A Surgical Framework for the Management of Incomplete Axillary Nerve Injuries.

BACKGROUND: Axillary nerve injury is the most common nerve injury affecting shoulder function. Nerve repair, grafting, and/or end-to-end nerve transfers are used to reconstruct complete neurotmetic axillary nerve injuries. While many incomplete axillary nerve injuries self-resolve, axonotmetic injuries are unpredictable, and incomplete recovery occurs. Similarly, recovery may be further inhibited by superimposed compression neuropathy at the quadrangular space. The current framework for managing incomplete axillary injuries typically does not include surgery. METHODS: This study is a retrospective analysis of 23 consecutive patients with incomplete axillary nerve palsy who underwent quadrangular space decompression with additional selective medial triceps to axillary end-to-side nerve transfers in 7 patients between 2015 and 2019. Primary outcome variables included the proportion of patients with shoulder abduction M3 or greater as measured on the Medical Research Council (MRC) scale, and shoulder pain measured on a Visual Analogue Scale (VAS). Secondary outcome variables included pre- and postoperative Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) scores. RESULTS: A total of 23 patients met the inclusion criteria and underwent nerve surgery a mean 10.7 months after injury. Nineteen (83%) patients achieved MRC grade 3 shoulder abduction or greater after intervention, compared with only 4 (17%) patients preoperatively (p = 0.001). There was a significant decrease in VAS shoulder pain scores of 4.2 ± 2.5 preoperatively to 1.9 ± 2.4 postoperatively (p < 0.001). The DASH scores also decreased significantly from 48.8 ± 19.0 preoperatively to 30.7 ± 20.4 postoperatively (p < 0.001). Total follow-up was 17.3 ± 4.3 months. CONCLUSION: A surgical framework is presented for the appropriate diagnosis and surgical management of incomplete axillary nerve injury. Quadrangular space decompression with or without selective medial triceps to axillary end-to-side nerve transfers is associated with improvement in shoulder abduction strength, pain, and DASH scores in patients with incomplete axillary nerve palsy.

Effects of Single-Dose Preoperative Pregabalin on Postoperative Pain and Opioid Consumption in Cleft Orthognathic Surgery.

BACKGROUND: Several studies have illustrated the efficacy of pregabalin in decreasing postoperative opioid use in adults undergoing orthognathic surgery. We aimed to study the effects of a single dose of preoperative pregabalin on total opioid consumption after orthognathic surgery in individuals with cleft lip and palate. METHODS: This is a retrospective cohort study of consecutive patients who underwent Le Fort I midface advancement between June 2012 and July 2019. All patients had a diagnosis of cleft lip and palate. The treatment group received a 1-time preoperative dose of pregabalin; the control group did not. Total morphine milligram equivalent (MME) consumption was calculated by adding intraoperative and postoperative opioid use during admission. RESULTS: Twenty-three patients were included in this study; 12 patients received pregabalin. The pregabalin group had significantly lower total opioid consumption (total MME 70.95 MME; interquartile range [IQR]: 24.65-150.17) compared to the control group (138.00 MME; IQR: 105.00-232.48) (MU = 31.00, P = 0.031). The difference in mean pain scores in the treatment group (3.21 ±â€Š2.03) and the control group (3.71 ±â€Š2.95) was not statistically significant (P = 0.651, 95% confidence interval -1.75 to 2.75). CONCLUSIONS: A 1-time preoperative dose of pregabalin before orthognathic surgery in patients with cleft lip and palate reduced total opioid consumption during admission without increasing patient pain. A single preemptive dose of pregabalin should be considered an effective adjunct to pain management protocols in patients undergoing orthognathic surgery.

En Bloc Capsulectomy for Breast Implant Illness: A Social Media Phenomenon?

