The Ptk2-Pma1 pathway enhances tolerance to terbinafine in Trichophyton rubrum.

The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both T. rubrum and S. cerevisiae, Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in S. cerevisiae. Overexpression of T. rubrum Pma1 (TrPma1) in T. rubrum Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes.

Is milbemycin a game changer against antifungal drug-resistant mycoses?

Milbemycin oximes are macrocyclic lactones that have a broad spectrum of activity against nematode infection in animals. They are known to block drug efflux, which increases the susceptibility of fungi to azoles. We investigated the effects of milbemycin on the azole susceptibility of fungi (Aspergillus fumigatus, Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum). To screen for changes in azole susceptibility, fungal growth was tested on a culture medium containing 1 µg/ml milbemycin. The results showed that milbemycin increased the azole susceptibility of azole-resistant strains of C. albicans, C. auris, C. neoformans, and T. rubrum. Thus, milbemycin might be useful against antifungal drug-resistant strains.

Milbemycin blocks drug efflux and increases the azole susceptibility of azole-resistant strains of Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum. This drug is expected to be a game changer against antifungal drug-resistant infections.

Two different types of tandem sequences mediate the overexpression of TinCYP51B in azole-resistant Trichophyton indotineae.

Trichophyton indotineae is an emerging dermatophyte that causes severe tinea corporis and tinea cruris. Numerous cases of terbinafine- and azole-recalcitrant T. indotineae-related dermatophytosis have been observed in India over the past decade, and cases are now being recorded worldwide. Whole genome sequencing of three azole-resistant strains revealed a variable number of repeats of a 2,404 base pair (bp) sequence encoding TinCYP51B in tandem specifically at the CYP51B locus position. However, many other resistant strains (itraconazole MIC ≥0.25 µg/mL; voriconazole MIC ≥0.25 µg/mL) did not contain such duplications. Whole-genome sequencing of three of these strains revealed a variable number of 7,374 bp tandem repeat blocks harboring TinCYP51B. Consequently, two types of T. indotineae azole-resistant strains were found to host TinCYP51B in tandem sequences (type I with 2,404 bp TinCYP51B blocks and type II with 7,374 bp TinCYP51B blocks). Using the CRISPR/Cas9 genome-editing tool, the copy number of TinCYP51B within the genome of types I and II strains was brought back to a single copy. The azole susceptibility of these modified strains was similar to that of strains without TinCYP51B duplication, showing that azole resistance in T. indotineae strains is mediated by one of two types of TinCYP51B amplification. Type II strains were prevalent among 32 resistant strains analyzed using a rapid and reliable PCR test.

Tacrolimus inhibits stress responses and hyphal formation via the calcineurin signaling pathway in Trichosporon asahii.

The pathogenic fungus Trichosporon asahii causes fatal deep-seated mycosis in immunocompromised patients. Calcineurin, which is widely conserved in eukaryotes, regulates cell growth and various stress responses in fungi. Tacrolimus (FK506), a calcineurin inhibitor, induces sensitivity to compounds that cause stress on the cell membrane and cell wall integrity. In this study, we demonstrated that FK506 affects stress responses and hyphal formation in T. asahii. In silico structural analysis revealed that amino acid residues in the binding site of the calcineurin-FKBP12 complex that interact with FK506 are conserved in T. asahii. The growth of T. asahii was delayed by FK506 in the presence of SDS or Congo red but not in the presence of calcium chloride. FK506 also inhibited hyphal formation in T. asahii. A mutant deficient of the cnb gene, which encodes the regulatory subunit B of calcineurin, exhibited stress sensitivities on exposure to SDS and Congo red and reduced the hyphal forming ability of T. asahii. In the cnb-deficient mutant, FK506 did not increase the stress sensitivity or reduce hyphal forming ability. These results suggest that FK506 affects stress responses and hyphal formation in T. asahii via the calcineurin signaling pathway.

Oxidative Functionalization of Catechol Derivatives Substituted with Electron-Withdrawing Groups.

