Midterm Outcomes of Multimodal Approach to Treating Severe Scoliosis in Patients With Osteogenesis Imperfecta.

INTRODUCTION: The surgical management of severe scoliosis in patients with osteogenesis imperfecta (OI) is challenging because of curve rigidity, small stature, and inherent bone fragility. This study evaluated the midterm outcomes of our multimodal approach to address these issues, integrating perioperative bisphosphonate therapy, preoperative/intraoperative traction, various osteotomies, segmental pedicle screw instrumentation with cement augmentation, and bone morphogenetic protein-2 application. METHODS: A single-center retrospective review of 30 patients (average age 14.1 ± 2.2 years; 18 were female) diagnosed with OI and scoliosis was conducted. These patients underwent posterior spinal fusion between 2008 and 2020 and completed a minimum follow-up of 2 years. We measured radiographic parameters at each visit and reviewed the incidence of complications. A mixed-effects model was used to evaluate changes in radiographic parameters from preoperative measurements to the first and latest follow-ups. RESULTS: The patient cohort consisted of 2 individuals with type I OI, 20 with type III, 6 with type IV, and 2 with other types (types V and VIII). Surgical intervention led to a notable improvement in the major curve magnitude from 76° to 36°, with no notable correction loss. In addition, the minor curve, apical vertical translation, lowest instrumented vertebra tilt, and pelvic obliquity were also improved. In the sagittal plane, thoracic kyphosis and lumbar lordosis remained unchanged while thoracolumbar kyphosis markedly improved. Two patients experienced proximal junctional kyphosis with screw pullout, one of whom required revision surgery. One patient developed a superficial infection that was successfully treated with oral antibiotics. No instances of neurologic deficits or cement extravasation were observed. DISCUSSION: This study demonstrated the effectiveness and safety of our multimodal approach to treating scoliosis in patients with OI, achieving a 53% major curve correction with minimal complications over 2-year follow-up. These findings provide notable insights into managing scoliosis in this population. LEVEL OF EVIDENCE: Level IV (case series).

Differences in spine growth potential for Sanders maturation stages 7A and 7B have implications for treatment of idiopathic scoliosis.

PURPOSE: This study aimed to clarify the differences in spine and total body height growth and curve progression between Sanders maturation stage (SMS) 7A and 7B in patients with adolescent idiopathic scoliosis (AIS). METHODS: This retrospective case-control study involving patients with AIS at SMS 7 evaluated the differential gains in the spine (T1-S1) and total body height and curve progression between SMS 7A and 7B. A validated formula was used to calculate the corrected height, accounting for height loss due to scoliosis. A multivariable non-linear and logistic regression model was applied to assess the distinct growth and curve progression patterns between the SMS 7 subtypes, adjusting for potential confounders. RESULTS: A total of 231 AIS patients (83% girls, mean age 13.9 ± 1.2 years) were included, with follow-up averaging 3.0 years. Patients at SMS 7A exhibited larger gains in spine height (9.9 mm vs. 6.3 mm) and total body height (19.8 mm vs. 13.4 mm) compared with SMS 7B. These findings remained consistent even after adjustments for curve magnitude. Non-linear regression models showed continued spine and total body height increases plateauing after 2 years, significantly greater in SMS 7A. More SMS 7A patients had curve progression over 10°, with an adjusted odds ratio of 3.31. CONCLUSION: This study revealed that patients staged SMS 7A exhibited more spine and total body growth and a greater incidence of substantial curve progression than those at 7B. These findings imply that delaying brace discontinuation until reaching 7B could be beneficial, particularly for those with larger curves. LEVEL OF EVIDENCE: Level III (Case-control study).

Osmotin1 is involved in rice resistance to Schizotetranychus oryzae (Acari: Tetranychidae) infestation.

