Gender differences in pediatric and adolescent melanoma: A retrospective analysis of 4645 cases.

BACKGROUND: There is paucity of data on how gender impacts melanoma prognosis in pediatric and adolescent patients. OBJECTIVES: This study explores gender differences in presentation and survival among pediatric and adolescent patients with melanoma. METHODS: The National Cancer Database 2004-2018 was queried for cases of primary invasive cutaneous melanoma in pediatric and adolescent patients (birth to 21 years) for a retrospective cohort study. RESULTS: Of the 4645 cases, 63.4% were female. Median Breslow depth was 1.05 mm for males (interquartile range 0.50-2.31) and 0.80 mm for females (interquartile range 0.40-1.67; P < .001). Trunk was the most common primary site for females (34.3%) and males (32.9%). More females than males were diagnosed with stage I disease (67.8% vs 53.6%). Males had higher rates of regional lymph node positivity (27.9% vs 18.1%; P < .001) and ulceration (17.1% vs 11.4%; P < .001). Five-year overall survival was 95.9% for females and 92.0% for males (P < .001). After adjusting for confounders, male gender independently increased mortality risk (reference: females; adjusted hazard ratio 1.57; 95% confidence interval 1.32-1.86). LIMITATIONS: Retrospective study. CONCLUSION: Males exhibited more aggressive pathologic features including greater Breslow thickness and higher ulceration and lymph node positivity rates. Male gender independently increased mortality risk.

Gestational glyphosate exposure and early childhood neurodevelopment in a Puerto Rico birth cohort.

INTRODUCTION: N-(phosphonomethyl)glycine, or glyphosate, is a non-selective systemic herbicide widely used in agricultural, industrial, and residential settings since 1974. Glyphosate exposure has been inconsistently linked to neurotoxicity in animals, and studies of effects of gestational exposure among humans are scarce. In this study we investigated relationships between prenatal urinary glyphosate analytes and early childhood neurodevelopment. METHODS: Mother-child pairs from the PROTECT-CRECE birth cohort in Puerto Rico with measures for both maternal urinary glyphosate analytes and child neurodevelopment were included for analysis (n = 143). Spot urine samples were collected 1-3 times throughout pregnancy and analyzed for glyphosate and aminomethylphosphonic acid (AMPA), an environmental degradant of glyphosate. Child neurodevelopment was assessed at 6, 12, and 24 months using the Battelle Developmental Inventory, 2nd edition Spanish (BDI-2), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. We used multivariable linear regression to examine associations between the geometric mean of maternal urinary glyphosate analytes across pregnancy and BDI-2 scores at each follow-up. Results were expressed as percent change in BDI-2 score per interquartile range increase in exposure. RESULTS: Prenatal AMPA concentrations were negatively associated with communication domain at 12 months (%change = -5.32; 95%CI: 9.04, -1.61; p = 0.007), and communication subdomain scores at 12 and 24 months. At 24 months, four BDI-2 domains were associated with AMPA: adaptive (%change = -3.15; 95%CI: 6.05, -0.25; p = 0.038), personal-social (%change = -4.37; 95%CI: 7.48, -1.26; p = 0.008), communication (%change = -7.00; 95%CI: 11.75, -2.26; p = 0.005), and cognitive (%change = -4.02; 95%CI: 6.72, -1.32; p = 0.005). Similar trends were observed with GLY concentrations, but most confidence intervals include zero. We found no significant associations at 6 months. CONCLUSIONS: Our results suggest that gestational exposure to glyphosate is associated with adverse early neurodevelopment, with more pronounced delays at 24 months. Given glyphosate's wide usage, further investigation into the impact of gestational glyphosate exposure on neurodevelopment is warranted.

The association between urinary glyphosate and aminomethyl phosphonic acid with biomarkers of oxidative stress among pregnant women in the PROTECT birth cohort study.

BACKGROUND: Glyphosate is a widely used herbicide in global agriculture. Glyphosate and its primary environmental degradate, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress in in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may be indicative of health effects caused by previous exposure via multiple mechanisms including oxidative stress. METHODS: Glyphosate and AMPA were measured in 347 urine samples collected between 16 and 20 weeks gestation and 24-28 weeks gestation from pregnant women in the PROTECT birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2α (8-iso-PGF2α), its metabolite 2,3-dinor-5,6-dihydro-15-F2 t-isoprostane (8-isoprostane metabolite) and prostaglandin-F2α (PGF2α), were also measured. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Potential nonlinear trends were also assessed using tertiles of glyphosate and AMPA exposure levels. RESULTS: No significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5-19.3%) higher 8-iso-PGF2α metabolite concentrations. Significant linear trends were also identified when examining tertiles of exposure variables. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6-26.5%) and 15.2% (1.8-30.3%) higher 8-isoprostane metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (-0.9 to 10.7%) higher 8-iso-PGF2α. CONCLUSIONS: Urinary concentrations of the main environmental degradate of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.

