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1.
Article in English | MEDLINE | ID: mdl-38968607

ABSTRACT

Fractures of the femoral head typically occur after high-energy trauma. Radiographs and cross-sectional imaging are used to appropriately classify and identify associated injuries or morphologic characteristics that may influence management. Identification of the radiographic and clinical hallmarks of an irreducible variant is critical to optimizing the patient's outcome. Nonsurgical treatment can be used in the setting of small, infrafoveal femoral head fractures without hip instability. When surgical treatment is indicated, an anterior (Smith-Petersen), posterior (Kocher-Langenbeck), or surgical hip dislocation approach may be used depending on injury details and surgeon preference. The purpose of this review was to summarize current evidence on femoral head fractures regarding indications, variant patterns, surgical approaches, and outcomes.

4.
J Orthop Trauma ; 37(9): 444-449, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37074805

ABSTRACT

OBJECTIVES: To examine the relationship between anticoagulant and antiplatelet drugs and surgical blood loss for geriatric patients undergoing cephalomedullary nail fixation of extracapsular proximal femur fractures. DESIGN: Multicenter, retrospective, cohort study using bivariate and multivariable regression analyses. SETTING: Two Level-1 trauma centers. PATIENTS: One thousand four hundred forty-two geriatric (ages 60-105 years) patients undergoing isolated primary intramedullary fixation of nonpathologic extracapsular hip fractures from 2009 to 2018 including 657 taking an antiplatelet drug alone (including aspirin), 99 taking warfarin alone, 37 taking a direct oral anticoagulant (DOAC) alone, 59 taking an antiplatelet drug and an anticoagulant, and 590 taking neither. INTERVENTION: Cephalomedullary nail fixation. MAIN OUTCOME MEASUREMENTS: Blood transfusion and calculated blood loss. RESULTS: More patients taking antiplatelet drugs required a transfusion than controls (43% vs. 33%, P < 0.001), whereas patients taking warfarin or DOACs did not (35% or 32% vs. 33%). Median calculated blood loss was increased in patients taking antiplatelet drugs (1275 mL vs. 1059 mL, P < 0.001) but not in patients taking warfarin or DOACs (913 mL or 859 mL vs. 1059 mL). Antiplatelet drugs were independently associated with an odds ratio of transfusion of 1.45 [95% confidence interval (CI), 1.1-1.9] in contrast with 0.76 (95% CI, 0.5-1.2) for warfarin and 0.67 (95% CI, 0.3-1.4) for DOACs. CONCLUSIONS: Geriatric patients taking warfarin (incompletely reversed) or DOACs lose less blood during cephalomedullary nail fixation of hip fractures than those taking aspirin. Delaying surgery to mitigate anticoagulant-related surgical blood loss may be unwarranted. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Anticoagulants , Hip Fractures , Humans , Aged , Anticoagulants/therapeutic use , Warfarin/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Cohort Studies , Blood Loss, Surgical , Hip Fractures/surgery , Hip Fractures/drug therapy , Aspirin
5.
Eur J Orthop Surg Traumatol ; 33(7): 2903-2909, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36906665

ABSTRACT

PURPOSE: Existing literature is discrepant on the differences in blood loss and need for transfusion between short and long cephalomedullary nails used for extracapsular geriatric hip fractures. However, prior studies used the inaccurate estimated rather than the more accurate 'calculated' blood loss based on hematocrit dilution (Gibon in IO 37:735-739, 2013, Mercuriali in CMRO 13:465-478, 1996). This study sought to clarify whether use of short nails is associated with clinically meaningful reductions in calculated blood loss and resultant need for transfusion. METHODS: A retrospective cohort study using bivariate and propensity score-weighted linear regression analyses was conducted examining 1442 geriatric (ages 60-105) patients undergoing cephalomedullary fixation of extracapsular hip fractures over 10 years at two trauma centers. Implant dimensions, pre and postoperative laboratory values, preoperative medications, and comorbidities were recorded. Two groups were compared based on nail length (greater or less than 235 mm). RESULTS: Short nails were associated with a 26% reduction in calculated blood loss (95% confidence interval: 17-35%; p < 10-14) and a 24-min (36%) reduction in mean operative time (95% confidence interval: 21-26 min; p < 10-71). The absolute reduction in transfusion risk was 21% (95% confidence interval: 16-26%; p < 10-13) yielding a number needed to treat of 4.8 (95% confidence interval: 3.9-6.4) with short nails to prevent one transfusion. No difference in reoperation, periprosthetic fracture, or mortality was noted between groups. CONCLUSION: Use of short compared to long cephalomedullary nails for geriatric extracapsular hip fractures confers reduced blood loss, need for transfusion, and operative time without a difference in complications.


