Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum.

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide-polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.

Wooden Chest syndrome: The atypical pharmacology of fentanyl overdose.

WHAT IS KNOWN AND OBJECTIVE: A large percentage of opioid overdose fatalities involve fentanyl or one of its legal or illegal analogs (F/FAs). Is there something about the pharmacology of these drugs that make them unusually dangerous in an overdose? COMMENT: Some of the reasons for the dangers of overdose of F/FAs is their high potency and low cost (that leads to wide distribution). But it is rarely asked if the basic pharmacology of F/FAs differ in some fundamental way from conventional opioids such as morphine and heroin. In addition to centrally mediated respiratory depression via opioid receptors, F/FAs cause rigidity in the key respiratory muscles of the chest, upper airway and diaphragm ("wooden chest syndrome," WCS) by a non-opioid mechanism. WHAT IS NEW AND CONCLUSION: WCS is an atypical pharmacology of F/FAs. Because of its rapid onset and non-opioid mechanism, WCS makes F/FA overdose particularly dangerous.

Overdoses due to fentanyl and its analogues (F/FAs) push naloxone to the limit.

WHAT IS KNOWN AND OBJECTIVE: Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose. COMMENT: Although naloxone is generally safe and effective at reversing respiratory depression caused by a conventional opioid such as morphine or heroin by competing with the opioid and displacing it from the µ-opioid receptor, questions increasingly are arising as to whether naloxone can adequately reverse opioid overdoses that may involve the potent opioids fentanyl and its analogues (F/FAs). In other words, as more and more opioid overdoses involve F/FAs, can naloxone keep up? WHAT IS NEW AND CONCLUSION: As a competitive antagonist at µ-opioid receptors, naloxone is often a life-saving agent in cases of overdose caused by conventional opioids, but it may not be versatile or powerful enough to combat the rising tide of overdoses due to fentanyl and its illicit analogues, or in cases of overdose involving combinations of opioids and non-opioids.

Antibacterial and antibiofilm effects of flufenamic acid against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are one of the most serious surgery complications, and their prevention is of utmost importance. Flufenamic acid is a non-steroid anti-inflammatory drug approved for clinical use to relieve inflammation and pain in rheumatoid arthritis patients. In this study, we explored the antibacterial efficacy of flufenamic acid and the mechanisms underlying this effect. By using minimal inhibitory concentration (MIC), time-kill, resistance induction assays, and the antibiotic synergy test, we demonstrated that flufenamic acid inhibited the growth of methicillin-resistant staphylococci and did not induce resistance when it was used at the MIC. Furthermore, flufenamic acid acted synergistically with the beta-lactam antibiotic oxacillin and did not show significant toxicity toward mammalian cells. The biofilm inhibition assay revealed that flufenamic acid could prevent biofilm formation on medical implants and destroy the ultrastructure of the bacterial cell wall. RNA sequencing and quantitative RT-PCR indicated that flufenamic acid inhibited the expression of genes associated with peptidoglycan biosynthesis, beta-lactam resistance, quorum sensing, and biofilm formation. Furthermore, flufenamic acid efficiently ameliorated a local infection caused by MRSA in mice. In conclusion, flufenamic acid may be a potent therapeutic compound against MRSA infections and a promising candidate for antimicrobial coating of implants and surgical devices.

Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, placebo-controlled pilot trial.

OBJECTIVE: This is the first randomized double-blinded, placebo-controlled pilot trial to investigate the efficacy of pamidronate in reducing radiological and clinical disease activity in chronic non-bacterial osteomyelitis (CNO). METHOD: Patients received pamidronate or placebo at baseline and weeks 12 and 24. Whole-body magnetic resonance imaging was performed at baseline and weeks 12 and 36, and computed tomography of the anterior chest wall (ACW) at baseline and week 36. Radiological disease activity was systematically scored in the ACW and spine. Patient-reported outcomes [visual analogue scale (VAS) pain, VAS global health, Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions (EQ-5D), and 36-item Short-Form Health Survey (SF-36)] and biomarkers of bone turnover and inflammation were assessed at baseline and weeks 1, 4, 12, 24, and 36. Data are expressed as median [interquartile range]. RESULTS: Fourteen patients were randomized and 12 were analysed. From baseline to week 36, the radiological disease activity score in the ACW decreased from 5 [4-7] to 2.5 [1-3] in the pamidronate group, but did not change in the placebo group (p = 0.04). From baseline to week 36, VAS pain and VAS global health tended to decrease more in the pamidronate than in the placebo group (p = 0.11, p = 0.08). Physical functioning (HAQ) and health-related quality of life (EQ-5D, SF-36) did not change. Biomarkers of bone turnover decreased only in the pamidronate group (p ≤ 0.02). CONCLUSION: Pamidronate may improve radiological and clinical disease activity in CNO. Methods to score radiological disease activity in adult CNO were suggested. Clinical Trials: NCT02594878.

