Successful treatment of two cases with Philadelphia-chromosome positive acute lymphoblastic leukemia who relapsed after allogeneic stem cell transplantation and the treatments with novel immunotherapies and ponatinib.

The outcomes of relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant to new drugs such as tyrosine kinase inhibitors, inotuzumab ozogamicin (InO) and blinatumomab are dismal. We treated two cases of Ph+ALL resistant to these drugs that achieved long-term survival after treatment with chimeric antigen receptor (CAR)-T cell therapy or a second allogeneic hematopoietic stem cell transplantation (HCT) with a sequential conditioning regimen. Case 1: A 15-year-old boy was diagnosed with Ph+ALL. Despite the second HCT after the treatment of ponatinib and blinatumomab, hematological relapse occurred. InO was ineffective and he was transferred to a CAR-T center. After the CAR-T cell therapy, negative measurable residual disease (MRD) was achieved and maintained for 38 months without maintenance therapy. Case 2: A 21-year-old man was diagnosed with Ph+ALL. Hematological relapse occurred after the first HCT. Despite of the treatment with InO, ponatinib, and blinatumomab, hematological remission was not achieved. The second HCT was performed using a sequential conditioning regimen with clofarabine. Negative MRD was subsequently achieved and maintained for 42 months without maintenance therapy. These strategies are suggestive and helpful to treat Ph+ALL resistant to multiple immunotherapies.

VEXAS syndrome.

VEXAS syndrome is a recently identified, adult-onset autoinflammatory disease caused by somatic mutations in UBA1. UBA1 is an X-linked gene encoding E1 ubiquitin activating enzyme and its mutation in hematopoietic stem and progenitor cells leads to their clonal expansion and myeloid-skewed differentiation. UBA1 mutations in VEXAS are clustered at the second methionine (p.Met41), eliminating UBA1b isoform translated from p.Met41. Loss of UBA1b impairs ubiquitination and activates innate immune pathways, leading to systemic autoinflammation manifested as recurrent fever, chondritis, pulmonary involvement, vasculitis, or neutrophilic dermatitis. VEXAS syndrome is frequently associated with hematological disorders such as myelodysplastic syndrome (MDS), plasma cell dyscrasia and venous thromboembolism. Macrocytic anemia/macrocytosis and vacuoles in myeloid/erythroid precursors are prominent features of VEXAS syndrome, and their presence in patients with autoinflammatory symptoms prompts physicians to screen for UBA1 variant. Treatment of VEXAS syndrome is challenging and no consistently effective therapies have been established. Anti-inflammation therapies including glucocorticoids and anti-interleukin-6 have shown limited efficacy, while azacytidine and JAK inhibitors such as ruxolitinib were found to induce favorable, mid-term responses. Hematopoietic stem cell transplantation is the only curative option for VEXAS and should be considered for younger, fit patients with poor prognostic factors or recalcitrant symptoms.

WT1-guided pre-emptive therapy after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia.

Measurable residual disease (MRD)-guided pre-emptive therapies are now widely used to prevent post-transplant hematological relapse in patients with acute myeloid leukemia (AML). This single-center retrospective study aimed to clarify the significance of pre-emptive treatment based on Wilms' tumor gene-1 mRNA (WT1) monitoring for MRD in patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with AML who received chemotherapy for hematological relapse or WT1 increase after allo-HSCT were eligible for inclusion. From January 2017 to June 2022, 30 patients with a median age of 57 (16-70) years were included and stratified into two groups: 10 with WT1 increase and 20 with hematological relapse. The median times from HCT to WT1 increase or hematological relapse were 309 days (range: 48-985) or 242 days (range: 67-1116), respectively. Less intensive chemotherapy using azacitidine or cytarabine was selected for all patients with WT1 increase and 12 (60%) with hematological relapse. The 1-year overall survival and event-free survival rates for WT1 increase and hematological relapse were 70% vs. 44% (P = 0.024) and 70% vs. 29% (P = 0.029), respectively. These real-world data suggest that WT1-guided pre-emptive therapy may be superior to therapy after hematological relapse in patients with AML who have undergone allo-HSCT.

