Case report: Management of pediatric gigantism caused by the TADopathy, X-linked acrogigantism.

X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene GPR101, a constitutively active stimulator of pituitary GH and prolactin secretion. GPR101 normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive GPR101 over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4C-seq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of first-generation somatostatin analogs.

Epileptic spasms in infants: can video-EEG reveal the disease's etiology? A retrospective study and literature review.

Objective: Epileptic spasms are a type of seizure defined as a sudden flexion or extension predominantly of axial and/or truncal limb muscles that occur with a noticeable periodicity. Routine electroencephalogram supports the diagnosis of epileptic spasms, which can occur due to different causes. The present study aimed to evaluate a possible association between the electro-clinical pattern and the underlying etiology of epileptic spasms in infants. Materials and methods: We retrospectively reviewed the clinical and video-EEG data on 104 patients (aged from 1 to 22 months), admitted to our tertiary hospital in Catania and the tertiary hospital in Buenos Aires, from January 2013 to December 2020, with a confirmed diagnosis of epileptic spasms. We divided the patient sample into structural, genetic, infectious, metabolic, immune, and unknown, based on etiology. Fleiss' kappa (К) was used to assess agreement among raters in the electroencephalographic interpretation of hypsarrhythmia. A multivariate and bivariate analysis was conducted to understand the role of the different video-EEG variables on the etiology of epileptic spasms. Furthermore, decision trees were constructed for the classification of variables. Results: The results showed a statistically significant correlation between epileptic spasms semiology and etiology: flexor spasms were associated with spasms due to genetic cause (87.5%; OR < 1); whereas mixed spasms were associated with spasms from a structural cause (40%; OR < 1). The results showed a relationship between ictal and interictal EEG and epileptic spasms etiology: 73% of patients with slow waves and sharp waves or slow waves on the ictal EEG, and asymmetric hypsarrhythmia or hemi hypsarrhythmia on the interictal EEG, had spasms with structural etiology, whereas 69% of patients with genetic etiology presented typical interictal hypsarrhythmia with high-amplitude polymorphic delta with multifocal spike or modified hypsarrhythmia on interictal EEG and slow waves on the ictal EEG. Conclusion: This study confirms that video-EEG is a key element for the diagnosis of epileptic spasms, also playing an important role in the clinical practice to determine the etiology.

Respiratory Changes in Ventilated and Not-Ventilated Neonates During and After Whole-Body Hypothermia: A Multicenter Retrospective Study.

The aim of this study was to describe whether whole-body hypothermia induced different respiratory changes in both invasively and noninvasively ventilated newborns and spontaneously breathing asphyxiated newborns during the course and after therapeutic hypothermia (TH). Data of 44 asphyxiated newborns undergoing TH at five different neonatal intensive care units in southern Italy were collected retrospectively between January 2018 and January 2021. For each type of ventilation, patient data on pH, partial pressure of Carbon Dioxide (pCO2), base excess, lactate, and heart rate were recorded before cooling was started and at 24, 48, 72, and 96 hours from its initiation. Patients were later subgrouped into spontaneously breathing, noninvasively ventilated, and mechanically ventilated groups. The average trend of each parameter was reported, and a nonparametric statistical analysis of differences among groups before initiation and at 96 hours was performed using the Kruskal-Wallis test. Our results confirmed previous findings (supported by a small amount of literature) that no increase in requests for respiratory support is recorded in asphyxiated newborns undergoing TH during and after the rewarming phase. Furthermore, no statistically significant differences in the analyzed parameters were found among spontaneously breathing, noninvasively ventilated, and mechanically ventilated newborns, suggesting that changes in parameters might be attributable to TH itself rather than to an improvement in the respiratory condition over time; otherwise, a difference between spontaneously breathing patients, by definition "stable" from a respiratory point of view, and those requiring any type of respiratory support would have been expected.

Urea/Creatinine Ratio's Correlation with Creatine Kinase Normalization in Pediatric COVID-19 Patients with Myositis: Evaluating Prognostic and Predictive Value.

Coronavirus disease 2019 (COVID-19) has been chiefly linked with substantial respiratory complications. However, emerging studies have brought attention to the occurrence of severe muscle inflammation (myositis) related to COVID-19, potentially leading to multi-organ failure and increased mortality. Myositis is generally characterized by heightened serum creatine kinase (CK) levels. Acute myositis is characterized by an infiltration of viruses into calf muscle fibers, which may cause a subsequent inflammatory response leading to calf muscle pain. Symptomatic and supportive management, along with explanation and reassurance, is all that is required in managing this condition. While the association between myositis and severe outcomes has been recognized in adults, it remains less understood in the pediatric population. The current retrospective study, conducted at Policlinico San Marco University Hospital in Catania, aimed to analyze clinical and laboratory factors associated with myositis in pediatric patients with SARS-CoV-2 infection. Between January 2022 and January 2023, ten pediatric patients diagnosed with myositis and SARS-CoV-2 infection were evaluated. The study highlighted clinical manifestations such as fever, calf muscle pain, and abnormal gait. Lab results showed elevated CK levels among other findings. All patients underwent treatment, with the majority recovering without complications. A notable correlation was observed between CK levels, blood urea nitrogen (BUN), and the urea/creatinine ratio (UCR). The study also discusses potential pathophysiological mechanisms behind SARS-CoV-2's impact on skeletal muscles, emphasizing an indirect inflammatory response. Our findings underscore that while myositis in children with SARS-CoV-2 infection appears to follow a benign and self-limiting trajectory, it is crucial to monitor specific markers for early intervention and management. Further research is warranted to elucidate the underlying mechanisms and improve clinical outcomes.

