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Enamel hypoplasia causes reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. A genome-wide association of enamel hypoplasia was performed in multiple cohorts, overall comprising 7,159 individuals ranging in age from 7-82 years. Mixed-models were used to test for genetic association while simultaneously accounting for relatedness and genetic population structure. Meta-analysis was then performed. More than 5 million single-nucleotide polymorphisms were tested in individual cohorts. Analyses of the individual cohorts and meta-analysis identified association signals close to genome-wide significance (P < 5ï´10-8), and many suggestive association signals (5ï´10-8 < P < 5ï´10-6) near genes with plausible roles in tooth/enamel development. The strongest association signal (P = 1.57ï´10-9) was observed near BMP2K in one of the individual cohorts. Additional suggestive signals were observed near genes with plausible roles in tooth development in the meta-analysis, such as SLC4A4 which can influence enamel hypoplasia. Additional human genetic studies are needed to replicate these results and functional studies in model systems are needed to validate our findings.
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BACKGROUND: Dental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent. METHODS: The aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18-60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification. RESULTS: We identified several suggestive loci (5 × 10-8 < P < 5 × 10-6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis. CONCLUSION: The results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.
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Fenda Labial , Fissura Palatina , Cárie Dentária , Adolescente , Adulto , Criança , Pré-Escolar , Índice CPO , Cárie Dentária/epidemiologia , Cárie Dentária/genética , Feminino , Estudo de Associação Genômica Ampla , Proteínas de Homeodomínio , Humanos , Masculino , Pessoa de Meia-Idade , Filipinas , Fatores de Transcrição , Adulto JovemRESUMO
Odontogenesis is a complex process, where disruption can result in dental anomalies and/or increase the risk of developing dental caries. Based on previous studies, certain dental anomalies tend to co-occur in patients, suggesting that these traits may share common genetic and etiological components. The main goal of this study was to implement a multivariate genome-wide association study approach to identify genetic variants shared between correlated structural dental anomalies and dental caries. Our cohort (N = 3,579) was derived from the Pittsburgh Orofacial Clefts Study, where multiple dental traits were assessed in both the unaffected relatives of orofacial cleft (OFC) cases (n = 2,187) and unaffected controls (n = 1,392). We identified four multivariate patterns of correlated traits in this data: tooth agenesis, impaction, and rotation (AIR); enamel hypoplasia, displacement, and rotation (HDR); displacement, rotation, and mamelon (DRM); and dental caries, tooth agenesis and enamel hypoplasia (CAH). We analyzed each of these four models using genome-wide multivariate tests of association. No genome-wide statistically significant results were found, but we identified multiple suggestive association signals (P < 10-5) near genes with known biological roles during tooth development, including ADAMTS9 and PRICKLE2 associated with AIR; GLIS3, WDR72, and ROR2 associated with HDR and DRM; ROBO2 associated with DRM; BMP7 associated with HDR; and ROBO1, SMAD2, and MSX2 associated with CAH. This is the first study to investigate genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.
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Genome-wide scans have shown that common risk alleles for orofacial clefts (OFC) tend to be located in noncoding regulatory elements and cumulatively explain only part of the heritability of OFCs. Low-frequency variants may account for some of the "missing" heritability. Therefore, we scanned low-frequency variants located within putative craniofacial enhancers to identify novel OFC risk variants and implicate new regulatory elements in OFC pathogenesis. Analyses were performed in a multiethnic sample of 1,995 cases of cleft lip with or without cleft palate (CL/P), 221 cases with cleft palate (CP) only, and 1,576 unaffected controls. One hundred and nineteen putative craniofacial enhancers identified from ChIP-Seq studies in craniofacial tissues or cell lines contained multiple low-frequency (0.01-1%) variants, which we genotyped in participants using a custom Illumina panel. Two complementary statistical approaches, sequence kernel association test and combined multivariate and collapsing, were used to test association of the aggregated low-frequency variants across each enhancer region with CL/P and CP. We discovered a significant association between CP and a branchial arch enhancer near FOXP1 (mm60; p-value = .0002). Additionally, we observed a suggestive association between CL/P and a forebrain enhancer near FOXE1 (hs1717; p-value = .001). These findings suggest that low-frequency variants in craniofacial enhancer regions contribute to the complex etiology of nonsyndromic OFCs.
