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1.
Plast Reconstr Surg ; 153(1): 154-163, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37199690

ABSTRACT

BACKGROUND: Targeted muscle reinnervation (TMR) is an effective technique for the prevention and management of phantom limb pain (PLP) and residual limb pain (RLP) among amputees. The purpose of this study was to evaluate symptomatic neuroma recurrence and neuropathic pain outcomes between cohorts undergoing TMR at the time of amputation (ie, acute) versus TMR following symptomatic neuroma formation (ie, delayed). METHODS: A cross-sectional, retrospective chart review was conducted using patients undergoing TMR between 2015 and 2020. Symptomatic neuroma recurrence and surgical complications were collected. A subanalysis was conducted for patients who completed Patient-Reported Outcome Measurement Information System (PROMIS) pain intensity, interference, and behavior scales and an 11-point numeric rating scale (NRS) form. RESULTS: A total of 105 limbs from 103 patients were identified, with 73 acute TMR limbs and 32 delayed TMR limbs. Nineteen percent of the delayed TMR group had symptomatic neuromas recur in the distribution of original TMR compared with 1% of the acute TMR group ( P < 0.05). Pain surveys were completed at final follow-up by 85% of patients in the acute TMR group and 69% of patients in the delayed TMR group. Of this subanalysis, acute TMR patients reported significantly lower PLP PROMIS pain interference ( P < 0.05), RLP PROMIS pain intensity ( P < 0.05), and RLP PROMIS pain interference ( P < 0.05) scores in comparison to the delayed group. CONCLUSIONS: Patients who underwent acute TMR reported improved pain scores and a decreased rate of neuroma formation compared with TMR performed in a delayed fashion. These results highlight the promising role of TMR in the prevention of neuropathic pain and neuroma formation at the time of amputation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Subject(s)
Nerve Transfer , Neuralgia , Neuroma , Phantom Limb , Humans , Retrospective Studies , Cross-Sectional Studies , Nerve Transfer/methods , Amputation, Surgical , Phantom Limb/etiology , Phantom Limb/prevention & control , Phantom Limb/surgery , Neuroma/etiology , Neuroma/prevention & control , Neuroma/surgery , Neuralgia/etiology , Neuralgia/prevention & control , Neuralgia/surgery , Muscles , Muscle, Skeletal/surgery , Amputation Stumps/surgery
2.
mSystems ; 8(5): e0066123, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37610205

ABSTRACT

IMPORTANCE: We show that simultaneous study of stool and nasopharyngeal microbiome reveals divergent timing and patterns of maturation, suggesting that local mucosal factors may influence microbiome composition in the gut and respiratory system. Antibiotic exposure in early life as occurs commonly, may have an adverse effect on vaccine responsiveness. Abundance of gut and/or nasopharyngeal bacteria with the machinery to produce lipopolysaccharide-a toll-like receptor 4 agonist-may positively affect future vaccine protection, potentially by acting as a natural adjuvant. The increased levels of serum phenylpyruvic acid in infants with lower vaccine-induced antibody levels suggest an increased abundance of hydrogen peroxide, leading to more oxidative stress in low vaccine-responding infants.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Vaccines , Infant , Child , Humans , Metabolome , Vaccination
4.
J Orthop ; 31: 117-120, 2022.
Article in English | MEDLINE | ID: mdl-35541569

ABSTRACT

Background: Hip disarticulations are proximal lower extremity amputations with high postoperative complication and mortality rates. The purpose of the study was to evaluate hip disarticulation outcomes at our institution. Targeted Muscle Reinnervation (TMR) is an effective surgical technique shown to reduce pain in amputees. A secondary goal of the study was to evaluate the impact of implementing TMR on this patient population. Methods: A retrospective review was performed for patients who underwent hip disarticulation with and without TMR between 2009 and 2020. Information on one-year mortality, thirty-day complication rates, operation times, surgical charges, and pain scores was collected. Results: Fifty-one patients underwent hip disarticulation, eight of which had TMR performed at the time of their hip disarticulation. The one-year mortality rate was 37% with 30-day infection, readmission, reoperation, and rates of 37%, 39%, and 27% respectively. The thirty-day major complication rate was 47% overall but not statistically significantly different between groups. There were no differences between groups with regard to 30-day readmission, reoperation, and infection rates. Conclusions: Our results represent one of the largest series of hip disarticulation outcomes. Performing TMR at the time of hip disarticulation did not negatively affect outcomes and may be a beneficial adjunct to improve pain. Further research is warranted.

