Enhancing Type 2 Diabetes Treatment Decisions With Interpretable Machine Learning Models for Predicting Hemoglobin A1c Changes: Machine Learning Model Development.

BACKGROUND: Type 2 diabetes (T2D) is a significant global health challenge. Physicians need to assess whether future glycemic control will be poor on the current trajectory of usual care and usual-care treatment intensifications so that they can consider taking extra treatment measures to prevent poor outcomes. Predicting poor glycemic control from trends in hemoglobin A1c (HbA1c) levels is difficult due to the influence of seasonal fluctuations and other factors. OBJECTIVE: We sought to develop a model that accurately predicts poor glycemic control among patients with T2D receiving usual care. METHODS: Our machine learning model predicts poor glycemic control (HbA1c≥8%) using the transformer architecture, incorporating an attention mechanism to process irregularly spaced HbA1c time series and quantify temporal relationships of past HbA1c levels at each time point. We assessed the model using HbA1c levels from 7787 patients with T2D seeing specialist physicians at the University of Tokyo Hospital. The training data include instances of poor glycemic control occurring during usual care with usual-care treatment intensifications. We compared prediction accuracy, assessed with the area under the receiver operating characteristic curve, the area under the precision-recall curve, and the accuracy rate, to that of LightGBM. RESULTS: The area under the receiver operating characteristic curve, the area under the precision-recall curve, and the accuracy rate (95% confidence limits) of the proposed model were 0.925 (95% CI 0.923-0.928), 0.864 (95% CI 0.852-0.875), and 0.864 (95% CI 0.86-0.869), respectively. The proposed model achieved high prediction accuracy comparable to or surpassing LightGBM's performance. The model prioritized the most recent HbA1c levels for predictions. Older HbA1c levels in patients with poor glycemic control were slightly more influential in predictions compared to patients with good glycemic control. CONCLUSIONS: The proposed model accurately predicts poor glycemic control for patients with T2D receiving usual care, including patients receiving usual-care treatment intensifications, allowing physicians to identify cases warranting extraordinary treatment intensifications. If used by a nonspecialist, the model's indication of likely future poor glycemic control may warrant a referral to a specialist. Future efforts could incorporate diverse and large-scale clinical data for improved accuracy.

Identifying factors associated with locomotive syndrome using machine learning methods: The third survey of the research on osteoarthritis/osteoporosis against disability study.

AIM: To identify factors associated with locomotive syndrome (LS) using medical questionnaire data and machine learning. METHODS: A total of 1575 participants underwent the LS risk tests from the third survey of the research on osteoarthritis/osteoporosis against disability study (ROAD) study. LS was defined as stage 1 or higher based on clinical decision limits of the Japanese Orthopaedic Association. A total of 1335 items of medical questionnaire data came from this study. The number of medical questionnaire items was reduced from 1335 to 331 in data cleaning. From the 331 items, identify factors associated with LS use by light gradient boosting machine-based recursive feature elimination with cross-validation. The performance of each set was evaluated using an average of seven performance metrics, including 95% confidence intervals, using a bootstrapping method. The smallest set of items is determined with the highest average of receiver operating characteristic area under the curve (ROC-AUC) under 20 items as association factors of LS. Additionally, the performance of the selected items was compared with the LS risk tests and Loco-check. RESULTS: The nine items have the best average ROC-AUC under 20 items. The nine items show an average ROC-AUC of 0.858 (95% confidence interval 0.816-0.898). Age and back pain during walking were strongly associated with the prevalence of LS. The ROC-AUC of nine items is higher than that of existing questionnaire-based LS assessments, including the 25-question Geriatric Locomotor Scale and Loco-check. CONCLUSIONS: The identified nine items could aid early LS detection, enhancing understanding and prevention. Geriatr Gerontol Int 2024; ••: ••-••.

Differences in clinical outcomes between men with mosaic Klinefelter syndrome and those with non-mosaic Klinefelter syndrome.

