A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia.

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Porcine small intestinal submucosa biomaterial graft for repair of a congenital pleuroperitoneal hernia in a kitten.

In this case, porcine small intestinal submucosa (pSIS) was used to repair a large congenital diaphragmatic hernia in a kitten. The pSIS was moistened in saline, folded in half, and sutured to the remnant of the right hemidiaphragm. The animal was determined to be doing well clinically and radiographically 12 wk after procedure. At 8.5 mo of age, the kitten was spayed, and the diaphragm was inspected, revealing a thin, semitransparent membrane at the central region of the previous pSIS graft. Serial thoracic radiographs may be an effective way to reach a diagnosis of a diaphragmatic hernia if not clearly identifiable on initial radiographs. Surgeons should be prepared to use alternative techniques to close large diaphragmatic defects. Porcine SIS was demonstrated to be a strong, easy-to-use, readily available, and effective technique to close a large defect in the diaphragm with excellent results in the short and medium terms. When hernia repair is employed in juvenile animals, reassessment of the diaphragmatic repair should be considered if future abdominal surgeries, such as ovariohysterectomies, are necessary. A functional 8-ply pSIS should be considered in cats and dogs as it has a lower complication and graft failure rate. Key clinical message: When serial radiographs fail to diagnose a diaphragmatic hernia when one is highly suspected, other modalities, such as ultrasonography or other contrast modalities, should be considered. A functional 8-ply pSIS should be considered to reconstruct the diaphragm, particularly in growing animals, as it is an effective graft with low complication and graft failure rates.

Greffe de biomatériau de sous-muqueuse intestinale porcine pour la réparation d'une hernie pleuropéritonéale congénitale chez un chatonDans ce cas, la sous-muqueuse intestinale porcine (pSIS) a été utilisée pour réparer une grande hernie diaphragmatique congénitale chez un chaton. La pSIS a été humidifiée dans une solution saline, pliée en deux et suturée au reste de l'hémidiaphragme droit. L'animal s'est avéré se porter bien cliniquement et radiographiquement 12 semaines après l'intervention. À l'âge de 8,5 mois, le chaton a été stérilisé et le diaphragme a été inspecté, révélant une fine membrane semi-transparente dans la région centrale de la greffe pSIS précédente. Des radiographies thoraciques en série peuvent être un moyen efficace de poser un diagnostic d'hernie diaphragmatique si elle n'est pas clairement identifiable sur les radiographies initiales. Les chirurgiens doivent être prêts à utiliser des techniques alternatives pour fermer les gros défauts diaphragmatiques. La SIS porcine s'est avérée être une technique solide, facile à utiliser, facilement disponible et efficace pour fermer un gros défaut du diaphragme avec d'excellents résultats à court et moyen terme. Lorsque la réparation d'une hernie est utilisée chez les animaux juvéniles, une réévaluation de la réparation diaphragmatique doit être envisagée si de futures chirurgies abdominales, telles que des ovariohystérectomies, sont nécessaires. Une pSIS fonctionnelle à 8 plis doit être envisagée chez les chats et les chiens car elle présente un taux de complications et d'échec de greffe plus faible.Message clinique clé :Lorsque les radiographies en série ne permettent pas de diagnostiquer une hernie diaphragmatique alors qu'elle est fortement suspectée, d'autres modalités, telles que l'échographie ou d'autres modalités de contraste, doivent être envisagées. Une pSIS fonctionnelle à 8 plis doit être envisagée pour reconstruire le diaphragme, en particulier chez les animaux en croissance, car il s'agit d'une greffe efficace avec un faible taux de complications et d'échec de greffe.(Traduit par Dr Serge Messier).

Physical Therapy Management of Congenital Muscular Torticollis: A 2024 Evidence-Based Clinical Practice Guideline From the American Physical Therapy Association Academy of Pediatric Physical Therapy.

BACKGROUND: Congenital muscular torticollis (CMT) is a postural condition evident shortly after birth. The 2013 CMT Clinical Practice Guideline (2013 CMT CPG) set standards for the identification, referral, and physical therapy management of infants with CMT, and its implementation resulted in improved clinical outcomes. It was updated in 2018 to reflect current evidence and 7 resources were developed to support implementation. Purpose: This 2024 CMT CPG is intended as a reference document to guide physical therapists, families, health care professionals, educators, and researchers to improve clinical outcomes and health services for children with CMT, as well as to inform the need for continued research. Results/Conclusions: The 2024 CMT CPG addresses: education for prevention, screening, examination and evaluation including recommended outcome measures, consultation with and referral to other health care providers, classification and prognosis, first-choice and evidence-informed supplemental interventions, discontinuation from direct intervention, reassessment and discharge, implementation and compliance recommendations, and research recommendations.