Subject(s)
Fracture Fixation, Intramedullary , Hip Fractures , Humans , Aged , Bone Nails , Retrospective Studies , Fracture Fixation, Intramedullary/adverse effects , Fracture Fixation, Intramedullary/methods , Hip Fractures/surgery , Bone Screws , Hemorrhage
6.
J Am Acad Orthop Surg ; 31(2): 81-86, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36580049

ABSTRACT

OBJECTIVE: Multiple comorbidities in hip fracture patients are associated with increased mortality and complications. The goal of this study was to characterize the relationship between specific patient factors including comorbidities and outcomes in geriatric hip fractures, including length of stay, unplanned ICU admission, discharge disposition, complications, and mortality. METHODS: This is a retrospective review of a trauma database from five Level 1 and Level 2 trauma centers of patients with hip fractures of the femoral neck and intertrochanteric region who underwent treatment using hip pinning, hemiarthroplasty, total hip arthroplasty, cephalomedullary nailing, or dynamic hip screw fixation. Mortality was the primary outcome variable (including in-hospital mortality, 30-day mortality, 60-day mortality, and 90-day mortality). Secondary outcome variables included in-hospital adverse events, unplanned transfer to the ICU, postoperative length of stay, and discharge disposition. Regression analyses were used for evaluation of relationships between comorbidities as independent variables and primary and secondary outcomes as dependent variables. RESULTS: Two thousand three hundred patients were included. The mortality was 1.8%, 7.0%, 10.9%, and 14.1% for in-hospital, 30-day, 60-day, and 90-day mortality, respectively. Diabetes and cognitive impairment present on admission were associated with mortality at all-time intervals. COPD was the only comorbidity that signaled in-hospital adverse event with an odds ratio of 1.67 (P = 0.012). No patient factors, time to surgery, or comorbidities signaled unplanned ICU transfer. Patients with renal failure and COPD had longer hospital stays after surgery. CONCLUSION: Geriatric hip fractures continue to have high short-term morbidity and mortality. Identifying patients with increased odds of early mortality and adverse events can help teams optimize care and outcomes. Patients with diabetes, cognitive impairment, renal failure, and COPD may benefit from continued and improved medical optimization during the perioperative period as well as being more closely managed by a medicine team without delaying time to the operating room.


Subject(s)
Fracture Fixation, Intramedullary , Hip Fractures , Pulmonary Disease, Chronic Obstructive , Renal Insufficiency , Humans , Aged , Fracture Fixation, Intramedullary/adverse effects , Comorbidity , Retrospective Studies , Renal Insufficiency/epidemiology , Renal Insufficiency/etiology , Pulmonary Disease, Chronic Obstructive/etiology
7.
Instr Course Lect ; 72: 343-356, 2023.
Article in English | MEDLINE | ID: mdl-36534866

ABSTRACT

The diagnosis and management of compartment syndrome remains challenging and controversial. There continues to be a significant burden of disease and substantial resource implications associated with fractures complicated by compartment syndrome. Achieving consensus opinions regarding the diagnosis and treatment of this problem has important implications given the profound effect on patient outcomes.