Purpose: This study compared the clinical outcomes of men with Klinfelter syndrome based on karyotype. Methods: The authors analyzed the outcomes of microdissection testicular sperm extraction (micro-TESE) performed on 57 patients with Klinfelter syndrome (KS) at our clinic. Results: The average ages of the non-mosaic and mosaic KS groups were 32.2 ± 4.8 and 45.9 ± 13.1 years, respectively. The sperm retrieval rates of the non-mosaic and mosaic KS groups were 46.5% (20/43) and 50.0% (7/14), respectively. The fertilization rates after intracytoplasmic sperm injection did not significantly differ between the non-mosaic and mosaic KS groups. The mosaic KS group had higher cleavage and blastocyst development rates than the non-mosaic KS group (72.2% vs. 96.2% and 30.5% vs. 44.7%, respectively). The group using motile sperm had better outcomes than the group using immotile sperm. The embryo transfer outcomes of the non-mosaic and mosaic KS groups did not significantly differ (clinical pregnancy rate: 28.0% vs. 20.7%, miscarriage rate: 14.3% vs. 33.3%, production rate per transfer: 22.0% vs. 13.8%, and production rate per case: 58.8% vs. 57.1%). Conclusions: Compared with the non-mosaic KS group, the mosaic KS group had significantly better intracytoplasmic sperm injection outcomes because of the higher utilization rate of motile sperm.

MYRF is associated with encephalopathy with reversible myelin vacuolization.

OBJECTIVE: Reversible myelin vacuolization is associated with variable conditions including mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), which is characterized by mildly impaired consciousness and transient splenial lesion. Familial and/or recurrent cases with a clinical diagnosis of MERS suggest the presence of genetic factors. METHODS: We examined a family in which the proband presented with a history of recurrent encephalopathy with extensive but reversible cerebral myelin vacuolization and neurological symptoms similar to those of MERS spanning 3 generations. Whole-exome sequencing was performed in family members. RESULTS: Eight rare nonsynonymous single-nucleotide variants shared by all patients were identified. By filtering genes expressed in the corpus callosum, we identified a heterozygous c.1208A>G predicting p.Gln403Arg in the highly conserved DNA-binding domain in the myelin regulatory factor (MYRF) gene. We subsequently screened the coding regions of MYRF by Sanger sequencing in our cohort comprised of 33 sporadic cases with MERS and 3 cases in another family with extensive myelin vacuolization, and identified the same heterozygous c.1208A>G in all affected members in the second family. Luciferase assay revealed that transcriptional activity of the N-terminal region of MYRF was significantly diminished by introducing the c.1208A>G variant. INTERPRETATION: MYRF is a transcriptional regulator that is necessary for oligodendrocyte differentiation and myelin maintenance. Functional defects of MYRF are likely to be causally associated with encephalopathy with extensive myelin vacuolization. We propose the term "MYRF-related mild encephalopathy with reversible myelin vacuolization." Our findings provide a new perspective on the pathogenesis of myelin vacuolization. Ann Neurol 2018;83:98-106.

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

OBJECTIVE: We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. METHODS: We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 µg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. RESULTS: Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 µg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. CONCLUSION: Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult.

A diagnostic approach for identifying anti-neuronal antibodies in children with suspected autoimmune encephalitis.

We assessed the validity of immunoblotting, immunohistochemistry (IHC), and immunocytochemistry (ICC) to detect anti-neuronal antibodies in an attempt to establish a diagnostic approach for pediatric autoimmune encephalitis. Both IHC and ICC had higher sensitivity than immunoblotting and could differentiate between antibodies directed towards intracellular and cell surface antigens. There was a significant correlation between the IHC and ICC results. When patients were divided into encephalitis and non-encephalitis groups, there was no difference in the positivity rate and staining pattern of IHC and ICC between them. In conclusion, IHC and ICC are useful methods to screen for anti-neuronal antibodies. A combination of IHC, ICC, and specific cell-based assays is expected to be an efficient approach for the diagnosis of autoantibody-mediated encephalitis.

Efficacy and safety of fosphenytoin for benign convulsions with mild gastroenteritis.

