TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway.

Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underlies facial shape variation, yet how those networks in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both TFAP2 family members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning and differentiation. Notably, Alx1, Alx3 and Alx4 (ALX) transcript levels are reduced, whereas ChIP-seq analyses suggest TFAP2 family members directly and positively regulate ALX gene expression. Tfap2a, Tfap2b and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish implies conservation of this regulatory axis across vertebrates. Consistent with this notion, tfap2a zebrafish mutants present with abnormal alx3 expression patterns, Tfap2a binds ALX loci and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development in part by activating expression of ALX transcription factor genes.

Taurolidine and Heparin as Catheter Lock Solution for Central Venous Catheters in Hemodialysis.

BACKGROUND: Chronic kidney disease can lead to end-stage renal disease, and the prevalence is increasing. Many patients starting hemodialysis require central venous catheters (CVCs). Catheter-related bloodstream infections (CRBSIs) are a common complication and lead to significant morbidity and mortality. Interventions to prevent CRBSI include antimicrobial lock therapy but concern for the development of antimicrobial resistance and adverse effects. Nonantimicrobial antiseptics as catheter lock solutions have also been used. Taurolidine and heparin catheter lock solution is first approved by the Food and Drug Administration for the prevention of CRBSI in patients on hemodialysis. Taurolidine has a unique mechanism of action and favorable safety profile. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Taurolidine and heparin catheter lock solution have both antimicrobial and anticoagulant properties. Taurolidine is derivative of the amino acid taurine, and heparin is derived from porcine intestinal mucosa. Taurolidine not only damages microbial cell walls but also prevents the adherence of microorganisms to biological surfaces, preventing biofilm formation. Taurolidine and heparin catheter lock solution is intended to be used intraluminally within the catheter and should be aspirated. Because it is used locally, limited pharmacokinetic and pharmacodynamic data are available. CLINICAL TRIALS: The LOCK-IT-100 trial is a randomized, double-blind, phase 3 study, which included 795 end-stage renal disease patients on hemodialysis with CVC. Taurolidine and heparin was compared with the control heparin alone. The results of the study showed a 71% risk reduction in CRBSI for taurolidine and heparin arm (95% confident interval, 38%-86%, P = 0.0006). Other studies have also shown that taurolidine lock solution leads to decreased CRBSI episodes. Several systematic reviews and meta-analysis consisted of taurolidine in adult, and pediatric populations also showed reduction in the incidence of CRBSIs. THERAPEUTIC ADVANCE: Taurolidine and heparin lock solution represents a novel preventive strategy for those undergoing hemodialysis through a CVC by reducing the risk of CRBSI. This is significant progress because there are no other similar options available for patients for whom catheters are the only options for their life-saving treatment.

Quality of Life Analysis in Patients with Retinitis Pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP) is a chronic progressive disease causing loss of visual acuity and ultimately blindness. This visual impairment can contribute to psychiatric comorbidity and worse overall quality of life (QOL). Our goal was to assess the relationship between the severity of disease for people with RP and QOL as it pertains to mental health, social support, disability resources, and financial factors. METHODS: This was a survey study conducted from June 2021 to February 2022 including 38 people with RP. QOL was assessed through a survey questionnaire focusing specifically on demographics, visual function, family, employment, social support, and mental health/well-being. Statistical analysis was conducted using a χ2 test for significance. RESULTS: A best corrected visual acuity (BCVA) of less than 20/200 (p = 0.0285) and living alone (p = 0.0358) were both statistically significant independent risk factors for experiencing depressive symptoms. Highest education level attained and unemployment rate were not found to be related to the development of depressive symptoms. Subjects had a higher unemployment rate (64% vs. US rate of 3.6%) and a high likelihood of reporting depressive symptoms (47.4%). CONCLUSION: People with RP are more likely to be unemployed and to develop depressive symptoms when compared to the general population. Similar to previous studies' findings, those with a BCVA of less than 20/200 were statistically more likely to experience depressive symptoms; living alone is a novel risk factor that is also associated with the presence of depressive symptoms. Contrary to prior findings, highest education level and unemployment status were found not to be related to the development of depressive symptoms. These patients may benefit from regular depression screenings and optional establishment of care with a psychiatrist or psychologist if they live alone or their BCVA is 20/200 or worse.

