Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

BACKGROUND: Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure. Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome. OBJECTIVES: To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 2 June 2023. SELECTION CRITERIA: We included only randomised clinical trials with a parallel-group design, which compared the TIPS placement with sham, no intervention, conventional therapy, or other therapies, in adults aged 18 years or older, regardless of sex or ethnicity, diagnosed with chronic liver disease and hepatorenal syndrome. We excluded trials of adults with kidney failure due to causes not related to hepatorenal syndrome, and we also excluded data from quasi-randomised, cross-over, and observational study designs as we did not design a separate search for such studies. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. morbidity due to any cause, and 3. serious adverse events. Our secondary outcomes were 1. health-related quality of life, 2. non-serious adverse events, 3. participants who did not receive a liver transplant, 4. participants without improvement in kidney function, and 5. length of hospitalisation. We performed fixed-effect and random-effects meta-analyses using risk ratio (RR) or Peto odds ratio (Peto OR), with 95% confidence intervals (CI) for the dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for the continuous outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included two randomised clinical trials comparing TIPS placement (64 participants) versus conventional treatment (paracentesis plus albumin 8 g/L of removed ascites) (66 participants). The co-interventions used in the trials were dietary treatment (sodium less than 60 mmoL/day), spironolactone (300 mg/day to 400 mg/day), and furosemide (120 mg/day). Follow-up was up to 24 months. Both were multicentre trials from Spain and the USA, and Germany, conducted between 1993 and 2002. Most participants were men (aged 18 to 75 years). We are uncertain about the effect of TIPS placement compared with conventional treatment, during the first 24 months of follow-up, on all-cause mortality (RR 0.88, 95% CI 0.55 to 1.38; 2 trials, 130 participants; I2 = 58%; very low-certainty evidence) and on the development of any serious adverse event (RR 1.60, 95% CI 0.10 to 24.59; 2 trials, 130 participants; I2 = 78%; very low-certainty evidence). The use of TIPS may or may not result in a decrease in overall morbidity such as bacterial peritonitis, encephalopathy, or refractory ascites, during the first 24 months of follow-up, compared with the conventional treatment (RR 0.95, 95% CI 0.77 to 1.18; 2 trials, 130 participants; I2 = 0%; low-certainty evidence). We are uncertain about the effect of TIPS placement versus conventional treatment on the number of people who did not receive a liver transplant (RR 1.03, 95% CI 0.93 to 1.14; 2 trials, 130 participants; I2 = 0%; very low-certainty evidence) or on the length of hospitalisation (MD -20.0 days, 95% CI -39.92 to -0.08; 1 trial, 60 participants; very low-certainty evidence). Kidney function may improve in participants with TIPS placement (RR 0.53, 95% CI 0.27 to 1.02; 1 trial, 70 participants; low-certainty evidence). No trials reported health-related quality of life, non-serious adverse events, or number of participants with improvement in liver function associated with the TIPS placement. Funding No trials reported sources of commercial funding or conflicts of interest between researchers. Ongoing studies We found one ongoing trial comparing TIPS with conventional therapy (terlipressin plus albumin) and listed one study as awaiting classification as no full-text article could be found. AUTHORS' CONCLUSIONS: TIPS placement was compared with conventional treatment, with a follow-up of 24 months, in adults with hepatorenal syndrome type 2. Based on two trials with insufficient sample size and trial limitations, we assessed the overall certainty of evidence as low or very low. We are unsure if TIPS may decrease all-cause mortality, serious adverse events, the number of people who did not receive a liver transplant, and the days of hospitalisation because of the very low-certainty evidence. We are unsure if TIPS, compared with conventional treatment, has better effects on overall morbidity (bacterial peritonitis, encephalopathy, or refractory ascites). TIPS may improve kidney function, but the certainty of evidence is low. The trials included no data on health-related quality of life, non-serious adverse events, and liver function associated with the TIPS placement. We identified one ongoing trial and one study awaiting classification which may contribute to the review when information becomes available.