[Spontaneous coronary artery dissection and physical activity - what we know and don't know]. / Råd om fysisk aktivitet efter spontan kranskärlsdissektion.

Patients suffering from a spontaneous coronary artery dissection (SCAD) are mostly younger to middle-aged women. There are very few data to guide physicians and physiotherapists on recommendations about physical activity for these patients. Based on the few studies that are available, aerobic activity at moderate levels and weightlifting with light weights appears safe. No studies are available on SCAD patients and aerobic activity, at more intensive levels. Follow-up studies after SCAD suggest that many patients receive advice with restrictions on physical activity resulting in a sedentary lifestyle.

Understanding post-operative refractive outcome in pediatrics after IOL implementation: factors and predictors.

BACKGROUND: In pediatric ophthalmology, calculating intra-ocular lens (IOL) power can be challenging. It is important to predict if the post-surgery refractive error (RE) will meet the intended refractive goal. In this study, we aimed to investigate the factors and predictors influencing RE outcomes in children undergoing IOL implantation. METHODS: This was a retrospective cross-sectional cohort study that involved 47 eyes with congenital cataracts underwent IOL implantation. Each patient underwent follow-up visits at two months and two years' post-surgery. The IOL power calculations were conducted using the Holladay 1 formula, and both the prediction error (PE) and absolute prediction error (APE) were calculated. RESULTS: The mean age was 6.52 ± 4.61 years, with an age range of 1-15 years. The mean IOL power was 20.31 ± 6.57 D, and the mean post-operative refraction was 1.31 ± 2.65 D. The mean of PE and APE were 0.67 ± 1.77 and 1.55 ± 1.06 D, respectively. Whereas PE was correlated to axial length with an R-value of - 0.29 (P = 0.04). The calculation method had a significant negative relationship with APE and PE, with coefficients of - 1.05 (P = 0.009) and - 1.81 (P = 0.009), respectively. CONCLUSION: High astigmatism was associated with greater errors in the refractive outcome. The calculation methods had the most considerable impact on the post-operative RE. The customization of surgical approaches to accommodate individual characteristics is crucial. Further research with diverse subgroups is needed to comprehensively understand the influence of each factor.

Congenital myopathies: pathophysiological mechanisms and promising therapies.

Congenital myopathies (CMs) are a kind of non-progressive or slow-progressive muscle diseases caused by genetic mutations, which are currently defined and categorized mainly according to their clinicopathological features. CMs exhibit pleiotropy and genetic heterogeneity. Currently, supportive treatment and pharmacological remission are the mainstay of treatment, with no cure available. Some adeno-associated viruses show promising prospects in the treatment of MTM1 and BIN1-associated myopathies; however, such gene-level therapeutic interventions target only specific mutation types and are not generalizable. Thus, it is particularly crucial to identify the specific causative genes. Here, we outline the pathogenic mechanisms based on the classification of causative genes: excitation-contraction coupling and triadic assembly (RYR1, MTM1, DNM2, BIN1), actin-myosin interaction and production of myofibril forces (NEB, ACTA1, TNNT1, TPM2, TPM3), as well as other biological processes. Furthermore, we provide a comprehensive overview of recent therapeutic advancements and potential treatment modalities of CMs. Despite ongoing research endeavors, targeted strategies and collaboration are imperative to address diagnostic uncertainties and explore potential treatments.

[Developments of high-throughput sequencing-based diagnosis of congenital thrombocytopenia/platelet disorders in a registry study].

