Flaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the Aedes genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently identified as ZIKV infection. ZIKV became widespread all over Brazil and was linked with potential cases of microcephaly.We report a case of a 28-year-old Colombian woman, who came to the Obstetric Department with an assumed conglomerate of fetal abnormalities detected via ultrasonography, which was performed at 29.5 weeks of gestation. The patient presented with multiple abnormalities, which range from a suggested Arnold-Chiari malformation, compromising the lateral and third ventricles, liver calcifications, bilateral pyelocalic dilatations, other brain anomalies, and microcephaly. At 12 weeks of gestation, the vertical transmission of ZIKV was suspected. At 38.6 weeks of gestation, the newborn was delivered, with the weight in the 10th percentile (3,180 g), height in the 10th percentile (48 cm), and cephalic circumference under the 2nd percentile (31 cm). Due to the physical findings, brain magnetic resonance imaging (MRI) was performed, revealing a small and deviated brain stem, narrowing of the posterior fossa, a giant posterior fossa cyst with ventricular dilatation, a severe cortical and white matter thinning, cerebellar vermis with hypoplasia, and superior and lateral displacement of the cerebellum. In addition, hydrocephalus was displayed by the axial sequence, and the cerebral cortex was also compromised with lissencephaly. Schizencephaly was found with left frontal open-lip, and no intracranial calcifications were found. Two novel heterozygous nonsense mutations were identified using whole-exome sequencing, and both are located in exon 8 under the affection of ZIKV congenital syndrome (CZS) that produced a premature stop codon resulting in the truncation of the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) protein.We used molecular and microbiological assessments to report the initial case of vertically transmitted ZIKV infection with congenital syndrome associated with a neurological syndrome, where a mutation in the CDK5RAP2 gene was also identified. The CDK5RAP2 gene encodes a pericentriolar protein that intervenes in microtubule nucleation and centriole attachment. Diallelic mutation has previously been associated with primary microcephaly.
Studies suggest that transplant patients are at risk for chronic rhinosinusitis (CRS). However, there is limited information in the literature regarding frequency and reasons for failure of adequate medical therapy. We aim to determine the risk factors associated with the development of medically recalcitrant CRS requiring endoscopic sinus surgery (ESS).Retrospective cohort.Mayo Clinic.This is a retrospective chart review of 925 transplant recipients seen at Mayo Clinic between 2017 and 2022.(1) a rhinologic consultation after transplant and (2) clinical diagnosis of CRS. A total of 549 patients met the inclusion criteria and were divided based on the need for ESS versus successful treatment with medical therapy. Univariate and logistic regression analyses were performed to identify risk factors and predictive variables related to failure of medical therapy.Of the 549 patients, 201/549 (37%) had medically recalcitrant disease requiring ESS, while 348/549 (63%) were successfully treated with medical therapy Based on logistic regression, patients with recurrent acute rhinosinusitis in the pretransplant period were 8.68 more likely to have a recalcitrant disease (95% confidence interval, 3.72-20.28, p < 0.0001). Some of the largest determinants of medical therapy failure in the posttransplant period were CRS with nasal polyps, odontogenic CRS, and noninvasive fungal sinusitis. The presence of neutropenia, aplastic anemia, and living transplant were also associated with medically recalcitrant CRS requiring ESS.Our predictive model identifies with high accuracy the patients who may be at risk of developing recalcitrant CRS in the organ transplant population.