BACKGROUND: En bloc capsulectomy has recently increased in prominence as a potential surgical therapy for patients with breast implant illness (BII). However, this procedure has chiefly been recommended for treating breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). OBJECTIVES: This study aimed to review the current literature and evaluate the public understanding of treatment options for BII via social media to characterize any potential communication disconnect between clinicians and patients. METHODS: An electronic literature review was performed to identify all available publications mentioning evidence-based support for en bloc capsulectomy as treatment for BII and BIA-ALCL. Twitter social media posts referencing BII or BIA-ALCL were analyzed from 2010 to 2019. Author identity and any mention of surgical treatment were assessed. RESULTS: A total of 115 publications on the subject of BII and 315 articles on BIA-ALCL were identified. En bloc resection was recommended only for patients with a diagnosis of BIA-ALCL. A total of 6419 tweets referencing BII and 6431 tweets referencing BIA-ALCL were identified. Tweets referencing BIA-ALCL were significantly more likely to be authored by physicians (25.9% vs 5.3%, P < 0.001), and tweets referencing BII were significantly more likely to mention any surgical treatment (7.8% vs 1.9%, P < 0.001) and en bloc capsulectomy (1.4% vs 0.3%, P < 0.001). CONCLUSIONS: This study demonstrates that a communication disconnect exists between the scientific literature and social media regarding treatment options for BII and BIA-ALCL. Physicians should be aware of these potential misconceptions to empathetically address patient concerns in a patient-centered manner.

Comparative Effectiveness of Transversus Abdominis Plane Blocks in Abdominally Based Autologous Breast Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The abdomen is the most common donor site in autologous microvascular free flap breast reconstruction and contributes significantly to postoperative pain, resulting in increased opioid use, length of stay, and hospital costs. Enhanced Recovery After Surgery (ERAS) protocols have demonstrated multiple clinical benefits, but these protocols are widely heterogeneous. Transversus abdominis plane (TAP) blocks have been reported to improve pain control and may be a key driver of the benefits seen with ERAS pathways. METHODS: A systematic review and meta-analysis of studies reporting TAP blocks for abdominally based breast reconstruction were performed. Studies were extracted from 6 public databases before February 2019 and pooled in accordance with the PROSPERO registry. Total opioid use, postoperative pain, length of stay, hospital cost, and complications were analyzed using a random effects model. RESULTS: The initial search yielded 420 studies, ultimately narrowed to 12 studies representing 1107 total patients. Total hospital length of stay (mean difference, -1.00 days; P < 0.00001; I = 81%) and opioid requirement (mean difference, -133.80 mg of oral morphine equivalent; P < 0.00001; I = 97%) were decreased for patients receiving TAP blocks. Transversus abdominis plane blocks were not associated with any significant differences in postoperative complications (P = 0.66), hospital cost (P = 0.22), and postoperative pain (P = 0.86). CONCLUSIONS: Optimizing postoperative pain management after abdominally based microsurgical breast reconstruction is invaluable for patient recovery. Transversus abdominis plane blocks are associated with a reduction in length of stay and opioid use, representing a safe and reasonable strategy for decreasing postoperative pain.

Outcomes for 160 Consecutive Lateral Arm Free Flaps for Head and Neck Reconstruction.

OBJECTIVE: Examine outcomes for lateral arm autologous tissue transfer in head and neck reconstruction. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary cancer center. METHODS: All patients who underwent traditional lateral arm, extended lateral arm, and lateral forearm flaps for head and neck reconstruction from 2012 to 2022 were assessed. Disabilities of the arm, shoulder, and hand (DASH) was measured. Factors associated with complications and enteral or mixed diet were evaluated by multivariable regression. RESULTS: Among 160 patients followed for a median of 2.3 ± 2.1 years, defects were 54% oral tongue, 18% external, 9% maxilla, 8% buccal mucosa, 9% floor of mouth, and 3% pharynx. Flap types (and median pedicle lengths) were 41% traditional lateral arm (8 cm), 25% extended lateral arm (11.5 cm), and 34% lateral forearm (14 cm). All donor sites were closed primarily; 19.6% and 0% of patients had increased DASH scores 2 and 12 weeks after reconstruction. Major complications occurred in 18.1% of patients, including 6.3% reoperation, 6.9% readmission, 3.7% fistula, and 1.8% flap loss. Complications were independently associated with peripheral vascular disease (odds ratio [OR]: 5.71, 95% confidence interval [CI]: 1.5-21.6, P = .01), pharyngeal defects (OR: 11.3, 95% CI: 1.4-94.5, P = .025), and interposition vein grafts (OR: 3.78, 95% CI: 1.1-13.3, P = .037). CONCLUSION: The lateral arm free flap was safe, versatile, and reliable for head and neck reconstruction with low donor-site morbidity. Complications occurred in a fifth of patients and were associated with peripheral vascular disease, pharyngeal defects, and vein grafts.

