Oral alkalinizing supplementation suppressed intrarenal reactive oxidative stress in mild-stage chronic kidney disease: a randomized cohort study.

BACKGROUND: The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD. METHODS: This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6 months (short-term study) for the primary endpoints and extended to 2 years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury. RESULTS: Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6 months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1 year, or p = 0.0186, vs. 2 years) and urinary excretion of 8-hydroxy-2'-deoxyguanosine (p = 0.0481, baseline vs. 6 months). CONCLUSION: This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.

Continuous diffuse brain atrophy independent of relapse as a hallmark of multiple sclerosis beginning from relapsing-remitting stage.

BACKGROUND: Neurodegenerative changes are observed in relapsing-remitting multiple sclerosis (RRMS) and are prominent in secondary progressive MS (SPMS). However, whether neurodegenerative changes accelerate and are altered after the transition into SPMS or in the presence of relapses remains uncertain. METHODS: In this study, 73 patients with MS (seven with relapsing RRMS, 56 with relapse-free RRMS, and 10 with relapse-free SPMS) were evaluated for brain segmental volume changes over a 2-year follow-up period. Volume change was calculated using a within-subject unbiased longitudinal image analysis model. RESULTS: The rates of brain volume change in the 11 brain regions evaluated were relatively similar among different brain regions. Moreover, they were similar among the relapsing RRMS, relapse-free RRMS, and SPMS groups, even after adjusting for age. CONCLUSIONS: The relatively constant brain segmental atrophy rate throughout the disease course, regardless of relapse episodes, suggests that RRMS and SPMS are continuous, uniform, and silent progressing brain atrophy diseases on a spectrum.

Risk Assessment of Critical Obstetric Bleeding With Low-Molecular-Weight Heparin.

BACKGROUND: Use of unfractionated heparin (UFH) during the peripartum period is considered to be a higher risk of critical obstetric bleeding compared to low-molecular-weight heparin (LMWH). However, the evidence for the safety of using LMWH during the peripartum period is currently lacking. METHODS: This study retrospectively investigated a nationwide medical database to clarify the safety of using LMWH during childbirth. The Japanese Nationwide Diagnosis Procedure Combination database was retrospectively reviewed, and data from women with childbirth between 2018 and 2022 were collected. RESULTS: Among the overall 354,299 women with childbirth, 3,099 were with obstetric disseminated intravascular coagulation (DIC), 484 were with critical obstetric bleeding requiring massive red blood cell (RBC) transfusion ≥4,000 cc, and 38 were with maternal death. Among the overall women, each of the anticoagulants other than LMWH was associated with critical obstetrical bleeding with an adjusted odds ratio (aOR) greater than 1.0, while LMWH was not associated with critical obstetrical bleeding (aOR, 0.54 (95% confidence interval, 0.11-2.71)). This finding did not change in subgroup analyses among those with Cesarean section. Furthermore, UFH was associated with critical bleeding among the 3,099 women with obstetrical DIC (aOR, 3.91 (2.83-5.46)), while LMWH was not (aOR, 0.26 (0.03-1.37)). CONCLUSION: The use of UFH was significantly associated with an increased critical obstetric hemorrhage requiring massive RBC transfusion or total hysterectomy. Meanwhile, the use of LMWH was not associated with increased critical obstetric bleeding. LMWH would be safer than UFH to be used for women during childbirth.

Post-Toilet Wiping Style Is Associated With the Risk of Urinary Tract Infection in Women.

INTRODUCTION: Urinary tract infection (UTI) has a lifetime incidence of ≥50% in women. A wide variety of clinical, physiological, and lifestyle risk factors for UTI have been identified, but the exact relationship between post-toilet anal and perineal hygiene practices, especially the wiping direction with toilet paper, and UTI risks has not been investigated yet. Therefore, this study cross-sectionally investigated the post-toilet wiping habit and lifetime UTI events in the general population. METHODS: Individuals who visited two hospitals in Japan between April 2020 and March 2023 were initially recruited. Self-reported questionnaires regarding post-toilet wiping habits and past UTI events were collected, and their relationship was investigated in males and females. Subgroup analyses by age were further performed to estimate the impact of age on the relationship. RESULTS: A total of 294 individuals (141 males and 153 females) agreed to participate and answered the question of post-toilet wiping direction. The number of individuals with post-toilet wiping with the arm from the front between the legs was 32 (23%) in males and 68 (44%) in females. The lifetime UTI events were more frequent in females than in males (p<0.0001). The impact of post-toilet wiping with the arm from the front between the legs on UTI events, adjusting for the age and history of diabetes mellitus, was not statistically significant both in males and females (p≥0.10 for both). Meanwhile, when the relationship was evaluated by different age groups, wiping habits from the front and UTI were significantly associated with each other in middle-aged women aged 40-59, whereas they were not in younger and older age groups. CONCLUSION: Approximately 40-50% of women performed post-toilet wiping with the arm from the front between the legs. This post-toilet wiping habit was suggested to be a potential risk of UTI in women, especially in middle-aged subgroups, and may be better to be changed to wiping from behind.