Regional Anesthesia in Cardiac Surgery: An Overview of Fascial Plane Chest Wall Blocks.

Optimal analgesia is an integral part of enhanced recovery after surgery (ERAS) programs designed to improve patients' perioperative experience and outcomes. Regional anesthetic techniques in a form of various fascial plane chest wall blocks are an important adjunct to the optimal postoperative analgesia in cardiac surgery. The most common application of fascial plane chest wall blocks has been for minimally invasive cardiac surgical procedures. An abundance of case reports has been described in the anesthesia literature and reports appear promising, yet higher-level safety and efficacy evidence is lacking. Those providing anesthesia for minimally invasive cardiac procedures should become familiar with fascial plane anatomy and block techniques to be able to provide enhanced postsurgical analgesia and facilitate faster functional recovery and earlier discharge. The purpose of this review is to provide an overview of contemporary fascial plane chest wall blocks used for analgesia in cardiothoracic surgery. Specifically, we focus on relevant anatomic considerations and technical descriptions including pectoralis I and II, serratus anterior, pectointercostal fascial, transverse thoracic muscle, and erector spine plane blocks. In addition, we provide a summary of reported local anesthetic doses used for these blocks and a current state of the literature investigating their efficacy, duration, and comparisons with standard practices. Finally, we hope to stimulate further research with a focus on delineating mechanisms of action of novel emerging blocks, appropriate dosing regimens, and subsequent analysis of their effect on patient outcomes.

Wooden chest syndrome: Beware of opioid antagonists, not just agonists.

BACKGROUND: In a constantly increasing world of opioid addiction, naloxone has become a topic of great discussion and use. With seemingly minimal side effects, naloxone has become one of the most wellknown and widely used reversal agents for opioid intoxication. While more common effects of using naloxone include agitation, abdominal cramps, piloerection, diarrhea, nausea, and yawning, lesser known side effects involve muscle spasms, flushing, hyperreflexia in neonates, and seizures. This case study demonstrates a side effect of rigidity secondary to IV naloxone that has not previously been documented. CASE: A 56 year old man was brought in by EMS after being found unresponsive in a car with a bag of drugs beside him. He was given 0.5 mg naloxone IV by EMS and immediately brought to the hospital. On arrival, the pt was noted to have tight rigidity of his upper extremities, with severe flexion. This presentation was not noted before the delivery of naloxone by EMS. CONCLUSIONS: While this case highlights a patient with a rare side effect of naloxone, it reminds physicians that all medications come with a cost. Of course, ABCs remain the highest priority of resuscitation, however when administering a medication to reverse a drug overdose, it is important to keep in mind all possible consequences of said agent. Recognizing that complete muscle rigidity may remain a result of naloxone administration allows physicians to perhaps save patients from further medical workup.

Adult Primary Peripheral PNET/Ewing's Sarcoma of the Cervical and Thoracic Spine.

This case report describes a patient with a rare occurrence of primary spinal intramedullary Ewing's sarcoma (ES) in the cervical and thoracic spine. The older age of disease occurrence, uncommon location in the cervical and thoracic spine, and EWSR1 gene fusion as the basis of diagnosis are unique features of this case. There is no clear protocol for treatment of primary extraskeletal ES of the spine, with controversy between evidence for pursuing surgery versus a combination of radiation and chemotherapy. Our patient was treated with temozolomide chemotherapy for recurrent metastatic disease of primary ES of the spine.

Thoracic wall blocks: From paravertebral to retrolaminar to serratus to erector spinae and back again - A review of evidence.

