Development of Novel Polysaccharide Membranes for Guided Bone Regeneration: In Vitro and In Vivo Evaluations.

INTRODUCTION: Guided bone regeneration (GBR) procedures require selecting suitable membranes for oral surgery. Pullulan and/or dextran-based polysaccharide materials have shown encouraging results in bone regeneration as bone substitutes but have not been used to produce barrier membranes. The present study aimed to develop and characterize pullulan/dextran-derived membranes for GBR. MATERIALS AND METHODS: Two pullulan/dextran-based membranes, containing or not hydroxyapatite (HA) particles, were developed. In vitro, cytotoxicity evaluation was performed using human bone marrow mesenchymal stem cells (hBMSCs). Biocompatibility was assessed on rats in a subcutaneous model for up to 16 weeks. In vivo, rat femoral defects were created on 36 rats to compare the two pullulan/dextran-based membranes with a commercial collagen membrane (Bio-Gide®). Bone repair was assessed radiologically and histologically. RESULTS: Both polysaccharide membranes demonstrated cytocompatibility and biocompatibility. Micro-computed tomography (micro-CT) analyses at two weeks revealed that the HA-containing membrane promoted a significant increase in bone formation compared to Bio-Gide®. At one month, similar effects were observed among the three membranes in terms of bone regeneration. CONCLUSION: The developed pullulan/dextran-based membranes evidenced biocompatibility without interfering with bone regeneration and maturation. The HA-containing membrane, which facilitated early bone regeneration and offered adequate mechanical support, showed promising potential for GBR procedures.

Molecular Detection and Typing of Treponema pallidum in Non-Ocular Samples from Patients with Ocular Syphilis.

INTRODUCTION: Ocular syphilis is a rare but potentially sight-threatening manifestation of infection with the spirochete Treponema pallidum subspecies pallidum. Molecular strain typing of clinical specimens obtained from patients with syphilis can provide useful epidemiological and clinical information. In this study, we assess the utility of non-ocular clinical samples in strain typing for patients with diagnosed ocular syphilis. METHODS: We collected samples of excess blood, serum, and cerebrospinal fluid (CSF) from 6 patients with ocular syphilis treated in 2013-2016. DNA was extracted, purified, and then analyzed using an enhanced molecular typing method including sequence analysis of tp0548, number of repeats in the arp gene, and restriction fragment length polymorphism of the tpr gene. RESULTS: Molecular strain typing based on tp0548 gene sequence analysis revealed two cases of type F and two cases of type G in 3 of 6 (50%) cases with CSF samples, 1 of which was obtained after starting antibiotics. In a patient with 2 distinct episodes, the same tp0548 type (type G) was identified in both episodes using different sample types (CSF, whole blood). Serum samples were available in 6 cases, but none were successfully typed with any of the methods. Amplification of the tpr and arp genes was unsuccessful in all cases. Overall, strain types were identified in 4 of the 7 episodes. CONCLUSION: Treponema pallidum strain types F and G were detected in CSF or whole blood in 4 of 7 episodes in this series. We demonstrate moderate sensitivity of strain typing in ocular syphilis using non-ocular clinical specimens.

3D-Printed Osteoinductive Polymeric Scaffolds with Optimized Architecture to Repair a Sheep Metatarsal Critical-Size Bone Defect.

The reconstruction of critical-size bone defects in long bones remains a challenge for clinicians. A new osteoinductive medical device is developed here for long bone repair by combining a 3D-printed architectured cylindrical scaffold made of clinical-grade polylactic acid (PLA) with a polyelectrolyte film coating delivering the osteogenic bone morphogenetic protein 2 (BMP-2). This film-coated scaffold is used to repair a sheep metatarsal 25-mm long critical-size bone defect. In vitro and in vivo biocompatibility of the film-coated PLA material is proved according to ISO standards. Scaffold geometry is found to influence BMP-2 incorporation. Bone regeneration is followed using X-ray scans, µCT scans, and histology. It is shown that scaffold internal geometry, notably pore shape, influenced bone regeneration, which is homogenous longitudinally. Scaffolds with cubic pores of ≈870 µm and a low BMP-2 dose of ≈120 µg cm-3 induce the best bone regeneration without any adverse effects. The visual score given by clinicians during animal follow-up is found to be an easy way to predict bone regeneration. This work opens perspectives for a clinical application in personalized bone regeneration.

