Medical care use and mortality rate after the onset of disability: A 6-year follow-up study based on national data in Taiwan.

BACKGROUND: The onset of disability is a major health challenge, and people with disability can be particularly underserved in the years immediately after the disability onset. OBJECTIVE: To analyze the excess mortality rate of people with recent-onset disability and their health-care utilization during the period after disability onset (1-6 years after onset). METHODS: We used whole-population claims data from 2015 to 2020 (for approximately 23 million individuals) from Taiwan's National Health Insurance (NHI) system. These NHI claims data were linked to the National Death Records and National Disability Registry. Each individual with a disability was followed until their death or December 31, 2020. The age-standardized mortality rate and outpatient and inpatient utilization were compared between individuals with and without disability. Finally, Cox regressions were estimated to determine excess mortality for the individuals with disability. RESULTS: The age-standardized mortality rates for the people with disability and those without disability were 1020.35/10,000 and 463.83/10,000, respectively. The people with disability utilized significantly more medical care under the NHI system. Mortality rates differed substantially among disability types. The Cox regression revealed a hazard ratio of 1.47 (95% CI = 1.46, 1.48) for all-cause mortality for people with disability, and significant sex differences in mortality risk were observed for some causes of death. CONCLUSION: According to the excess mortality rates within 6 years of disability onset observed in this study, the NHI may not be sufficient to reduce health disparity between people with and without disabilities. In addition, specific characteristics of each type of disability should be considered.

Medication adherence in patients with type 2 diabetes after disability onset: a difference-in-differences analysis using nationwide data.

BACKGROUND: Effectively managing the coexistence of both diabetes and disability necessitates substantial effort. Whether disability onset affects adherence to type 2 diabetes medication remains unclear. This study investigated whether disability onset reduces such adherence and whether any reduction varies by disability type. METHODS: This study used the National Disability Registry and National Health Insurance Research Database from Taiwan to identify patients with type 2 diabetes who subsequently developed a disability from 2013 to 2020; these patients were matched with patients with type 2 diabetes without disability onset during the study period. Type 2 diabetes medication adherence was measured using the medication possession ratio (MPR). A difference-in-differences analysis was performed to determine the effect of disability onset on the MPR. RESULTS: The difference-in-differences analysis revealed that disability onset caused a reduction of 5.76% in the 1-year MPR (P < 0.001) and 13.21% in the 2-year MPR (P < 0.001). Among all disability types, organ disabilities, multiple disabilities, rare diseases, and a persistent vegetative state exhibited the largest reductions in 2-year MPR. CONCLUSIONS: Policies aimed at improving medication adherence in individuals with disabilities should consider not only the specific disability type but also the distinct challenges and barriers these patients encounter in maintaining medication adherence.

Ultrahigh frequency transcutaneous electrical nerve stimulation for neuropathic pain alleviation and neuromodulation.

A challenging complication in patients with peripheral compressive neuropathy is neuropathic pain. Excessive neuroinflammation at the injury site worsens neuropathic pain and impairs function. Currently, non-invasive modulation techniques like transcutaneous electrical nerve stimulation (TENS) have shown therapeutic promise with positive results. However, the underlying regulatory molecular mechanism for pain relief remains complex and unexplored. This study aimed to validate the therapeutic effect of ultrahigh frequency (UHF)-TENS in chronic constriction injury of the rat sciatic nerve. Alleviation of mechanical allodynia was achieved through the application of UHF-TENS, lasting for 3 days after one session of therapy and 4 days after two sessions, without causing additional damage to the myelinated axon structure. The entire tissue collection schedule was divided into four time points: nerve exposure surgery, 7 days after nerve ligation, and 1 and 5 days after one session of UHF therapy. Significant reductions in pain-related neuropeptides, MEK, c-Myc, c-FOS, COX2, and substance P, were observed in the injured DRG neurons after UHF therapy. RNA sequencing of differential gene expression in sensory neurons revealed significant downregulation in Cables, Pik3r1, Vps4b, Tlr7, and Ezh2 after UHF therapy, while upregulation was observed in Nfkbie and Cln3. UHF-TENS effectively and safely relieved neuropathic pain without causing further nerve damage. The decreased production of pain-related neuropeptides within the DRG provided the therapeutic benefit. Possible molecular mechanisms behind UHF-TENS may result from the modulation of the NF-κB complex, toll-like receptor-7, and phosphoinositide 3-kinase/Akt signaling pathways. These results suggest the neuromodulatory effects of UHF-TENS in rat sciatic nerve chronic constriction injury, including alleviation of neuropathic pain, amelioration of pain-related neuropeptides, and regulation of neuroinflammatory gene expression. In combination with the regulation of related neuroinflammatory genes, UHF-TENS could become a new modality for enhancing the treatment of neuropathic pain in the future.