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Encéfalo/anormalidades , Fenda Labial/diagnóstico , Fenda Labial/genética , Fissura Palatina/diagnóstico , Fissura Palatina/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Sequências Reguladoras de Ácido Nucleico , Alelos , Elementos Facilitadores Genéticos , Estudos de Associação Genética/métodos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Objective: The present report describes an alternative technique of using a flow- through, double-paddle, fibular, osteocutaneous free flap based on one perforator from the peroneal system and one perforator from the anterior tibial system for a through-and-through mandibular defect. Methods: The patient was a 65-year-old man who underwent a composite resection of the floor of the mouth, mandible, and chin pad due to recurrent oral cavity squamous cell carcinoma. The fibula was harvested with one posterior-lateral septal perforator from the peroneal system and with a second skin perforator from the anterior tibial system to perfuse a 15 × 14 cm skin island. The anterior tibial perforator was anastomosed to the distal end of the peroneal artery in a flow-through technique, and the area between the peroneal and tibial perforators was de-epithelialized to reconstruct separately the floor of mouth and cutaneous defects. Results: Good inflow and outflow of both skin islands were noted at the end of the procedure, and the patient recovered successfully without any fistulas or donor site morbidity. Conclusions: Perforators from the anterior tibial system should be considered for large, through-and-through mandibular defects when using 2 perforators from the peroneal system is not possible. In addition, we believe the flow-through technique can be useful in patients with vessel-depleted necks and provides a suitable match for vessel size between an anterior tibial perforator and the distal end of the peroneal system.
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IMPORTANCE: Flap choice and design are crucial to the success of free flap reconstruction of the head and neck. These are dependent on donor and recipient site characteristics. OBJECTIVE: To demonstrate indications and outcomes of a single-pedicle anterolateral thigh flap (standard ALT flap) vs a thigh free flap with 2 pedicles in head and neck reconstruction. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case series of consecutive patients treated in a tertiary academic care center between October 2011 and June 2017 by a single reconstructive microsurgeon was carried out. Eighty-one patients underwent reconstruction of a cutaneous and/or mucosal defect of the head and neck. Patients with a composite mandibular defect who received both a fibular flap and a thigh flap were excluded. Those with less than 6 months of follow-up were excluded. MAIN OUTCOMES AND MEASURES: Patient characteristics and clinical variables, including age, sex, primary diagnosis/indication for reconstruction, type of flap, dimensions of flap, and number of perforators in the flap, were collected. Optimal cutoff values to quantitate the differences in length and width between the standard ALT and 2-pedicle thigh flaps were determined using receiver operating characteristic (ROC) curve analysis and the Youden Index. The types of flap were compared to determine any difference in flap complications including flap loss, venous congestion, and poor wound healing. RESULTS: Of the 81 patients (mean [SD] age, 58.2 [15.9] years; 62 [76.5%] men), 57 and 18 patients were reconstructed with a standard ALT flap and a thigh flap with 2 pedicles, respectively. Six patients underwent multiple simultaneous thigh (MST) flaps. Defect size (width ≥12 cm, standard ALT: 95% CI, 7.6-9.7; thigh flap with 2 pedicles: 95% CI, 7.0-17.4; P = .02; length ≥17 cm, standard ALT: 95% CI, 11.9-15.2; thigh flap with 2 pedicles: 95% CI, 13.6-30.0; P = .001), the presence of divergent mucosal defects, and through-and-through oral cavity/pharyngeal defects were associated with the use of 2 pedicles. Within groups of thigh flaps with 2 pedicles and MST flaps, there were no flap complications (ie, partial loss, venous congestion, or wound healing issues from poor perfusion). CONCLUSIONS AND RELEVANCE: Harvesting a thigh flap with 2 pedicles has the potential to reduce flap complications and should be considered for divergent and wide or long defects. Width and length measurements respectively of 12 cm and 17 cm are reasonable numbers to initially consider when deciding whether to include a second pedicle. LEVEL OF EVIDENCE: 3.
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Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Coxa da Perna , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Velopharyngeal dysfunction (VPD) occurs when the muscular soft palate (velum) and lateral pharyngeal walls are physically unable to separate the oral and nasal cavities during speech production leading to hypernasality and abnormal speech reduction. Because VPD is often associated with overt or submucous cleft palate, it could be present as a subclinical phenotype in families with a history of orofacial clefting. A key assumption to this model is that the overt and subclinical manifestations of the orofacial cleft phenotype exist on a continuum and therefore share common etiological factors. We performed a genome-wide association study in 976 unaffected relatives of isolated CP probands, 54 of whom had VPD. Five loci were significantly (p < 5 × 10-8) associated with VPD: 3q29, 9p21.1, 12q21.31, 16p12.3 and 16p13.3. An additional 15 loci showing suggestive evidence of association with VPD were observed. Several genes known to be involved in orofacial clefting and craniofacial development are located in these regions, such as TFRC, PCYT1A, BNC2 and FREM1. Although further research is necessary, this could be an indication for a potential shared genetic architecture between VPD and cleft palate, and supporting the hypothesis that VPD is a subclinical phenotype of orofacial clefting.