Fluid dynamics characterisation of a rotating bioreactor for tissue engineering.

Biological scaffolds composed of extracellular matrix (ECM) derived from decellularised tissue are increasingly used in regenerative medicine. In this project, a flow perfusion bioreactor (the rotary cell culture system (RCCS), commercially available from Synthecon (Houston, TX)) is used in order to obtain some esophageal extracellular matrix. A theoretical mechanical characterisation of this experimental set-up is provided. Due to the combination of rotation and perfusion, some spiral Poiseuille flow is created inside the tubular esophagus. In a transverse section, a particle (or cell) experiences simultaneously gravitational, Archimedes, centrifugal, Coriolis, and drag forces. In a frame of reference rotating with angular velocity ω, the particle follows a periodic nearly circular path in the clockwise direction, associated with a very slow centrifugal drift towards the esophagus wall. It appears that moderate perfusion rate and rotation speed (ω < 20 rpm and Q < 30 ml/min) are appropriate experimental conditions for esophagus tissue engineering using the RCCS Synthecon bioreactor.

Corticosteroid Use in Otolaryngology: Current Considerations During the COVID-19 Era.

OBJECTIVE: To offer pragmatic, evidence-informed advice on administering corticosteroids in otolaryngology during the coronavirus disease 2019 (COVID-19) pandemic, considering therapeutic efficacy, potential adverse effects, susceptibility to COVID-19, and potential effects on efficacy of vaccination against SARS-CoV-2, which causes COVID-19. DATA SOURCES: PubMed, Cochrane Library, EMBASE, CINAHL, and guideline databases. REVIEW METHODS: Guideline search strategies, supplemented by database searches on sudden sensorineural hearing loss (SSNHL), idiopathic facial nerve paralysis (Bell's palsy), sinonasal polyposis, laryngotracheal disorders, head and neck oncology, and pediatric otolaryngology, prioritizing systematic reviews, randomized controlled trials, and COVID-19-specific findings. CONCLUSIONS: Systemic corticosteroids (SCSs) reduce long-term morbidity in individuals with SSNHL and Bell's palsy, reduce acute laryngotracheal edema, and have benefit in perioperative management for some procedures. Topical or locally injected corticosteroids are preferable for most other otolaryngologic indications. SCSs have not shown long-term benefit for sinonasal disorders. SCSs are not a contraindication to vaccination with COVID-19 vaccines approved by the US Food and Drug Administration. The Centers for Disease Control and Prevention noted that these vaccines are safe for immunocompromised patients. IMPLICATIONS FOR PRACTICE: SCS use for SSNHL, Bell's palsy, laryngotracheal edema, and perioperative care should follow prepandemic standards. Local or topical corticosteroids are preferable for most other otolaryngologic indications. Whether SCSs attenuate response to vaccination against COVID-19 or increase susceptibility to SARS-CoV-2 infection is unknown. Immunosuppression may lower vaccine efficacy, so immunocompromised patients should adhere to recommended infection control practices. COVID-19 vaccination with Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccines is safe for immunocompromised patients.

Pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile infection following major head and neck free and pedicled flap surgeries.