Increasing Trend and Effects of Pediatric Palliative Care on Children With Noncancer Diagnoses.

OBJECTIVES: Pediatric palliative care (PPC), especially among noncancer pediatric patients, faces challenges including late referral, limited patient care, and insufficient data for Asian patients. METHODS: This retrospective cohort study used the integrative hospital medical database between 2014 and 2018 to analyze the clinical characteristics, diagnoses, and end-of-life care for patients aged less than 20 who had died in our children's hospital, a tertiary referral medical center implementing PPC shared-care. RESULTS: In our cohort of 323 children, 240 (74.3%) were noncancer patients who a younger median age at death (5 vs. 122 months, P < 0.001), lower rate of PPC involvement (16.7 vs. 66%, P < 0.001), and fewer survival days after PPC consult compared to cancer patients (3 vs. 11, P = 0.01). Patients not receiving PPC had more ventilator support (OR 9.9, P < 0.001), and less morphine use on their final day of life (OR 0.1, P < 0.001). Also, patients not receiving PPC had more cardiopulmonary resuscitation on the last day of life (OR 15.3, P < 0.001) and died in the ICU (OR 8.8, P < 0.001). There was an increasing trend of noncancer patients receiving PPC between 2014 and 2018 (P < 0.001). CONCLUSIONS: High disparities exist between children receiving PPC in cancer versus noncancer patients. The concept of PPC is gradually becoming accepted in noncancer children and is associated with more pain-relief medication and less suffering during end-of-life care.

XIST/let-7i/HMGA1 axis maintains myofibroblasts activities in oral submucous fibrosis.

Long non-coding RNA XIST promotes the development of various types of head and neck cancers, but its role in the progression of precancerous oral submucous fibrosis (OSF) has not been determined yet. As such, we aimed to examine whether XIST implicates in the regulation of myofibroblast activation. Our results showed that the expression of XIST was upregulated in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs), and the silencing of XIST downregulated several myofibroblasts features. We demonstrated that elevation of let-7i after inhibition of XIST may lead to reduced myofibroblast activation. On the contrary, overexpression of high mobility group AT-Hook 1 (HMGA1) following the suppression of let-7i may result in enhanced myofibroblast activities. Moreover, we showed that the suppressive effect of silencing of XIST on myofibroblasts hallmarks was reversed by let-7i inhibition or HMGA1 overexpression, suggesting the pro-fibrotic property of XIST was mediated by downregulation of let-7i and upregulation of HMGA1. These findings revealed that myofibroblast activation of fBMFs may attribute to the alteration of the XIST/let-7i/HMGA1 axis. Therapeutic approaches to target this axis may serve as a promising direction to ameliorate the malignant progression of OSF.

Eyelid and scleral thermal injury following phacoemulsification in silicone oil: a case report.

BACKGROUND: Phacoemulsification has been the mainstay method for extracapsular cataract extraction surgery in the anterior segment; for cases of posterior drop of lens fragments into the vitreous, a posterior segment phacoemulsification instrument (fragmatome; Alcon, Inc., Fort Worth, TX) can be employed to remove the dislocated lens materials. Studies have reported on thermal injury to the cornea during phacmoemulsification of the anterior segment. However, few studies have investigated thermal burn in the simultaneous sclera and eyelid induced by the fragmatome. Currently, there is no reports and lack of optimal strategy for the management of nucleus drop in a vitreous cavity filled with silicon oil. CASE PRESENTATION: We present the case of a 53-year-old male patient with a thermal burn wound on the upper eyelid and sclera following phacoemulsification for a dropped lens in a silicone oil-filled vitreous. We further designed an experiment to verify our hypothesis that thermal injury could be induced by the high temperature of the metal tip during phacoemulsification in silicone oil. In our experiment, during 420 s of continuous ultrasonic wave, the temperature of the fragmatome tip in the balanced salt solution (BSS) increased from 22.0 to 24.0 ºC, while the temperature of the fragmatome tip in the silicone oil group increased from 22.0 to 43.0 ºC. CONCLUSIONS: The temperature of the fragmatome tip increased significantly in silicone oil compared to BSS in the experiment. Thus, physicians should be aware of possible thermal complications when using fragmatome in eyes filled with silicone oil.