Catechols possessing electron-withdrawing groups at the C3 position effectively underwent oxidative functionalization at the C4 position in the presence of phenyliodine(III) diacetate (PIDA) and heteroarene nucleophiles (e.g., indole, indazole, and benzotriazole) to produce the corresponding biaryl products. The PIDA-mediated oxidation of catechol derivatives afforded the ortho-benzoquinone intermediate, which subsequently underwent regioselective nucleophilic addition to the α,ß-unsaturated carbonyl moiety of ortho-benzoquinone using indole, indazole, and benzotriazole to give 4-substituted catechol derivatives in a one-pot manner. Notably, the nucleophilic substitution positions of indazole and benzotriazole were perfectly controlled. Additionally, the reaction using N-methylaniline as the nucleophile afforded a tertiary amine product.

Long Amplification PCR (LA-PCR) Detection of Azole Resistant Trichophyton indotineae.

Trichphyton indotineae, a species newly designated in 2020 independent of T. interdigitale, comprises highly terbinafine (TRF)-resistant dermatophytosis that is epidemic in North India and spreding to worldwide. Some clinical isolates of T. indotineae have been resistance both TRF and azoles that might be caused the treatment failure. To detect the azole resistance strains, we developed a long amplification PCR (LA-PCR) detection method for the tandem repeat of the CYP51B (encoding sterol 14a-demethylase gene) in T. indotineae. Contrasting the drug susceptibility test results with the LA-PCR results confirmed a trend toward low susceptibility to azole antifungal agents in strains with amplifications of 9.5 kbp or greater (3 or more copies of CYP51B). Our results suggest that the method could be detected rapidly of low-susceptibility strains to azole antifungal agents.

Predictors of good outcome after anterior decompression and fusion in patients with ossification of the posterior longitudinal ligament of the thoracic spine.

BACKGROUND: There are few reports concerning determinants of the surgical outcome of anterior decompression and fusion (ADF) when performed for ossification of the posterior longitudinal ligament of the thoracic spine (T-OPLL). We investigated prognostic factors associated with neurological recovery in the patients with T-OPLL. METHODS: This retrospective study included consecutive cases of T-OPLL patients from January 2002 to January 2020 and minimum one-year follow-up. Data were collected for sex, age, body mass index, preoperative manual muscle test score for the weakest muscle, surgical data, and preoperative and postoperative findings on radiographs, magnetic resonance images, and computed tomography scans. Imaging data were also collected, including preoperative kyphotic angles, canal occupancy ratio, type of OPLL, and high-intensity areas on T2-weighted images. The Japanese Orthopaedic Association score for thoracic myelopathy (T-JOA) was used to evaluate the recovery of the thoracic myelopathy. The patients were categorized according to whether the improvement in T-JOA score was >50% or ≤50%. RESULTS: Forty-six patients who underwent anterior procedures for T-OPLL were included in the study. Preoperative and postoperative T-JOA scores were 4.2 ± 2.3 and 7.9 ± 2.1, respectively. The improvement in the T-JOA score was 54.5 ± 25.6%. The proportion of patients with beak-type OPLL was significantly higher in the >50% JOA improvement group (23/27) than in the ≤50% group (9/19) (p = 0.009) and the canal occupancy ratio was significantly lower in the >50% group (56.3 ± 12.2% vs 64.4 ± 8.73%; p = 0.0163). There were no significant between-group differences in other factors. CONCLUSIONS: Beak-type ossification and a low canal occupancy ratio are predictors of good outcome after ADF in patients with T-OPLL. ADF should be considered in patients with either or both of these features.

Pelvic incidence is a risk factor for lower instrumented vertebra failure in adult spinal deformity patients who underwent corrective fusion terminating at the L5 vertebra.

