Recent Strategies to Combat Biofilms Using Antimicrobial Agents and Therapeutic Approaches.

Biofilms are intricate bacterial assemblages that attach to diverse surfaces using an extracellular polymeric substance that protects them from the host immune system and conventional antibiotics. Biofilms cause chronic infections that result in millions of deaths around the world every year. Since the antibiotic tolerance mechanism in biofilm is different than that of the planktonic cells due to its multicellular structure, the currently available antibiotics are inadequate to treat biofilm-associated infections which have led to an immense need to find newer treatment options. Over the years, various novel antibiofilm compounds able to fight biofilms have been discovered. In this review, we have focused on the recent and intensively researched therapeutic techniques and antibiofilm agents used for biofilm treatment and grouped them according to their type and mode of action. We also discuss some therapeutic approaches that have the potential for future advancement.

Presynaptic NMDARs on spinal nociceptor terminals state-dependently modulate synaptic transmission and pain.

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca2+ influx via PreNMDARs. Small conductance Ca2+-activated K+ (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization.

Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery.

Neural stem cell (NSC) transplantation is a promising strategy for replacing lost neurons following spinal cord injury. However, the survival and differentiation of transplanted NSCs is limited, possibly owing to the neurotoxic inflammatory microenvironment. Because of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages, we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase (AR), a key enzyme in the polyol pathway of glucose metabolism, would provide a more beneficial microenvironment for NSC survival and differentiation. Here, we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries. M2 macrophages promoted the differentiation of NSCs into neurons in vitro. Transplantation of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional recovery. Our findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.

The twisted structure of the rat Achilles tendon.

The rat is frequently used as a model to study the characteristics, aetiology and pathology of the Achilles tendon. However, though the structure of the human Achilles tendon has been extensively investigated, the anatomical structure of the rat Achilles tendon remains unclear, which impedes the ability to use rats to study Achilles tendinopathy. The purpose of this study was to reveal the structure of the rat Achilles tendon and to explore its similarities with the human Achilles tendon through an anatomical dissection of 80 rat Achilles tendons (40 female, 40 male). This study found that the subtendons of the rat Achilles tendon originating from the triceps surae muscle were twisted, and each subtendon also had its own torsion. The extent of these two types of torsion could be very different between rats. Alterations in this torsion may result in distinct stress fields in the Achilles tendon, which may play a critical role in the pathogenesis of Achilles tendinopathy. This study provides an important basis to support the use of rats as model animals to investigate the characteristics of the human Achilles tendon and Achilles tendinopathy.

An Optimized Enhanced Recovery After Surgery (ERAS) Pathway Improved Patient Care in Adolescent Idiopathic Scoliosis Surgery: A Retrospective Cohort Study.

OBJECTIVE: An optimized Enhanced Recovery After Surgery (ERAS) program is lacking for adolescent idiopathic scoliosis (AIS). The aim of the present study was to evaluate the impact and feasibility of an optimized ERAS pathway in patients with surgically treated AIS. METHODS: In total, 79 patients with AIS who underwent corrective surgery without 3-column osteotomy were recruited from Xijing Hospital of the Fourth Military Medical University between 2012 and 2018. Forty-four patients were treated according to a traditional protocol and 35 were managed using an optimized ERAS pathway, which was designed and implemented by a multidisciplinary team. The following data were collected and retrospectively analyzed, demographic characteristics, Cobb angle, curve type (Lenke), surgical duration, fusion level, correction rate, estimated blood loss, postoperative hemoglobin level, postoperative pain score, pain relief time, hemovac drainage, drainage removal time, first ambulation time, length of hospital stay, and postoperative complications. RESULTS: There was no significant difference between the traditional and ERAS groups with respect to demographic characteristics, Cobb angle, curve type (Lenke), fusion level, and correction rate. However, the ERAS group had a shorter surgical duration, less blood loss and hemovac drainage, a higher postoperative hemoglobin level, and earlier pain relief, ambulation, and discharge. The rates of postoperative nausea and vomiting were lower in the ERAS group than in the traditional group. CONCLUSIONS: The ERAS pathway is capable of improving the perioperative status of patients with AIS by offering stronger analgesia, faster ambulation, and earlier discharge.

