Reconstructive Limb Salvage After COVID-19-Induced Gangrene and Amputation.

This case series describes the clinical course and reconstructive methods utilized for patients with diabetes and significant gangrene and necrosis following coronavirus disease 2019 (COVID-19) infection. COVID-19 produces mainly respiratory symptoms but has a variety of atypical presentations and sequelae. Serious complications are increased in patients with underlying medical conditions such as diabetes mellitus. By generating a prothrombotic milieu, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases the risk for arterial and venous thromboses. Inflammatory damage and micro-thromboses are thought to contribute to acro-ischemia, colloquially known as 'COVID toes,' which presents cutaneously as chilblain-like lesions. Necrosis can be severe and devastating, often resulting in major amputation. Two exemplary case reports are presented herein: first, a 57-year-old female presented for vascular evaluation with pedal gangrene to the midfoot one month after developing painful discoloration in her right toe. After angioplasty restored pedal blood flow, she received a transmetatarsal amputation (TMA) with a local tissue flap. Second, a 41-year-old female presented for vascular evaluation with extensive pedal gangrene three months after hospitalization for COVID-19. After arteriotomy improved pedal blood flow, she underwent a Lisfranc amputation followed by superficial circumflex iliac artery perforator (SCIP) flap reconstruction. Sufficient evidence suggests that COVID-19 impairs microcirculatory function and can be especially detrimental in diabetic patients. Reconstructive techniques in patients with severe gangrene with COVID toes help patients regain functionality.

Determining Accurate Dye Combinations for Sentinel Lymph Node Detection: A Systematic Review.

Background: Lymphatic dyes are commonly used to map the drainage path from tumor to lymphatics, which are biopsied to determine if spread has occurred. A blue dye in combination with technetium-99 is considered the gold standard for mapping, although many other dyes and dye combinations are used. Not all of these substances have the same detection efficacy. Methods: A systematic review of PubMed, SCOPUS, Web of Science, and Medline was performed. The predefined search terms were (indocyanine green OR isosulfan blue OR lymphazurin OR patent blue OR methylene blue OR fluorescein OR technetium-99) AND combination AND dye AND (sentinel lymph node biopsy OR lymphedema OR lymphatics OR lymph OR microsurgery OR cancer OR tumor OR melanoma OR carcinoma OR sarcoma). Results: The initial search returned 4267 articles. From these studies, 37 were selected as candidates that met inclusion criteria. After a full-text review, 34 studies were selected for inclusion. Eighty-nine methods of sentinel lymph node (SLN) detection were trialed using 22 unique dyes, dye combinations, or other tracers. In total, 12,157 SLNs of 12,801 SLNs were identified. Dye accuracy ranged from 100% to 69.8% detection. Five dye combinations had 100% accuracy. Dye combinations were more accurate than single dyes. Conclusions: Combining lymphatic dyes improves SLN detection results. Replacing technetium-99 with ICG may allow for increased access to SLN procedures with comparable results. The ideal SLN tracer is a low-cost molecule with a high affinity for lymphatic vessels due to size and chemical composition, visualization without specialized equipment, and no adverse effects.

Reliability of an AI-Powered Application Across Different Mobile Devices for Assessment of Chronic Wounds.

Objective: Evaluate the inter- and intrarater reliability of a wound assessment tool in iPhone 12 and 13 mini modalities against a validated iPad mini/Structure Sensor configuration. Approach: We assessed a wound measurement application (eKare inSight®) for result consistency in patients presenting with wounds. Assessments were analyzed using a two-way analysis of variance. Intraclass correlation coefficient (ICC) was computed for intrarater (ICC1,1) and inter-rater (ICC2,1) analysis using a two-way random effects model. Paired t-test assessed the statistical difference between measurement methods. Results: Forty-two lesions were analyzed with surface areas ranging from 0.2 to 23 cm2 (average 4.33 ± 5.44 cm2). A high level of reliability was observed for repeat wound area measurements by the same examiner (ICC1,1 = 0.997) and between examiners with iPhone 13 mini (ICC2,1 = 0.998). There was no significant difference between iPhone 12 and iPad mini/Structure Sensor (p = 0.78) or between iPhone 13 mini and iPhone 12 (p = 0.22). Minimal difference existed between iPhone 13 mini and iPad mini/Structure Sensor (p = 0.049, Cohen's d = 0.01). Innovation: Increased pervasiveness of smartphones in clinical care, coupled with advances in smartphone imaging and machine learning, allows for a potential solution to the problem of fast and accurate wound measurements. The application investigated produces wound measurement results quickly and with demonstrated accuracy. It does not require a calibration sticker or reference marker and allows for automatic wound boundary delineation. Conclusion: The results of this study suggest that a digital planimetry mobile application may offer high levels of reliability across devices and users.

