Phytic Acid Maintains Peripheral Neuron Integrity and Enhances Survivability against Platinum-Induced Degeneration via Reducing Reactive Oxygen Species and Enhancing Mitochondrial Membrane Potential.

Phytic acid (PA) has been reported to possess anti-inflammatory and antioxidant properties that are critical for neuroprotection in neuronal disorders. This raises the question of whether PA can effectively protect sensory neurons against chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy is a dose-limiting side effect of chemotherapy treatment often characterized by severe and abnormal pain in hands and feet resulting from peripheral nerve degeneration. Currently, there are no effective treatments available that can prevent or cure peripheral neuropathies other than symptomatic management. Herein, we aim to demonstrate the neuroprotective effects of PA against the neurodegeneration induced by the chemotherapeutics cisplatin (CDDP) and oxaliplatin. Further aims of this study are to provide the proposed mechanism of PA-mediated neuroprotection. The neuronal protection and survivability against CDDP were characterized by axon length measurements and cell body counting of the dorsal root ganglia (DRG) neurons. A cellular phenotype study was conducted microscopically. Intracellular reactive oxygen species (ROS) was estimated by fluorogenic probe dichlorofluorescein. Likewise, mitochondrial membrane potential (MMP) was assessed by fluorescent MitoTracker Orange CMTMRos. Similarly, the mitochondria-localized superoxide anion radical in response to CDDP with and without PA was evaluated. The culture of primary DRG neurons with CDDP reduced axon length and overall neuronal survival. However, cotreatment with PA demonstrated that axons were completely protected and showed increased stability up to the 45-day test duration, which is comparable to samples treated with PA alone and control. Notably, PA treatment scavenged the mitochondria-specific superoxide radicals and overall intracellular ROS that were largely induced by CDDP and simultaneously restored MMP. These results are credited to the underlying neuroprotection of PA in a platinum-treated condition. The results also exhibited that PA had a synergistic anticancer effect with CDDP in ovarian cancer in vitro models. For the first time, PA's potency against CDDP-induced PN is demonstrated systematically. The overall findings of this study suggest the application of PA in CIPN prevention and therapeutic purposes.

Electrical stimulation enhances mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathy.

Electrical stimulation (ESTIM) has shown to be an effective symptomatic treatment to treat pain associated with peripheral nerve damage. However, the neuroprotective mechanism of ESTIM on peripheral neuropathies is still unknown. In this study, we identified that ESTIM has the ability to enhance mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathies (CIPNs). CIPN is a debilitating and painful sequalae of anti-cancer chemotherapy treatment which results in degeneration of peripheral nerves. Mitochondrial dynamics were analyzed within axons in response to two different antineoplastic mechanisms by chemotherapy drug treatments paclitaxel and oxaliplatin in vitro. Mitochondrial trafficking response to chemotherapy drug treatment was observed to decrease in conjunction with degeneration of distal axons. Using low-frequency ESTIM, we observed enhanced mitochondrial trafficking to be a neuroprotective mechanism against CIPN. This study confirms ESTIM enhances regeneration of peripheral nerves by increased mitochondrial trafficking.

Mitochondrial trafficking as a protective mechanism against chemotherapy drug-induced peripheral neuropathy: Identifying the key site of action.

AIMS: Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect seen in patients who have undergone most chemotherapy treatments to which there are currently no treatment methods. CIPN has been shown to cause axonal degeneration leading to Peripheral Neuropathy (PN), which can lead to major dosage reduction and may prevent further chemotherapy treatment due to oftentimes debilitating pain. Previously, we have determined the site-specific action of Paclitaxel (PTX), a microtubule targeting agent, as well as the neuroprotective effect of Fluocinolone Acetonide (FA) against Paclitaxel Induced Peripheral Neuropathy (PIPN). MAIN METHODS: Mitochondrial trafficking analysis was determined for all sample sets, wherein FA showed enhanced anterograde (axonal) mitochondrial trafficking leading to neuroprotective effects for all samples. KEY FINDINGS: Using this system, we demonstrate that PTX, Monomethyl auristatin E (MMAE), and Vincristine (VCR), are toxic at clinically prescribed levels when treated focally to axons. However, Cisplatin (CDDP) was determined to have a higher toxicity when treated to cell bodies. Although having different targeting mechanisms, the administration of FA was determined to have a significant neuroprotective effect for against all chemotherapy drugs tested. SIGNIFICANCE: This study identifies key insights regarding site of action and neuroprotective strategies to further development as potential therapeutics against CIPN. FA was treated alongside each chemotherapy drug to identify the neuroprotective effect against CIPN, where FA was found to be neuroprotective for all drugs tested. This study found that treatment with FA led to an enhancement in the anterograde movement of mitochondria based on fluorescent imaging.