Neurological complications of thoracic posterior vertebral column resection for severe congenital spinal deformities.

PURPOSE: The risk of neurological injury during vertebral column resection is high. In this study, we investigated the incidence and risk factors for neurological complications when treating spinal deformities by thoracic posterior vertebral column resection (PVCR). METHODS: Between 2008 and 2013, there were 62 consecutive patients (34 female patients and 28 male; the mean age: 16.3 years, range 6-46 years) treated with thoracic PVCR. We retrospectively reviewed the clinical records to obtain demographic and radiographic data, operative time, estimated blood loss (EBL, the ratio between circulating and lost blood), bleeding volume (the lost blood), number of vertebrae fused, number of vertebrae resected, usage of titanium mesh cage, and intraoperative neuromonitoring data. Multi-factor logistic regression was used to find the major risk factors for neurological complications. RESULTS: The average follow-up period was 46 months (range 24-88 months); no patients were lost to follow up. The average operative time was 524.8 ± 156.8 min (range 165.0-880.0 min), the average bleeding volume was 2585 ± 2210 ml (100-9600 ml), and the average estimated blood loss was 75.8% (9-278%). Ten patients (16.1%) developed post-operative neurological complications (nine transient and one permanent). Multi-factor logistic regression revealed that the risk factors for neurological complications were age ≥18 years, pulmonary dysfunction, and EBL >50%. CONCLUSIONS: Thoracic PVCR can lead to satisfactory outcomes in the treatment of severe spinal deformities. Risk factors for neurological complications include the age over 18 years, presence of pulmonary dysfunction, and EBL greater than 50%. The pulmonary dysfunction can be regarded as the most valuable indicator to measure the severity of the spine deformity.

Safety and Efficacy of Single-Stage Surgical Treatment for Congenital Scoliosis Associated with Intraspinal Mass.

For congenital scoliosis associated with intraspinal anomaly, surgical treatment is often advocated. However, the safety and efficacy of single-stage intraspinal mass resection and scoliosis correction remain unclear. The purpose of this study was to retrospectively evaluate the feasibility and risk factors of single-stage surgical treatment for congenital scoliosis associated with intraspinal mass. Patients' clinical records were reviewed for demographic and radiographic data, operating time, intraoperative blood loss, perioperative complications, and postoperative pathologic results. Two female and 5 male patients with an average age of 19.14 ± 7.52 years (range, 11-31 years) were evaluated. Patients were followed for a minimum of 24 months after initial surgical treatment, with an average of 49.71 ± 32.90 months (range, 27-99 months). Spinal curvature was corrected from an average of 69.57 ± 20.44° to 29.14 ± 9.87°, demonstrating a mean correction rate of 55.05% ± 18.75%. No obvious loss of correction was observed at the final follow-up. Complications included transient neurologic deficit, cerebrospinal fluid leakage, and intraspinal mass recurrence in 1 patient each. There was no paralysis or permanent nerve damage. In conclusion, simultaneous intraspinal mass resection and scoliosis correction appears to be safe and effective.

Safety and Efficacy of One-stage Spinal Osteotomy for Severe and Rigid Congenital Scoliosis Associated with Split Spinal Cord Malformation.

STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To retrospectively evaluate the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and progressive congenital scoliosis (CS) associated with split spinal cord malformation (SSCM). SUMMARY OF BACKGROUND DATA: For severe and rigid spinal deformity, spinal osteotomies are often advocated for correcting the deformity. However, the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and rigid CS with SSCM have been unclear thus far. METHODS: Patients were treated by one-stage spinal osteotomy between September 2007 and June 2011 in our hospital. The clinical records were reviewed for demographic and radiographical data, operative time, intraoperative blood loss, blood transfusion, perioperative complications, and functional outcomes. RESULTS: There were 18 females and 11 males with an average age of 15.5 ± 3.6 years (range, 12-28 yr). Spinal cord was longitudinally split by a bony spur in 11 patients (type I SSCM) and by a fibrous band in 18 patients (type II SSCM). Patients were observed for a minimum of 24 months after initial surgical treatment with an average follow-up of 43.0 ± 17.1 months (range 24-68 mo) from September 2007 to June 2013. The mean operative time and average blood loss of type ISSCM was significantly greater than those of type II SSCM (P < 0.05). The major curve was corrected from an average of 97.2°± 17.8° to 35.7°± 15.9°, a mean correction rate of 64.3% ± 11.0%. The average loss of correction at final follow-up was 2.9% for major curves. The overall complication rate was 24.1%, including transient neurological deterioration in 3 patients, cerebrospinal fluid leakage in 2 patients, urinary tract infection in 1 patient and pleural rupture in 1 patient. CONCLUSION: Relative to multistage corrective surgery, one-stage spinal osteotomy is effective for the correction of severe CS and SSCM without increasing the rate of surgical complications. However, surgical treatment of type I SSCM does require more operating time and blood loss. LEVEL OF EVIDENCE: 4.

