Effect of individualized occupational therapy on cognition among patients with schizophrenia: A randomized controlled trial.

This study aimed to evaluate the feasibility and efficacy of individualized occupational therapy (IOT) plus group occupational therapy (GOT) as standard care for cognition compared to GOT alone, and to determine which IOT component has the greatest effect on cognitive outcome in patients with schizophrenia. This study was conducted at 14 clinical sites across Japan and enrolled recently hospitalized patients with schizophrenia. The IOT consisted of motivational interview, self-monitoring, individualized visits, craft activities, individualized psychoeducation, and discharge planning. Among the 68 patients who were randomized to the GOT + IOT group (n = 34) and GOT alone group (n = 34), 67 completed the trial (GOT + IOT group, n = 34; GOT alone group, n = 33). There were significant improvements in change from baseline to post-treatment between the groups in verbal memory, working memory, verbal fluency, attention, executive function domains, and the composite score of the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS composite score was significantly associated with the number of craft activity sessions. The addition of IOT to GOT has a favorable feasibility profile and efficacy for cognition in schizophrenia. Craft activity is the most effective IOT component in improving cognition.

Incidence of menstrual cycle abnormalities and polycystic ovary syndrome in female Japanese patients with type 1 diabetes mellitus. The role of androgens.

Type 1 diabetes mellitus (T1DM) adversely affects gonadal function. This study aimed to define the characteristics and factors associated with menstrual cycle abnormalities and polycystic ovary syndrome (PCOS) in Japanese patients with T1DM. Our study enrolled 157 patients, including 55 with oligomenorrhea (prolonged menstrual cycle) and 102 without oligomenorrhea. LH/FSH ratio (p = 0.04) and total testosterone levels (p = 0.03) were significantly higher in the oligomenorrhea group than in the non-oligomenorrhea group. No significant differences were found between the two groups regarding age at menarche, age at T1DM diagnosis, treatment, glycated hemoglobin, or total daily insulin dose. Of the 55 patients in the oligomenorrhea group, 27 were diagnosed with PCOS based on the Rotterdam criteria. We concluded that female patients with T1DM, as well as abnormal menstrual cycles and hyperandrogenism, may suffer from undiagnosed PCOS and should be referred to a gynecologist for full assessment, diagnosis, and treatment.

Superficial small cerebellar infarcts in cerebral amyloid angiopathy on 3 T MRI: A preliminary study.

BACKGROUND: Strictly superficial cerebellar microbleeds and cerebellar superficial siderosis have been considered markers of advanced cerebral amyloid angiopathy (CAA), but there are few studies on cerebellar ischemic lesions in CAA. We investigated the presence of superficial small cerebellar infarct (SCI) ≤15 mm and its relation to magnetic resonance imaging (MRI) markers in patients with probable CAA. METHODS: Eighty patients with probable CAA were retrospectively evaluated. The presence of superficial SCIs was examined, along with cerebellar microbleeds and cerebellar superficial siderosis, using 3-T MRI. Lobar cerebral microbleeds, cortical superficial siderosis (cSS), enlargement of the perivascular space in the centrum semiovale, and white matter hyperintensity were assessed and the total CAA-small vessel disease (SVD) score was calculated. RESULTS: Nine of the 80 patients (11.3%) had a total of 16 superficial SCIs. By tentatively defining SCI <4 mm as cerebellar microinfarcts, 8 out of 16 (50%) superficial SCIs corresponded to cerebellar microinfarcts. The total CAA-SVD score was significantly higher in patients with superficial SCIs (p = 0.01). The prevalence of cSS (p = 0.018), cortical cerebral microinfarct (p = 0.034), and superficial cerebellar microbleeds (p = 0.006) was significantly higher in patients with superficial SCIs. The number of superficial cerebellar microbleeds was also significantly higher in patients with superficial SCIs (p = 0.001). CONCLUSIONS: Our results suggest that in patients with CAA, superficial SCIs (including microinfarcts) on MRI may indicate more severe, advanced-stage CAA. These preliminary findings should be verified by larger prospective studies in the future.

Treatment interruption in hypertensive patients during the COVID-19 pandemic: An interrupted time series analysis using prescription data in Okayama, Japan.