Subject(s)
Compartment Syndromes , Fractures, Bone , Humans , Compartment Syndromes/diagnosis , Compartment Syndromes/etiology , Fractures, Bone/complications , Consensus
8.
J Bone Joint Surg Am ; 103(9): 821-828, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33617164

ABSTRACT

BACKGROUND: The anterior approach to the cervical spine is commonly used to treat cervical pathology. It is, however, associated with high rates of dysphagia, which may be associated with substantial patient morbidity. Perioperative corticosteroid administration has been advocated to decrease dysphagia rates; its efficacy, however, remains uncertain. We conducted a meta-analysis of randomized trials to determine the efficacy of perioperative corticosteroid administration in reducing postoperative dysphagia as well as any adverse effects, such as pseudarthrosis and infection. METHODS: We conducted a systematic search of electronic databases (MEDLINE, Embase, CENTRAL [Cochrane Central Register of Controlled Trials], ClinicalTrials.gov) to identify randomized controlled trials (RCTs) that evaluated corticosteroids versus any comparator for prevention of postoperative dysphagia after anterior cervical spine procedures. Two independent reviewers used the GRADE (Grades of Recommendation Assessment, Development and Evaluation) criteria to assess eligibility and risk of bias, perform data extraction, and rate the quality of evidence. The primary outcome was severity of postoperative dysphagia. We conducted meta-analyses of dysphagia (both overall and by delivery method), pseudarthrosis, and postoperative infection. RESULTS: After screening of 927 articles, a total of 7 studies were eligible for final inclusion. These included 431 patients, of whom 247 received corticosteroids and 184 received placebo or a control treatment. Moderate-quality evidence demonstrated a significant improvement in postoperative dysphagia rates (odds ratio, 0.35; 95% confidence interval, 0.20 to 0.63; p < 0.001), and this finding was robust to both permutation analyses and sensitivity analyses removing the studies with a high risk of bias. There was no significant difference between intravenous and local steroid administration (p = 0.16). There were no documented infections. There was no significantly increased risk of pseudarthrosis in those receiving steroids compared with placebo or a control treatment (p = 0.13). CONCLUSIONS: This meta-analysis found moderate-quality evidence supporting the use of perioperative corticosteroid administration as an adjunct to anterior cervical spinal procedures. Patients treated with corticosteroids intravenously or locally had significantly decreased severity of dysphagia. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Deglutition Disorders/prevention & control , Postoperative Complications/prevention & control , Severity of Illness Index , Spinal Fusion/adverse effects , Adrenal Cortex Hormones/administration & dosage , Confidence Intervals , Deglutition Disorders/epidemiology , Humans , Incidence , Injections, Intravenous , Odds Ratio , Perioperative Care , Pseudarthrosis/prevention & control , Publication Bias , Randomized Controlled Trials as Topic , Spinal Fusion/methods , Surgical Wound Infection/prevention & control
9.
J Orthop Trauma ; 34 Suppl 2: S37-S38, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32639352

ABSTRACT

Extraarticular fractures of the distal tibia have historically been treated with open reduction and fixation with plates and screws. This technique requires a more extensive dissection and comes with a higher risk of wound complications than intramedullary nail fixation. This article and the accompanying video demonstrate the use of closed reduction and suprapatellar nail fixation appropriate for the treatment of most extraarticular distal tibial fractures. A variety of treatment decisions are discussed, including the nail insertion method, fixation of associated fibular fractures, and postoperative immobilization.


Subject(s)
Ankle Fractures , Fracture Fixation, Intramedullary , Tibial Fractures , Ankle Fractures/diagnostic imaging , Ankle Fractures/surgery , Bone Nails , Bone Plates , Humans , Tibia , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery
10.
Clin Spine Surg ; 33(10): 400-407, 2020 12.
Article in English | MEDLINE | ID: mdl-32554986

