A comprehensive review of genetic causes of obesity.

BACKGROUND: Obesity is a multifactorial chronic disease with a high, increasing worldwide prevalence. Genetic causes account for 7% of the cases in children with extreme obesity. DATA SOURCES: This narrative review was conducted by searching for papers published in the PubMed/MEDLINE, Embase and SciELO databases and included 161 articles. The search used the following search terms: "obesity", "obesity and genetics", "leptin", "Prader-Willi syndrome", and "melanocortins". The types of studies included were systematic reviews, clinical trials, prospective cohort studies, cross-sectional and prospective studies, narrative reviews, and case reports. RESULTS: The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight. However, several important aspects of the pathophysiology of obesity remain unknown. Genetic causes of obesity can be grouped into syndromic, monogenic, and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years, hyperphagia, or a family history of extreme obesity. A microarray study, an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose. There are three therapeutic levels: lifestyle modifications, pharmacological treatment, and bariatric surgery. CONCLUSIONS: Genetic study technologies are in constant development; however, we are still far from having a personalized approach to genetic causes of obesity. A significant proportion of the affected individuals are associated with genetic causes; however, there are still barriers to its approach, as it continues to be underdiagnosed. Video Abstract (MP4 1041807 KB).

Ifosfamide-induced nephrotoxicity in oncological patients.

INTRODUCTION: Ifosfamide is an alkylating chemotherapeutic agent used in the treatment of various neoplasms. Its main adverse effects include renal damage. AREAS COVERED: A comprehensive review was conducted, including 100 articles from the Scielo, Scopus, and EMBASE databases. Ifosfamide-induced nephrotoxicity is attributed to its toxic metabolites, such as acrolein and chloroacetaldehyde, which cause mitochondrial damage and oxidative stress in renal tubular cells. Literature review found a 29-year average age with no gender predominance and a mortality of 13%. Currently, no fully effective strategy exists for preventing ifosfamide-induced nephrotoxicity; however, hydration, forced diuresis, and other interventions are employed to limit renal damage. Long-term renal function monitoring is essential for patients treated with ifosfamide. EXPERT OPINION: Ifosfamide remains essential in neoplasm treatment, but nephrotoxicity, often compounded by coadministered drugs, poses diagnostic challenges. Preventive strategies are lacking, necessitating further research. Identifying timely risk factors can mitigate renal damage, and a multidisciplinary approach manages established nephrotoxicity. Emerging therapies may reduce ifosfamide induced nephrotoxicity.

Ifosfamide is a type of chemotherapy used to treat different types of cancers. However, one of its main side effects is kidney damage. Researchers reviewed 100 articles from medical databases to understand how ifosfamide affects the kidneys. The kidney damage is caused by harmful substances produced when ifosfamide is broken down in the body. These substances can harm the cells in the kidneys. Studies have shown that 13% of the patients treated with ifosfamide can die. Currently, there is no perfect way to prevent kidney damage from ifosfamide, but doctors try to protect the kidneys by giving patients plenty of fluids and using other treatments, so it's important for patients who receive ifosfamide to have their kidney function checked regularly. Although ifosfamide is effective against cancer, its potential kidney side effects should be carefully considered by doctors when deciding on the best treatment for each patient.

Cushing disease in pediatrics: an update.

Cushing disease (CD) is the main cause of endogenous Cushing syndrome (CS) and is produced by an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma. Its relevance in pediatrics is due to the retardation of both growth and developmental processes because of hypercortisolism. In childhood, the main features of CS are facial changes, rapid or exaggerated weight gain, hirsutism, virilization, and acne. Endogenous hypercortisolism should be established after exogenous CS has been ruled out based on 24-hour urinary free cortisol, midnight serum or salivary cortisol, and dexamethasone suppression test; after that, ACTH dependence should be established. The diagnosis should be confirmed by pathology. The goal of treatment is to normalize cortisol level and reverse the signs and symptoms. Treatment options include surgery, medication, radiotherapy, or combined therapy. CD represents a challenge for physicians owing to its multiple associated conditions involving growth and pubertal development; thus, it is important to achieve an early diagnosis and treatment in order to control hypercortisolism and improve the prognosis. Its rarity in pediatric patients has led physicians to have limited experience in its management. The objective of this narrative review is to summarize the current knowledge about the pathophysiology, diagnosis, and treatment of CD in the pediatric population.

Late Diagnosis of Partial Androgen Insensitivity Syndrome in a Peruvian Child.

Disorders of sexual differentiation are congenital pathologies characterized by atypical development of genetic, gonadal, or phenotypic sex. These are caused by the alteration of any primordial phases of sexual development and may be evident at birth or in the later stage of life. Here, we present the case of a nine-year-old Peruvian school patient who has female gender assigned at birth, has no contributory antecedents and was found to have clitoromegaly and hypospadia on physical examination. In the blood tests, anti-Müllerian hormone and testosterone were found, and 46 XY karyotype and sex-determining region Y (SRY) genes were present. On abdominal ultrasound, testicles were found in the inguinal canals. The human chorionic gonadotropin (HCG) stimulation test was conducted, which allowed us to rule out defects in testosterone biosynthesis and enzyme defects in dihydrotestosterone production; the main suspected diagnosis was partial androgen insensitivity syndrome (PAIS). A multidisciplinary medical meeting was held, accepting the patient's desire to opt for the male gender, after acceptance by the parents. Thus, the patient underwent bilateral orchidopexy and genitoplasty. He is currently receiving therapy with testosterone, with an adequate response to the treatment and the molecular study confirmed the androgen-receptor gene mutation. In conclusion, we highlight the importance of a timely multidisciplinary diagnosis and management of disorders of sexual differentiation to avoid premature gender assignment and major social and family repercussions that it implies.