Low Hemoglobin Level and Elevated Inflammatory Hematological Ratios Associated With Depression and Sleep Disturbance.

BACKGROUND: The relationship between blood cell profiles, including hemoglobin (Hb) levels and inflammatory hematological ratios, and mental health problems currently remains unclear. AIM: This study aimed to investigate the relationship between blood cell profiles and mental health issues, including depressive state and sleep disturbance, while adjusting for potential demographic confounders. METHODOLOGY: This retrospective, cross-sectional, observational study used a population-based medical database from the Tohoku Medical Megabank Project with more than 60,000 volunteers. Data on age, sex, daily tobacco use, body mass index, and self-reported scores on the Kessler Psychological Distress Scale (K6), Athens Insomnia Scale (AIS), and the Center for Epidemiologic Studies Depression Scale (CES-D) were collected. RESULTS: A total of 62,796 volunteers (23,663 males and 39,133 females), aged ≥20 years at the time of the blood test, agreed to participate in this study. Among the evaluated blood cell profiles, Hb, hematocrit, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were significantly correlated with the K6, AIS, and CES-D scores, with strong statistical significance (p<0.0001 for all) in bivariate correlation analyses. A significant adjusted odds ratio (aOR) of the Hb level for elevated CES-D scores (aOR=0.965 [95% CI: 0.949-0.981], p<0.0001) was confirmed after adjusting for demographic data and daily tobacco use using a logistic regression model. Sensitivity analyses revealed that these associations existed in both males and females but were more prominent in the former. In male participants, a low Hb level was significantly associated with an elevated AIS score. The evaluated inflammatory hematological ratios, including NLR, PLR, and monocyte-to-lymphocyte ratio (MLR), also showed significant aORs with the K6, AIS, and CES-D scores after adjusting for demographic background. CONCLUSION: Low Hb levels and elevated inflammatory hematological ratios (NLR, MLR, and PLR) were associated with depressive state and sleep disturbances in the general population.

Stochastic models for the onset and disease course of multiple sclerosis.

OBJECTIVE: Exact causes and mechanisms regulating the onset and progression in many chronic diseases, including multiple sclerosis (MS), remain uncertain. Until now, the potential role of random process based on stochastic models in the temporal course of chronic diseases remains largely unevaluated. Therefore, the present study investigated the applicability of stochastic models for the onset and disease course of MS. METHODS: Stochastic models with random temporal process in disease activity, underlying clinical relapse and/or subclinical brain atrophy, were developed. The models incorporated parameters regarding the distribution of temporal changes in disease activity and the drift constant. RESULTS: By adjusting the parameters (temporal change dispersion and drift constant) and the threshold for the onset of disease, the stochastic disease progression models could reproduce various types of subsequent disease course, such as clinically isolated syndrome (monophasic), relapsing-remitting MS, primary-progressive MS, and secondary-progressive MS. Furthermore, the disease prevalence and distribution of onset age could be also reproduced with stochastic models by adjusting the parameters. The models could further explain why approximately half of the patients with relapsing-remitting MS will eventually experience a transition to secondary-progressive MS. CONCLUSION: Stochastic models with random temporal changes in disease activity could reproduce the characteristic onset age distribution and disease course forms in MS. Further studies by using real-world data to underscore the significance of random process in the occurrence and progression of MS are warranted.

A Reduction in the Number of Hospitalized Cases of Acute Meningitis during the COVID-19 Pandemic in Japan.

