Surface-functionalized SERS platform for deep learning-assisted diagnosis of Alzheimer's disease.

Early diagnosis of Alzheimer's disease is crucial to stall the deterioration of brain function, but conventional diagnostic methods require complicated analytical procedures or inflict acute pain on the patient. Then, label-free Surface-enhanced Raman spectroscopy (SERS) analysis of blood-based biomarkers is a convenient alternative to rapidly obtain spectral information from biofluids. However, despite the rapid acquisition of spectral information from biofluids, it is challenging to distinguish spectral features of biomarkers due to interference from biofluidic components. Here, we introduce a deep learning-assisted, SERS-based platform for separate analysis of blood-based amyloid ß (1-42) and metabolites, enabling the diagnosis of Alzheimer's disease. SERS substrates consisting of Au nanowire arrays are fabricated and functionalized in two characteristic ways to compare the validity of different Alzheimer's disease biomarkers measured on our SERS system. The 6E10 antibody is immobilized for the capture of amyloid ß (1-42) and analysis of its oligomerization process, while various self-assembled monolayers are attached for different dipole interactions with blood-based metabolites. Ultimately, SERS spectra of blood plasma of Alzheimer's disease patients and human controls are measured on the substrates and classified via advanced deep learning techniques that automatically extract informative features to learn generalizable representations. Accuracies up to 99.5% are achieved for metabolite-based analyses, which are verified with an explainable artificial intelligence technique that identifies key spectral features used for classification and for deducing significant biomarkers.

Percutaneous Vertebroplasty in a Patient with Chronic Back Pain Caused by Multiple Schmorl's Nodes: A Case Report.

Background and Objectives: Schmorl's nodes (SNs), formed by the herniation of intervertebral discs into adjacent vertebral bodies, are generally asymptomatic and do not require treatment. However, certain types of SNs can cause intractable back pain. Case Presentation: A 63-year-old man presented to our hospital with back pain after a fall 1 month prior. Physical examination revealed back pain that worsened with movement and paraspinal tenderness. Magnetic resonance imaging (MRI) performed immediately after presentation revealed subacute to chronic compression fractures with SNs at the upper endplates of the 11th and 12th thoracic and 1st lumbar vertebrae. Pain (numeric rating scale (NRS), 7-8/10) persisted despite 6 months of conservative treatment and MRI revealed increased signal intensity in T2-weighted images in the regions around the SNs. Based on these findings, an epidural nerve block was performed, and then repeated; however, no significant improvement was observed. Percutaneous vertebroplasty (PVP) was performed at the 11th and 12th thoracic and 1st lumbar vertebrae. Pain levels decreased substantially 1 week after PVP (NRS, 3-4/10). Subsequent treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids for two weeks further reduced pain levels (NRS, 1-2/10), following which steroid use was discontinued and NSAID use became intermittent. At the six-month follow-up, pain levels remained low and the patient reported an improvement in activity levels of 90% or more. Conclusions: This case report demonstrates that PVP safely and effectively improved symptoms in a patient with multiple SNs and intractable back pain. Nevertheless, further research, particularly large-scale randomized prospective studies, is necessary to validate the long-term efficacy and safety of this intervention.

The effect of low-intensity cold atmospheric plasma jet on photoaging-induced hyperpigmentation in mouse model.