Physician perspectives on complementary and alternative medicine in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic and often debilitating inflammatory condition characterized by frequent nodules, abscesses, sinus tracts, and scars impacting the intertriginous areas. Many patients with HS often report limited treatment success and symptom coverage with conventional therapies. Recent studies have reported the widespread use of complementary and alternative medicine (CAM) among patients with HS. In this study, our aim was to examine current physician practice patterns, opinions, and comfort with recommending CAM. Our results indicate that provider comfort and opinions on CAM varied based on the provider's experiences, demographics, and the CAM modality itself. Overall, nearly two-thirds (n = 30, 61.2%) of respondents agreed that CAM and conventional medicine were more effective together than either alone. Meanwhile, 44.9% (n = 22) of respondents routinely recommend CAM while 64.6% (n = 31) of respondents reported that they are routinely asked about CAM. The majority (n = 41, 83.7%) of respondents indicated a lack of scientific evidence in the medical literature as a barrier to recommending CAM along with efficacy concerns (n = 34, 69.4%) and ability to recommend reputable CAM products (n = 32, 65.3%) and practitioners (n = 32, 65.3%). Future investigations are warranted to establish a better understanding of the efficacy and benefit of CAM methods in conjunction with conventional methods.

Perspectives of Pediatric Providers Regarding Clinical Use of Pharmacogenetics.

INTRODUCTION: A major goal of the current personalized medicine era is to utilize pharmacogenetics (PGx) in order to influence how medications and therapies are prescribed by providers. However, disparities for prescribing medications between adults and children exist. Research has shown that children are not just small adults and there are different challenges for pediatric providers in regards to ordering and interpreting PGx tests. The goal of this study was to obtain an initial understanding of current pharmacogenetic testing by pediatric providers, as well as determine perceived barriers. METHODS: We distributed an online survey to pediatric providers at six different institutions across the U.S. RESULTS: Of the 252 respondents who completed the survey, 24 percent reported previously ordering PGx tests, however, over 90 percent of respondents reported they would feel more comfortable ordering and interpreting results with the assistance of a pharmacist, geneticist, genetic counselor or PGx expert. Additionally, participants identified specific barriers towards the utilization of PGx testing, as well as suggested solutions to overcome these barriers, including increasing provider education regarding testing, collaboration through a multidisciplinary team approach and established PGx programs. CONCLUSION: As the pharmacogenetic field continues to demonstrate clinical utility in the pediatric population, it will be important to continuously identify and address barriers that exist for providers to allow for more successful implementation of PGx in the pediatric setting, as well as enhance patient care.

Distinct Mechanisms of Dissemination of NDM-1 Metallo-ß-Lactamase in Acinetobacter Species in Argentina.

A 4-year surveillance of carbapenem-resistant Acinetobacter spp. isolates in Argentina identified 40 strains carrying blaNDM-1 Genome sequencing revealed that most were Acinetobacter baumannii, whereas seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. blaNDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non-A. baumannii strains. A resistance gene island carrying blaPER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains.

Classification and mitigation of negative injection experiences with biologic medications.

Injection site reactions with biologic medications are encountered with variable frequency. Although there is no clear definition, they commonly manifest with pain and irritation at the injection site. Previously proposed reaction classification systems may be impractical or insufficient, and more intuitive nomenclature may benefit clinical dermatologists and patients. Negative injection experiences (NIE) are common reasons for biologic medication nonadherence. Here we provide clinical classifications and recommendations for mitigating these reactions. We categorized NIEs into the following: (a) physical, due to the needle and injection process, (b) irritant, related to properties of the injected solution, and (c) allergic, both immediate and delayed.

Alleviating and exacerbating foods in hidradenitis suppurativa.

While dietary triggers have been investigated in acne and other inflammatory follicular dermatoses, there is a paucity of data on diet and hidradenitis suppurativa (HS). We sought to identify exacerbating and alleviating foods in HS patients. An anonymous survey was distributed via HS Facebook support groups and in person at HS specialty clinics. Participants were asked to select all that apply from a list to indicate foods that worsen and make HS better including sweet foods, breads and pasta, red meat, chicken, fish, canned foods, fruits, vegetables, dairy, high-fat foods, I do not know, and no. Only 12.0% (n = 89/744) identified alleviating foods while 32.6% (n = 237/728) identified HS-symptom-exacerbating foods. The most commonly reported exacerbating foods were sweets (67.9%), bread/pasta/rice (51.1%), dairy (50.6%), and high-fat foods (44.2%). The most commonly reported alleviating foods included vegetables (78.7%), fruit (56.2%), chicken (51.7%), and fish (42.7%). Further studies are required to evaluate the mechanistic links between diet and HS. HS patients may benefit from receiving dietary counseling as part of a comprehensive HS management plan.