BACKGROUND: Factors related to postoperative mechanical failure after long fusion with lower instrumented vertebra (LIV) at L5 have not been well investigated. Elucidating such factors may allow us to perform alternatives to spinopelvic fusion for adult spinal deformity (ASD) cases. We investigated the incidence and risk factors of LIV failure in patients with ASD who underwent surgical treatment of long corrective fusion until the L5 vertebrae. METHODS: Between 2009 and 2018, 52 patients who underwent corrective fusions to L5 were followed-up for at least one-year. We evaluated the associated patient factors for LIV failure which include loosening of the pedicle screw of LIV, fracture of LIV, distal junctional kyphosis (DJK). RESULTS: The mean age of the participants was 71.2 ± 7.59 (range, 44-84). LIV failure occurred in 20 patients (38.5%), and 6 patients (11.5%) underwent secondary surgery for caudal segments. The mean pelvic incidence (PI) was 52.5 ± 9.8 in the failure group versus 45.3 ± 11.4 in non-failure group (P = 0.02) and pelvic tilt (PT) was 39.1 ± 9.0 versus 32.4 ± 13.0. There were no significant differences in sex, age, body mass index, number of levels fused, and other radiographic data. Logistic regression analysis that included T1 pelvic angle, PT, PI - postoperative LL and PI also identified PI as the only significant determinant of LIV failure (OR = 1.07, P = 0.034). Receiver operating characteristic analysis demonstrated that a PI over 50.0° was associated with LIV failure (sensitivity 63%, specificity 70%, AUC 0.694). CONCLUSION: LIV failure was frequently observed after long corrective fusion for patients with ASD. High PI was found to be a significant risk factor for the LIV failure.

Gene Amplification of CYP51B: a New Mechanism of Resistance to Azole Compounds in Trichophyton indotineae.

Trichophyton indotineae causes dermatophytosis that is resistant to terbinafine and azole compounds. The aim of this study was to determine the mechanisms of resistance to itraconazole (ITC) and voriconazole (VRC) in strains of T. indotineae. Two azole-sensitive strains (ITC MIC < 0.125 µg/mL; VRC MIC < 0.06 µg/mL) and four azole-resistant strains (ITC MIC ≥ 0.5 µg/mL; VRC MIC ≥ 0.5 µg/mL) were used for the investigation. The expression of MDR genes encoding multidrug transporters of the ABC family for which orthologs have been identified in Trichophyton rubrum and those of CYP51A and CYP51B encoding the targets of azole antifungal compounds were compared between susceptible and resistant strains. TinMDR3 and TinCYP51B were overexpressed in T. indotineae resistant strains. Only small differences in susceptibility were observed between TinMDR3 disruptants and parental strains overexpressing TinMDR3. Whole-genome sequencing of resistant strains revealed the creation of a variable number of TinCYP51B tandem repeats at the specific position of their genomes in three resistant strains. Downregulation of TinCYP51B by RNA interference (RNAi) restored the susceptibility of azole-resistant strains. In contrast, overexpression of TinCYP51B cDNA conferred resistance to a susceptible strain of T. indotineae. In conclusion, the reduced sensitivity of T. indotineae strains to azoles is mainly due to the overexpression of TinCYP51B resulting from additional copies of this gene.

Establishment of a gene recombination method for a major human skin commensal fungus, Malassezia restricta, using Agrobacterium tumefaciens-mediated gene transfer system.

Malassezia restricta is the most predominant fungus in the microbiome of human skin. This microorganism can cause or exacerbate Malassezia-associated skin dermatitis, seborrheic dermatitis, atopic dermatitis, and pityriasis versicolor. The virulence factors of M. restricta have not been analyzed because a gene recombination system has not been developed. In this study, we established an Agrobacterium tumefaciens-mediated gene transfer (ATMT) system, optimized for generating gene-deficient mutants of M. restricta. A mutant of FKB1 gene, which encodes the FKBP12 protein that binds to the calcineurin inhibitor tacrolimus, was generated using the ATMT system. Subsequently, the FKB1 gene was reintroduced into the FKB1 gene-deficient mutant for obtaining a gene-complemented strain. The wild-type strain of M. restricta was sensitive to tacrolimus, whereas the FKB1 gene-deficient mutant was resistant to tacrolimus; the phenotypic drug susceptibility in the mutant was restored by reintroducing the FKB1 gene. Contrastingly, the FKB1 gene-deficient mutant was not resistant to cyclosporine A, which also inhibits calcineurin by binding to cyclophilin A. The gene recombination system for M. restricta will facilitate in elucidating the molecular mechanisms causing Malassezia-associated dermatitis.

