Sarcopenia, adiposity and large discordance between cystatin C and creatinine-based estimated glomerular filtration rate in patients with cancer.

BACKGROUND: Creatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While cystatin C-based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition defined by computed tomography (CT) scans and discordance between creatinine, eGFRCRE and eGFRCYS in adult patients with cancer. METHODS: This study is a cross-sectional study of consecutive adults with cancer with an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010 and January 2022. Muscle and adipose tissue cross-sectional areas were measured at the level of the third lumbar vertebral body using a validated deep-learning pipeline. CT-defined sarcopenia was defined using independent sex-specific cut-offs for skeletal muscle index (<39 cm2/m2 for women and <55 cm2/m2 for men). High adiposity was defined as the highest sex-specific quartile of the total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discordance, defined by eGFRCYS > 30% lower than eGFRCRE; the secondary outcome was eGFRCYS > 50% lower than eGFRCRE. The odds of eGFR discordance were estimated using multivariable logistic regression modelling. Unadjusted spline regression was used to evaluate the relationship between skeletal muscle index and the difference between eGFRCYS and eGFRCRE. RESULTS: Of the 545 included patients (mean age 63 ± 14 years, 300 [55%] females, 440 [80.7%] non-Hispanic white), 320 (58.7%) met the criteria for CT-defined sarcopenia, and 136 (25%) had high adiposity. A total of 259 patients (48%) had >30% eGFR discordance, and 122 (22.4%) had >50% eGFR discordance. After adjustment for potential confounders, CT-defined sarcopenia and high adiposity were both associated with >30% eGFR discordance (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12-3.24; aOR 2.01, 95% CI 1.15-3.52, respectively) and >50% eGFR discordance (aOR 2.34, 95% CI 1.21-4.51; aOR 2.23, 95% CI 1.19-4.17, respectively). A spline model demonstrated that as skeletal muscle index decreases, the predicted difference between eGFRCRE and eGFRCYS widens considerably. CONCLUSIONS: CT-defined sarcopenia and high adiposity are both independently associated with large eGFR discordance. Incorporating valuable information from body composition analysis derived from CT scans performed as a part of routine cancer care can impact the interpretation of GFR estimates.

Adverse kidney outcomes of CDK 4/6 inhibitors for metastatic breast cancer.

Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly improved overall and progression free survival of patients with metastatic breast cancer, but their effect on short and long-term kidney function is unknown. We found that early, mild estimated glomerular filtration rate (eGFR) decline was common in patients treated with CDK 4/6 inhibitors; however, severe kidney injury is rare and long-term eGFR decline is uncommon.

Effect of remdesivir on adverse kidney outcomes in hospitalized patients with COVID-19 and impaired kidney function.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for mortality from COVID-19. Remdesivir has been shown to shorten time to recovery in patients with severe COVID-19. However, exclusion of patients with severe kidney function impairment in clinical trials has led to concerns about kidney safety of remdesivir in patients with pre-existing kidney disease. METHODS: Retrospective propensity score matched cohort study of hospitalized patients with COVID-19 admitted with estimated glomerular filtration rate (eGFR) between 15 - 60 mL/min/1.73m2. Remdesivir-treated patients were 1:1 matched to historical comparators admitted during the first wave of COVID-19 (between March-April 2020) prior to emergency use authorization of remdesivir using propensity scores accounting for factors predicting treatment assignment. Dependent outcomes included in-hospital peak creatinine, incidence of doubling of creatine, rate of kidney replacement therapy initiation and eGFR among surviving patients at day 90. RESULTS: 175 remdesivir-treated patients were 1:1 matched to untreated historical comparators. Mean age was 74.1 (SD 12.8), 56.9% were male, 59% patients were white, and the majority (83.1%) had at least one co-morbidity. There were no statistically significant differences in peak creatinine during hospitalization (2.3mg/dL vs. 2.5 mg/dL, P = 0.34), incidence of doubling of creatinine (10.3% vs. 13.1%, P = 0.48), and rate of kidney replacement therapy initiation (4.6% vs. 6.3%, P = 0.49) in remdesivir-treated patients versus matched untreated historical comparators, respectively. Among surviving patients, there was no difference of the average eGFR at day 90 (54.7 ± 20.0 mL/min/1.73m2 for remdesivir-treated patients vs. 51.7 ± 19.5 mL/min/1.73m2 for untreated comparators, P = 0.41). CONCLUSIONS: Remdesivir use in patients with impaired kidney function (eGFR between 15 - 60 mL/min/1.73m2) who present to the hospital with COVID-19 is not associated with increased risk of adverse kidney outcomes.

