The Role of Botulinum Neurotoxin A in the Conservative Treatment of Fractures: An Experimental Study on Rats.

This paper explores the role of botulinum neurotoxin in aiding fracture recovery through temporary muscle paralysis. Specifically, it investigates the effects of botulinum neurotoxin-induced paralysis of the sternocleidomastoid muscle on clavicle fractures in rats. The research aims to assess safety, effectiveness, and the impact on fracture healing. Healthy male Albino Wistar rats were divided into four groups: clavicle fracture, botulinum neurotoxin injection, both, and control. Surgeries were conducted under anaesthesia, and postoperatively, animals were monitored for 28 days. Euthanasia and radiological assessment followed, examining fracture healing and muscle changes, while tissues were histopathologically evaluated. The modified Lane-Sandhu scoring system was used for the radiographic evaluation of clavicle fractures, and the results varied from complete healing to nonunion. Histopathological examination at 28 days postfracture showed fibrous tissue, mesenchymal cells, and primary callus formation in all groups. Despite varied callus compositions, botulinum neurotoxin administration did not affect clavicle healing, as evidenced by similar scores to the control group. Several studies have explored botulinum neurotoxin applications in fracture recovery. Research suggests its potential to enhance functional recovery in certain types of fractures. Theoretical benefits include managing muscle spasticity, aiding reduction techniques, and preventing nonunion. However, botulinum neurotoxin's transient effect and nonuniversal applications should be considered. The present study found that botulinum toxin had no clear superiority in healing compared to controls, while histological evaluation showed potential adverse effects on muscle tissue. Further research is essential to understand its risk-benefit balance and long-term effects.

Dyspnea induced by hemidiaphragmatic paralysis after ultrasound-guided supraclavicular brachial plexus block in a morbidly obese patient.

RATIONALE: Hemidiaphragmatic paralysis (HDP) is a frequent complication of the brachial plexus block, caused by unintentional blockade of ipsilateral phrenic nerve. HDP did not rise enough alarm and attention to most anesthesiologists, because most patients with no coexisting comorbid diseases are asymptomatic and able to tolerate it. However, it may cause severe respiratory complication for patients with preexisting compromised cardiorespiratory function. PATIENT CONCERNS: A 67-year-old woman with morbidly obesity was planned to receive opening reduction and internal fixation of right humeral shaft fracture under regional anesthesia considering less respiratory and cardiovascular system interference compared with general anesthesia. DIAGNOSES: After ultrasound guided supraclavicular brachial plexus block, the patient developed severe hypoxia and hypercapnia.Unintentional block of phrenic nerve and diaphragm paralysis was diagnosed by diaphragm ultrasound, which was considered as the main reason of severe hypoxia. INTERVENTIONS: It led to a conversion from regional anesthesia to general anesthesia with endotracheal intubation for patient's safety and smooth operation. OUTCOMES: The unintentional phrenic nerve block leads to a prolonged ventilation time, length of stay in intensive care unit and length of stay in hospital. LESSONS: This case report highlights the risk of diaphragm paralysis in morbidly obese patients. Though new diaphragm sparing brachial plexus block (BPB) methods were developed intended to reduce the risk of HDP, no approaches could absolutely spare phrenic nerve involvement. Therefore, clinicians should always consider the risk of HDP associated with BPBs. For each individual, a detailed preoperative evaluation and sufficient preparation are paramount to avoid serious complications.

Subcoracoid tunnel block as an alternative infraclavicular brachial plexus approach -a case series.

BACKGRUOND: Magnetic resonance neurography shows the brachial plexus cords in the subcoracoid tunnel beneath the pectoralis minor. With an ultrasound scan along the brachial line, the brachial plexus cords in the subcoracoid tunnel can be targeted using an in-plane needle approach. We describe this new approach to the infraclavicular block called the "subcoracoid tunnel block." CASE: Twenty patients were administered with the ultrasound-guided subcoracoid tunnel block for the below-elbow surgery. The contact of the needle tip with cords was visible in all 20 patients. With neurostimulation, the posterior cord was identified in 11 (55%) and medial cord in 9 (45%) patients on the first needle pass. The subcoracoid tunnel block was successful in 16 patients (80%). CONCLUSIONS: Our case series shows that the subcoracoid tunnel block is an excellent alternative technique for the infraclavicular block. Its advantages include better needle-cord visibility and easy identification of the brachial plexus cords.

A multicenter, randomized comparison between 2, 5, and 8 mg of perineural dexamethasone for ultrasound-guided infraclavicular block.