Remission Strategies with Fat Grafting to Prevent Recurrence of Pedal Ulcerations and Pain: A Case Series.

Background: Foot deformities and gait abnormalities can result in locally elevated peak pedal pressures or atypical pedal biomechanics. Combined with underlying comorbidities such as neuropathy, stroke, atrophic fat padding and history of ulcerations, this can lead to recurrent ulcerations and pain. Pedal fat grafting (PFG) is a treatment modality that has been shown to reduce peak pressures and accelerate wound healing. This study aimed to investigate the utility of PFG to treat and prevent ulcerations. Methods: We retrospectively analyzed medical history, demographics, wound volume at time of procedure, volume of fat injected, surgical outcomes, and presence of new wounds in 15 patients who underwent PFG at Keck Hospital between 2018 and 2023. Results: Seventeen feet from 15 patients (63 ±â€…12 years old, body mass index 30.9 ±â€…3.1) received PFG with an average volume of fat injected of 10.7 mL and procedure time of 84.6 minutes. At the time of PFG, nine wounds were present on nine feet with an average wound volume of 1.6 ±â€…2.7 cm3. Average follow-up was 6.9 months (range 1-36 months), with no complications or recurrent ulcerations since the procedure. Conclusions: PFG is a promising treatment option for reducing peak pedal pressure and preventing ulcer recurrence in patients with various conditions. Further study is warranted for long-term follow-up.

Extreme Limb Salvage: The Thin SCIP Flap for Distal Amputation Coverage in Highly Comorbid Patients.

INTRODUCTION: Limb length preservation is correlated with overall survival. Successful free flap coverage of fore-, mid- and hind-foot amputations can prevent more proximal below-knee amputations but is challenging in patients with multiple comorbidities. The thin superficial circumflex iliac artery perforator (SCIP) flap is well-suited for these patients as it provides thin, pliable tissue from a favorable donor site. METHODS: A retrospective review of all patients with distal amputations requiring coverage with a thin SCIP flap between 2016 to 2022 was performed. Patient demographics, amputation levels, and wound characteristics as well as flap and microsurgery details were analyzed. The primary outcome was limb salvage. Secondary outcomes included partial flap necrosis, flap revision rate and additional postoperative complications. RESULTS: Thirty-two patients (mean age 57.3) underwent reconstruction of fore-, mid- and hindfoot amputations with thin SCIP flaps (mean follow-up 36 months). Twenty-eight patients (87.5%) had diabetes, 27 (84.4%) had peripheral artery disease and 15 (46.9%) were dialysis-dependent. Average flap size was 59.5cm2 and average flap thickness was 5.7mm. Successful limb salvage was achieved in 27 patients (84.3%). Three cases (9.4%) had total flap loss. Twenty-one flaps (65.6%) had partial necrosis of which 12 (57.1%) healed with conservative management and seven (33.3 %) healed after late revision. CONCLUSION: The thin SCIP flap is a useful option for coverage of distal pedal amputations in patients with significant comorbidities. Despite higher rates of partial flap necrosis, free flap reconstruction allowed for high rates of limb salvage in a challenging patient population.

Comparative Evaluation of the Electronic Residency Application Service Versus the Plastic Surgery Common Application to a Single Institution in the 2022 Integrated Plastic Surgery Match.