BACKGROUND: Cold atmospheric plasma (CAP) produces reactive oxygen/nitrogen species (RONS) in the target and can induce cytoprotective effects by activating hormesis-related pathways when its intensity is in the low range. OBJECTIVES: The aim of this study is to evaluate the effect of low-intensified CAP (LICAP) on skin with photoaging-induced hyperpigmentation in an animal model. METHODS: Changes in cell viability and RONS production following LICAP treatment were measured. For the in vivo study, 30 hairless mice underwent antecedent photoaging induction followed by the allocated therapy (i.e., LICAP, topical ascorbic acid (AA), or both). During the first 4 weeks of the treatment period (8 weeks), ultraviolet (UV)-B irradiation was concurrently administered. Visual inspection and measurement of the melanin index (MI) were performed to assess the change in skin pigmentation at Weeks 0, 2, 4, 6, and 8. RESULTS: RONS production increased linearly until the saturation point. Cell viability was not significantly affected by LICAP treatment. At Week 8, MI was significantly decreased in every treatment group compared with the values at Week 0 and Week 4. The treatment effect of the concurrent therapy group was superior to that of the LICAP and AA groups. CONCLUSION: LICAP appears to be a novel modality for photoprotection and pigment reduction in photodamaged skin. LICAP treatment and topical AA application seem to exert a synergistic effect.

Use of Hypoxic Respiratory Challenge for Differentiating Alzheimer's Disease and Wild-Type Mice Non-Invasively: A Diffuse Optical Spectroscopy Study.

Alzheimer's disease is one of the most critical brain diseases. The prevalence of the disease keeps rising due to increasing life spans. This study aims to examine the use of hemodynamic signals during hypoxic respiratory challenge for the differentiation of Alzheimer's disease (AD) and wild-type (WT) mice. Diffuse optical spectroscopy, an optical system that can non-invasively monitor transient changes in deoxygenated (ΔRHb) and oxygenated (ΔOHb) hemoglobin concentrations, was used to monitor hemodynamic reactivity during hypoxic respiratory challenges in an animal model. From the acquired signals, 13 hemodynamic features were extracted from each of ΔRHb and -ΔOHb (26 features total) for more in-depth analyses of the differences between AD and WT. The hemodynamic features were statistically analyzed and tested to explore the possibility of using machine learning (ML) to differentiate AD and WT. Among the twenty-six features, two features of ΔRHb and one feature of -ΔOHb showed statistically significant differences between AD and WT. Among ML techniques, a naive Bayes algorithm achieved the best accuracy of 84.3% when whole hemodynamic features were used for differentiation. While further works are required to improve the approach, the suggested approach has the potential to be an alternative method for the differentiation of AD and WT.

Spinal Cord Injury and Postdural Puncture Headache following Cervical Interlaminar Epidural Steroid Injection: A Case Report.

Background: Cervical interlaminar epidural steroid injection (CIESI) is increasingly used as an interventional treatment for pain originating from the cervical spine. However, serious neurological complications may occur during CIESI because of direct nerve damage following inappropriate needle placement. Case report: A 35-year-old woman presented with posterior neck pain radiating to the left upper arm. Cervical magnetic resonance imaging (MRI) revealed left C6 nerve impingement. CIESI under fluoroscopic guidance was performed at another hospital using the left C5/6 interlaminar approach. Immediately after the procedure, the patient experienced dizziness, decreased blood pressure, motor weakness in the left upper arm, and sensory loss. She visited our emergency department with postdural puncture headache (PDPH) that worsened after the procedure. Post-admission cervical MRI revealed intramedullary T2 high signal intensity and cord swelling from the C4/5 to C6/7 levels; thus, a diagnosis of spinal cord injury was made. The patient's PDPH spontaneously improved after 48 h. However, despite conservative treatment with steroids, the decrease in abduction of the left fifth finger and loss of sensation in the dorsum of the left hand persisted for up to 6 months after the procedure. As noticed in the follow-up MRI performed 6 months post-procedure, the T2 high signal intensity in the left intramedullary region had decreased compared to that observed previously; however, cord swelling persisted. Furthermore, left C7/8 radiculopathy with acute denervation was confirmed by electromyography performed 6 months after the procedure. Conclusions: Fluoroscopy does not guarantee the prevention of spinal cord penetration during CIESI. Moreover, persistent neurological deficits may occur, particularly due to intrathecal perforation or drug administration during CIESI. Therefore, in accordance with the recommendations of the Multisociety Pain Workgroup, we recommend performing CIESI at the C6/7 or C7/T1 levels, where the epidural space is relatively large, rather than at the C5/6 level or higher.