5.
J Am Coll Surg ; 234(5): 883-889, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35426401

ABSTRACT

BACKGROUND: Phantom limb pain (PLP) and residual limb pain (RLP) are debilitating sequelae of major limb amputation. Targeted muscle reinnervation (TMR), when performed at the time of amputation, has been shown to be effective for management of this pain; however, its long-term effects and the longitudinal trend of patient-reported outcomes is unknown. The purpose of this study was to characterize the longitudinal patient-reported outcomes of pain and quality of life following TMR at the time of initial amputation. STUDY DESIGN: A prospective case series of patients undergoing major limb amputation with TMR performed at the time of amputation were followed from October 2015 to December 2020 with outcomes measured 3, 6, 12, and 18 months or longer after amputation and TMR. Outcomes included patient-reported severity of PLP and RLP as measured by the numeric rating scale (NRS). Secondary outcomes included the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Pain Behavior Questionnaires. RESULTS: Eighty-one patients with 83 treated limbs were included in the study, and 23 patients completed surveys at 18 months or later, with an average follow-up time of 2.4 years. By 3 months after operation, all patient-reported outcomes for PLP and RLP were consistent with previously reported data that demonstrated superiority to non-TMR amputees. Mixed-model linear regression analysis showed that PLP NRS severity scores continued to improve over the study period (p = 0.022). The remaining outcomes for RLP severity and PROMIS quality-of-life measures demonstrated that these scores remained stable over the study period (p > 0.05). CONCLUSION: TMR is an effective surgical procedure that improves the chances of having reduced RLP and PLP when performed at the time of amputation, and our study demonstrates the long-term durability of its efficacy.


Subject(s)
Phantom Limb , Quality of Life , Amputation, Surgical/adverse effects , Humans , Muscle, Skeletal , Patient Reported Outcome Measures , Phantom Limb/etiology
6.
Plast Reconstr Surg Glob Open ; 9(5): e3542, 2021 May.
Article in English | MEDLINE | ID: mdl-34881140

ABSTRACT

Targeted muscle reinnervation (TMR) surgery has been shown to aid in prevention and treatment of neuropathic pain. Technical and anatomical descriptions of TMR surgery for upper extremity amputees (including transradial, transhumeral, and forequarter amputations) have been reported, yet such descriptions of TMR surgery for partial hand amputations are currently lacking. Herein we outline the technique of different types of partial hand amputation TMR surgeries to serve as a reference and guide. A retrospective review was performed by our multi-institutional team to identify clinical cases where partial hand TMR surgeries were performed. Patient demographics, characteristics, amputation subtype, nerve transfer, pain score, pain outcome, and functional outcome data were collected and analyzed. From January 2018 to September 2019, 13 patients underwent partial hand TMR procedures. Eight cases resulted from trauma, and 6 were secondary to oncologic procedures. The amputations consisted of 8 ray, 2 trans-metacarpal, 2 radial-sided hand, and 1 index finger amputation with recurrent painful neuromas. Twelve patients were weaned off narcotics completely and only 3 remained on a neuromodulator for ongoing pain control. Technical considerations for partial hand TMR surgery have been outlined, with early pilot data showing beneficial pain control outcomes.