Background: The COVID-19 pandemic has impacted healthcare behaviors, leading to fewer pediatric visits in Japan and potentially fewer visits by adult patients. However, existing Japanese studies on treatment interruptions have generally relied on questionnaire-based methods. In this study, we assessed the impact of the pandemic on antihypertensive treatment interruption using real-world prescription data. Methods: We conducted an interrupted time series analysis using the National Health Insurance Database in Okayama Prefecture, Japan. Participants included individuals aged 40-69 years with at least one antihypertensive prescription between 2018 and 2020. Treatment interruption was defined as a 3-month or longer gap in prescriptions after medication depletion. We used segmented Poisson regression with models unadjusted and adjusted for seasonality and over-dispersion to assess monthly treatment interruptions before and after Japan's April 2020 emergency. Results: During the study period, 23.0% of 55,431 participants experienced treatment interruptions. Cyclical fluctuations in interruptions were observed. The crude analysis indicated a 1.2-fold increase in treatment interruptions following the pandemic; however, the adjusted models showed no significant changes. Even among higher-risk groups, such as women, younger adults, and those with shorter prescriptions, no significant alterations were observed. Conclusion: We found no significant impact of the COVID-19 pandemic on antihypertensive treatment interruption in Okayama Prefecture. The less severe outbreak in the area or increased use of telemedicine and extended prescriptions may have contributed to treatment continuity. Further research is needed using a more stable and comprehensive database, broader regional data, and detailed prescription records to validate and extend our findings.

Characteristics of macrophage aggregates prepared by rotation culture and their response to polymeric materials.

Understanding the interaction between macrophages and biomaterials is important for the creation of new biomaterials and the development of technologies to control macrophage function. Since macrophages are strongly adhesive, caution is required when performing in vitro evaluations. Similarly, when THP-1 cells, macrophage precursor cells, are differentiated into macrophages using phorbol-12-myristate-13-acetate (PMA), it becomes difficult to detach them from the adherent substrate, which has been a problem on investigation of immunological responses to biomaterials. In this study, the interaction of THP-1 cell-differentiated macrophages with biomaterials was analyzed based on a new method of seeding THP-1 cells. THP-1 cells were cultured in static and rotation culture without and with PMA. In undifferentiated THP-1 cells, there was no change in cellular function between static and rotation cultures. In rotation culture with PMA, THP-1 cells differentiated and formed macrophage aggregates. IL-1ß and MRC1 expression in macrophage aggregates was examined after differentiation and M1/M2 polarization. Macrophage aggregates in rotation culture tended to be polarized toward M2 macrophages compared with those in static culture. In the evaluation of the responses of macrophage aggregates to several kinds of polymeric materials, macrophage aggregates showed different changes in MRC1 expression over time at 30, 50, and 70 rpm. Rotation speed of 30 rpm was considered most appropriate condition in that it gave stable results with the same trend as obtained with static culture. The use of macrophage aggregates obtained by rotational culture is expected to provide new insights into the evaluation of inflammatory properties of biomaterials.

Treatment strategy for maturity-onset diabetes of the young 3 (MODY3): Experience with two sisters and their mother.

Maturity onset diabetes of the young (MODY) is a relatively young-onset diabetes mellitus with an autosomal dominant inheritance. Among these phenotypes, MODY3, caused by mutations in HNF1A, is one of the most frequent. Although MODY3 is known to respond markedly to sulfonylureas (SU), many cases require insulin therapy. However, there are no clear guidelines for factors to consider when introducing antidiabetic drugs and insulin. This report describes a familial case in which an older sister was diagnosed with diabetes and subsequently with MODY3, followed by the onset of diabetes in the younger sister and mother. The elder sister initially denied insulin treatment and exhibited a suboptimal response to SU but finally agreed to insulin use. The mother initially selected insulin therapy because of the challenges associated with adherence to strict dietary therapy. Conversely, the younger sister responded positively to SU and maintained effective glycemic control. The management of MODY3, even though they have the same single-gene mutation and similar residual insulin secretion at diagnosis, should be flexibly individualized for each family member to ensure long-term adherence and appropriate glycemic control.

Pulvinar quantitative susceptibility mapping predicts visual hallucinations post-deep brain stimulation in Parkinson's disease.