A multitude of thoracic wall blocks have been described, including parasternal-intercostal plane, Pecs I and II, serratus anterior plane, paraspinal-intercostal plane, erector spinae plane blocks, and retrolaminar blocks. They are almost all fascial plane blocks, relying on passive spread of local anesthetic to target nerves within the plane or in adjacent tissue compartments. They have emerged as attractive alternatives to thoracic paravertebral and epidural blocks because of their relative simplicity and safety. Although research into these techniques is still at an early stage, the available evidence indicates that they are effective in reducing opioid requirements and improving the pain experience in a wide range of clinical settings. They are best employed as part of multimodal analgesia with other systemic analgesics, rather than as sole anesthetic techniques. Catheters may be beneficial in situations where moderate-to-severe pain is expected for >12 h, although the optimal dosing regimen requires further investigation.

Induction chemoradiation is associated with improved survival in chest wall invasion lung cancer.

OBJECTIVE: To determine if induction chemotherapy with concurrent high-dose radiation followed by resection is associated with improved survival in patients with nonsuperior sulcus lung cancer with chest wall invasion. METHODS: We performed a retrospective review of clinical T3 (chest wall invasion) N0/N1 patients with non-small cell lung cancer who underwent surgical resection between January 1, 1992, and January 31, 2017. Exclusion criteria included superior sulcus tumors and resection performed for palliation/recurrence. Patients undergoing induction chemoradiation followed by surgical resection were compared to those undergoing resection first or those receiving induction radiation followed by resection. Overall survival was calculated using the Kaplan-Meier method. RESULTS: Thirty-four patients were included in the analysis, with 5-year overall survival (OS) of 30%. By clinical stage, 31 (91%) were IIB (T3N0) and 3 (9%) were IIIA (T3N1). Sixteen patients (47%) received induction chemoradiation before surgery. Of the remaining 18 patients, 5 (15%) received induction radiation followed by surgery, and 13 (38%) underwent surgery as the first treatment. Three patients belonging to the group not receiving induction chemoradiation died within 30 days after surgery and were excluded from survival analysis. In the remaining 31 patients, induction chemoradiation was associated with improved 5-year OS (53% for induction chemoradiation vs 7% for others; P<0.01). Disease recurrence was evident in 9 cases, 2 (12.5%) in the induction chemoradiation group and 7 (46.6%) in the others (median disease-free time 103.0 months for induction chemoradiation group vs 8.0 months for others; P<0.01). CONCLUSION: In patients with nonsuperior sulcus lung cancer with chest wall invasion, induction chemoradiation therapy followed by resection is associated with improved OS.

Review of Procedures for Reconstruction of Soft Tissue Chest Wall Defects Following Advanced Breast Malignancies.

The purpose of this article is to review closure options for complex chest wounds in patients with locally advanced breast cancer. Experiences of the plastic and oncologic surgery teams at Moffitt Cancer Center were reviewed, and the literature researched for various surgical options of complex chest wound closure. Multiple treatment modalities exist for reconstruction of complex chest wall wounds with the external oblique and V-Y latissimus dorsi musculocutaneous advancement flaps serving as workhorses in reconstruction. Treatment of cancer has moved from simply a surgical solution to include other modalities such as hormonal therapy, chemotherapy, and radiation-the latter 2 having serious consequences for wound healing. A team approach and knowledge of available flap options are vital for closure of complex wounds in a timely manner. Appropriate planning can optimize the primary goal of the oncologic surgeon to remove the cancer and the plastic surgeon's objective to reconstruct the defect and achieve a closed, durable wound prior to chemotherapy and radiation. We present the experience at the Moffitt Cancer Center in reconstructing challenging chest defects and review the reconstructive ladder.

Aminophylline increases parasternal muscle action in awake canines.

The traditional theophylline bronchodilator, aminophylline, is still widely used, especially in the treatment of COPD. The effects of aminophylline on ventilation and action of the costal diaphragm have been previously defined, but other respiratory muscles - notably the chest wall, are not well determined. Therefore, we investigated the effects of aminophylline on the Parasternal intercostal, a key obligatory inspiratory muscle, examining muscle length, shortening and EMG. We studied 11 awake canines, chronically implanted with sonomicrometer crystals and fine-wire EMG electrodes in the parasternal muscle. Ventilatory parameters, muscle length (shortening), and moving average muscle EMG activity, were measured at baseline and with aminophylline, during resting and hypercapnic stimulated breathing. Experiments were carried out prior to administration of aminophylline (baseline), and 1.5 h after loading and ongoing infusion. Minute ventilation, tidal volume and respiratory frequency all increased significantly with aminophylline, both during resting breathing and at equivalent levels of hypercapnic stimulated breathing. Parasternal baseline muscle length was entirely unchanged with aminophylline. Parasternal shortening increased significantly with aminophylline while corresponding parasternal EMG activity remained constant, consistent with increased contractility. Thus, in awake, intact mammals, aminophylline, in the usual therapeutic range, elicits increased ventilation and increased contractility of all primary inspiratory respiratory muscles, including both chest wall and diaphragm.