Failed Targeted Muscle Reinnervation: Findings at Revision Surgery and Concepts for Success.

Although it was initially described for improved myoelectric control, targeted muscle reinnervation (TMR) has quickly gained popularity as a technique for neuroma control. With this rapid increase in utilization has come broadening indications and variability in the described technique. As a result, it becomes difficult to interpret published outcomes. Furthermore, there is no literature discussing the management of failed cases which are undoubtedly occurring. Methods: This is a retrospective case series of two patients who underwent revision surgery for failed TMR. The authors also review the current literature on TMR and outline technical and conceptual pitfalls and pearls based on our local experience. Results: Excessive donor nerve redundancy, kinking, donor-recipient nerve size mismatch, superficial placement of the nerve coaptation, inappropriate target selection, and incomplete target muscle denervation were identified as technical pitfalls of TMR surgery. Techniques to avoid these pitfalls were described. Conclusions: Although TMR has been a major development in amputee care for both pain management and improved myoelectric control, it is important to acknowledge that it is not a foolproof surgery and does not provide a guaranteed result. Failed cases of TMR represent opportunities to learn about factors contributing to unfavorable outcomes and refine our techniques empirically.

Nerve transfers for femoral nerve palsy: an updated approach and surgical technique.

OBJECTIVE: Femoral nerve palsy results in significant impairment of lower extremity function due to the loss of quadriceps muscle function. The authors have previously described their techniques utilizing the anterior obturator and sartorius nerves for transfer in cases of femoral nerve palsy presenting within 1 year of injury. In the current study, the authors discuss their updated techniques, results, and approach to partial and complete femoral nerve palsies using femoral nerve decompression and nerve transfers. METHODS: They conducted a retrospective review of patients with femoral nerve palsies treated with their technique at the Washington University School of Medicine in 2008-2019. Primary outcomes were active knee extension Medical Research Council (MRC) grades and visual analog scale (VAS) pain scores. RESULTS: Fourteen patients with femoral nerve palsy were treated with femoral nerve decompression and nerve transfer: 4 with end-to-end (ETE) nerve transfers, 6 with supercharged end-to-side (SETS) transfers, and 4 with ETE and SETS transfers, using the anterior branch of the obturator nerve, the sartorius branches, or a combination of both. The median preoperative knee extension MRC grade was 2 (range 0-3). The average preoperative VAS pain score was 5.2 (range 1-9). Postoperatively, all patients attained an MRC grade 4 or greater and subjectively noted improved strength and muscle bulk and more natural gait. The average postoperative pain score was 2.3 (range 0-6), a statistically significant improvement (p = 0.001). CONCLUSIONS: Until recently, few treatments were available for high femoral nerve palsy. A treatment strategy involving femoral nerve decompression and nerve transfers allows for meaningful functional recovery and pain relief in cases of partial and total femoral nerve palsy. An algorithm for the management of partial and complete femoral nerve palsies and a detailed description of surgical techniques are presented.

The two-handed template for planning fibular free flap reconstruction of the head and neck.

Fibular free flap reconstruction of head and neck defects is complex, and the anatomic relationships among components of the fibular flap pose challenges to reconstructive surgeons. Various techniques have been employed in planning for fibular free flap procedures, but these are often cumbersome and difficult to implement in clinically. We devised a simplistic tool for pre-operative leg selection, wherein the surgeon uses two hands to represent the various components of the fibular flap. The senior author has used this method to aid in leg selection for fibular free flaps. In all cases, utilization of this technique allowed for appropriate leg selection relative to the location of the vascular pedicle and posterior crural septum. The two-handed template for fibular free flap reconstruction is a simple, reproducible, and affordable tool that can aid reconstructive surgeons when they are planning to use a fibular flap.