Advances in neonatal cell therapies: Proceedings of the First Neonatal Cell Therapies Symposium (2022).

Despite considerable advances, there is a need to improve the outcomes of newborn infants, especially related to prematurity, encephalopathy and other conditions. In principle, cell therapies have the potential to protect, repair, or sometimes regenerate vital tissues; and improve or sustain organ function. In this review, we present highlights from the First Neonatal Cell Therapies Symposium (2022). Cells tested in preclinical and clinical studies include mesenchymal stromal cells from various sources, umbilical cord blood and cord tissue derived cells, and placental tissue and membrane derived cells. Overall, most preclinical studies suggest potential for benefit, but many of the cells tested were not adequately defined, and the optimal cell type, timing, frequency, cell dose or the most effective protocols for the targeted conditions is not known. There is as yet no clinical evidence for benefit, but several early phase clinical trials are now assessing safety in newborn babies. We discuss parental perspectives on their involvement in these trials, and lessons learnt from previous translational work of promising neonatal therapies. Finally, we make a call to the many research groups around the world working in this exciting yet complex field, to work together to make substantial and timely progress to address the knowledge gaps and move the field forward. IMPACT: Survival of preterm and sick newborn infants is improving, but they continue to be at high risk of many systemic and organ-specific complications. Cell therapies show promising results in preclinical models of various neonatal conditions and early phase clinical trials have been completed or underway. Progress on the potential utility of cell therapies for neonatal conditions, parental perspectives and translational aspects are discussed in this paper.

Evaluating the Efficacy and Pharmacoeconomics of Semaglutide and Tirzepatide in the Setting of Obesity.

BACKGROUND: Obesity is a major and growing public health concern. The associated cost for obesity and its related comorbidities is approximately 30% of US health care expenditures annually. As additional pharmacotherapeutic options join the market to combat obesity, it is important to understand the financial impact it may have on overall health care costs. This article explores the efficacy and pharmacoeconomics of incretin mimetics, semaglutide and tirzepatide, in the setting of obesity. AREA OF UNCERTAINTY: The cost of incretin mimetics (semaglutide and tirzepatide) and its overall impact on obesity management within the health care arena is being explored. The cost comparison of these medications is to be determined; however, it may represent an added cost to the total US health care expenditures. DATA SOURCES: A PubMed and Google Scholar search was conducted using various search terms (eg, semaglutide, tirzepatide, pharmacoeconomics, and obesity). THERAPEUTIC ADVANCES: Based on the data reviewed, both semaglutide and tirzepatide are effective medication options for obesity management. Obesity-related management expenditures exceed $173 billion for the US health care system annually. The cost needed to treat for 1% of weight loss with semaglutide and tirzepatide was reported as $1845 and $985, respectively. More than 40% of adults (60 years or older) experience obesity. If 1%, 5%, or 10% of this population is treated with semaglutide, the annual Medicare costs will translate to excess of $2.6 billion, $13.3 billion, and $26.8 billion, respectively. Tirzepatide is not yet approved in the United States for obesity and its financial impact remains to be seen. CONCLUSIONS: Obesity is associated with burdensome health complications and costs. Semaglutide and tirzepatide are effective drug options for the management of obesity. The cost of these medications will no doubt present a challenge to the total health care expenditures, although the cost-benefit ratio may ultimately be favorable.

Anakinra-An Interleukin-1 Receptor Antagonist for COVID-19.