Higher versus lower protein intake in formula-fed term infants.

BACKGROUND: Many infants are fed infant formulas to promote growth. Some formulas have a high protein content (≥ 2.5 g per 100 kcal) to accelerate weight gain during the first year of life. The risk-benefit balance of these formulas is unclear. OBJECTIVES: To evaluate the benefits and harms of higher protein intake versus lower protein intake in healthy, formula-fed term infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, OpenGrey, clinical trial registries, and conference proceedings in October 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of healthy formula-fed infants (those fed only formula and those given formula as a complementary food). We included infants of any sex or ethnicity who were fed infant formula for at least three consecutive months at any time from birth. We excluded quasi-randomized trials, observational studies, and infants with congenital malformations or serious underlying diseases. We defined high protein content as 2.5 g or more per 100 kcal, and low protein content as less than 1.8 g per 100 kcal (for exclusive formula feeding) or less than 1.7 g per 100 kcal (for complementary formula feeding). DATA COLLECTION AND ANALYSIS: Four review authors independently assessed the risk of bias and extracted data from trials, and a fifth review author resolved discrepancies. We performed random-effects meta-analyses, calculating risk ratios (RRs) or Peto odds ratios (Peto ORs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. We used the GRADE approach to evaluate the certainty of the evidence. MAIN RESULTS: We included 11 RCTs (1185 infants) conducted in high-income countries. Seven trials (1629 infants) compared high-protein formula against standard-protein formula, and four trials (256 infants) compared standard-protein formula against low-protein formula. The longest follow-up was 11 years. High-protein formula versus standard-protein formula We found very low-certainty evidence that feeding healthy term infants high-protein formula compared to standard-protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.05 SDs, 95% CI -0.09 to 0.19; P = 0.51, I2 = 61%; 7 studies, 1629 participants), stunting (MD in height-for-age z-score 0.15 SDs, 95% CI -0.05 to 0.35; P = 0.14, I2 = 73%; 7 studies, 1629 participants), and wasting (MD in weight-for-height z-score -0.12 SDs, 95% CI -0.31 to 0.07; P = 0.20, I2 = 94%; 7 studies, 1629 participants) in the first year of life. We found very low-certainty evidence that feeding healthy infants high-protein formula compared to standard-protein formula has little or no effect on the occurrence of overweight (RR 1.26, 95% CI 0.63 to 2.51; P = 0.51; 1 study, 1090 participants) or obesity (RR 1.96, 95% CI 0.59 to 6.48; P = 0.27; 1 study, 1090 participants) at five years of follow-up. No studies reported all-cause mortality. Feeding healthy infants high-protein formula compared to standard-protein formula may have little or no effect on the occurrence of adverse events such as diarrhea, vomiting, or milk hypersensitivity (RR 0.93, 95% CI 0.76 to 1.13; P = 0.44, I2 = 0%; 4 studies, 445 participants; low-certainty evidence) in the first year of life. Standard-protein formula versus low-protein formula We found very low-certainty evidence that feeding healthy infants standard-protein formula compared to low-protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.0, 95% CI -0.43 to 0.43; P = 0.99, I2 = 81%; 4 studies, 256 participants), stunting (MD in height-for-age z-score -0.01, 95% CI -0.36 to 0.35; P = 0.96, I2 = 73%; 4 studies, 256 participants), and wasting (MD in weight-for-height z-score 0.13, 95% CI -0.29 to 0.56; P = 0.54, I2 = 95%; 4 studies, 256 participants) in the first year of life. No studies reported overweight, obesity, or all-cause mortality. Feeding healthy infants standard-protein formula compared to low-protein formula may have little or no effect on the occurrence of adverse events such as diarrhea, vomiting, or milk hypersensitivity (Peto OR 1.55, 95% CI 0.70 to 3.40; P = 0.28, I2 = 0%; 2 studies, 206 participants; low-certainty evidence) in the first four months of life. AUTHORS' CONCLUSIONS: We are unsure if feeding healthy infants high-protein formula compared to standard-protein formula has an effect on undernutrition, overweight, or obesity. There may be little or no difference in the risk of adverse effects between infants fed with high-protein formula versus those fed with standard-protein formula. We are unsure if feeding healthy infants standard-protein formula compared to low-protein formula has any effect on undernutrition. There may be little or no difference in the risk of adverse effects between infants fed with standard-protein formula versus those fed with low-protein formula. The findings of six ongoing studies and two studies awaiting classification studies may change the conclusions of this review.