ABSTRACT

STUDY DESIGN: Systematic review. OBJECTIVE: To review the current clinical use of 3-dimensional printed (3DP) patient-specific implants in the spine. SUMMARY OF BACKGROUND DATA: Additive manufacturing is a transformative manufacturing method now being applied to spinal implants. Recent innovations in technology have allowed the production of medical-grade implants with unprecedented structure and customization, and the complex anatomy of the spine is ideally suited for patient-specific devices. Improvement in implant design through the process of 3DP may lead to improved osseointegration, lower subsidence rates, and faster operative times. METHODS: A comprehensive search of the literature was conducted using Ovid MEDLINE, EMBASE, Scopus, and other sources that resulted in 1842 unique articles. All manuscripts describing the use of 3DP spinal implants in humans were included. Two independent reviewers (N.W. and N.E.S.) assessed eligibility for inclusion. The following outcomes were collected: pain score, Japanese Orthopedic Association (JOA) score, subsidence, fusion, Cobb angle, vertebral height, and complications. No conflicts of interest existed. No funding was received for this work. RESULTS: A total of 17 studies met inclusion criteria with a total of 35 patients. Only case series and case reports were identified. Follow-up times ranged from 3 to 36 months. Implant types included vertebral body replacement cages, interbody cages, sacral reconstruction prostheses, iliolumbar rods, and a posterior cervical plate. All studies reported improvement in both clinical and radiographic outcomes. 11 of 35 cases showed subsidence >3 mm, but only 1 case required a revision procedure. No migration, loosening, or pseudarthrosis occurred in any patient on the basis of computed tomography or flexion-extension radiographs. CONCLUSIONS: Results of the systematic review indicate that 3DP technology is a viable means to fabricate patient-matched spinal implants. The effects on clinical and radiographic outcome measures are still in question, but these devices may produce favorable subsidence and pseudoarthrosis rates. Currently, the technology is ideally suited for complex tumor pathology and atypical bone defects. Future randomized controlled trials and cost analyses are still needed. LEVEL OF EVIDENCE: IV-systematic review.


Subject(s)
Prostheses and Implants , Spinal Fusion , Cervical Vertebrae , Humans , Osseointegration , Printing, Three-Dimensional , Radiography
11.
J Spine Surg ; 6(1): 136-144, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32309652

ABSTRACT

Stereotactic navigation is quickly establishing itself as the gold standard for accurate placement of spinal instrumentation and providing real-time anatomic referencing. There have been substantial improvements in computer-aided navigation over the last decade producing improved accuracy with intraoperative scanning while shortening registration time. The newest iterations of modeling software create robust maps of the anatomy while tracking software localizes instruments in multiple display modes. As a result, stereotactic navigation has become an effective adjunct to spine surgery, particularly improving instrumentation accuracy in the setting of atypical anatomy. This article provides an overview of stereotactic navigation applied to complex cervical spine surgery, details the means for registration and direct referencing, and shares our preferred methods to implement this promising technology.

12.
J Arthroplasty ; 35(4): 960-965.e1, 2020 04.
Article in English | MEDLINE | ID: mdl-31924487

ABSTRACT

BACKGROUND: This cohort study was designed to determine the discrepancy between the quantity of opioid prescribed vs that which was consumed after total knee arthroplasty (TKA) and total hip arthroplasty (THA) in opioid-naive patients. METHODS: Seven hundred twenty-three opioid-naive patients (426 TKAs and 297 THAs) from 7 hospitals in Michigan were contacted within 3 months of their surgery. Opioid prescribing and self-reported consumption was calculated in oral morphine equivalents (OMEs). Secondary outcomes included opioid refill in the first 90 days, pain in the first 7 days post-operatively, and satisfaction with pain care. RESULTS: For TKA, the mean prescribing was 632 mg OME (±229), and the mean consumption was 416 mg (±279). For THA, the mean prescribing was 584 mg OME (±335), and the mean consumption was 285 mg (±301). There were no associations between the amount of opioid prescribed and the likelihood of refill, post-operative pain, or satisfaction with pain control. The amount of opioid prescribed was associated with increased consumption, such that each increase of 1 pill was associated with approximately an additional half pill consumed after adjusting for other covariates. Moreover, 48.2% felt that they received "More" or "Much more" opioid than they needed. CONCLUSION: We recommend no more than 50 tablets of 5 mg oxycodone or its equivalent after TKA and 30 tablets after THA. Although dose reductions in other surgeries have not resulted in harm, continued assessment is needed to ensure that there are no unintended effects of opioid reduction, including worsened pain, decreased satisfaction, emergency department visits, or hospital readmissions. LEVEL OF EVIDENCE: Level III; Retrospective, cohort study.