Low-intensity cold atmospheric plasma reduces wrinkles on photoaged skin through hormetic induction of extracellular matrix protein expression in dermal fibroblasts.

BACKGROUND: Recent evidence indicates that cold atmospheric plasma (CAP) can upregulate the production of extracellular matrix (ECM) proteins in dermal fibroblasts and enhance transdermal drug delivery when applied at a low intensity. OBJECTIVES: The aim of this study was to evaluate the effect of low-intensity CAP (LICAP) on photoaging-induced wrinkles in an animal model and the expression profiles of ECM proteins in human dermal fibroblasts. METHODS: Each group was subjected to photoaging induction and allocated to therapy (LICAP, topical polylactic acid (PLA), or both). The wrinkles were evaluated via visual inspection, quantitative analysis, and histology. The expression of collagen I/III and fibronectin was assessed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunofluorescence. The amount of aqueous reactive species produced by LICAP using helium and argon gas was also measured. RESULTS: Wrinkles significantly decreased in all treatment groups compared to those in the untreated control. The differences remained significant for at least 4 weeks. Dermal collagen density increased following LICAP and PLA application. LICAP demonstrated a hormetic effect on ECM protein expression in human dermal fibroblasts. The production of reactive species increased, showing a biphasic pattern, with an initial linear phase and a slow saturation phase. The initial linearity was sustained for a longer time in the helium plasma (~60 s) than in the argon plasma (~15 s). CONCLUSION: LICAP appears to be a novel treatment option for wrinkles on the photodamaged skin. This treatment effect seems to be related to its hormetic effect on dermal ECM production.

Static and Dynamic Biomaterial Engineering for Cell Modulation.

In the biological microenvironment, cells are surrounded by an extracellular matrix (ECM), with which they dynamically interact during various biological processes. Specifically, the physical and chemical properties of the ECM work cooperatively to influence the behavior and fate of cells directly and indirectly, which invokes various physiological responses in the body. Hence, efficient strategies to modulate cellular responses for a specific purpose have become important for various scientific fields such as biology, pharmacy, and medicine. Among many approaches, the utilization of biomaterials has been studied the most because they can be meticulously engineered to mimic cellular modulatory behavior. For such careful engineering, studies on physical modulation (e.g., ECM topography, stiffness, and wettability) and chemical manipulation (e.g., composition and soluble and surface biosignals) have been actively conducted. At present, the scope of research is being shifted from static (considering only the initial environment and the effects of each element) to biomimetic dynamic (including the concepts of time and gradient) modulation in both physical and chemical manipulations. This review provides an overall perspective on how the static and dynamic biomaterials are actively engineered to modulate targeted cellular responses while highlighting the importance and advance from static modulation to biomimetic dynamic modulation for biomedical applications.

Quality Assessment and Relevant Clinical Impact of Randomized Controlled Trials of Varicocele: Next Step to Good-Quality Randomized Controlled Trial of Varicocele Treatment.

PURPOSE: To assess the quality of randomized controlled trials (RCTs) on varicocele published from 1979 to 2017. MATERIALS AND METHODS: We searched for original RCT on varicocele published between 1979 and 2017. Jadad scale, van Tulder scale, and Cochrane Collaboration Risk of Bias Tool were used to analyze RCT quality over time. Effects on RCT quality including funding source, Institutional Review Board (IRB) approval, and intervention were assessed. Treatment parameters of varicocele were also analyzed. RESULTS: Blinding and allocation concealment were described in 25.9% and 9.4% of RCT, respectively. Both tended to increase and a sharp dip in allocation concealment was observed in 2010-2017. Jadad scores increased steadily from 1979 to 2017 (1.28±0.59 to 2.19±1.10, p<0.01). Van Tulder scores tended to increase from 1979 to 2017 (4.21±0.94 to 5.58±1.58, p<0.01). RCTs with funding statements had higher Jadad (Yes vs. No, 3.25±0.50 vs. 1.70±0.97; p<0.01) and van Tulder (Yes vs. No, 7.25±1.26 vs. 4.81±1.26; p<0.01) scores than unfunded RCTs. IRB approval and intervention were associated with better quality. CONCLUSIONS: The number of RCTs on varicocele increased from 1979 to 2017. Also, quality improved over time with increasing IRB approval, funding, and multicenter trial. Most RCTs on varicocele reported the use of surgical treatment. RCTs of surgical treatments have limitations to satisfy the condition of RCT to conduct, but their quality has improved over time.