Effect of Topical Antifungal Luliconazole on Hyphal Morphology of Trichophyton mentagrophytes Grown on in vitro Onychomycosis Model.

Luliconazole, recently launched in Japan, is a novel topical imidazole antifungal agent for the treatment of onychomycosis. Using in vitro onychomycosis model, the effect of luliconazole on the morphology of the growing hyphae of Trichophyton mentagrophytes was investigated by scanning electron microscopy (SEM). The model was produced by placing human nail pieces on an agar medium seeded with conidia of T. mentagrophytes. After incubating the agar medium for 3 days, luliconazole was applied to the surface of the nail in which hyphal growth was recognized, then cultured for up to 24 h. The initial change after treatment with the drug was the formation of fine wrinkles on the surface of the hyphae, eventually, the hyphae were flattened, and after that, no hyphal growth was observed. On the other hand, when the nails were pretreated with luliconazole for 1 h, no hyphal growth was observed even after culturing for 24 h. This study suggests that luliconazole has a strong antifungal activity by inhibiting the ability of fungi to grow and the drug has both excellent nail permeation and retention properties.

A comparative study of surgical outcomes between anterior cervical discectomy with fusion and selective laminoplasty for cervical spondylotic myelopathy.

BACKGROUND: Few studies have directly compared anterior and posterior surgical approaches in cervical spondylotic myelopathy (CSM) patients with short-segment disease. We aimed to examine and compare surgical outcomes of anterior cervical discectomy with fusion (ACDF) and selective laminoplasty (S-LAMP) in CSM patients with 1- or 2-level disease. METHODS: Forty-six patients, who received surgeries for CSM, were prospectively investigated; 24 underwent ACDF and 22 underwent S-LAMP. Average follow-up was 3.5 years. The following pre- and postoperative radiographic measurements were recorded: (1) C2-7 angle, (2) local angle (lordotic Cobb angle at operative level), (3) cervical sagittal vertical axis (SVA) (center of gravity of the head-C7 SVA), and (4) C7 slope. Outcomes were evaluated using the Japanese Orthopedic Association scoring system for cervical myelopathy (C-JOA score), neck pain visual analog scale, and neck disability index (NDI). RESULTS: There were no significant differences in patient demographics between the two groups. Postoperatively, C2-7 angle, local angle, cervical SVA, C7 slope, C-JOA score, and neck pain and NDI scores were not significantly different between the two groups; however, the recovery rate of the C-JOA score was superior in the ACDF group (57.5%) compared to the S-LAMP group (42.1%). The recovery rate of the C-JOA score in the local lordosis subgroup (local angle ≥ 0°) showed no significant difference between the two surgical groups. However, in the local kyphosis subgroup (local angle < 0°), C-JOA score recovery rate was worse after S-LAMP (20.4%) than ACDF (57.9%); local angle also worsened postoperatively after S-LAMP. CONCLUSIONS: In patients with local lordosis at the segments of cervical spondylosis and spinal cord compression, S-LAMP showed equivalent surgical outcomes (neurological recovery, neck pain and NDI scores, and cervical alignment) to ACDF. However, in patients with local kyphosis, S-LAMP worsened the kyphosis and resulted in worse neurological recovery.

Impact of body mass index on surgical outcomes and complications in adult spinal deformity.

