Efficacy and safety of fenoldopam for the treatment of hypertensive crises in children with kidney disease: a retrospective study.

BACKGROUND: Hypertensive crises in children represent critical medical situations characterized by severe hypertension and potential organ damage. Fenoldopam, a dopaminergic medication, offers a viable therapeutic option for managing such clinical scenarios. We aimed to evaluate efficacy and safety of fenoldopam in the management of hypertensive urgencies and emergencies. METHODS: This retrospective analysis focused on pediatric patients affected by acute or chronic kidney disease, aged 1 month-18 years, admitted to the Pediatric Nephrology and the Pediatric Intensive Care Unit at University-Hospital of Padua, Italy, who presented with a hypertensive crisis treated with fenoldopam between March 2010 and December 2022. RESULTS: The study included 74 patients with median age 10 years (interquartile range [IQR] 4-15 years) who received 102 fenoldopam infusions. Seventy-two percent were already receiving antihypertensive treatment before admission. In all cases, fenoldopam was associated with a reduction of blood pressure (BP) after 8 h of treatment, but in 87% of patients reduction of the initial mean arterial pressure (MAP) was higher than 25% of calculated drop pressure. MAP normalized in 26% of cases after 24 h and in 35% after 48 h. Occurrence of hypotension was 7%, while hypokalemia was observed in 13% of cases. Patients who presented a MAP reduction not exceeding 25% of calculated drop pressure received a lower median fenoldopam dose (0.2 mcg/kg/min; IQR 0.1-0.2) compared with patients having a MAP reduction > 25% of calculated drop pressure (0.4 mcg/kg/min; IQR 0.2-0.6; p = 0.002). CONCLUSIONS: Fenoldopam seems effective and safe for the treatment of hypertensive crises in children with kidney disease, at a starting dose of 0.2 mcg/kg/min. Strict BP monitoring is required to identify possible excessive drop pressure in the first hours of infusion.

Cutaneous melanoma in older patients.

BACKGROUND: In industrialized countries, the aging population is steadily rising. The incidence of cutaneous malignant melanoma (CMM) is highest in old people. This study focuses on the clinicopathological profile of CMM and indicators of diagnostic-therapeutic performance in older patients. METHODS: This retrospective population-based cohort study included 1,368 incident CMM, as recorded in 2017 by the Regional Veneto Cancer Registry (Northeast Italy). Older subjects were defined as ≥ 80, old as 65-79, and adults as < 65 years of age. The strength of association between pairs of variables was tested by Cramer's-V. Using age groups as the dependent variable, ordered logistic regression was fitted using the clinicopathological CMM profiles as covariates. In each of the three age-groups, the indicators of clinical performance were computed using the Clopper-Pearson exact method. RESULTS: Compared to patients aged younger than 80 years (1,187), CMM in older patients (181; 13.2%) featured different CMM topography, a higher prevalence of ulcers (43.3% versus 12.7%; p < 0.001), a higher Breslow index (p < 0.001), a lower prevalence of tumor-infiltrating lymphocytes (64.4% versus 76.5%, p < 0.01), and a more advanced pTNM stage at clinical presentation (p < 0.001). Elderly patients with a positive sentinel-lymph node less frequently underwent sentinel- lymph node biopsy and lymphadenectomy (60.0% versus 94.2%, and 44.4% versus 85.5%, respectively; p < 0.001). CONCLUSIONS: In older CMM patients, the clinicopathological presentation of CMM shows a distinctive profile. The present results provide critical information to optimize secondary prevention strategies and refine diagnostic-therapeutic procedures tailored to older patients.

Cutaneous melanoma in adolescents and young adults.

BACKGROUND: Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population. OBJECTIVE: To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category. METHODS: This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method. RESULTS: In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004). CONCLUSIONS: In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients.

Nadir creatinine as a predictor of renal outcomes in PUVs: A systematic review and meta-analysis.