Unilateral pulmonary hemorrhage caused by negative pressure pulmonary edema: A case report.

BACKGROUND: Unilateral pulmonary hemorrhage is typically reported in young and healthy men with upper respiratory tract obstruction during anesthesia in special situations. Negative pressure in the lungs is created, resulting in negative pressure pulmonary edema (NPPE). CASE SUMMARY: A 78-year-old male patient diagnosed with spinal stenosis was admitted to receive a unilateral laminectomy with bilateral decompression. The patient had been diagnosed with hypertension four years earlier and asthma more than 70 years earlier. We experienced a unilateral alveolar hemorrhage associated with NPPE that occurred in a longstanding asthma patient who bit the intubated endotracheal tube for a short period during posture change at the end of surgery. Because diffuse alveolar hemorrhage accompanied by NPPE was caused in this case by airway obstruction in an older patient with asthma without known risk factors, anesthesiologists should be careful not to induce airway irritation during anesthesia awakening in asthma patients. CONCLUSION: Because diffuse alveolar hemorrhage accompanied by NPPE can occur, anesthesiologists should take care not to induce airway irritation.

JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer's disease model.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by cognitive dysfunction and memory loss as the main symptoms. The deposition of amyloid beta (Aß) and tau hyperphosphorylation are hallmarks of AD and are major therapeutic targets. However, the exact etiology has not yet been fully elucidated; thus, no drug that cures the disease has been approved. JBPOS0101 is a phenyl carbamate compound that has been tested as a drug for epileptic diseases. In our previous study, we showed that JBPOS0101 attenuated the accumulation of Aß as well as the deficits in learning and memory in the 5xFAD mouse model. Here, we tested the dose effect (70 or 35 mg/kg) of JBPOS0101 on the memory defect and pathological markers and further investigated the underlying mechanisms in 5xFAD mice. In the behavior tests, JBPOS0101 treatment ameliorated deficits in learning and memory. Moreover, JBPOS0101 attenuated Aß accumulation and tau phosphorylation. The elevated phosphorylation levels of the active GSK3ß form (GSK3ß-y216) in 5xFAD, which are responsible for tau phosphorylation, decreased in the JBPOS0101-treated groups. Furthermore, the elevation of reactive astrocytes and microglia in 5xFAD mice was attenuated in JBPOS0101-treated groups. These data suggest that JBPOS0101 may be a new drug candidate to lessen amyloid- and tau-related pathology by regulating glial cells.

Protein arginine methyltransferase-1 stimulates dopaminergic neuronal cell death in a Parkinson's disease model.

Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (MPP+), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased PRMT1 expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by PRMT1 overexpression. MPP+-induced cell death was attenuated by PRMT1 knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by MPP+. Moreover, we found that PRMT1 positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated PRMT1 expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in PRMT1 haploinsufficient (prmt1+/-) mice. These data suggest that PRMT1 is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose PRMT1 as a new target to develop a potential treatment of PD.

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases.