Autologous Platelet-Rich Growth Factor Reduces M1 Macrophages and Modulates Inflammatory Microenvironments to Promote Sciatic Nerve Regeneration.

The failure of peripheral nerve regeneration is often associated with the inability to generate a permissive molecular and cellular microenvironment for nerve repair. Autologous therapies, such as platelet-rich plasma (PRP) or its derivative platelet-rich growth factors (PRGF), may improve peripheral nerve regeneration via unknown mechanistic roles and actions in macrophage polarization. In the current study, we hypothesize that excessive and prolonged inflammation might result in the failure of pro-inflammatory M1 macrophage transit to anti-inflammatory M2 macrophages in large nerve defects. PRGF was used in vitro at the time the unpolarized macrophages (M0) macrophages were induced to M1 macrophages to observe if PRGF altered the secretion of cytokines and resulted in a phenotypic change. PRGF was also employed in the nerve conduit of a rat sciatic nerve transection model to identify alterations in macrophages that might influence excessive inflammation and nerve regeneration. PRGF administration reduced the mRNA expression of tumor necrosis factor-α (TNFα), interleukin-1ß (IL-1ß), and IL-6 in M0 macrophages. Increased CD206 substantiated the shift of pro-inflammatory cytokines to the M2 regenerative macrophage. Administration of PRGF in the nerve conduit after rat sciatic nerve transection promoted nerve regeneration by improving nerve gross morphology and its targeted gastrocnemius muscle mass. The regenerative markers were increased for regrown axons (protein gene product, PGP9.5), Schwann cells (S100ß), and myelin basic protein (MBP) after 6 weeks of injury. The decreased expression of TNFα, IL-1ß, IL-6, and CD68+ M1 macrophages indicated that the inflammatory microenvironments were reduced in the PRGF-treated nerve tissue. The increase in RECA-positive cells suggested the PRGF also promoted angiogenesis during nerve regeneration. Taken together, these results indicate the potential role and clinical implication of autologous PRGF in regulating inflammatory microenvironments via macrophage polarization after nerve transection.

Fucoidan-Mediated Inhibition of Fibrotic Properties in Oral Submucous Fibrosis via the MEG3/miR-181a/Egr1 Axis.

Oral submucous fibrosis (OSF) is a chronic fibrotic remodeling disease that can progress to oral cancer. However, efficient clinical diagnosis and treatment methods for OSF are still lacking. This study investigated the anti-fibrotic effect of fucoidan on oral fibrosis. To evaluate the fibrotic ability (myofibroblast activities), we performed wound-healing, Transwell migration, and collagen contraction assays by using patient-derived normal and fibrotic buccal submucous fibroblasts (BMFs and fBMFs, respectively). RNA-sequencing and dual-luciferase reporter and RNA immunoprecipitation chip assays were performed to identify the clinical significance and molecular mechanism of non-coding RNAs. Fucoidan suppressed the myofibroblast activities and inhibited the MEG3 in fBMFs. MEG3 was overexpressed in the OSF tissue and was positively associated with myofibroblast markers. Knockdown of MEG3 markedly inhibited myofibroblast activities, which were restored by inhibiting miR-181a and overexpressing Egr1. The results from luciferase reporter and RIP assays confirmed that MEG3 functioned as a competing endogenous RNA (ceRNA) and could directly target miR-181a, thereby preventing the miR-181a-mediated translational repression of Egr1. This study demonstrated that MEG3 exerts a profibrotic effect on OSF by targeting miR-181a/Egr1. Therefore, the administration of fucoidan may serve as a potential therapeutic strategy for OSF by targeting the overexpression of MEG3.

microRNA-1266-5p directly targets DAB2IP to enhance oncogenicity and metastasis in oral cancer.