BACKGROUND: Several studies have reported that overweightness and obesity are associated with higher complication rates in lumbar spine surgery. However, little is known about the effect of obesity on postoperative complications in adult spinal deformity (ASD) surgery, especially in the elderly. This study aimed to examine the effect of body mass index (BMI) on surgical outcomes and postoperative complications in elderly ASD patients undergoing surgical correction in Japan. METHODS: We conducted a retrospective, multicenter, observational study of 234 consecutive patients diagnosed with ASD who underwent corrective surgery. Patients were divided into two groups according to BMI, BMI <25 (153 patients, mean age 71.9 years) and BMI ≥ 25 (overweight/obese, 81 patients, mean age 73.3 years). Radiographic results and perioperative complications were compared between the two groups. RESULTS: Surgical complications occurred in approximately 20% of patients in each group; complications did not significantly differ between the two groups. A greater proportion of patients in the BMI ≥ 25 group experienced mechanical failure and DJK, although the difference was not significant. Preoperative mean lumbar lordosis (LL), pelvic incidence (PI) minus LL, sacral slope (SS) and sagittal vertical axis (SVA) were similar in the BMI < 25 and BMI ≥ 25 groups. However, the BMI ≥25 group had lower mean LL (p = 0.015) and higher PI minus LL (p = 0.09) postoperatively. The BMI ≥25 groups also had significantly smaller LL (p = 0.026), smaller SS (p = 0.049) and higher SVA (p = 0.041) at the final follow-up, compared to the BMI < 25 group. CONCLUSIONS: In the present study, no difference in medical or surgical complications after ASD surgery was found between overweight/obese patients (BMI ≥ 25) and those with BMI < 25. However, correction of LL and SVA was smaller in patients with overweight/obese patients.

The impact of diabetes mellitus on spinal fracture with diffuse idiopathic skeletal hyperostosis: A multicenter retrospective study.

BACKGROUND: Patients with diffuse idiopathic skeletal hyperostosis (DISH) are susceptible to spinal column injuries with neurological deterioration. Previous studies indicated that the prevalence of diabetes mellitus (DM) in patients with DISH was higher than that in patients without DISH. This study investigates the impact of DM on surgical outcomes for spinal fractures in patients with DISH. METHODS: We retrospectively evaluated 177 spinal fractures in patients with DISH (132 men and 45 women; mean age, 75 ± 10 years) who underwent surgery from a multicenter database. The subjects were classified into two groups according to the presence of DM. Perioperative complications, neurological status by Frankel grade, mortality rate, and status of surgical site infection (SSI) were compared between the two groups. RESULTS: DM was present in 28.2% (50/177) of the patients. The proportion of men was significantly higher in the DM group (DM group: 86.0% vs. non-DM group: 70.1%) (p = 0.03). The overall complication rate was 22.0% in the DM group and 19.7% in the non-DM group (p = 0.60). Poisson regression model revealed that SSI was significantly associated with DM (DM group: 10.0% vs. non-DM group: 2.4%, Relative risk: 4.5) (p = 0.048). Change in neurological status, mortality rate, instrumentation failure, and nonunion were similar between both groups. HbA1c and fasting blood glucose level (SSI group: 7.2% ± 1.2%, 201 ± 67 mg/dL vs. non-SSI group: 6.6% ± 1.1%, 167 ± 47 mg/dL) tended to be higher in patients with SSI; however, there was no significant difference. CONCLUSIONS: In spinal fracture in patients with DISH, although DM was an associated factor for SSI with a relative risk of 4.5, DM did not negatively impact neurological recovery. Perioperative glycemic control may be useful for preventing SSI because fasting blood glucose level was high in patients with SSI.

Revisiting the synthesis of aryl nitriles: a pivotal role of CAN.

Facilitated by the dual role of Ceric Ammonium Nitrate (CAN), herein we report a cost-effective approach for the cyanation of aryl iodides/bromides with CAN-DMF as an addition to the existing pool of combined cyanation sources. In addition to being an oxidant, CAN acts as a source of nitrogen in our protocol. The reaction is catalyzed by a readily available Cu(ii) salt and the ability of CAN to generate ammonia in the reaction medium is utilized to eliminate the additional requirement of a nitrogen source, ligand, additive or toxic reagents. The mechanistic study suggests an evolution of CN- leading to the synthesis of a variety of aryl nitriles in moderate to good yields. The proposed mechanism is supported by a series of control reactions and labeling experiments.

Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2.

BACKGROUND: Dermatophytes showing reduced sensitivity to antifungal agents have emerged in several countries. One terbinafine resistant strain of Trichophyton rubrum, TIMM20092, also showed reduced sensitivity to itraconazole (ITC) and voriconazole (VRC). The expression of two genes (TruMDR2 and TruMDR3) encoding multidrug transporters of the ABC family was found to be highly up-regulated in this strain. Deletion of TruMDR3 in TIMM20092 abolished its resistance to VRC but only slightly reduced its resistance to ITC. OBJECTIVES: We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092. METHODS: The deletion of TruMDR2 by gene replacement was performed in TIMM20092 and one TruMDR3-lacking mutant (∆TruMDR3) previously generated from TIMM20092. TruMDR2 single and TruMDR2/TruMDR3 double mutants (∆TruMDR2 and ∆TruMDR2/3) were successfully obtained, respectively. RESULTS: The suppression of TruMDR2 was shown to abolish resistance to ITC in TIMM20092 and the TruMDR3-lacking mutant, strongly suggesting that TruMDR2 is a major contributor to ITC resistance in TIMM20092. CONCLUSIONS: Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.

Surgical outcomes of the thoracic ossification of ligamentum flavum: a retrospective analysis of 61 cases.

BACKGROUND: Thoracic ossification of ligamentum flavum (T-OLF), as one of the causes of thoracic myelopathy, is often combined with other spinal disorders. Concurrent lumbar spinal canal stenosis (LCS) is often obscured by symptoms due to T-OLF, leading to difficulty in identifying the origin of these neurological findings. It is common to be misdiagnosed or delayed diagnosis due to the complicated nature. We evaluated the prevalence, distribution, and clinical characteristics of OLF, especially in patients with LCS. METHODS: The authors performed a retrospective analysis of the outcomes of 61 patients who underwent thoracic surgeries performed for symptomatic T-OLF. In all the patients, whole spine lesions were evaluated preoperatively. We examined the factors related to poor outcomes (the recovery rate of the Japanese Orthopedic Association score for thoracic myelopathy is less than 40%) following OLF surgeries. We compared the clinical outcomes according to whether there was concurrent LCS, and determined the optimal surgical approach. RESULTS: The occurrence of T-OLF increased with age. Forty-six cases (75.4%) were considered to be tandem T-OLF and LCS (LCS group). An advanced age, and concurrent LCS were associated with a poor outcome after the surgery. The LCS group significantly included a greater number of elderly, and more light-weighted patients with Modic change in thoracic spine and a greater sagittal vertical axis, resulting in the lower neurological recovery. Additional lumbar surgery (13cases) effectively improved both the T-JOA and L-JOA scores (from 6.5 ± 2.0 points to 8.0 ± 1.8 points, p = 0.0406, and from 14.5 ± 4.7 points to 20.7 ± 2.6 points, p = 0.001, respectively) in OLF patients with LCS. CONCLUSIONS: T-OLF was highly associated with other spinal disorders. Poor outcomes in T-OLF surgery could be associated with age and concurrent LCS, and an additional surgery for another lumbar lesion significantly improved neurological findings in T-OLF patients.

Ruthenium-on-Carbon-Catalyzed Facile Solvent-Free Oxidation of Alcohols: Efficient Progress under Solid-Solid (Liquid)-Gas Conditions.

A protocol for the ruthenium-on-carbon (Ru/C)-catalyzed solvent-free oxidation of alcohols, which proceeds efficiently under solid-solid (liquid)-gas conditions, was developed. Various primary and secondary alcohols were transformed to corresponding aldehydes and ketones in moderate to excellent isolated yields by simply stirring in the presence of 10% Ru/C under air or oxygen conditions. The solvent-free oxidation reactions proceeded efficiently regardless of the solid or liquid state of the substrates and reagents and could be applied to gram-scale synthesis without loss of the reaction efficiency. Furthermore, the catalytic activity of Ru/C was maintained after five reuse cycles.

