Raphe glucose-sensing serotonergic neurons stimulate KNDy neurons to enhance LH pulses via 5HT2CR: rat and goat studies.

Dysfunction of central serotonergic neurons is known to cause depressive disorders in humans, who often show reproductive and/or glucose metabolism disorders. This study examined whether dorsal raphe (DR) serotonergic neurons sense high glucose availability to upregulate reproductive function via activating hypothalamic arcuate (ARC) kisspeptin neurons (= KNDy neurons), a dominant stimulator of gonadotropin-releasing hormone (GnRH)/gonadotropin pulses, using female rats and goats. RNA-seq and histological analysis revealed that stimulatory serotonin-2C receptor (5HT2CR) was mainly expressed in the KNDy neurons in female rats. The serotonergic reuptake inhibitor administration into the mediobasal hypothalamus (MBH), including the ARC, significantly blocked glucoprivic suppression of luteinizing hormone (LH) pulses and hyperglycemia induced by intravenous 2-deoxy-D-glucose (2DG) administration in female rats. A local infusion of glucose into the DR significantly increased in vivo serotonin release in the MBH and partly restored LH pulses and hyperglycemia in the 2DG-treated female rats. Furthermore, central administration of serotonin or a 5HT2CR agonist immediately evoked GnRH pulse generator activity, and central 5HT2CR antagonism blocked the serotonin-induced facilitation of GnRH pulse generator activity in ovariectomized goats. These results suggest that DR serotonergic neurons sense high glucose availability to reduce gluconeogenesis and upregulate reproductive function by activating GnRH/LH pulse generator activity in mammals.

Relationship between Treatment Choices according to the Modified Osteoporotic Fracture Score and Posttreatment Radiographic Outcomes.

STUDY DESIGN: Retrospective observational study. PURPOSE: To evaluate the modified osteoporotic fracture (mOF) scores in three treatment groups and compare imaging findings in patients treated and not treated according to the mOF score-based treatment recommendation. OVERVIEW OF LITERATURE: The osteoporotic fracture (OF) score was established by the AO Spine to guide therapeutic decisions. To enhance its applicability, a mOF score was recently introduced. METHODS: Consecutive patients diagnosed with OFs at Fujieda Heisei Memorial Hospital were divided into three groups: nonsurgical therapy, balloon kyphoplasty (BKP), and open surgery groups. The mOF score was calculated, and the levels of independence and posttreatment imaging data were compared between patients treated and not treated according to the mOF score-based treatment recommendation. RESULTS: In total, 118 patients were included (nonsurgical therapy, n=57; BKP, n=48; open surgery, n=13), of whom 100 (85%) received treatment consistent with the mOF score-based treatment recommendation. In the BKP and open surgery groups, the mOF scorebased treatment recommendations were consistent with the actual treatment in 93% of the patients. However, in the nonsurgical group, the mOF score-based treatment recommendation was not consistent with the actual treatment in 25% of the patients. In this group, patients not treated according to the mOF score had significantly shorter vertebral body height, greater local kyphosis, and smaller sacral slope after treatment than patients treated according to the mOF score-based treatment recommendation. CONCLUSIONS: In the BKP and open surgery groups, the mOF scores were consistent with actual clinical selection. In the nonsurgical therapy group, patients not treated according to the mOF score-based treatment recommendation exhibited severe vertebral body deformity and a less well-balanced spine shape after treatment. The mOF score may help in selecting suitable treatments for OFs.

Differences in the Demographics and Clinical Characteristics between the Ossification of the Posterior Longitudinal Ligament and Ossification of the Ligamentum Flavum in Patients Who Underwent Thoracic Spinal Surgery for Compressive Myelopathy.

Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are related diseases associated with the ossification of spinal ligaments that can occasionally lead to thoracic myelopathy. We retrospectively analyzed the clinical data of 34 consecutive patients who underwent thoracic spinal surgeries for OPLL and/or OLF at our hospital between July 2010 and June 2022, and statistically compared data between patients with thoracic OPLL (TOPLL; n = 12) and those with thoracic OLF (TOLF; n = 22). The mean age of the TOPLL group was significantly lower than that of the TOLF group (53.7 vs. 68.4 years). The TOPLL group exhibited a greater female predominance than the TOLF group (58.3% vs. 18.2%). The median body mass index of the TOPLL group was significantly higher than that of the TOLF group (33.0 vs. 26.0 kg/m2). Patients with TOPLL significantly required instrumented fusion and repetitive surgical intervention more than those with TOLF (83.3% vs. 9.1%; 50.0% vs. 0.0%). Although neurological deterioration just after the intervention was more common in patients with TOPLL (41.7% vs. 4.6%), no difference was observed in thoracic Japanese Orthopaedic Association score and recovery rate in the chronic phase between TOPLL and TOLF. The TOPLL group had a younger onset, female dominance, and a greater degree of obesity when compared with the TOLF group. The surgery for TOPLL is challenging, considering that it requires long-range decompression and fusion, subsequent operations, careful management, and long-term follow-up, when compared to TOLF, which necessitates only simple decompression.

Screening for prostate cancer in a city in Japan: age-specific prostate-specific antigen cutoff thresholds.

PURPOSE: Older men have higher prostate-specific antigen levels than younger men. However, the current Japanese Urological Association guidelines recommend secondary screening at a cutoff value of 4.0 ng/mL, even in older men. Here, we reexamined the cutoffs for older men using a prostate screening cohort in Japan and first performed an analysis to determine the indication cutoffs for detecting positive biopsies. METHODS: Data from 68,566 prostate cancer screenings in the city in 2018 were combined with cancer registration data. The optimal prostate-specific antigen levels to predict prostate cancer in different age groups were calculated using receiver operating characteristic curves after determining whether a cancer was registered within one year of screening. RESULTS: At the conventional prostate-specific antigen threshold of 4.0 ng/mL, the sensitivity, specificity, and negative predictive value were 94.9%, 91.7%, and 91.7%, respectively. The optimal prostate-specific antigen cutoff values for patients aged 50-59 years, 60-69 years, 70-79 years, and over 80 years were 3.900 ng/mL, 4.014 ng/mL, 4.080 ng/mL, and 4.780 ng/mL, respectively. CONCLUSIONS: The sensitivity and specificity of prostate cancer screening in the city were high, indicating a highly accurate screening. The prostate-specific antigen threshold was 4.78 ng/mL in patients older than 80 years. A higher prostate-specific antigen threshold may be useful in men over 80 years of age to avoid excess biopsy and reduce costs. Our results suggest that the current Japanese method of using PSA 4.0 ng/mL as a cutoff regardless of age may not be preferable for older men.

Analysis of Neurogenic Bowel and Bladder Dysfunction Following Decompression Surgery for Cervical Spondylotic Myelopathy: A Prospective Cohort Study.

STUDY DESIGN: A prospective observational study. OBJECTIVES: To investigate preoperative prevalence of neurogenic bowel dysfunction and neurogenic bladder in patients with degenerative cervical myelopathy (DCM) and examine the degree and timing of symptom improvement after cervical decompression surgery. Factors contributing to symptom improvement were also analyzed. METHODS: Among 75 patients with DCM who underwent cervical decompression, Constipation Scoring System (CSS) score, International Prostate Symptoms Score (IPSS), and Japanese Orthopaedic Association (JOA) score were assessed before surgery and 1, 3, 6, and 12 months after. Prevalence rates were calculated. Data regarding patient age, sex, disease status, disease duration, lesion level, and score changes was prospectively recorded and analyzed. RESULTS: The prevalence rates of defecation and urinary dysfunction before surgery were 41.3% and 34.7%, respectively. Among the patients with defecation dysfunction, the number of patients who improved 1, 3, 6, and 12 months after surgery was 10, 9, 9, and 6, respectively. Among the patients with urinary dysfunction, the corresponding number of patients was 12, 10, 11, and 11, respectively. None of the factors we examined were significantly associated with improvement in either CSS or IPSS score; however, improvement of lower extremity JOA score tended to be associated with improvement in both. CONCLUSIONS: The prevalence of symptoms of defecation and urinary dysfunction in patients with DCM was 41.3% and 34.7%, respectively. Decompression surgery improved symptoms in 20% to 46% of patients.