Genomic Analysis of two NDM-1 Providencia stuartii Strains Recovered from a Single Patient.

In the last years, an increasing number of untreatable infections caused by drug-resistant microbes have impacted the health care system. Worldwide, infections caused by carbapenem-resistant (CR) Gram-negative bacilli have dramatically increased. Among the CR-Gram-negative bacilli, those producing carbapenemases, such as NDM-1, are the main concern. Different Enterobacterales harboring NDM-1 have been reported lately. Providencia stuartii, a member of the Morganellaceae family, is ubiquitous in the environment, but is also known to cause nosocomial infections. Here we describe the genomic analysis of two NDM-1- producing P. stuartii strains recovered from the same patient as well as other carbapenem resistant strains recovered from the same hospital. As a result of the genomic analysis thirteen resistance genes, including three to ß-lactams (blaOXA-1, blaTEM-1, blaNDM-1), four to aminoglycosides (aphA6, aac(3)-IId, aac(2')-Ia, aac(6')-Ib-cr5), one to sulfonamides (sul1), two to chloramphenicol (catB3, catA3), one to rifampicin, one to bleomycin (ble), and one to tetracycline (tet(B)) were found. Moreover, a variety of mobile genetic elements, such as insertion sequences, plasmids and phage- related sequences, were found within P. stuartii genomes. The spread of carbapenem-resistant isolates remains a significant clinical and public health concern. Therefore, we considered that the detection of CR isolates is an essential step in addressing this problem.

Effect of Host Human Products on Natural Transformation in Acinetobacter baumannii.

Our previous data show that serum albumin can trigger natural transformation in Acinetobacter baumannii. However, extracellular matrix/basal membrane components, norepinephrine, and mucin did not have a significant effect on this process. Therefore, the effect of human products appears to be albumin specific, as both BSA and HSA have been shown to increase of natural transformation.

A Study on Acinetobacter baumannii and Staphylococcus aureus Strains Recovered from the Same Infection Site of a Diabetic Patient.

Diabetic foot ulcer infections are frequently polymicrobial in nature and exhibit increased morbidity and mortality, as well as, treatment failures. Interactions between Acinetobacter baumannii and Staphylococcus aureus were studied, which showed strain-dependent changes in growth and antibiotic susceptibility. This study examined the interactions between two clinical strains of A. baumannii (1929) and S. aureus (1928) that were recovered from skin and soft tissues of a diabetic patient. When S. aureus 1928 and A. baumannii 1929 were co-cultured together, there was no significant decrease in growth in either clinical strains, indicating that both strains can co-exist in the same site of infection. Additionally, neither strains experienced statistically significant changes in susceptibility. These findings highlight that these two pathogens can be found in the same niche of infection, which may lead to more aggressive outcome of the infection.

Whole Genome Sequence Analysis of Burkholderia contaminans FFH2055 Strain Reveals the Presence of Putative ß-Lactamases.

Burkholderia contaminans is a member of the Burkholderia cepacia complex (Bcc), a pathogen with increasing prevalence among cystic fibrosis (CF) patients and the cause of numerous outbreaks due to the use of contaminated commercial products. The antibiotic resistance determinants, particularly ß-lactamases, have been poorly studied in this species. In this work, we explored the whole genome sequence (WGS) of a B. contaminans isolate (FFH 2055) and detected four putative ß-lactamase-encoding genes. In general, these genes have more than 93% identity with ß-lactamase genes found in other Bcc species. Two ß-lactamases, a class A (Pen-like, suggested name PenO) and a class D (OXA-like), were further analyzed and characterized. Amino acid sequence comparison showed that Pen-like has 82% and 67% identity with B. multivorans PenA and B. pseudomallei PenI, respectively, while OXA-like displayed strong homology with class D enzymes within the Bcc, but only 22-44% identity with available structures from the OXA family. PCR reactions designed to study the presence of these two genes revealed a heterogeneous distribution among clinical and industrial B. contaminans isolates. Lastly, blaPenO gene was cloned and expressed into E. coli to investigate the antibiotic resistance profile and confers an extended-spectrum ß-lactamase (ESBL) phenotype. These results provide insight into the presence of ß-lactamases in B. contaminans, suggesting they play a role in antibiotic resistance of these bacteria.