OBJECTIVES: Medical postoperative infections (MPIs) are important causes of morbidity following major head and neck free and pedicled flap reconstruction, but the incidence, time of onset, and microbiology are not well characterized. MATERIALS AND METHODS: Medical records were reviewed of all head and neck flap surgeries performed 2009-2014 at an academic medical center. Postoperative pneumonia, urinary tract infection (UTI), bloodstream infection (BSI), Clostridioides difficile (CDI), and surgical site infections (SSI) were noted. Catheter-associated UTI (CAUTI), central line-associated BSI (CLABSI), and methicillin-resistant Staphylococcus aureus (MRSA) BSI were also evaluated. RESULTS: Following 715 free (540) or pedicled (175) flap surgeries, 14.1% of patients developed ≥one MPI including pneumonia (10.6%), UTI (2.1%), BSI (0.7%), and CDI (2.4%). Onset was ≤7 days in 77%. The MPI incidence in free vs pedicled flaps was similar. By multivariate analysis, age ≥65 and clindamycin perioperative prophylaxis were associated with increased MPI risk, clean class surgery with decreased risk. The incidence of CAUTI (<1.0%), CLABSI (0.1%), and hospital-onset MRSA BSI (0.1%) was low. SSI rate (7.8% overall) was higher in patients who developed pneumonia (18.4 vs 6.6, p = 0.004). MPI cultures grew gram-negative bacilli or S. aureus in 75%. The length of stay was longer in patients who developed a MPI than those who did not (17.4 vs 10.4 days, p < 0.0001). CONCLUSIONS: One-seventh of major head and neck flap surgeries were complicated by MPIs, three-quarters of infections developed within 1 week postoperatively. Gram-negative bacilli and S. aureus were the predominant pathogens.

Comparison of amniotic membrane versus the induced membrane for bone regeneration in long bone segmental defects using calcium phosphate cement loaded with BMP-2.

Thanks to its biological properties, the human amniotic membrane (HAM) combined with a bone substitute could be a single-step surgical alternative to the two-step Masquelet induced membrane (IM) technique for regeneration of critical bone defects. However, no study has directly compared these two membranes. We first designed a 3D-printed scaffold using calcium phosphate cement (CPC). We assessed its suitability in vitro to support human bone marrow mesenchymal stromal cells (hBMSCs) attachment and osteodifferentiation. We then performed a rat femoral critical size defect to compare the two-step IM technique with a single-step approach using the HAM. Five conditions were compared. Group 1 was left empty. Group 2 received the CPC scaffold loaded with rh-BMP2 (CPC/BMP2). Group 3 and 4 received the CPC/BMP2 scaffold covered with lyophilized or decellularized/lyophilized HAM. Group 5 underwent a two- step induced membrane procedure with insertion of a polymethylmethacrylate (PMMA) spacer followed by, after 4 weeks, its replacement with the CPC/BMP2 scaffold wrapped in the IM. Micro-CT and histomorphometric analysis were performed after six weeks. Results showed that the CPC scaffold supported the proliferation and osteodifferentiation of hBMSCs in vitro. In vivo, the CPC/BMP2 scaffold very efficiently induced bone formation and led to satisfactory healing of the femoral defect, in a single-step, without autograft or the need for any membrane covering. In this study, there was no difference between the two-step induced membrane procedure and a single step approach. However, the results indicated that none of the tested membranes further enhanced bone healing compared to the CPC/BMP2 group.

Isavuconazole Treatment of Invasive Fungal Sinusitis: A Post Hoc Analysis of the SECURE and VITAL Trials.

This post hoc analysis of international phase III isavuconazole trials identified 50 patients (90% immunocompromised or diabetic) with invasive fungal sinusitis (88% mucormycetes, Aspergillus) who received isavuconazole as primary (n = 33) or salvage (n = 17) therapy for a median of 82 days (range, 2-882). Overall survival was 82% at day 42 and 70% at day 84.

A Cluster of Corneal Donor Rim Cultures Positive for Achromobacter Species Associated With Contaminated Eye Solution.