BACKGROUND: The Plastic Surgery Common Application (PSCA) has emerged as a low-cost alternative application portal to the Electronic Residency Application Service (ERAS) for integrated plastic surgery applicants. During the 2021 to 2022 application cycle, our plastic surgery residency program accepted both the PSCA and ERAS applications to help recruit candidates otherwise deterred by prohibitively high application costs. We sought to determine how the PSCA compared with the ERAS application in a standardized review of applications scores. METHODS: The PSCA and ERAS applications from 28 candidates who received interviews from the Keck School of Medicine were analyzed. These 56 applications were randomly assigned across 22 independent reviewers. Each reviewer scored applications on a scale of 1 to 5 with regard to communication skills, leadership, intellectual curiosity, compatibility with the program, service, and perseverance. Mean scores between the applications were compared using 2-tailed z tests, with statistical significance set at P < 0.05. RESULTS: The 56 residency applications had a combined mean score of 4.21 (95% confidence interval [CI], 4.13-4.29). The mean score of PSCA applications (4.19; 95% CI, 4.08-4.31) did not significantly differ from the mean score of ERAS applications (4.24; 95% CI, 4.12-4.35; P = 0.57). The PSCA and ERAS applications did not have a significant difference in the mean scores for any review category. CONCLUSION: There was no difference between the overall scores and the scores of each review category between the PSCA and ERAS applications, suggesting that the PSCA may be a reasonable alternative to ERAS for medical students applying to plastic surgery residency.

The Free Superficially Based Low-Abdominal Mini Flap for Oncoplastic Breast Reconstruction.

SUMMARY: Volume replacement in oncoplastic breast reconstruction most commonly uses pedicled flaps. In thin patients with small breasts, free-tissue transfer may be better suited to preserve breast size. Evidence on microvascular oncoplastic reconstruction is limited, and reconstruction has often required sacrifice of potential future donor sites. The free superficially based low-abdominal mini (SLAM) flap uses a narrow strip of lower abdominal tissue based on superficial perfusion of the abdominal wall that is anastomosed to chest wall perforators to preserve the ability to perform future abdominally based autologous breast reconstruction. Five patients underwent reconstruction with SLAM flaps for immediate oncoplastic reconstruction. Their mean age was 49.8 years, and their mean body mass index was 23.5. Tumor location was most commonly in the lower outer quadrant (40%). Average lumpectomy weight was 30 g. Two flaps were based on the superficial inferior epigastric artery, and three, on the superficial circumflex iliac artery. Recipient vessels included internal mammary perforators (40%), serratus branch (20%), lateral thoracic vessel branch (20%), and lateral intercostal perforators (20%). All patients underwent radiation therapy without delay and maintained volume, symmetry, and contour at an average period of 11.7 months after surgery. There were no cases of flap loss, fat necrosis, or delayed wound healing. The free SLAM flap allows for immediate oncoplastic breast reconstruction in thin, small-breasted patients with limited regional tissue without sacrificing future potential donor sites for autologous breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Simultaneous Segmentation and Classification of Pressure Injury Image Data Using Mask-R-CNN.

Background: Pressure injuries (PIs) impose a substantial burden on patients, caregivers, and healthcare systems, affecting an estimated 3 million Americans and costing nearly $18 billion annually. Accurate pressure injury staging remains clinically challenging. Over the last decade, object detection and semantic segmentation have evolved quickly with new methods invented and new application areas emerging. Simultaneous object detection and segmentation paved the way to segment and classify anatomical structures. In this study, we utilize the Mask-R-CNN algorithm for segmentation and classification of stage 1-4 pressure injuries. Methods: Images from the eKare Inc. pressure injury wound data repository were segmented and classified manually by two study authors with medical training. The Mask-R-CNN model was implemented using the Keras deep learning and TensorFlow libraries with Python. We split 969 pressure injury images into training (87.5%) and validation (12.5%) subsets for Mask-R-CNN training. Results: We included 121 random pressure injury images in our test set. The Mask-R-CNN model showed overall classification accuracy of 92.6%, and the segmentation demonstrated 93.0% accuracy. Our F1 scores for stages 1-4 were 0.842, 0.947, 0.907, and 0.944, respectively. Our Dice coefficients for stages 1-4 were 0.92, 0.85, 0.93, and 0.91, respectively. Conclusions: Our Mask-R-CNN model provides levels of accuracy considerably greater than the average healthcare professional who works with pressure injury patients. This tool can be easily incorporated into the clinician's workflow to aid in the hospital setting.