7.
BMJ Open ; 11(11): e050173, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34782341

ABSTRACT

INTRODUCTION: Nipple-sparing mastectomy (NSM) can be performed for the treatment of breast cancer and risk reduction, but total mammary glandular excision in NSM can be technically challenging. Minimally invasive robot-assisted NSM (RNSM) has the potential to improve the ergonomic challenges of open NSM. Recent studies in RNSM demonstrate the feasibility and safety of the procedure, but this technique is still novel in the USA. METHODS AND ANALYSIS: This is a single-arm prospective pilot study to determine the safety, efficacy and potential risks of RNSM. Up to 12 RNSM will be performed to assess the safety and feasibility of the procedure. Routine follow-up visits and study assessments will occur at 14 days, 30 days, 6 weeks, 6 months and 12 months. The primary outcome is to assess the feasibility of removing the breast gland en bloc using the RNSM technique. To assess safety, postoperative complication information will be collected. Secondary outcomes include defining benefits and challenges of RNSM for both surgeons and patients using surveys, as well as defining the breast and nipple-areolar complex sensation recovery following RNSM. Mainly, descriptive analysis will be used to report the findings. ETHICS AND DISSEMINATION: The RNSM protocol was reviewed and approved by the US Food and Drug Administration using the Investigational Device Exemption mechanism (reference number G200096). In addition, the protocol was registered with ClinicalTrials.gov (NCT04537312) and approved by The Ohio State University Institutional Review Board, reference number 2020C0094 (18 August 2020). The results of this study will be distributed through peer-reviewed journals and presented at surgical conferences. TRIAL REGISTRATION NUMBER: NCT04537312.


Subject(s)
Breast Neoplasms , Mammaplasty , Robotics , Breast Neoplasms/surgery , Clinical Trials as Topic , Feasibility Studies , Female , Humans , Mastectomy , Nipples/surgery , Pilot Projects , Prospective Studies , Retrospective Studies
8.
Front Pediatr ; 9: 722483, 2021.
Article in English | MEDLINE | ID: mdl-34589455

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic led to day care and school closures and children staying home for several months. When they gradually returned, aggressive regulations were implemented in New York State to reduce viral transmission. Method: An ongoing prospective study occurring in the Rochester, NY region, focused on early childhood respiratory infectious diseases, afforded an opportunity to assess the impact of the pandemic on the incidence of these illnesses in a primary care outpatient setting. Physician-diagnosed, medically attended infection visits were assessed in two child cohorts, age 6-36 months old: from March 15 to December 31, 2020 (the pandemic period) compared to the same months in 2019 (prepandemic). Nasopharyngeal colonization by potential otopathogens during healthy/well-child and acute otitis media (AOM) visits was evaluated. Results: One hundred and forty-four children were included in the pandemic cohort and 215 in the prepandemic cohort. The pandemic cohort of children experienced 1.8-fold less frequent infectious disease visits during the pandemic (p < 0.0001). Specifically, visits for AOM were 3.7-fold lower (p < 0.0001), viral upper respiratory infections (URI) 3.8-fold lower (p < 0.0001), croup 27.5-fold lower (p < 0.0001), and bronchiolitis 7.4-fold lower (p = 0.04) than the prepandemic cohort. Streptococcus pneumoniae (p = 0.03), Haemophilus influenzae (p < 0.0001), and Moraxella catarrhalis (p < 0.0001) nasopharyngeal colonization occurred less frequently among children during the pandemic. Conclusion: In primary care pediatric practice, during the first 9 months of the COVID-19 pandemic, significant decreases in the frequency of multiple respiratory infections and nasopharyngeal colonization by potential bacterial respiratory pathogens occurred in children age 6-36 months old.

9.
Neurol Res Pract ; 3(1): 41, 2021 Aug 09.
Article in English | MEDLINE | ID: mdl-34365971

ABSTRACT

BACKGROUND: To prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists. METHODS: We assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy. At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis. Participants were randomly assigned to MRI sets. Effects of examiners' specialty, duration of training and professional experience on detection rate of epileptogenic lesions were investigated. RESULTS: Fourty-eight neurologists, 22 epileptologists, 20 radiologists and 21 neuroradiologists read 1323 MRI scans. Overall, 613 of 1101 (55.7%) epileptogenic lesions were detected. Long-term epilepsy associated tumors (182/221, 82.4%) were found more frequently than gliotic scar, hemosiderin or cavernoma (157/220, 71.4%), hippocampal sclerosis or limbic encephalitis (141/220, 64.1%), nodular heterotopia (68/220, 30.9%) and focal cortical dysplasias (65/220, 29.5%, p < 0.001). Provision of a focus hypothesis improved the detection of hippocampal sclerosis or limbic encephalitis (86/110, 78.2% vs 55/110, 50%, p < 0.001) and focal cortical dysplasias (40/110, 36.4% vs 25/110, 22.7%, p = 0.037). Neuroradiologists and epileptologists were more likely than radiologists and neurologists to be amongst the most successful readers. In multivariable analysis, type of epileptogenic lesion, specialty of MRI reader, and provision of focus hypothesis predicted correct identification of epileptogenic lesions. CONCLUSIONS: Epileptogenic lesions are often not recognized on MRI even by expert readers. Their detection can be improved by providing a focus hypothesis. These results stress the need for training in the MRI characteristics of epilepsy - specific pathology, and, most importantly, interdisciplinary communication between neurologists/epileptologists and (neuro)radiologists to improve detection of epileptogenic lesions.