Prognostic factors for neurological outcome after anterior decompression and fusion for proximal-type cervical spondylotic amyotrophy - A retrospective analysis of 77 cases.

BACKGROUND: Decompression through an anterior approach is theoretically effective for the surgical treatment of cervical spondylotic amyotrophy (CSA), because the pathology usually locates at the anterior side. However, most previous studies investigated posterior surgery or a mix of anterior surgery and posterior surgery in their investigation. Only a few small case series have investigated the surgical outcomes of anterior decompression and fusion (ADF). Therefore, we conducted a multicenter retrospective study that included patients who underwent ADF for proximal-type CSA. METHODS: We analyzed the outcomes of 77 consecutive spinal surgeries performed on proximal-type CSA patients who underwent ADF. Preoperative and postoperative manual muscle tests (MMT) and the patients' backgrounds, radiological findings, and complications were reviewed. We divided the cases into two groups, good-outcome group (MMT improvement â‰§ 2 or improved to MMT 5) and poor-outcome group (others) and evaluated the prognostic factors for outcomes. RESULTS: Of the 77 patients, 48 (62%) showed good neurological outcome. Multiple compressive lesions at anterior horn (AH) and/or ventral nerve roots (VNRs) were detected in 66 patients (85.7%) on the magnetic resonance images. The patients with a single compressive lesion at VNR or AH tended to show good neurological recovery when compare to those with multiple lesions. Age and duration of symptoms were related to the poor outcome in univariate analysis. Duration of symptoms was an independent factor associated with postoperative neurological outcome. The cut-off value for poor outcome was 7.0 months for the symptom duration (sensitivity: 79%, specificity: 54%, area under the curve: 0.69). CONCLUSIONS: Patients with proximal-CSA were more likely to have multiple compressive lesions at an AH and/or a VNR. The prognostic factor for poor neurological outcome was duration of symptoms of ≥7 months.

Risk factors for delayed diagnosis of spinal fracture associated with diffuse idiopathic skeletal hyperostosis: A nationwide multiinstitution survey.

BACKGROUND: Patients with DISH are susceptible to spinal fractures and subsequent neurological impairment, including after minor trauma. However, DISH is often asymptomatic and fractures may have minimal symptoms, which may lead to delayed diagnosis. The purpose of this study was to identify risk factors for delayed diagnosis of spinal fractures in patients with diffuse idiopathic skeletal hyperostosis (DISH). METHODS: The subjects were 285 patients with DISH surgically treated at 18 medical centers from 2005 to 2015. Cause of injury, imaging findings, neurological status at the times of injury and first hospital examination, and the time from injury to diagnosis were recorded. A delayed diagnosis was defined as that made >24 h after injury. RESULTS: Main causes of injury were minor trauma due to a fall from a standing or sitting position (51%) and high-energy trauma due to a fall from a high place (29%) or a traffic accident (12%). Delayed diagnosis occurred in 115 patients (40%; 35 females, 80 males; mean age 76.0 ± 10.4 years), while 170 (60%; 29 females, 141 males; mean age 74.6 ± 12.8 years) had early diagnosis. Delayed group had a significantly higher rate of minor trauma (n = 73, 63% vs. n = 73, 43%), significantly more Frankel grade E (intact neurological status) cases at the time of injury (n = 79, 69% vs. n = 73, 43%), and greater deterioration of Frankel grade from injury to diagnosis (34% vs. 8%, p < 0.01). In multivariate analysis, a minor trauma fall (OR 2.08; P < 0.05) and Frankel grade E at the time of injury (OR 2.29; P < 0.01) were significantly associated with delayed diagnosis. CONCLUSION: In patients with DISH, it is important to keep in mind the possibility of spinal fracture, even in a situation in which patient sustained only minor trauma and shows no neurological deficit. This is because delayed diagnosis of spinal fracture can cause subsequent neurological deterioration.