PURPOSE: To investigate a cluster of corneoscleral rim cultures positive for Achromobacter species over a 6-month period at Massachusetts Eye and Ear. METHODS: An increased rate of positive corneal donor rim cultures was noted at Massachusetts Eye and Ear between July and December 2017. Positive cultures were subjected to identification and antimicrobial susceptibility testing by phenotypic (MicroScan WalkAway) and genotypic (16S rDNA sequencing) methods. Samples of the eye wash solution (GeriCare) used in the eye bank were also evaluated. Antimicrobial activity of Optical-GS against Achromobacter spp. at 4°C and 37°C was assessed by time-kill kinetics assay. RESULTS: Of 99 donor rims cultured, 14 (14.1%) grew bacteria with 11 (78.6%) due to uncommon nonfermenting Gram-negative bacilli. These had been identified by standard automated methods as Achromobacter (n = 3), Alcaligenes (n = 3), Ralstonia (n = 2), Pseudomonas (n = 2), and Stenotrophomonas (n = 1). Eight of these 11 isolates were subsequently available for molecular identification, and all were identified as Achromobacter spp. Six bottles of eyewash solution were evaluated and were positive for abundant Achromobacter spp. (3.4 × 105 ± 1.1 CFU/mL). Optisol-GS had no bactericidal activity against Achromobacter spp. at 4°C after 24-hour incubation but was bactericidal at 37°C. None of the patients who had received the contaminated corneas developed postoperative infection. CONCLUSIONS: An eyewash solution arising from a single lot was implicated in the contamination of donor rims by Achromobacter spp. The isolates were able to survive in the Optisol-GS medium at the recommended storage temperature. This highlights the need to continue improving protocols for tissue preparation and storage.

Prophylactic antibiotics after endoscopic sinus surgery for chronic rhinosinusitis: a randomized, double-blind, placebo-controlled noninferiority clinical trial.

BACKGROUND: Surgeons commonly prescribe prophylactic antibiotics after endoscopic sinus surgery (ESS), yet minimal data exist to support this practice. In this study we aimed to assess the impact of post-ESS antibiotics on infection, quality of life (QOL), and endoscopic scores. METHODS: This was a randomized, double-blind, placebo-controlled, noninferiority trial comparing amoxicillin-clavulanate vs placebo after ESS (NCT01919411, ClinicalTrials.gov). Adults (N = 77) with chronic rhinosinusitis (CRS) refractory to appropriate medical therapy who underwent ESS were randomized to antibiotics (N = 37) or placebo (N = 40) and followed clinically (mean ± standard deviation: 1.3 ± 0.3 and 8.8 ± 3.9 weeks postoperatively). At baseline and follow-up, QOL was measured with 22-item Sino-Nasal Outcome Test questionnaires and Lund-Kennedy endoscopic scores were evaluated. Outcomes were analyzed with repeated-measures analysis of variance and analysis of covariance and z tests for proportions. RESULTS: Placebo was noninferior to antibiotic prophylaxis with regard to postoperative SNOT-22 scores (ß = 0.18, 2-tailed p < 0.05). There were no significant differences between the antibiotic and placebo groups in LK score trajectories over time (p = 0.63) or in postoperative infection rates (2.6% vs 2.4%, respectively; p = 0.96). The rate of diarrhea was significantly higher in the antibiotic group (24.3% vs 2.5%; relative risk = 10.8; p = 0.02). CONCLUSION: Although statistically underpowered, the results suggest placebo was noninferior to prophylactic antibiotics after ESS for CRS regarding postoperative sinonasal-specific QOL. There were no significant differences in postoperative endoscopic scores or rates of infection, but the rate of diarrhea was significantly higher in the antibiotic group. These findings add to the growing evidence that routine use of prophylactic postoperative antibiotics does not improve outcomes post-ESS and significantly increases the rate of diarrhea.

Multicenter Pilot Study to Assess a Biphasic Calcium Phosphate Implant for Functional and Aesthetic Septorhinoplasty.