Large-vessel vasculitis possibly induced by BRAF and MEK inhibitors for BRAF V600E positive lung adenocarcinoma.

The combination therapy of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors is approved for treating patients with BRAF V600E-positive tumours, including melanoma and lung cancer. Several case reports indicated autoimmune side effects associated with the use of BRAF and MEK inhibitors. Still, the effects of these drugs on the immune system were not fully elucidated. Here, we report a patient with large-vessel vasculitis diagnosed after initiation of treatment with dabrafenib and trametinib for BRAF V600E-positive metastatic lung adenocarcinoma. She was a never-smoker woman in her early 70s who presented with a chronic cough and was diagnosed with BRAF V600E-positive metastatic lung adenocarcinoma by transbronchial lung biopsy. She was successfully treated with prednisolone and methotrexate while BRAF and MEK inhibitors were continued. We should be careful about autoimmune diseases using BRAF and MEK inhibitors.

Successful Pregnancy and Delivery After Frozen-thawed Embryo Transfer Following the Third Discontinuation of Tyrosine Kinase Inhibitor in a Woman with Chronic Myeloid Leukemia.

Assisted reproductive technology is a viable option for pregnant women with chronic myeloid leukemia. We herein report the case of a patient who underwent successful fertility treatment with frozen embryo preservation at 36 years of age, followed by embryo transfer at 39 years of age, thus resulting in pregnancy and delivery after a third discontinuation of tyrosine kinase inhibitors (TKI). Despite the difficulty of long-term TKI withdrawal, the patient's strong desire for a baby led to a successful pregnancy and delivery with no apparent deformities or abnormalities. Thus, our case highlights the importance of collaboration between reproductive medicine physicians and hematologists.

Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Background: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Methods: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. Results: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Conclusions: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

Risk factors for early-onset adjacent segment degeneration after one-segment posterior lumbar interbody fusion.

Adjacent segment degeneration (ASD) is a major postoperative complication associated with posterior lumbar interbody fusion (PLIF). Early-onset ASD may differ pathologically from late-onset ASD. The aim of this study was to identify risk factors for early-onset ASD at the cranial segment occurring within 2 years after surgery. A retrospective study was performed for 170 patients with L4 degenerative spondylolisthesis who underwent one-segment PLIF. Of these patients, 20.6% had early-onset ASD at L3-4. In multivariate logistic regression analysis, preoperative larger % slip, vertebral bone marrow edema at the cranial segment on preoperative MRI (odds ratio 16.8), and surgical disc space distraction (cut-off 4.0 mm) were significant independent risk factors for early-onset ASD. Patients with preoperative imaging findings of bone marrow edema at the cranial segment had a 57.1% rate of early-onset ASD. A vacuum phenomenon and/or concomitant decompression at the cranial segment, the degree of surgical reduction of slippage, and lumbosacral spinal alignment were not risk factors for early-onset ASD. The need for fusion surgery requires careful consideration if vertebral bone marrow edema at the cranial segment adjacent to the fusion segment is detected on preoperative MRI, due to the negative impact of this edema on the incidence of early-onset ASD.