BACKGROUND AND OBJECTIVES: This multicenter, randomized trial compared 2, 5, and 8 mg of perineural dexamethasone for ultrasound-guided infraclavicular brachial plexus block. Our research hypothesis was that all three doses of dexamethasone would result in equivalent durations of motor block (equivalence margin=3.0 hours). METHODS: Three hundred and sixty patients undergoing upper limb surgery with ultrasound-guided infraclavicular block were randomly allocated to receive 2, 5, or 8 mg of preservative-free perineural dexamethasone. The local anesthetic agent (35 mL of lidocaine 1%-bupivacaine 0.25% with epinephrine 5 µg/mL) was identical in all subjects. Patients and operators were blinded to the dose of dexamethasone. During the performance of the block, the performance time, number of needle passes, procedural pain, and complications (vascular puncture, paresthesia) were recorded. Subsequently a blinded observer assessed the success rate (defined as a minimal sensorimotor composite score of 14 out of 16 points at 30 min), onset time as well as the incidence of surgical anesthesia (defined as the ability to complete surgery without local infiltration, supplemental blocks, intravenous opioids, or general anesthesia). Postoperatively, the blinded observer contacted patients with successful blocks to inquire about the duration of motor block, sensory block, and postoperative analgesia. The main outcome variable was the duration of motor block. RESULTS: No intergroup differences were observed in terms of technical execution (performance time/number of needle passes/procedural pain complications), onset time, success rate, and surgical anesthesia. Furthermore, all three doses of dexamethasone provided similar durations of motor block (14.9-16.1 hours) and sensory block. Although 5 mg provided a longer analgesic duration than 2 mg, the difference (2.7 hours) fell within our pre-established equivalence margin (3.0 hours). CONCLUSIONS: 2, 5, and 8 mg of dexamethasone provide clinically equivalent sensorimotor and analgesic durations for ultrasound-guided infraclavicular block. Further trials are required to compare low (ie, 2 mg) and ultra-low (eg, 0.5-1 mg) doses of perineural dexamethasone for brachial plexus blocks. TRIAL REGISTRATION NUMBER: TCTR20150624001.

Reduced Hemidiaphragmatic Paresis With a "Corner Pocket" Technique for Supraclavicular Brachial Plexus Block: Single-Center, Observer-Blinded, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Hemidiaphragmatic paresis is common after supraclavicular brachial plexus block (SCBPB). In this randomized trial, we compared the incidence of hemidiaphragmatic paresis in patients who had local anesthetic injected primarily in the corner pocket (defined as the intersection of the first rib and subclavian artery) during SCBPB with that of patients who underwent injection primarily inside the neural cluster. METHODS: Thirty-six patients scheduled for right elbow, forearm, wrist, or hand surgery under SCBPB (using 12.5 mL of 0.75% ropivacaine and 12.5 mL of 2% lidocaine with 1:200,000 epinephrine) were randomly assigned to 1 of 2 groups. In group CP, local anesthetic was injected primarily in the corner pocket (20 mL) and secondarily inside the neural cluster (5 mL). In group NC, local anesthetic was deposited primarily inside the neural cluster (20 mL) and secondarily in the corner pocket (5 mL). The primary outcome was the incidence of hemidiaphragmatic paresis, as measured by M-mode ultrasonography 30 minutes after SCBPB. RESULTS: The incidence of hemidiaphragmatic paresis was significantly lower in group CP than in group NC (27.8% vs 66.7%, P = 0.019). The median decreases in forced expiratory volume at 1 second (7.5% [interquartile range, 3.3%-17.1%] vs 24.4% [interquartile range, 10.2%-31.2%]; P = 0.010) and forced vital capacity (6.4% [interquartile range, 3.3%-11.1%] vs 19.3% [interquartile range, 13.7%-33.2%]; P = 0.001) were also lower in group CP than in group NC. CONCLUSIONS: The incidence of hemidiaphragmatic paresis was effectively reduced when local anesthetic was injected primarily in the corner pocket during right-sided SCBPB. However, the 28% incidence of hemidiaphragmatic paresis associated with the corner pocket technique may still represent a prohibitive risk for patients with preexisting pulmonary compromise. CLINICAL TRIAL REGISTRATION: This study was registered at Clinical Trial Registry of Korea, identifier KCT0001769.

Comparison of Anterior Suprascapular, Supraclavicular, and Interscalene Nerve Block Approaches for Major Outpatient Arthroscopic Shoulder Surgery: A Randomized, Double-blind, Noninferiority Trial.