10.
PLoS Comput Biol ; 17(3): e1008751, 2021 03.
Article in English | MEDLINE | ID: mdl-33765014

ABSTRACT

The sequences of antibodies from a given repertoire are highly diverse at few sites located on the surface of a genome-encoded larger scaffold. The scaffold is often considered to play a lesser role than highly diverse, non-genome-encoded sites in controlling binding affinity and specificity. To gauge the impact of the scaffold, we carried out quantitative phage display experiments where we compare the response to selection for binding to four different targets of three different antibody libraries based on distinct scaffolds but harboring the same diversity at randomized sites. We first show that the response to selection of an antibody library may be captured by two measurable parameters. Second, we provide evidence that one of these parameters is determined by the degree of affinity maturation of the scaffold, affinity maturation being the process by which antibodies accumulate somatic mutations to evolve towards higher affinities during the natural immune response. In all cases, we find that libraries of antibodies built around maturated scaffolds have a lower response to selection to other arbitrary targets than libraries built around germline-based scaffolds. We thus propose that germline-encoded scaffolds have a higher selective potential than maturated ones as a consequence of a selection for this potential over the long-term evolution of germline antibody genes. Our results are a first step towards quantifying the evolutionary potential of biomolecules.


Subject(s)
Antibodies/genetics , Gene Library , Computational Biology , DNA/genetics , Evolution, Molecular , Humans
11.
Expert Rev Med Devices ; 18(4): 367-374, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33686906

ABSTRACT

INTRODUCTION: Lymphedema has traditionally been managed through noninvasive means with complete decongestive therapy. However, complete decongestive therapy is an intensive program that requires lifelong adherence by patients with lymphedema. More recently, reconstructive surgical procedures have shown promise in improving lymphedema by physiologically restoring lymphatic function. One of these types of procedures, lymphaticovenular anastomosis, relies on technological advances in imaging, particularly indocyanine green lymphangiography. AREAS COVERED: This article reviews indocyanine green and near-infrared fluorescence imaging. In addition, this article discusses the application of this imaging to the preoperative, intraoperative, and postoperative assessment of the lymphatic system in the setting of lymphaticovenular anastomosis surgery. EXPERT OPINION: Indocyanine green lymphangiography offers significant advantages over other types of imaging of the lymphatic system. In the future, it is hopeful that additional options for these imaging devices will become available which may increase their accessibility by centers interested in performing reconstructive lymphatic surgery, including in relation to cost. Finally, more studies with higher levels of evidence are needed to better define the long-term outcomes associated with lymphatic surgery including LVA. In this regard, practitioners should fully harness the information conferred by ICG lymphangiography as both a clinical and research tool.


Subject(s)
Indocyanine Green/chemistry , Lymphatic Vessels/surgery , Optical Imaging , Plastic Surgery Procedures , Spectroscopy, Near-Infrared , Anastomosis, Surgical , Humans , Lymphatic Vessels/diagnostic imaging , Lymphography
12.
Expert Rev Med Devices ; 18(2): 151-160, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33496626

ABSTRACT

Introduction: Negative pressure wound therapy (NPWT) has become a mainstay in the armamentarium for wound care. Since the initial commercial vacuum-assisted closure device became available in 1995, subsequent research has confirmed the positive physiological effects of negative pressure on wound healing. Traditionally, NPWT has been used to improve healing of open nonsurgical wounds by secondary intention. However, the clinical applications of NPWT have significantly broadened, and now also include use in open surgical wounds, closed surgical incisions, and skin graft surgery. In addition, devices have evolved and now include functionality and features such as instillation, antimicrobial sponges, and portability.Areas covered: This article reviews the history, background, and physiology underlying NPWT, as well as the most commonly used devices. In addition, an evidence-based discussion of the current clinical applications of NPWT is presented, with a focus on those with high levels of evidence.Expert opinion: Future directions for device development include modifications to increase ease of use by patients and to allow its use in a broader array of anatomic areas. Lastly, more research with high levels of evidence is needed to better define the outcomes associated with NPWT, including in relation to specific clinical applications and cost.