Present and future: Infectious tropical travel rashes and the impact of climate change.

In this article, we discuss pertinent cutaneous findings with which patients may present after travel to tropical destinations. We address arthropod-borne infectious diseases such as cutaneous leishmaniasis, Chagas disease, cutaneous larva migrans, and myiasis. We discuss other relevant diseases with cutaneous signs such as monkey pox and severe acute respiratory syndrome coronavirus 2. We provide clinicians with information regarding the background, diagnosis, treatment, and prevention of these tropical rashes. In addition, we address the impact that climate change will have on the temporal and geographic incidence of these rashes. Viral, fungal, and vector-borne diseases have seen a geographic expansion into more northern latitudes. Among these are tick-borne Lyme disease, aquatic snail-related seabather's eruption, and atopic dermatitis. As these diseases spread, we believe that the updated information within this article is significant to the practicing physician in today's warming world.

Cutaneous coronavirus disease 2019 in children: a clinical primer for diagnosis and treatment.

PURPOSE OF REVIEW: This review examines the global literature regarding rashes encountered in children and adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and aims to provide practicing pediatricians with an understanding of the relationship between instances of rashes and coronavirus disease 2019 (COVID-19) in children in order to effectively evaluate and treat patients. RECENT FINDINGS: The true incidence of cutaneous reactions in children infected with SARS-CoV-2 is not known. Children's immune systems differ from those of adults and rashes as a manifestation of immune responses, in turn, differ in morphology and distribution. Rarely, children develop a severe multisystem inflammatory syndrome that has overlapping clinical features with Kawasaki disease. In addition, vaccinations produce rashes similar to natural infections. The rashes associated with COVID-19 vaccination are mild and transient, and should not preclude vaccination. Lastly, children who chronically wear masks are more likely to experience flaring of acne around the nose and mouth ('maskne') and facial conditions such as seborrheic dermatitis. SUMMARY: There are ongoing worldwide registries, clinical and basic science studies to better understand the burden of skin disease and pathophysiology of rashes seen in patients infected with COVID-19. Robust vaccination programs should be encouraged as a way to contain viral spread among children and the greater population.

New science and treatment paradigms for atopic dermatitis.

PURPOSE OF THE REVIEW: The prevalence of atopic dermatitis is increasing in industrialized countries for unclear reasons. One theory centers on reduced exposure to microbes during infancy and childhood. Alterations in the epidermal permeability barrier, place certain patients at risk for the immunological dysfunction seen in atopic dermatitis. This review examines current research pertaining to the epidermal permeability barrier, the cutaneous microbiome, and the immunology of atopic dermatitis. New collaborative research has led to evidence-based management guidelines. RECENT FINDINGS: Increased skin barrier permeability and dysfunction of innate and adaptive immunity cause atopic dermatitis. Genetic and environmental factors leading to decreased filaggrin underlie many cases of atopic dermatitis. Defective epidermal barrier function allows for an increased density of Staphylococcus aureus and a subsequent shift in adaptive immunity to a type 2 immune response. Multiple evaluation and management guidelines have been published based on current available evidence. These guidelines highlight state of the art management of seven main areas: inflammation, infection, irritation, itch, ichthyosis (dry skin), immunological influences, and impeding (comorbid) conditions. SUMMARY: Pediatricians are central to the successful diagnosis and management of atopic dermatitis. Increased basic and clinical research and well published clinical guidelines will lead to improved outcomes for the patients and families affected by this chronic relapsing disorder.