Background/purpose: Oral cancer has been recognized as one of the most common malignancies worldwide and ranks the fifth leading cause of cancer death in Taiwan. A variety of studies have demonstrated that microRNAs are involved in the regulation of the hallmarks of oral carcinogenesis. Nevertheless, the effect of miR-1266-5p on the tumorigenesis of oral cancer has not been investigated, and not to mention, its functional role in oral cancer. Materials and methods: The upregulation of miR-1266-5p in SASVO3 and SASM5 cells was identified by RNA-Seq and examined by qRT-PCR analysis. The phenotypic assays including proliferation activity, migration capacity, invasion, wound healing, and colony-forming abilities were conducted in oral cancer cells after knockdown of miR-1266-5p. Luciferase reporter and western blotting were used to validate DAB2IP was a direct target of miR-1266-5p in oral cancer. Results: We identified that miR-1266-5p was significantly overexpressed in highly tumorigenic SASVO3 cells and metastatic SASM5 cells. qRT-PCR revealed that miR-1266 significantly increased upregulated in oral cancer and lymph node metastatic tissues compared to normal counterparts We found that downregulation of miR-1266-5p inhibited the proliferation and clonogenicity capacities of SASVO3 cells. Knockdown of miR-1266-5p also inhibited migration/invasion and self-renewal abilities in SASM5 cells. Moreover, we validated miR-1266-5p directly bound to the 3'UTR of DAB2IP in oral cancer cells. We found that DAB2IP knockdown reversed the inhibitory effects of self-renewal and migration mediated by silencing of miR-1266-5p. Conclusion: miR-1266 functions as a biomarker in oral cancer patients, and downregulation of miR-1266 may ameliorate the oncogenic and metastasis potential of oral cancer by targeting DAB2IP.

The functional roles of microRNAs in the pathogenesis of oral submucous fibrosis.

Oral potentially malignant disorders (OPMD) are lesions that may precede the onset of cancers in the oral cavity, and oral submucosal fibrosis (OSF) is one of the OPMD that is usually found in the buccal mucosa. Considerable effort has been made to elucidate the pathogenesis of OSF, and emerging evidence has suggested that microRNAs may play significant roles in the development of OSF. Several studies demonstrated that aberrant expression of miRNAs is also observed in the fibrotic BMFs (fBMFs) derived from OSF tissues. For instance, it has been shown that miR-10b, miR-21, and miR-1246 are significantly elevated, and miR-29b, miR-200b, and miR-200c are reduced in fBMFs. This review systematically summarizes the current knowledge regarding the aberrant expression of microRNAs, molecular mechanisms underlying oral fibrogenesis by the dysregulated microRNAs, and how the interaction between microRNAs and long non-coding RNAs contributes to the progression of OSF. An overview of the modes of action by these microRNAs will provide a fundamental basis for clinical application.

Citrus depressa Hayata peel ameliorates nonalcoholic fatty liver and modulates the activity of hepatic drug-metabolizing enzymes and transporters in rats fed a high-fat diet.

Citrus depressa Hayata is a small, green citrus fruit native to Taiwan and Japan. Citrus peel contains polymethoxylated flavones, including nobiletin and tangeretin, and may exhibit strong antioxidant and anti-inflammatory activities. A preliminary study revealed that Citrus depressa Hayata peel (CDHP) ethanolic extract reduced fat accumulation and the concentration of reactive oxygen species in human HepG2 cells exposed to oleic acid. The effects of CDHP on the activity of hepatic drug-metabolizing enzymes and membrane transporters in high-fat (HF) diet-induced fatty liver were investigated. Male rats were fed a low-fat diet, a HF diet, and a HF diet containing 4% CDHP for 11 weeks. The low-fat and HF diet respectively contained 13.5% and 38.1% of daily total calories from dietary fat. CDHP supplementation reduced the HF diet-induced accumulation of triglycerides in the liver and lowered hepatic fatty acid synthase activity. Higher faecal excretions of cholesterol, triglycerides, and total bile acids were observed after CDHP treatment. CDHP lowered the HF diet-induced increase in the mRNA expressions of nuclear factor erythroid 2-related factor 2, aryl hydrocarbon receptor, pregnane X receptor, and peroxisome proliferator-activated receptor-α and the activities of cytochrome P-450 (CYP)1A1, 1A2, 2B, and 2E1. However, increased hepatic CYP3A activity was observed in rats fed the HF diet containing CDHP. A higher hepatic multidrug resistance-associated protein 2 level was observed after CDHP treatment. After CDHP administration (1 g per kg body weight) for 1 h, nobiletin was found in plasma and various tissues and was abundant in the liver. An in vitro study revealed that the activity of various CYP enzymes in liver microsomes was inhibited by CDHP ethanolic extract and nobiletin, with IC50 values ranging from 18.5 to 54.4 µg ml-1 and from 13.0 to 33.2 µM, respectively. The results of this study suggest that CDHP might reduce hepatic steatosis and alter drug-metabolizing enzymes and transporters in HF diet-induced nonalcoholic fatty liver diseases.