Unrecognized dural tear during percutaneous endoscopic lumbar surgery confirmed with myelography.

Iatrogenic dural tear is usually recognized during the surgery. We describe a rare case of unrecognized dural tear caused by percutaneous endoscopic lumbar surgery at another hospital clearly confirmed with dynamic myelography. Although magnetic resonance imaging of the lumbar spine showed no obvious fluid collection suggesting dural tear, dynamic myelography revealed leakage of intradural subarachnoid contrast medium along root sleeve into the intervertebral disc space. In the setting of endoscopic spine surgery, incidental dural tear might be overlooked due to the narrow and fluid-filled surgical field. Dynamic myelography is useful to evaluate the precise condition caused by unrecognized dural tear.

Postoperative intractable leg pain caused by dislocation of drainage tube.

Background: A wide variety of conditions can cause recurrent postoperative lumbar radiculopathy. Case Description: A 49-year-old female developed sudden recurrent postoperative right leg pain after a right-sided L5S1 microdiskectomy for a herniated disc. Emergent magnetic resonance and computed tomography studies demonstrated migration of the drainage tube into the right L5S1 lateral recess compromising the S1 nerve root. Following drain removal, the patient's right reg pain immediately resolved. Conclusion: Migration of a lumbar wound drain into the operated lateral recess following a lumbar diskectomy may result in acute, recurrent/intractable radicular pain that was readily resolved with drain removal.

Effect of a neurokinin 3 receptor-selective agonist administration on the embryos recovered from superovulated cows.

Superovulation (SOV) treatment of cows results in unovulated follicles and inconsistent quality of the recovered embryos. It has been demonstrated that luteinizing hormone (LH) secretion is suppressed during SOV treatment of cows, which may cause insufficient follicle development and variation in the development of recovered embryos and unovulated follicles. Pulsatile gonadotropin-releasing hormone/LH secretion is controlled by the activity of kisspeptin, neurokinin B and dynorphin (KNDy) neurons in the arcuate nucleus in many mammals. As neurokinin B promotes the activity of KNDy neurons, we hypothesized that senktide, a neurokinin B receptor agonist, has the potential as a therapeutic drug to improve the ovulation rate and quality of recovered embryos in SOV-treated cows via stimulation of LH secretion. Senktide was administered intravenously (30 or 300 nmol/min) for 2 h, beginning from 72 h after the start of SOV treatment. LH secretion was examined before and after administration, and embryos were collected 7 d after estrus. Senktide administration increased LH secretion in SOV-treated cows. The ratios of code 1, code 1 and 2, and blastocyst stage embryos to recovered embryos were increased by senktide (300 nmol/min) administration. Moreover, the mRNA levels of MTCO1, COX7C, and MTATP6 were upregulated in recovered embryos of senktide (300 nmol/min)-administered animals. These results indicate that the administration of senktide to SOV-treated cows enhances LH secretion and upregulates the expression of genes involved in mitochondrial metabolism in embryos, thereby improving embryo development and embryo quality.

Association of 25-hydroxyvitamin D with risk of overall and colorectal cancer among Japanese using a Mendelian randomization approach.

The association between vitamin D and total and colorectal cancer risk was inconsistent in observational studies. We conducted Mendelian randomization approach in which the effect of confounding might be reduced. 110 single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D concentrations were systematically selected according to the "GWAS Catalog" from all ethnic populations. For the SNP-vitamin D concentration association, 3978 individuals from two Japanese cohorts were included. Regarding SNP-total and colorectal cancer association, 4543 cancer cases and 14,224 controls and 7936 colorectal cancer cases and 38,042 controls, respectively were included from the Japanese Consortium of Genetic Epidemiology and other studies in Japan. There was no significant association between the genetically predicted plasma 25-hydroxyvitamin D concentration and total or colorectal cancer in any of the MR analyses. Odds ratios per doubling in vitamin D concentration were 0.83 (95% confidence interval [CI] 0.63-1.09) for total cancer and 1.00 (95% CI 0.80-1.24) for colorectal cancer in inverse variance weighted method, 0.83 (95% CI 0.57-1.19) for total cancer and 1.01 (95% CI 0.75-1.37) for colorectal cancer in MR-Egger method. Consistent with previous MR analyses among European ancestries, there was no significant association identified between 25-hydroxyvitamin D levels and total or colorectal cancer among Asians.