Combined pectoralis and rectus abdominis flaps are associated with improved outcomes in sternal reconstruction.

BACKGROUND: Mortality increases nearly 5-fold in the approximately 5% of patients who develop sternal wound complications after cardiothoracic surgery. Flap-based reconstruction can improve outcomes by providing well-vascularized soft tissue for potential space obliteration, antibiotic delivery, and wound coverage; however, reoperation and readmission rates remain high. This study used the high case volume at a tertiary referral center and a diverse range of reconstructive approaches to compare various types of flap reconstruction. Combined (pectoralis and rectus abdominis) flap reconstruction is hypothesized to decrease sternal wound complication-related adverse outcomes. METHODS: A retrospective cohort study of consecutive adult patients treated for cardiothoracic surgery sternal wound complications between 2008 and 2018 was performed. Patient demographics, comorbidities, wound characteristics, surgical parameters, and perioperative data were collected. Multivariable regression modeling with stepwise forward selection was used to characterize predictive factors for sternal wound-related readmissions and reoperations. RESULTS: In total, 215 patients were assessed for sternal wound reconstruction. Patient mortality at 1 year was 12.4%. Flap selection was significantly associated with sternal wound-related readmissions (P = .017) and reoperations (P = .014). Multivariate regression demonstrated rectus abdominis flap reconstruction independently predicted increased readmissions (odds ratio 3.4, P = .008) and reoperations (odds ratio 2.9, P = .038). Combined pectoralis and rectus abdominis flap reconstruction independently predicted decreased readmissions overall (odds ratio 0.4, P = .031) and in the deep sternal wound subgroup (odds ratio 0.1, P = .033). CONCLUSION: Although few factors can be modified in this complex highly comorbid population with a challenging and rare surgical problem, consideration of a more surgically aggressive multiflap reconstructive approach may be justified to improve outcomes.

Two-incision Approach for the Open Reduction Internal Fixation of Intra-articular Hamate Body Fractures Using a Cannulated Headless Compression Screw.

Fractures of the hamate are relatively rare and there is a paucity of literature describing their natural history, indications for operative fixation, surgical techniques, and outcomes. Most authors recommend operative fixation of displaced intra-articular coronal hamate body fractures, and a dorsal approach with Kirschner wires has most commonly been recommended to achieve this. In this report, a 2-incision approach to the hamate is presented that facilitates rigid internal fixation of coronal hamate body fractures with a cannulated headless compression screw and minimizes the possibility of iatrogenic injury to critical branches of the ulnar nerve. The authors summarize a series of 2 patients with displaced, intra-articular coronal hamate body fractures of differing severity treated successfully with the proposed approach.

Foot Salvage with Selective Arterialization of Pedal Venosomes.

BACKGROUND: Lower extremity salvage using microvascular flaps can be considered in high-functioning patients, but indications for salvage are often restricted by distal microvascular disease that may threaten the foot as a whole. Selective arterialization of specific pedal venosomes is a novel potential solution to this problem. METHODS: A 48-year-old man with a chronic left plantar forefoot wound, osteomyelitis of the second and third metatarsal heads, and critical limb ischemia was evaluated for foot salvage. Despite a patent popliteal to posterior tibial bypass graft, residual ischemia was present in the first and second toes due to severe microvascular disease. This wound was reconstructed with a free partial medial rectus abdominis flow-through flap based on the medial branch of the deep inferior epigastric artery. The lateral branch was used as a flow-through vessel to arterialize the dorsal veins of the first webspace. RESULTS: Arterialization of the first webspace veins resulted in an immediate intraoperative improvement of the color of the first and second toes, along with creation of an arterial Doppler signal. The flap effectively covered the wound. The patient went on to heal completely and return to unrestricted ambulation. Transcutaneous oxygen measurement values of the dorsal foot improved from 35.8 mm Hg preoperatively to 48.3 mm Hg postoperatively. CONCLUSIONS: In patients with focal areas of critical ischemia, selective arterialization of the venous system may be an effective method of preventing tissue loss and improving wound healing. A flow-through flap can be used to accomplish this in tandem with wound reconstruction.