The development of treatment for neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is facing medical challenges due to the increasingly aging population. However, some pharmaceutical companies have ceased the development of therapeutics for NDs, and no new treatments for NDs have been established during the last decade. The relationship between ND pathogenesis and risk factors has not been completely elucidated. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where oxidative stress and disrupted Ca2+ homeostasis consequently lead to neuronal apoptosis. Reactive oxygen species (ROS) -sensitive TRP channels can be key risk factors as polymodal sensors, since progressive late onset with secondary pathological damage after initial toxic insult is one of the typical characteristics of NDs. Recent evidence indicates that the dysregulation of TRP channels is a missing link between disruption of Ca2+ homeostasis and neuronal loss in NDs. In this review, we discuss the latest findings regarding TRP channels to provide insights into the research and quests for alternative therapeutic candidates for NDs. As the structures of TRP channels have recently been revealed by cryo-electron microscopy, it is necessary to develop new TRP channel antagonists and reevaluate existing drugs.

Carboxylic Acid-Functionalized, Graphitic Layer-Coated Three-Dimensional SERS Substrate for Label-Free Analysis of Alzheimer's Disease Biomarkers.

Surface-enhanced Raman spectroscopy (SERS)-based protein analysis is a promising alternative to existing early stage diagnoses. However, SERS research conducted thus far accompanies challenges such as nonuniformity of plasmonic nanostructures, irregular coating of analytes, and denaturation of proteins, which seriously limit the practicability of suggested approaches. Here, we introduce a carboxylic acid-functionalized and graphitic nanolayer-coated three-dimensional SERS substrate (CGSS) fabricated by sequential nanotransfer printing. The substrate consists of well-defined, uniform gold nanowire arrays for effective Raman signal enhancement and a strong protein-immobilization layer. With an enhancement factor (EF) of 5.5 × 105, on par with the highest ever reported values, the CGSS allows the detection of protein conformational changes and the determination of protein concentration via Raman measurements. Exploiting the CGSS, we successfully measured the SERS spectra of Alzheimer's biomarkers, tau protein and amyloid ß, based on which secondary structural changes were analyzed quantitatively.

Avenanthramide-C Restores Impaired Plasticity and Cognition in Alzheimer's Disease Model Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and dementia with no effective treatment. Here, we investigated a novel compound from oats named avenanthramide-C (Avn-C), on AD-related memory impairment and behavioral deficits in transgenic mouse models. Acute hippocampal slices of wild-type or AD transgenic mice were treated with Avn-C in the presence or absence of oligomeric Aß42. LTP analyses and immunoblotting were performed to assess the effect of Avn-C on Aß-induced memory impairment. To further investigate the effect of Avn-C on impaired memory and Aß pathology, two different AD transgenic mice (Tg2576 and 5XFAD) models were orally treated with either Avn-C or vehicle for 2 weeks. They were then assessed for the effect of the treatment on neuropathologies and behavioral impairments. Avn-C reversed impaired LTP in both ex vivo- and in vivo-treated AD mice hippocampus. Oral administration (6 mg/kg per day) for 2 weeks in AD mice leads to improved recognition and spatial memory, reduced caspase-3 cleavage, reversed neuroinflammation, and to accelerated glycogen synthase kinase-3ß (pS9GSK-3ß) and interleukin (IL-10) levels. Avn-C exerts its beneficial effects by binding to α1A adrenergic receptors to stimulate adenosine monophosphate-activated kinase (AMPK). All of the beneficial effects of Avn-C on LTP retrieval could be blocked by prazosin hydrochloride, a specific inhibitor of α1A adrenergic receptors. Our findings provide evidence, for the first time, that oats' Avn-C reverses the AD-related memory and behavioral impairments, and establish it as a potential candidate for Alzheimer's disease drug development.

TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease.

Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16­carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization. Especially, neurodevelopment is regulated by balancing the level of synaptic protein palmitoylation/depalmitoylation. Recently, we revealed the pathological role of the transient receptor potential canonical type 5 (TRPC5) channel in striatal neuronal loss during Huntington's disease (HD), which is abnormally activated by oxidative stress. Here, we report a mechanism of TRPC5 palmitoylation at a conserved cysteine residue, that is critical for intrinsic channel activity. Furthermore, we identified the therapeutic effect of TRPC5 depalmitoylation by enhancing the TRPC5 membrane instability on HD striatal cells in order to lower TRPC5 toxicity. Collectively, these findings suggest that controlling S-palmitoylation of the TRPC5 channel as a potential risk factor can modulate TRPC5 channel expression and activity, providing new insights into a therapeutic strategy for neurodegenerative diseases.