Background: Posterior urethral valves (PUVs) represent the most severe pediatric obstructive uropathy, responsible for chronic renal failure in up to 65% of cases and progression to end-stage kidney disease (ESKD) in about 8%-21% of patients. Unfortunately, renal outcomes have poorly improved over time. The key point is to identify patients at risk; thus, several prenatal and postnatal prognostic factors have been analyzed to improve clinical outcomes. Postnatal nadir creatinine seems to accurately predict long-term renal prognosis, but there is no definitive evidence to support this finding. Objective: We performed a systematic review with meta-analysis to analyze the predictive value of nadir creatinine on long-term renal function in infants with PUVs. Methods: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Cochrane Library were systematically searched for studies published from January 2008 to June 2022. All the articles were checked independently by two reviewers in two steps. Results: A total of 24 articles were screened, and 13 were included for data extraction. Data from 1,731 patients with PUVs were analyzed, with a mean follow-up of 5.5 years; of these, on average, 37.9% developed chronic kidney disease (CKD) and 13.6% developed ESKD. All the articles evaluated nadir creatinine as a predictor of CKD, most using a level of 1 mg/dL, with statistical significance at the 5% level. The relative risk of developing CKD in patients with creatinine values higher than the nadir cutoff considered was 7.69 (95% CI: 2.35-25.17, I 2 = 92.20%, p < 0.001). Conclusions: Nadir creatinine is the best prognostic factor for long-term renal function in patients affected by PUV. A value above the cutoff of 1 mg/dL should be considered a significant predictor for the risk of CKD and ESKD. Further studies are needed to define different nadir creatinine cutoffs for better stratification of the different CKD stages and for the development of reliable scores, which include the association of several variables.

The Prevalent Comorbidome at the Onset of Psoriasis Diagnosis.

INTRODUCTION: Psoriasis (PsO) is currently regarded as a systemic inflammatory disease with a growing burden of post-diagnosis associated comorbidities. To determine the initial burden of comorbiditis we evaluated the comorbidome at PsO onset. METHODS: In a matched case-control study, we extracted data on 57,228 patients and 125 morbidities from the Clalit Health Services Israeli insurance database. PsO cases were matched with control individuals by sex and age at enrolment. As pre-existing comorbidities, we considered all conditions already present in controls at the same age as the matched PsO case at the time of their diagnosis. To test for differences in the odds of comorbidities between the case and control groups, logistic regression analyses were run to calculate the odds ratio (OR) for each comorbidity, after which the comorbidome was graphically represented. RESULTS: In this study we enrolled 28,614 PsO patients and 28,614 controls with an average age of 45.3 ± 19.6 years. At the time of diagnosis, PsO patients were more likely to be diagnosed with 2-4 comorbidities (28.8% vs 23.8%) and > 5 (19.6% vs 12.9%,). PsO patients' specific comorbidomes evidenced several pathological cores: autoimmune and inflammatory systemic diseases [i.e., hidradenitis suppurativa (OR 3.55, 95% CI 1.88-7.28) or polymyalgia rheumatica (OR 3.01 95% CI 1.96-4.77)], inflammatory bowel diseases [i.e., Crohn's disease (OR 2.99 95% CI 2.20-4.13)], pulmonary inflammatory diseases [i.e., chronic obstructive pulmonary disease (OR 1.81 95% CI 1.61-2.04)], hepatological diseases [i.e., cirrhosis (OR 2.00 95% CI 1.36-3.00)], endocrine diseases [dysthyroidisms (OR 1.82 95% CI 1.30-2.59)], mental disorders [i.e., depression (OR 1.72 95% CI 1.57-1.87)], and cardiovascular diseases (i.e., hypertension (OR 1.47 95% CI 1.41-1.53)]. CONCLUSION: The PsO-onset comorbidome may help health professionals plan more comprehensive patient management. By screening for these common PsO-linked conditions, early diagnosis and treatment may become more frequent, thus greatly benefiting patients on their medical journey.

Sex Differences in Cutaneous Melanoma: Incidence, Clinicopathological Profile, Survival, and Costs.

Background: This study aims to provide a comprehensive overview of sex-related characteristics of cutaneous malignant melanoma (CMM), with special reference to its incidence, clinicopathological profile, overall survival, and treatment-related costs. Methods: This retrospective cohort study included all 1,279 CMM patients who were registered in 2015 in the Veneto Cancer Registry (a population-based registry including all 4,900,000 regional residents). The by-sex comparisons included tumor stage and site, histological subtype, and other clinical-pathological variables. A Cox regression analysis was used to test the association between sex and survival, adjusting for the main covariates. Treatment costs were calculated by linking patients with several administrative regional databases. Results: Age-specific incidence rates were significantly higher for men among people >50 years old. For men, the trunk was the most common primary site (59.3%), whereas for women the lower limbs (32.1%) were the most common primary site, followed by the trunk (31.8%), which was lower than for men (p < 0.001). At presentation, the frequency of early stage CMM was higher among women, who also featured a significantly lower risk of death (p = 0.016), after adjusting for covariates. Men also incurred higher costs for melanoma treatment in the first year after their diagnosis. Conclusions: Among younger adults, CMM was more common in women, whereas among older adults, it was more common in men. Sex also influences patients' histopathological characteristics at diagnosis. Women had better overall survival after adjusting for demographic, pathological, and clinical profiles. The costs of treatment were also lower for women with CMM.

Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants.

