Response to oral iron therapy in children with anemia of chronic kidney disease.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD) and oral iron is recommended as initial therapy. However, response to iron therapy in children with non-dialysis CKD has not been formally assessed. METHODS: We reviewed medical records of pediatric patients with stages II-IV CKD followed in two New York metropolitan area medical centers between 2010 and 2020 and identified subjects who received oral iron therapy. Response to therapy at follow-up visits was assessed by improvement of hemoglobin, resolution of anemia by the 2012 KDIGO definition, and changes in iron status. Potential predictors of response were examined using regression analyses (adjusted for age, sex, eGFR, and center). RESULTS: Study criteria were met by 65 children (median age 12 years, 35 males) with a median time between visits of 81 days. Median eGFR was 44 mL/min/1.73 m2, and 40.7% had glomerular CKD etiology. Following iron therapy, hemoglobin improved from 10.2 to 10.8 g/dL (p < 0.001), hematocrit from 31.3 to 32.8% (p < 0.001), serum iron from 49 to 66 mcg/dL (p < 0.001), and transferrin saturation from 16 to 21.4% (p < 0.001). There was no significant change in serum ferritin (55.0 to 44.9 ng/mL). Anemia (defined according to KDIGO) resolved in 29.3% of children. No improvement in hemoglobin/hematocrit was seen in 35% of children, and no transferrin saturation improvement in 26.9%. There was no correlation between changes in hemoglobin and changes in transferrin saturation/serum iron, but there was an inverse correlation between changes in hemoglobin and changes in ferritin. The severity of anemia and alkaline phosphatase at baseline inversely correlated with treatment response. CONCLUSIONS: Anemia was resistant to 3 months of oral iron therapy in ~ 30% of children with CKD. Children with more severe anemia at baseline had better treatment response, calling for additional studies to refine approaches to iron therapy in children with anemia of CKD and to identify additional predictors of treatment response.

Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy.

Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of combined therapy. Methods: TTFields arrays were attached to a warm saline water bath and salt was added until the TTFields generator reached the maximal 2000 mA peak-to-peak current. A ball cube phantom containing 2 orthogonal films surrounded by fiducials was placed in the water phantom, CT scanned, and a radiation treatment plan with 58 isocentric beams was created using a 3 cm circular collimator. Fiducial tracking was used to deliver radiation, the films were scanned, and end-to-end targeting error was measured with vendor-supplied software. In addition, radiation effects on electric fields generated by the TTFields system were assessed by examining logfiles generated from the field generator. Results: With TTFields arrays in place and powered on, the robotic radiosurgery system achieved a final targeting result of 0.47 mm, which was well within the submillimeter specification. No discernible effects on TTFields current output beyond 0.3% were observed in the logfiles when the radiation beam pulsed on and off. Conclusion: A robotic radiosurgery system was used to verify that radiation targeting was not adversely affected when the TTFields arrays were in place and the TTFields delivery device was powered on. In addition, this study verified that radiation delivered simultaneously with TTFields did not interfere with the generation of the electric fields.

Estimating the tolerance of brachial plexus to hypofractionated stereotactic body radiotherapy: a modelling-based approach from clinical experience.

BACKGROUND: Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor. METHODS: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting. RESULTS: This analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3-4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3-4 fractions. CONCLUSIONS: This analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

COVID-19 in Patients with CKD in New York City.