Objective The changes in the prevalence of acute meningitis during the coronavirus disease 2019 (COVID-19) pandemic remain unclear. This study aimed to compare the prevalence of acute meningitis before and during the COVID-19 pandemic in Japan. Methods We retrospectively reviewed the Japanese nationwide administrative medical payment system database, Diagnosis Procedure Combination (DPC), from 2016 to 2022. A total of 547 hospitals consistently and seamlessly offered DPC data during this period. The study period was divided into the following three periods: April 2016 to March 2018 (fiscal years 2016-2017), April 2018-March 2020 (2018-2019), and April 2020-March 2022 (2020-2021). Results Among the 28,161,806 patients hospitalized during the study period, 28,399 were hospitalized for acute meningitis: 16,678 for viral/aseptic type, 6,189 for bacterial type, 655 for fungal type, 429 for tuberculous, 2,310 for carcinomatous type, and 2,138 for other or unknown types of meningitis. A significant decrease during the pandemic was confirmed in viral (n=7,032, n=5,775, and n=3,871 in each period; p<0.0001) and bacterial meningitis (n=2,291, n=2,239, and n=1,659; p<0.0001) cases. Meanwhile, no decrease was observed in fungal meningitis (n=212, n=246, and n=197; p=0.056) or carcinomatous meningitis (n=781, n=795, and n=734; p=0.27). The decrease in the number of tuberculous meningitis cases was equivocal (n=166, n=146, and n=117; p=0.014). The decrease during the pandemic was more remarkable in younger populations aged <50 years than in older populations, both for viral and bacterial meningitis. Conclusion The number of hospitalized cases of acute meningitis clearly decreased during the COVID-19 pandemic, especially for viral and bacterial meningitis in younger populations aged <50 years.

Improved Activities of Daily Living With Adjunctive Intravenous Steroids in Bacterial Meningitis: A Nationwide, Population-Based Medical Database Study.

The benefit of using adjunctive intravenous steroids (IVS) to reduce the neurological sequelae in bacterial meningitis remains inconclusive. This study evaluated the effect of IVS on improving the subsequent Activities of Daily Living (ADL) in bacterial meningitis by analyzing data from a large nationwide administrative medical database in Japan. Data from 1,132 hospitals, covered by the administrative Diagnosis Procedure Combination (DPC) payment system from 2016 to 2022, were evaluated. The ADL levels at admission and discharge were measured using the Barthel Index (BI). Out of the cumulative 47,366,222 patients hospitalized, 8,736 were diagnosed with acute bacterial meningitis and had BI data available. The BI at discharge, adjusted for sex, age, and BI at admission, was significantly better among those treated with IVS (p<0.0001). Exploratory subgroup analyses suggested that this benefit is expected across a broad spectrum of bacterial species. In summary, the use of IVS for improving the subsequent ADL level in bacterial meningitis was suggested.

Basal Ganglia Atrophy and Impaired Cognitive Processing Speed in Multiple Sclerosis.

Impaired cognitive processing speed is among the important higher brain dysfunctions in multiple sclerosis (MS). However, the exact structural mechanisms of the dysfunction remain uncertain. This study aimed to identify the brain regions associated with the impaired cognitive processing speed in MS by comparing the cognitive processing speed, measured using the Cognitive Processing Speed Test (CogEval) z-score, and brain regional volumetric data. Altogether, 80 patients with MS (64 with relapsing-remitting MS [RRMS] and 16 with secondary progressive MS [SPMS]) were enrolled. Consequently, CogEval z-scores were worse in patients with SPMS than in those with RRMS (p=0.001). In the univariate correlation analyses, significant correlations with CogEval z-score were suggested in the MS lesion volume (p<0.001; Spearman's rank correlation test) and atrophies in the cerebral cortex (p=0.031), cerebral white matter (p=0.013), corpus callosum (p=0.001), thalamus (p=0.001), and putamen (p<0.001). Multiple linear regression analysis revealed that putamen atrophy was significantly associated with CogEval z-score (p=0.038) independent of volume in other brain regions, while thalamic atrophy was not (p=0.79). Univariate correlation analyses were further performed in each of RRMS and SPMS. None of the evaluated volumetric data indicated a significant correlation with the CogEval z-score in RRMS. Meanwhile, atrophies in the cerebral white matter (p=0.008), corpus callosum (p=0.002), putamen (p=0.011), and pallidum (p=0.017) demonstrated significant correlations with CogEval z-score in SPMS. In summary, the putamen could be an important region of atrophy contributing to the impaired cognitive speed in MS, especially in the later disease stages after a transition to SPMS.

Enlarged choroid plexus in multiple sclerosis is associated with increased lesion load and atrophy in white matter but not gray matter atrophy.