Congenital thrombocytopenia/platelet disorders are heterogeneous disorders of platelet number and/or function. Pathogenic variants in the genes implicated in megakaryocyte differentiation and platelet formation cause thrombocytopenia in these patients. Recent advances have elucidated several causative genes for these disorders, but identifying the underlying causative genes remains challenging. Patients with these disorders often receive inappropriate treatments, including glucocorticoids and splenectomy, for chronic immune thrombocytopenia (ITP). In Japan, we have developed a diagnostic system using high-throughput DNA sequencing with a multigene panel and established a registry. Between 2018 and 2023, 245 patients were enrolled and analyzed. Pathogenic variants in 17 genes (42 MYH9, 19 ANKRD26, 17 ITGA2B/ITGB3, 8 ACTN1, 8 WAS, 6 ETV6, 6 VWF, 5 CYCS, and 14 others) were identified in 125 patients (51.0%). An additional 29 patients (11.8%) had suspected pathogenic variants under investigation. We also found that immature platelet fraction (IPF%) is useful in the differential diagnosis because the median IPF% in MYH9 disorders, 48.7%, was significantly higher than in all other groups (chronic ITP, 13.4%; controls, 2.6%). The results of this study provide new insight into congenital thrombocytopenia/platelet disorders.

[Familial Hypocalciuric Hypercalcemia Type 1 Likely Secondary to a New Inactivating Mutation of CASR].

Familial Hypocalciuria Hypercalcemia (FHH) is an inherited disease with autosomal dominant transmission characterized by the presence of usually mild-to-moderate hypercalcemia, hypophosphatemia, hypocalciuria, and normal or moderately increased PTH values. Generally, FFH is asymptomatic although symptoms related to elevated plasma calcium values such as asthenia, intense thirst, polyuria, polydipsia or confusional state may occur. Three types of FHH, which differ in the genetic alterations underlying the condition, are described. The majority of FHH cases are classified as type 1 (about 65 percent of cases), due to mutation in the gene for the calcium-sensitive receptor CASR, expressed on chromosome (Chr) 3q13.3-21, which encodes for a calcium-sensitive receptor G-protein-coupled protein of the plasma membrane. FHH types 2 and 3 are due to GNA11 and AP2S1 mutations, respectively, and other genes involved in the pathogenesis of the disease have likely yet to be identified. Rarely, familial hypocalciuric hypercalcemia may not recognize a genetic cause but be caused by autoantibodies directed against CASR. The frequency of the disease is not known and is estimated, probably by default, because of paucisymptomatic presentation of the disease, to be around 1:80000 cases. Recognition of FHH is especially important for differential diagnosis with primary hyperparathyroidism, which has a much higher incidence, about 1:1000 cases. This allows for the identification of patients at risk for chondrocalcinosis and/or pancreatitis. Clinical suspicion must be raised in cases of hypercalcaemia associated with hypocalciuria, and genetic analysis is fundamental in the differential diagnosis toward forms of primary hyperparathyroidism that might result in unnecessary surgical interventions. We describe a clinical case in which a novel inactivating mutation of CASR leading to FHH type 1 was found.

Are important predictors of adverse outcome in children with symptomatic congenital cytomegalovirus infection overlooked in clinical settings?

OBJECTIVE: Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations. METHODS: This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years. RESULTS: Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes. CONCLUSION: Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late.

First report of surgery for congenital biliary dilatation using the hinotori™ Surgical Robot System (with video).

Robot-assisted surgery for congenital biliary dilatation has been evolving primarily with the da Vinci® Surgical System. The hinotori™ Surgical Robot System, developed in Japan, received approval for gastroenterological surgery in 2022. We present the inaugural case of congenital biliary dilatation surgery utilizing the hinotori™ system. A 57-year-old woman was referred to our institution for evaluation and treatment of common bile duct dilatation classified under Todani Type Ia congenital biliary dilatation. Robotic resection of the extrahepatic bile duct and hepaticojejunostomy with Roux-en-Y were performed. The operation lasted 292 min with minimal blood loss (10 mL). The patient had an uneventful postoperative course and was discharged 10 days after surgery. Robotic surgery using the hinotori™ system for congenital biliary dilatation can be safely performed.

[Clinical and genetic characterization of three families with Nance-Horan syndrome caused by NHS gene mutations].