Subject(s)
Negative-Pressure Wound Therapy/instrumentation , Clinical Trials as Topic , Cost-Benefit Analysis , Equipment Design/economics , Humans , Negative-Pressure Wound Therapy/economics , Skin Transplantation , Wound Healing/physiology
13.
Breast ; 55: 25-29, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33310481

ABSTRACT

INTRODUCTION: While the long-term oncologic safety of robot-assisted nipple sparing mastectomy (RNSM) remains to be elucidated, histologically detected residual breast tissue (RBT) can be a surrogate for oncologically sound mastectomy. The objective of this study is to determine the presence of RBT after RNSM. METHODS: Between August 2019-January 2020, we completed 5 cadaveric RNSMs. Full thickness biopsies from the mastectomy skin flap were obtained from predefined locations radially around the mastectomy skin envelop and nipple areolar complex to histologically evaluate for RBT. RESULTS: The first case was not technically feasible due to inability to obtain adequate insufflation. Five mastectomy flaps were analyzable. The average mastectomy flap thickness was 2.3 mm (range 2-3 mm) and the average specimen weight was 382.72 g (range 146.9-558.3 g). Of 70 total biopsies, RBT was detected in 11 (15.7%) biopsies. Most common location for RBT was in the nipple-areolar complex, with no RBT detected from the peripheral skin flaps. CONCLUSIONS: In this cadaveric study, RNSM is feasible leaving minimal RBT on the mastectomy flap. The most common location for RBT is in the periareolar location consistent with previous published findings after open NSM. Clinical studies are underway to evaluate the safety of RNSM.


Subject(s)
Breast Neoplasms , Mammaplasty , Mastectomy, Subcutaneous , Robotics , Breast Neoplasms/surgery , Female , Humans , Mastectomy , Nipples/surgery , Organ Sparing Treatments , Retrospective Studies
14.
Cureus ; 12(9): e10393, 2020 Sep 11.
Article in English | MEDLINE | ID: mdl-33062513

ABSTRACT

We report our experience with next-generation incisional negative pressure wound therapy (iNPWT) applied after major limb amputation or amputation revision. In this high-risk patient population, the need for reliable post-operative soft tissue management is imperative. In both cases reported, healing was uncomplicated. Using the next generation iNPWT in this unique way optimizes the post-operative residual limb by improved incision healing, residual limb edema reduction, and reduced risk of surgical site infection (SSI). This is the first case report of its kind reporting a novel use of next-generation iNPWT, and it demonstrates a need to examine this particular use further.