Importance: A validated biomaterial would have several medical advantages in septorhinoplasties requiring a large-volume graft such as avoiding donor site morbidity, making ambulatory surgery possible, and reducing surgical costs. Objective: To assess the safety and efficacy of a ceramic to treat saddle and crooked noses. The main endpoint was the biocompatibility of the implant. The secondary endpoint was its functional and aesthetic efficacy. Design, Setting, and Participants: The nasal septum (NASEPT) study is a pilot multicenter noncomparative prospective phase IIa clinical trial. The biomaterial tested was a biphasic calcium phosphate implant composed of 75% hydroxyapatite and 25% beta tri calcium phosphate. This versatile material can be used to replace septal skeleton when it is absent or nonusable. We included 25 patients with a multifractured osseous and cartilaginous framework after several traumas or surgeries. The implant placement technique was identical to an extracorporeal septoplasty through the external approach. Main Outcomes and Measures: The primary endpoint was the occurrence of expected adverse and severe adverse events. The secondary endpoints were clinical functional and aesthetic results and histological microscopic modifications. Results: Any extrusion, infection, pain, and epistaxis were observed. All implants were placed in a sagittal, straight, and solid position without extralobular depression. Comparisons between pre- and postoperative symptoms showed that nasal comfort (p < 10-4) and quality of life (p < 10-4) were dramatically improved in all patients. The nasolabial angle (p = 0.047) and the columellar projection (p = 0.024) were improved after surgery. Histological data showed little submucosal inflammation at 6 months with well-differentiated epithelium. The mean follow-up was 23 months: three patients underwent revision surgery for functional or aesthetic details and four implants were removed (16%) owing to a foreign body reaction between 17 and 74 months. Conclusion and Relevance: The NASEPT implant meets functional and aesthetic requirements in complex septorhinoplasties but its long-term biocompatibility needs to be improved. It could potentially avoid donor site morbidity.

Comparison of Two Percutaneous Atrial Septal Defect Occluders for Device Healing and Nickel Release in a Chronic Porcine Model.

AIMS: To investigate the healing process and nickel release of the Hyperion occluder (Comed BV, Netherlands), as compared to the Amplatzer septal occluder (ASO) (St. Jude Medical Inc., St. Paul, MN, USA) in a chronic swine model. BACKGROUND: Some long-term complications occurring after percutaneous atrial septal defect (ASD) closure may be partially associated with an inappropriate healing of the device and increased nickel release. There is no direct comparative study of different occluders for healing and nickel release. METHODS: After percutaneous ASD creation, 12 pigs were implanted with 15 mm Hyperion (n = 6) and 15 mm ASO (n = 6) devices. After 1 month (n = 3 for each device) and 3 months (n = 3 for each device) of follow-up, device explantation was performed and healing was assessed using histopathological workup. Systemic and tissular nickel release was performed. RESULTS: Implantation was successful in 100% without complications. Device coverage was observed as early as 1 month after implantation and was almost complete after 3 months. A granulation tissue with a predominantly mononuclear inflammatory reaction was observed in contact with nitinol wires while an inflammatory reaction was seen in contact with textile fibers. We found no statistically significant difference between the 2 devices whether for histological grading scores or systemic nickel release, regardless to follow-up duration. CONCLUSIONS: In this preclinical study, we demonstrated that Amplatzer septal occluder and Hyperion occluder were not significantly different for device healing and nickel release processes.

In vitro comparison of three percutaneous atrial septal defect closure devices for endothelialisation and haemocompatibility.

BACKGROUND: Percutaneous device closure of atrial septal defect (ASD) is the gold-standard treatment, but several delayed complications may occur as a result of incomplete device endothelialisation. AIMS: In this in vitro study, we compared three ASD closure devices [Nit-Occlud® ASD-R (device 1); Hyperion™ ASDO (device 2); and Amplatzer™ Septal Occluder (device 3)] in terms of the endothelialisation process, using human endothelial progenitors cells (EPCs), and haemocompatibility. METHODS: EPCs from umbilical cord blood were extracted, cultured and characterised. Device samples were seeded with 100,000 cells/cm2. EPC adhesion was investigated at 3 and 24hours, and EPC proliferation was monitored, which allowed longitudinal follow-up (days 1-12). Haemocompatibility of device samples was assessed using a complement C3a assay and platelet and coagulation activation. RESULTS: With regard to EPC adhesion and proliferation, no statistically significant differences were found between the three devices. We observed for each device a significant time-dependent EPC proliferation, appearing at day 8 for devices 2 and 3 and day 10 for device 1. No complement or platelet activation occurred within 15minutes of contact with devices. However, there was minimal activation of coagulation for the three devices. CONCLUSIONS: In this in vitro study we showed that, despite the three ASD occluders having different device designs and coatings, adhesion and proliferation of human endothelial cells was similar for all devices. This should be further confirmed by similar studies including shear stress forces and anti-thrombotic treatments.