Efficacy and safety of quinolones for the treatment of uncomplicated urinary tract infections in women: a network meta-analysis.

INTRODUCTION AND HYPOTHESIS: Uncomplicated urinary tract infection (uUTI) is defined as the presence of pathogenic organisms in the urinary tract without anatomical and functional abnormalities, is accompanied by inflammatory leukocytes and cytokines and may or may not develop clinical symptoms. The frequency of uncomplicated urinary tract infection is higher in young women. Several quinolone treatment regimens are available; however, since we do not know which is the best antibiotic regimen for the treatment of this urinary infection, we analyzed the published evidence and conducted a systematic review with network meta-analysis. The aim was to compare and hierarchize quinolones according to their efficacy and safety and to identify the best treatment for uncomplicated urinary tract infection in women through a systematic review with network meta-analysis. METHODS: Medline, Embase, LILACS, Cochrane CENTRAL and other databases were searched for trials. Bias in the trials was assessed using the Cochrane Collaboration tool. To analyze efficacy and adverse events, for direct comparisons, we obtained risk ratios and 95% confidence intervals by applying a fixed-effects model using tau2 and Q2 tests to calculate the heterogeneity. For the network meta-analysis, we analyzed the indirect comparisons by Bucher's method. RESULTS: We included 18 trials (8765 women). For premenopausal women, ofloxacin had a 57% probability of achieving remission but an 83% frequency of adverse events. For postmenopausal women, ofloxacin was 82% more effective for remission, with a 49% frequency of adverse events, compared with other types of quinolones. CONCLUSIONS: Compared with other quinolones, ofloxacin 200 mg once daily for a treatment duration < 3 days provides the highest clinical and bacteriological remission rates with the lowest relapse and resistance rates for the treatment of women with uUTIs. However, additional trials are needed to confirm our findings, especially when the treatment duration exceeds 3 days.

Variants in ARID5B gene are associated with the development of acute lymphoblastic leukemia in Mexican children.

A high impact of ARID5B SNPs on acute lymphoblastic leukemia (ALL) susceptibility has been described in Hispanic children; therefore, it is relevant to know if they influence the high incidence of childhood-ALL in Mexicans. Seven SNPs (rs10821936, rs10994982, rs7089424, rs2393732, rs2393782, rs2893881, rs4948488) of ARID5B were analyzed in 384 controls and 298 ALL children using genomic DNA and TaqMan probes. The SNPs were analyzed for deviation of Hardy-Weinberg equilibrium; Fisher's exact test was used to compare the genotypic and allelic frequencies between controls and patients. The association between SNPs and ALL susceptibility was calculated, and haplotype and ancestry analyses were conducted. All SNPs were associated with ALL, pre-B ALL, and hyperdiploid-ALL susceptibility (p < 0.05). No association with T-ALL and gene fusions was found (p > 0.05). The seven SNPs were associated with risk of pre-B ALL in younger children; however, rs2393732, rs2393782, rs2893881, and rs4948488 were not associated with susceptibility in older children and adolescents. The CAG haplotype (rs10821936, rs10994982, rs7089424) was strongly associated with ALL risk in our population (p < 0.00001). The frequency of all risk alleles in our ALL, pre-B, and hyperdiploid-ALL patients was higher than that in Hispanic children reported. This is the first report showing the association between rs2393732, rs2393782, and rs4948488 with pre-B hyperdiploid-ALL children. The G allele at rs2893881 confers major risk for pre-B hyperdiploid-ALL in Mexican (OR, 2.29) than in Hispanic children (OR, 1.71). The genetic background of our population could influence the susceptibility to ALL and explain its high incidence in Mexico.