15.
J Neurosurg Spine ; 34(2): 277-282, 2020 Oct 23.
Article in English | MEDLINE | ID: mdl-33096531

ABSTRACT

OBJECTIVE: The consequences of failed spinal hardware secondary to wound complications can increase the burden on the patient while also significantly escalating the cost of care. The objective of this study was to demonstrate the effectiveness of a protocol-based multidisciplinary approach in optimizing wound outcome in complex oncological spine care patients. METHODS: A retrospective consecutive case series was performed from 2015 to 2019 of all patients who underwent oncological spine surgery. A protocol was established to identify oncological patients at high risk for potential wound complications. Preoperative and postoperative treatment plans were developed by the multidisciplinary tumor board team members. Wound healing risk factors such as diabetes, obesity, prior spine surgery, pre- or postoperative chemotherapy or radiation exposure, perioperative steroid use, and poor nutritional status were recorded. Operative details, including the regions of spinal involvement, presence of instrumentation, and number of vertebral levels operated on, were reviewed. Primary outcomes were the length of hospitalization and major (requiring reoperation) and minor wound complications in the setting of the aforementioned identified risk factors. RESULTS: A total of 102 oncological cases were recorded during the 5-year study period. Of these patients, 99 had local muscle flap reconstruction with layered closure over their surgical hardware. The prevalence of smoking, diabetes, and previous spine surgery for the cohort was 21.6%, 20.6%, and 27.5%, respectively. Radiation exposure was seen in 72.5% of patients (37.3% preoperative vs 48% postoperative exposure). Chemotherapy was given to 66.7% of the patients (49% preoperatively and 30.4% postoperatively). The rate of perioperative steroid exposure was 60.8%. Prealbumin and albumin levels were 15.00 ± 7.47 mg/dL and 3.23 ± 0.43 mg/dL, respectively. Overall, an albumin level of < 3.5 mg/dL and BMI < 18.5 were seen in 64.7% and 13.7% of the patients, respectively. The mean number of vertebral levels involved was 6.76 ± 2.37 levels. Instrumentation of 7 levels or more was seen in 52.9% of patients. The average spinal wound defect size was 22.06 ± 7.79 cm. The rate of minor wound complications, including superficial skin breakdown (epidermolysis) and nonoperative seromas, was 6.9%, whereas that for major complications requiring reoperation within 90 days of surgery was 2.9%. CONCLUSIONS: A multidisciplinary team approach utilized in complex multilevel oncological spine reconstruction surgery optimizes surgical outcomes, reduces morbidities, and improves care and satisfaction in patients with known risk factors.

16.
SAGE Open Med ; 8: 2050312120959180, 2020.
Article in English | MEDLINE | ID: mdl-32974021

ABSTRACT

The life altering nature of major limb amputations may be further complicated by neuroma formation in up to 60% of the estimated 2 million major limb amputees in the United States. This can be a source of pain and functional limitation of the residual limb. Pain associated with neuromas may limit prosthetic limb use, require reoperation, lead to opioid dependence, and dramatically reduce quality of life. A number of management options have been described including excision alone, excision with repair, excision with transposition, and targeted muscle reinnervation. Targeted muscle reinnervation has been shown to reduce phantom limb and neuroma pain for patients with upper and lower extremity amputations. It may be performed at the time of initial amputation to prevent pain development or secondarily for the treatment of established pain. Encouraging outcomes have been reported, and targeted muscle reinnervation is emerging as a leading surgical technique for pain prevention in patients undergoing major limb amputations and pain management in patients with pre-existing amputations.

17.
J Biol Chem ; 295(45): 15342-15365, 2020 11 06.
Article in English | MEDLINE | ID: mdl-32868295

ABSTRACT

The contraction and relaxation of the heart is controlled by stimulation of the ß1-adrenoreceptor (AR) signaling cascade, which leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation. Phosphorylation is counteracted by the main cardiac protein phosphatases, PP2A and PP1. Both kinase and phosphatases are sensitive to intramolecular disulfide formation in their catalytic subunits that inhibits their activity. Additionally, intermolecular disulfide formation between PKA type I regulatory subunits (PKA-RI) has been described to enhance PKA's affinity for protein kinase A anchoring proteins, which alters its subcellular distribution. Nitroxyl donors have been shown to affect contractility and relaxation, but the mechanistic basis for this effect is unclear. The present study investigates the impact of several nitroxyl donors and the thiol-oxidizing agent diamide on cardiac myocyte protein phosphorylation and oxidation. Although all tested compounds equally induced intermolecular disulfide formation in PKA-RI, only 1-nitrosocyclohexalycetate (NCA) and diamide induced reproducible protein phosphorylation. Phosphorylation occurred independently of ß1-AR activation, but was abolished after pharmacological PKA inhibition and thus potentially attributable to increased PKA activity. NCA treatment of cardiac myocytes induced translocation of PKA and phosphatases to the myofilament compartment as shown by fractionation, immunofluorescence, and proximity ligation assays. Assessment of kinase and phosphatase activity within the myofilament fraction of cardiac myocytes after exposure to NCA revealed activation of PKA and inhibition of phosphatase activity thus explaining the increase in phosphorylation. The data suggest that the NCA-mediated effect on cardiac myocyte protein phosphorylation orchestrates alterations in the kinase/phosphatase balance.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Myocytes, Cardiac/drug effects , Oxidants/pharmacology , Phosphoprotein Phosphatases/antagonists & inhibitors , Receptors, Adrenergic, beta-1/metabolism , Signal Transduction , Acetates/pharmacology , Animals , Cattle , Cyclic AMP-Dependent Protein Kinases/metabolism , Diamide/pharmacology , Humans , Male , Mice , Myocytes, Cardiac/metabolism , Nitroso Compounds/pharmacology , Oxidation-Reduction , Phosphoprotein Phosphatases/metabolism , Phosphorylation/drug effects , Rabbits , Rats , Rats, Wistar , Signal Transduction/drug effects
18.
Plast Reconstr Surg Glob Open ; 8(3): e2689, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32537346