Down-regulation of miR-29c promotes the progression of oral submucous fibrosis through targeting tropomyosin-1.

BACKGROUND/PURPOSE: Various microRNAs (miRs) have been found to be associated with the development of the precancerous condition of the oral cavity, oral submucous fibrosis (OSF). The expression of miR-29c is dysregulated in oral cancer, but its role in OSF has not been investigated. The purpose of the study is to investigate the functional role of miR-29c and its target in OSF. METHODS: The expression levels of miR-29c in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were assessed using next-generation sequencing and real-time Polymerase Chain Reaction (PCR) analysis. MiR-29c mimic and inhibitors were employed to examine its functional role of myofibroblast transdifferentiation. In addition, several myofibroblast phenotypes, such as collagen gel contraction and migration were tested, and a luciferase reporter assay was conducted to confirm the relationship between miR-29c and its predicted target, tropomyosin-1 (TPM1). RESULTS: We observed that miR-29c expression was downregulated in fBMFs. fBMFs transfected with miR-29c mimics exhibited reduced migration ability and collagen gel contractility, whereas inhibition of miR-29c in normal BMFs induced the myofibroblast phenotypes. Results from the luciferase reporter assay showed that TPM1 was a direct target of miR-29c and the expression of TPM1 was suppressed in the fBMFs transfected with miR-29c mimics. Besides, we confirmed that the expression of miR-29c was indeed downregulated in OSF specimens. CONCLUSION: MiR-29c seems to exert an inhibitory effect on myofibroblast activation, such as collagen gel contractility and migration ability, via suppressing TPM1. These results suggested that approaches to upregulate miR-29c may be able to ameliorate the progression of OSF.

Sodium phenylbutyrate inhibits Schwann cell inflammation via HDAC and NFκB to promote axonal regeneration and remyelination.

BACKGROUND: Epigenetic regulation by histone deacetylases (HDACs) in Schwann cells (SCs) after injury facilitates them to undergo de- and redifferentiation processes necessary to support various stages of nerve repair. Although de-differentiation activates the synthesis and secretion of inflammatory cytokines by SCs to initiate an immune response during nerve repair, changes in either the timing or duration of prolonged inflammation mediated by SCs can affect later processes associated with repair and regeneration. Limited studies have investigated the regulatory processes through which HDACs in SCs control inflammatory cytokines to provide a favorable environment for peripheral nerve regeneration. METHODS: We employed the HDAC inhibitor (HDACi) sodium phenylbutyrate (PBA) to address this question in an in vitro RT4 SC inflammation model and an in vivo sciatic nerve transection injury model to examine the effects of HDAC inhibition on the expression of pro-inflammatory cytokines. Furthermore, we assessed the outcomes of suppression of extended inflammation on the regenerative potential of nerves by assessing axonal regeneration, remyelination, and reinnervation. RESULTS: Significant reductions in lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (tumor necrosis factor-α [TNFα]) expression and secretion were observed in vitro following PBA treatment. PBA treatment also affected the transient changes in nuclear factor κB (NFκB)-p65 phosphorylation and translocation in response to LPS induction in RT4 SCs. Similarly, PBA mediated long-term suppressive effects on HDAC3 expression and activity. PBA administration resulted in marked inhibition of pro-inflammatory cytokine secretion at the site of transection injury when compared with that in the hydrogel control group at 6-week post-injury. A conducive microenvironment for axonal regrowth and remyelination was generated by increasing expression levels of protein gene product 9.5 (PGP9.5) and myelin basic protein (MBP) in regenerating nerve tissues. PBA administration increased the relative gastrocnemius muscle weight percentage and maintained the intactness of muscle bundles when compared with those in the hydrogel control group. CONCLUSIONS: Suppressing the lengthened state of inflammation using PBA treatment favors axonal regrowth and remyelination following nerve transection injury. PBA treatment also regulates pro-inflammatory cytokine expression by inhibiting the transcriptional activation of NFκB-p65 and HDAC3 in SCs in vitro.