BACKGROUND: COVID-19 has affected millions of people, and several chronic medical conditions appear to increase the risk of severe COVID-19. However, our understanding of COVID-19 outcomes in patients with CKD remains limited. METHODS: This was a retrospective cohort study of patients with and without CKD consecutively admitted with COVID-19 to three affiliated hospitals in New York City. Pre-COVID-19 CKD diagnoses were identified by billing codes and verified by manual chart review. In-hospital mortality was compared between patients with and without underlying CKD. Logistic regression was used to adjust this analysis for confounders and to identify patient characteristics associated with mortality. RESULTS: We identified 280 patients with CKD, and 4098 patients without CKD hospitalized with COVID-19. The median age of the CKD group was 75 (65-84) years, and age of the non-CKD group 62 (48-75) years. Baseline (pre-COVID-19) serum creatinine in patients with CKD was 1.5 (1.2-2.2) mg/dl. In-hospital mortality was 30% in patients with CKD versus 20% in patients without CKD (P<0.001). The risk of in-hospital death in patients with CKD remained higher than in patients without CKD after adjustment for comorbidities (hypertension, diabetes mellitus, asthma, and chronic obstructive pulmonary disease), adjusted OR 1.4 (95% CI,1.1 to 1.9), P=0.01. When stratified by age, elderly patients with CKD (age >70 years) had higher mortality than their age-matched control patients without CKD. In patients with CKD, factors associated with in-hospital mortality were age (adjusted OR, 1.09 [95% CI, 1.06 to 1.12]), P<0.001, baseline and admission serum phosphorus (adjusted OR, 1.5 [95% CI, 1.03 to 2.1], P=0.03 and 1.4 [95% CI, 1.1 to 1.7], P=0.001), serum creatinine on admission >0.3 mg/dl above the baseline (adjusted OR 2.6 [95% CI, 1.2 to 5.4]P=0.01), and diagnosis of acute on chronic kidney injury during hospitalization (adjusted OR 4.6 [95% CI, 2.3 to 8.9], P<0.001). CONCLUSIONS: CKD is an independent risk factor for COVID-19-associated in-hospital mortality in elderly patients. Acute-on-chronic kidney injury increases the odds of in-hospital mortality in patients with CKD hospitalized with COVID-19.

Tumor necrosis factor-alpha is associated with mineral bone disorder and growth impairment in children with chronic kidney disease.

BACKGROUND: Mineral and bone disorder (MBD) and growth impairment are common complications of pediatric chronic kidney disease (CKD). Chronic inflammation detrimentally affects bone health and statural growth in non-CKD settings, but the impact of inflammation on CKD-MBD and growth in pediatric CKD remains poorly understood. This study assessed associations between inflammatory cytokines with biomarkers of CKD-MBD and statural growth in pediatric CKD. METHODS: This is a cross-sectional study of children with predialysis CKD stages II-V. Cytokines (IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, interferon-γ), bone alkaline phosphatase (BAP), and procollagen type 1 N-terminal propeptide (P1NP) were measured at the same time as standard CKD-MBD biomarkers. Associations between cytokines, CKD-MBD biomarkers, and height z-score were assessed using linear regression analysis. RESULTS: Among 63 children, 52.4% had stage 3 CKD, 76.2% non-glomerular CKD etiology, and 21% short stature. TNF-α was the only cytokine associated with parathyroid hormone (PTH) independent of glomerular filtration rate. After stratification by low, medium, and high TNF-α tertiles, significant differences in PTH, serum phosphorus, alkaline phosphatase, BAP, P1NP, and height z-score were found. In a multivariate analysis, TNF-α positively associated with phosphorus, PTH, and alkaline phosphatase and inversely associated with height z-score, independent of kidney function, age, sex, and active vitamin D analogue use. CONCLUSIONS: TNF-α is positively associated with biomarkers of CKD-MBD and inversely associated with height z-score, indicating that inflammation likely contributes to the development of CKD-MBD and growth impairment in pediatric CKD. Prospective studies to definitively assess causative effects of inflammation on bone health and growth in children with CKD are warranted.

Thymosin alpha 1: A comprehensive review of the literature.

Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.

Trends in Hospitalization and Inpatient Outcomes of Behçet's Disease: A Nationwide Inpatient Sample Study.