ABSTRACT

Symptomatic neuromas and pain caused by nerve transection injuries can adversely impact a patient's recovery, while also contributing to increased dependence on opioid and other pharmacotherapy. These sources of pain are magnified following amputation surgeries, inhibiting optimal prosthetic wear and function. Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) represent modern advances in addressing amputated peripheral nerves. These techniques offer solutions by essentially providing neuromuscular targets for transected peripheral nerves "to grow into and reinnervate." Recent described benefits of these techniques include reports on pain reduction or ablation (eg, phantom limb pain, residual limb pain, and/or neuroma pain).1-6 We describe a technical adaptation combining TMR with a "pedicled vascularized RPNI (vRPNI)." The TMR with the vRPNI surgical technique described offers the advantage of having a distal target nerve and a target muscle possessing deinnervated motor end plates which may potentially enhance nerve regeneration and muscle reinnervation, while also decreasing amputated nerve-related pain.

19.
Int Wound J ; 17(2): 387-393, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31858713

ABSTRACT

Wound infection involving hardware can be notoriously difficult to treat, often requiring the removal of the infected implant. The goal of this study was to determine the utility of instillation negative pressure wound therapy to help eradicate infection and allow for definitive wound closure in patients without removing the infected hardware. A retrospective review was performed on the outcomes of 28 patients who presented with open wounds with exposed or infected hardware and who were treated with a combination of surgical debridement and negative pressure wound therapy with instillation (NPWTi). Eleven patients were treated for infected spinal hardware, 12 for extremity, and 5 for sternal hardware. Twenty-five of 28 (89%) patients had successful retention or replacement of hardware, with clearance of infection and healed wounds. Original hardware was maintained in 17 of 28 (61%) patients. In 11 patients, original hardware was removed, with subsequent replacement in eight of those patients after a clean wound was achieved. Average time to definitive closure was 12.6 days. Average follow-up was 135 days. This series supports NPWTi as an effective adjunct therapy to help expeditiously eradicate hardware infection, allowing for hardware retention.


Subject(s)
Debridement/instrumentation , Negative-Pressure Wound Therapy/instrumentation , Surgical Wound Infection/therapy , Therapeutic Irrigation/methods , Wound Healing , Adult , Aged , Equipment Design , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
20.
Adv Wound Care (New Rochelle) ; 8(8): 368-373, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31346491

ABSTRACT

Objective: To evaluate our institutional experience of incisional negative pressure wound therapy (iNPWT) applied immediately after major limb amputation closure or amputation revision closure. Approach: A retrospective review was performed on 25 patients who underwent major limb amputation or amputation revision and had iNPWT placed intraoperatively upon incision closure. Results: Twenty-one patients underwent lower extremity amputation and four underwent upper extremity amputation. Seventeen were primary amputations and eight were amputation revisions. No patients developed dehiscence, seroma, or hematoma. One patient developed a surgical site infection (4%) that was treated with oral antibiotics. The average time to eligibility for prosthetic fitting for lower extremity amputations was 6.3 weeks. Innovation: Amputee patients have increased wound healing demands that can impact prosthetic wear and ambulation status. Stump incisions are located at the distal end of their extremities and often are in areas that have had prior surgical procedures performed. Thus, blood supply to the incision site may not be optimal. iNPWT is an effective incision management technique to promote healing and decrease postoperative complications in this patient population, which can lead to increased mortality. Conclusion: iNPWT is an effective technique of minimizing wound complications in the amputee and should be considered in this high-risk patient population.

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