PURPOSE: We have reported the relationship between low pulvinar nuclei (PN) intensity in susceptibility-weighted imaging and the appearance of visual hallucinations and cognitive function. The aim of the study was to examine the changes in the quantitative susceptibility mapping (QSM) in patients with Parkinson's disease (PD) who underwent deep brain stimulation (DBS) and verify whether the PN susceptibility value (SV) on QSM can predict visual hallucination and cognitive changes after DBS. METHODS: This study examined 24 patients with PD who underwent DBS along with QSM imaging on magnetic resonance imaging (MRI). All MRIs were performed within 3 months before surgery. The PN SV was further assessed based on the QSM. Then, associations were examined among cognitive changes, hallucination, and PN SV. The cognitive function of the patient was compared immediately before surgery and at 1 year postoperatively. RESULTS: Visual hallucinations were observed in seven patients during the follow-up period. The PN SV was ≥0.045 ppm in nine patients with PD, and six of them had visual hallucinations, whereas only one of 15 patients with PD with SV of <0.045 ppm had visual hallucinations (Fisher's exact test, p = .0037). CONCLUSIONS: The SV of >0.045 ppm at the PN in QSM in patients with PD may provide useful information suggesting visual hallucination and cognitive deterioration after DBS treatment.

Magnetic resonance imaging and neuropsychological findings for predicting of cognitive deterioration in memory clinic patients.

Objective: The severity of cerebral small vessel disease (SVD) on magnetic resonance imaging (MRI) has been assessed using hypertensive arteriopathy SVD and cerebral amyloid angiopathy (CAA)-SVD scores. In addition, we reported the modified CAA-SVD score including cortical microinfarcts and posterior dominant white matter hyperintensity. Each SVD score has been associated with cognitive function, but the longitudinal changes remain unclear. Therefore, this study prospectively examined the prognostic value of each SVD score, imaging findings of cerebral SVD, and neuropsychological assessment. Methods: This study included 29 patients diagnosed with mild cognitive impairment or mild dementia at memory clinic in our hospital, who underwent clinical dementia rating (CDR) and brain MRI (3D-fluid attenuated inversion recovery, 3D-double inversion recovery, and susceptibility-weighted imaging) at baseline and 1 year later. Each SVD score and neuropsychological tests including the Mini-Mental State Examination, Japanese Raven's Colored Progressive Matrices, Trail Making Test -A/-B, and the Rivermead Behavioral Memory Test were evaluated at baseline and 1 year later. Results: Twenty patients had unchanged CDR (group A), while nine patients had worsened CDR (group B) after 1 year. At baseline, there was no significant difference in each SVD score; after 1 year, group B had significantly increased CAA-SVD and modified CAA-SVD scores. Group B also showed a significantly higher number of lobar microbleeds than group A at baseline. Furthermore, group B had significantly longer Japanese Raven's Colored Progressive Matrices and Trail Making test-A times at baseline. After 1 year, group B had significantly lower Mini-Mental State Examination, Japanese Raven's Colored Progressive Matrices, and Rivermead Behavioral Memory Test scores and significantly fewer word fluency (letters). Conclusion: Patients with worsened CDR 1 year after had a higher number of lobar microbleeds and prolonged psychomotor speed at baseline. These findings may become predictors of cognitive deterioration in patients who visit memory clinics.

Effect of 2-week postpartum check-ups on screening positive for postpartum depression: a population-based cohort study using instrumental variable estimation in Japan.

BACKGROUND: Postpartum depression is experienced by approximately 10% of women and affects the health and development of their children. Although it is recommended that all mothers have the opportunity for early detection and intervention for postpartum depression, it is unclear whether early postpartum check-ups help to reduce postpartum depression. OBJECTIVE: The aim of this study was to assess the effect of 2-week postpartum check-ups on screening positive for postpartum depression in Japan. METHODS: This was a population-based cohort study that used the administrative database of Tsuyama, Japan. Participants were women who received postpartum home visits from a public health nurse in Tsuyama during the fiscal years 2017-2019. Data were obtained on participant's attendance at a 2-week postpartum check-up and their responses on the Edinburgh Postpartum Depression Scale. Owing to the initiation of a publicly funded postpartum check-up programme, participants were pseudo-randomly assigned to receive/not receive a 2-week postpartum check-up. We conducted instrumental variable estimation to assess the causal effects of the check-up on screening positive for postpartum depression. RESULTS: The characteristics of the 1,382 participants did not differ by fiscal year of childbirth. We found a 6.7% (95% confidence interval 2.2-11.2) reduction in the prevalence of screening positive for postpartum depression as an effect of 2-week postpartum check-ups among women received 1-month postpartum home visits. CONCLUSION: The results suggest that 2-week postpartum check-ups are effective in reducing the prevalence of screening positive for postpartum depression among 1-month postpartum women. Despite some limitations, early postpartum care could reduce postpartum depression.

Association between behavioral and psychological symptoms and cerebral small vessel disease MRI findings in memory clinic patients.

Objectives: Cerebral small vessel disease (SVD) is commonly observed among elderly individuals with cognitive impairment and has been recognized as a vascular contributor to dementia and behavioral and psychological symptoms (BPS), however, the relationship between BPS and SVD burden remains unclear. Methods: We prospectively recruited 42 patients with mild cognitive impairment (MCI) or mild dementia from the memory clinic in our hospital, who were assigned to either a clinical dementia rating (CDR) of 0.5 or 1.0, respectively. The presence of BPS was determined through interviews with caregivers. The patients underwent brain MRI and three types of SVD scores, total, cerebral amyloid angiopathy (CAA), and modified CAA, were assigned. Patients were also evaluated through various neuropsychological assessments. Results: The CDR was significantly higher in patients with BPS (p = 0.001). The use of antihypertensive agents was significantly higher in patients without BPS (p = 0.038). The time taken to complete trail making test set-A was also significantly longer in patients with BPS (p = 0.037). There was no significant difference in total SVD and CAA-SVD score (p = 0.745, and 0.096) and the modified CAA-SVD score was significantly higher in patients with BPS (p = 0.046). In addition, the number of total CMBs and lobar CMBs was significantly higher in patients with BPS (p = 0.001 and 0.001). Receiver operating characteristic curves for BPS showed that for modified CAA-SVD, a cutoff score of 3.5 showed 46.7% sensitivity and 81.5% specificity. Meanwhile, for the total number of cerebral microbleeds (CMBs), a cut-off score of 2.5 showed 80.0% sensitivity and 77.8% specificity and for the number of lobar CMBs, a cut-off score of 2.5 showed 73.3% sensitivity and 77.8% specificity. Conclusion: Overall, patients with BPS showed worse CDRs, reduced psychomotor speed, higher modified CAA-SVD scores, larger numbers of total and lobar CMBs. We propose that severe modified CAA scores and higher numbers of total and lobar CMBs are potential risk factors for BPS in patients with mild dementia or MCI. Therefore, by preventing these MRI lesions, the risk of BPS may be mitigated.

Preparation of mineralized pericardium by alternative soaking for soft-hard interregional tissue application.

Recent applications of decellularized tissues include the ectopic use of sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are modified (or fabricated) with the desired functions for application to the target (transplanted or used) tissue, including soft-hard interregional tissues, such as ligaments, tendons, and periodontal ligaments. This study aimed to prepare a mineralized decellularized pericardium to construct a soft-hard interregional tissue by 3D fabrication of decellularized pericardium, for example, rolling up to a cylindrical form. The decellularized pericardial tissue was prepared using the high hydrostatic pressurization (HHP) and surfactants method. The pericardium consisted of bundles of aligned fibers, and the bundles were slightly disordered when prepared with the surfactant decellularization method compared with that prepared using the HHP decellularization method. Mineralization of the decellularized pericardium was performed using an alternate soaking process with various cycles. The surface of the decellularized pericardium was covered with calcium phosphate precipitates, which accumulated on the surface with an increasing number of soaking cycles. The inside of the HHP decellularized pericardium was mineralized uniformly, whereas the mineralization of the decellularized pericardium decreased toward the interior. These findings suggest that the decellularization method strongly affects the structure and mineralized parts of the decellularized pericardium. The mineralized decellularized pericardium could be a candidate material for reconstructing alternative interregional tissues, such as ligaments and tendons.

Impact of spontaneous liposome modification with phospholipid polymer-lipid conjugates on protein interactions.

Liposome surface coating has been studied to avoid the immunological responses caused by the complement system, and alternative materials to poly(ethylene glycol) (PEG) have been explored recently since the production of anti-PEG IgM antibodies has been found in humans. We previously reported a liposome coating with poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC))-conjugated lipids (PMPC-lipids) and demonstrated its protective effect on blood protein interactions. Here, we attempted to modify the liposome surface by exogenously adding PMPC-lipids, which were spontaneously incorporated into the outer membrane via hydrophobic interactions. The polymerization degree of the PMPC segment was regulated from 10 to 100. The incorporated ratio of PMPC-lipid increased with a decrease in the degree of PMPC polymerization. Due to surface modification with PMPC-lipids, increase in the length of the PMPC-chain increased the size of the liposomes. The modified liposomes were kept stable for 14 d in terms of their size, polydispersity, and surface properties, where approximately 70% of PMPC-lipids were incorporated into the liposome surface. We demonstrated that liposome surface modification with PMPC-lipids can inhibit protein adsorption when exposed to serum, regardless of the degree of polymerization of PMPC. In addition, the PMPC-lipid modified surface was not recognized by the anti-PEG IgM antibody, whereas PEG-lipid was recognized by the antibody. Thus, we successfully fabricated an inert liposome surface via spontaneous modification with PMPC-lipids, where only the outer bilayer surface was modified. This technique can be available for full loading of water-soluble active pharmaceutical ingredient inside the modified liposome.

Titanium Nanosurface with a Biomimetic Physical Microenvironment to Induce Endogenous Regeneration of the Periodontium.

The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around artificial teeth (dental implants) provides a cost-effective solution for the extension of healthy life expectancy but remains a challenge in regenerative medicine. Biomimetics can create smart biomaterials that tune endogenous cells at a tissue-material interface. Here, we created a smart titanium nanosurface mimicking the surface nanotopography and micromechanical properties of the tooth root cementum (TRC), which is essential for the induction of dentoalveolar fibrous joints to regenerate the periodontium. After transplantation into the rat renal capsule, only the titanium artificial tooth with the TRC-mimetic nanosurface formed a complex dentoalveolar fibrous joint structure, with bone tissue, periodontal ligament (PDL), and TRC, in the decellularized jawbone matrix. TRC-mimetic titanium implants induce the formation of functional periodontium, even in a jawbone implantation model, which generally causes osseointegration (ankyloses). In human PDL cells, TRC analogousness in the surface mechanical microenvironment regulates matrix mineralization through bone sialoprotein expression and phosphorus metabolism, which are critical for cementogenesis. Therefore, the titanium nanosurfaces with nanotopographical and mechanical microenvironments mimicking the TRC surface induce dentoalveolar fibrous joints for periodontal regeneration by interfacial tuning of endogenous cells.

In Vitro Tissue Reconstruction Using Decellularized Pericardium Cultured with Cells for Ligament Regeneration.

Recent applications of decellularized tissues have included the ectopic use of their sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are fabricated with the desired functions to employ them to a target tissue. The aim of this study was to develop a 3D reconstruction method using a recellularized pericardium to overcome the difficulties in cell infiltration into tight and dense tissues, such as ligament and tendon tissues. Decellularized pericardial tissues were prepared using the high hydrostatic pressurization (HHP) and surfactant methods. The pericardium consisted of bundles of aligned fibers. The bundles were slightly disordered in the surfactant decellularization method compared to the HHP decellularization method. The mechanical properties of the pericardium were maintained after the HHP and surfactant decellularizations. The HHP-decellularized pericardium was rolled up into a cylindrical formation. Its mechanical behavior was similar to that of a porcine anterior cruciate ligament in tensile testing. NIH3T3, C2C12, and mesenchymal stem cells were adhered with elongation and alignment on the HHP- and surfactant-decellularized pericardia, with dependences on the cell type and decellularization method. When the recellularized pericardium was rolled up into a cylinder formation and cultured by hanging circulation for 2 days, the cylinder formation and cellular elongation and alignment were maintained on the decellularized pericardium, resulting in a layer structure of cells in a cross-section. According to these results, the 3D-reconstructed decellularized pericardium with cells has the potential to be an attractive alternative to living tissues, such as ligament and tendon tissues.

Cerebral Microbleeds With Atrial Fibrillation After Ablation Therapy.

BACKGROUND: The prevalence of cerebral microbleeds (CMBs) is significantly higher in patients with atrial fibrillation (AF) than in those without AF. CMBs in patients with AF have been reported to be primarily of the lobar type, but the exact cause of this remains unknown. We investigated the possibility that hemorrhagic transformation of embolic microinfarction can account for de novo lobar CMBs. METHODS: A total of 101 patients who underwent ablation therapy for AF were prospectively registered, and 72 patients completed the assessment with MRI 6 months after catheter ablation. Brain MRI, including diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI), were examined at 1-3 days (baseline) and 6 months after catheter ablation. We quantitatively evaluated the spatial and temporal distribution of embolic microinfarctions and de novo CMBs. RESULTS: Of the 101 patients, 68 were enrolled in this study. Fifty-nine patients (86.8%) showed embolic microinfarctions on baseline DWI immediately after catheter ablation. There were 137 CMBs in SWI, and 96 CMBs were of the lobar type. Six months later, there were 208 CMBs, including 71 de novo CMBs, and 60 of 71 (84.5%) were of the lobar type. Of the 71 de novo CMBs, 56 (78.9%) corresponded to the location of previous embolic microinfarctions found on baseline DWI. The platelet count was significantly lower and hematocrit/hemoglobin and Fazekas score were higher in the group with de novo CMBs than in the group without de novo CMBs. CONCLUSION: De novo CMBs frequently appeared after catheter ablation therapy. Our results suggest that embolic microinfarction can cause lobar CMBs.

Age at menarche in Japanese patients with type 1 diabetes mellitus: a look at changes since 1960s.

Menarche is delayed in patients with type 1 diabetic mellitus (T1DM) compared to non-diabetics. The purpose of this survey study was to define the age of onset of menarche in Japanese patients with T1DM, as well the secular trends in menarcheal age across the period of 1976-2020 and determine the effects of T1DM and disease management on that age. The study subjects (n = 155) were recruited from among Japanese T1DM patients who visited the outpatient clinic of the Department of Pediatrics, Osaka City University Hospital. The study subjects experienced menarche during 1976-2020. They were divided into the menarche-post-T1DM group (n = 117) and the menarche-pre-T1DM group (n = 38), in whom menarche occurred after or before the diagnosis of T1DM, respectively. The time of birth was also stratified into five decade/time bins extending from 1960s to 2000s. The subjects filled a questionnaire on menarche. Other clinical information was obtained from the medical records. The median age at menarche was 12.5 years (11.3-13.4) (25th-75th percentile) for the menarche-post-T1DM group and 11.8 years (10.9-13.0) for the menarche-pre-T1DM group (p = 0.024). Menarche occurred at a significantly younger age in recent years in the menarche-post-T1DM group (r = -0.209, p = 0.023), but no such trend was found in the control group. Analysis of data of subjects born after 1990 still showed significant delay associated with T1DM [post-T1DM group: 12.3 years (11.3-13.2), pre-T1DM group: 11.8 years (11.0-12.2), p = 0.045]. The results suggest that recent advances in insulin therapy seem to improve metabolism under T1DM but might have not enough impact on menarche in Japanese girls.

Demography, trade and state power: a tripartite model of medieval farming/language dispersals in the Ryukyu Islands.

Hunter-gatherer occupations of small islands are rare in world prehistory and it is widely accepted that island settlement is facilitated by agriculture. The Ryukyu Islands contradict that understanding on two counts: not only did they have a long history of hunter-gatherer settlement, but they also have a very late date for the onset of agriculture, which only reached the archipelago between the eighth and thirteenth centuries AD. Here, we combine archaeology and linguistics to propose a tripartite model for the spread of agriculture and Ryukyuan languages to the Ryukyu Islands. Employing demographic growth, trade/piracy and the political influence of neighbouring states, this model provides a synthetic yet flexible understanding of farming/language dispersals in the Ryukyus within the complex historical background of medieval East Asia.

Relationship Between Bedside Ketone Levels and Time to Resolution of Diabetic Ketoacidosis: A Retrospective Cohort Study.

INTRODUCTION: There is no information on the factors that influence the time required to induce resolution of diabetic ketoacidosis (DKA). New methods are currently available for bedside measurement of serum 3-hydroxybutyrate (3HB). The aim of this study was to determine the relationship between serum 3HB and the time to DKA resolution. METHODS: We reviewed the medical records of patients with type 1 diabetes (T1D) and a history of DKA who were admitted to the Department of Pediatrics, Osaka City University Hospital, between November 2008 and October 2018. DKA resolution was defined as 3HB below 1.0 mmol/L as measured by a bedside ketone meter. RESULTS: Data of 52 T1D-DKA episodes were analyzed (median age, 8.0 years; 20 male patients; 32 female patients; new T1D diagnosis, n = 13; established diagnosis, n = 39). In all cases, correction of serum 3HB was an important aspect of T1D management. The median time to DKA resolution (defined as the time from the start of insulin infusion until the fall of 3HB level to below 1.0 mmol/L) was 11 and 10 h in new and established T1D cases, respectively. 3HB on admission and the required insulin infusion dose per body weight, but not blood pH level on admission, correlated with time to DKA resolution. There was no relationship between blood pH level and 3HB on admission. CONCLUSIONS: Our results showed that DKA resolution could be achieved within 10-11 h when DKA treatment is guided by bedside 3HB monitoring without any severe complications. Blood 3HB level is a potentially suitable marker for the severity and resolution of DKA.