Carnitine palmitoyltransferase II (CPT II) deficiency responsible for refractory cardiac arrhythmias, acute multiorgan failure and early fatal outcome

Background: Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inborn error of mitochondrial fatty acid metabolism with autosomal recessive pattern of inheritance. Its phenotype is highly variable (neonatal, infantile, and adult onset) on the base of mutations of the CPT II gene. In affected subjects, long-chain acylcarnitines cannot be subdivided into carnitine and acyl-CoA, leading to their toxic accumulation in different organs. Neonatal form is the most severe, and all the reported patients died within a few days to 6 months after birth. Hereby, we report on a male late-preterm newborn who presented refractory cardiac arrhythmias and acute multiorgan (hepatic, renal, muscular) injury, leading to cerebral hemorrhage, hydrocephalus, cardiovascular failure and early (day 5 of life) to death. Subsequently, extended metabolic screening and target next generation sequencing (NGS) analysis allowed the CPT II deficiency diagnosis. Case presentation: The male proband was born at 36+ 4 weeks of gestation by spontaneous vaginal delivery. Parents were healthy and nonconsanguineous, although both coming from Nigeria. Family history was unremarkable. Apgar score was 9/9. At birth, anthropometric measures were as follows: weight 2850 g (47th centile, -0.07 standard deviations, SD), length 50 cm (81st centile, + 0.89 SD) and occipitofrontal circumference (OFC) 35 cm (87th centile, + 1.14 SD). On day 2 of life our newborn showed bradycardia (heart rate around 80 bpm) and hypotonia, and was then transferred to the Neonatal Intensive Care Unit (NICU). There, he subsequently manifested many episodes of ventricular tachycardia, which were treated with pharmacological (magnesium sulfate) and electrical cardioversion. Due to the critical conditions of the baby (hepatic, renal and cardiac dysfunctions) and to guarantee optimal management of the arrythmias, he was transferred to the Pediatric Cardiology Reference Center of our region (Sicily, Italy), where he died 2 days later. Thereafter, the carnitines profile evidenced by the extended metabolic screening resulted compatible with a fatty acid oxidation defect (increased levels of acylcarnitines C16 and C18, and low of C2); afterwards, the targeted next generation sequencing (NGS) analysis revealed the known c.680 C > T p. (Pro227Leu) homozygous missense mutation of the CPTII gene, for diagnosis of CPT II deficiency. Genetic investigations have been, then, extended to the baby's parents, who were identified as heterozygous carriers of the same variant. When we meet again the parents for genetic counseling, the mother was within the first trimester of her second pregnancy. Therefore, we offered to the couple and performed the prenatal target NGS analysis on chorionic villi sample, which did not detect any alterations, excluding thus the CPT II deficiency in their second child. Conclusions: CPTII deficiency may be suspected in newborns showing cardiac arrhythmias, associated or not with hypertrophic cardiomyopathy, polycystic kidneys, brain malformations, hepatomegaly. Its diagnosis should be even more suspected and investigated in cases of increased plasmatic levels of creatine phosphokinase and acylcarnitines in addition to kidney, heart and liver dysfunctions, as occurred in the present patient. Accurate family history, extended metabolic screening, and multidisciplinary approach are necessary for diagnosis and adequate management of affected subjects. Next generation sequencing (NGS) techniques allow the identification of the CPTII gene mutation, essential to confirm the diagnosis before or after birth, as well as to calculate the recurrence risk for family members. Our report broads the knowledge of the genetic and molecular bases of such rare disease, improving its clinical characterization, and provides useful indications for the treatment of patients

Markers for the detection of Lewy body disease versus Alzheimer's disease in mild cognitive impairment: a systematic review and meta-analysis

Background Mild cognitive impairment (MCI) may evolve into dementia. Early recognition of possible evolution to Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) is of importance, but actual diagnostic criteria have some limitations. In this systematic review and meta-analysis, we aimed to find the most accurate markers that can discriminate patients with DLB versus AD, in MCI stage. Methods We searched several databases up to 17 August 2023 including studies comparing markers that may distinguish DLB-MCI from AD-MCI. We reported data regarding sensitivity, specificity, and the area under the curves (AUCs) with their 95% confidence intervals (CIs). Results Among 2219 articles initially screened, eight case-control studies and one cohort study were included for a total of 832 outpatients with MCI. The accuracy of cerebrospinal fluid (CSF) markers was the highest among the markers considered (AUC > 0.90 for the CSF markers), with the AUC of CSF A beta 42/A beta 40 of 0.94. The accuracy for clinical symptom scales was very good (AUC = 0.93), as evaluated in three studies. Although limited to one study, the accuracy of FDG-PET (cingulate island sign ratio) was very good (AUC = 0.95) in discriminating DLB from AD in MCI, while the accuracy of SPECT markers and EEG frequencies was variable. Conclusions Few studies have assessed the accuracy of biomarkers and clinical tools to distinguish DLB from AD at the MCI stage. While results are promising for CSF markers, FDG-PET and clinical symptoms scales, more studies, particularly with a prospective design, are needed to evaluate their accuracy and clinical usefulness

Older People Hospitalized for COVID-19: Prognostic Role of Multidimensional Prognostic Index and Other Prognostic Scores