The burden of childhood cancer in Mexico: Implications for low- and middle-income countries.

In Mexico, childhood cancer incidence and mortality have increased in the last decade. Through government actions since 2005, the Popular Medical Insurance (PMI) program for childhood cancer was created. The objective of PMI was to offer early cancer diagnosis, standardized treatment regimens, and numerous pediatric oncology residency programs. It has also accredited 55 national hospitals for the care of these children. Current problems still present under the PMI include shortage of pediatric oncologists and nurses and high rate of abandonment of treatment. Our aim is to describe the current scenario of childhood cancer care in Mexico, especially from the perspective of the PMI and how it has impacted human resources, infrastructure, and medical education.

Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma.

Osteosarcoma is the most common primary bone tumor, yet there have been no substantial advances in treatment or survival in three decades. We examined 59 tumor/normal pairs by whole-exome, whole-genome, and RNA-sequencing. Only the TP53 gene was mutated at significant frequency across all samples. The mean nonsilent somatic mutation rate was 1.2 mutations per megabase, and there was a median of 230 somatic rearrangements per tumor. Complex chains of rearrangements and localized hypermutation were detected in almost all cases. Given the intertumor heterogeneity, the extent of genomic instability, and the difficulty in acquiring a large sample size in a rare tumor, we used several methods to identify genomic events contributing to osteosarcoma survival. Pathway analysis, a heuristic analytic algorithm, a comparative oncology approach, and an shRNA screen converged on the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway as a central vulnerability for therapeutic exploitation in osteosarcoma. Osteosarcoma cell lines are responsive to pharmacologic and genetic inhibition of the PI3K/mTOR pathway both in vitro and in vivo.

Current outlook of childhood cancer epidemiology in a middle-income country under a public health insurance program.

In Mexico, childhood cancer (0-18 years) is treated in a multidisciplinary way while providing care for more than half of the affected children through a public medical insurance. This insurance is given to all children who do not have any health care coverage in Mexico. This program is offered to the poorest of all Mexicans. All the children with this disease are submitted to pathology diagnosis and treatment according to national treatment protocols from 57 accredited medical institutions. From 2007 to 2015, a total of 24,039 children with cancer have been registered; the male gender predominates by 55%. The highest incidence was in the group aged between 0 and 4 years. Every year, there has been an increment in registration. In 2015, there were 3,433 new patients with an incidence of 150.1/million. In the same year, the incidence for all types of leukemia increased to 89.5/million. But for acute lymphoblastic leukemia, the incidence was found to be 79.8/million, which is extremely high. The mortality rate for all these patients in 2015 was 5.3/100,000. However, with regard to children aged between 15 and 18 years, the mortality rate was 8.5/100,000. Abandonment rate was 10%, and there were nine state institutions that had a mortality rate between 25% and 50% among their patients. Coincidentally, as per the Human Development Index, the parameters for education, health, and income were low for those nine institutions. The purpose of this work is to show the epidemiology and the burden we are facing due to this disease.

Descriptive Epidemiology in Mexican children with cancer under an open national public health insurance program.