BACKGROUND: Rice is one of the most consumed cereals in the world. Productivity losses are caused by different biotic stresses. One of the most common is the phytophagous mite Schizotetranychus oryzae Rossi de Simons (Acari: Tetranychidae), which inhibits plant development and seed production. The identification of plant defense proteins is important for a better understanding of the mite-plant interaction. We previously detected a high expression of Osmotin1 protein in mite-resistant rice cultivars, under infested conditions, suggesting it could be involved in plant defense against mite attack. We therefore aimed to evaluate the responses of three rice lines overexpressing Osmotin1 (OSM1-OE) and three lines lacking the Osmotin1 gene (osm1-ko) to mite attack. RESULTS: The numbers of individuals (adults, immature stages, and eggs) were significantly lower in OSM1-OE lines than those in wild-type (WT) plants. On the other hand, the osm1-ko lines showed larger numbers of mites per leaf than WT plants. When plants reached the full maturity stage, two out of the three infested OSM1-OE lines presented lower plant height than WT, while the three osm1-ko lines (infested or not) presented higher plant height than WT. The reduction in seed number caused by mite infestation was lower in OSM1-OE lines (12-19%) than in WT plants (34%), while osm1-ko lines presented higher reduction (24-54%) in seed number than WT plants (13%). CONCLUSION: These data suggest that Osmotin1 is involved in rice resistance to S. oryzae infestation. This is the first work showing increased plant resistance to herbivory overexpressing an Osmotin gene. © 2023 Society of Chemical Industry.

Bone alterations of pamidronate therapy in children with cerebral palsy complicating orthopedic management.

Cerebral palsy (CP) is a heterogeneous group of disorders with different clinical types and underlying genetic variants. Children with CP are at risk for fragility fractures secondary to low bone mineral density, and although bisphosphonates are prescribed for the treatment of children with bone fragility, there is limited information on long-term bone impact and safety. Children with CP usually present overtubulated bones, and the thickening of cortical bone by pamidronate treatment can potentially further narrow the medullary canal. Our purpose was to report bone alterations attributable to pamidronate therapy that impact orthopedic care in children with CP. The study consisted of 41 children with CP treated with pamidronate for low bone mineral density from 2006 to 2020. Six children presented unique bone deformities and unusual radiologic features attributed to pamidronate treatment, which affected their orthopedic care. The cases included narrowing of the medullary canal and sclerotic bone, atypical femoral fracture, and heterotopic ossification. Treatment with bisphosphonate reduced the number of fractures from 101 in the pretreatment period to seven in the post-treatment period (P < 0.001). In conclusion, children with CP treated with bisphosphonate have a reduction in low-energy fractures; however, some fractures still happen, and pamidronate treatment can lead to bone alterations including medullary canal narrowing with sclerotic bone and atypical femoral fractures. In very young children, failure to remodel may lead to thin, large femoral shafts with cystic medullary canals. More widespread use of bisphosphonates in children with CP may make these bone alterations more frequent. Level of evidence: Level IV: Case series with post-test outcomes.

Urban sewage sludge stabilization by alkalization-composting-vermicomposting process: Crop-livestock residue use.

Waste management practices are vital for human health and the environment in a world where natural resources stress is expected to increase with the growth of population. Our study aimed to evaluate the potential use of crop-livestock residue as a bulking agent associated with the ideal level of hydrated lime for the stabilization and sanitization of urban sewage sludge through the alkalization-composting process. Therefore, we determined the alkalization efficiency on the heavy metal concentration in urban sewage sludge, quantified the viable eggs of helminths in pure and alkalized sludge, and measured the rate of earthworms (Eisenia fetida) surviving in the vermicomposting process using different levels of alkalized urban sewage sludge associated with crop-livestock residue. Four sequential trials were carried out in a completely randomized design with three replicates. The lime alkalization reduced the levels of Ba, As, Pb, Cu, Cr, Mo, Ni, and Zn compared to the pure urban sewage sludge. Using 30% w/w of lime in the urban sewage sludge (SS-30) for composting process reduced the viable helminth eggs by 71, 72, and 69% for sugarcane bagasse (Saccharum officinarum; SB), fresh chopped Napier-grass (Pennisetum purpureum; NG), and bovine ruminal content (BR), respectively. The ideal level of hydrated lime for stabilization and sanitization of urban sewage sludge was found to be 30%, which was able to reduce the heavy metals. The residues have the potential as a bulking agent for the composting of urban sewage sludge when associated with alkalization. The lime alkalization decreases the total number of helminth eggs and the number of viable eggs. The possibility of starting a vermicomposting using the mixtures is promising, evidenced by the earthworm survival in composting urban sewage sludge mixed with crop-livestock residues after 45 days of composting. The earthworm survival is maintained by an association of at least 80% of the crop-livestock residues.

Walking status and spinopelvic parameters in young children with achondroplasia: 10-year follow-up.