JBPOS0101 attenuates amyloid-ß accumulation and memory loss in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a major neurodegenerative disorder characterized by the accumulation of amyloid-ß (Aß) in the brain. Defects in Aß clearance or the interference of Aß homeostasis could result in Aß aggregation. JBPOS0101 has been studied for its antiepileptic activity. It showed a neuroprotective effect and prevented memory deficits in lithium-pilocarpine-induced status epilepticus rats. In this study, we tested the effect of JBPOS0101 in an AD model. We showed that JBPOS0101 attenuated the accumulation of Aß in 5XFAD mouse brains. Moreover, the treatment of JBPOS0101 rescued the deficits in learning and memory in 5XFAD mice. These data suggest that JBPOS0101 could be a potential therapeutic drug candidate for AD.

Improved memory and reduced anxiety in δ-catenin transgenic mice.

δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about δ-catenin deficiency mice were performed. However, the effect of δ-catenin overexpression in the brain has not been investigated as yet. Therefore we generated a δ-catenin overexpressing mouse model. To generate a transgenic mouse model overexpressing δ-catenin in the brain, δ-catenin plasmid having a Thy-1 promotor was microinjected in C57BL/6 mice. Our results showed δ-catenin transgenic mice expressed higher levels of N-cadherin, ß-catenin, and p120-catenin than did wild type mice. Furthermore, δ-catenin transgenic mice exhibited better object recognition, better sociability, and lower anxiety than wild type mice. However, both mice groups showed a similar pattern in locomotion tests. Although δ-catenin transgenic mice show similar locomotion, they show improved sociability and reduced anxiety. These characteristics are opposite to the symptoms of autism or mental retardation, which are caused when δ-catenin is deficient. These results suggest that δ-catenin may alleviate symptoms of autism, Alzheimer's disease and mental retardation.

Simultaneous analysis by Quadrupole-Orbitrap mass spectrometry and UHPLC-MS/MS for the determination of sedative-hypnotics and sleep inducers in adulterated products.

Adulterated products are continuously detected in society and cause problems. In this study, we developed and validated a method for determining synthetic sedative-hypnotics and sleep inducers, including barbital, benzodiazepam, zolpidem, and first-generation antihistamines, in adulterated products using Quadrupole-Orbitrap mass spectrometry and ultrahigh performance liquid chromatography with tandem mass spectrometry. In Quadrupole-Orbitrap mass spectrometry analysis, target compounds were confirmed using a combination of retention time, mass tolerance, mass accuracy, and fragment ions. For quantification, several validation parameters were employed using ultrahigh performance liquid chromatography with tandem mass spectrometry. The limit of detection and limit of quantitation was 0.05-53 and 0.17-177 ng/mL, respectively. The correlation coefficient for linearity was more than 0.995. The intra- and interassay accuracies were 86-110 and 84-111%, respectively. Their precision values were evaluated as within 4.0 (intraday) and 10.7% (interday). Mean recoveries of target compounds in adulterated products ranged from 85 to 116%. The relative standard deviation of stability was less than 10.7% at 4°C for 48 h. The 144 adulterated products obtained over 3 years (2014-2016) from online and in-person vendors were tested using established methods. After rapidly screening with Quadrupole-Orbitrap mass spectrometry, the detected samples were quantified using ultrahigh performance liquid chromatography with tandem mass spectrometry. Two of them were adulterated with phenobarbital.

Medial Soft-Tissue Realignment Versus Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation: Systematic Review.