The effect of two doses of fentanyl on chest wall rigidity at equipotent doses of isoflurane in dogs.

OBJECTIVE: To evaluate the effect of two doses of fentanyl upon chest wall rigidity of dogs anesthetized at equipotent doses of isoflurane [1.3 minimum alveolar concentration (MACISO) of each dose of fentanyl]. STUDY DESIGN: Prospective crossover randomized study. ANIMALS: A group of eight male Beagle dogs, approximately 1 year old and weighing 12.1 ± 1.6 kg (mean ± standard deviation). METHODS: The dogs were anesthetized with isoflurane and instrumented for the measurement of esophageal pressure (PESO), flow (V˙) and volume (V). Chest wall elastance (ECW) was estimated by multiple linear regression of the model. PESO(t) = V˙(t) × RCW + V(t) × ECW + EEPESO where t is time, RCW is chest wall resistance and EEPESO is end-expiratory PESO. Chest wall compliance (CCW) was calculated as 1/ECW and normalized to the body weight of each dog (mL cmH2O-1 kg-1). Anesthesia was maintained at 1.3 MACISO for at least 15 minutes and CCW recorded (CCW-ISO). The dogs were randomly assigned to the lower fentanyl dose [loading dose (33 µg kg-1) and infusion (0.2 µg kg-1 minute-1)] or the higher fentanyl dose [loading dose (102 µg kg-1) and infusion (0.8 µg kg-1 minute-1)]. After 60 minutes of fentanyl infusion, CCW was recorded for each dose (CCW-FENT). During fentanyl infusion, the dogs were maintained at equipotent doses of isoflurane (1.3 MACISO for each fentanyl dose). A two-way analysis of variance followed by a Bonferroni test was used to compare CCW-ISO and CCW-FENT in both treatments and CCW-FENT between treatments. A p value <0.05 was considered significant. RESULTS: Neither of the fentanyl doses decreased CCW and there was no difference in CCW-FENT between doses. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl at the studied doses did not result in chest wall rigidity in dogs anesthetized with equipotent doses of isoflurane (1.3 MACISO).

Long term use of bevacizumab in the treatment of triple negative breast cancer with giant tumor in chest wall: A case report.

RATIONALE: Triple-negative breast cancer (TNBC) is associated with unfavorable prognosis due to lack of targeted agents. Bevacizumab, an anti-angiogenic monoclonal antibody against vascular endothelial growth factor A, has shown clinical effects in patients with TNBC. PATIENT CONCERNS: We reported a 49-year-old woman presenting with a giant breast tumor. DIAGNOSES: Stage IV TNBC with chest wall metastasis. INTERVENTIONS: The patient underwent long-term use of bevacizumab combined with chemotherapy. OUTCOMES: The patient was on follow-up for 46 months, a remarkable improvement of the chest wall cutaneous lesion was observed. LESSONS: Bevacizumab may provide benefits for TNBC patients with chest wall metastasis.

A comparison between skin dose of breast cancer patients at the breast region, measured by thermoluminescent dosimeter in the presence and absence of bolus.

AIM: The aim of this study was to measure entrance skin dose (ESD) on the breast of patients who had undergone radiotherapy following surgery, in the presence and absence of bolus. MATERIALS AND METHODS: In this study, the ESD on the breast of 22 female patients was measured using thermoluminescent dosimeter-100 chips. For each patient, the ESD was measured 3 times (once without bolus and twice using bolus). The bolus types used in this study include super flab and wax. RESULTS: The average ESDs on the breast of patients (from both medial and lateral tangential fields) in the presence of the super flab bolus and absence of bolus were 225.8 and 148.17 cGy, respectively, that when using the bolus, around 52% increasing in ESD was observed. The results showed a significant relationship between the ESD on the breast of patients and bolus types (P = 0.002); in addition, correlation coefficient between the two boluses (super flab and wax) was 0.615 (r = 0.615). CONCLUSION: When using the bolus in postmastectomy irradiation, it is noted that in dose delivery to the chest wall, surgical scar or skin of the treated region should be considered. The use of the bolus as a substance that increases of the skin dose can sometimes cause an excessive increase in skin dose that may cause severe skin reactions and underdosing of underlying tissues. Furthermore, using wax bolus in regions that do not require a lot of shaping of bolus is affordable.