Predicting length of stay in head and neck patients who undergo free flap reconstruction.

OBJECTIVE: Understanding factors that affect postoperative length of stay (LOS) may improve patient recovery, hasten postoperative discharge, and minimize institutional costs. This study sought to (a) describe LOS among head and neck patients undergoing free flap reconstruction and (b) identify factors that predict increased LOS. METHODS: A retrospective cohort was performed of 282 head and neck patients with free flap reconstruction for oncologic resection between 2011 and 2013 at a tertiary academic medical center. Patient demographics, tumor characteristics, and surgical and infectious complications were characterized. Multivariable regression identified predictors of increased LOS. RESULTS: A total of 282 patients were included. Mean age was 64.7 years (SD = 12.2) and 40% were female. Most tumors were located in the oral cavity (53.9% of patients), and most patients underwent radial forearm free flap (RFFF) reconstruction (RFFF-73.8%, anterolateral thigh flap-11.3%, and fibula free flap-14.9%). Intraoperative complications were rare. The most common postoperative complications included nonwound infection (pneumonia [PNA] or urinary tract infection [UTI]) (15.6%) and wound breakdown/fistula (15.2%). Mean and median LOS were 13 days (SD = 7.7) and 10 days (interquartile range = 7), respectively. Statistically significant predictors of increased LOS included flap take back (Beta coefficient [C] = +4.26, P < .0001), in-hospital PNA or UTI (C = +2.52, P = .037), wound breakdown or fistula (C = +5.0, P < .0001), surgical site infection (C = +3.54, P = .017), and prior radiation therapy (C = +2.59, P = .004). CONCLUSION: Several perioperative factors are associated with increased LOS. These findings may help with perioperative planning, including the need for vigilant wound care, optimization of antibiotics prophylaxis, and institution-level protocols for postoperative care and disposition of free flap patients. LEVEL OF EVIDENCE: 2b; retrospective cohort.

Assessment of fresh and preserved amniotic membrane for guided bone regeneration in mice.

Thanks to its biological properties, the human amniotic membrane (HAM) can be used as a barrier membrane for guided bone regeneration (GBR). However, no study has assessed the influence of the preservation method of HAM for this application. This study aimed to establish the most suitable preservation method of HAM for GBR. Fresh (F), cryopreserved (C) lyophilized (L), and decellularized and lyophilized (DL) HAM were compared. The impact of preservation methods on collagen and glycosaminoglycans (GAG) content was evaluated using Masson's trichrome and alcian blue staining. Their suture retention strengths were assessed. In vitro, the osteogenic potential of human bone marrow mesenchymal stromal cells (hBMSCs) cultured on the four HAMs was evaluated using alkaline phosphatase staining and alizarin red quantification assay. In vivo, the effectiveness of fresh and preserved HAMs for GBR was assessed in a mice diaphyseal bone defect after 1 week or 1 month healing. Micro-CT and histomorphometric analysis were performed. The major structural components of HAM (collagen and GAG) were preserved whatever the preservation method used. The tearing strength of DL-HAM was significantly higher. In vitro, hBMSCs seeded on DL-HAM displayed a stronger ALP staining, and alizarin red staining quantification was significantly higher at Day 14. In vivo, L-HAM and DL-HAM significantly enhanced early bone regeneration. One month after the surgery, only DL-HAM slightly promoted bone regeneration. Several preserving methods of HAM have been studied for bone regeneration. Here, we have demonstrated that DL-HAM achieved the most promising results for GBR.

Comparison of the impact of preservation methods on amniotic membrane properties for tissue engineering applications.