Deterioration of mitochondrial biogenesis and degradation in the endometrium is a cause of subfertility in cows.

To investigate possible causes of reproductive failure, we conducted global endometrial gene expression analyses in fertile and subfertile cows. Ingenuity pathway analysis showed that RICTOR and SIRT3 are significant upstream regulators for highly expressed genes in fertile cows, and are predicted to be activated upstream regulators of normal mitochondrial respiration. Canonical pathway analysis revealed that these highly expressed genes are involved in the activation of mitochondrial oxidative phosphorylation. Therefore, in subfertile cows, the inactivation of RICTOR and SIRT3 may correlate with decreased capacity of mitochondrial respiration. Furthermore, the expression levels of most mitochondrial DNA genes and nuclear genes encoding mitochondrial proteins were higher in subfertile cows. The mitochondrial DNA copy number was significantly higher in the endometrium of subfertile cows, whereas the ATP content did not differ between fertile and subfertile cows. Quantitative reverse transcription-PCR analysis demonstrated that the expression of PGC1a, TFAM, MFN1, FIS1, and BCL2L13 were significantly lower in subfertile cows. In addition, transmission electron microscopy images showed mitochondrial swelling in the endometrial cells of the subfertile cow. These results suggest that poor-quality mitochondria accumulate in the endometrium owing to a reduced capacity for mitochondrial biogenesis, fusion, fission, and degradation in subfertile cows, and may contribute to infertility.

Ultraearly Hematoma Evacuation (<12 Hours) Associated with Better Functional Outcome in Patients with Symptomatic Spontaneous Spinal Epidural Hematoma.

BACKGROUND: Early decompressive surgery within 24 hours improves the functional outcome of patients with traumatic spinal cord injury; however, little is known about the effect of early surgery for spontaneous spinal epidural hematoma (SSEH). In this study, we aimed to investigate the effectiveness of ultraearly hematoma evacuation (<12 hours) for SSEH. METHODS: Patients with SSEH treated with surgical hematoma evacuation at our institution between January 2000 and July 2021 were retrospectively analyzed. Neurologic function was evaluated using the American Spinal Injury Association Impairment Scale (AIS). AIS grades A-C were defined as severe, and grades D and E as mild. AIS grades D and E at the final follow-up were considered favorable outcomes. Preoperative status and postoperative treatment results were compared between patients who had hematoma evacuation within 12 hours of onset and those who underwent surgery after 12 hours. RESULTS: Twenty-five consecutive patients were included in the analysis. Preoperatively, 23 patients (92.0%) had severe AIS. Fourteen (56.0%) patients underwent early surgery. At the final follow-up, 21 patients (84.0%) achieved favorable outcomes. Patients treated with ultraearly surgery had significantly better outcomes (100% vs. 63.6%, P = 0.03). Additionally, the time from onset to surgery was significantly shorter in patients with AIS improvement by 2 or more grades than that in patients with AIS improvement of 1 or less (median 8 hours vs. 14 hours, P = 0.0001). CONCLUSIONS: Ultraearly surgery within 12 hours for SSEH was associated with better functional outcomes.

Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation.