Case report: Incidence and prognostic value of brain MRI lesions and elevated cerebrospinal fluid protein in children with Guillain-Barré syndrome.

Background: Guillain-Barrè syndrome (GBS) is an acute immune-mediated disorder affecting peripheral nerves and nerve roots with a variable clinical course and outcome. Epidemiologic analyses have revealed that the incidence of the syndrome increases linearly among the age. The clinical diagnosis of GBS is based on the family history, physical and neurological examination, electrodiagnostic exams, and cerebrospinal fluid analysis with the classical presence of albumin-cytologic dissociation. Prognosis is associated with the severity of clinical signs and the type of peripheral nerves involved. Methods: This study aims to clarify which clinical features can be used for prognostic purposes. We evaluated the correlation between (1) brain MRI lesions and grade of disability; (2) brain MRI lesions and elevated cerebrospinal fluid (CSF) protein; and (3) increased levels of CSF protein and grade of disability. Statistical analysis extracted from these data indicated a good correlation to be a prognostic indicator in children affected by GBS. We found little evidence regarding laboratory tests, imaging, and prognosis. We enrolled 12 continuous patients who met the Brighton criteria for GBS in this retrospective study. Each patient was clinically evaluated at the time of disease onset to assess the GBS disability score and after 2 weeks. Results: We estimated Pearson's correlation index to evaluate the possible correlation between MRI and disability and CSF protein levels and disability. The correlation coefficient was 0.92 and 0.85, respectively. In addition, we developed a graph to see the trend of the disability values, proteins in the CSF, and damage assessed with MRI in the 12 patients. It seems that these parameters have a parallel trend and a good correlation in each patient. Finally, we calculated the correlation between MRI and CSF protein values, with an r-value of 0.87. The values suggest a correlation among the MRI score, CSF protein, and prognosis. Conclusion: The MRI and CSF laboratory parameters can be important tools for the clinician not only for diagnosis but also to evaluate the possible worsening of general conditions or the need to prepare measures to support life parameters. Patients who need ventilatory support could be established early from patients who have less severe GBS and can begin rehabilitation earlier. We suggest MRI should be performed routinely in children with GBS to be able to estimate the evolution of the clinical condition.

Ketogenic diet in pediatric seizures: a randomized controlled trial review and meta-analysis.

BACKGROUND: The ketogenic diet is a non-pharmacologic treatment option for children with drug-resistant epilepsy. This systematic review and meta-analysis aimed to assess the efficacy of the ketogenic diet on seizures frequency in children. METHODS: We reviewed the literature using Cochrane, EMBASE, MEDLINE, and highly qualified journals.Randomized controlled trials were chosen to investigate the seizures-free regime or at least 50% seizures reduction after three months from the starting of the ketogenic diet or earlier. We have selected articles from January 2011 to January 2020.Eight articles were eligible. The data show a significant reduction in seizure frequency in the dietary treatment pediatric population. The rate of a seizures-free regime or at least 50% seizures reduction was 48.31% of patients in the intervention group. RESULTS: Our overall meta-analysis underlined the significant efficacy. The KD group is 5.6 times more likely than the control group to have a 50% reduction of seizures after three months of the diet or earlier.QUADAS and AMSTAR assessments showed a low risk of bias and adequate accuracy. CONCLUSION: The results show that the KD reduces seizure frequency in children with drug-refractory epilepsy. KD is an effective treatment option for children and adolescents with refractory epilepsy.

Age, homocysteine, and oxidative stress: relation to hypertension and type 2 diabetes mellitus.

OBJECTIVES: Hyperhomocysteinemia and oxidative stress are independent risk factors for cardiovascular events, which occur more frequently in old age. We evaluated these parameters in relation to age and the presence of hypertension and type 2 diabetes mellitus. METHODS: Two hundred eighty-two subjects (female/male: 142/140; 141 were >65 years and 141 were <65 years; mean age 73.9 +/- 6.6 years and 52.5 +/- 8.2 years, respectively) were randomly recruited from those attending our institution. Blood pressure, anthropometric parameters, oxidative stress parameters (reactive oxygen species [ROS] and malondialdehyde [MDA]), and homocysteine levels were evaluated in participants. RESULTS: Homocysteine (2.9 +/- 0.06 vs. 2.3 +/- 0.03 micromol/L, p < 0.001) and oxidative stress (ROS: 10.8 +/- 0.3 vs. 8.1 +/- 0.3 mmol/L, p < 0.001; MDA: 1.62 +/- 0.05 vs. 1.21 +/- 0.05 nmol/mL, p < 0.001) were significantly higher in older vs. younger subjects without hypertension or diabetes. However, homocysteine and MDA were not significantly different in older vs. younger hypertensive subjects (homocysteine: 3.0 +/- 0.03 vs. 2.9 +/- 0.04 micromol/L, p = NS; MDA: 1.7 +/- 0.07 vs. 1.4 +/- 0.06 nmol/mL, p = NS) and in older vs. younger diabetic hypertensive subjects (homocysteine: 3.02 +/- 0.05 vs. 2.9 +/- 0.05 micromol/L, p = NS; ROS: 10.7 +/- 0.7 vs. 9.7 +/- 0.8 mmol/L, p = NS; MDA: 1.6 +/- 0.10 vs. 1.5 +/- 0.12 nmol/mL, p = NS). CONCLUSIONS: Aging is accompanied by elevated homocysteine and oxidative stress levels similar to those observed in younger subjects with hypertension or diabetes mellitus, independent of age. Hence, these conditions appear to accelerate the age-dependent increase in homocysteine and oxidative stress.