During the SARS-CoV-2 pandemic, frailty and patients’ poor outcomes seem to be closely related. However, there is no clear indication of the significance of this connection and the most adequate risk index in clinical practice. In this study, we compared a short version of MPI (multidimensional prognostic index) and other two prognostic scores for COVID-19 as potential predictors of poor patient outcomes. The patients were consecutively enrolled in the hospital of Palermo for COVID-19. The accuracy of Brief-MPI, 4C score and COVID-GRAM score in points was evaluated using the area under the curve (AUC) with 95% CI, taking mortality or sub-ICU admission as outcome. The study included 112 participants (mean age 77.6, 55.4% males). During a mean of 16 days of hospitalization, Brief-MPI significantly increased by 0.03 ± 0.14 (p = 0.04), whilst COVID-GRAM did not. Brief-MPI, 4C score and COVID-GRAM scores had good accuracy in predicting negative outcomes (AUC > 0.70 for all three scores). Brief-MPI was significantly associated with an increased mortality/ICU admission risk, indicating the importance of multidimensional impairment in clinical decision-making with an accuracy similar to other prognostic scores commonly used in COVID-19 study, providing information regarding domains for which interventions can be proposed

Caustic Ingestion in Children. One Year Experience in Three Italian Referral Centers

Objectives: Despite the efforts to reduce the exposure to corrosive household products, caustic ingestion in children is currently a significant medical problem. The aims of the present study were to evaluate the clinical consequences of caustic ingestion and to identify prognostic factors that could concur in driving both diagnostic and therapeutic management. Methods: All consecutive children referred for ingestion of a caustic substance from June 2017 to June 2018 were enrolled. Medical records, laboratory and endoscopic findings were reviewed and analyzed. Results: We enrolled 44 children with caustic ingestion. Alkaline agents were ingested by 26/44 (59.1%) patients, while acid agents were ingested by 18/44 patients (40.9%). Alkaline rather than acid agents were associated with a worse endoscopic score (r:0.45) and a higher probability of early esophageal stricture occurrence (r:0.38). The specific risk of the presence of severe esophageal lesions rose progressively with increasing number of symptoms while no esophageal injury was found in asymptomatic patients. Conclusions: Our data suggest that endoscopic evaluation is mandatory in symptomatic patients to direct therapeutic management, but it could be avoided in asymptomatic patients after accidental ingestion, particularly if the ingestion is only suspected and patients have no oropharyngeal burns

Multidimensional Frailty and Vaccinations in Older People: A Cross-Sectional Study

It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association are still missing. Therefore, we aimed to investigate the prevalence of four recommended vaccinations (influenza, herpes zoster, pneumococcal and diphtheria-tetanus-pertussis) and the association with multidimensional frailty assessed using a self-reported comprehensive geriatric assessment tool, i.e., the multidimensional prognostic index (SELFY-MPI). Older participants visiting the outpatient clinic of Azienda Ospedaliera Universitaria, Palermo, Italy were included. The SELFY-MPI questionnaire score was calculated based on eight different domains, while the vaccination status was determined using self-reported information. We included 319 participants from the 500 initially considered (63.8%). Vaccination against influenza was observed in 70.5% of the cases, whilst only 1.3% received the vaccination against diphtheria-tetanus-pertussis. Participants with higher SELFY-MPI scores were more likely to report vaccination against pneumococcus (45.6 vs. 28.3%, p = 0.01), whilst no significant differences were observed for the other vaccinations. In conclusion, the coverage of recommended vaccinations is low. Higher SELFY-MPI scores and vaccination status, particularly anti-pneumococcus, appear to be associated, but future studies are urgently needed for confirming that frailty is associated with vaccination status in older people

Association between depression and incident dementia: Longitudinal findings from the share study

Background: The association between depression and dementia is still unclear, particularly regarding depression as a potential risk factor preceding dementia. Therefore, we aimed to verify if the presence of depression at baseline may increase the risk of dementia and cognitive impairment during 15 years of follow-up in the SHARE (Survey of Health, Aging and Retirement in Europe) study. Methods: Depressive symptoms were defined using the EURO-D, with a score ≥4 indicative of depression. Incident dementia was ascertained using self-reported data and caregivers' information, cognitive impairment using objective cognitive tests. Cox regression analysis, adjusted for 10 baseline confounders, was run and hazard ratios (HRs), with their 95% confidence intervals, were estimated. Results: In total 22,789 participants were included in the present analysis (mean age 64.2 years) and were predominantly female. The prevalence of depression at baseline was 24.9%. Over 15 years of follow-up, the onset of dementia occurred a median 2 years earlier in people with depression compared to those without. Depression at the baseline significantly increased the risk of dementia in the overall sample (HR = 1.74; 95% CI: 1.54–1.95) and the risk of cognitive impairment (HR = 1.15; 95% CI: 1.06–1.25). For dementia, the association was stronger in people less than 60 years (HR = 2.07; 95% CI: 1.42–3.02) than in participants aged ≥80 years (HR = 1.47; 95% CI: 1.14–1.91). A similar trend was observed for cognitive impairment. Among the single items of the EURO-D, loss of concentration was the strongest individual variable predicting the onset of dementia. Conclusions: Depression increased the risk of dementia and cognitive impairment, particularly in younger adults, whereas loss of concentration was the strongest individual predicting variable of dementia. These findings demonstrate the need for early detection of depression for preventing future cognitive worsening.</p

Markers for the detection of Lewy body disease versus Alzheimer's disease in mild cognitive impairment: a systematic review and meta-analysis

No description supplied</p

Markers for the detection of Lewy body disease versus Alzheimer's disease in mild cognitive impairment: a systematic review and meta-analysis

No description supplied</p