School-Aged Anthropometric Outcomes After Endoscopic or Open Repair of Metopic Synostosis.

BACKGROUND AND OBJECTIVES: Metopic craniosynostosis can be treated by fronto-orbital advancement or endoscopic strip craniectomy with postoperative helmeting. Infants younger than 6 months of age are eligible for the endoscopic repair. One-year postoperative anthropometric outcomes have been shown to be equivalent, with significantly less morbidity after endoscopic treatment. The authors hypothesized that both repairs would yield equivalent anthropometric outcomes at 5-years postoperative. METHODS: This study was a retrospective chart review of 31 consecutive nonsyndromic patients with isolated metopic craniosynostosis treated with either endoscopic or open correction. The primary anthropometric outcomes were frontal width, interfrontal divergence angle, the Whitaker classification, and the presence of lateral frontal retrusion. Peri-operative variables included estimated blood loss, rates of blood transfusion, length of stay, and operating time. RESULTS: There was a significantly lower rate of lateral frontal retrusion in the endoscopic group. No statistically significant differences were found in the other 3 anthropometric outcomes at 5-years postoperative. The endoscopic group was younger at the time of surgery and had improved peri-operative outcomes related to operating time, hospital stay and blood loss. Both groups had low complication and reoperation rates. CONCLUSIONS: In our cohort of school-aged children with isolated metopic craniosynostosis, patients who underwent endoscopic repair had superior or equivalent outcomes on all 4 primary anthropometric measures compared with those who underwent open repair. Endoscopic repair was associated with significantly faster recovery and decreased morbidity. Endoscopic repair should be considered in patients diagnosed with metopic craniosynostosis before 6 months of age.

Femoral nerve decompression and sartorius-to-quadriceps nerve transfers for partial femoral nerve injury: a cadaveric study and early case series.

OBJECTIVE: Partial femoral nerve injuries cause significant disability with ambulation. Due to their more proximal and superficial location, sartorius branches are often spared in femoral nerve injuries. In this article, the authors report the benefits of femoral nerve decompression, demonstrate the feasibility of sartorius-to-quadriceps nerve transfers in a cadaveric study, describe the surgical technique, and report clinical results. METHODS: Four fresh-frozen cadaveric lower limbs were dissected for anatomical analysis of the sartorius nerve. In addition, a retrospective review of patients with partial femoral nerve injuries treated with femoral nerve decompression and sartorius-to-quadriceps nerve transfers was conducted. Pre- and postoperative knee extension Medical Research Council (MRC) grades and pain scores (visual analog scale) were collected. RESULTS: Up to 6 superficial femoral branches innervate the sartorius muscle just distal to the inguinal ligament. Each branch yielded an average of 672 nerve fibers (range 99-1850). Six patients underwent femoral nerve decompression and sartorius-to-quadriceps nerve transfers. Four patients also had concomitant obturator-to-quadriceps nerve transfers. At final follow-up (average 13.4 months), all patients achieved MRC grade 4-/5 or greater knee extension. The average preoperative pain score was 5.2, which decreased to 2.2 postoperatively (p = 0.03). CONCLUSIONS: Femoral nerve decompression and nerve transfer using sartorius branches are a viable tool for restoring function in partial femoral nerve injuries. Sartorius branches serve as ideal donors in quadriceps nerve transfers because they are expendable, are close to their recipients, and have an adequate supply of nerve fibers.

Enhanced Recovery With Paravertebral and Transversus Abdominis Plane Blocks in Microvascular Breast Reconstruction.