Background and Objectives: Condoliase, a chondroitin sulfate ABC endolyase, is a novel and minimally invasive chemonucleolytic drug for lumbar disc herniation. Despite the growing number of treatments for lumbar disc herniation, the predicting factors for poor outcomes following treatment remain unclear. The aim of this study was to determine the predictive factors for unsuccessful clinical outcome following condoliase therapy. Material and Methods: We performed a retrospective single-center analysis of 101 patients who underwent chemonucleolysis with condoliase from January 2019 to December 2021. Patients were divided into good outcome (i.e., favorable outcome) and poor outcome (i.e., requiring additional surgical treatment) groups. Patient demographics and imaging findings were collected. Clinical outcomes were evaluated using the numerical rating scale and Japanese Orthopaedic Association scores at baseline and at 1- and 3-month follow-up. Pretreatment indicators for additional surgery were compared between the 2 groups. Results: There was a significant difference in baseline leg numbness between the good outcome and poor outcome groups (6.27 ± 1.90 vs. 4.42 ± 2.90, respectively; p = 0.033). Of the 101 included patients, 32 received a preoperative computed tomography scan. In those patients, the presence of calcification or ossification in disc hernia occurred more often in the poor outcome group (61.5% vs. 5.3%, respectively; p < 0.001; odds ratio = 22.242; p = 0.014). Receiver-operating characteristics curve analysis for accompanying calcification or ossification showed an area under the curve of 0.858 (95% confidence interval, 0.715−1.000; p = 0.001). Conclusions: Calcified or ossified disc herniation may be useful predictors of unsuccessful treatment in patients with condoliase administration.

A Privacy-Preserving Distributed Medical Data Integration Security System for Accuracy Assessment of Cancer Screening: Development Study of Novel Data Integration System.

BACKGROUND: Big data useful for epidemiological research can be obtained by integrating data corresponding to individuals between databases managed by different institutions. Privacy information must be protected while performing efficient, high-level data matching. OBJECTIVE: Privacy-preserving distributed data integration (PDDI) enables data matching between multiple databases without moving privacy information; however, its actual implementation requires matching security, accuracy, and performance. Moreover, identifying the optimal data item in the absence of a unique matching key is necessary. We aimed to conduct a basic matching experiment using a model to assess the accuracy of cancer screening. METHODS: To experiment with actual data, we created a data set mimicking the cancer screening and registration data in Japan and conducted a matching experiment using a PDDI system between geographically distant institutions. Errors similar to those found empirically in data sets recorded in Japanese were artificially introduced into the data set. The matching-key error rate of the data common to both data sets was set sufficiently higher than expected in the actual database: 85.0% and 59.0% for the data simulating colorectal and breast cancers, respectively. Various combinations of name, gender, date of birth, and address were used for the matching key. To evaluate the matching accuracy, the matching sensitivity and specificity were calculated based on the number of cancer-screening data points, and the effect of matching accuracy on the sensitivity and specificity of cancer screening was estimated based on the obtained values. To evaluate the performance, we measured central processing unit use, memory use, and network traffic. RESULTS: For combinations with a specificity ≥99% and high sensitivity, the date of birth and first name were used in the data simulating colorectal cancer, and the matching sensitivity and specificity were 55.00% and 99.85%, respectively. In the data simulating breast cancer, the date of birth and family name were used, and the matching sensitivity and specificity were 88.71% and 99.98%, respectively. Assuming the sensitivity and specificity of cancer screening at 90%, the apparent values decreased to 74.90% and 89.93%, respectively. A trial calculation was performed using a combination with the same data set and 100% specificity. When the matching sensitivity was 82.26%, the apparent screening sensitivity was maintained at 90%, and the screening specificity decreased to 89.89%. For 214 data points, the execution time was 82 minutes and 26 seconds without parallelization and 11 minutes and 38 seconds with parallelization; 19.33% of the calculation time was for the data-holding institutions. Memory use was 3.4 GB for the PDDI server and 2.7 GB for the data-holding institutions. CONCLUSIONS: We demonstrated the rudimentary feasibility of introducing a PDDI system for cancer-screening accuracy assessment. We plan to conduct matching experiments based on actual data and compare them with the existing methods.

Thoracic synovial cyst in patient with diffuse idiopathic skeletal hyperostosis.