Investigation of biomarkers to predict outcomes in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Various biomarkers have been developed and evaluated to predict the prognosis and complications of allogeneic hematopoietic cell transplantation (HCT). Most previous studies conducted on different biomarkers evaluated single effects such as those associated with inflammation, immunology, iron metabolism, and nutrition, and only a few studies have comprehensively analyzed markers. OBJECTIVE: The study aimed to survey comprehensive multiple markers prior to HCT and extract those that significantly predict the outcomes. STUDY DESIGN: A prospective multicenter observational study was performed. (UMIN000013506) Patients undergoing HCT for hematologic diseases were consecutively enrolled. Besides the usual clinical biomarkers, serum samples for extra-clinical biomarkers were collected and cryopreserved before starting the conditioning regimen. A total of 32 candidate biomarkers were selected, 23 from hematology, biochemistry, immunology, nutrition, and iron metabolism, and 9 from composite markers. Based on the area under the curve (AUC) values for survival, promising biomarkers was extracted. Internal validation for these markers was applied based on bootstrap methods. Setting the cut-off values for them, log-rank test was applied and outcomes including overall survival (OS), relapse, and non-relapse mortality (NRM) were evaluated using multivariate analyses. Furthermore, detailed analysis including transplant-related complications and external validation were conducted focusing on C-reactive protein (CRP) to platelet (Plt) ratio. RESULTS: A total of 152 patients with hematologic malignancies were enrolled from April 2014 to March 2017. CRP, soluble interleukin-2 receptor (IL2R), CRP to albumin (Alb) ratio, CRP to Plt ratio, Plt to IL2R ratio, and IL2R to Alb ratio were identified as promising markers. Internal validation successfully confirmed their reliability of AUC and multivariate analysis demonstrated the statistical significance between the higher and the lower markers. Above all, a higher CRP to Plt ratio was significantly associated with a lower OS (hazard ratio [HR] 2.77; 95% confidence interval [CI] 1.30-5.91; P = 0.008) and higher non-relapse mortality rates (HR 2.79; 95%CI 1.14-6.80; P = 0.024) at 180 days. Furthermore, univariate analysis showed that a higher CRP to Plt ratio was significantly associated with a higher incidence of sinusoidal obstructive syndrome (P < 0.001) and bloodstream infection (P = 0.027). An external validation test confirmed the significance of the CRP to Plt ratio for these outcomes. CONCLUSION: The multicenter prospective observational study successfully identified significant biomarkers in patients with hematologic malignancies who received HCT. In particular, CRP to Plt ratio was identified as a novel and useful biomarker for predicting transplant outcomes. Further investigations are needed to validate the novel markers, analysis of the pathophysiology, and application to treatment settings other than HCT.

Acute mixed-lineage leukemia treated with desensitization therapy prior to HLA-haploidentical transplantation with high donor-specific antibodies.

A 43-year-old woman was referred to our department for hematopoietic stem cell transplantation for acute myeloid leukemia, as she failed to achieve remission following induction therapy. Umbilical cord blood transplantation was initially planned; however, multiple anti-human leukocyte antigen (HLA) antibodies with a mean fluorescence intensity of over 10,000 were detected, and optimal umbilical cord blood could not be obtained. The plan was then switched to peripheral blood stem cell transplantation (PBSCT) from the patient's son, who had a 5/8 HLA haploidentical match. However, the patient had donor-specific antibodies against the donor's HLA-B 0702 and HLA-C 0702. To address this issue, after rituximab therapy, the patient was given platelet transfusions from B0702- and C0702-positive donors on day - 1 and day 0, and immunoglobulin on day 0, followed by PBSCT. Donor-specific antibodies decreased by over 90%, and engraftment was confirmed on day 13. Since then, the patient has remained relapse-free and healthy. This case suggests that appropriate management of donor-specific antibodies can enable safe transplantation, even in donors who test positive for these antibodies.

Association of high disease activity and serum IL-6 levels with the incidence of inflammatory major organ events in Behçet disease: a prospective registry study.

Background: Little is known about the relationship between the disease activity of Behçet disease (BD) and the incidence of inflammatory major organ events. Objectives: In this prospective registry study, we investigated the association between the Behçet Disease Current Activity Form (BDCAF) and incidence of inflammatory major organ events, defined as the inflammation of the ocular, central nervous, intestinal, and vascular systems in BD. Methods: We enrolled participants from Japanese multicenter prospective cohorts. The BDCAF was evaluated annually. BD-related symptoms, including inflammatory major organ events, were monitored. The association between BDCAF and inflammatory major organ events was analyzed by time-to-event analysis. An unsupervised clustering of the participants' BDCAF, therapeutic agents, and multiple serum cytokines was also performed to examine their association with inflammatory major organ events. Results: A total of 260 patients were included. The patients had a median BDCAF score of 2 [Interquartile range, 1-3] at the enrolment and remained disease active at 1- and 2-year follow-ups, indicating residual disease activity in BD. Patients with a BDCAF score of 0 had a longer inflammatory major organ event-free survival at 52 weeks than those with a score of 1 or higher (p=2.2 x 10-4). Clustering analysis revealed that patients who did not achieve remission despite treatment with tumor necrosis factor inhibitors had high serum inflammatory cytokine levels and incidences of inflammatory major organ events. Among the elevated cytokines, IL-6 was associated with inflammatory major organ events. Conclusion: This study suggests that treatment strategies targeting overall disease activity and monitoring residual serum IL-6 may help prevent inflammatory major organ events in BD.