BACKGROUND: The interscalene nerve block provides analgesia for shoulder surgery, but is associated with diaphragm paralysis. One solution may be performing brachial plexus blocks more distally. This noninferiority study evaluated analgesia for blocks at the supraclavicular and anterior suprascapular levels, comparing them individually to the interscalene approach. METHODS: One hundred-eighty-nine subjects undergoing arthroscopic shoulder surgery were recruited to this double-blind trial and randomized to interscalene, supraclavicular, or anterior suprascapular block using 15 ml, 0.5% ropivacaine. The primary outcome was numeric rating scale pain scores analyzed using noninferiority testing. The predefined noninferiority margin was one point on the 11-point pain scale. Secondary outcomes included opioid consumption and pulmonary assessments. RESULTS: All subjects completed the study through the primary outcome analysis. Mean pain after surgery was: interscalene = 1.9 (95% CI, 1.3 to 2.5), supraclavicular = 2.3 (1.7 to 2.9), suprascapular = 2.0 (1.4 to 2.6). The primary outcome, mean pain score difference of supraclavicular-interscalene was 0.4 (-0.4 to 1.2; P = 0.088 for noninferiority) and of suprascapular-interscalene was 0.1 (-0.7 to 0.9; P = 0.012 for noninferiority). Secondary outcomes showed similar opioid consumption with better preservation of vital capacity in the anterior suprascapular group (90% baseline [P < 0.001]) and the supraclavicular group (76% [P = 0.002]) when compared to the interscalene group (67%). CONCLUSIONS: The anterior suprascapular block, but not the supraclavicular, provides noninferior analgesia compared to the interscalene approach for major arthroscopic shoulder surgery. Pulmonary function is best preserved with the anterior suprascapular nerve block.

Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures.

Successful recovery from a subclavicular ulcer caused by lenvatinib for thyroid cancer: a case report.

BACKGROUND: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding. CASE PRESENTATION: We report a case of a 53-year-old woman, who underwent repeated neck dissections and RAI therapy after total thyroidectomy in an outside hospital. Pathology revealed a papillary carcinoma of the tall cell variant. Locoregional recurrence was not under control; therefore, she visited our hospital. Although surgery was performed for locoregional recurrences three times in our hospital, they were not under control and distant metastases were found in the lung and bone a year later. Therefore, although sorafenib was initiated, the locoregional recurrence progressed 6 months later and computed tomography (CT) showed a 7-cm mass in the right subclavicular lesion. Lenvatinib was started at a dose of 24 mg daily. However, although tumor was rapidly reduced, an ulcer occurred in the right subclavicular lesion and was gradually increasing in size. The pulsation of subclavicular artery was found in the deep portion of the ulcer. Therefore, a pectoralis major myocutaneous flap was transplanted to cover the ulcer. Lenvatinib was an antiangiogetic TKI; therefore, it was preoperatively discontinued for 8 days and postoperatively for 12 days. The postoperative course was uneventful. CONCLUSIONS: Fistula formation or bleeding is known to be a severe side effect of antiangiogenic TKIs such as lenvatinib or sorafenib. There is a possibility that severe complications can occur when initiating TKIs in patients whose tumor has invaded into the skin, vessels, trachea, esophagus, and other areas. Therefore, it is necessary to use antiangiogenic TKIs very carefully. It is important to determine the appropriate time to start TKIs; however, there is no established protocol for this, and it is a problem that needs urgent attention.

Management of complex regional pain syndrome type I in upper extremity-evaluation of continuous stellate ganglion block and continuous infraclavicular brachial plexus block: a pilot study.

UNLABELLED: Interventional pain management techniques play an important role in the multidisciplinary approach to management of complex regional pain syndrome (CRPS). In this preliminary study we compared the efficacy of continuous stellate ganglion (CSG) block with that of continuous infraclavicular brachial plexus (CIBP) block in management of CRPS type I of upper extremity. METHODS: Thirty-three patients with CRPS type I of upper extremity were randomly assigned to either CSG or CIBP group. Patients were treated for 1 week with continuous infusion of 0.125% bupivacaine at 2and 5mL/h, respectively. Catheter was removed at 1 week and patients were followed up for 4 weeks. The outcome was evaluated in terms of neuropathic pain scale score (NPSS), edema scores (Grades 0-2), and range of motion (ROM) of all upper extremity joints (Grades 0-2). RESULTS: CIBP group showed statistically significant improvement in NPSS compared with CSG group during the first 12 hours after the procedures (P value <0.05). After 12 hours, the NPSS was comparable between the groups. At 4 weeks, both groups showed clinically significant improvement in edema score and ROM of all upper extremity joints when compared with the baseline. CONCLUSION: This preliminary study suggests that CIBP block and CSG block may be feasible and effective interventional techniques for the management of CRPS type I of upper extremities. Hence, we recommend a larger well-randomized, well-controlled, clinical trial to confirm our findings and determine if any significant difference exists between the groups in terms of long-term pain relief and functional restoration.