PURPOSE: Thoracolumbar kyphosis (TLK) is common in children with achondroplasia and resolves in 90% by 10 years of age. Our purpose was to describe the natural progression of TLK in a cohort of pre-walking children with achondroplasia. METHODS: A single-center, retrospective review identified 62 children (32 male, 30 female) with achondroplasia. Clinical information and sagittal spinopelvic parameters were collected. The children were divided into positive pelvic tilt (PT) and negative PT. All parents were routinely counseled about unsupported sitting. RESULTS: Spontaneous resolution rate was 64.5% at 1-year post-walking, 74.2% at 5 years of age, and 88.7% at 10 years of age. None of the children required posterior spinal decompression and fusion for progressive deformity or symptomatic spinal stenosis. At 1-year post-walking, the negative PT group had a higher sacral slope (p = 0.006), higher lumbar lordosis (p < 0.001), and lower pelvic incidence (p < 0.001). This relationship remained constant up to 10 years of age, and there was no association with TLK. CONCLUSION: In this largest series to date, spontaneous resolution of TLK in children with achondroplasia was 64.5% at 1-year post-walking, 74.2% at 5 years of age, and 88.7% in children followed to 10 years of age. With early identification and regular follow-up with patient education, no patient in this series required treatment or developed symptomatic spinal stenosis. While not predictive of resolution of TLK, the dichotomous presentation of PT in young children with achondroplasia persists at 5 and 10 years of age and reliably predicts the spinopelvic parameters. LEVEL OF EVIDENCE: III-retrospective comparative study.

Subclassification of Sanders Maturation Stage 3 Demonstrates Differences in Spine and Total Height Velocity Between 3A and 3B in Patients with Idiopathic Scoliosis.

STUDY DESIGN: A single-center retrospective case-control study. OBJECTIVE: To compare the spine and total height velocity between Sanders maturation stage (SMS) 3A and 3B. SUMMARY OF BACKGROUND DATA: Identifying SMS 3 is critical for treating growing children because it represents the early phase of rapid adolescent growth. However, there is limited literature available that clearly describes the growth differences between 3A and 3B. METHODS: The current study included consecutive patients with idiopathic scoliosis staged SMS 3 from January 2012 to December 2021. T1-S1 spine height, total body height, and curve magnitude were measured at the initial and follow-up visits. In addition to the spine and total height velocity calculated per month, corrected height velocity was estimated for curve magnitude using a validated formula. Mann-Whitney U test was used to compare SMS 3A and 3B outcomes, followed by a multiple linear regression model to evaluate the association of the SMS subclassifications to growth velocity adjusted for confounding factors. RESULTS: A total of 204 patients (66% girls, mean age: 12.3±1.3 y) met the inclusion criteria. Patients staged SMS 3A had higher spine height velocity (mm/month) in both girls (2.3 vs. 1.5, P<0.001) and boys (2.6 vs. 1.7, P<0.001), as well as total height velocity (mm/month; (5.8 vs. 4.3, P<0.001 for girls; 6.6 vs. 4.5, P<0.001 for boys). Corrected velocity showed similar results with greater spine and total height velocity in SMS 3A. Multivariate analysis indicated a significant association of the SMS subclassification to the spine and total height velocity. The scoliosis curve progression was comparable between SMS 3A and 3B. CONCLUSION: SMS 3A and 3B had differential growth velocity in the spine and total body height. These results advocated the significance of SMS 3 subclassification for managing scoliosis treatment, including observation, bracing, and surgical interventions with fusion and growth modulation. LEVEL OF EVIDENCE: Level III (Case-control study).

Closed displaced femur fractures in children with nonambulatory cerebral palsy.

Femoral fractures in children withcerebral palsy (CP) represent a frequent medical problem, and treatment represents a challenge. The purpose of this study was to review the closed displaced femoral fractures in our population of nonambulatory children with CP to compare the results of nonoperative and operative treatment modalities to improve the care of these children. From 2006 to 2020, children with nonambulatory CP were selected with inclusion criteria of displaced femoral fracture and were divided into nonoperative and operative groups. Forty-four children met the inclusion criteria. The nonoperative group included 23 children and the operative group included 21 children. Mechanism of injury was unknown in 48% of the fractures. Fourteen (25%) fractures occurred after a femoral plate fixation during a reconstructive hip surgery, and 38 (86%) children had osteopenia. Our results reveal a high prevalence of osteopenia, low-energy trauma, malunion in nonoperative treatment, and peri-implant fractures. Suspicion of child abuse should be considered when the fracture has an unclear mechanism of the injury. Removal of proximal femoral implants may be considered to prevent peri-implant fractures. Femoral fractures should preferably be treated nonoperatively. Operative treatment should be considered for diaphyseal fractures in children capable of standing transfers, larger children, children with more severe spasticity or movement disorder or those who have suffered a high-energy fracture. Due to the high prevalence of proximal fractures in the presence of hardware, operative treatment is usually required for these fractures. In contrast, distal fractures are adequately managed nonoperatively.

