Early ambulation after fibular free flap surgery is associated with reduced length of stay, increased mobility independence, and discharge to home.

BACKGROUND: Fibula free flaps (FFF) are one of the most common bony flaps utilized. This paper describes a quality improvement project aimed at increasing early ambulation. METHODS: A review of FFF patients at an academic hospital was completed (2014-2023). In 2018, an institutional change to encourage early ambulation without placement of a boot was made. Changes in hospital disposition and physical therapy outcomes were evaluated. RESULTS: A total of 168 patients underwent FFF reconstruction. There was a statistically significant lower length of stay in Group 2 (early ambulation, no boot) (8.1 vs. 9.4; p = 0.04). A higher rate of discharge to a skilled nursing facility was noted in Group 1 (delayed ambulation with boot) (21.3% vs. 11.9%; p = 0.009). A higher proportion of patients in Group 2 demonstrated independence during bed mobility, transfers, and gait (p < 0.05). CONCLUSIONS: Early ambulation without boot placement after FFF is associated with decreased length of hospital stay, improved disposition to home and physical therapy outcomes.

Smartphone Use for Patient Photography by Plastic Surgery Trainees.

Medical photography has become essential to patient care, trainee education, and research in highly visual specialties such as plastic surgery. As smartphone technology advances, plastic surgeons and trainees are using their personal smartphones to take medical photographs prompting ethical and legal concerns about patient consent and privacy. This study aims to determine the prevalence of personal smartphone use for patient photography among plastic surgery trainees, evaluate encryption practices, and establish understanding of current guidelines. Through a survey of 71 plastic surgery trainees throughout the United States, we show that 99% use their personal cell phone to take medical photographs while only 65% use HIPAA-compliant photo storage applications, and only 49% are aware of standard guidelines. This highlights that personal smartphone use among plastic surgery trainees is ubiquitous and there is a need for additional education and access to HIPAA-compliant photo storage applications.

Success of Implantable Doppler Probes for Monitoring Buried Free Flaps.

OBJECTIVE: The objective of this study is to describe the operative success of completely buried free flaps and to determine the safety/reliability of using implantable dopplers for postoperative monitoring in completely buried free flaps. STUDY DESIGN: A retrospective chart review was conducted from 2014 to 2020. Patients were included who had implantable dopplers placed for monitoring a completely buried free flap without a visible skin paddle. SETTING: Single academic cancer hospital. METHODS: Patient charts were reviewed to determine flap viability after surgery, need for reoperation, and ability of implanted doppler probes to detected change in free flap status. RESULTS: A total of 65 patients were included. Locations of flaps were as follows: pharynx, 76.9%; skull base, 7.7%; trachea, 6.2%; esophagus, 4.6%; and facial reanimation, 4.6%. Types of free flaps performed included radial forearm (50.8%), anterolateral thigh (44.6%), and gracilis (4.6%). One patient (1.5%) returned to the operating room for vascular compromise, which was accurately detected by the implantable doppler and salvaged. All free flaps were viable upon hospital discharge based on clinical examination and implantable doppler signals. There were no complications related to implantable doppler use. CONCLUSIONS: Implantable dopplers are an effective method for evaluating postoperative success of completely buried free flaps. In our series utilizing implantable dopplers, buried free flap survival was higher than traditionally thought. The use of implanted dopplers for monitoring buried free flaps allows for an effective, cosmetically appealing, and simplified reconstructive technique.

A protein quality control pathway at the mitochondrial outer membrane.

Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins. However, quality control (QC) pathways for misfolded mitochondrial proteins remain poorly defined. Here, we establish temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in Saccharomyces cerevisiae. The ts- proteins sen2-1HAts and sam35-2HAts are degraded from the MOM by the ubiquitin-proteasome system. Ubiquitination of sen2-1HAts is mediated by the ubiquitin ligase (E3) Ubr1, while sam35-2HAts is ubiquitinated primarily by San1. Mitochondria-associated degradation (MAD) of both substrates requires the SSA family of Hsp70s and the Hsp40 Sis1, providing the first evidence for chaperone involvement in MAD. In addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex, Doa1 and a mitochondrial pool of the transmembrane Cdc48 adaptor, Ubx2, are implicated in their degradation. This study reveals a unique QC pathway comprised of a combination of cytosolic and mitochondrial factors that distinguish it from other cellular QC pathways.