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Estudo de Associação Genômica Ampla , Insuficiência Velofaríngea/patologia , Adolescente , Adulto , Antígenos CD/genética , Criança , Colina-Fosfato Citidililtransferase/genética , Fissura Palatina/genética , Fissura Palatina/patologia , Proteínas de Ligação a DNA/genética , Feminino , Loci Gênicos , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores da Transferrina/genética , Insuficiência Velofaríngea/genética , Adulto JovemRESUMO
The biological relatives of offspring with nonsyndromic orofacial clefts have been shown to exhibit distinctive facial features, including excess asymmetry, which are hypothesized to indicate the presence of genetic risk factors. The significance of excess soft tissue nasal asymmetry in at-risk relatives is unclear and was examined in the present study. Our sample included 164 unaffected parents from families with a history of orofacial clefting and 243 adult controls. Geometric morphometric methods were used to analyze the coordinates of 15 nasal landmarks collected from three-dimensional facial surface images. Following generalized Procrustes analysis, Procrustes ANOVA and MANOVA tests were applied to determine the type and magnitude of nasal asymmetry present in each group. Group differences in mean nasal asymmetry were also assessed via permutation testing. We found that nasal asymmetry in both parents and controls was directional in nature, although the magnitude of the asymmetry was greater in parents. This was confirmed with permutation testing, where the mean nasal asymmetry was significantly different (p < .0001) between parents and controls. The asymmetry was greatest for midline structures and the nostrils. When subsets of parents were subsequently analyzed and compared (parents with bilateral vs. unilateral offspring; parents with left vs. right unilateral offspring), each group showed a similar pattern of asymmetry and could not be distinguished statistically. Thus, the side of the unilateral cleft (right vs. left) in offspring was not associated with the direction of the nasal asymmetry in parents.
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Fissura Palatina/genética , Assimetria Facial/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Nariz/anormalidades , Nariz/diagnóstico por imagem , PaisRESUMO
Arteriovenous malformations (AVMs) are a type of high-flow vascular malformation that are characterized by abnormal capillary communications between the arterial and venous systems. While they are most commonly located in the head and neck region, their appearance in the nose is considerably rare, resulting in a paucity of literature regarding the surgical management of these lesions. We present the case of a 13-year-old male with a 6.5 × 6 cm AVM of the nose with a history of frequent nosebleeds since early childhood, often requiring aggressive measures, such as silver nitrate cauterization for control. Use of nasal decongestants and aminocaproic acid provided only transient improvement. After determination of arterial supply, AVM was approached with a combination of preoperative selective embolization and surgical excision with subsequent forehead flap defect coverage. Due to the size and complexity of this AVM, extra precautions were taken to avoid severe intraoperative bleeding, and femoral sheaths were placed prior to excision. The patient tolerated the procedure well, and with subsequent debulking surgery and Laser Hair Removal achieved an acceptable cosmetic outcome.
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Reconstruction of a composite maxillary defect is frequently performed with a fibular osteocutaneous free flap to address both the bony and mucosal defect. If during the harvest of the fibula a distal skin perforator is not present due to vascular variations, reconstruction can potentially be done using the soleus muscle for filling of the palatal mucosal defect. An additional challenge arises when the accompanying skin paddle that has been harvested is not perfused, but the fibula remains viable. This case report describes salvage following loss of the skin paddle in an osteocutaneous fibular free flap by designing a fibular flow-through flap using a proximal peroneal perforator free flap. The use of this second free flap allows a skin paddle to be positioned on the distal fibular segment, provides a surgical backup, and limits the donor sites to the same extremity.