BACKGROUND: Enlargement of the choroid plexus (CP) is reported to associate with inflammatory activity and contribute to brain atrophy in patients with multiple sclerosis (pwMS). However, a recent study in healthy volunteers (HVTs) has suggested that CP enlargement can be attributed to ventriculomegaly. OBJECTIVES: To clarify the pathological significance of the enlargement of CP in multiple sclerosis (MS). METHODS: A total of 102 pwMS (89 with relapsing-remitting MS and 13 with secondary progressive MS) and 41 HVTs were cross-sectionally evaluated using brain volumetry. The CP volume was compared between disease groups and investigated for the relationships with other brain regional volumes. RESULTS: CP volume was significantly larger in pwMS than in HVTs in the univariate analysis, but not in multivariable analysis. Meanwhile, the CP and lateral ventricle (LV) volumes were significantly correlated. CP enlargement was significantly associated with increased lesion load and cerebral white matter (WM) atrophy, even after adjusting for LV volume. In contrast, multivariable analyses revealed that LV enlargement, but not CP enlargement, was associated with total gray matter (GM) atrophy. CONCLUSION: CP enlargement was closely associated with LV enlargement. After adjusting for LV volume, CP enlargement in pwMS was associated with increased lesion load and WM atrophy but not GM atrophy.

Demographic profiles and risk factors for mortality in acute meningitis: A nationwide population-based observational study.

Aim: Acute meningitis encompasses bacterial, viral (aseptic), fungal, tuberculous, and carcinomatous meningitis. The rate and risks of mortality in each type remain uncertain. This study aimed to elucidate these aspects in each type of meningitis. Methods: This study utilized Japan's nationwide administrative Diagnosis Procedure Combination (DPC) database. Patients with acute meningitis, treated at 1132 DPC-covered hospitals from 2016 to 2022, were enrolled. Results: Among 47,366,222 cumulative hospitalized patients, 48,758 (0.10%) were hospitalized with acute meningitis. The types of meningitis were as follows: 10,338 with bacterial, 29,486 with viral/aseptic, 965 with fungal, 678 with tuberculous, and 3790 with carcinomatous meningitis. Bacterial and viral meningitis exhibited bimodal age distributions, with the first peak occurring at 0-9 years. The median onset age was below 50 years only in viral meningitis. The mortality rate was the highest in carcinomatous meningitis (39%), followed by fungal meningitis (21%), and the lowest in viral meningitis (0.61%). Mortality rates increased with age across all meningitis types, but this trend was less prominent in carcinomatous meningitis. The duration from admission to mortality was longer in fungal and tuberculous meningitis compared with other types. Staphylococcus aureus in bacterial meningitis (adjusted odds ratio 1.71; p = 0.0016) and herpes simplex virus in viral meningitis (adjusted odds ratio 1.53; p = 0.0467) exhibited elevated mortality rates. Conclusion: Distinct demographic profiles and mortality rates were observed among different meningitis types. The high mortality rates in less common types of meningitis emphasize the necessity to further optimize the required diagnostic and treatment strategies.

Prenatal hypertension as the risk of eclampsia, HELLP syndrome, and critical obstetric hemorrhage.

Critical bleeding is a common cause of maternal mortality in obstetric patients. However, the non-obstetric factors underlying critical obstetric bleeding remain uncertain. Therefore, this study aimed to clarify the impact of chronic hypertension on obstetric hemorrhage by evaluating a nationwide administrative database in Japan. Women who gave birth between 2018 and 2022 were enrolled. The primary outcome was critical hemorrhage requiring massive red blood cell (RBC) transfusion during childbirth. In total, 354, 299 eligible women were selected from the database. The maternal mortality rate was >1.0% among those who received a massive RBC transfusion (≥4000 cc), and this amount was used as the cutoff of the outcome. Critical hemorrhage was less frequent with elective Caesarean section (CS) compared with vaginal childbirth or emergent CS (odds ratio [OR], 0.38; 95% confidence interval, 0.30-0.47). Multiple logistic regression analysis adjusting for these obstetric risks revealed that a higher maternal age (adjusted OR [aOR] per 1 year, 1.07 [1.05-1.09]); oral medications with prednisolone (aOR, 2.5 [1.4-4.4]), anti-coagulants (aOR, 10 [5.4-19]), and anti-platelets (aOR, 2.9 [1.3-6.4]); and a prenatal history of hypertension (aOR, 2.5 [1.5-4.4]) and hypoproteinemia (aOR, 5.8 [1.7-20]) are the risks underlying critical obstetric hemorrhage. Prenatal history of hypertension was significantly associated with obstetric disseminated intravascular coagulation (OR, 1.9 [1.5-2.4]); Hemolysis, Elevated Liver enzymes, and Low platelet count (HELLP) syndrome (OR, 3.3 [2.7-4.2]); and eclampsia (OR, 6.1 [4.6-8.1]). In conclusion, a maternal prenatal history of hypertension is associated with the development of HELLP syndrome, eclampsia, and resultant critical hemorrhage. The incidence of HELLP syndrome and eclampsia increased more than fivefold in the presence of prenatal hypertension. However, the likelihood of subsequently developing DIC or experiencing critical bleeding did not change by the presence of prenatal hypertension.