BACKGROUND: All the children registered at the National Council for the Prevention and Treatment of Childhood Cancer were analyzed. The rationale for this Federal Government Council is to financially support the treatment of all children registered into this system. All patients are within a network of 55 public certified hospitals nationwide. METHODS: In the current study, data from 2007 to 2012 are presented for all patients (0-18 years) with a pathological diagnosis of leukemia, lymphoma and solid tumors. The parameters analyzed were prevalence, incidence, mortality, and abandonment rate. RESULTS: A diagnosis of cancer was documented in 14,178 children. The incidence was of 156.9/million/year (2012). The median age was 4.9. The most common childhood cancer is leukemia, which occurs in 49.8% of patients (2007-2012); and has an incidence rate of 78.1/million/year (2012). The national mortality rate was 5.3/100,000 in 2012, however in the group between 15 to 18 years it reaches a level of 8.6. CONCLUSIONS: The study demonstrates that there is a high incidence of childhood cancer in Mexico. In particular, the results reveal an elevated incidence and prevalence of leukemia especially from 0 to 4 years. Only 4.7% of these patients abandoned treatment. The clinical outcome for all of the children studied improved since the establishment of this national program.

Ambroxol for women at risk of preterm birth for preventing neonatal respiratory distress syndrome.

BACKGROUND: Respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant (an active agent that keeps pulmonary alveoli open and facilitates the entry of air to the lungs, thus improving the oxygenation of the newborn).A number of interventions such as pulmonary surfactant and prenatal corticosteroids are used to prevent RDS. Ambroxol has been studied as a potential agent to prevent RDS, but effectiveness and safety has yet to be evaluated. OBJECTIVES: To evaluate the efficacy and safety of giving ambroxol to pregnant women who are at risk of preterm birth, for preventing neonatal RDS. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 November 2013), CENTRAL (The Cochrane Library 2013, Issue 11),Embase (1988 to November 2013), MEDLINE (PubMed 1970 to November 2013), LILACS (1982 to November 2013), the WHO International Clinical Trials Registry Platform (ICTRP) (November 2013) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the administration of ambroxol given to pregnant women at risk of preterm birth versus placebo, antenatal corticosteroids (betamethasone or dexamethasone), or no treatment.We did not identify any trials comparing ambroxol with dexamethasone (corticosteroid) in this review. Nor did we identify any trials comparing ambroxol combined with corticosteroid versus corticosteroid alone, or placebo/no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: We included 14 studies (in 18 trial reports), involving 1047 pregnant women at risk of preterm birth with 1077 newborns. However, three of the included studies did not report on this review's outcomes of interest. We carried out two main comparisons: ambroxol versus antenatal corticosteroids (betamethasone); and ambroxol versus placebo or no treatment. Seven RCTs provided data for our comparison of ambroxol versus corticosteroid (betamethasone) and two trials contributed data to our comparison of ambroxol compared to placebo or no treatment.The included studies were generally judged as having either 'low' risk of bias or 'unclear' risk of bias (because the trial reports provided insufficient details about methods of sequence generation, allocation concealment and blinding). Primary outcomesThere was no clear evidence of a difference in the incidence of RDS among newborns born to women who received ambroxol when compared to newborns of women who were given the corticosteroid, betamethasone (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07, seven RCTs, 728 women/758 newborns, moderate quality evidence) or placebo/no treatment (average RR 0.74; 95% CI 0.46 to 1.20, two studies, 204 women/204 newborns,T2= 0.07; I(2)= 53%, low-quality evidence). Results were imprecise and consistent with appreciable benefit as well as negligible effect.Similarly, there was no clear evidence of a difference in the rates of perinatal mortality between the group of women who received ambroxol and women in the corticosteroid (betamethasone) group (RR 0.51, 95% CI 0.23 to 1.12, six studies, 648 women/657 newborns, moderate quality evidence) or the placebo/no treatment group (RR 0.61; 95% CI 0.19 to 1.98, one study, 116 women/116 newborns, low-quality evidence).In terms of maternal adverse effects, there was no clear differences (in nausea or vomiting) between those women who received ambroxol compared to either those women who received corticosteroids (betamethasone) (average RR 3.45; 95% CI 0.34 to 35.51, three studies, 305 women, T(2)= 2.82; I(2)= 67%, very low-quality evidence), or women who received placebo or no treatment (RR 1.79; 95% CI 0.45 to 7.13, one study, 116 women, low-quality evidence). No other adverse effects (e.g. diarrhoea, gastric irritation and headache) were reported in the included studies. Secondary outcomesFor the review's secondary outcomes, none of the included studies reported on the incidence of bronchopulmonary dysplasia, periventricular haemorrhage, necrotising enterocolitis or rate of maternal mortality.One small trial (involving 88 women) comparing ambroxol with placebo or no treatment, reported no difference between groups in terms of the need for mechanical ventilation in the neonate (RR 0.94; 95% CI 0.73 to 1.21, 88 women/88 babies, low-quality evidence) or the administration of pulmonary surfactant (RR 1.19; 95% CI 0.61 to 2.30, one RCT, 88 women/88 babies, low-quality evidence). AUTHORS' CONCLUSIONS: This review is based on very low to moderate quality evidence from 14 small trials (many are published in the form of conference abstracts with minimal methodological details provided). There is insufficient evidence to support or refute the practice of giving ambroxol to women at risk of preterm birth for preventing neonatal RDS, perinatal mortality and adverse effects. More research is needed in order to fully evaluate the benefits and risks of this intervention.

Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.

N-acetylcysteine (NAC) is a membrane-permeable cysteine precursor capable of enhancing the intracellular cysteine pool, enhancing cellular glutathione (GSH) synthesis, and thus potentiating the endogenous antioxidant mechanism. Late administration of NAC after cisplatin has been shown in different in vivo studies to reduce the side effects caused by various toxicities at different levels without affecting the antitumor efficacy of platinum, improving total and enzymatic antioxidant capacity and decreasing oxidative stress markers. These characteristics provide NAC with a rationale as a potentially effective chemo protectant in cisplatin-based therapeutic cycles. NAC represents a potential candidate as a chemoprotective agent to decrease toxicities secondary to cisplatin treatment. It suggests that it could be used in clinical trials, whereby the effective dose, timing, and route should be adjusted to optimize chemoprotection. This review provides an overview of the effect of NAC on cisplatin toxicity, a drug widely used in the clinic in adults and children.

Immunotherapy for Pediatric Gliomas: CAR-T Cells Against B7H3: A Review of the Literature.

BACKGROUND: B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer. OBJECTIVE: This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients. RESULTS: Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success. CONCLUSION: Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.

Virtual reality as a non-medical tool in the treatment of anxiety, pain, and perception of time in children in the maintenance phase of acute lymphoblastic leukemia treatment.

Introduction: Management of pediatric cancer patients involves invasive procedures such as punctures, injections, catheter placements, and chemotherapy which can generate fatigue, nausea, vomiting, anxiety, and pain. Virtual Reality (VR) is a nonpharmacological intervention classified as a cognitive-behavioral method to relieve symptoms. Methods: We designed a crossover protocol and included 20 patients between 9 and 12 years old; ten were male. All patients had acute lymphoblastic leukemia diagnosis and were treatedwith St. Jude's XV protocol in the maintenance phase. Pain and anxiety were measured with validated scales in the pediatric population. Results: Although we used a small group of patients, we found statistical difference in the reduction of anxiety and perception of time. Discussion: These results open a window to non-pharmacological treatments and show a strategy to improve quality of life in children inside the hospital.

Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

Challenges in Treating Pediatric Cancer Patients during the COVID-19 Pandemic: Balancing Risks and Care.

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and PaxlovidTM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2.

Impact of treatment and clinical characteristics on the survival of children with medulloblastoma in Mexico.