Familial Chylomicronemia Syndrome-Induced Acute Necrotizing Pancreatitis during Pregnancy.

Acute pancreatitis is a rare condition in pregnancy, associated with a high mortality rate. Hypertriglyceridemia represents its second most common cause. We present the case of a 38-year-old woman in the 24th week of gestation with a history of hypertriglyceridemia and recurrent episodes of pancreatitis. She was admitted to our hospital with acute pancreatitis due to severe hypertriglyceridemia. She was stabilized and treated with fibrates. Despite her favorable clinical course, she developed a second episode of acute pancreatitis complicated by multi-organ dysfunction and pancreatic necrosis, requiring a necrosectomy. The pregnancy was ended by cesarean section, after which three plasmapheresis sessions were performed. She is currently asymptomatic with stable triglyceride levels. Acute pancreatitis due to hypertriglyceridemia represents a diagnostic and therapeutic challenge in pregnant women, associated with serious maternal and fetal complications. When primary hypertriglyceridemia is suspected, such as familial chylomicronemia syndrome, the most important objective is preventing the onset of pancreatitis.

Bilateral Neonatal Adrenal Hemorrhage Associated With Severe Maternal COVID-19 Infection.

Adrenal hemorrhage is the most common cause of adrenal mass in newborns. We present a case of a full-term male, born by cesarean section due to acute fetal distress from a mother with severe coronavirus disease 2019 (COVID-19) infection. He was diagnosed with hypoxic-ischemic encephalopathy, multifactorial shock, and early neonatal sepsis. On the seventh day of hospitalization, hemoglobin dropped and thus blood transfusion was required, and abdominal ultrasound showed bilateral adrenal hemorrhage. He developed relative adrenal insufficiency without either hemodynamic instability or electrolyte imbalances. The use of parenteral corticosteroids was not required. Follow-up ultrasonography and adrenal axis laboratory examination revealed complete resolution of adrenal hemorrhage. Neonatal adrenal hemorrhage has a wide variety of clinical manifestations. Ultrasound is preferred for both initial screening and follow-up evaluation. Adrenal insufficiency occurs rarely in neonatal adrenal hemorrhage. Treatment is usually conservative. We emphasize the importance of a timely diagnosis and clinical follow-up of adrenal hemorrhage in neonates with fetal distress born from mothers with severe COVID-19.

Factores de riesgo y displasia broncopulmonar en recién nacidos prematuros de muy bajo peso al nacer / Risk factors and bronchopulmonary dysplasia in very low weight premature infants

Introducción: La displasia broncopulmonar es la secuela más común relacionada con los recién nacidos prematuros de muy bajo peso al nacer, derivada de la inmadurez pulmonar y en algunos casos del tratamiento. Objetivo: Identificar los factores de riesgo maternos y neonatales asociados a displasia broncopulmonar en recién nacidos prematuros de muy bajo peso al nacer. Métodos: La muestra estuvo conformada por 205 recién nacidos prematuros de muy bajo peso al nacer en el Hospital Belén de Trujillo, durante el período 2008-2015. El grupo de casos y el de controles fueron 41 pacientes con diagnóstico de displasia broncopulmonar y 164 pacientes sin diagnóstico de este trastorno respiratorio y que se ajustaran a los criterios de exclusión. Resultados: Los factores de riesgo asociados a displasia broncopulmonar fueron dos o más episodios de sepsis tardía (OR= 5,12; IC95 por ciento: 1,87-14,06), la prematuridad extrema (OR= 4,86; IC95 por ciento: 1,71-13,80), el peso extremadamente bajo al nacer (OR= 2,72; IC95 por ciento: 0,93- 7,94) y la reanimación neonatal (OR= 2,28; IC95 por ciento: 0,89-5,87). Conclusiones: La prematuridad extrema y dos episodios o más de sepsis tardía fueron los factores de riesgo que más se relacionan con la aparición de displasia broncopulmonar en recién nacidos prematuros de muy bajo peso al nacer(AU)

Introduction: Bronchopulmonary dysplasia is the most common sequelae related to very low birth weight premature infants, and it is derived from pulmonary immaturity and in some cases from treatment. Objective: To identify maternal and neonatal risk factors associated with bronchopulmonary dysplasia in very low birth weight premature infants. Methods: The sample was composed of 205 very low birth weight premature infants at Belén of Trujillo Hospital during the period 2008-2015. The group of cases and controls were 41 patients with diagnosis of bronchopulmonary dysplasia and 164 patients with no diagnosis of this respiratory disorder, respectively, and that both groups adjusted with exclusion criteria. Results: Risk factors associated with bronchopulmonary dysplasia were 2 or more episodes of late onset sepsis (OR=5.12; IC95 percent: 1,87-14,06), extreme prematurity (OR= 4.86; IC95 percent: 1.7-13.80), extremely low birth weight (OR= 2.72; IC95 percent: 0.9-7.94) and neonatal resuscitation (OR= 2.28; IC95 percent: 0.89-5.87). Conclusions: Extreme prematurity and 2 or more episodes of late onset sepsis were the most associated risk factors to the onset of bronchopulmonary dysplasia in very low birth weight premature infants(AU)