Surgical Treatment of Congenital Scoliosis Associated With Tethered Cord by Thoracic Spine-shortening Osteotomy Without Cord Detethering.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To investigate the safety and efficacy of spine-shortening osteotomy for congenital scoliosis with tethered cord. SUMMARY OF BACKGROUND DATA: Conventional surgery for congenital scoliosis associated with tethered cord risks the complications of detethering. Spine-shortening osteotomy holds the potential to correct scoliosis and decrease spinal cord tension simultaneously without an extra detethering procedure, but no data on this issue is available. METHODS: 21 patients (14 females and 7 males, average age 15.4 yr) underwent spine-shortening osteotomy without detethering. All of the patients had tethered cord. Patients with main curve more than 90° underwent vertebral column resection (VCR), whereas the others had pedicle subtraction osteotomy (PSO) performed. The average postoperative follow-up period was 45.2 months. RESULTS: The mean operation time was 544.5 min with average blood loss of 2769.1 ml. The deformity correction was 61.3% in the coronal plane and 43.9° in the sagittal plane. 10 patients had neurological deficits preoperatively. At the final follow-up, the deficits in 8 (80%) patients were significantly improved, whereas 2 (20%) remained unchanged. At final follow-up, 71.4% (5/7) patients reported improvement in motor function, 100% (3/3) had improved pain scores, and 75% (3/4) reported better sensory function after the spine-shortening osteotomy. Urinary dysfunction and bowel incontinence present preoperatively in 3 patients all recovered by final follow-up. 5 (23.8%) patients incurred complications including temporary neurological deterioration in 1 patient, urinary tract infection in 2 patients, cerebrospinal fluid leakage in 1 patient, and blood loss more than 5000 ml in 1 patient. CONCLUSION: Spine-shortening osteotomy is a safe and effective procedure for congenital scoliosis associated with tethered cord. Spine-shortening osteotomy at the thoracic apical vertebrae level not only corrects the spine deformity but also simultaneously releases the tension of the tethered cord, resulting in improved neurologic function.

Successful treatment of a patient with congenital kyphoscoliosis associated with tethered cord.

Tethered cord is a common finding in congenital scoliosis. The most frequently advocated approach for this condition is to perform prophylactic detethering of the cord before scoliosis corrective surgery. The authors report on a 14-year-old patient with congenital thoracic kyphoscoliosis associated with a tethered cord, who developed progressive paraparesis and was successfully treated by posterior spine shortening osteotomy alone without prophylactic untethering. The patient had a 103° scoliotic curve together with a 93° kyphotic curve with an apical vertebra of T-7. Furthermore, he developed a significant progression of neurological deficits, including weakness of both legs and urinary and bowel incontinence. Preoperative MRI revealed that the spinal cord was entrapped by the apical vertebra and the low-placed conus medullaris was at approximately L-5. A posterior vertebral column resection of T-7 was performed for the purpose of simultaneously correcting the kyphoscoliosis and releasing tension on the tethered cord without a true detethering surgery. The patient's spinal cord function recovered completely from Frankel D to Frankel E by 6 months after the procedure. Evaluation at 31 months after surgery showed maintenance of good curve correction and normal neurological function.

Non-fusion and growing instrumentation in the correction of congenital spinal deformity associated with split spinal cord malformation: an early follow-up outcome.