Proteins are molecules that need to fold into the right shape to do their job. If proteins lose that shape, not only do they stop working but they risk clumping together and becoming toxic, potentially leading to disease. Fortunately, the cell has quality control systems that normally detect and remove misfolded proteins before they can cause damage to the cell. First, sets of proteins known as chaperones recognize the misfolded proteins, and then another class of proteins attaches a molecular tag, known as ubiquitin, to the misshapen proteins. When several ubiquitin tags are attached to a protein, forming chains of ubiquitin, it is transported to a large molecular machine within the cell called the proteasome. The proteasome unravels the protein and breaks it down into its constituent building blocks, which can then be used to create new proteins. Proteins are found throughout the different compartments of the cell and quality control processes have been well-studied in some parts of the cell but not others. Metzger et al. have now revealed how the process works on the surface of mitochondria, the compartment that provides the cell with most of its energy. To do this, they used baker's yeast, a model laboratory organism that shares many fundamental properties with animal cells, but which is easier to manipulate genetically. The quality control process was studied using two mitochondrial proteins that had been mutated to make them sensitive to changes in temperature. This meant that, when the temperature increased from 25°C to 37°C, these proteins would begin to unravel and trigger the clean-up operation. This approach has been used previously to understand the quality control processes in other parts of the cell. By removing different quality control machinery in turn from the yeast cells, Metzger et al. could detect which were necessary for the process on mitochondria. This showed that there were many similarities with how this process happen in other parts of the cell but that the precise combination of chaperones and enzymes involved was distinct. Furthermore, when the proteasome was not working, the misfolded proteins remained on the mitochondria, showing that they are not transported to other parts of the cell to be broken down. In the future, understanding this process could help to find potential drug targets for mitochondrial diseases. The next steps will be to see how well these findings apply to human and other mammalian cells.

Surgical Management of Vestibular Schwannoma: Practice Pattern Analysis via NSQIP.

OBJECTIVE: Characterize current perspectives in the surgical management of vestibular schwannoma (VS) to guide otolaryngologists in understanding United States practice patterns. METHODS: A retrospective analysis of ACS-NSQIP database was performed to abstract all patients from 2008 to 2016 who underwent VS resection using ICD-9/10 codes 225.1 and D33.3, respectively. The specific surgical approach employed was identified via CPT codes 61520, 61526/61596, and 61591, which represent retrosigmoid (RS), translabyrinthine (TL) and middle cranial fossa (MCF) approaches, respectively. Analyzed outcomes include general surgical complications, total length of stay, and reoperation. RESULTS: A total of 1671 VS cases were identified, 1266 (75.7%) were RS, 292 (17.5%) were TL, and 114 (6.8%) were MCF. The annual number of cases increased over the study period from 15 to 375, which is chiefly attributed to increased institutional participation in ACS-NSQIP. Perioperative variables including BMI (P < .001), ASA class (P = .004), ethnicity (P = .008), operative time (P < .001), and reoperation (P < .001) were found to be statistically significant between cohorts. Increased utilization of RS approach was consistent over the entire study period, with significantly more RS performed than either TL or MCF. Finally, a statistically significant difference with respect to general surgical complication rates was not noted between surgical approaches. CONCLUSIONS: There is increased employment of RS approach for the operative management of VS, which likely is the result of increased reliance on both stereotactic radiosurgery and observation as alternative treatment strategies.

Sinonasal Disease in Total Laryngectomy Patients.

OBJECTIVE: Total laryngectomy (TL) results in complete abolition of nasal airflow, with notable pathologic alterations of the intranasal mucosa, mucociliary clearance, and nasal cycle. Despite these observed morphological changes, it remains unclear whether this subpopulation of patients experiences clinically significant sinonasal disease. The goal of this study was to identify rhinosinusitis in TL patients using radiographic imaging. METHODS: An Institutional Review Board-approved retrospective review (January 2005-July 2017) identified 50 patients who underwent radiographic imaging before and after TL. The Lund-Mackay Staging System (LM) was applied to 197 surveillance computed tomography scans. Surveyed patients also underwent investigation of current sinonasal symptomatology using the SNOT-22 questionnaire. Simple linear regression was modeled to LM scores; tests of statistical significance were estimated via the method of Kenward and Roger. RESULTS: The mean age was 62.4 years, with a 5:1 male-to-female ratio. The mean SNOT-22 score was 27.4 (range, 5-33). A median of 3 scans was obtained, 49% within 12 months after TL. The mean (± standard deviation) postoperative LM score was 2.7 ± 3.97 points (range, 0-19). For every 1 month after TL, postoperative LM was +0.01 point (P = .49). Conversely, for every +1 point in preoperative LM, postoperative LM was +1.08 points (P < .001). Two patients required functional endoscopic sinus surgery after TL for persistent sinonasal disease. CONCLUSIONS: Preoperative sinonasal disease burden likely plays an important role in the development of clinically significant rhinosinusitis in TL patients. Correlating radiographic findings to validated outcome measures remains a critical aspect of determining optimal surgical candidates; this arena is still under investigation in this unique patient cohort.

Individual Patient-reported Activity Levels Before and After Joint Arthroplasty Are Neither Accurate nor Reproducible.