Objective After an extensive review of the literature, we discovered that no study had addressed trends in hospitalization for people with Behçet's disease (BD). Hence, in this study, we explore multiple variables in patients with BD in the US for the year 2016. Methods We analyzed the data relating to hospitalized patients for the year 2016 using the National Inpatient Sample (NIS) database with a listed discharge diagnosis of BD based on the International Classification of Diseases, 10th Revision (ICD-10) diagnosis code M35.2. The mean age in years, alive discharges, lumbar puncture procedures, type of hospital, the Charlson Comorbidity Index (CCI), comorbidities, mean length of stay (LOS) and factors affecting it, and total cost and charges for the admissions were analyzed. A p-value of <.05 was considered statistically significant. Results A total of 2,605 discharges with the diagnoses of BD were identified among 35.7 million overall discharges in 2016. Among patients hospitalized with underlying BD, the majority were white and female. The mean hospital LOS was 5.57 ± 0.37 days, which is higher than in the general population and statistically significant (5.57 days vs 4.62 days; p: 0.009). Mean LOS in patients undergoing lumbar puncture was 8.54 ± 2.91 days. Patients with BD had lower medical comorbidity burden (16.9% with a CCI of ≥3) vs the general population (24.67% with a CCI of ≥3) (p: 0.00). Medical comorbidities with a statistically significant difference in their prevalence in the two groups were renal disease, dementia, peptic ulcer disease, heart failure, rheumatologic disorders, malignancy, and dyslipidemia. Conclusion Increased awareness about this rare condition in an inpatient setting will help in the early identification of the disease and associated complications. This will help caregivers to provide quality care in a timely manner, thereby decreasing the morbidity, mortality, LOS, and hospital costs associated with BD.

Pleomorphic Pulmonary Manifestations of IgG4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder which has been first reported in 2001 by Hamano and colleagues in a patient with autoimmune sclerosing pancreatitis. Almost every organ in the human body can be affected by IgG4-RD from infiltration with IgG4-positive plasma cells. Involvement of lungs with IgG4 is reported previously, but still, there is no clear picture of the pathophysiology behind lung involvement. Here, we are presenting a patient who has IgG4-RD presenting as pseudotumor of the lungs.

An Overlapping Case of IgG4-Related Disease and Systemic Lupus Erythematosus.

We are reporting a case of a 63-year-old Chinese female who presented to the rheumatology clinic with positive antinuclear antibody and unintentional weight loss along with lymphadenopathy. Further workup revealed eosinophilia, elevated anti-double stranded DNA, serum protein, and serum IgG4 (immunoglobulin G4). The patient was diagnosed with systemic lupus erythematosus. Due to the raised IgG4 level along with eosinophilia and diffuse lymphadenopathy, IgG4-related systemic disease was suspected. It was confirmed with IgG4 staining on lymph node biopsy. Our case is presenting the fact that systemic lupus erythematosus and IgG4-related disease can be present in the same patient with multiple overlapping features making accurate diagnosis challenging.

Osteitis Condensans Ilii: An Uncommon Cause of Back Pain.

Osteitis condensans ilii (OCI) is a benign cause of low back pain, which is self-limiting. Though OCI is still an orthopedic mystery, mechanical stress across the joint is a significant triggering factor according to the prevailing theories. The traditional location of involvement is around the ileum, and can be misinterpreted as sacroiliac joint (SIJ) involvement. We present a case of bilateral OCI with sclerosis based on radiological finding in a 30-year-old female presenting with chronic low back pain.

Role of PCDH 1 Gene in the Development of Childhood Asthma and Other Related Phenotypes: A Literature Review.

The asthma gene PCDH 1, encoding protocadherin-1, is a cellular adhesion molecule which plays an important role in epithelial barrier formation and repair. PCDH 1 is a novel susceptible gene not only in childhood asthma but also in eczema and other atopic phenotypes. In this article, we reviewed relevant articles from PubMed, Google Scholar, Science Direct and included all available significant pieces of information about the PCDH 1 association with asthma and other atopic or non-atopic phenotypes. It is very interesting that cigarette smoking can induce changes in PCDH 1 expression but how the changes in PCDH 1 induce asthma is still not clear. PCDH 1 gene polymorphism also sometimes plays role in asthma and bronchial hyperresponsiveness (BHR) pathogenesis as well as in allergic dermatitis.

Immunotherapy in Advanced Non-small Cell Lung Cancer Patients: Ushering Chemotherapy Through the Checkpoint Inhibitors?

New ways of exploiting the immune system for cancer treatment have been tested for decades with moderate outcomes. Based on previous immunotherapy knowledge, agents targeting immune checkpoints seem to be remarkably effective in a wide range of tumors. Immune checkpoint inhibitors in metastatic non-small cell lung cancer (NSCLC) provide longlasting responses in specific patients. Nevertheless, with overall response rates ≤ 20%, combinational protocols for various patient subgroups are needed. A good partner treatment to immunotherapy could be chemotherapy, as it successfully modulates the immune response either by controlling or enhancing the antitumor immune activity. Primary research provides promising results in metastatic NSCLC patients using this approach, but further large-scale trials are needed. The implementation of immunotherapy in nonmetastatic cases is also appealing. We review the potential clinical benefits of immunotherapy alone or in concert with chemotherapy in NSCLC.