Cutaneous manifestations of systemic viral diseases in neonates: an update.

PURPOSE OF REVIEW: Dermatologic findings may be the first signs of a neonatal viral infection. This review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus, enterovirus, and Zika virus] that present with cutaneous manifestations in the neonate. RECENT FINDINGS: HSV DNA polymerase chain reaction of plasma and cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have expanded utility in assessing prognosis and acyclovir therapeutic efficacy. Maternal antiviral suppressive therapy may alter the clinical appearance of congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella zoster immune globulin, is a US Food and Drug Administration approved form of prophylaxis for varicella. The Centers for Disease Control and Prevention has expanded the period of VariZIG eligibility for preterm infants, a group particularly susceptible to severe varicella infection. For severe neonatal enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an effective therapy. Human Parechovirus type 3, a strain within a newly formed viral genus, has a similar, and potentially underestimated, clinical presentation to enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in the neonate may present with a nonspecific macular and papular rash. As this rash is not specific, obtaining a maternal travel history and, if appropriate, requesting additional diagnostic testing are critical for early diagnosis. SUMMARY: Neonatal rashes may be harmless and transient, whereas others may reflect the presence of a severe systemic illness. Recognizing key cutaneous features of viral-associated rashes may aid in the prompt and accurate diagnosis and treatment of neonatal viral illnesses.

FastPop: a rapid principal component derived method to infer intercontinental ancestry using genetic data.

BACKGROUND: Identifying subpopulations within a study and inferring intercontinental ancestry of the samples are important steps in genome wide association studies. Two software packages are widely used in analysis of substructure: Structure and Eigenstrat. Structure assigns each individual to a population by using a Bayesian method with multiple tuning parameters. It requires considerable computational time when dealing with thousands of samples and lacks the ability to create scores that could be used as covariates. Eigenstrat uses a principal component analysis method to model all sources of sampling variation. However, it does not readily provide information directly relevant to ancestral origin; the eigenvectors generated by Eigenstrat are sample specific and thus cannot be generalized to other individuals. RESULTS: We developed FastPop, an efficient R package that fills the gap between Structure and Eigenstrat. It can: 1, generate PCA scores that identify ancestral origins and can be used for multiple studies; 2, infer ancestry information for data arising from two or more intercontinental origins. We demonstrate the use of FastPop using 2318 SNP markers selected from the genome based on high variability among European, Asian and West African (African) populations. We conducted an analysis of 505 Hapmap samples with European, African or Asian ancestry along with 19661 additional samples of unknown ancestry. The results from FastPop are highly consistent with those obtained by Structure across the 19661 samples we studied. The correlations of the results between FastPop and Structure are 0.99, 0.97 and 0.99 for European, African and Asian ancestry scores, respectively. Compared with Structure, FastPop is more efficient as it finished ancestry inference for 19661 samples in 16 min compared with 21-24 h required by Structure. FastPop also provided scores based on SNP weights so the scores of reference population can be applied to other studies provided the same set of markers are used. We also present application of the method for studying four continental populations (European, Asian, African, and Native American). CONCLUSIONS: We developed an algorithm that can infer ancestries on data involving two or more intercontinental origins. It is efficient for analyzing large datasets. Additionally the PCA derived scores can be applied to multiple data sets to ensure the same ancestry analysis is applied to all studies.

Childhood skin and soft tissue infections: new discoveries and guidelines regarding the management of bacterial soft tissue infections, molluscum contagiosum, and warts.