STUDY DESIGN: A retrospective case review. INTRODUCTION: To evaluate the safety and efficacy of the non-fusion technique in achieving and maintaining the proper correction for congenital spinal deformity (CSD) and allowing normal spinal growth in patients with split spinal cord malformation (SSCM). MATERIALS AND METHODS: Seven patients who had CSD and SSCM were adopted, with a mean age of 8 years. All the patients in this study received Halo-gravity traction (HGT) prior to expansion of the spine and instrumentation with vertical expandable titanium prosthetic rib, growing rod or their hybrid. Five of them underwent opening wedge thoracoplasty simultaneously. And the two patients with type I SSCM underwent bony spur excision in the initial surgery before corrective manipulation. Then all the patients received a lengthened operation every six months. Changes of their major curve and length of T1-S1 spine were measured, and complications, neurological status were recorded. All the patients were followed up with an average of 32.6 months. RESULTS: Their mean major curve improved from 90.1° to 58.6° with a correction rate of 34.9 %. The T1-S1 length increased from 26.3 to 34.7 cm at final follow-up. Especially, one of the type I SSCM patients whose neurological deterioration was found preoperatively was significantly improved. CONCLUSION: Preoperative Halo-gravity traction followed by non-fusion and growing instrumentation may be effective and safe for young children of CSD associated with SSCM. But it is an ongoing study and additional large multicenter studies are necessary to further assess the safety and efficacy of non-fusion and growing instrumentation.

Staged corrective surgery for complex adolescent kyphoscoliosis caused by back scalding during the childhood period.

INTRODUCTION: Adolescent scar contracture kyphoscoliosis is a very rare disease. METHODS AND RESULTS: Here, we present the case of a 21-year-old man who was scalded due to ebullient water when he was 10 years old. Moreover, kyphoscoliosis was found when he was 12 years old and developed rapidly. Thereafter, no management was proposed before his consultation at our center. On examination, kyphoscoliosis was detected in thoracolumbar, the trunk deviated to the right on standing view, extensive contractured scar presented on the right side of the back, abdomen, chest wall, hip, right thighs and armpit anterior, especially in the right flank. A one-stage correction was deemed too risky, we therefore released contractured scar during the first stage with the defect of soft tissue protected by vacuum sealing drainage and then performed skeletal traction with halo and bilateral femoral pins. A reasonable correction was achieved without any neurological deficits 1 month after traction. Next, a second-stage operation was taken to translate a free anterolateral thigh myocutaneous flap to overlay the extensive defect of soft tissue. 1.5 months later, a third posterior segmental pedicle screw instrumented fusion with Smith-Peterson osteotomy between T9 and L2 was performed. Postoperative recovery was uneventful and as there were no complications, he was discharged 10 days after the third surgery. At 2-year follow-up the patient's outcome is excellent with balance and correction of the deformity. CONCLUSION: Based this grand round case and relevant literature, we discuss the different options for the treatment of adolescent scar contracture scoliosis.

Safety and efficacy of 1-stage surgical treatment of congenital spinal deformity associated with split spinal cord malformation.

STUDY DESIGN: Retrospective clinical study. OBJECTIVE: The aim of this study was to evaluate retrospectively the safety and efficacy of 1-stage surgical treatment of 45 consecutive patients, who had progressive congenital spinal deformity associated with split spinal cord malformation (SSCM). SUMMARY OF BACKGROUND DATA: For correction of progressive congenital spinal deformity with SSCM, it has been reported that all SSCM should be operated on before any orthopedic intervention, and then surgery for correction and stabilization of the spinal deformity should be performed 3 to 6 months later. Recently, different viewpoints have been approved, and the common treatment of these 2 associated conditions needs to be re-evaluated. METHODS: Patients had 1-stage surgery. After exposure of the determined levels and placement of instruments, bony spur was resected in the patients of type 1; in patients of type 2, we did nothing to the SSCM. In the corrective stage of surgery, posterior fusion surgery was performed in 38 patients; nonfusion surgery was performed in 7 patients. RESULTS: Thirty-six female patients and 9 male patients formed the basis of the study. The mean age was 14 years, and the mean follow-up period was 31 months. Type 1 SSCM was in 15 patients, and type 2 SSCM was in 30 patients. Seven patients had progressive neurological deteriorations preoperatively. The mean major curves were corrected from an average of 73.7° to 33.5°, with a correction rate of 54.5%. The overall complication was transient, including 2 patients of neurological compromise and 1 patient of cerebrospinal fluid leakage. The average loss of correction at final follow-up was 2.5° for major curves. CONCLUSION: The 1-stage surgical treatment of congenital spinal deformity associated with SSCM provides a satisfactory option to improve the spinal deformity without significant complications effectively. Neurosurgical interventions are recommended to patients with type 1 SSCM before spinal deformity surgery; however, patients with type 2 SSCM can be treated safely without a need of neurosurgical intervention.