Human amniotic membrane (hAM) is considered as an attractive biological scaffold for tissue engineering. For this application, hAM has been mainly processed using cryopreservation, lyophilization and/or decellularization. However, no study has formally compared the influence of these treatments on hAM properties. The aim of this study was to develop a new decellularization-preservation process of hAM, and to compare it with other conventional treatments (fresh, cryopreserved and lyophilized). The hAM was decellularized (D-hAM) using an enzymatic method followed by a detergent decellularization method, and was then lyophilized and gamma-sterilized. Decellularization was assessed using DNA staining and quantification. D-hAM was compared to fresh (F-hAM), cryopreserved (C-hAM) and lyophilized/gamma-sterilized (L-hAM) hAM. Their cytotoxicity on human bone marrow mesenchymal stem cells (hBMSCs) and their biocompatibility in a rat subcutaneous model were also evaluated. The protocol was effective as judged by the absence of nuclei staining and the residual DNA lower than 50 ng/mg. Histological staining showed a disruption of the D-hAM architecture, and its thickness was 84% lower than fresh hAM (p < 0.001). Despite this, the labeling of type IV and type V collagen, elastin and laminin were preserved on D-hAM. Maximal force before rupture of D-hAM was 92% higher than C-hAM and L-hAM (p < 0.01), and D-hAM was 37% more stretchable than F-hAM (p < 0.05). None of the four hAM were cytotoxic, and D-hAM was the most suitable scaffold for hBMSCs proliferation. Finally, D-hAM was well integrated in vivo. In conclusion, this new hAM decellularization process appears promising for tissue engineering applications.

Postoperative care in an intermediate-level medical unit after head and neck microvascular free flap reconstruction.

OBJECTIVE: The need for intensive care unit (ICU) admission and mechanical ventilation after head and neck microvascular free flap reconstructive surgery remains controversial. Our institution has maintained a longstanding practice of immediately taking patients off mechanical ventilation with subsequent transfer to intermediate, non-ICU level of care with specialized otolaryngologic nursing. Our objective was to describe postoperative outcomes for a large cohort of patients undergoing this protocol and to examine the need for routine ICU transfer. MATERIALS AND METHODS: We performed a retrospective review of 512 consecutive free flaps treated with a standard protocol of immediate postoperative transfer to an intermediate-level care unit with specialized otolaryngology nursing. Outcome measures included ICU transfer, ventilator requirement, flap failure, postoperative complications, and length of stay. Predictors of ICU transfer were identified by multivariable logistic regression. RESULTS: The vast majority of patients did not require intensive care. Only a small fraction (n = 18 patients, 3.5%) subsequently transferred to the ICU, most commonly for respiratory distress, cardiac events, and infection. The most common complications were delirium/agitation (n = 55; 10.7%) and pneumonia (n = 51; 10.0%). Sixty-five cases (12.7%) returned to the OR, most commonly for hematoma/bleeding (n = 41; 8.0%) and anastomosis revision (n = 20; 3.9%). Heavy alcohol consumption and greater number of medical comorbidities were significant predictors of subsequent ICU transfer. CONCLUSIONS: Among head and neck free flap patients, routine cessation of mechanical ventilation and transfer to intermediate-level care with specialized ENT nursing was found to be safe with infrequent subsequent ICU transfer and low complication rates. Routine transfer to intermediate-level care in this population may prevent unnecessary ICU utilization and facilitate the delivery of high-value, disease-centered care. LEVEL OF EVIDENCE: 3b.

Esophageal tissue engineering: from bench to bedside.

For various esophageal diseases, the search for alternative techniques for tissue repair has led to significant developments in basic and translational research in the field of tissue engineering. Applied to the esophagus, this concept is based on the in vitro combination of elements judged necessary for in vivo implantation to promote esophageal tissue remodeling. Different methods are currently being explored to develop substitutes using cells, scaffolds, or a combination of both, according to the severity of lesions to be treated. In this review, we discuss recent advances in (1) cell sheet technology for preventing stricture after extended esophageal mucosectomy and (2) full-thickness circumferential esophageal replacement using tissue-engineered substitutes.