Background: Spinal synovial cysts, attributed to degenerative changes of the facet joints, commonly occur at the sites of segmental spinal instability. Here, we present a patient with diffuse idiopathic skeletal hyperostosis (DISH) who developed a T10/T11 synovial cyst contributing to myelopathy that resolved following surgical cyst excision. Case Description: A 69-year-old male presented with progressive numbness and paraparesis for 2-month duration. The thoracic MR spine showed synovial cyst at the T10/T11 level, while the computed tomography confirmed DISH fusion between the T4 and T10 levels. Following a laminectomy with cyst excision, the patient's symptoms resolved and he sustained no recurrent dynamic instability. Conclusion: A patient with DISH presented with the new onset of myelopathy attributed to a T10/T11 thoracic synovial cyst; following cyst excision, the patient's myelopahty resolved.

Retro-odontoid pseudotumor presenting double layer on MRI: A case report.

Background: Retro-odontoid pseudotumors (ROPs) typically present as a single mass posterior to the odontoid ranging from isointense to hypointense relative on T1-weighted magnetic resonance (MR) imaging (MRI T1WI). Here, a patient with ROP exhibited the double-layer sign on the MRI T1WI characterized by an initial ventral layer posterior to the odontoid process followed by a secondary dorsal layer. Case Description: An 84-year-old male presented with cervical myelopathy attributed to ROP resulting in atlantoaxial instability on dynamic X-ray studies, and the double-layer sign on the T1 MR accompanied by a cystic component. MR following C1-C2 posterior fusion, the patient's myelopathy resolved and both layers spontaneously regressed on the follow-up MR studies. Conclusion: The MR-documented double layer sign with ROP, likely attributable to reactive hypertrophy of the transverse ligament with cystic components, may demonstrate spontaneous MR regression with symptom resolution following a C1-C2 posterior fusion.

COVID-19-related stigma and its relationship with mental wellbeing: A cross-sectional analysis of a cohort study in Japan.

Objective: Social stigma related to coronavirus disease (COVID-19), i. e., COVID-19 stigma, forms a burden on people socially, economically, and mentally. This study assessed COVID-19 stigma using a scale to identify a population likely to exhibit higher prejudice against COVID-19 itself as well as those infected with COVID-19. Methods: We adapted and modified the Cancer Stigma Scale to assess COVID-19 stigma and used it as the baseline survey of a cohort study in Japan. The questionnaire was disseminated to 1,573 participants (51.7% men) between December 2020 and March 2021. The questionnaire items included the infection status of individuals close to the respondent and their preventive behaviors related to COVID-19, quality of life (QOL; using the EuroQoL 5-Dimension 5-Level [EQ-5D-5L]), and psychological distress (using the 6-item Kessler Psychological Distress Scale [K6]). Exploratory and confirmatory factor analyses were performed to validate the COVID-19 stigma scale, and we further used the structural equation modeling (SEM) to assess the relationship with QOL and psychological distress. Results: COVID-19 stigma was calculated for the 257 (16.3%) participants who responded to the questionnaire. The mean age (standard deviation) was 54.5 (14.4) years, and 50.2% were men. Factor analysis revealed a five-factor model: Awkwardness (feeling uncomfortable being with a person infected before), Severity (fear of not being able to return to normal after infection), Avoidance (attitude of avoiding infected persons), Policy Opposition (expecting more public funding investment), and Personal Responsibility (believing that infected persons themselves are responsible for their infection). Participants > 70 years had the highest scores among other age groups considering all factors except for Policy Opposition. Standardized coefficients in SEM for COVID-19 stigma (latent variable) was highest for Severity (beta = 0.86). Regression coefficients of COVID-19 stigma on K6 and QOL were 0.21 (95% confidence interval [CI] 0.074-0.342) and -0.159 (95% CI -0.295-0.022), respectively. Conclusion: People aged ≥ 70 years are more likely to exhibit COVID-19 stigma. Additionally, the results indicate that COVID-19 stigma impacts QOL and psychological distress.

Availability of Financial and Medical Resources for Screening Providers and Its Impact on Cancer Screening Uptake and Intervention Programs.