Evaluation of Statistical Approaches in Developing a Predictive Model of Severe COVID-19 during Early Phase of Pandemic with Limited Data Resources.

As evidence of risk factors for severe cases of coronavirus disease 2019 (COVID-19) was uncertain in early phases of the pandemic, the development of an efficient predictive model for severe cases to triage high-risk individuals represented an urgent yet challenging issue. It is crucial to select appropriate statistical models when available data and evidence are limited. This study was conducted to assess the accuracy of different statistical models in predicting severe cases using demographic data from patients with COVID-19 prior to the emergence of consequential variants. We analyzed data from 929 consecutive patients diagnosed with COVID-19 prior to March 2021, including their age, sex, body mass index, and past medical histories, and compared areas under the receiver operating characteristic curve (ROC AUC) between different statistical models. The random forest (RF) model, deep learning (DL) models with not too many neurons, and naïve Bayes model exhibited AUC measures of > 0.70 with the validation datasets. The naïve Bayes model performed the best with the AUC measures of > 0.80. The accuracies in RF were more robust with narrower distribution of AUC measures compared to those in DL. The benefit of performing feature selection with a training dataset before building models was seen in some models, but not in all models. In summary, the naïve Bayes and RF models exhibited ideal predictive performance even with limited available data. The benefit of performing feature selection before building models with limited data resources depended on machine learning methods and parameters.

Progression independent of relapses in aquaporin4-IgG-seropositive neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and multiple sclerosis.

OBJECTIVES: To determine whether progression independent of relapse activity (PIRA) is present in Aquaporin4-IgG-seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD), Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and relapsing remitting Multiple sclerosis (RRMS). METHODS: We retrospectively studied the change in EDSS, confirmed disability worsening (CDW) (i.e., PIRA), and new MRI lesions in AQP4+NMOSD, and MOGAD and MS patients. Linear mixed-effect regression model was used to compare the longitudinal changes in EDSS, and Cox regression was used to compare changes in MRI. RESULTS: The estimated mean ΔEDSS in the AQP4+NMOSD and matched MS group were +0.06 (95%CI: -0.40, +0.52, p = 0.76), and +0.02 (95%CI: -0.05, +0.08, p = 0.6) respectively. The same estimate was -0.08 (95%CI: -0.18, +0.02, p = 0.12) in MOGAD and +0.05 (95%CI: -0.05, +0.15, p = 0.35) in matched MS group. Comparing groups for the presence of CDW (i.e., PIRA) showed that PIRA is more associated with MS compared to AQP4+NMOSD (p = 0.02) and MOGAD (p<0.001). Compared to their matched MS groups, the annualized rate of PIRA was significantly lower in AQP4 (0.08 vs 0.44; p<0.0001), and MOG groups (0.04 vs 0.13; p<0.0001). New T2 or enhancing lesions on brain MRI were higher in MS compared to AQP4+NMOSD and MOGAD patients. CONCLUSION: Relapse-independent changes in the EDSS, CDW, and MRI activity are not common in AQP4+NMOSD and MOGAD, especially when compared with MS. Since our patients were on relapse prevention therapies at the time of EDSS measurements, our study supports the importance of preventing relapses in AQP4+NMOSD and MOGAD and suggests different pathologic mechanisms of relapse-free neurological damage between MS and AQP4+NMOSD/MOGAD.

Blood Culture Result Profile in Patients With Central Line-Associated Bloodstream Infection (CLABSI): A Single-Center Experience.