Subject(s)
Analgesics, Opioid , Arthroplasty, Replacement, Knee , Arthroplasty, Replacement, Knee/adverse effects , Cohort Studies , Humans , Michigan/epidemiology , Pain, Postoperative/drug therapy , Pain, Postoperative/epidemiology , Practice Patterns, Physicians' , Retrospective Studies
13.
Plast Reconstr Surg ; 141(1): 33-39, 2018 01.
Article in English | MEDLINE | ID: mdl-28915211

ABSTRACT

The deep inferior epigastric perforator (DIEP) flap is a workhorse of breast reconstruction. Risks of herniation derive from violation of the rectus abdominis muscle anterior rectus sheath and might be reduced by minimally invasive laparoscopic dissection ("MILD") of the deep inferior epigastric vessels. The authors performed a feasibility study on five anatomical subjects and performed a secondary right breast reconstruction on a 67-year-old woman. A 30-degree laparoscope was used with laparoscopy ports inset to preserve the flap. Blunt preperitoneal dissection followed by carbon dioxide insufflation allowed the deep inferior epigastric pedicle to be dissected and clip-sectioned. The anterior rectus sheath was opened around the perforating vessels, and the flap was anastomosed on the internal mammary vessels. The length of incision in the anterior rectus sheath was compared between laparoscopic and conventional approaches. The mean incision length in the anterior rectus sheath was 3 cm versus 12 cm in the classic approach. Average duration of laparoscopic flap harvest was 50 minutes, including a mean of 30 minutes for deep inferior epigastric dissection. Adhesions led to a 1-cm peritoneal laceration in our first anatomical subject. There were no preoperative or postoperative complications in the clinical case. The clinical procedure duration was 8 hours 15 minutes, with the anterior rectus sheath incision reduced from the conventional 12 cm to 5 cm. Flap ischemia lasted 50 minutes. The patient was discharged on postoperative day 5. This anatomical study and first successful laparoscope-assisted DIEP flap harvest prove that reduced trauma to the anterior rectus sheath is feasible and promising.


Subject(s)
Dissection/methods , Epigastric Arteries/surgery , Laparoscopy/methods , Mammaplasty/methods , Perforator Flap/surgery , Aged , Feasibility Studies , Female , Humans
14.
J Clin Invest ; 127(4): 1165-1171, 2017 Apr 03.
Article in English | MEDLINE | ID: mdl-28165341

ABSTRACT

Parasitic worms infect billions of people worldwide. Current treatments rely on a small group of drugs that have been used for decades. A shortcoming of these drugs is their inability to target the intractable infectious stage of the parasite. As well-known therapeutic targets in mammals, nuclear receptors have begun to be studied in parasitic worms, where they are widely distributed and play key roles in governing metabolic and developmental transcriptional networks. One such nuclear receptor is DAF-12, which is required for normal nematode development, including the all-important infectious stage. Here we review the emerging literature that implicates DAF-12 and potentially other nuclear receptors as novel anthelmintic targets.


Subject(s)
Antinematodal Agents/therapeutic use , Drug Delivery Systems/methods , Helminth Proteins , Nematoda , Receptors, Cytoplasmic and Nuclear , Animals , Helminth Proteins/agonists , Helminth Proteins/antagonists & inhibitors , Helminth Proteins/genetics , Helminth Proteins/metabolism , Humans , Nematoda/genetics , Nematoda/metabolism , Nematode Infections/drug therapy , Nematode Infections/genetics , Nematode Infections/metabolism , Receptors, Cytoplasmic and Nuclear/agonists , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism
16.
Lancet ; 388(10052): 1398-1407, 2016 Oct 01.
Article in English | MEDLINE | ID: mdl-27567680