Initial Clinical Experience with a Simple, Home System for Early Detection and Monitoring of Diabetic Foot Ulcers: The Foot Selfie.

BACKGROUND: Diabetic foot ulcers (DFUs) are a leading cause of disability and morbidity. There is an unmet need for a simple, practical, home method to detect DFUs early and remotely monitor their healing. METHOD: We developed a simple, inexpensive, smartphone-based, "Foot Selfie" system that enables patients to photograph the plantar surface of their feet without assistance and transmit images to a remote server. In a pilot study, patients from a limb-salvage clinic were asked to image their feet daily for six months and to evaluate the system by questionnaire at five time points. Transmitted results were reviewed weekly. RESULTS: Fifteen patients (10 male) used the system after approximately 5 minutes of instruction. Participants uploaded images on a median of 76% of eligible study days. The system captured and transmitted diagnostic quality images of the entire plantar surface of both feet, permitting clinical-management decisions on a remote basis. We monitored 12 active wounds and 39 pre-ulcerative lesions (five wounds and 13 pre-ulcerative lesions at study outset); we observed healing of seven wounds and reversal of 20 pre-ulcerative lesions. Participants rated the system as useful, empowering, and preferable to their previous methods of foot screening. CONCLUSIONS: With minimal training, patients transmitted diagnostic-quality images from home on most days, allowing clinicians to review serial images. This system permits inexpensive home foot screening and monitoring of DFUs. Further studies are needed to determine whether it can reduce morbidity of DFUs and/or the associated cost of care. Artificial intelligence integration could improve scalability.

Artificial Intelligence for Predicting and Diagnosing Complications of Diabetes.

Artificial intelligence can use real-world data to create models capable of making predictions and medical diagnosis for diabetes and its complications. The aim of this commentary article is to provide a general perspective and present recent advances on how artificial intelligence can be applied to improve the prediction and diagnosis of six significant complications of diabetes including (1) gestational diabetes, (2) hypoglycemia in the hospital, (3) diabetic retinopathy, (4) diabetic foot ulcers, (5) diabetic peripheral neuropathy, and (6) diabetic nephropathy.

Autologous Minimally Manipulated Homologous Adipose Tissue (AMHAT) for Treatment of Nonhealing Diabetic Foot Ulcers.

Diabetic foot complications are increasingly burdensome for patients, clinicians, and society. Development of innovative therapies to support good quality basic care is a priority among those with an interest in this area. One of these involves scanning and printing tissues to match and conform to a defect (so-called 3D printing). Methods: A single-arm pilot study of ten consecutive patients with a history of a chronic diabetic foot ulcer (DFU), treated with autologous minimally manipulated homologous adipose tissue (AMHAT), dispensed by a specialized 3D bioprinter, Dr. INVIVO, was performed. Patients with nonhealing DFUs present for more than 4 weeks and refractory to standard-of-care therapies were included. Wounds were treated with a single application of AMHAT, and then followed up weekly for up to 12 weeks, or until the wounds healed. The primary outcome measure was complete epithelialization of the wound up to 12 weeks after the treatment. Secondary outcome measures included wound size and/or volume reduction, assessment of ulcer grade, and time to closure. Results: Five wounds were healed by 5 weeks and one at 8 weeks. The mean percent area reduction at 12 weeks was 78.3% (SD: 33.23). Complete closure was achieved in 60% of wounds. The mean time to closure in these wounds was 49.1 days (95% CI, 29.9-68.3). No adverse events were reported. Conclusions: Single treatment of bioprinted AMHAT appears to be a safe and potentially effective treatment modality for patients with chronic DFUs. Further studies are warranted to explore the full potential of 3D bioprinting for tissue repair in this high-risk population.

Outcomes of Local versus Free Flaps for Lower Extremity Trauma.