The Neurocognitive Effects of Ghrelin-induced Signaling on the Hippocampus: A Promising Approach to Alzheimer's Disease.

The communication between the gastrointestinal tract and the central nervous system (CNS) allows for certain peptide hormones to influence neurocognitive function. Ghrelin, also known as the 'hunger hormone,' has the unique ability to enter the CNS and interact with the growth hormone secretagogue receptor (GHS-R) within the hippocampus. Upon interaction with ghrelin, a conformational change in the receptor causes an increase in transcription factors to foster a wide array of physiologic changes in response to caloric deprivation. With the GHS-R in a relatively high concentration within the hippocampus, ghrelin can promote memory, spatial, learning, and behavioral effects. In fact, ghrelin appears to also have a neuroprotective and neuromodulatory response once active within the hippocampal dentate gyrus. Through the GHS-R, higher levels of ghrelin may alter cognitive circuitry and offer a possible link to the treatment of some pathologies implicated in neurological dysfunction. Alzheimer's disease (AD) is already becoming a significant target for ghrelin neuroreceptor therapy. In such experimental models, ghrelin has been shown to combat this degenerative process by eliciting an ameliorative and regenerative response. Although trials and research are still ongoing, further studies are indicated as early research into this adjuvant therapy is promising. The research team explored the effects of ghrelin by reviewing the downstream signaling modifications of ghrelin's interaction with a specific CNS receptor, the GHS-R. Although the GHS-R is found in multiple locations within the CNS, the team investigated the role of the GHS-R within the hippocampus to focus solely on the neurocognitive implications of ghrelin. The team noted which signaling pathways in particular that ghrelin initiated and used this approach to determine whether ghrelin may have any therapeutic benefits. The team explored the possible therapeutic indications of ghrelin by looking at studies conducted with a specific neurodegenerative disease known to target the hippocampus.

Fok-I, Bsm-I, and Taq-I Variants of Vitamin D Receptor Polymorphism in the Development of Autism Spectrum Disorder: A Literature Review.

The role of vitamin D in the development of autism spectrum disorder (ASD) is of intensified interest in medical science in recent years. Vitamin D has a significant role in neurogenesis, neuroprotection, and neurodevelopment. Due to the close association of vitamin D with the brain, it has been found that in the pathophysiology of several neuropsychiatric disorders vitamin D receptor (VDR) polymorphism plays a significant role. In this review article, we looked for a relation between VDR polymorphism and ASD. We systemically reviewed all the potential articles on the relation between VDR polymorphism and ASD. We found that several VDR variants FokI, BsmI, and TaqI polymorphisms are related to ASD. Even paternal VDR polymorphism can be a causative factor for ASD in the offspring. The relation between FokI (ff) genotype polymorphism and increased level of serum 1,25(OH)D3 in ASD patients is a very significant finding. Variation of ASD-related genotypes in different ethnic population raises a big question on whether the environmental factors also can do changes in human genotypes leading to ASD.

Pulmonary Involvement in Crohn's Disease: A Rare Case Report.

Crohn's disease (CD) is a granulomatous inflammatory disease that can involve any part of the gastrointestinal tract, from mouth to anus. In most cases, it remits and relapses in the terminal ileum, requiring treatment via steroid boluses. In rare cases, however, CD can involve the pulmonary system presenting as dyspnea on exertion and dry cough. We present a case of a 38-year-old man who developed shortness of breath, cough, and wheezing for one month after a colectomy procedure due to recurrent toxic megacolon. He recovered and tolerated extubation successfully and was prescribed mesalamine as maintenance therapy for CD. His pulmonary symptoms after the colectomy, along with his imaging and pulmonary function tests, indicated pulmonary involvement in the lungs as a progression of the primary inflammatory bowel disease. After confirming this diagnosis, he was treated with oral high-dose steroids after successful diagnosis, and the patient's symptoms improved dramatically. This case highlights often overlooked CD bronchopulmonary involvement in the postoperative period.