ABSTRACT

BACKGROUND: More than 30 face transplantations have been done worldwide since 2005 but no documented long-term follow-up has been reported in the literature. We aimed to answer remaining question about the long-term risks and benefits of face transplant. METHODS: In this single-centre, prospective, open study, we assessed 20 patients presenting with facial defects. Ten patients were selected, and, after three were secondarily excluded, seven were transplanted: two with neurofibromatosis 1, one with a burn, and four with self-inflicted facial gunshot injuries. We report the long-term outcomes of six face allotransplant recipients at an average of 6 years (range 3·4-9 years) after the transplantation. All admissions to hospital except for planned revisions and immunosuppressive follow-up therapy were reported as adverse events (safety endpoint). Predefined immunological, metabolic, surgical, and social integration endpoints were collected prospectively. Patients underwent quantitative health-related quality of life assessments through Short Form 36 health questionnaires. This study was registered with ClinicalTrials.gov, number NCT00527280. FINDINGS: Two of seven patients died: one at 65 days due to transplant destruction with concomitant pseudomonas infection and the second at 3·4 years after transplantation by suicide. The six patients alive at long-term follow-up presented with functional transplants. Safety endpoints were related to infection in the first month, acute rejection from 1 day to 7 years after transplantation, or side-effects of immunosuppressive therapy. Recurrent rejection episodes justified maintenance therapy with high-dose steroids at high levels in all patients at last follow-up, yet none of the patients developed diabetes. Three patients were found to have hypertension with one requiring therapy. All patients had a noticeable reduction in glomerular filtration rate. All recipients and their families accepted their transplant. Improvements in social integration and quality of life were highly variable among the patients and depended on baseline levels and psychiatric comorbidities. INTERPRETATION: These long-term results show the crucial effect of patients' social support and pre-existing psychiatric conditions on the risk-benefit ratio of facial transplantation. Careful preoperative patient selection and long-term postoperative follow-up programmes under strict institutional review board controls should be used for any future grafts of this type. FUNDING: Protocole Hospitalier de Recherche Clinique (PHRC) National.

17.
Plast Reconstr Surg ; 136(3): 362e-369e, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26313841

ABSTRACT

BACKGROUND: Abdominal wall defects remain a significant cause of morbidity and mortality in the United States. Postoperative rehabilitation programs have been used consistently in many surgical subspecialties with exceptional results. Such programs have proven to decrease the total time patients require to resume daily activities. The authors describe a systematic rehabilitation protocol developed with the physical medicine and rehabilitation department that has significantly decreased recurrence rates in patients undergoing complex abdominal wall reconstruction. METHODS: A retrospective analysis was carried out on patients presenting for open repair of an abdominal wall defect performed by a single surgeon. Over a 5-year period, there were 275 consecutive patients divided into two similar groups: one group consisted of 137 patients that received abdominal wall rehabilitation; a second group of 138 patients did not. Patient demographics including body mass index, number of hernia defects, number of previous repairs/abdominal operations, defect size, operative time, blood loss, and postoperative complications including recurrence were collected. RESULTS: Patients enrolled in the abdominal wall rehabilitation program were found to have fewer recurrences at follow-up, with statistical significance compared with those that were not enrolled in the program. CONCLUSIONS: The implementation of the abdominal wall rehabilitation program has resulted in a decrease in recurrence rates following complex abdominal wall hernia repair and reconstruction. This is an innovative system that uses rehabilitation and physical therapy to enhance the psychosocial and occupational status of patients by improving recurrence rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Subject(s)
Abdominal Wall/surgery , Hernia, Ventral/surgery , Herniorrhaphy/rehabilitation , Physical Therapy Modalities , Postoperative Care/methods , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hernia, Ventral/rehabilitation , Humans , Male , Middle Aged , Recovery of Function , Recurrence , Retrospective Studies , Treatment Outcome
18.
Plast Reconstr Surg ; 136(2): 377-385, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25946603