Introduction: Data on medulloblastoma outcomes and experiences in low- and middle-income countries, especially in Latin America, is limited. This study examines challenges in Mexico's healthcare system, focusing on assessing outcomes for children with medulloblastoma in a tertiary care setting. Methods: A retrospective analysis was conducted, involving 284 patients treated at 21 pediatric oncology centers in Mexico. Results: High-risk patients exhibited markedly lower event-free survival than standard-risk patients (43.5% vs. 78.3%, p<0.001). Influential factors on survival included anaplastic subtype (HR 2.4, p=0.003), metastatic disease (HR 1.9, p=0.001); residual tumor >1.5cm², and lower radiotherapy doses significantly impacted event-free survival (EFS) and overall survival (OS). Platinum-based chemotherapy showed better results compared to the ICE protocol in terms of OS and EFS, which was associated with higher toxicity. Patients under 3 years old displayed notably lower OS and EFS compared to older children (36.1% vs. 55.9%, p=0.01).

Clinical practice guidelines for diagnostic and treatment of the chronic heart failure.

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications.

La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad.

Perinucleolar Compartment (PNC) Prevalence as an Independent Prognostic Factor in Pediatric Ewing Sarcoma: A Multi-Institutional Study.

The perinucleolar compartment (PNC) is a small nuclear body that plays important role in tumorigenesis. PNC prevalence correlates with poor prognosis and cancer metastasis. Its expression in pediatric Ewing sarcoma (EWS) has not previously been documented. In this study, we analyzed 40 EWS tumor cases from Caucasian and Hispanic patients for PNC prevalence by immunohistochemical detection of polypyrimidine tract binding protein and correlated the prevalence with dysregulated microRNA profiles. EWS cases showed staining ranging from 0 to 100%, which were categorized as diffuse (≥77%, n = 9, high PNC) or not diffuse (<77%, n = 31) for low PNC. High PNC prevalence was significantly higher in Hispanic patients from the US (n = 6, p = 0.017) and in patients who relapsed with metastatic disease (n = 4; p = 0.011). High PNC was associated with significantly shorter disease-free survival and early recurrence compared to those with low PNC. Using NanoString digital profiling, high PNC tumors revealed upregulation of eight and downregulation of 18 microRNAs. Of these, miR-320d and miR-29c-3p had the most significant differential expression in tumors with high PNC. In conclusion, this is the first study that demonstrates the presence of PNC in EWS, reflecting its utility as a predictive biomarker associated with tumor metastasis, specific microRNA profile, Hispanic ethnic origin, and poor prognosis.

Intestinal Ewing sarcoma: An unusual presentation in the pediatric age.

BACKGROUND: Ewing's Sarcoma (ES) is the second most common type of bone cancer, with an annual incidence of 2.9:100,000. Extraosseous cases represent 15%; however, there are no reported cases of ES located in the intestine in the pediatric population. CASE REPORT: We describe the case of a 14-year-old male patient, previously healthy, who started with an anemic syndrome, weight loss, and diaphoresis of 8 weeks of evolution. After visiting a physician, who documented the presence of anemia, the patient was referred to the National Institute of Pediatrics. Physical examination showed grade III-IV systolic murmur, splenomegaly, and pain in the left hemiabdomen with no irradiation. Computed axial tomography showed a mass-dependent on the peritoneum and intestinal loop. A biopsy of the lesion showed intestinal ES. The lesion was completely resected, and the patient was treated with chemotherapy and radiotherapy. Thirty months after diagnosis, the patient has no evidence of tumor activity. CONCLUSIONS: Extraosseous presentation of ES in pediatric age is rare. There are no reports of intestinal ES in the Latin American pediatric population, although eight case reports were found in adults. ES is curable by a combination of chemotherapy, radiotherapy, and surgery. The medical literature indicates that the extraosseous presentation should receive the same treatment as the osseous presentation, which can provide a survival rate of up to 70% if there is no evidence of metastasis (which most frequently is observed in the lung).