Rhomboid Intercostal and Subserratus Plane Block: A Cadaveric and Clinical Evaluation.

BACKGROUND AND OBJECTIVES: Fascial plane blocks are rapidly emerging to provide safe, feasible alternatives to epidural analgesia for thoracic and abdominal pain. We define a new option for chest wall and upper abdominal analgesia, termed the rhomboid intercostal and subserratus plane (RISS) block. The RISS tissue plane extends deep to the erector spinae muscle medially and deep to the serratus anterior muscle laterally. We describe a 2-part proof-of-concept study to validate the RISS block, including a cadaveric study to evaluate injectate spread and a retrospective case series to assess dermatomal coverage and analgesic efficacy. METHODS: For the cadaveric portion of the study, bilateral ultrasound-guided RISS blocks were performed on 6 fresh cadavers with 30 mL of 0.5% methylcellulose with india ink. For the retrospective case series, we present 15 patients who underwent RISS block or RISS catheter insertion for heterogeneous indications including abdominal surgery, rib fractures, chest tube-associated pain, or postoperative incisional chest wall pain. RESULTS: In the cadaveric specimens, we identified staining of the lateral branches of the intercostal nerves from T3 to T9 reaching the posterior primary rami deep to the erector spinae muscle medially. In the clinical case series, dermatomal coverage was observed in the anterior hemithorax with visual analog pain scores less than 5 in patients who underwent both single-shot and continuous catheter infusions. CONCLUSIONS: Our preliminary cadaveric and clinical data suggest that RISS block anesthetizes the lateral cutaneous branches of the thoracic intercostal nerves and can be used in multiple clinical settings for chest wall and upper abdominal analgesia.

Evaluation of lung and chest wall mechanics during anaesthesia using the PEEP-step method.

BACKGROUND: Postoperative pulmonary complications are common. Between patients there are differences in lung and chest wall mechanics. Individualised mechanical ventilation based on measurement of transpulmonary pressures would be a step forward. A previously described method evaluates lung and chest wall mechanics from a change of ΔPEEP and calculation of change in end-expiratory lung volume (ΔEELV). The aim of the present study was to validate this PEEP-step method (PSM) during general anaesthesia by comparing it with the conventional method using oesophageal pressure (PES) measurements. METHODS: In 24 lung healthy subjects (BMI 18.5-32), three different sizes of PEEP steps were performed during general anaesthesia and ΔEELVs were calculated. Transpulmonary driving pressure (ΔPL) for a tidal volume equal to each ΔEELV was measured using PES measurements and compared to ΔPEEP with limits of agreement and intraclass correlation coefficients (ICC). ΔPL calculated with both methods was compared with a Bland-Altman plot. RESULTS: Mean differences between ΔPEEP and ΔPL were <0.15 cm H2O, 95% limits of agreements -2.1 to 2.0 cm H2O, ICC 0.6-0.83. Mean differences between ΔPL calculated by both methods were <0.2 cm H2O. Ratio of lung elastance and respiratory system elastance was 0.5-0.95. CONCLUSIONS: The large variation in mechanical properties among the lung healthy patients stresses the need for individualised ventilator settings based on measurements of lung and chest wall mechanics. The agreement between ΔPLs measured by the two methods during general anaesthesia suggests the use of the non-invasive PSM in this patient population. CLINICAL TRIAL REGISTRATION: NCT 02830516.

Negative-pressure wound therapy and early pedicle flap reconstruction of the chest wall after epirubicin extravasation.

PURPOSE: Accidental extravasation is a serious iatrogenic injury among patients receiving anthracycline-containing chemotherapy. The aim of this work is to present a combination therapy for chest wall reconstruction following epirubicin extravasation. METHODS: Herein, we report a 68-year-old woman with massive soft tissue necrosis of the anterolateral chest wall after epirubicin extravasation from a port implanted in the subclavicular area. RESULTS: The necrotic tissue was resected, the port was removed, and negative-pressure wound therapy was applied. Three weeks later, a latissimus dorsi pedicle flap was successfully used to cover the defect. CONCLUSIONS: To the best of the authors' knowledge, this is the first report of a strategy comprising the combination of negative-pressure wound therapy and a latissimus pedicle flap for reconstruction of the chest wall after soft tissue necrosis following epirubicin extravasation.