BACKGROUND: Patients often are asked to report walking distances before joint arthroplasty and when discussing their results after surgery, but little evidence demonstrates whether patient responses accurately represent their activity. QUESTIONS/PURPOSES: Are patients accurate in reporting distance walked, when compared with distance measured by an accelerometer, within a 50% margin of error? METHODS: Patients undergoing THA or TKA were recruited over a 16-month period. One hundred twenty-one patients were screened and 66 patients (55%) were enrolled. There were no differences in mean age (p = 0.68), proportion of hips versus knees (p = 0.95), or sex (p = 0.16) between screened and enrolled patients. Each patient wore a FitBit Zip accelerometer for 1 week and was blinded to its measurements. The patients reported their perceived walking distance in miles daily. Data were collected preoperatively and 6 to 8 weeks postoperatively. Responses were normalized against the accelerometer distances and Wilcoxon one-tailed signed-rank testing was performed to compare the mean patient error with a 50% margin of error, our primary endpoint. RESULTS: We found that patients' self-reported walking distances were not accurate. The mean error of reporting was > 50% both preoperatively (p = 0.002) and postoperatively (p < 0.001). The mean magnitude of error was 69% (SD 58%) preoperatively and 93% (SD 86%) postoperatively and increased with time (p = 0.001). CONCLUSIONS: Patients' estimates of daily walking distances differed substantially from those patients' walking distances as recorded by an accelerometer, the accuracy of which has been validated in treadmill tests. Providers should exercise caution when interpreting patient-reported activity levels. LEVEL OF EVIDENCE: Level III, diagnostic study.

Proteomic Analysis of Early Diabetic Retinopathy Reveals Mediators of Neurodegenerative Brain Diseases.

Purpose: Current evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy. Our main goal was to examine whether, in the diabetic human retina, common proteins and pathways are shared with brain neurodegenerative diseases. Methods: A proteomic analysis was performed on three groups of postmortem retinas matched by age: nondiabetic control retinas (n = 5), diabetic retinas without glial activation (n = 5), and diabetic retinas with glial activation (n = 5). Retinal lysates from each group were pooled and run on an SDS-PAGE gel. Bands were analyzed sequentially by liquid chromatography-mass spectrometry (LC/MS) using an Orbitrap Mass Spectrometer. Results: A total of 2190 proteins were identified across all groups. To evaluate the association of the identified proteins with neurological signaling, significant signaling pathways belonging to the category "Neurotransmitters and Other Nervous System Signaling" were selected for analysis. Pathway analysis revealed that "Neuroprotective Role of THOP1 in Alzheimer's Disease" and "Unfolded Protein Response" pathways were uniquely enriched in control retinas. By contrast, "Dopamine Degradation" and "Parkinson's Signaling" were enriched only in diabetic retinas with glial activation. The "Neuregulin Signaling," "Synaptic Long Term Potentiation," and "Amyloid Processing" pathways were enriched in diabetic retinas with no glial activation. Conclusions: Diabetes-induced retinal neurodegeneration and brain neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, share common pathogenic pathways. These findings suggest that the study of neurodegeneration in the diabetic retina could be useful to further understand the neurodegenerative processes that occur in the brain of persons with diabetes.

The Ubiquitin Ligase (E3) Psh1p Is Required for Proper Segregation of both Centromeric and Two-Micron Plasmids in Saccharomyces cerevisiae.

Protein degradation by the ubiquitin-proteasome system is essential to many processes. We sought to assess its involvement in the turnover of mitochondrial proteins in Saccharomyces cerevisiae We find that deletion of a specific ubiquitin ligase (E3), Psh1p, increases the abundance of a temperature-sensitive mitochondrial protein, mia40-4pHA, when it is expressed from a centromeric plasmid. Deletion of Psh1p unexpectedly elevates the levels of other proteins expressed from centromeric plasmids. Loss of Psh1p does not increase the rate of turnover of mia40-4pHA, affect total protein synthesis, or increase the protein levels of chromosomal genes. Instead, psh1Δ appears to increase the incidence of missegregation of centromeric plasmids relative to their normal 1:1 segregation. After generations of growth with selection for the plasmid, ongoing missegregation would lead to elevated plasmid DNA, mRNA, and protein, all of which we observe in psh1Δ cells. The only known substrate of Psh1p is the centromeric histone H3 variant Cse4p, which is targeted for proteasomal degradation after ubiquitination by Psh1p However, Cse4p overexpression alone does not phenocopy psh1Δ in increasing plasmid DNA and protein levels. Instead, elevation of Cse4p leads to an apparent increase in 1:0 plasmid segregation events. Further, 2 µm high-copy yeast plasmids also missegregate in psh1Δ, but not when Cse4p alone is overexpressed. These findings demonstrate that Psh1p is required for the faithful inheritance of both centromeric and 2 µm plasmids. Moreover, the effects that loss of Psh1p has on plasmid segregation cannot be accounted for by increased levels of Cse4p.

Dynamics of the human gut microbiome in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.