Surgical treatment of Candida albicans spondylodiscitis.

Introduction: Spinal infection poses a demanding diagnostic and treatment problem for which a multidisciplinary approach with spine surgeons, radiologists, and infectious disease specialists is required. Infections are usually caused by bacterial microorganisms, although fungal infections can also occur. Most patients with spinal infections diagnosed in the early stages can be successfully managed conservatively with antibiotics, bed rest, and spinal braces. In cases of gross or pending instability, progressive neurological deficits, failure of conservative treatment, spinal abscess formation, severe symptoms indicating sepsis, and failure of previous conservative treatment, surgical treatment is required. Case presentation: A 64-year-old male presented to the Outpatient Department with a complaint of pain in bilateral upper extremities for 4 months. The pain was shooting in type, radiating to bilateral arms, forearms, and hands with no aggravating and relieving factors. He is a known case of carcinoma pyriform sinus for which he underwent various cycles of chemotherapy. Ten years later, a tracheostomy was performed for laryngeal edema, and again, an endoscopic gastrostomy was performed due to feeding difficulties. He then developed fever and cervical pain along with pain in the bilateral upper extremities. An infectious etiology was suspected for which multiple antibiotics were started with no positive response. An MRI was performed, which was suggestive of spondylodiscitis probably of tubercular origin. A biopsy was done to confirm the diagnosis, following which antitubercular (HRZE) therapy was started. He was also treated with Duloxetine and gabapentin, which resulted in minor improvements. Subsequent MRIs showed diffuse involvement of the multiple cervical vertebrae along with cord compression. Two stages of anterior corpectomy followed by posterior instrumentation were done. Following the procedure, the patient developed an infection, which was managed with antibiotics. The titanium implant was not removed. A muscle graft was planned with the pectoralis muscle and flap closure was done. The tissue was also sent for Gram stain, AFB stain, and GeneXpert, which showed normal findings. Finally, in tissue culture, Candida albicans was isolated. On performing the enzyme immunoassay test, it was found to be Aspergillus (Galactomannan antigen) positive as well. Antitubercular treatment was stopped. Then, he was managed with an antifungal, oral voriconazole, for the duration of 1 and a half years. Clinical discussion: Patients diagnosed with Candida spondylodiscitis tend to have favorable outcomes, likely linked to timely identification, thorough surgical debridement, and proper azole medication. Our case achieved success by promptly identifying and confirming it through tissue culture, detecting spinal cord compression, decompressing it, and initiating specific antifungal treatment. A delay in commencing antifungal therapy has been associated with poorer outcomes, especially in neurological health. Our patient received voriconazole for a full year, suggesting that favorable outcomes are achievable for fungal spondylodiscitis with swift and appropriate surgery and antifungal medication. Conclusion: In summary, evaluation for fungal infection is essential in all cases of unexplained spinal infection in immunocompromised patients, regardless of presentation. If the antifungal treatment proves ineffective, a surgical approach is typically employed for the management of fungal spondylodiscitis. Our report details a successful case of fungal spondylodiscitis treated with a surgical approach and highlights the potential for a fungal infection to be a causative factor in noncompressive myelopathy, which may be sometimes mistaken for radiation myelitis.

Ultrasonography guided erector spinae block in spinal surgery for pain management with enhanced recovery: A comparative study.