An Exploratory Survey on the Care for Ataxic Patients in the American Continents and the Caribbean.

Little is known about access of rare disease carriers to health care. To increase this knowledge, the Pan American Hereditary Ataxia Network (PAHAN) conducted an exploratory survey about care for hereditary ataxias in American continents and the Caribbean. A questionnaire was sent to health professionals about the hereditary ataxias identified; access to care; and local teaching and research. The number of ataxics under current care per 100,000 inhabitants was subtracted from the expected overall prevalence of 6/100,000, to estimate the prevalence of uncovered ataxic patients. Local Human Development Indexes (HDI) were used to measure socio-economic factors. Twenty-six sites participated. Twelve sites had very high, 13 had high, and one site had medium HDI. Participants reported on 2239 and 602 patients with spinocerebellar ataxias and recessive forms under current care. The number of patients under current care per inhabitants varied between 0.14 and 12/100,000. The estimated prevalence of uncovered ataxic patients was inversely proportional to HDIs (rho = 0.665, p = 0.003). Access to diagnosis, pre-symptomatic tests, and rehabilitation were associated with HDIs. More and better molecular diagnostic tools, protocols and guidelines, and professional training for ataxia care were the top priorities common to all respondents. Evidence of inequalities was confirmed. Lower HDIs were associated with high potential numbers of uncovered ataxic subjects, and with lack of molecular diagnosis, pre-symptomatic testing, and rehabilitation. More and better diagnostic tools, guidelines, and professional training were priorities to all sites. PAHAN consortium might help with the last two tasks.

Pain perception genes, asthma, and oral health: A reverse genetics study.

Pain is an experience of a subjective nature, interpreted in a personal way and according to an extensive palette of factors unique to each individual. Orofacial pain can be acute or chronic and it is usually the main reason for the patient to seek dental care. Pain perception varies widely among individuals. This variability is considered a mosaic of factors, which include biopsychosocial factors and genetic factors. Understanding these differences can be extremely beneficial for pain management in a personalized and more efficient way. We performed association studies to investigate phenotypes associated with genetic markers in pain-related genes in two groups of patients who received more or less anesthesia during dental treatment. The study group was comprised of 1289 individuals participating in the Dental Registry and DNA Repository Project (DRDR) of the University of Pittsburgh, with 900 participants in the group that received the most anesthesia and 389 constituting the comparison group that received less anesthesia. We tested 58 phenotypes and genotypic data of seven SNPs in genes that are associated with pain perception, pain modulation and response to drugs used in pain treatment: COMT (rs4818 and rs6269), GCH1 (rs3783641), DRD2 (rs6276), OPRM1 (rs1799971), SCN9A (rs6746030) and SCN10A (rs6795970). The analysis revealed a protective effect of rs1799971 on asthma in the total sample. rs3783641 was associated with salivary secretion disorders in females who received more anesthesia. rs1799971 was also associated with periodontitis in Whites who received less anesthesia. rs4818 was associated with disease and other tongue conditions in the group composed of Blacks who received less anesthesia. In conclusion, our study implicated variants in pain-related genes in asthma and oral phenotypes.

Mathematical models to identify high-performance players for the Brazilian under-19 men's volleyball team.

The objective of this study was to identify parameters that best discriminate between selected and non-selected players for the Brazilian under-19 men's volleyball team and propose mathematical models to identify high-performance players. To this end, 18 selected (16.89±0.96 years) and 138 non-selected (16.91±0.74 years) players for the under-19 team were assessed for the training profile, anthropometric profile, and physical performance level. The discriminant function analysis was used to build the models, with a significance of α<0.05. The spike jump reach showed a greater correlation with the discriminant scores obtained in the two models (r=0.701; r=0.782). The 10 variables included in Model 1 helped identify 88.9% of the players selected in their group of origin; Model 2 - obtained by the spike jump reach and duration of playing experience - identified 83.3% of the players selected. Therefore, coaches should be aware that differences between the selected and non-selected players are multi-factorial, with the spike jump reach being the most relevant assessment factor. Furthermore, good players for the selection can be identified using the two models: Model 1 promises greater success with ten assessments, whereas Model 2 allows the identification of suitable players for the under-19 men's volleyball team with only two simple assessments.