PURPOSE: We have shown previously that a preoperative paravertebral nerve block is associated with improved postoperative recovery in microvascular breast reconstruction. The purpose of this study was to compare the outcomes of a complete enhanced recovery after surgery (ERAS) protocol with complete regional anesthesia coverage to our traditional care with paravertebral block. PATIENTS AND METHODS: This was a retrospective cohort study of 83 patients who underwent autologous breast reconstruction by T.M.M. between May 2014 and February 2018 at a tertiary academic center. Patients in the ERAS group were additionally administered acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin, a transversus abdominis plane block (liposomal or plain bupivacaine), and primarily oral opioids postoperatively. The patients were mobilized earlier with more rapid diet progression. All patients received a preoperative paravertebral block. RESULTS: Forty-four patients in the ERAS cohort were compared with 39 retrospective controls. The 2 groups were similar with respect to demographics and comorbidities. The ERAS cohort required significantly less opioids (291 vs 707 mg oral morphine equivalent, P < .0001) with unchanged postoperative pain scores and a shorter time to oral only opioid use (16.0 vs 78.2 hours, P < .0001). Median length of stay (3.20 vs 4.62, P < .0001) and time to independent ambulation (1.86 vs 2.88, P < .0001) were also significantly decreased in the ERAS cohort. Liposomal bupivacaine use did not significantly affect the results (P ⩾ .2). CONCLUSIONS: Implementation of a robust enhanced recovery protocol with complete regional anesthesia coverage was associated with significantly decreased opioid use despite unchanged pain scores, with improved markers of recovery including length of stay, time to oral only narcotics, and time to independent ambulation.

The Analgesic Effects of Liposomal Bupivacaine versus Bupivacaine Hydrochloride Administered as a Transversus Abdominis Plane Block after Abdominally Based Autologous Microvascular Breast Reconstruction: A Prospective, Single-Blind, Randomized, Controlled Trial.

BACKGROUND: Postoperative pain control after abdominally based autologous microvascular breast reconstruction is critical to functional recovery, patient satisfaction, and early discharge. The transversus abdominis plane block using 0.25% bupivacaine hydrochloride has been shown to be effective, but it is limited by a short duration of effect. Liposomal bupivacaine is a recently U.S. Food and Drug Administration-approved preparation of bupivacaine that can provide up to 72 hours of pain relief. The purpose of this randomized, controlled trial was to compare the analgesic efficacy of liposomal bupivacaine and conventional bupivacaine. METHODS: This study was a prospective, single-blind, randomized, controlled trial of 44 patients undergoing abdominally based autologous breast reconstruction between June of 2016 and February of 2018 performed by a single surgeon. Each patient was randomized to receive either 266 mg of liposomal bupivacaine or 75 mg of conventional bupivacaine to the transversus abdominis plane at the conclusion of the reconstruction procedure. All patients were managed postoperatively according to an enhanced recovery protocol. RESULTS: In our study of 44 patients, 22 patients received a transversus abdominis plane block with conventional bupivacaine and 22 patients received liposomal bupivacaine. There were no significant differences with regard to any outcome measure. No differences were found in total opioid consumption (p = 0.98), Quality of Recovery-15 scores (p = 0.72), pain scores (p = 0.39), or length of stay (p = 0.20). CONCLUSION: In the setting of a robust enhanced recovery after surgery protocol, liposomal bupivacaine does not confer advantages over conventional bupivacaine when used as single injections in transversus abdominis plane blocks after abdominally based microvascular breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Interdisciplinary Management of Minimally Displaced Orbital Roof Fractures: Delayed Pulsatile Exophthalmos and Orbital Encephalocele.

Traumatic orbital roof fractures are rare and are managed nonoperatively in most cases. They are typically associated with severe mechanisms of injury and may be associated with significant neurologic or ophthalmologic compromise including traumatic brain injury and vision loss. Rarely, traumatic encephalocele or pulsatile exophthalmos may be present at the time of injury or develop in delayed fashion, necessitating close observation of these patients. In this article, we describe two patients with minimally displaced blow-in type orbital roof fractures that were later complicated by orbital encephalocele and pulsatile exophthalmos, prompting urgent surgical intervention. We also suggest a management algorithm for adult patients with orbital roof fractures, emphasizing careful observation and interdisciplinary management involving plastic surgery, neurosurgery, and ophthalmology.

mTORC2 (Rictor) in Alzheimer's Disease and Reversal of Amyloid-ß Expression-Induced Insulin Resistance and Toxicity in Rat Primary Cortical Neurons.