Case Report: Kasai Operation in Biliary Atresia After Extensive Bowel Resection.

Biliary atresia (BA) is a major and devastating cholestatic liver disease in infancy. The Kasai procedure is an operation to re-establish bile flow from the liver into the intestine that can prevent the young infant from progressing rapidly to cirrhosis. The standard Kasai procedure includes the removal of extrahepatic bile duct remnants and reconstruction. We report a case of BA with short bowel due to previous small intestinal volvulus. This full-term female infant received extensive small bowel resection after birth due to intestinal volvulus. The length of the residual small bowel was 55 cm with an intact ileocecal valve. Because of progressive cholestasis and clay stool, another laparotomy was performed under the diagnosis of BA on the 52 days old. After dissection of the hepatic portal area, a segment of the colon instead of intestine was used as a biliary conduit to avoid further shortening her small bowel. The patient recovered from the procedure uneventfully and the parenteral nutrition was discontinued 2 weeks later. Two episodes of cholangitis happened after discharge. She gradually resumed body weight gain and the bilirubin level returned to normal range 6 months after the operation. This unique case demonstrated successful use of this specific procedure in the patient with BA and short bowel that have never been reported in the literature.

Thrombomodulin facilitates peripheral nerve regeneration through regulating M1/M2 switching.

BACKGROUND: Excessive inflammation within damaged tissue usually leads to delayed or insufficient regeneration, and nerves in the peripheral nervous system (PNS) generally do not recover fully following damage. Consequently, there is growing interest in whether modulation of the inflammatory response could help to promote nerve regeneration in the PNS. However, to date, there are no practical therapeutic strategies for manipulating inflammation after nerve injury. Thrombomodulin (TM) is a transmembrane glycoprotein containing five domains. The lectin-like domain of TM has the ability to suppress the inflammatory response. However, whether TM can modulate inflammation in the PNS during nerve regeneration has yet to be elucidated. METHODS: We investigated the role of TM in switching proinflammatory type 1 macrophages (M1) to anti-inflammatory type 2 macrophages (M2) in a human monocytic cell line (THP-1) and evaluated the therapeutic application of TM in transected sciatic nerve injury in rats. RESULTS: The administration of TM during M1 induction significantly reduced the expression levels of inflammatory cytokines, including TNF-a (p < 0.05), IL-6 (p < 0.05), and CD86 (p < 0.05), in THP-1 cells. Simultaneously, the expression levels of M2 markers, including IL-10 (p < 0.05) and CD206 (p < 0.05), were significantly increased in TM-treated THP-1 cells. Inhibition of IL-4R-c-Myc-pSTAT6-PPARγ signaling abolished the expression levels of IL-10 (p < 0.05) and CD206 (p < 0.05). The conditioned medium (CM) collected from M1 cells triggered an inflammatory response in primary Schwann cells, while CM collected from M1 cells treated with TM resulted in a dose-dependent reduction in inflammation. TM treatment led to better nerve regeneration when tested 6 weeks after injury and preserved effector muscle function. In addition, TM treatment reduced macrophage infiltration at the site of injury and led to potent M1 to M2 transition, thus indicating the anti-inflammatory capacity of TM. CONCLUSIONS: Collectively, our findings demonstrate the anti-inflammatory role of TM during nerve regeneration. Therefore, TM represents a potential drug for the promotion and modulation of functional recovery in peripheral nerves that acts by regulating the M1/M2 ratio.

Use of Anterolateral Thigh Flap and Fibula Flap in Oncologic Maxillary Reconstruction: An Algorithm Approach.