Objective: To explore the clinical phenotypes and pathogenic gene variation characteristics of three Chinese Han ethnic families affected by Nance-Horan syndrome, a rare X-linked genetic disorder. Methods: A pedigree investigation study was conducted at the First Affiliated Hospital of Zhengzhou University, collecting clinical data from three Chinese Han families with Nance-Horan syndrome between February 2009 and September 2018. Detailed family histories, comprehensive ophthalmological and systemic examinations were documented. Pedigree charts were created, and genetic inheritance patterns were analyzed to preliminarily diagnose the probands and other affected individuals. Genomic DNA was extracted from peripheral blood samples of family members, and next-generation sequencing was used to screen for target gene variations, which were confirmed by Sanger sequencing. Pathogenicity of the genetic variants and their impact on three-dimensional protein structure were analyzed using MutationTaster and computer-aided protein modeling. Results: In Family 1, there are 5 patients, including 4 females (aged 42, 37, 9 and 7) and 1 males (aged 12). In Family 2, there are 5 patients, including 3 females (aged 54, 32 and 16) and 2 males (aged 26 and 9). In Family 3, there are 8 patients, including 5 females (aged 69, 42, 37, 35 and 14) and 3 males (aged 10, 7 and 4). All probands in the three families exhibited nuclear cataracts with typical congenital hereditary cataract features, but no noticeable abnormalities in facial appearance or teeth. Next-generation sequencing identified new variation sites in the NHS gene, specifically c.2519_2520del, exon3del, and c.3847C>T. These variations included nonsense mutation p.(Ser840*), exon deletion p.(?), and nonsense mutation p.(Gln1283*). Combined clinical and genetic sequencing results confirmed X-linked Nance-Horan syndrome in all three families. Bioinformatics analysis indicated these variation sites were pathogenic and resulted in abnormal three-dimensional protein structures, likely being the main cause of Nance-Horan syndrome. Conclusion: The majority of patients from the three Nance-Horan syndrome families studied were affected by congenital hereditary cataracts characterized by nuclear opacities.The NHS gene variations c.2519_2520del, exon3del, and c.3847C>T are newly identified pathogenic sites in Nance-Horan syndrome, reported for the first time across three different families.

Vascularized Femoral Myo-Periosteal Graft for Congenital Pseudarthrosis of the Tibia: A Case Report.

Pure vascularized periosteal transplants have been shown to be extremely effective at achieving rapid bone healing in children with biologically complex non-union. Free tibial and fibular periosteal transplants are generally indicated when large periosteal flaps are necessary. We report using a vascularized femoral myo-periosteal graft (VFMPG) to treat distal tibial osteotomy non-union in a six-year-old boy with congenital pseudarthrosis of the tibia. The graft consisted of a 9 cm myo-periosteal flap (after 50% of elastic retraction) that incorporated the vastus intermedius muscle and diaphyseal femoral periosteum nourished by the descending branch of the lateral circumflex femoral vessels. Plantaris medialis was used as a recipient vessel. Healing occurred 10 weeks after surgery. The patient resumed gait and sports activity without orthosis. No donor or recipient site complications occurred 17 months after surgery. Employing a VFMPG might be an alternative to other free or large vascularized periosteal flaps currently in use for complex pediatric non-unions.

Comparative efficacy of probing with or without intubation, and/or inferior turbinate fracture in simple congenital nasolacrimal duct obstruction: a randomized clinical trial.

To compare the success rates of probing with or without monocanalicular intubation, and/or inferior turbinate fracture in resolving simple congenital nasolacrimal duct obstruction (CNLDO). A randomized, double-blind clinical trial was conducted on children aged 12-36 months exhibiting symptoms of epiphora and/or mucous discharge along with a positive fluorescein dye disappearance test (DDT). Patients were randomly assigned to one of the following interventions: (1) probing; (2) probing and monocanalicular intubation; (3) probing and inferior turbinate fracture; (4) probing, inferior turbinate fracture, and monocanalicular intubation. Participants were categorized into two age groups (12-24 months and 24-36 months) and assessed for resolution of CNLDO three months post-surgery. Success was defined as the absence of epiphora or mucopurulent discharge and a negative DDT. Among the 201 participants, 51 underwent probing alone, 53 underwent probing with intubation, 47 underwent probing with turbinate fracture, and 50 underwent probing with turbinate fracture and intubation. No significant differences were observed in age, gender, or laterality of the disease between the groups (Ps > 0.05). While there was no significant difference in success rates among interventions in both age groups (Ps > 0.05), patients aged 24-36 months who underwent interventions involving intubation exhibited a significantly higher success rate compared to those without intubation (93.0% vs. 76.2%; P = 0.018). However, this difference was not observed in patients aged 12-24 months (95.7% vs. 92.9%; P = 0.551). Incorporating interventions such as intubation and/or turbinate fracture alongside conventional probing does not significantly alter the success rate of simple CNLDO resolution in children aged 12-24 months. However, older patients (24-36 months) may derive greater benefits from interventions involving intubation.

Case report: Granulocyte-macrophage colony-stimulating factor sargramostim did not rescue the neutrophil phenotype in two patients with JAGN1-mutant severe congenital neutropenia.

Background: Homozygous or compound heterozygous mutations in JAGN1 cause severe congenital neutropenia. JAGN1-mutant patients present with severe early-onset bacterial infections and most have been described as low-responders to recombinant granulocyte colony-stimulating factor (G-CSF) therapy. In a murine, hematopoietic JAGN1 knockout model, which displays susceptibility to Candida albicans infection in the absence of neutropenia, treatment with granulocyte-macrophage-CSF (GM-CSF) was able to restore the functional defect of neutrophils. Patients: We present two unrelated patients with biallelic JAGN1 mutations, who were both treated with subcutaneous GM-CSF (sargramostim) after treatment failure to G-CSF. The first patient was an 18-year-old pregnant woman who received GM-CSF at 12 weeks of gestation up to a dose of 10 µg/kg/d for 7 days. The second patient was a 5-month-old girl who received GM-CSF for a total of 9 days at a dose of up to 20 µg/kg/d. GM-CSF did not increase neutrophil counts in our patients. Treatment was stopped when neutrophil numbers declined further, no beneficial effect was noticed, and patients presented with infections. No adverse effects were observed in either patient and the fetus. Both patients ultimately underwent successful hematopoietic stem cell transplantation. Discussion: Both patients showed a high recurrence rate of severe infections on G-CSF treatment. GM-CSF therapy did not ameliorate the clinical phenotype, in contrast to the improvement of neutrophil function observed in the JAGN1 mouse model. No major additional extra-hematopoietic manifestations were evident in our patients. Conclusion: In two unrelated patients, GM-CSF did not have any beneficial effect on neutrophil counts. Patients with JAGN1-mutant SCN with reduced G-CSF responsiveness and elevated infection rate should be evaluated early for stem cell transplantation.

Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey.

PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease. METHODS: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed. RESULTS: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs. CONCLUSIONS: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.

Systematic review on molecular detection of congenital and neonatal infections caused by TORCH and SARS-CoV-2 in newborns' cerebrospinal fluid.

OBJECTIVE: To verify the use and identify advantages of molecular methods for congenital infections diagnosis in cerebrospinal fluid of neonates. DATA SOURCE: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under CRD42021274210. The literature search was performed in databases: PubMed, Virtual Health Library/ Latin American and Caribbean Center on Health Sciences Information (VHL/BIREME), Scopus, Web of Science, Excerpta Medica database (EMBASE), Cochrane, ProQuest, and EBSCOhost. The search was carried out from August to October 2021 and updated in December 2022, respecting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The selection sequence was: 1) Duplicate title removal; 2) Examination of titles and abstracts; 3) Full-text retrieval of potentially relevant reports; and 4) Evaluation of the full text according to eligibility criteria by two independent authors. Inclusion criteria considered randomized and non-randomized control trials, longitudinal, cross-sectional, and peer-reviewed studies in humans, published in English, Spanish, Italian, and Portuguese, with newborns up to 28 days old who had congenital neuroinfections by toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH), and others such as Treponema pallidum, Zika, parvovirus B-19, varicella zoster, Epstein-Barr, and SARS-CoV2, diagnosed by polymerase chain reaction (PCR). Two evaluators extracted the following information: author, year of publication, nationality, subjects, study type, methods, results, and conclusion. DATA SYNTHESIS: The most studied pathogen was herpes simplex. Several articles reported only nonspecific initial symptoms, motivating the collection of cerebrospinal fluid and performing PCR for etiological investigation. CONCLUSIONS: Molecular methods are effective to detect pathogen genomes in cerebrospinal fluid, which can impact clinical evolution and neurological prognosis.

Congenital Diarrhoeas and Enteropathies.