The Cardiovascular Health Integrated Lifestyle Diet (CHILD) Lowers LDL-Cholesterol Levels in Brazilian Dyslipidemic Pediatric Patients.

OBJECTIVE: To analyze the impact of the CHILD-2 diet on the lipid profile of Brazilian children and adolescents with dyslipidemia. METHODS: This is a quasi-experimental study, where 149 participants (5-17 years) with mild-to-moderate hypercholesterolemia were divided into two groups (GI: low or normal weight; n = 58 and GII: overweight; n = 91). Both groups underwent the CHILD-2 diet, characterized by 25-30% total fat and less than 7% of low-saturated fat (SF) for 6 months. Changes from baseline in the lipid profile, including Total cholesterol (TC), LDL-C, triacylglycerols and glucose concentrations, dietary and anthropometric data were examined at 3 and 6 months. Longitudinal analyses were performed using linear mixed-effects models in SAS. RESULTS: Serum LDL-C concentrations reduced over time compared with baseline (Δ = -5.1 mg/dL; p < 0.01), with no difference between groups (p = 0.35). TC concentrations decreased by -2.0 mg/dL (p < 0.01); but no difference was observed between groups. We found no significant changes in body mass index/age Z scores after a dietary intervention compared with baseline in both groups (p = 0.94). CONCLUSION: Despite the modest reduction, our findings confirm that children with dyslipidemia can benefit from the CHILD-2 diet combined with a healthy lifestyle.

New SHH and Known SIX3 Variants in a Series of Latin American Patients with Holoprosencephaly.

Holoprosencephaly (HPE) is the failure of the embryonic forebrain to develop into 2 hemispheres promoting midline cerebral and facial defects. The wide phenotypic variability and causal heterogeneity make genetic counseling difficult. Heterozygous variants with incomplete penetrance and variable expressivity in the SHH, SIX3, ZIC2, and TGIF1 genes explain ∼25% of the known causes of nonchromosomal HPE. We studied these 4 genes and clinically described 27 Latin American families presenting with nonchromosomal HPE. Three new SHH variants and a third known SIX3 likely pathogenic variant found by Sanger sequencing explained 15% of our cases. Genotype-phenotype correlation in these 4 families and published families with identical or similar driver gene, mutated domain, conservation of residue in other species, and the type of variant explain the pathogenicity but not the phenotypic variability. Nine patients, including 2 with SHH pathogenic variants, presented benign variants of the SHH, SIX3, ZIC2, and TGIF1 genes with potential alteration of splicing, a causal proposition in need of further studies. Finding more families with the same SIX3 variant may allow further identification of genetic or environmental modifiers explaining its variable phenotypic expression.

Mucopolysaccharidosis VII in Brazil: natural history and clinical findings.

BACKGROUND: Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme ß-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum. METHODS: We conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the "MPS Brazil Network" who were known to be alive in 2020 in Brazil (N = 13). Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population. RESULTS: The majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant. CONCLUSIONS: This case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including a spectrum of severity and delayed diagnosis.

Genotype-phenotype studies in a large cohort of Brazilian patients with Hunter syndrome.

Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype-phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020. We genotyped 280 of these patients (55.9%), which were assigned to 206 different families. Point mutations were present in 70% of our patients, being missense variants the most frequent. We correlated the IDS pathogenic variants identified with the phenotype (neuronophatic or non-neuronopathic). Except for two half-brothers, there was no discordance in the genotype-phenotype correlation among family members, nor among MPS II patients from different families with the same single base-pair substitution variant. Mothers were carriers in 82.0% of the cases. This comprehensive study of the molecular profile of the MPS II cases in Brazil sheds light on the genotype-phenotype correlation and helps the better understanding of the disease and the prediction of its clinical course, enabling the provision of a more refined genetic counseling to the affected families.

Pigments from Antarctic bacteria and their biotechnological applications.