Background: Improved and efficient management of pain can certainly aid enhanced recovery after spinal surgery. Our aim is to evaluate the effect of ESPB in thoracic and lumbar surgeries where we have evaluated VAS for pain, cumulative analgesics consumptions, length of hospital stay and post-operative complications. Methods: A cross-sectional comparative study done in HAMS among the erector spinae block group and control group. The analysis of different variable was done according to standard statistical analysis. For quantitative data, univariate and multivariate analysis was performed to determine statistically significant differences using student's t-test for continuous variables. Results: 60 patients were analyzed, 30 got spinae block and 30 in control group.The mean pain score for spinae block group were 1.90 ± 0.712 and 3.27 ± 1.230 for control group (p < 0.001). Cumulative mean analgesic consumption values for spinae block vs. control groups were 0.030 ± 0.042 mg vs. 0.091 ± 0.891 mg (p = 0.001) for fentanyl; 1.06E4 ± 2833.300 mg vs. 1.53E4 ± 2848.349 mg (p < 0.001) for paracetamol; 213 ± 64.656 mg vs. 494 ± 58.816 mg (p < 0.001) for ketorol; 5440.00 ± 2060.064 mg vs. 8667.50 ± 2275.006 mg (p < 0.001) for ibuprofen and 121.67 ± 31.303 mg vs. 185.00 ± 51.108 mg (p < 0.001) for tramadol. Conclusions: The ESPB technique shows early discharge from hospital and lower cumulative analgesics consumption which indicates enhanced recovery after spine surgery than control group. Improvement of pain using VAS shows immediate post-operative period recovery in those who receives spinae block.

Primary spinal Non-Hodgkin Lymphoma presenting as impending cauda equina syndrome: A case report.

Introduction: Malignant lymphoma (ML) can involve the central nervous system either primarily or by secondary spread, which tends to occur late in the disease as part of widespread dissemination. Lymphoma presenting as primary tumors of the spinal cord is extremely uncommon. Primary spinal lymphoma if detected early can have a good prognosis with no relapse after effective treatment. Case presentation: A 32 years old male patient presented with the symptoms of impending cauda equina syndrome which was managed with surgery and chemotherapy. The patient was successfully treated without the relapse of his condition at his 6 months follow-up scan.Discussion: Primary spinal non-Hodgkin lymphoma is a rare entity among extranodal non-Hodgkin lymphoma. MRI is usually non-confirmatory and needs immunohistochemistry for the correct diagnosis. R-CHOP regimen is the standard chemotherapy regimen. Surgical decompression is required in cases of impending neurological injury along with radiotherapy. Conclusion: Primary spinal epidural diffuse large B-cell lymphoma should be considered as a differential diagnosis in patients presenting with back pain and symptoms of impending cauda equina syndrome. It is important to early detect and treat the disease to prevent permanent neurological injury and metastasis.

Lipofibromatous hamartoma of sciatic nerve: A case report.

Introduction: Lipofibromatous hamartoma of the nerve is the fibro-fatty overgrowth within the nerve. Most commonly they occur in the median nerve, ulnar nerves, and a few other nerves but the involvement of the sciatic nerve is very rare. The fibro-fatty infiltration causes palpable neurogenic mass and clinically presents lump, moderate numbness, tingling sensation, and pain in its territory. Magnetic resonance imaging is the gold standard for diagnosis. Case presentation: We present a case of a 65 years old female, who presented to OPD with a tingling sensation which progressed to pain in the gluteal region and was associated with a tender swelling. MRI showed a giant space-occupying lesion in the sciatic nerve course. The mass was excised and then sent to the histopathological examination which designated the mass as lipofibromatous hamartoma. Discussion: Unless debilitating, lipomatosis of the nerve doesn't require any intervention as it is a benign condition. Lipofibromatous hamartoma is attributed to the accumulation of fatty and fibrous tissue in the epineurium. Diffusion-weighted imaging in association with conventional magnetic resonance imaging has increased diagnostic yield. The lesion was iso-intense to the subcutaneous fat and there were fine fibrillar appearances inside of it. Simple mass excision was performed on our patient without complications. Conclusion: Lipofibromatous hamartoma of the nerve are rare soft tissue tumors of nerves and sciatic nerve involvement is even rarer. Correct and careful interpretation of the MRI findings can lead to diagnosis with ease and help prevent unnecessary biopsies.