INTRODUCCIÓN: El sarcoma de Ewing (SE) es el segundo tipo cáncer más común de hueso, cuya incidencia anual es de 2.9:100,000. Los casos extraóseos representan el 15%; sin embargo, no existen reportes en la literatura de casos de SE ubicados en el intestino en la población pediátrica. CASO CLÍNICO: Se describe el caso de un paciente de sexo masculino de 14 años, previamente sano, que inició con síndrome anémico, pérdida de peso y diaforesis de 8 semanas de evolución. Acudió con un médico, quien documentó la presencia de anemia y lo refirió al Instituto Nacional de Pediatría. A la exploración física presentaba soplo sistólico grado III-IV, esplenomegalia y dolor en hemiabdomen izquierdo sin irradiaciones. La tomografía axial computarizada mostró una masa dependiente del peritoneo y asa intestinal. La biopsia de la lesión reportó SE intestinal. Se resecó por completo la lesión y el paciente recibió tratamiento con quimioterapia y radioterapia. Después de 30 meses del diagnóstico, el paciente se encuentra sin datos de actividad tumoral. CONCLUSIONES: La presentación extraósea del SE en edad pediátrica es rara. No existen reportes de presentación de SE intestinal en la población pediátrica latinoamericana, aunque se encontraron ocho reportes de caso en adultos. El SE es curable mediante la combinación de quimioterapia, radioterapia y cirugía. La literatura médica indica que la presentación extraósea debe recibir el mismo tratamiento que la ósea, lo cual puede proporcionar una sobrevida de hasta el 70% si no hay evidencia de metástasis (que ocurre más frecuentemente a pulmón).

Triple-hit explanation for the worse prognosis of pediatric acute lymphoblastic leukemia among Mexican and Hispanic children.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among Mexican and Hispanic children and the first cause of death by disease in Mexico. We propose a "triple-hit" explanation for the survival gap affecting this population. The first hit can be attributed to epidemiology and social, cultural, and economic burdens. The second hit refers to cancer biology, with a high incidence of unfavorable genetic characteristics associated with an unfavorable response to treatment and, subsequently, poor survival. Finally, the third hit relates to sub-optimal treatment and support. Society and culture, leukemia biology, and treatment approach limitations are key factors that should not be seen apart and must be considered comprehensively in any strategy to improve the prognosis of Mexican and Hispanic children with ALL.

Clinical characteristics and mortality predictors of patients with cancer hospitalized by COVID-19 in a pediatric third-level referral center.

Background: More than 135 million COVID-19 cases (coronavirus disease 2019) have been reported worldwide until today, with over 2.9 million deaths. Several studies have demonstrated that disease severity is lower in the pediatric population than in adults; however, differences are described in patients with chronic diseases, including oncological patients. Current world literature suggests patients with comorbidities, including cancer, have an increased risk of unfortunate outcomes. Therefore, our objective was to describe the clinical characteristics and epidemiological factors associated with mortality in a cohort of pediatric cancer patients hospitalized for COVID-19. Methods: This is a retrospective, descriptive study of the cases of patients with cancer hospitalized for COVID-19. A total of 40 pediatrics were included in the analysis. Data from pediatric patients with COVID-19 included clinical and epidemiological records, laboratory, imaging studies, COVID-19 diagnostic methods, and medical treatment. Results: Of the 40 pediatric patients admitted with cancer with a confirmed diagnosis of COVID-19, 42.5% were solid tumors, 40% leukemias, and 17.5% lymphomas. The clinical parameters associated with mortality were stage IV tumor (p = 0.029) and intubation (p < 0.001). The biochemical factors associated with lower survival were thrombocytopenia under 25,000 cells/mm3 (p < 0.001), D-dimer over 1 µg/ml (p = 0.003), clinical malnutrition (p = 0.023), and disseminated intravascular coagulation (p = 0.03). Conclusion: Our findings showed that the fever was the most frequent symptom, and the clinical parameters associated with mortality were stage IV tumor, intubation, saturation percentage, RDW, platelets, creatinine, ALT, D-dimer, ferritin, and FiO2 percentage. The thrombocytopenia, D-dimer, nutritional status, and disseminated intravascular coagulation were significantly associated with lower survival.