PURPOSE: To compare the clinical outcomes between medial soft-tissue surgery and medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation without any evident predisposing factors. METHODS: A literature search was performed on the established medical databases MEDLINE, EMBASE, and the Cochrane register. The inclusion criteria were as follows: English-language papers for recurrent patellar dislocation without any evident predisposing factors, clinical trial(s) with clear description of surgical technique, adult subjects, medial soft-tissue surgery or MPFL reconstruction without combined surgery, and a follow-up longer than 2 years. The methodological quality of all articles was assessed by 2 authors according to the Coleman methodology score. RESULTS: Thirteen studies (mean Coleman methodology score value, 74.1; standard deviation, 11.5) were included in the analysis. Five studies reported the outcomes of patients undergoing medial soft-tissue surgery, compared with 7 studies reporting MPFL reconstruction. Overall, 109 patients underwent medial soft-tissue surgery with a minimum 2-years follow-up, compared with 308 patients of MPFL reconstruction. There was one direct comparative study between medial soft-tissue surgery and MPFL reconstruction. Of the patients who received medial soft-tissue surgery, 0 to 9.7% experienced redislocation, compared with 0 to 10.7% of the MPFL reconstruction group. The ranges of differences in Kujala scores were 23.6 to 31.7 points in patients who underwent medial soft-tissue surgery and 23.11 to 38.8 points in patients who underwent MPFL reconstruction. The ranges of postoperative congruence angles were -14.4° to 8.2° for medial soft-tissue surgery and -7.7° to -5.2° for MPFL reconstruction. The ranges of postoperative lateral patellofemoral angles were 7.9° to 9.4° for medial soft-tissue surgery and 5° to 5.3° for MPFL reconstruction. CONCLUSIONS: All studies on medial soft-tissue surgery and MPFL reconstruction for recurrent patellar dislocation without predisposing factors showed satisfactory outcomes despite the use of numerous surgical techniques, graft types, and follow-up periods. LEVEL OF EVIDENCE: Level IV, Systematic Review.

Effect of soft tissue laxity of the knee joint on limb alignment correction in open-wedge high tibial osteotomy.

PURPOSE: Open-wedge high tibial osteotomy (HTO) cannot always accurately correct limb alignment, resulting in under- or over-correction. This study assessed the relationship between soft tissue laxity of the knee joint and alignment correction in open-wedge HTO. METHODS: This prospective study involved 85 patients (86 knees) undergoing open-wedge HTO for primary medial osteoarthritis. The mechanical axis (MA), weight-bearing line (WBL) ratio, and joint line convergence angle (JLCA) were measured on radiographs preoperatively and after 6 months, and the differences between the pre- and post-surgery values were calculated. Post-operative WBL ratios of 57-67 % were classified as acceptable correction. WBL ratios <57 and >67 % were classified as under- and over-corrections, respectively. RESULTS: Preoperative JLCA correlated positively with differences in MA (r = 0.358, P = 0.001) and WBL ratio (P = 0.003). Difference in JLCA showed a stronger correlation than preoperative JLCA with differences in MA (P < 0.001) and WBL ratio (P < 0.001). Difference in JLCA was the only predictor of both difference in MA (P < 0.001) and difference in WBL ratio (P < 0.001). The difference between pre- and post-operative JLCA differed significantly between the under-correction, acceptable-correction, and over-correction groups (P = 0.033). Preoperative JLCA, however, did not differ significantly between the three groups. Neither preoperative JLCA nor difference in JLCA correlated with change in posterior slope. CONCLUSIONS: Preoperative degree of soft tissue laxity in the knee joint was related to the degree of alignment correction, but not to alignment correction error, in open-wedge HTO. Change in soft tissue laxity around the knee from before to after open-wedge HTO correlated with both correction amount and correction error. Therefore, a too large change in JLCA from before to after open-wedge osteotomy may be due to an overly large reduction in JLCA following osteotomy, suggesting alignment over-correction during surgery. LEVEL OF EVIDENCE: II.