Symptomatic phrenic nerve palsy after supraclavicular block in an obese man.

Regional anesthesia has an expanding role in upper extremity surgery. Brachial plexus blocks offer several advantages including providing effective analgesia, reducing narcotic requirements, and facilitating ambulatory care surgery. Despite the popularity of nerve blocks, the surgeon must not forget the complications associated with regional anesthesia. This article describes a case of symptomatic phrenic nerve palsy after supraclavicular brachial plexus block in an obese man. A 46-year-old obese man underwent a left-sided supraclavicular block in preparation for decompression of Guyon's canal for ulnar mononeuropathy at the wrist. The patient experienced acute-onset dyspnea, chest discomfort, and anxiety, and physical examination demonstrated reduced breath sounds in the left hemithorax. Chest radiographs documented elevation of the left hemidiaphragm consistent with an iatrogenic phrenic nerve palsy. The patient was admitted for 23-hour observation and underwent an uncomplicated ulnar nerve decompression under Bier block anesthesia 1 week later. No long-term sequelae have been identified; however, there was a delay in surgical care, admission to the hospital, and transient pulmonary symptoms. We attribute this complication to significant abdominal obesity causing compromised pulmonary reserve and poor tolerance of transient hemidiaphragmatic paresis. In recent studies, waist circumference and abdominal height were inversely related to pulmonary function. We suspect that the incidence of symptomatic phrenic nerve palsy associated with brachial plexus blocks will increase as the prevalence of obesity increases in this country.

Potential conversion of adult clavicle-derived chondrocytes into neural lineage cells in vitro.

Neural stem cells (NSC) can be isolated from a variety of adult tissues and become a valuable cell source for the repair of peripheral and central nervous diseases. However, their origin and identity remain controversial because of possible de-differentiation/trans-differentiation or contaminations by hematopoietic stem cells (HSCs) or mesenchymal stem cells (MSCs). We hypothesize that the commonly used NSC culture medium can induce committed cartilage chondrocytes to de-differentiate and/or trans-differentiate into neural cell lineages. Using a biological isolation and purification method with explants culture, we here show that adult rat clavicle cartilage chondrocytes migrate out from tissue blocks, form sphere-like structures, possess the capability of self-renewal, express nestin and p75NTR, markers for neural crest progenitors, and differentiate into neurons, glia, and smooth muscle cells. Comparing with adult cartilage, the spherical-forming neural crest cell-like cells downregulate the chondrocytic marker genes, including collagen II, collagen X, and sox9, as well as neural-lineage repressors/silencers REST and coREST, but upregulate a set of well-defined genes related to neural crest cells and pro-neural potential. Nerve growth factor (NGF) and glial growth factor (GGF) increase glial and neuronal differentiation, respectively. These results suggest that chondrocytes derived from adult clavicle cartilage can become neural crest stem-like cells and acquire neuronal phenotypes in vitro. The possible de-differentiation/trans-differentiation mechanisms underlying the conversion were discussed.

Double- vs. single-injection infraclavicular plexus block in the emergency setting: higher success rate with lower volume of local anaesthetic.

BACKGROUND AND OBJECTIVES: Infraclavicular plexus block has many advantages of particular interest in the emergency setting. However, the number of nerve stimulations needed to optimize the technique remains unclear. We evaluated both the local anaesthetic requirement and the success rate of Sim's derived infraclavicular plexus block performed with a nerve stimulator when either one or two responses were sought. METHODS: In this prospective study, 50 patients who presented for distal upper limb surgery were randomized into two groups: in Group 1, ropivacaine 0.75% 40 mL was injected when nerve stimulation elicited a distal motor response (median, ulnar or radial). In Group 2, only 30 mL of the same local anaesthetic was injected, 7 mL to the musculocutaneous nerve and 23 mL to the median, ulnar or radial nerves. Sensory and motor blocks were tested at 5-min intervals over 30 min. RESULTS: The time to perform the block was similar in both groups. The success rate of the block increased from 80% in the single-stimulation group to 92% in the double-stimulation group (not significant). The onset time of sensory and motor block was shorter and block extension was greater in ulnar, antebrachial cutaneous and brachial cutaneous nerve distributions in the multistimulation group (P < 0.05). CONCLUSIONS: We conclude that only 30 mL of local anaesthetic seems to be sufficient to ensure a high level of success when performing an infraclavicular block with stimulation of both the musculocutaneous nerve and median, ulnar or radial nerve.