BACKGROUND: Coronavirus disease (COVID-19) caused by SARS-CoV-2 virus caused a global pandemic in 2019. There are limited pharmacologic options available. The Food and Drug Administration initiated an emergency use authorization process to expedite pharmacologic agents to treat COVID-19. There are several agents available through the emergency use authorization process, ritonavir-boosted nirmatrelvir, remdesivir, and baricitinib. Anakinra is an interleukin (IL)-1 receptor antagonist that exhibits properties in fighting against COVID-19. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Anakinra is a recombinant IL-1 receptor antagonist. The epithelial cell damage that may occur with COVID-19 enhances the release of IL-1, which plays a central role in severe cases. Thus, drugs that inhibit the IL-1 receptor may be beneficial in the management of COVID-19. Anakinra has good bioavailability after subcutaneous injection and a half-life of up to 6 hours. CLINICAL TRIALS: The SAVE-MORE, double-blind, randomized controlled trial, phase 3 evaluated the efficacy and safety of anakinra. Anakinra 100 mg was given subcutaneously daily for up to 10 days in patients with moderate and severe COVID-19 and plasma suPAR ≥6 ng/mL. Anakinra group had a 50.4% fully recovered with no viral RNA detected on day 28 versus 26.5% for placebo, and more than 50% of relative decrease in mortality. A significantly decreased risk of worse clinical outcome was observed. THERAPEUTIC ADVANCE: COVID-19 causes global pandemic and a serious viral disease. There are limited therapy options to combat this deadly disease. Anakinra is an IL-1 receptor antagonist and shown to be effective for the treatment of COVID-19 in some trials but not others. Anakinra, the first in this class, seems to have a mix result for the treatment of COVID-19.

Tirzepatide: A Dual Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 Agonist for the Management of Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes is a chronic disease that can lead to many complications, and controlling glucose balance is essential. Incretin hormones are produced in the gut and are essential to maintaining glucose homeostasis. Their effects range from increasing insulin synthesis, insulin secretion, and glucose sensing and decreasing glucagon secretion to promote satiety and suppressing appetite. Tirzepatide is a first in class dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP) analog approved for the management of adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise. PHARMACODYNAMICS AND PHARMACOKINETICS: Tirzepatide is a synthetic chemical structure based on the GIP sequence and consists of 39 amino acid peptides. Tirzepatide increases insulin secretion, reduces glucagon release in a glucose-dependent manner, decreases fasting and postprandial glucose levels, promotes satiety, decreases body weight, and delays gastric emptying. Pharmacodynamics and pharmacokinetics properties of tirzepatide were similar in patients with kidney and hepatic impairment, and its metabolites are excreting through urine and feces. CLINICAL TRIALS: The SURPASS trials are pivotal phase 3 trials assessing the efficacy and safety of tirzepatide as monotherapy and as an add-on to different antihyperglycemic drugs for the management of T2DM. Tirzepatide consistently showed reductions in HbA1c, as well as benefits with weight loss, with common adverse events reported related to gastrointestinal issues. THERAPEUTIC ADVANCE: Tirzepatide is a novel first in class dual GIP and glucagon-like peptide-1 agonist that improves overall glycemic control as an adjunct to diet and exercise. It has the potential benefits in other therapeutic areas such as obesity.

Conventional Fossil Fuel Extraction, Associated Biogeochemical Processes, and Topography Influence Methane Groundwater Concentrations in Appalachia.

The production of fossil fuels, including oil, gas, and coal, retains a dominant share in US energy production and serves as a major anthropogenic source of methane, a greenhouse gas with a high warming potential. In addition to directly emitting methane into the air, fossil fuel production can release methane into groundwater, and that methane may eventually reach the atmosphere. In this study, we collected 311 water samples from an unconventional oil and gas (UOG) production region in Pennsylvania and an oil and gas (O&G) and coal production region across Ohio and West Virginia. Methane concentration was negatively correlated to distance to the nearest O&G well in the second region, but such a correlation was shown to be driven by topography as a confounding variable. Furthermore, sulfate concentration was negatively correlated with methane concentration and with distance to coal mining in the second region, and these correlations were robust even when considering topography. We hypothesized that coal mining enriched sulfate in groundwater, which in turn inhibited methanogenesis and enhanced microbial methane oxidation. Thus, this study highlights the complex interplay of multiple factors in shaping groundwater methane concentrations, including biogeochemical conversion, topography, and conventional fossil extraction.

Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury: A Systematic Review & Meta-Analysis of Preclinical Studies.

Perinatal brain injury is a major contributor to long-term adverse neurodevelopment. There is mounting preclinical evidence for use of umbilical cord blood (UCB)-derived cell therapy as potential treatment. To systematically review and analyse effects of UCB-derived cell therapy on brain outcomes in preclinical models of perinatal brain injury. MEDLINE and Embase databases were searched for relevant studies. Brain injury outcomes were extracted for meta-analysis to calculate standard mean difference (SMD) with 95% confidence interval (CI), using an inverse variance, random effects model. Outcomes were separated based on grey matter (GM) and white matter (WM) regions where applicable. Risk of bias was assessed using SYRCLE, and GRADE was used to summarise certainty of evidence. Fifty-five eligible studies were included (7 large, 48 small animal models). UCB-derived cell therapy significantly improved outcomes across multiple domains, including decreased infarct size (SMD 0.53; 95% CI (0.32, 0.74), p < 0.00001), apoptosis (WM, SMD 1.59; 95%CI (0.86, 2.32), p < 0.0001), astrogliosis (GM, SMD 0.56; 95% CI (0.12, 1.01), p = 0.01), microglial activation (WM, SMD 1.03; 95% CI (0.40, 1.66), p = 0.001), neuroinflammation (TNF-α, SMD 0.84; 95%CI (0.44, 1.25), p < 0.0001); as well as improved neuron number (SMD 0.86; 95% CI (0.39, 1.33), p = 0.0003), oligodendrocyte number (GM, SMD 3.35; 95 %CI (1.00, 5.69), p = 0.005) and motor function (cylinder test, SMD 0.49; 95 %CI (0.23, 0.76), p = 0.0003). Risk of bias was determined as serious, and overall certainty of evidence was low. UCB-derived cell therapy is an efficacious treatment in pre-clinical models of perinatal brain injury, however findings are limited by low certainty of evidence.

Exploring the Inner Lens: Examining Oncology Consultants' Use of Competency and Assessment Frameworks in Clinical Teaching Settings.

Medical education in oncology has adopted a competency-based medical education (CBME) approach in Canada. Oncologist competencies are arranged within assessment frameworks, but it is unknown whether oncologists routinely use assessment frameworks when determining what to teach oncology trainees. Understanding oncologists' actual approaches to assessment and teaching as a form of enacted CBME could inform and focus faculty development efforts. Using a participatory action research approach, oncology faculty were interviewed regarding their teaching practices and use of assessment frameworks. Faculty suggestions regarding challenges in setting teaching goals and completing assessment within the CBME paradigm were solicited. Furthermore, teaching objectives developed by faculty in-house were assessed regarding the domains of competence targeted. Thirty-one of the 40 faculty members in the Department of Oncology, Western University, agreed to participate. Trainee factors (training level, areas of interest), faculty personal values and experience, the teaching setting, and some components of frameworks (medical expert, communicator, advocate, and professional) were articulated as determinants of teaching goals. Of the 1117 in-house objectives reviewed, 76% focused on the medical role. Faculty held widely disparate views on assessment framework features which would enable teaching and assessment. Oncology faculty members used a multifaceted approach to determine what to teach trainees. This approach contains elements both of the conventional apprenticeship models under which many faculty members themselves were trained and of the CBME paradigm. Future research should focus on exploring ways to resolve the tension between established individual teaching approaches and nationally standardized competency frameworks which are being implemented.

The Role of Iron-Based Phosphate Binder in the Treatment of Hyperphosphatemia.