ABSTRACT

BACKGROUND: Lateral abdominal wall defects are a significant contributor to patient morbidity and mortality in the United States. Reconstruction involving flank hernias and bulges is relatively scarce in the literature despite its serious consequences. The authors aim to identify an objective approach for the evaluation and successful repair of defects of the lateral abdominal wall. METHODS: A retrospective analysis was carried out on patients presenting for open repair of a lateral wall defect performed by a single surgeon. Over a 5-year period, there were 29 consecutive patients with a mean follow-up period of 21.2 months. Patient demographics including body mass index, number of hernia defects, number of previous repairs/abdominal operations, defect size, operative time, blood loss, and complications (e.g., recurrence/bulge, seroma, hematoma, wound infection, persistent pain, skin breakdown, and fascial dehiscence) were collected. RESULTS: Patients who underwent flank hernia repairs using an inlay/underlay nonbridged technique with the use of acellular dermal matrix had low recurrence and overall complication rates. Only one patient (3.4 percent) had a recurrence at follow-up, and another patient (3.4 percent) had developed a bulge. CONCLUSIONS: The authors' data indicate successful results when their technique is applied. Proper patient selection is essential, along with a thorough understanding of anatomy and techniques for successful reconstruction. The authors recommend using an inlay (preferred) or underlay repair with acellular dermal matrix to reinforce the surrounding musculofascial closure. This technique, in conjunction with the authors' holistic abdominal wall reconstruction protocol, has optimized outcomes and identified a successful multidisciplinary strategy for the reconstruction of lateral wall defects. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Subject(s)
Hernia, Ventral/diagnosis , Hernia, Ventral/surgery , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Surgical Mesh , Wound Healing/physiology , Cohort Studies , Evidence-Based Medicine , Female , Flank Pain/etiology , Flank Pain/prevention & control , Follow-Up Studies , Hernia, Ventral/complications , Humans , Male , Recurrence , Retrospective Studies , Risk Assessment , Severity of Illness Index , Skin, Artificial , Surgical Wound Dehiscence/surgery , Tensile Strength , Treatment Outcome
19.
Biochemistry ; 46(49): 14010-7, 2007 Dec 11.
Article in English | MEDLINE | ID: mdl-18004886

ABSTRACT

Cytochrome P450s are a superfamily of heme containing enzymes that use molecular oxygen and electrons from reduced nicotinamide cofactors to monooxygenate organic substrates. The fatty acid hydroxylase P450BM-3 has been particularly widely studied due to its stability, high activity, similarity to mammalian P450s, and presence of a cytochrome P450 reductase domain that allows the enzyme to directly receive electrons from NADPH without a requirement for additional redox proteins. We previously characterized the substrate N-palmitoylglycine, which found extensive use in studies of P450BM-3 due to its high affinity, high turnover number, and increased solubility as compared to fatty acid substrates. Here, we report that even higher affinity substrates can be designed by acylation of other amino acids, resulting in P450BM-3 substrates with dissociation constants below 100 nM. N-Palmitoyl-l-leucine and N-palmitoyl-l-methionine were found to have the highest affinity, with dissociation constants of less than 8 nM and turnover numbers similar to palmitic acid and N-palmitoylglycine. The interactions of the amino acid side chains with a hydrophobic pocket near R47, as revealed by our crystal structure determination of N-palmitoyl-l-methionine bound to the heme domain of P450BM-3, appears to be responsible for increasing the affinity of substrates. The side chain of R47, previously shown to be important in interactions with negatively charged substrates, does not interact strongly with N-palmitoyl-l-methionine and is found positioned at the enzyme-solvent interface. These are the tightest binding substrates for P450BM-3 reported to date, and the affinity likely approaches the maximum attainable affinity for the binding of substrates of this size to P450BM-3.


Subject(s)
Bacterial Proteins/metabolism , Cytochrome P-450 Enzyme System/metabolism , Fatty Acids/metabolism , Mixed Function Oxygenases/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Binding Sites , Crystallization , Crystallography, X-Ray , Cytochrome P-450 Enzyme System/chemistry , Cytochrome P-450 Enzyme System/genetics , Leucine/analogs & derivatives , Leucine/metabolism , Methionine/analogs & derivatives , Methionine/metabolism , Mixed Function Oxygenases/chemistry , Mixed Function Oxygenases/genetics , Models, Molecular , NADPH-Ferrihemoprotein Reductase , Palmitic Acids/metabolism , Substrate Specificity
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