BACKGROUND: Maxillary defects after oncologic resection can lead to not only cosmetic deformity but also functional problem. Reconstruction of maxillary defects remains the most challenging endeavor for plastic surgeons. An algorithm to guide plastic surgeons in selecting either the anterolateral thigh flap or the fibula flap for oncologic maxillary reconstruction has not been well established. METHODS: Patients who underwent oncologic maxillectomy and free flap reconstruction from August 2012 to April 2018 were enrolled for retrospective chart review. Their operative findings and postoperative outcomes were analyzed as a case series. The reconstructive plan was decided using the 4 essential components in sequence: the anterior maxillary arch, orbital floor, eyeball, and oro-sinonasal communication, which are the main considerations in the established classification systems. Accordingly, when the anterior maxillary arch was lost or when the orbital floor was lost with eyeball preservation, a fibula flap was used. Otherwise, an anterolateral thigh flap was used. RESULTS: Various maxillectomy defects were successfully reconstructed using an anterolateral thigh flap and a fibula flap. The defect types and corresponding reconstruction were fit into our proposed algorithm and classification. The corresponding outcomes were satisfactory. CONCLUSION: The proposed algorithm by using the anterolateral thigh flap and the fibula flap for oncologic maxillary reconstruction is feasible, simple, and effective.

Comparison of flap outcomes between single- and multiple-perforator-based free anterolateral thigh flap in head and neck reconstruction.

INTRODUCTION: The number of perforators required for safe perfusion remains under debate. This study aimed to determine whether a single- or multiple-perforator-based anterolateral thigh flap yields better flap outcomes in head and neck reconstruction. PATIENTS AND METHODS: Between August 2012 and July 2016, 180 men and 4 women with a mean age of 52.8 ± 9.8 years underwent head and neck anterolateral thigh flap reconstruction for oncologic defect in 181 cases, plate exposure in two cases, and trismus release in one case. The flap was patched for inner or external lining, folded for through-through defect, or tubed for cervical esophageal reconstruction. Of 184 flaps, 136 (73.9%) were based on multiple perforators (range, 2-5 perforators), whereas 48 (26.1%) were based on a single perforator. The demographics, operative findings, and flap outcomes were compared. RESULTS: The prevalence of systemic diseases between groups was comparable. The mean flap size in the single-perforator group was smaller (92.8 ± 36.8 vs. 140.5 ± 99.9 cm2 , P < .0001). Twenty-one flaps (11.4%) required emergency take-back and 13 (61.9%) were successfully salvaged. Eight flaps failed, yielding a 95.7% flap survival rate. The single-perforator group had a significantly higher rate of emergency take-back for vascular compromise (8/48 (16.7%) vs. 8/136 (5.9%), P = .035), a decreased salvage success rate (2/8 (25.0%) vs. 11/13 (84.6%), P = .018), and a corresponding lower flap survival rate (42/48 (87.5%) vs. 134/136 (98.5%), P = .004). CONCLUSION: Whenever possible, we recommend including multiple cutaneous perforators in anterolateral thigh flaps to yield better flap outcomes in head and neck reconstruction.

Surgical Algorithmic Approach to Facilitate Primary Closure of the Anterolateral Thigh Flap Donor Site in Head and Neck Reconstruction.

BACKGROUND: Use of the anterolateral thigh (ALT) flap has gained popularity in head and neck reconstruction. However, donor sites that cannot achieve primary closure are reported to have poorer functional and aesthetic outcomes. Therefore, we propose an algorithm to facilitate primary closure of the donor site. METHODS: Since May 2013, when an attempt at donor site direct closure failed, we have used a VY advancement flap or a propeller flap for primary closure of the donor site, using the remnant lateral thigh perforator or nearby medial thigh perforator. Otherwise, a skin graft was used. A total of 91 patients were enrolled in this algorithmic approach. We retrospectively reviewed patients with head and neck cancer who underwent cancer ablation and immediate ALT flap reconstruction since August 2010. The patients were then categorized into a "before" group and an "after" group according to the application time of the algorithm. Their demographics, intraoperative findings, and postoperative outcomes were analyzed. RESULTS: A total of 321 patients (309 men, 12 women) were enrolled, with 230 patients in the before group and 91 patients in the after group, with a mean age of 52.9 years. The mean size of the flap was 130 cm, with a mean width of 8.1 cm. No statistical difference existed between the groups. The donor site was directly closed in 82 patients (35.7%) in the before group. Using the perforator-based flap in 21 patients (23.1%), the donor site was closed primarily in 72 patients (79.1%) in the after group, contributing to a significantly higher donor site closure rate (P < 0.001). The average operative time was 348.7 minutes. The overall flap survival rate was 97.2%, donor-site complication rate was 6.9%, and hospitalization length was 23.5 days. None showed statistical differences between the groups. CONCLUSIONS: The proposed algorithm may considerably increase the primary closure rate of the ALT flap donor site.