A case of Bloom syndrome manifesting with therapy-related myelodysplastic syndromes harboring a novel BLM gene variant.

Bloom syndrome (BS) is an autosomal recessive genetic disorder caused by variants in the BLM gene. BS is characterized by distinct facial features, elongated limbs, and various dermatological complications including photosensitivity, poikiloderma, and telangiectatic erythema. The BLM gene encodes a RecQ helicase critical for genome maintenance, stability, and repair, and a deficiency in functional BLM protein leads to genomic instability and high predisposition to various types of cancers, particularly hematological and gastrointestinal malignancies. Here, we report a case of BS with a previously unreported variant in the BLM gene. The patient was a 34-year-old woman who presented with short stature, prominent facial features, and a history of malignancies, including lymphoma, breast cancer, and myelodysplastic syndromes (MDS). She was initially treated with azacitidine for MDS and showed transient improvement, but eventually died at age of 35 due to progression of MDS. Genetic screening revealed compound heterozygous variants in the BLM gene, with a recurrent variant previously reported in BS in one allele and a previously unreported variant in the other allele. Based on her characteristic clinical features and the presence of heterozygous variants in the BLM gene, she was diagnosed with BS harboring compound heterozygous BLM variants.

Impact of malnutrition on mortality and neurological recovery of older patients with spinal cord injury.

This retrospective cohort study established malnutrition's impact on mortality and neurological recovery of older patients with cervical spinal cord injury (SCI). It included patients aged ≥ 65 years with traumatic cervical SCI treated conservatively or surgically. The Geriatric Nutritional Risk Index was calculated to assess nutritional-related risk. Overall, 789 patients (mean follow-up: 20.1 months) were examined and 47 had major nutritional-related risks on admission. One-year mortality rate, median survival time, neurological recovery, and activities of daily living (ADL) at 1 year post-injury were compared between patients with major nutrition-related risk and matched controls selected using 1:2 propensity score matching to adjust for age, pre-traumatic neurological impairment, and activity. In the Kaplan-Meier analysis, the median survival times were 44.9 and 76.5 months for patients with major nutrition-related risk and matched controls, respectively (p = 0.015). Matched controls had more individuals with a neurological improvement of American Spinal Injury Association Impairment Scale ≥ 1 grade (p = 0.039) and independence in ADL at 1 year post-injury than patients with major nutrition-related risk (p < 0.05). In conclusion, 6% of older patients with cervical SCI had major nutrition-related risks; they showed a significantly higher 1 year mortality rate, shorter survival time, poorer neurological improvement, and lower ADL at 1 year post-injury than matched controls.

Neurological recovery rate and predictive factors of incomplete AIS grade C spinal cord injury in the older aged population.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To define the prognosis and predictive factors for neurological improvement in older patients with incomplete spinal cord injury (SCI) of American Spinal Injury Association Impairment Scale grade C (AIS-C). SETTINGS: Multi-institutions in Japan. METHODS: We included patients aged ≥65 years with traumatic SCI of AIS-C who were treated conservatively or surgically with >3 follow-up months. To identify factors related to neurological improvement, patients were divided into three groups according to their neurological status at the final follow-up, with univariate among-group comparisons of demographics, radiographic, and therapeutic factors. Significant variables were included in the multivariate logistic regression analysis. RESULTS: Overall, 296 older patients with SCI of AIS-C on admission were identified (average age: 75.2 years, average follow-up: 18.7 months). Among them, 190 (64.2%) patients improved to AIS-D and 21 (7.1%) patients improved to AIS-E at final follow-up. There were significant among-group differences in age (p = 0.026), body mass index (p = 0.007), status of pre-traumatic activities of daily living (ADL) (p = 0.037), and serum albumin concentrations (p = 0.011). Logistic regression analysis showed no significant differences in variables in the stratified group of patients who improved to AIS-D. Meanwhile, serum albumin was a significant variable in patients who improved to AIS-E (p = 0.026; OR: 6.20, pre-traumatic ADL was omitted due to data skewness). CONCLUSIONS: Most older patients with incomplete AIS-C SCI demonstrated at least 1 grade of neurological improvement. However, <10% of patients achieved complete recovery. Key predictors of complete recovery were high serum albumin levels on admission and independent pre-traumatic ADL. SPONSORSHIP: No funding was received for this study.