PURPOSE OF REVIEW: Pediatric skin and soft tissue infections (SSTIs) constitute a significant number of office-based pediatric visits. With SSTIs on the rise, it is not only important to effectively treat the individual, but to do so appropriately and cost-consciously. In this article, we highlight new research related to the treatment of bacterial skin infections, molluscum contagiosum, and cutaneous warts, with the goal of guiding pediatricians in their practice against these common skin conditions. RECENT FINDINGS: Recent data supports the use of topical antibiotics for noncomplicated impetigo. Systemic antibiotics covering gram-positive cocci are recommended for complicated cases of impetigo and deeper nonpurulent SSTIs. Localized purulent bacterial SSTIs can be treated with incision and drainage alone but more systemic involvement warrants treatment with systemic antibiotics covering Staphylococcus aureus species, especially community acquired methicillin-resistant S. aureus. For the treatment of molluscum contagiosum, topical cantharidin has a high satisfaction rate among patients and providers. Potassium hydroxide solution is a potentially effective and cheap form of molluscum contagiosum treatment. Imiquimod, however, has an unfavorable efficacy and safety profile as a therapy for molluscum contagiosum. Regarding warts, high-risk human papilloma virus strains have been detected in cutaneous warts in children. SUMMARY: The high-risk human papilloma virus vaccine may play a role in treating pediatric cutaneous warts in the future, and topical squaric acid dibutylester may effectively treat recalcitrant warts. Finally, both molluscum contagiosum and warts have a high rate of resolution after an extended period of time without any intervention.

Dermal melanocytosis and associated disorders.

PURPOSE OF REVIEW: Dermal melanocytosis is commonly seen in the newborn period and is frequently a concern to parents and providers. Four clinically distinct entities are recognized: nevus of Ota, nevus of Ito, Mongolian spots, and dermal melanocyte hamartoma. This article reviews these disorders, with special emphasis on melanocyte biology and important associated systemic disorders such as rare malignant transformations and inborn errors of metabolism. RECENT FINDINGS: Recent findings have highlighted the increased risk of malignancy in patients with nevus of Ota, especially ocular, central nervous system, and cutaneous tumors. Although rarely seen, cutaneous melanoma occurs in association with nevus of Ito. Extensive, dark, and progressive Mongolian spots may be more likely than isolated lesions to be associated with inborn errors of metabolism, such as Hurler's disease and monosialotetrahexosylganglioside (GM1) gangliosidosis. New laser technology utilizing Q-switched alexandrite lasers has shown promise for the cosmetic improvement of dermal melanocytosis. SUMMARY: While most dermal melanocytosis resolves by the toddler years and does not pose long-term risks to the affected individuals, some patients may have underlying associated conditions that pose significant health concerns. Pediatric care providers must be familiar with these associated conditions and refer to a dermatologist when in doubt, to confirm the diagnosis and determine appropriate follow-up care.

What's new with common, uncommon and rare rashes in childhood.

PURPOSE OF REVIEW: Children with rashes account for many of the outpatient visits to a general pediatrician. As such, pediatricians are often the first to identify and treat these rashes. Establishing an approach to common, uncommon and rare pediatric rashes assists in accurate assessment. This review highlights newly identified clinical patterns and disease severity. RECENT FINDINGS: Group A ß-hemolytic streptococci (GABHS) have been shown to be an important cause of intertrigo and to cause more widespread disease in some instances. Superficial skin infections with GABHS have been associated with strains secreting exfoliating toxins, whereas deeper infections have been associated with superantigen toxins. Hand-foot-and-mouth disease (HFMD) outbreaks have occurred with more virulent strains, causing more widespread disease that may be confused with eczema herpeticum or varicella. Mycoplasma pneumoniae has been shown to be an important cause of common disorders such as urticaria, and less common disorders such as Stevens-Johnson syndrome and Mycoplasma-associated mucositis. Recurrent toxin-mediated erythema is a recently described entity that must be differentiated from Kawasaki disease. SUMMARY: The number of rashes acquired in childhood is vast, requiring the pediatrician to be able to identify worrisome rashes from those with a more benign course. Key clinical signs may assist in clinical diagnosis and treatment.

Cosmeceuticals for children: should you care?