BACKGROUND: Lower extremity reconstruction often requires soft tissue transfer for limb salvage. Flaps are allocated based on injury size, location, and shape coupled with surgeon expertise. Ideally, vascularized tissue should have similar outcomes across local and free tissue transfers. By evaluating outcomes from a Level 1 trauma center, we aim to provide recommendations regarding surgical management of leg reconstruction with respect to local versus free flap implementation. METHODS: This retrospective review evaluated patient medical history, demographics, flap characteristics, and outcomes from LAC + USC between 2007-2021 using an internal database. Outcomes included failure rates, complications, and ambulation. RESULTS: 357 lower extremity flaps were placed on 322 patients; 187 (52.4%) were local and 170 (47.6.%) were free flaps. Twenty-one (11.2%) local flaps suffered significantly more postoperative hardware infections and/or osteomyelitis compared to nine (5.3%) free flaps. Eleven (5.9%) local flaps developed partial necrosis, four requiring revision; 12 (6.4%) total local flaps required revision. Comparatively, sixteen (9.4%) free flaps developed partial necrosis, seven requiring revision; 18 (10.6%) total free flaps required revision. Flap survival was 96.3% for local versus 93.5% for free flaps. Percentage of fully ambulatory patients and time to final ambulation was not significant across cohorts. DISCUSSION: Local flaps may portent higher risk for infection; though the cause is not clear, the results may be confounded by comorbidities. Nevertheless, there were no significant differences in flap survival or number of fully ambulatory patients across cohorts. Future studies should evaluate aesthetic results and patient satisfaction across flap types.

Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer.

BACKGROUND: In 2007, we reported a summary of data comparing diabetic foot complications to cancer. The purpose of this brief report was to refresh this with the best available data as they currently exist. Since that time, more reports have emerged both on cancer mortality and mortality associated with diabetic foot ulcer (DFU), Charcot arthropathy, and diabetes-associated lower extremity amputation. METHODS: We collected data reporting 5-year mortality from studies published following 2007 and calculated a pooled mean. We evaluated data from DFU, Charcot arthropathy and lower extremity amputation. We dichotomized high and low amputation as proximal and distal to the ankle, respectively. This was compared with cancer mortality as reported by the American Cancer Society and the National Cancer Institute. RESULTS: Five year mortality for Charcot, DFU, minor and major amputations were 29.0, 30.5, 46.2 and 56.6%, respectively. This is compared to 9.0% for breast cancer and 80.0% for lung cancer. 5 year pooled mortality for all reported cancer was 31.0%. Direct costs of care for diabetes in general was $237 billion in 2017. This is compared to $80 billion for cancer in 2015. As up to one-third of the direct costs of care for diabetes may be attributed to the lower extremity, these are also readily comparable. CONCLUSION: Diabetic lower extremity complications remain enormously burdensome. Most notably, DFU and LEA appear to be more than just a marker of poor health. They are independent risk factors associated with premature death. While advances continue to improve outcomes of care for people with DFU and amputation, efforts should be directed at primary prevention as well as those for patients in diabetic foot ulcer remission to maximize ulcer-free, hospital-free and activity-rich days.

Wavefront Field Mapping Reveals a Physiologic Network Between Drivers Where Ablation Terminates Atrial Fibrillation.

BACKGROUND: Localized drivers are proposed mechanisms for persistent atrial fibrillation (AF) from optical mapping of human atria and clinical studies of AF, yet are controversial because drivers fluctuate and ablating them may not terminate AF. We used wavefront field mapping to test the hypothesis that AF drivers, if concurrent, may interact to produce fluctuating areas of control to explain their appearance/disappearance and acute impact of ablation. METHODS: We recruited 54 patients from an international registry in whom persistent AF terminated by targeted ablation. Unipolar AF electrograms were analyzed from 64-pole baskets to reconstruct activation times, map propagation vectors each 20 ms, and create nonproprietary phase maps. RESULTS: Each patient (63.6±8.5 years, 29.6% women) showed 4.0±2.1 spatially anchored rotational or focal sites in AF in 3 patterns. First, a single (type I; n=7) or, second, paired chiral-antichiral (type II; n=5) rotational drivers controlled most of the atrial area. Ablation of 1 to 2 large drivers terminated all cases of types I or II AF. Third, interaction of 3 to 5 drivers (type III; n=42) with changing areas of control. Targeted ablation at driver centers terminated AF and required more ablation in types III versus I (P=0.02 in left atrium). CONCLUSIONS: Wavefront field mapping of persistent AF reveals a pathophysiologic network of a small number of spatially anchored rotational and focal sites, which interact, fluctuate, and control varying areas. Future work should define whether AF drivers that control larger atrial areas are attractive targets for ablation.