Tabular Two-Dimensional Correlation Analysis for Multifaceted Characterization Data.

We propose tabular two-dimensional correlation spectroscopy analysis for extracting features from multifaceted characterization data, essential for understanding material properties. This method visualizes similarities and phase lags in structural parameter changes through heatmaps, combining hierarchical clustering and asynchronous correlations. We applied the proposed method to data sets of carbon nanotube (CNT) films annealed at various temperatures and revealed the complexity of their hierarchical structures, which include elements such as voids, bundles, and amorphous carbon. Our analysis addresses the challenge of attempting to understand the sequence of structural changes, especially in multifaceted characterization data where 11 structural parameters derived from eight characterization methods interact with complex behavior. The results show how phase lags (asynchronous changes from stimuli), and parameter similarities can illuminate the sequence of structural changes in materials, providing insights into phenomena such as the removal of amorphous carbon and graphitization in annealed CNTs. This approach is beneficial even with limited data and holds promise for a wide range of material analyses, demonstrating its potential in elucidating complex material behaviors and properties.

Pretransplantation Inflammatory and Nutritional Status in Elderly Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Value of C-Reactive Protein-to-Albumin Ratio.

There are no clear criteria for selecting elderly patients with hematologic malignancies eligible for allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to evaluate inflammatory and nutritional status biomarkers as prognostic indicators of allogeneic HSCT in elderly patients. We compared the prognostic effects of 4 representative pretransplantation biomarkers: C-reactive protein-to-albumin ratio (CAR), Glasgow Prognostic Score (GPS), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR). A total of 143 patients age ≥60 years who underwent their first allogeneic HSCT for a hematologic malignancy were enrolled between 2010 and 2020 in our single-center cohort. The median patient age was 65 years (range, 60 to 72 years). Pretransplantation high CAR, high GPS, and low PNI scores were associated with poor overall survival (OS), but the AGR was not associated with OS. Among the 4 biomarkers, CAR stratified OS most significantly (P < .001). Multivariate analyses identified only high CAR as an independent prognostic factor associated with OS (hazard ratio [HR], 1.98; P = .031) and showed that a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥3 also was associated with OS (HR, 2.04; P = .012). High CAR was correlated with poor performance status, male sex, and high Disease Risk Index, but not with high HCT-CI score. When the patients were stratified into 3 groups according to a composite risk assessment using CAR and HCT-CI, the 3-year OS decreased significantly with increasing scores (82.8%, 50.3%, and 27.0%, respectively; P < .0001). In conclusion, CAR is the most useful prognostic indicator among the inflammatory and nutritional status biomarkers for allogeneic HSCT in elderly patients. Inflammatory and nutritional status in the elderly may be important prognostic factors for allogeneic HSCT independent of HCT-CI score.