Hyperphosphatemia is a well-known complication of kidney disease. Phosphate binders are a mainstay treatment, but despite the existence of several phosphate binders, there is no one best approach to manage hyperphosphatemia. Phosphate binders are calcium-based, non-calcium- based, and others. While calcium-based phosphate binders are used frequently, they may cause hypercalcemia. Conversely, lanthanum carbonate and sevelamer were not linked to hypercalcemia but are costlier. The most recently developed class of phosphate binders is the ironbased ferric citrate and sucroferric oxyhydroxide. These have an important role in controlling phosphate levels due to their ability to lower the phosphate while concurrently providing iron sources. This review provides pharmacological profiles of different phosphate binders and their clinical usages, and further elaborates on their place in hyperphosphatemia management.

Proton Pump Inhibitors and Kidney Disease: An Intertwined Relationship.

Many patients with kidney disease are taking proton pump inhibitors (PPIs) for various gastrointestinal conditions. There are concerns about inappropriate usage of PPIs with unknown consequences, which include worsening kidney function. PPI use has been associated with kidney damage; however, a clear etiology of the association is uncertain. Potential mechanisms theorized for PPI-induced kidney damage include hypersensitivity, hypomagnesemia, gut microbiota alterations, uremic toxins, gastrointestinal hormones, and oxidative stress. Patients with kidney disease who are taking long-term PPI therapy require close monitoring for any signs and symptoms of kidney disease. Improper use of PPIs should also be reassessed and de-prescribed as indicated.

Cross-sectional survey of Australian and New Zealand clinical staff to explore attitudes regarding medication prescription and administration during neonatal emergencies.

AIM: To survey Australasian neonatal medical and nursing staff to determine confidence regarding medication use, prior experience with medication errors and common resources utilised in neonatal emergencies. METHODS: Data were collected through a cross-sectional online survey distributed to clinical staff affiliated with the Australian and New Zealand Neonatal Network. Information collected included: demographics, confidence in medication use, medication errors and resources used to assist with medication administration. Outcomes were compared between medical staff and nursing staff, and between clinical staff with differing levels of clinical experience (<5 years, 5-10 years and >10 years). RESULTS: Respondents (n = 133) were most confident in calculating medication doses (89%, n = 119), but least confident in prescribing medication (50%, n = 67). Nurses were more likely to be confident than doctors with respect to appropriately diluting and drawing up medication (88% nurses vs. 28% doctors, P < 0.0001), and administering intravenous medications to critically ill neonates (97% nurses vs. 82% doctors, P < 0.01). Over half of respondents reported being personally involved in a medication error in the last 12 months: 33% had been involved in an error related to delayed administration, 18% related to incorrect documentation and 17% related to an incorrect dose. Free-text responses highlighted issues relating to adrenaline (epinephrine) administration and difficulties with equipment (syringe drivers and/or infusion pumps). CONCLUSIONS: Medication errors in neonatal emergencies are common. Strategies to reduce such errors should be implemented in settings where neonates may require emergency care or resuscitation.

DART: diagnostic-CT-enabled planning: a randomized trial in palliative radiation therapy (study protocol).

BACKGROUND: Palliative radiotherapy (PRT) is an effective treatment for managing symptoms of advanced cancer. At least half of all radiation treatments are delivered with palliative intent, aimed at relieving symptoms, such as pain or shortness of breath. Symptomatic patients must receive PRT quickly, therefore expeditious treatment planning is essential. Standard radiation planning requires a dedicated CT scan acquired at the cancer centre, called a 'CT simulation', which facilitates treatment planning (i.e. tumor delineation, placement of radiation beams and dose calculation). However, the CT simulation process creates a bottleneck and often leads to delays in starting treatment. Other researchers have indicated that CT simulation can be replaced by the use of standard diagnostic CT scans for target delineation and planning, which are normally acquired through the radiology department as part of standard patient workup. The goals of this feasibility study are to assess the efficacy, acceptability and scalability of diagnostic-CT-enabled planning, compared to conventional CT simulation planning, for patients receiving PRT to bone, soft tissue and lung disease. METHODS: This is a randomized, phase II study, with 33 PRT patients to be randomized in a 1:2 ratio between conventional CT simulation (Arm 1), and the diagnostic CT enabled planning workflow (Arm 2). Patients will be stratified by treatment target volume (bone and soft tissue metastasis vs. primary or metastatic intrathoracic disease targets). The primary endpoint is the amount of time the patient spends at the cancer centre. Secondary endpoints include efficacy (rate of plan deliverability and rate of plan acceptability on blinded dose distribution review), stakeholder acceptability (based on patient and clinician perception of acceptability questionnaires) and scalability. DISCUSSION: This study will investigate the efficacy, acceptability and scalability of a "sim-free" PRT pathway compared to conventional CT simulation. The workflow may provide opportunity for resource optimization by using pre-existing diagnostic imaging and requires minimal investment due to its similarity to current PRT models. It also offers potential benefit to patients by eliminating an imaging procedure, reducing the amount of time spent at the cancer centre, and expediting time to treatment. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05233904. Date of registration: February 10, 2022; current version: 1.4 on April 29, 2022.

Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy.

BACKGROUND: Patients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease. METHODS: Up to 48 patients with polymetastatic cancer (> 10 sites) will be enrolled on this phase I, modified 3 + 3 design trial. Eligible patients will have exhausted (or refused) standard systemic therapy options. SABR will be delivered as an escalating number of weekly fractions of 6 Gy, starting at 6 Gy × 2 weekly fractions (dose level 1). The highest dose level (dose level 4) will be 6 Gy × 5 weekly fractions. Feasibility and safety of SABR will be evaluated 6 weeks following treatment using a composite endpoint of successfully completing treatment as well as toxicity outcomes. DISCUSSION: This study will be the first to explore delivering SABR in patients with polymetastatic disease. SABR will be planned using the guiding principles of: strict adherence to dose constraints, minimization of treatment burden, and minimization of toxicity. As this represents a novel use of radiotherapy, our phase I study will allow for careful selection of the MTD for exploration in future studies. TRIAL REGISTRATION: This trial was prospectively registered in ClinicalTrials.gov as NCT04530513 on August 28, 2020.

Diphenhydramine Use in End-Stage Kidney Disease.

BACKGROUND: Diphenhydramine is commonly used in patients with kidney disease and end-stage kidney disease (ESKD) for sleep, allergic reactions, itching, and dialysis treatment related complications, and misuse associated with diphenhydramine is also reported. Diphenhydramine's pharmacokinetics property is reviewed and discussed. AREAS OF UNCERTAINTY: Diphenhydramine is highly bound to albumin. The safety profile and dosing information of diphenhydramine use in ESKD population is lacking. The purpose of this study is to provide an overview of diphenhydramine pharmacokinetic properties and evaluate diphenhydramine use in ESKD population. DATA SOURCES: A literature search was conducted during Spring 2019 using PubMed, CINAHL, Cochrane, Ovid, and Google Scholar. Search terms used include "diphenhydramine abuse," "diphenhydramine dialysis," and "diphenhydramine kidney disease." RESULTS: There is lack of studies available for diphenhydramine, kidney disease, and dialysis. There were case reports of diphenhydramine abuse and toxicity due to overdose. Diphenhydramine is highly bound to protein that limits its ability to dialyze, and therefore, it may predispose to side effects. Information on diphenhydramine used in the dialysis population is scarce, and dosing toxicity is unknown. CONCLUSIONS: The data available for use of diphenhydramine in ESKD and dialysis are limited. Clinicians should use caution with the use of diphenhydramine in this population.

Role of Potassium-Sparing Diuretics in the Management of Hypokalemia in Peritoneal Dialysis.

BACKGROUND: Patients with kidney disease are at a higher risk of experiencing potassium imbalance. The kidney plays an important role in maintaining potassium homeostasis. A common dyskalemia that peritoneal dialysis (PD) patients experience is hypokalemia. AREAS OF UNCERTAINTY: Potassium-sparing diuretics such as spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Owing to its potassium-sparing effects, it may correct hypokalemia that PD patients experience. The proper usage of potassium-sparing diuretics in PD patients and data on the efficacy and safety are being explored. DATA SOURCES: Four relevant trials were identified. One randomized double-blind placebo-controlled cross-over study (n = 20), one interventional study without the control group (n = 20), one retrospective single-center chart review (n = 53), and one cross-sectional review (n = 75) trial. The randomized controlled trial did not note a statistically significant change in K levels (P > 0.05); the other 3 trials observed an increase in potassium levels in the potassium-sparing diuretics groups, but trials contained small participants and inadequate statistic rigor. THERAPEUTIC OPINIONS: The role of potassium-sparing diuretics use for hypokalemia management in PD patients remains unclear.

Mannitol Role in the Management of Intradialytic Hypotension.

BACKGROUND, AREAS OF UNCERTAINTY: Intradialytic hypotension (IDH) is one of the most common complications of the hemodialysis procedure. Although there are no clear-cut answers as to the best strategy on the management of IDH, data suggest that the administration of osmotically active drugs may decrease the occurrence of blood pressure decline during dialysis. The use of mannitol for IDH management in hemodialysis patients is scarce. This article highlights the use and benefits of mannitol and to assess the role of mannitol role in the management of IDH. DATA SOURCES: Primary literature identified through MEDLINE/PubMed database and Google Scholar with no restrictions. Relevant and current literatures related to mannitol and IDH were used. RESULTS AND DATA SYNTHESIS: Multiple studies have shown the benefits of mannitol for the management of IDH. Because of its oncotic effect, mannitol increases plasma osmolality to maintain adequate blood pressure and prevent the occurrence of IDH. Two observational studies and several reports were identified as being the most recent and applicable to clinical practice. Studies and data on the use of mannitol in IDH are scarce or outdated. The 2 studies used in this article conclude that mannitol carries benefits for both the adult and pediatric population. However, additional research in the future will be needed to confirm the evidence for various age groups. These 2 observational trials were also very small in number, and any future studies conducted should have a longer duration and larger population size. Although lacking data, these studies will suffice in introducing the benefits of mannitol in IDH. CONCLUSIONS: Mannitol may be considered for the management of IDH; however, additional studies are required to evaluate the long-term risk and benefits associated with mannitol, as it carries a risk of accumulation in the body.

Loop Diuretics: Clinical Application Information for Nephrology Nurses and Practitioners.

Loop diuretic medications work by inhibiting sodium reabsorption in the renal tubules. The net effect is increasing in urinary sodium and water excretion. Loop diuretics are routinely used for many clinical indications, and nephrology practitioners are well informed in the management of their use in daily practice. This article highlights key information on the most commonly used loop diuretics (e.g., furosemide and torsemide) and provides important clinical features related to pharmacokinetics properties, dosing consideration, route of administration, side effects, and other considerations for practitioners.

Rescue bevacizumab following symptomatic pseudoprogression of a tectal glioma post-radiotherapy: a case report and review of the literature.

PURPOSE: Radiation-induced pseudoprogression is a subacute clinical entity that is distinct from radiation necrosis and mimics tumor progression. Bevacizumab is a well-described treatment option for radiation necrosis, but its role in pseudoprogression is not clearly defined. METHODS: We report a case of radiation-induced pseudoprogression rescued with bevacizumab in a 20-year-old man with a biopsy-proven low-grade astrocytoma of the tectum. A review of the literature was also conducted specific to bevacizumab as a treatment for symptomatic pseudoprogression after radiotherapy for CNS tumors. RESULTS: This patient was treated with definitive intensity modulated stereotactic radiotherapy at a total dose of 54 Gy delivered in 30 daily fractions. Six weeks after radiotherapy the patient developed progressive headache, weakness and a documented deterioration in vision, which was accompanied by worsening of radiographic findings. A diagnosis of pseudoprogression was made and after limited benefit from a trial of dexamethasone, four cycles of bevacizumab were administered which resulted in rapid clinical and radiographic improvement. CONCLUSIONS: Our findings support the potential use of bevacizumab as a rescue agent for symptomatic pseudoprogression.