Mammalian target of rapamycin complex 1 (mTORC1), a nutrient sensor and central controller of cell growth and proliferation, is altered in various models of Alzheimer's disease (AD). Even less studied or understood in AD is mammalian target of rapamycin complex 2 (mTORC2) that influences cellular metabolism, in part through the regulations of Akt/PKB and SGK. Dysregulation of insulin/PI3K/Akt signaling is another important feature of AD pathogenesis. We found that both total mTORC1 and C2 protein levels and individual C1 and C2 enzymatic activities were decreased in human AD brain samples. In two rodent AD models, mTORC1 and C2 activities were also decreased. In a neuronal culture model of AD characterized by accumulation of cellular amyloid-ß (Aß)42, mTORC1 activity was reduced. Autophagic vesicles and markers were correspondingly increased and new protein synthesis was inhibited, consistent with mTORC1 hypofunction. Interestingly, mTORC2 activity in neural culture seemed resistant to the effects of intracellular amyloid. In various cell lines, Aß expression provoked insulin resistance, characterized by inhibition of stimulated Akt phosphorylation, and an increase in negative mTORC1 regular, p-AMPK, itself a nutrient sensor. Rapamycin decreased phospho-mTOR and to lesser degree p-Rictor. This further suppression of mTORC1 activity protected cells from Aß-induced toxicity and insulin resistance. More striking, Rictor over-expression fully reversed the Aß-effects on primary neuronal cultures. Finally, using in vitro assay, Rictor protein addition completely overcame oligomeric Aß-induced inhibition of the PDK-Akt activation step. We conclude that striking a new balance by restoring mTORC2 abundance and/or inhibition of mTORC1 has therapeutic potential in AD.

Surgical Management of Chronic Wounds.

In this article, we outline the important role the surgeon plays in the management of chronic wounds. Debridement and washout are required for grossly infected wounds and necrotizing soft tissue infections. Cutaneous cancers such as squamous cell carcinomas may contribute to chronic wounds and vice versa; if diagnosed, these should be treated with wide local excision. Arterial, venous, and even lymphatic flows can be restored in select cases to enhance delivery of nutrients and removal of metabolic waste and promote wound healing. In cases where vital structures, such as bones, joints, tendons, and nerves, are exposed, vascularized tissue transfers are often required. These tissue transfers can be local or remote, the latter of which necessitates anastomoses of arteries and veins. Pressure sores are managed by relieving pressure, treating acute trauma or infection, and using rotation fasciocutaneous flaps. Lastly, the surgeon must always consider the possibility of osteomyelitis and retained foreign body as etiology for chronic wounds.

The Mechanism of Hyperbaric Oxygen Therapy in the Treatment of Chronic Wounds and Diabetic Foot Ulcers.

Non-healing wounds are a growing public health concern, and more than $25 billion per year in the US are spent caring for patients with chronic wounds. Many of these patients are referred to specialized wound centers, where hyperbaric oxygen therapy (HBO2T) has become a mainstay in healing wounds, especially diabetic foot ulcers (DFU). However, it is costly, with a typical course of therapy running into the tens of thousands of dollars. Presently, as many as 30-40% of DFU patients with Wagner's Grade 3 and 4 ulcers treated with HBO2T fail to heal by 24 weeks. Unfortunately, the patient will have already received lengthy therapy (30-60 daily treatments over 6-10 week time period) before having the wound deemed non-responsive. Currently, practitioners employ a combination of clinical markers, diagnostic testing and a four-week preliminary healing response, but this approach is inaccurate and delays definitive identification of HBO2T responder and non-responder phenotypes.