Interventions for residents and medical/financial resources available to screening providers can improve cancer screening rates. Yet the mechanisms by which the interactions of these factors affect the screening rates remain unknown. This study employed structural equation modeling to analyze the mechanisms underlying these factors. Data for Japanese municipalities' medical/financial status, their implementation of screening interventions, and the number of municipality-based cancer screening appointments from April 2016 to March 2017 were obtained from an open database. Five cancer screenings were included: gastric, lung, colorectal, breast, and cervical cancer screening; all are nationally recommended for population screening in Japan. We defined two latent variables, namely, intervention for residents and medical/financial resources, and then analyzed the relationships between these variables and screening rates using structural equation modeling. Models were constructed for gastric, lung, and breast cancer screening, and similar relationships were observed. With these cancer types, medical/financial resources affected the intervention for residents, directly affecting screening rates. One limitation of this study is that it only included screening by municipalities, which may cause selection bias. In conclusion, financial pressures and lack of medical resources may cause a reduction in screening intervention programs, leading to stagnant screening rates. Ensuring consistent implementation of interventions for residents may improve local and regional cancer screening rates.

Destructive spondylodiscitis associated with SAPHO syndrome: A case report and literature review.

Background: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare sterile inflammatory disease characterized by cutaneous and osteoarticular lesions. Associated spinal lesions chronically manifest slight or no neurological symptoms. Only rarely does destructive spondylodiscitis occur. Case Description: A 62-year-old female with palmoplantar pustulosis presented with a rapidly progressive quadriparesis. When the cervical MR showed destructive spondylodiscitis at the C5-C7 level, the patient underwent anterior debridement followed by posterior reconstruction/fixation. The histopathology showed a nonspecific inflammatory process with vertebral sclerosis consistent with the diagnosis of SAPHO; cultures were negative. Postoperatively, the patient's symptoms improved and SAPHO did not recur. Conclusion: Destructive spondylodiscitis associated with SAPHO syndrome is uncommon. Early diagnosis and surgical treatment result in the best outcomes.

Blood Lipids and the Risk of Colorectal Cancer: Mendelian Randomization Analyses in the Japanese Consortium of Genetic Epidemiology Studies.

The associations between blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), and colorectal cancer risk are controversial. We evaluated potential causal relationships between blood lipids and colorectal cancer risk. Using the baseline data from the Japanese Consortium of Genetic Epidemiology studies, we estimated the single-nucleotide polymorphism (SNP)-exposure associations (n = 34,546 for TC, n = 50,290 for HDL-C, n = 51,307 for triglycerides, and n = 30,305 for LDL-C). We also estimated the SNP-outcome associations in another Japanese dataset (n = 7,936 colorectal cancer cases and n = 38,042 controls). We conducted Mendelian randomization (MR) analyses for the association between each blood lipid type and the risk of colorectal cancer using an inverse variance-weighted method. The total variances explained by the selected SNPs in TC (68 SNPs), HDL-C (50 SNPs), log-transformed triglycerides (26 SNPs), and LDL-C (35 SNPs) were 7.0%, 10.0%, 6.2%, and 5.7%, respectively. The odds ratios for colorectal cancer were 1.15 [95% confidence interval (CI), 1.01-1.32] per 1 standard deviation (SD; 33.3 mg/dL) increase in TC, 1.11 (95% CI, 0.98-1.26) per 1 SD (15.4 mg/dL) increase in HDL-C, 1.06 (95% CI, 0.90-1.26) per 1 SD (0.5 log-mg/dL) increase in log-transformed triglycerides, and 1.17 (95% CI, 0.91-1.50) per 1 SD (29.6 mg/dL) increase in LDL-C. Sensitivity analyses consistently suggested the positive association between TC and colorectal cancer, whereas results of each lipid component were inconsistent. In conclusion, this large MR study of a Japanese population showed a potentially causal association between high TC and colorectal cancer risk, although the association between each lipid component and colorectal cancer remained inconclusive. PREVENTION RELEVANCE: In this large MR analysis of a Japanese population, a positive association was found between genetically predicted high total cholesterol (TC) levels and an increased risk of colorectal cancer. Therefore, lowering TC levels by lifestyle modifications or medications may be justified for the purpose of preventing colorectal cancer.