Azithromycin in an older woman with diabetic gastroparesis.

Diabetic neuropathy is a common chronic complication of diabetes and cause of significant morbidity and mortality, because it may involve the autonomous and peripheral nervous systems. Autonomic diabetic neuropathy is a challenging chronic complication of long-standing diabetes manifested with hypotension, syncope, gastroparesis, diarrhea, constipation, bladder dysfunction, sexual dysfunction, cardiac arrest, and/or sudden death. We present a case of diabetic gastroparesis in an older woman. The patient was an 83-year-old woman with a 40-year history of type 2 diabetes who was admitted with hypoglycemia, malnutrition, persistent vomiting, and obstinate constipation. After several unsuccessful attempts with different therapies, we administered intravenous azithromycin (500 mg/day). After 3 days of treatment, vomiting was resolved and the patient evacuated normal feces, with notable improvement in the general conditions and metabolic control. Because diabetic gastroparesis frequently is difficult to manage clinically and there are few beneficial therapeutic choices available at present, the macrolide antibiotic azithromycin, which has strong prokinetic properties, may be a useful option in the treatment of this complex condition.

Cardiovascular risk factors in centenarians.

Several studies have shown that centenarians have better cardiovascular risk profiles compared to younger old people. Some reports have revealed that cardiovascular diseases (i.e. hypertension, diabetes, angina and/or myocardial infarction) are less common in centenarians respect to 70 and 80 years old persons. In order to explain this evidence, there is a growing number of hypothesis that consider a combination of genetic factors and lifestyle aspects to elucidate the exceptional longevity of centenarians, able to overcome the most frequent mortality cause, which is a cardiovascular event. It has been suggested that a role on this better cardiovascular risk profile may be played by the increasing use of pharmacologic treatments in the elderly population (specially for hypertension and dyslipidemia), but the contribution of drug treatments to promote extreme longevity is not confirmed. Furthermore, centenarians in general have needed fewer drugs at younger ages due to a healthy lifestyle. The importance of the genetic contribution is demonstrated by the inheritance of low-risk cardiovascular profiles in centenarian offspring and lower prevalence of cardiovascular diseases in this population as compared with their spouses or with age-matched subjects without centenarian parents. Another advantage in centenarians' offspring seems to be a delay in the onset for cardiovascular diseases, respect to age- and sex-matched controls. Cardiovascular risk factors mirror the factors that contribute to longevity. Hence, it is not surprising that these risk factors are less prevalent in centenarians when compared to younger old individuals.

Blood pressure and cardiovascular risk profiles of Africans who migrate to a Western country.

OBJECTIVES: Africans who live in Western countries have a higher prevalence of hypertension and other cardiovascular risk factors than do age-matched Africans who live in Africa. We conducted a community survey to evaluate cardiovascular risk in Africans who recently migrated to Italy. METHODS: Participants (N=83) from sub-Saharan Africa were recruited from an outpatient clinic for immigrants. Information on immigration date, family history of cardiovascular disease, physical activity, and smoking was obtained for all participants. Anthropometric parameters, blood pressure measurements, and laboratory analyses--including lipid profiles, plasma glucose, renal function, and serum and urinary electrolytes--were performed. RESULTS: Although participants who had recently arrived in Italy had a low cardiovascular risk, the correlations were significant between the length of time in Italy and body weight (r=.47, P<.001), body mass index (r=.59, P<.0001), waist circumference (r=.54, P<.0001), total cholesterol (r=.41, P<.001), low-density lipoprotein cholesterol (r=.46, P<.0001), systolic blood pressure (r=.31, P<.01), and diastolic blood pressure (r=.23, P<.05). The rise in systolic and diastolic blood pressure was positively correlated with body weight, body mass index, and waist circumference (P<.05 for all) and inversely correlated with 24-hour urinary potassium (systolic blood pressure, r=-.35, P<.01; diastolic blood pressure, r=-.42, P<.0001). CONCLUSIONS: The length of residence in Italy is associated with progressive modifications in cardiovascular risk even in a relatively short period of time. The inverse correlation between blood pressure and urinary potassium may reflect dietary changes, with a possible reduction in fruit and vegetable consumption compared with their original diet.