Online webinar training to analyse complex atrial fibrillation maps: A randomized trial.

BACKGROUND: Specific tools have been recently developed to map atrial fibrillation (AF) and help guide ablation. However, when used in clinical practice, panoramic AF maps generated from multipolar intracardiac electrograms have yielded conflicting results between centers, likely due to their complexity and steep learning curve, thus limiting the proper assessment of its clinical impact. OBJECTIVES: The main purpose of this trial was to assess the impact of online training on the identification of AF driver sites where ablation terminated persistent AF, through a standardized training program. Extending this concept to mobile health was defined as a secondary objective. METHODS: An online database of panoramic AF movies was generated from a multicenter registry of patients in whom targeted ablation terminated non-paroxysmal AF, using a freely available method (Kuklik et al-method A) and a commercial one (RhythmView-method B). Cardiology Fellows naive to AF mapping were enrolled and randomized to training vs no training (control). All participants evaluated an initial set of movies to identify sites of AF termination. Participants randomized to training evaluated a second set of movies in which they received feedback on their answers. Both groups re-evaluated the initial set to assess the impact of training. This concept was then migrated to a smartphone application (App). RESULTS: 12 individuals (median age of 30 years (IQR 28-32), 6 females) read 480 AF maps. Baseline identification of AF termination sites by ablation was poor (40%±12% vs 42%±11%, P = 0.78), but similar for both mapping methods (P = 0.68). Training improved accuracy for both methods A (P = 0.001) and B (p = 0.012); whereas controls showed no change in accuracy (P = NS). The Smartphone App accessed AF maps from multiple systems on the cloud to recreate this training environment. CONCLUSION: Digital online training improved interpretation of panoramic AF maps in previously inexperienced clinicians. Combining online clinical data, smartphone apps and other digital resources provides a powerful, scalable approach for training in novel techniques in electrophysiology.

Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation: Reconciling Putative Mechanisms Using Multiple Mapping Techniques.

BACKGROUND: Mechanisms for persistent atrial fibrillation (AF) are unclear. We hypothesized that putative AF drivers and disorganized zones may interact dynamically over short time scales. We studied this interaction over prolonged durations, focusing on regions where ablation terminates persistent AF using 2 mapping methods. METHODS: We recruited 55 patients with persistent AF in whom ablation terminated AF prior to pulmonary vein isolation from a multicenter registry. AF was mapped globally using electrograms for 360±45 cycles using (1) a published phase method and (2) a commercial activation/phase method. RESULTS: Patients were 62.2±9.7 years, 76% male. Sites of AF termination showed rotational/focal patterns by methods 1 and 2 (51/55 vs 55/55; P=0.13) in spatially conserved regions, yet fluctuated over time. Time points with no AF driver showed competing drivers elsewhere or disordered waves. Organized regions were detected for 61.6±23.9% and 70.6±20.6% of 1 minute per method (P=nonsignificant), confirmed by automatic phase tracking (P<0.05). To detect AF drivers with >90% sensitivity, 8 to 32 s of AF recordings were required depending on driver definition. CONCLUSIONS: Sites at which persistent AF terminated by ablation show organized activation that fluctuate over time, because of collision from concurrent organized zones or fibrillatory waves, yet recur in conserved spatial regions. Results were similar by 2 mapping methods. This network of competing mechanisms should be reconciled with existing disorganized or driver mechanisms for AF, to improve clinical mapping and ablation of persistent AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.

Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells.

Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread.

Medico-legal aspects of complications following pain relieving blocks.

Nerve blocks administered for the relief of chronic pain are sometimes followed by complications which give rise to litigation. The grounds for legal action may be that: (1) complications were caused by the procedure; (2) the patient did not consent to the procedure; (3) the procedure was carried out inexpertly; (4) the wrong procedure was performed; (5) the treatment of the complication was inadequate. Many of these problems can be avoided by care in the selection, investigation and documentation of cases, by considered choice and meticulous performance of the block(s) and by adequate attention to aftercare.