Pigments from microorganisms have triggered great interest in the market, mostly by their "natural" appeal, their favorable production conditions, in addition to the potential new chemical structures or naturally overproducing strains. They have been used in: food, feed, dairy, textile, pharmaceutical, and cosmetic industries. The high rate of pigment production in microorganisms recovered from Antarctica in response to selective pressures such as: high UV radiation, low temperatures, and freezing and thawing cycles makes this a unique biome which means that much of its biological heritage cannot be found elsewhere on the planet. This vast arsenal of pigmented molecules has different functions in bacteria and may exhibit different biotechnological activities, such as: extracellular sunscreens, photoprotective function, antimicrobial activity, biodegradability, etc. However, many challenges for the commercial use of these compounds have yet to be overcome, such as: the low stability of natural pigments in cosmetic formulations, the change in color when subjected to pH variations, the low yield and the high costs in their production. This review surveys the different types of natural pigments found in Antarctic bacteria, classifying them according to their chemical structure. Finally, we give an overview of the main pigments that are used commercially today.

Extracorporeal Membrane Oxygenation in COVID-19 Treatment: a Systematic Literature Review.

INTRODUCTION: The present study intends to systematically review the literature on the use of extracorporeal membrane oxygenation (ECMO) in patients with coronavirus disease 2019 (COVID-19). METHODS: The research was carried out according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). Studies were selected from PubMed/MEDLINE and LILACS databases between December 2019 and May 17 2020, using the descriptors "ECMO AND COVID-19", "Extracorporeal Membrane Oxygenation AND COVID-19", "ECLS AND COVID-19", and "Extracorporeal Life Support AND COVID-19". Exclusion criteria were government epidemiological bulletins, comments, literature reviews, and articles without full access to content. RESULTS: Two hundred and thirty-three scientific productions were found, however only 18 did not met the exclusion criteria and could be included in this study, amouting to a total of 911 patients - 624 (68.5%) men, 261 (28.6%) women, and 26 (2.8%) without sex information. The mean age of the patients was 53.7 years. ECMO was necessary in 274 (30.1%) people (200 [73%] submitted to veno-venous ECMO, nine [3.3%] to veno-arterial ECMO, and seven [2.5%] moved between these two types or needed a more specific ECMO according to the disease prognosis). Five studies did not specify the type of ECMO used, amounting 57 (20.8%) patients. Five patients (1.8%) were discharged, 77 (28.1%) died, 125 (45.6%) remained hospitalized until publication time of their respective studies, and 67 patients (24.4%) had no outcome information. CONCLUSION: It is evident that more research, covering larger populations, must be carried out in order to clearly elucidate the role of ECMO in the treatment of COVID-19.

Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients.

Phenylketonuria (PKU) is a common inborn error of amino acid metabolism in which the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine, is functionally impaired due to pathogenic variants in the PAH gene. Thirty-four Brazilian patients with a biochemical diagnosis of PKU, from 33 unrelated families, were analyzed through next-generation sequencing in the Ion Torrent PGM™ platform. Phenotype-genotype correlations were made based on the BioPKU database. Three patients required additional Sanger sequencing analyses. Twenty-six different pathogenic variants were identified. The most frequent variants were c.1315+1G>A (n = 8/66), c.473G>A (n = 6/66), and c.1162G>A (n = 6/66). One novel variant, c.524C>G (p.Pro175Arg), was found in one allele and was predicted as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) criteria. The molecular modeling of p.Pro175Arg indicated that this substitution can affect monomers binding in the PAH tetramer, which could lead to a change in the stability and activity of this enzyme. Next-generation sequencing was a fast and effective method for diagnosing PKU and is useful for patient phenotype prediction and genetic counseling.

Update on the approach to smoking in patients with respiratory diseases.

Smoking is the leading cause of respiratory disease (RD). The harmful effects of smoking on the respiratory system begin in utero and influence immune responses throughout childhood and adult life. In comparison with "healthy" smokers, smokers with RD have peculiarities that can impede smoking cessation, such as a higher level of nicotine dependence; nicotine withdrawal; higher levels of exhaled carbon monoxide; low motivation and low self-efficacy; greater concern about weight gain; and a high prevalence of anxiety and depression. In addition, they require more intensive, prolonged treatment. It is always necessary to educate such individuals about the fact that quitting smoking is the only measure that will reduce the progression of RD and improve their quality of life, regardless of the duration and severity of the disease. Physicians should always offer smoking cessation treatment. Outpatient or inpatient smoking cessation treatment should be multidisciplinary, based on behavioral interventions and pharmacotherapy. It will thus be more effective and cost-effective, doubling the chances of success.