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Multiple, simultaneous skin cancers of the face are common. This is the first description of reconstructing discontinuous facial defects (i.e., separate sites of the face) with simultaneous ulnar perforator flaps. The distinct innovations of this multiple flap design are the ability to restrict the harvest site to one extremity, to obtain vein and arterial grafts from the same extremity, and to create multiple flaps with minimal hirsutism and bulk. We present a case of a 57-year-old male with multiple basal cell carcinomas who underwent wide local excisions of the right upper lip and cheek and of the left lower eyelid and infraorbital cheek. Two left-sided ulnar perforator free flaps were used for reconstruction with the outcome of normal oral competence and eyelid function. When faced with discontinuous facial defects, reconstruction with simultaneous ulnar perforator flaps is a useful option because of the advantages of matching the thinness and pliability of the resected skin, reducing the number of harvest sites and preventing the distortion and contraction that can be seen with local advancement flaps or skin grafts.
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Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common human birth defects with complex etiology. Although genome-wide association studies have successfully identified a number of risk loci, these loci only account for about 20% of the heritability of orofacial clefts. The "missing" heritability may be found in rare variants, copy number variants, or interactions. In this study, we investigated the role of low-frequency variants genotyped in 1995 cases and 1626 controls on the Illumina HumanCore + Exome chip. We performed two statistical tests, Sequence Kernel Association Test (SKAT) and Combined Multivariate and Collapsing (CMC) method using two minor allele frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of NSCL/P. Low-frequency variants in other genes were associated with decreased risk of NSCL/P. These results demonstrate that low-frequency variants contribute to the genetic etiology of NSCL/P.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , Enzimas Reparadoras do DNA/genética , Glicoproteínas/genética , Proteínas de Membrana/genética , Proteínas Repressoras/genética , Alelos , Encéfalo/fisiopatologia , Fenda Labial/fisiopatologia , Fissura Palatina/fisiopatologia , Exoma/genética , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , População Branca/genéticaRESUMO
BACKGROUND AND HYPOTHESIS: Chronic ear infections are a common occurrence in children with orofacial clefts involving the secondary palate. Less is known about the middle ear status of individuals with isolated clefts of the lip, although several studies have reported elevated rates of ear infection in this group. The purpose of this retrospective study was to test the hypothesis that chronic ear infections occur more frequently in isolated cleft lip cases (n = 94) compared with controls (n = 183). METHODS: A questionnaire was used to obtain information on history of chronic ear infection. The association between ear infection status (present/absent) and cleft lip status (cleft lip case/control) was tested using both chi-square and logistic regression. RESULTS AND CONCLUSIONS: The reported occurrence of chronic ear infection was significantly greater in cleft lip cases (31%) compared with unaffected controls (11%). After adjusting for age and sex, having a cleft lip increased the odds of being positive for ear infection by a factor greater than 3 (odds ratio = 3.698; 95% confidence interval = 1.91 to 7.14). Within cleft lip cases, there was no difference in the occurrence of ear infection by defect laterality or by the type of clefting present in the family history. Although velopharyngeal insufficiency was present in 18.4% of our cleft lip sample, there was no statistical association between ear infection and abnormal speech patterns. These results may have potential implications both for the clinical management of isolated cleft lip cases and for understanding the etiology of orofacial clefting.
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Fenda Labial/complicações , Otite Média/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Doença Crônica , Feminino , Humanos , Masculino , Otite Média/epidemiologia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Since the 1960s, multiple studies have reported a tendency toward hypertelorism in individuals with nonsyndromic orofacial clefts (OFCs). However, the association between specific cleft types and increased interorbital distance has been inconsistent. Using three-dimensional (3D) surface imaging, we tested whether different forms of clefting showed evidence of increased interorbital distance. METHODS: Intercanthal and outercanthal distances and intercanthal indices were calculated from 3D facial surface images of 287 individuals with repaired OFCs. Raw measurements were converted to sex and age-normalized Z-scores. Mean Z-scores for individuals with cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) were compared with reference normative values (controls) and one another directly using t tests and analysis of variance. RESULTS: The CLP group showed a significant increase in intercanthal width (P = .001) and intercanthal index (P < .001) compared with reference norms. The CP group showed a significant decrease (P < .001) in outercanthal width. The CL group showed no difference from reference norms. The proportion of clinically hyperteloric individuals was generally low but highest in the CLP group (7.4%). Cleft severity had little effect on interorbital spacing. CONCLUSIONS: Individuals with CLP exhibited on average a tendency toward mild hypertelorism, driven primarily by an increase in intercanthal distance. This tendency was not seen in CL or CP.