The Effect of Discharging Patients with Low Hemoglobin Levels on Hospital Readmission and Quality of Life after Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective cohort. PURPOSE: This study aims to evaluate the impact of anemia on functional outcomes, health-related quality of life (HRQoL), and early hospital readmission (EHR) rates after adult spinal deformity (ASD) surgery at the time of discharge from the hospital. OVERVIEW OF LITERATURE: Concerns with risks of transfusion, insufficient evidence for its benefits, and the possibility of associated adverse outcomes have led to restrictive transfusion practices. Therefore, patients are discharged according to patient blood management programs that are implemented in hospitals nationwide to reduce unnecessary blood transfusions. However, not many comprehensive kinds of studies exist on the effect of postoperative anemia on functional life and complications. METHODS: Anemia severity was defined following the 2011 World Health Organization guidelines. All patients had HRQoL tests as well as complete blood counts pre- and postoperatively. EHR is the admission within 30 days of discharge and was used as the dependent parameter. RESULTS: This study comprised 225 surgically treated ASD patients with a median age of 62.0 years, predominantly women (80%). Of the 225 patients, 82, 137, and six had mild, moderate, and severe anemia at the time of discharge, respectively. Seventeen of the patients (mild [11, 64.7%]; moderate [5, 29.4%]; severe [1, 5.9%]) were readmitted within 30 days. The mean hemoglobin values were higher in readmitted patients (p=0.071). Infection was the leading cause of readmission (n=12), but a low hemoglobin level was not observed in any of these patients at the time of discharge. Except for Scoliosis Research Society-22 questionnaire, HRQoL improvements did not reach statistical significance in early readmitted patients in the first year after surgery. CONCLUSIONS: The results of this study demonstrated that the occurrence and the severity of postoperative anemia are not associated with EHR in surgically treated patients with ASD. The findings of the current research suggested that clinical awareness of the parameters other than postoperative anemia may be crucial. Thus, improvements in HRQoL scores were poor in early readmitted patients 1 year after surgery.

Anterior Spinal Artery Syndrome: Rare Precedented Reason of Postoperative Plegia After Spinal Deformity Surgery: Report of 2 Cases.

BACKGROUND: Complications in spinal deformity surgery vary from insignificant to severe. Apart from direct mechanical insult, ischemia can also cause spinal cord injury. Ischemic injury may be detected during surgery or may manifest itself postoperatively. We present 2 cases of anterior spinal artery syndrome. CASE DESCRIPTION: In the first case, a 12-year-old girl developed anterior spinal artery syndrome resulting in total quadriplegia 8 hours after spinal deformity surgery. She was treated with a steroid, immunoglobulin, and low-molecular-weight heparin. She showed complete recovery at 1 year postoperatively both clinically and radiographically. In the second case, a 62-year-old woman experienced sudden loss of motor evoked potentials intraoperatively during dural tear repair after sagittal and coronal alignment was established. The paraplegic patient was diagnosed with anterior spinal artery syndrome at the thoracic level postoperatively. She was treated with a steroid and heparin. At 1 year postoperatively, she has gained much of her strength and has myelomalacia in her spinal cord. CONCLUSIONS: Anterior spinal artery syndrome is a serious condition with a generally poor prognosis. Though treatment should be directed at the underlying cause, the best strategy is to prevent it from occurring. Peroperative blood pressure control, intraoperative neuromonitoring, avoidance from mechanical stress during surgery, and close neurologic and hemodynamic monitorization postoperatively should be performed.

Does the Application of Topical Intrawound Vancomycin Powder Affect Deep Surgical Site Infection and the Responsible Organisms after Spinal Surgery?: A Retrospective Case Series with a Historical Control Group.

STUDY DESIGN: Retrospective case series with a historical control group. PURPOSE: To compare the deep wound infection rates in patients undergoing spinal surgery with the application of topical intrawound vancomycin powder (TIVP) in the surgical site in addition to standard systemic prophylaxis with those in a matched historical cohort of patients for whom TIVP was not used. OVERVIEW OF LITERATURE: Surgical site infection (SSI) after spine surgery is debilitating and is responsible for a significant increase in the health care costs, hospital stay, and morbidities. Although the application of TIVP before surgical closure is a promising method for reducing the SSI rate after spine surgery, its use is controversial, and currently, research trials are focusing on identifying its safety, efficacy, and the potential patient population. METHODS: A group of 88 patients who underwent posterior spinal surgery with TIVP administration (treatment group) was compared to a historical control group of 70 patients who had received only standard systemic intravenous prophylaxis (control group) for the analysis of deep SSI rate and the involved organisms. RESULTS: The overall rate of deep SSIs was 2.5% (4/158). All the SSIs were observed in patients who had posterior instrumentation and fusion for ≥3 levels. In the treatment group, the SSI rate was 3.4% (3/88), and the bacteria isolated were Escherichia coli (n=2) and Pseudomonas aeruginosa (n=1). In the control group, the infection rate was 1.4% (1/70), and the isolated bacteria were Morganella morganii and Staphylococcus epidermidis. No statistically significant association was found between the SSI rates of the treatment and control groups. CONCLUSIONS: Although the difference in the SSI rates was not statistically significant, the present results suggest that TIVP administration could not reduce the risk of deep SSIs after spinal surgery. Moreover, TIVP administration might also affect the underlying pathogens by increasing the propensity for gram-negative species.