Population testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Notably, we find that genomic surveillance systems which rely on antigen population testing to identify samples for sequencing will bias detection of escape antigen test variants. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, including in contexts where the use of antigen tests is widespread.

Direct Costs of Care for Adults with Soft Tissue Sarcomas: A Population-Based Study.

The clinical treatment of soft tissue sarcoma (STS) has evolved substantially over the last decade. This population-based cohort study based on real-world data included all incidental STS recorded by the Veneto Cancer Registry in 2017. Data on hospital admissions, emergency department and outpatient visits, drug prescriptions, and use of medical devices within two years from STS diagnosis were obtained from administrative databases. The average per-patient real-world costs over this two-year period, in total and by single expenditure item, were calculated and stratified by stage of disease at diagnosis, tumor histology and tumor site. The mean total cost per patient amounted to EUR 16,793. A higher TNM stage at diagnosis was associated with higher healthcare costs, as follows: compared with stage I, the average total cost per patient was 1.32, 2.18 and 3.36 times greater for stages II, III and IV, respectively. Hospital stays generated the greatest costs (averaging EUR 7950 per patient), followed by outpatient visits (mean EUR 3947 per patient) and drug prescriptions (mean EUR 3664 per patient). Given the paucity of population-based studies, the present results can serve as a reference for further cost-effectiveness analyses on care strategies for patients with STS.

Systematic Review and Meta-Analysis of Surgical Treatment for Isolated Local Recurrence of Pancreatic Cancer.

PURPOSE: To perform a systematic review and meta-analysis on the outcome of surgical treatment for isolated local recurrence of pancreatic cancer. METHODS: A systematic review and meta-analysis based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was conducted in PubMed, Scopus, and Web of Science. RESULTS: Six studies concerning 431 patients with recurrent pancreatic cancer met the inclusion criteria and were included in the analysis: 176 underwent redo surgery, and 255 received non-surgical treatments. Overall survival and post-recurrence survival were significantly longer in the re-resected group (ratio of means (ROM) 1.99; 95% confidence interval (CI), 1.54-2.56, I2 = 75.89%, p = 0.006, and ROM = 2.05; 95% CI, 1.48-2.83, I2 = 76.39%, p = 0.002, respectively) with a median overall survival benefit of 28.7 months (mean difference (MD) 28.7; 95% CI, 10.3-47.0, I2 = 89.27%, p < 0.001) and median survival benefit of 15.2 months after re-resection (MD 15.2; 95% CI, 8.6-21.8, I2 = 58.22%, p = 0.048). CONCLUSION: Resection of isolated pancreatic cancer recurrences is safe and feasible and may offer a survival benefit. Selection of patients and assessment of time and site of recurrence are mandatory.

The Prognostic Value of Low Muscle Mass in Pancreatic Cancer Patients: A Systematic Review and Meta-Analysis.

Low muscle mass is associated with reduced survival in patients with different cancer types. The interest in preoperative sarcopenia and pancreatic cancer has risen in the last decade as muscle mass loss seems to be associated with poorer survival, higher postoperative morbidity, and mortality. The aim of the present study was to review the literature to compare the impact of low muscle mass on the outcomes of patients undergoing surgery for pancreatic adenocarcinoma. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and 10 articles were analyzed in detail and included in the meta-analysis. Data were retrieved on 2811 patients undergoing surgery for pancreatic cancer. Meta-analysis identified that patients with low muscle mass demonstrated a significantly reduced OS when compared to patients without alterations of the muscle mass (ROM 0.86; 95% CI: 0.81-0.91, p < 0.001), resulting in a 14% loss for the former. Meta-analysis failed to identify an increase in the postoperative complications and length of stay of patients with low muscle mass. Our analysis confirms the role of low muscle mass in influencing oncologic outcomes in pancreatic cancer. Its role on surgical outcomes remains to be established.

The Role of Positron Emission Tomography in Clinical Management of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas represent a heterogeneous group of tumors, increasingly diagnosed in clinical practice. An early differential diagnosis between malignant and benign lesions is crucial to patient management and the choice of surgery or observation. The therapeutic approach is currently based on a patient's clinical, biochemical, and morphological characteristics. The latest published International Consensus Guidelines (ICG) make no mention of the role of metabolic assessments of IPMNs. The aim of this study was to review the current literature, examining the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in IPMN management. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 10 articles were analyzed in detail, focusing on the value of PET as opposed to other standard imaging criteria. Data were retrieved on 419 patients. The 18-FDG-PET proved more sensitive, specific, and accurate than the ICG criteria in detecting malignant IPMNs (reaching 80%, 95%, and 87% vs. 67%, 58%, and 63%, respectively). Metabolic assessments may be used as an additional tool for the appropriate management of patients with doubtful imaging findings.