Background Central line-associated bloodstream infection (CLABSI) is among the most common bloodstream infections in the university hospital and intensive care unit settings. This study evaluated the routine blood test findings and microbe profiles of bloodstream infection (BSI) by the presence and types of central vein (CV) access devices (CVADs). Methods A total of 878 inpatients at a university hospital who were clinically suspected for BSI and underwent blood culture (BC) testing between April 2020 and September 2020 were enrolled. Data regarding age at BC testing, sex, WBC count, serum C-reactive protein (CRP) level, BC test results, yielded microbes, and usage and types of CVADs were evaluated. Results The BC yields were detected in 173 patients (20%), suspected contaminating pathogens in 57 (6.5%), and 648 (74%) with a negative yield. The WBC count (p=0.0882) and CRP level (p=0.2753) did not significantly differ between the 173 patients with BSI and the 648 patients with negative BC yields. Among the 173 patients with BSI, 74 used CVADs and met the diagnosis of CLABSI; 48 had a CV catheter, 16 had CV access ports, and 10 had a peripherally inserted central catheter (PICC). Patients with CLABSI showed lower WBC counts (p=0.0082) and serum CRP levels (p=0.0024) compared to those with BSI who did not use CVADs. The most commonly yielded microbes in those with CV catheters, CV-ports, and PICC were Staphylococcus epidermidis (n=9; 19%), Staphylococcus aureus (n=6; 38%), and S. epidermidis (n=8; 80%), respectively. Among those with BSI who did not use CVADs, Escherichia coli (n=31; 31%) was the most common pathogen, followed by S. aureus (n=13; 13%). Conclusion Patients with CLABSI showed lower WBC counts and CRP levels than those with BSI who did not use CVADs. Staphylococcus epidermidis was among the most common microbes in CLABSI and accounted for the majority of yielded microbes in patients who used PICC.

Recently Added Frameshift Mutation in Human Monkeypox Virus (hMPXV) OPG191 Gene.

Human monkeypox virus (hMPXV) has caused sporadic outbreaks intermittently across countries in recent years, with the largest outbreak in 2022. However, the underlying mechanisms remain unclear. This study searched for recently developed structural variants of the viral genome. A total of 22 hMPXV whole genome sequences were randomly selected from the National Center for Biotechnology Information GenBank sequence database for initial screening. As a result, a recent frameshift mutation based on a 2-base insertion in a coding region was identified at the 3' terminal of the OPG191 gene, which encodes MPXVgp168 (B7R) protein. With this insertion, the protein was prematurely truncated, and the last 11 amino acids were missing, with 3 alternative amino acids added. Among the hMPXV genome sequences registered in the GenBank database as of January 2023, 61 sequences lacked the 2-base insertion and 3,362 sequences were inserted. All 61 sequences without mutations were collected before 2020, whereas 3,358 (99.9%) of the 3,362 sequences with the insertion were collected during or after 2022. These findings imply that a 2-base insertion has recently emerged and has been fixed among the virus population that prevailed in 2022. In summary, a recently emerged frameshift mutation with a 2-base insertion was identified in hMPXV OPG191 gene. Although the structural and functional consequences of this mutation on virulence and infectivity are unknown, research on the possible associations between this mutation and recent hMPXV outbreaks is warranted.

Associations between neuromyelitis optica spectrum disorder, Sjögren's syndrome, and conditions with electrolyte disturbances.

OBJECTIVE: Electrolyte disorders are among the important conditions negatively affecting the disease course of neuromyelitis optica spectrum disorder (NMOSD). Possible mechanisms may include renal tubular acidosis (RTA) accompanying Sjögren's syndrome (SS), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and central diabetes insipidus (DI). Currently, the overlap profiles between these conditions remain uncertain. METHODS: This cross-sectional study collected data from the nationwide administrative Diagnosis Procedure Combination (DPC) database and evaluated the overlap profiles. RESULTS: Among the 28,285,908 individuals from 1203 DPC-covered hospitals, 8477 had NMOSD, 174108 had SS, 4977 had RTA, 7640 had SIADH, and 24,789 had central DI. Of those with NMOSD, 986 (12%) had SS. The odds ratio (OR) for a diagnosis of NMOSD in those with SS compared with those without was 21 [95% confidence interval (CI), 20-23]. Overlap between NMOSD and SS was seen both in males (OR, 28 [95% CI, 23-33]) and females (OR, 16 [15-17]) and was more prominent in the younger population. Among patients with SS, the prevalence of RTA was lower in patients with NMOSD compared with those without NMOSD. Patients with NMOSD showed a higher prevalence of SIADH (OR, 11 [7.5-17]; p < 0.0001) and DI (OR, 3.7 [2.4-5.3]; p < 0.0001). Comorbid SS in NMOSD was associated with a higher prevalence of DI. CONCLUSIONS: Patients with NMOSD are likely to have SS, SIADH, and central DI. RTA in SS does not facilitate the overlap between NMOSD and SS. SS in NMOSD may predispose patients to DI.