Notably, Lm infection after tolerance did not rescue alloreactive T cell memory differentiation or functionality. CoB and antigen persistence were sufficient together but not separately to achieve alloreactive T cell dysfunction, and conventional immunosuppression could substitute for CoB. Antigen persistence was required, as early but not late surgical allograft removal precluded the acquisition of T cell dysfunction. Our results demonstrate transplant tolerance-associated T cell-intrinsic dysfunction that is resistant to memory development even after Lm-mediated disruption of tolerance.

A curious case of ovarian cysts.

ABSTRACT: Benign mature cystic teratomas are a form of ovarian germ cell tumor that originates from primordial germ cells in the ovaries. Of the three types of teratoma neoplasms, benign mature cystic teratomas (also called dermoid cysts) are the most common. Patients may present with intermittent abdominal or pelvic pain, abdominal enlargement, dysmenorrhea, dyspareunia, or may be asymptomatic. Clinicians should have a high suspicion for benign mature cystic teratomas, which account for more than 20% of all ovarian neoplasms. This article focuses on the clinical symptoms, ovarian growth characteristics, pathophysiology, potential complications, management options, and recurrence of benign mature cystic teratomas.

Early pregnancy loss.

ABSTRACT: Previously called spontaneous abortion, early pregnancy loss (EPL) is the preferred term encompassing threatened abortion, incomplete abortion, complete abortion, and anembryonic pregnancy. EPL has many causes, including chromosomal abnormalities, immunologic and infectious causes, and underlying maternal risk factors. Because many patients present with first-trimester bleeding, clinicians must know the appropriate evaluation and management techniques.

Evaluation of the returning traveler with fever and neurologic symptoms.

ABSTRACT: Exposure to infectious disease increases in tandem with international travel rates. Globally, up to 70% of travelers to developing countries report health problems while traveling, most being self-limiting. Few travelers are ill enough to seek medical care while abroad or upon returning home. Although fever is one of the more common symptoms in these travelers, little attention has been paid to those who return with fever and neurologic symptoms. This article describes conditions that can present with fever and neurologic changes and how to evaluate patients in a timely manner to prevent progression of neural dysfunction and spread of disease in local communities.

Postpartum hemorrhage.

Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide, and incidence in the United States, although lower than in some resource-limited countries, remains high. Women of color are at a disproportionate risk of developing a life-threatening postpartum hemorrhage. Risk assessment tools are available but because they lack specificity and sensitivity, all pregnant women are considered at risk. Early identification of and intervention in a hemorrhage requires an interdisciplinary team approach to care and can save the lives of thousands of women each year.

Intrathecal hydromorphone as an analgesia option for gynecology patients.

Enhanced recovery after surgery (ERAS) is a multimodal perioperative strategy originally developed to attenuate the postsurgical stress response in patients after colorectal surgery. Patients undergoing gynecologic surgery who had ERAS had significantly shorter hospital length of stay, reduced hospital-related costs, and acceptable pain management with reduced opioid use, without compromising patient satisfaction. Intrathecal hydromorphone is an effective alternative ERAS protocol analgesia for these patients and will not compromise patient outcomes or healthcare costs.

Locally advanced breast cancer treated with neoadjuvant chemotherapy and adjuvant radiotherapy: a retrospective cohort analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used to treat locally advanced breast cancer (LABC). Improved response to NAC correlates with better survival outcomes. The dual purpose of this study is to report recurrence and survival outcomes for LABC patients treated with NAC, surgery and adjuvant radiotherapy and to correlate these outcomes with tumour response after NAC using multiple response assessment methods. METHODS: All LABC patients treated for curative intent with NAC, surgery, and adjuvant radiotherapy at our institute between January 2009 and December 2014 were included for analysis. NAC was mostly anthracycline and taxane-based; radiotherapy consisted of 50 Gy to the breast/chest wall and regional lymph nodes. Response to NAC was categorized using synoptic pathology reports, modified-RECIST and Chevallier scores. Survival curves were generated by the Kaplan-Meier method and compared using the log-rank test. RESULTS: The cohort included 103 patients nearly equally divided between Stage II (n = 53) and Stage III (n = 50). Rates of locoregional control (LRC), recurrence-free survival (RFS), and overall survival (OS) were 99, 98, and 100% at 1 year and 89, 69 and 77% at 5 years, respectively. Responses to NAC did not correlate with LRC (p > 0.05) but did correlate with RFS and OS (p < 0.05), except that the Chevallier score did not predict RFS (p = 0.06). Using bivariate Cox modeling tumour size before (p = 0.003) and after (p < 0.001) NAC, stage group (p = 0.05), and response assessed by synoptic pathology (p = 0.05), modified-RECIST (p = 0.001), and Chevallier score (p = 0.015) all predicted for RFS. No factors predicted for LRC. CONCLUSION: Pathologic response by all tested methods correlated with improved survival but were not associated with decreased LRC.

Overview of breast cancer.

Each year, more than 250,000 women in the United States are diagnosed with invasive breast cancer. Although overall mortality for breast cancer patients has declined, it is still the second most common cause of cancer death in women. This article provides an overview of nonmetastatic breast cancer in women, including general features, diagnostic considerations, and treatments for the most common breast cancer subtypes.

Procalcitonin-guided treatment of lower respiratory tract infections.

The FDA recently approved a procalcitonin assay for use in hospitals and EDs to help prescribers determine if an antibiotic should be prescribed and for what duration. This article reviews the use of procalcitonin testing and evidence-based medical decision-making for patients with sepsis or lower respiratory tract infections.

Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment diffuse optical spectroscopic texture analysis.

BACKGROUND: Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pretreatment DOS functional maps for predicting LABC response to NAC. METHODS: Locally advanced breast cancer patients (n=37) underwent DOS breast imaging before starting NAC. Breast tissue parametric maps were constructed and texture analyses were performed based on grey-level co-occurrence matrices for feature extraction. Ground truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller-Payne pathological response criteria. The capability of DOS textural features computed on volumetric tumour data before the start of treatment (i.e., 'pretreatment') to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naive Bayes, and k-nearest neighbour classifiers. RESULTS: Data indicated that textural characteristics of pretreatment DOS parametric maps can differentiate between treatment response outcomes. The HbO2 homogeneity resulted in the highest accuracy among univariate parameters in predicting response to chemotherapy: sensitivity (%Sn) and specificity (%Sp) were 86.5% and 89.0%, respectively, and accuracy was 87.8%. The highest predictors using multivariate (binary) combination features were the Hb-contrast+HbO2-homogeneity, which resulted in a %Sn/%Sp=78.0/81.0% and an accuracy of 79.5%. CONCLUSIONS: This study demonstrated that the pretreatment DOS texture features can predict breast cancer response to NAC and potentially guide treatments.

Caring for a patient with first-trimester bleeding.

This article provides a review of the general features, clinical assessment, diagnosis, and treatment of bleeding in the first trimester of pregnancy.

Understanding the new pregnancy and lactation drug labeling.

Recent changes to the FDA's drug labeling rules clarify the risk of drugs for patients who are pregnant or lactating and remove A, B, C, D, and X as risk categories. Drugs are now categorized by risk for pregnancy, lactation, and women and men of reproductive potential. Risk summaries and clinical considerations in the new labeling can help prescribers and patients make informed decisions about medication use.

LDL-Binding IL-10 Reduces Vascular Inflammation in Atherosclerotic Mice.

Atherosclerosis is a chronic inflammatory disease associated with the accumulation of low-density lipoprotein (LDL) in arterial walls. Higher levels of the anti-inflammatory cytokine IL-10 in serum are correlated with reduced plaque burden. However, cytokine therapies have not translated well to the clinic, partially due to their rapid clearance and pleiotropic nature. Here, we engineered IL-10 to overcome these challenges by hitchhiking on LDL to atherosclerotic plaques. Specifically, we constructed fusion proteins in which one domain is IL-10 and the other is an antibody fragment (Fab) that binds to protein epitopes of LDL. In murine models of atherosclerosis, we show that systemically administered Fab-IL-10 constructs bind circulating LDL and traffic to atherosclerotic plaques. One such construct, 2D03-IL-10, significantly reduces aortic immune cell infiltration to levels comparable to healthy mice, whereas non-targeted IL-10 has no therapeutic effect. Mechanistically, we demonstrate that 2D03-IL-10 preferentially associates with foamy macrophages and reduces pro-inflammatory activation markers. This platform technology can be applied to a variety of therapeutics and shows promise as a potential targeted anti-inflammatory therapy in atherosclerosis.

Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics.

Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients that reduces efficacy and increases adverse reactions. Our laboratory has shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer, p(Man). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We find that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by T regulatory cells. We identify increased T cell receptor signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.

A serine-conjugated butyrate prodrug with high oral bioavailability suppresses autoimmune arthritis and neuroinflammation in mice.

Butyrate-a metabolite produced by commensal bacteria-has been extensively studied for its immunomodulatory effects on immune cells, including regulatory T cells, macrophages and dendritic cells. However, the development of butyrate as a drug has been hindered by butyrate's poor oral bioavailability, owing to its rapid metabolism in the gut, its low potency (hence, necessitating high dosing), and its foul smell and taste. Here we report that the oral bioavailability of butyrate can be increased by esterifying it to serine, an amino acid transporter that aids the escape of the resulting odourless and tasteless prodrug (O-butyryl-L-serine, which we named SerBut) from the gut, enhancing its systemic uptake. In mice with collagen-antibody-induced arthritis (a model of rheumatoid arthritis) and with experimental autoimmune encephalomyelitis (a model of multiple sclerosis), we show that SerBut substantially ameliorated disease severity, modulated key immune cell populations systemically and in disease-associated tissues, and reduced inflammatory responses without compromising the global immune response to vaccination. SerBut may become a promising therapeutic for autoimmune and inflammatory diseases.