The Influence of Diagnosis, Age, and Gender on Surgical Outcomes in Patients With Adult Spinal Deformity.

STUDY DESIGN: Retrospective review of prospectively collected data from a multicentric database. OBJECTIVES: To determine the clinical impact of diagnosis, age, and gender on treatment outcomes in surgically treated adult spinal deformity (ASD) patients. METHODS: A total of 199 surgical patients with a minimum follow-up of 1 year were included and analyzed for baseline characteristics. Patients were separated into 2 groups based on improvement in health-related quality of life (HRQOL) parameters by minimum clinically important difference. Statistics were used to analyze the effect of diagnosis, age, and gender on outcome measurements followed by a multivariate binary logistic regression model for these results with statistical significance. RESULTS: Age was found to affect SF-36 PCS (Short From-36 Physical Component Summary) score significantly, with an odds ratio of 1.017 (unit by unit) of improving SF-36 PCS score on multivariate analysis (P < .05). The breaking point in age for this effect was 37.5 years (AUC = 58.0, P = .05). A diagnosis of idiopathic deformity would increase the probability of improvement in Oswestry Disability Index (ODI) by a factor of 0.219 and in SF-36 PCS by 0.581 times (P < .05). Gender was found not to have a significant effect on any of the HRQOL scores. CONCLUSIONS: Age, along with a diagnosis of degenerative deformity, may have positive effects on the likelihood of improvement in SF-36 PCS (for age) and ODI (for diagnosis) in surgically treated patients with ASD and the breaking point of this effect may be earlier than generally anticipated. Gender does not seem to affect results. These may be important in patient counseling for the anticipated outcomes of surgery.

Cryo-Compression Therapy After Elective Spinal Surgery for Pain Management: A Cross-Sectional Study With Historical Control.

OBJECTIVE: Postoperative dynamic cryo-compression (DC) therapy has been proposed as a method of reducing pain and the inflammatory response in the early postoperative period after orthopedic joint reconstruction surgery. Our aim was to analyze the analgesic efficacy of DC therapy after adult lumbar spinal surgery. METHODS: DC was applied for 30 minutes every 6 hours after surgery. Pain was measured by a visual analogue scale (VAS) in the preoperative period, immediately after surgery, and every 6 hours postoperatively for the first 72 hours of the hospital stay. Patients' pain medication requirements were monitored using the patient-controlled analgesia system and patient charts. Twenty patients who received DC therapy were compared to 20 historical controls who were matched for demographic and surgical variables. RESULTS: In the postanesthesia care unit, the mean VAS back pain score was 5.87 ± 0.9 in the DC group and 6.95±1.0 (p=0.001) in the control group. The corresponding mean VAS scores for the DC vs. control groups were 3.8±1.1 vs. 5.4±0.7 (p < 0.001) at 6 hours postoperatively, and 2.7±0.7 vs. 6.25±0.9 (p<0.001) at discharge, respectively. The cumulative mean analgesic consumption of paracetamol, tenoxicam, and tramadol in the DC group vs. control group was 3,733.3±562.7 mg vs. 4,633.3±693.5 mg (p<0.005), 53.3±19.5 mg vs. 85.3±33.4 mg (p<0.005), and 63.3±83.4 mg vs. 393.3±79.9 mg (p<0.0001), respectively. CONCLUSION: The results of this study demonstrated a positive association between the use of DC therapy and accelerated improvement in patients during early rehabilitation after adult spine surgery compared to patients who were treated with painkillers only.