PURPOSE OF REVIEW: Cosmeceuticals are substances that exert physiologic changes to the skin for aesthetic purposes and are popular alternatives to invasive cosmetic procedures for antiaging. Cosmeceuticals are being used on children; yet studies of cosmeceuticals in the pediatric population are limited. RECENT FINDINGS: Cosmeceuticals remain an unrecognized category by the US Food and Drug Administration, and therefore stringent regulatory pathways do not exist to guide research and marketing. To date, no safety and efficacy study exists on cosmeceutical use in pediatric patients. Increasing knowledge of the mechanisms underlying intrinsic and extrinsic skin aging, including reactive oxygen species formation, effects of declining hormones, and ultraviolet radiation, forms the scientific basis for common cosmeceuticals such as retinoids, botanicals such as soy isoflavones, and even moisturizers and sunscreen. Virtually all studies on cosmeceuticals have been performed in women with varying degrees of skin aging. The cosmeceuticals most likely to be used by younger children are moisturizers and sunscreens. As the popularity and availability of other antiaging cosmeceuticals grow, practitioners will encounter more and more beauty-conscious teenagers using these products for preventive rather than restorative purposes. SUMMARY: Pediatricians should be familiar with the use of common cosmeceuticals used in children, especially the use of broad-spectrum sunscreen. In the future, more children will be exposed to cosmeceuticals and may experience side effects such as contact dermatitis and skin irritation.

Core concepts in congenital melanocytic nevi and infantile hemangiomas.

PURPOSE OF REVIEW: Congenital melanocytic nevi (CMN) and infantile hemangiomas are commonly encountered in newborns and may present diagnostic and therapeutic dilemmas for medical practitioners. Herein, we review and discuss these two important clinical entities and focus on core issues and recent advances. RECENT FINDINGS: Melanoma risk for patients with CMN is greatest in infants with large CMN located on the trunk, CMN greater than 40 cm, and multiple satellite nevi. Recent histological and molecular findings have been described to assist in differentiating benign proliferative nodules arising in CMN from melanoma. Multiple CMN and associated neurological lesions have recently been shown to be due to a single postzygotic mutation in NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog]. Over the last several years, numerous advancements have occurred in redefining the clinical course of infantile hemangiomas, describing clinical syndromes associated with infantile hemangiomas and treating complicated infantile hemangiomas. The nonselective ß-blocker propranolol has become first-line therapy for the treatment of complicated infantile hemangiomas. Topical timolol shows promise for the treatment of certain types of infantile hemangiomas. SUMMARY: Although most CMN and infantile hemangiomas do not require active intervention, understanding which lesions may impact the overall health of the infant assists in early intervention. This article touches on core concepts in the clinical evaluation and treatment of CMN and infantile hemangioma.

Current principles of sunscreen use in children.

PURPOSE OF REVIEW: Physicians need to be prepared to counsel patients on why and how to protect themselves from damaging ultraviolet (UV) radiation, including the proper use of sunscreens. In this article, we review the interplay between UV radiation, sunscreens and the skin, highlighting current controversies and recommendations surrounding sunscreen use. RECENT FINDINGS: An important concept is that excessive UV exposure has long-term damaging effects on the skin beyond the immediate sunburn. Recent discoveries of the role of UVA radiation in skin cancer development have set high standards for broad-spectrum coverage to be met by sunscreens. Current evidence does not support an association between sunscreen use and melanoma, systemic toxicity or vitamin D deficiency. Although sunscreen application is the most common modality for sun protection, many people do not use it correctly. Regular sunscreen use during childhood and adolescence can significantly reduce lifetime incidence of skin cancer; therefore, targeting children in pediatric offices regarding unprotected UV exposure may be a practical approach. SUMMARY: Sunscreens continue to be a major method of photoprotection among the public, offering numerous benefits that clearly outweigh potential risks; however, optimizing the use of sunscreens, especially among children and adolescents, remains a major challenge.