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Antropometria/métodos , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Hipertelorismo/diagnóstico por imagem , Imageamento Tridimensional , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Fenda Labial/complicações , Fissura Palatina/complicações , Feminino , Humanos , Hipertelorismo/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE The authors' goals in this study were to describe a series of dog attacks on children that required neurosurgical consultation and to better understand the pattern of injuries inflicted, the circumstances that place children at risk for attack, and the dog breeds involved. In addition, the authors review the surgical and medical management of these patients. METHODS The authors performed a retrospective review of all children requiring neurosurgical consultation for dog bite at a regional Level 1 pediatric trauma center over a 15-year period. RESULTS A total of 124 children with dog bites to the head, face, and neck were evaluated in the emergency department. Of these, 17 children (13.7%) incurred injuries requiring neurosurgical consultation. Fifty-three percent of victims were female. The mean age at the time of attack was 30 months. Twelve (71%) of the attacks were perpetrated by the family pet, and 13 (76%) occurred at the patient's home. Breeds involved in the attacks included German Shepherd, Pit Bull, American Bulldog, large mixed breed, Labrador Retriever, and Akita, with German Shepherds and Akitas being the most frequently involved. Neurosurgical injuries included nondepressed skull fracture in 5, depressed skull fracture in 10, intracranial hemorrhage in 5, cerebral contusions in 4, dural laceration in 4, pneumocephalus in 5, clinically evident CSF leak in 3, spinal fracture with complete spinal cord injury in 1, stroke in 2, vascular injury in 2, and cranial nerve injury (hypoglossal and facial nerve) in 1. Prophylactic antibiotics were administered in 16 patients (94%). Only 1 patient had a confirmed infection involving the site of injury. Neurosurgical intervention was required in 10 patients (59%) and ranged in severity from debridement and closure of a complex scalp wound to decompressive craniectomy. Neurological deficits, all of which were considered catastrophic, developed in 3 patients (18%). CONCLUSIONS Dog attacks on children requiring neurosurgical consultation commonly involve the family pet, which is usually a large-breed dog with no history of prior aggression. Neurosurgical injuries often involve the cranial vault, with depressed skull fractures being the most common injury pattern. Most patients do not suffer a neurological deficit, although catastrophic neurological injury may occur. Prophylactic antibiotics are commonly used and surgical intervention is required in the majority of cases.
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Mordeduras e Picadas/diagnóstico , Mordeduras e Picadas/cirurgia , Traumatismos Craniocerebrais/diagnóstico , Traumatismos Craniocerebrais/cirurgia , Animais , Mordeduras e Picadas/complicações , Criança , Pré-Escolar , Traumatismos Craniocerebrais/etiologia , Cães , Serviço Hospitalar de Emergência/tendências , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Centros de Traumatologia/tendênciasRESUMO
Indocyanine green angiography (SPY) was used to guide arterial selection for an anterolateral thigh free flap in the setting of severe peripheral vascular disease. SPY technology serves as a novel and sensitive intraoperative tool to predict decreased tissue perfusion from vessel sacrifice for flap harvest. Change in SPY time parameters measuring superficial blood flow distal to the donor site while temporarily intraoperatively clamping different possible arterial pedicles can optimize free flap design to avoid iatrogenic critical limb ischemia.
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BACKGROUND: The purpose of this study was to investigate the incidence of symptomatic and asymptomatic deep venous thrombosis in patients undergoing harvest of a free flap from the lower extremity who were receiving standard chemoprophylaxis while hospitalized. METHODS: A retrospective review of 65 consecutive patients undergoing surgery between 2011 and 2013 was performed to determine the incidence of symptomatic deep venous thrombosis. These patients were screened for deep venous thrombosis based on development of symptoms. Prospective evaluation of a similar consecutive population of 37 patients between 2014 and 2015 was then performed to determine the incidence of asymptomatic deep venous thrombosis. These patients underwent routine duplex ultrasonography of both legs at postoperative weeks 1 and 4. RESULTS: Symptomatic deep venous thrombosis occurred in 2.9 percent of all patients. In the prospective cohort, 8.1 percent of the patients were found to have an acute deep venous thrombosis by postoperative week 1. At postoperative week 4, 16.7 percent of the patients developed a new, acute deep venous thrombosis. The estimated costs of screening and treating deep venous thrombosis in the retrospective group and the prospective group were $222 and $2259, respectively. The cost of routine chemoprophylaxis without duplex screening for an additional 14 days after discharge was $125 per patient. CONCLUSIONS: The rate of asymptomatic deep venous thrombosis may be much higher than previously appreciated in this population of very high-risk patients, especially during the 2 weeks after discharge. Extending the duration of chemoprophylaxis to 4 weeks after surgery may be warranted. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.