Background: DiGeorge syndrome (DG) is a genetic disorder associated with 22q11 deletion. It involves various phenotypes, including craniofacial abnormalities, congenital heart disorders, endocrine dysfunction, cognitive deficits, and psychiatric disorders. Cases commonly involve multiple anomalies. However, little is known about the condition of the oral cavity in this disorder, although palate fissure, abnormal mandible, malocclusion, and tooth hypoplasia have been identified. We aimed to determine the odontological features of patients with 22q11.2 microdeletion, in relation to gingival health and oral hygiene. We report the systemic manifestations of nine patients and results of oral evaluation of two patients. In the oral examination, oral hygiene and gingivitis were evaluated. Case Presentation: In terms of the systemic manifestations, we found high frequencies of low weight and height at birth. In terms of the oral manifestations, both examined patients presented malocclusion, enamel hypoplasia, dental crowding, anodontia, and healthy periodontium. Conclusion: Although DG has been documented to involve periodontium disease, the patients in this study exhibited more dental manifestations such as enamel defects, misalignment between the teeth and the two dental arches, anodontia, and dental crowding. As such, a multidisciplinary approach combining dentistry and healthcare is recommended in this case. Keywords: DiGeorge syndrome 22q11.2 deletion, oral manifestations, facial dysmorphism, case report
Currently there are more than 10,000 rare diseases that affect about 7% of the world's population. Up to 40% of rare genetic disorders present craniofacial dysmorphologies, which can vary from subtle facial anomalies to severe malformations. Visual assessment of facial dysmorphology is commonly used for clinical diagnosis, patient management and treatment monitoring. However, qualitative descriptions are usually vague and quantitative approaches using craniofacial phenotypes for the diagnosis of rare diseases are based on North American and European populations, disregarding the influence of population ancestry on facial variation, as in Latin-America. In this study, we assessed facial dysmorphologies associated to three different genetic disorders (Down (DS), Morquio (MS) and Noonan syndrome (NS)) in a Latin-American population from Cali (Colombia). We recorded the coordinates of 18 facial landmarks in 2D images from 34 pediatric patients (19 DS, 8 MS, 6 NS) and 75 controls and quantified facial differences between patients and control groups using Euclidean Distance Matrix Analysis (EDMA). Comparisons between control and syndromic phenotypes indicated that individuals diagnosed with DS and MS presented the largest percentage of dysmorphologies, with respectively 56.2% and 54.9% of significantly different facial traits. In NS, the percentage decreased to 12.4%. Each syndrome presented a characteristic facial pattern. In DS, all facial structures were affected, with a 6% increase of relative distance between the eyes and a 7-10% reduction in facial height. The eyes and nose were most affected in MS, but not the mouth, with higher hypertelorism and facial reduction than in DS (9% and 8-17%). In NS, facial differences were more subtle and affected mainly the eyes and mouth, reducing the relative distance between them from 1 to 4% in patients as compared to controls. Our study provides a precise quantitative comparison of facial dysmorphologies in three genetic disorders that in the future can be compared with other world-wide populations to test whether facial traits associated to disease are altered by different evolutionary and adaptive histories of human populations.
Abstract Objectives Reconstructing the hypopharynx while preserving the larynx poses a complex surgical challenge due to the limited space and the high position of the hypopharynx in the neck. We present our experience with hypopharyngeal reconstruction and larynx preservation using an ileal free flap. Case presentation Six consecutive cases were reported (age range 17–75; 2 females). Indications for surgery were tumor excision, postexcision flap failure, postradiation stenosis, caustic ingestion injury, and cervical esophageal perforation. The larynx was preserved in four cases. Graft survival rate was 100 %. Videofluoroscopic swallowing studies conducted at postoperative day 20–80 were normal in three cases. Two cases presented with stenosis but responded well to endoscopic dilations. Unfortunately, the third case expired due to tumor recurrence. Conclusions The ileal free flap is a surgical alternative for the reconstruction of the hypopharynx, especially in cases where the larynx is preserved.
CYP2C19 is a highly polymorphic gene that encodes an enzyme with the same name and whose function is associated with the metabolism of many important drugs, such as proton pump inhibitors (such as esomeprazole, which is used for the treatment of acid peptic disease). Genetic variants in CYP2C19 alter protein function and affect drug metabolism. This study aims to genotypically and phenotypically characterize the genetic variants in the CYP2C19 gene in 12 patients with acid peptic disorders and different therapeutic profiles to proton pump inhibitor (PPI) drugs. The patients were randomly selected from a controlled, randomized and blinded clinical pilot trial of 33 patients. We determined the presence and frequency of single nucleotide polymorphisms (SNPs) within exons 1-5 and 9, the intron-exon junctions, and a fragment in the 3' UTR region of the CYP2C19 gene using Sanger sequencing. Undescribed polymorphisms were analyzed by free online bioinformatics tools to evaluate the potential molecular effects of these genetic variants.We identified nine polymorphisms, six of which had no reported functions. One of these genetic variants, with a functional impact, not yet reported (p.Arg132Trp) was predicted by bioinformatic tools as potentially pathogenic. This finding suggests that p.Arg132Trp could be related to poor metabolizers of drugs metabolized by CYP2C19.We identified the genotype spectrum of variants in CYP2C19. The genotype spectrum of variants in CYP2C19 could predict the treatment response and could support to evaluate clinical efficacy in patients treated with esomeprazole.