Early Versus Delayed Surgery for Elderly Traumatic Cervical Spinal Injury: A Nationwide Multicenter Study in Japan.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: The effectiveness of early surgery for cervical spinal injury (CSI) has been demonstrated. However, whether early surgery improves outcomes in the elderly remains unclear. This study investigated whether early surgery for CSI in elderly affects complication rates and neurological outcomes. METHODS: This retrospective multicenter study included 462 patients. We included patients with traumatic acute cervical spinal cord injury aged ≥65 years who were treated surgically, whereas patients with American Spinal Injury Association (ASIA) Impairment Scale E, those with unknown operative procedures, and those waiting for surgery for >1 month were excluded. The minimum follow-up period was 6 months. Sixty-five patients (early group, 14.1%) underwent surgical treatment within 24 hours, whereas the remaining 397 patients (85.9%) underwent surgery on a standby basis (delayed group). The propensity score-matched cohorts of 63 cases were compared. RESULTS: Patients in the early group were significantly younger, had significantly more subaxial dislocations (and fractures), tetraplegia, significantly lower ASIA motor scores, and ambulatory abilities 6 months after injury. However, no significant differences in the rate of complications, ambulatory abilities, or ASIA Impairment Scale scores 6 months after injury were observed between the matched cohorts. At 6 months after injury, 61% of the patients in the early group (25% unsupported and 36% supported) and 53% of the patients in the delayed group (34% unsupported and 19% supported) were ambulatory. CONCLUSIONS: Early surgery is possible for CSI in elderly patients as the matched cohort reveals no significant difference in complication rates and neurological or ambulatory recovery between the early and delayed surgery groups.

Comparison of standardized prophylactic high-dose and intrathecal methotrexate for DLBCL with a high risk of CNS relapse.

The efficacy of high-dose methotrexate (HD-MTX) for central nervous system (CNS) relapse prophylaxis in patients with high-risk diffuse large B-cell lymphoma (DLBCL) is controversial. We compared the prophylactic effects of HD-MTX and intrathecal methotrexate (IT-MTX) on CNS relapse in high-risk DLBCL, in a multicenter retrospective study. A total of 132 patients with DLBCL at high risk of CNS relapse who received frontline chemotherapy and IT-MTX from 2003 to 2013 (n = 34) or HD-MTX from 2014 to 2020 (n = 98) were included. After a median follow-up of 52 months (range: 9-174), 11 patients had isolated CNS relapse: six (6.1%) in the HD-MTX group and five (14.7%) in the IT-MTX group. The median time until CNS relapse was 38 months (range: 11-122), and the cumulative incidence of CNS relapse at 3 years was 3.9% in the HD-MTX group and 6.1% in the IT-MTX group (P = 0.93). Similar results were obtained after adjusting for background factors using propensity score-matched analysis (4.5% HD-MTX vs. 7.6% IT-MTX, P = 0.84). The CNS relapse rate in HD-MTX-treated patients was equivalent to that in IT-MTX patients, demonstrating that HD-MTX was not superior to IT-MTX in preventing CNS relapse.

Pregnancy outcomes in patients with familial Mediterranean fever: systematic review and meta-analysis.

OBJECTIVE: The relationship between FMF and pregnancy outcomes remains unclear. This systematic review and meta-analysis aimed to clarify this association. METHODS: Electronic databases-PubMed, Web of Science, Cochrane, and EMBASE-were searched on 20 December 2022, using specific search terms. Case-control, cohort, and randomized clinical trial studies comparing patients with FMF and healthy controls were considered eligible. We excluded systematic reviews, meta-analyses, case series with fewer than five cases, republished articles without new findings on pregnancy outcomes, studies targeting paternal FMF, and those not published in English. The results were summarized in the form of odds ratios (ORs) and 95% CIs, using a random-effects model. This study was registered in the University hospital Medical Information Network Clinical Trials Registry (Japan) as UMIN000049827. RESULTS: The initial electronic search identified 611 records, of which 9 were included in this meta-analysis (177 735 pregnancies, 1242 with FMF, and 176 493 healthy controls). FMF was significantly associated with increased odds of preterm deliveries (OR, 1.67; 95% CI, 1.05-2.67; I2 = 22%) and insignificantly associated with increased odds of fetal growth restriction (OR, 1.45; 95% CI, 0.90-2.34; I2 = 0%) and hypertensive disorders during pregnancy (OR, 1.28; 95% CI, 0.87-1.87; I2 = 0%). CONCLUSION: FMF was significantly associated with preterm delivery and insignificantly associated with fetal growth restriction and hypertensive disorders. All of the included studies were observational studies. Treatment characteristics were not fully collected from the articles, and further analysis of treatments for FMF in pregnancy is still warranted.

Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: A retrospective multicenter study.

BACKGROUND: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. METHODS: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. RESULTS: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. CONCLUSIONS: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly.