Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment.

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Anterior Gradient Protein 3 and S100 Calcium-Binding Protein P Levels in Different Endometrial Epithelial Compartments May Play an Important Role in Recurrent Pregnancy Failure.

Recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) are distressing conditions without effective treatments. The luminal epithelium (LE) is integral in determining receptivity of the endometrium, whereas functionalis glands and stroma aid in nurturing early embryo development. Calcium signalling pathways are known to be of vital importance to embryo implantation and pregnancy establishment, and anterior gradient protein 3 (AGR3) and S100 calcium-binding protein P (S100P) are involved with these pathways. We initially examined 20 full-thickness endometrial biopsies from premenopausal women across the menstrual cycle to characterize levels of AGR3 protein in each endometrial sub-region at the cellular level. A further 53 endometrial pipelle biopsies collected in the window of implantation were subsequently assessed to determine differential endometrial AGR3 and S100P levels relevant to RIF (n = 13) and RPL (n = 10) in comparison with parous women (n = 30) using immunohistochemistry. Significantly higher AGR3 and S100P immunostaining was observed in ciliated cells of the LE of women with recurrent reproductive failure compared with parous women, suggesting aberrant subcellular location-associated pathophysiology for these conditions. The nuclear localisation of S100P may allow transcriptional regulatory function, which is necessary for implantation of a viable pregnancy. Further work is thus warranted to assess their utility as diagnostic/therapeutic targets.

Predictors of outcome among patients on extracorporeal membrane oxygenation as a bridge to lung transplantation.

BACKGROUND: There is a lack of data regarding clinical variables associated with successful bridge to lung transplantation (LT) using extracorporeal membrane oxygenation (ECMO) support. METHODS: We reviewed the institutional database for patients supported with veno-venous (VV) or veno-arterial ECMO as a bridge to LT (n=25; mean age: 50.6±14.2 years). We recorded clinical and laboratory variables, findings on echocardiogram and development of organ dysfunction along with hospital and one-year survival. Variables were compared between patients successfully bridged to LT versus those who were not. RESULTS: The most common diagnostic group was interstitial lung disease (18/25, 72%). VV-ECMO was used in the majority (84%). Fifteen patients (60%) were successfully bridged to LT, and the majority were alive at 1 year (14/15, 93.3%). The presence of right ventricular systolic dysfunction on pre-ECMO echocardiogram was associated with increased risk of unsuccessful bridging (OR, 95% CI: 2.67, 1.01-6.99, P=.041). While on ECMO, trough albumin levels <2.5 gm%, peak blood urea nitrogen levels >35 mg/dL and positive fluid balance were also associated with failure to bridge to LT. CONCLUSIONS: Among patients awaiting LT, the presence of RV systolic dysfunction before ECMO initiation along with worsening renal functions, low albumin levels, and volume overload is associated with poor outcomes.

Discussing and Teaching About Race and Health Inequities.

Health inequities are prevalent in our medical institutions and result in unfair access to and delivery of health care. Some of the most profound health disparities are related to race, which has erroneously been used to make biological inferences to explain disease states in medicine. Our profession continues to shift away from such race-based medical narratives, which do not examine how social determinants of health, social injustice, systemic racism, and existing power structures shape health outcomes toward a health equity mindset and race-conscious medicine. Clinician educators are responsible for teaching and engaging with learners around issues of inequity in medicine, although many may feel they lack the knowledge or skills to do so. Opportunities for conversations on health equity abound, either as a response to statements made by clinical peers or patients, or through direct clinical care of affected populations. In this paper, we focus our discussion of health equity around the topic of race corrections in spirometry, which is one of several salient areas of conversation in the field of pulmonary medicine undergoing reconciliation. We review basic definitions and concepts in health equity and apply three strategies to engage in conversations around equity with colleagues and learners: actively learning and reflecting on health inequities, recognizing and naming inequities, and consciously role-modeling equity-conscious language and care. We also will summarize strategies for implementing health equity concepts into the continuum of medical education and our clinical learning environments.

Hearing conservation measures of effectiveness across the Department of Defense.

This article summarizes the findings from the first report of the new, standard Measures of Effectiveness developed by the Department of Defense (DoD) Hearing Conservation Program Working Group in 2018. When examining periodic hearing test results of DoD personnel, the overall risk of potential hearing injury/illness was stable from 2012 through 2018. The National Guard and Reserve components showed a higher potential risk of hearing loss, possibly related to lower compliance on follow-up tests when a shift in hearing occurred. Finally, the overall percentage of DoD personnel (who received periodic hearing tests) with hearing impairment decreased over the years presented.

Controlling the formation of cyanine dye H- and J-aggregates with cucurbituril hosts in the presence of anionic polyelectrolytes.

The presence of anionic polyelectrolytes enhances the tendency of cationic cyanine dyes to form aggregates in aqueous media. In this work we investigate the interactions between two cyanine dyes, pseudoisocyanine (PIC) and pinacyanol (PIN), with polystyrenesulfonate (PSS) as the key additive to develop J- and H-aggregates. We also take advantage of the binding properties of the cucurbit[7]uril (CB7) host to control formation of these aggregates through its host-guest interactions with the dye molecules. UV/Vis absorption spectroscopic studies clearly demonstrate the PSS-enhanced formation of J-aggregates in the case of PIC and H-aggregates in the case of PIN. Electrostatic interactions between the cyanine dye molecules and the polyelectrolyte chains assist the formation of J- or H-aggregates at very low dye concentrations (ca. 10 microM). Optimum development of dye aggregates was observed at a sulfonate/dye molar ratio of about 3:1. Departures from this stoichiometric ratio seem to perturb the optimal aggregate structure. Furthermore, the presence of CB7 was found to effectively disrupt the interactions responsible for dye aggregation. Thus, CB7 completely disrupts the J-aggregates formed by PIC and the H-aggregates (as well as lower concentrations of J-aggregates) formed by PIN. UV/Vis and emission spectroscopic studies clearly indicate that binding of CB7 to both dye molecules removes them from the aggregate structures. Our spectroscopic data clearly indicate that regulation of the relative molar ratios of dye, CB7 host, and polyelectrolyte sulfonate groups leads to a quantitative control of dye aggregation, yielding variable amounts of PIC J- and PIN H-aggregates in these solutions.

Control of H- and J-aggregate formation via host-guest complexation using cucurbituril hosts.

The binding interactions between two cyanine dyes, pseudoisocyanine (PIC) and pinacyanol (PIN), and the cucurbit[n]uril hosts, cucurbit[7]uril (CB7) and cucurbit[6]uril (CB6), were investigated by electronic absorption spectroscopy and DFT computational methods. The CB7 host forms more stable complexes with both dyes than CB6 and the computational studies suggest that the cavity of the smaller host CB6 is not threaded by the dyes. The equilibrium association constants (K) for complexation by CB7 were measured and found to be 2.05 x 10(4) and 3.84 x 10(5) M(-1) for PIC and PIN, respectively, in aqueous media at 23 degrees C. CB7 complexation was found to effectively disrupt the intermolecular forces responsible for the aggregation of both dyes. Thus, CB7 completely disrupts the J-aggregates formed by PIC and the H-aggregates (as well as lower concentrations of J-aggregates) formed by PIN. In both cases a competing guest, 1-aminoadamantane (AD), could be used to adjust the extent of aggregation of the cyanine dye. AD regulates aggregate formation because it forms an extremely stable complex with CB7 (K approximately = 10(12) M(-1)) and exerts a tight control on the CB7 concentration available to interact and bind with the dye.