ABSTRACT Background In sinonasal cancer (SNC), treatment with proton therapy (PT) provides excellent local control, especially after gross total resection. Because of the heterogeneity and rarity of this disease site, a comprehensive assessment of toxicity, survival, and control rates is lacking. Our primary objective was to assess the toxicity outcomes of PT in SNC patients, with a secondary aim of assessing survival and tumor control after PT. Methods PubMed, Embase, EBSCO, Scopus, Science Direct, Web of Science, Ovid, Proquest, and Cochrane Library were searched from inception to August 2024 reporting PT acute and late toxicity, survival, and tumor control outcomes in SNC patients. A random‐effect meta‐analysis was used to assess the pooled safety, survival, and tumor control outcomes. The primary analysis was to report acute and late toxicity. The secondary aims included overall survival (OS), disease‐free survival (DFS), local control (LC), regional control (RC), and distant metastasis control (DMC) rate. Results Fourteen studies were included for qualitative analysis. We pooled data from 756 patients who received PT for SNC. Among acute toxicity (AT), there was a 31.9% occurrence rate of grade ≥ 3 events, whereas within late toxicity (LT), grade ≥ 3 events occurred at a rate of 35.3%. Most LT (62.1%) were classified as grade 2, with the most frequent being ocular (24.8%) or neurological (18.4%) toxicities. The most common grade ≥ 3 toxicities were mucositis (15.3%) in AT and ocular toxicity (9.6%) in LT. The pooled 5‐year OS, DFS, LC, RC, and DMC were 36.8%, 34.2%, 35.6%, 28.6%, and 54.3%, respectively. Conclusion Our analysis demonstrates that PT‐treated SNC patients experience acceptable rates of acute and LT consistent with other published outcomes with highly conformal radiation techniques. PT demonstrates favorable OS and DFS. Further prospective and comparative effectiveness research is needed to better quantify the magnitude of the benefit of PT or other forms of radiation modalities.
Background: Respiratory recurrent papillomatosis (RRP) is a fatal disease with no known cure. In severe RRP cases, systemic bevacizumab (SB) could be used as adjuvant therapy. Objective: This study aims to determine the extent and type of evidence in relation to the clinical outcomes of RRP after SB treatment. Methods: Participants with RRP of all genders are included in this scoping review. There were no exclusion criteria (country, language, or document type). The information sources included experimental, quasi-experimental, and analytical observational studies. Unpublished data will not be covered, but gray literature was covered. Screening, paper selection, and data extraction were all done by two independent reviewers. This procedure was performed blindly. Results: Of the 175 unique records found, 15 were eligible for inclusion. Fourteen studies were included after applying inclusion and exclusion criteria. Thirty-four patients in these studies came from the United States, India, Germany, Colombia, Argentina, Chile, and Spain. In total, 17 and 34 patients were below 18 years old and were adults respectively. The most commonly reported dose was 10 mg/kg, which was received by 25 (73.5%) patients. According to reports, 58.8% of patients completed the questionnaire. Twelve (35%) patients did not require a repeat surgery. The time interval between surgical procedures has increased for patients who require them. Conclusion: SB may be a promissory treatment and control option for RRP. More research is needed to evaluate the efficiency and adverse effects in various populations.
Key points The study found a higher incidence of chronic rhinosinusitis (CRS) and recalcitrant CRS in cadaveric organ transplant recipients compared to those receiving living donor transplants. Recipients of cadaveric transplants were 1.32 times more likely to develop CRS and 1.68 times more likely to develop medically recalcitrant CRS. Living kidney transplants significantly reduced the risk of developing CRS (OR = 0.12) and recalcitrant CRS (OR = 0.11), highlighting a potentially protective effect against these conditions. In contrast, cadaveric liver transplants were associated with an increased risk of CRS and medically recalcitrant CRS. Kaplan–Meier survival analysis indicated a significant difference in time to CRS onset between cadaveric and living donor transplants. Median time to CRS onset was longer for living donor recipients (21.1 months) compared to cadaveric recipients (15.6 months). This study underscores the need for transplant teams and otolaryngologist to consider donor type during transplant follow‐up due to differing risks of CRS development.