Atorvastatin reduces calcification in rat arteries and vascular smooth muscle cells.

To examine the in vivo effects of atorvastatin (AT) on arterial calcification in rats, arterial calcification was established by subcutaneous injection of vitamin D3 and Warfarin. Intragastric administration of AT began 4 days before establishment of arterial calcification in the AT group (n=6). Blood samples were taken and abdominal aortas were collected and stained. After induction of calcification, plasma Ca(2+) levels in the CA and AT groups were significantly higher than those before treatment and in the untreated controls. Plasma Ca(2+) levels in the AT group were significantly lower than in the CA group. The relative calcification area in aortic specimens from the AT group was significantly smaller than in the CA group. Rat aortic vascular smooth muscle cells (VMSC) were isolated from abdominal aortic segments and pre-treated with AT (1, 5, or 10 µM) for 24 hr. Cells in the calcification (CA) group and the AT group were cultured with ß-glycerophosphate, insulin and vitamin C for 14 days to induce cell calcification. Calcium deposition and alkaline phosphatase activity were significantly increased in the CA group compared to untreated controls (p<0.01). This effect was ameliorated by AT (all p<0.01). In vivo administration of AT reduced arterial calcification and plasma Ca(2+) concentration. In vitro, AT reduced calcification markers in rat aortic vascular smooth muscle cells.

[The effect of alendronate on arterial calcification in rat model].

OBJECTIVE: To study the effect of alendronate on artery calcification in rats. METHODS: (1) 4-week SD male rats were randomly divided into 3 groups: alendronate group (AL, n = 6), calcification group (CA, n = 6) and normal group (N, n = 6). In AL and CA group, artery calcification of rat was established by subcutaneous injection of vitamin D3 (300,000 U x kg(-1) x d(-1) for 3 days) and Warfarin (15 mg x 100 g(-1) x 12 h(-1) for 4 days); In AL group, at 4 days before establishment of artery calcification, alendronate (1 mg x kg(-1) x 24 h(-1)) was administered with subcutaneous injection and continued to be given to the end of the study. Abdominal aortae were collected for paraffin section and stained with von Kossa staining to observe the area of calcification. (2) Rat aortic vascular smooth muscle cells (VSMC) were cultured in vitro with tissue explant. All cells were divided into 5 groups: normal group, calcification group (control group), and alendronate 10(-9), 10(-7) and 10(-5) mol/L group. Before inducing calcification, alendronate 10(-9), 10(-7) and 10(-5) mol/L group were individually pre-treated with final concentrations of 10(-9), 10(-7) and 10(-5) mol/L alendronate for 24 hours. Beta-glycerophosphate were then added in the calcification group and in all the alendronate groups to induce VSMC calcification. All cells were cultured for 14 days. Cell crawling slice was applied to Alizarin red S staining to observe VSMC calcification. Colorimetric method was applied to measure the contents of Ca2+, cell proteins, and ALP activity. The ratio of contents of Ca2+ and cell proteins was cell calcium deposits. Cell proliferation was measured with tetrazolium salt (MTT) method. RESULTS: (1) With von Kossa staining the black deeply stained structure was found to be decreased in AL group. (2) As compared with the control group, in all the alendronate groups, showed that the number of calcium nodules [(6.8 +/- 2.7, 6.2 +/- 4.2, 5.3 +/- 2.4) % vs (7.4 +/- 3.8)%], and cell calcium depositions [(5.2 +/- 1.2, 4.8 +/- 1.7, 3.5 +/- 1.8)% vs (5.6 +/- 1.6)%], cell ALP activity and cell proliferation decreased significantly and dose-dependently. CONCLUSION: Alendronate can inhibit the artery calcification in rats.