Congenital diarrhoeas and enteropathies (CODE) are a heterogeneous group of disorders. Many affected infants present with catastrophic dehydration in the first few days of life, although the clinical phenotype is variable. Advances in the understanding of underlying pathomechanisms and genetic testing, as well as improved management, in particular intravenous nutrition support, have allowed affected patients to survive well beyond childhood. Awareness and understanding of these rare diseases are hence needed, both amongst paediatricians and adult physicians. In this review, we discuss the different groups of disorders based on a review of the current literature and provide a diagnostic and therapeutic approach. Many of the subtypes of CODE result in the need for prolonged or indefinite parenteral nutrition. Further research is needed to identify new CODE to improve the recognition and management of these children, which can assist in developing new targeted therapies and potentially a long-term cure.

Prevention of congenital chagas disease by trypanocide treatment in women of reproductive age: A meta-analysis of observational studies.

BACKGROUND: Maternal-foetal transmission of Chagas disease (CD) affects newborns worldwide. Although Benznidazole and Nifurtimox therapies are the standard treatments, their use during pregnancy is contra-indicated. The effectiveness of trypanocidal medications in preventing congenital Chagas Disease (cCD) in the offsprings of women diagnosed with CD was highly suggested by other studies. METHODS: We performed a systematic review and meta-analysis of studies evaluating the effectiveness of treatment for CD in women of childbearing age and reporting frequencies of cCD in their children. PubMed, Scopus, Web of Science, Cochrane Library, and LILACS databases were systematically searched. Statistical analysis was performed using Rstudio 4.2 using DerSimonian and Laird random-effects models. Heterogeneity was examined with the Cochran Q test and I2 statistics. A p-value of <0.05 was considered statistically significant. RESULTS: Six studies were included, comprising 744 children, of whom 286 (38.4%) were born from women previously treated with Benznidazole or Nifurtimox, trypanocidal agents. The primary outcome of the proportion of children who were seropositive for cCD, confirmed by serology, was signigicantly lower among women who were previously treated with no congenital transmission registered (OR 0.05; 95% Cl 0.01-0.27; p = 0.000432; I2 = 0%). In women previously treated with trypanocidal drugs, the pooled prevalence of cCD was 0.0% (95% Cl 0-0.91%; I2 = 0%), our meta-analysis confirms the excellent effectiveness of this treatment. The prevalence of adverse events in women previously treated with antitrypanocidal therapies was 14.01% (95% CI 1.87-26.14%; I2 = 80%), Benznidazole had a higher incidence of side effects than Nifurtimox (76% vs 24%). CONCLUSION: The use of trypanocidal therapy in women at reproductive age with CD is an effective strategy for the prevention of cCD, with a complete elimination of congenital transmission of Trypanosoma cruzi in treated vs untreated infected women.

Prenatal diagnosis and outcome of congenital dacryocystoceles.

OBJECTIVE: To determine the incidence and present our experience with prenatal diagnosis and postnatal outcome of dacryocystocele. MATERIAL AND METHODS: All cases of congenital dacryocystocele diagnosed in our center between 2020 and 2022 were identified in our database to establish the incidence of these defects. The medical records were then reviewed for gestational age, gender, size, and side of dacryocystocele and postnatal outcome. RESULTS: A total of 26 cases with dacryocystoceles were found at a mean gestation age of 30 weeks (range, 29-33 weeks). The overall incidence was 1.35%, there was an obvious female predominance (73%), 69% of cases were unilateral and 31% were bilateral. There were no serious associated anomalies. The postnatal outcome was obtained in 88% of cases (23/26), in 39% (9 out of 23) cases the dacryocystocele was confirmed postnatally, and in 7 (77%) of these it was complicated by dacryocystitis. The spontaneous resolution was more likely in the right-sided lesions, and this was statistically significant. The treatment in cases with dacryocystitis involved massage and local antibiotics and was successful in 71% of cases. 2 cases (29%) suffer from recurrent dacryocystitis and are followed up with recurrent probing and local antibiotics. No breathing difficulties were described postnatally in our study group. CONCLUSION: The overall prenatal incidence of dacryocystocele was 1.35%. The outcome is favorable, 61% of dacryocystoceles in our study resolved spontaneously and in no case postnatal breathing complications were reported. Dacryocystitis was common in persisting cases but was usually treated successfully by massage and antibiotics. The right-sided dacryocystoceles are more likely to resolve spontaneously than left-sided, and this was the only significant factor predicting persistence.