OBJECTIVE: To clarify the efficacy and safety of fosphenytoin for seizures in children with benign convulsions and mild gastroenteritis. METHODS: Using the mailing list of the Annual Zao Conference on Pediatric Neurology, we recruited patients who met the following criteria: (1) clinical diagnosis of benign convulsions with mild gastroenteritis and (2) treatment with intravenous fosphenytoin. Benign convulsions with mild gastroenteritis were defined as a condition of (a) seizures associated with gastroenteritis without electrolyte imbalance, hypoglycemia, or dehydration in patients (b) between 6 months and 3 years of age with (c) no preexisting neurological disorders, (d) no impaired consciousness, and (e) a body temperature less than 38.0 °C before and after the seizures. The efficacy of fosphenytoin was categorized as effective when cessation of seizures was achieved. RESULTS: Data from 16 child patients were obtained (median age, 20 months). Seizures were completely controlled after the initial dose of fosphenytoin in 14 of 16 patients. The median loading dose of fosphenytoin was 22.5 mg/kg. In 10 patients, fosphenytoin was administered after other antiepileptic drugs such as diazepam and midazolam were used. Adverse effects of fosphenytoin, excessive sedation, or intravenous fluid incompatibility were not observed in any patients. CONCLUSION: Fosphenytoin is effective and well tolerated among children with benign convulsions with mild gastroenteritis.

Anti-aquaporin 4 antibody-positive acute disseminated encephalomyelitis.

OBJECTIVE: To describe the clinical and neuroimaging features of a young female patient with acute disseminated encephalomyelitis associated with anti-aquaporin-4 antibodies. METHODS: The patient had mild encephalopathy 14 days after influenza vaccination. Cerebrospinal fluid analysis revealed an increased cell count and a marked increase in myelin basic protein. Magnetic resonance imaging (MRI) demonstrated multiple lesions in the juxtacortical white matter. The patient was diagnosed with acute disseminated encephalomyelitis and treated with methylprednisolone pulse therapy. She recovered in 1 month. However, right retrobulbar optic neuritis appeared 2 months after discharge, and serum anti-aquaporin 4 antibodies were measured with a cell-based assay. RESULTS: Anti-aquaporin 4 antibodies were present in the patient's serum. She was treated with a prolonged course of oral prednisolone. The patient was negative for serum anti-aquaporin 4 antibodies 8 months after the second clinical event, and prednisolone was discontinued 13 months after the second clinical event. Serum anti-aquaporin 4 antibodies remained negative 4 months after the discontinuation of prednisolone. There was no evidence of relapse at 9 months after discontinuation of steroids. CONCLUSIONS: This case will expand the spectrum of anti-aquaporin-4 antibody-related central nervous system disorders. The measurement of anti-aquaporin 4 antibody may be considered in patients with a clinical diagnosis of acute disseminated encephalomyelitis and a second clinical event within a short interval.

[Two cases of preceded aortic valve replacement for severe aortic stenosis before the cancer operations].

We report two cases of aortic valve replacement (AVR) for severe aortic stenosis (AS) before the cancer operations. Severe AS poses a great risk for noncardiac surgery. In the ACC/AHA 2007 Guideline on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery, if the AS is symptomatic, elective noncardiac surgery should generally be postponed or canceled. Such patients require AVR before elective noncardiac surgery. On the other hand, in patients with severe AS who refuse cardiac surgery, noncardiac surgery can be performed with a mortality risk of approximately 10%. In our cases, severe AS was found in the preoperative examination. We informed them about necessary AVR before noncardiac surgery, and patients consented to our suggestion. AVR was performed around 7 days after this consent, and cancer operation was performed around 30 days after the AVR. However, there are no clear guidelines for this interval between AVR and cancer operation. In our cases the patients underwent the cardiac surgery and noncardiac surgery in a short period without serious complication in the perioperative management. It is very important to discuss among surgeon, cardiovascular surgeon, cardiologist and anesthesiologist. Especially anesthesiologist should take an important role in organizing these departments for such patients.

[Unilateral deterioration of regional cerebral oxygen saturation in a patient with bilateral stenosis of the internal carotid artery during laparoscopic operation].

A 73-year-old woman with bilateral internal carotid artery stenosis, 80% in the left and 70% in the right, was scheduled for a laparoscopic operation for sigmoidrectal colon cancer. During the operation, general anesthesia was maintained with propofol and fentanyl, combined with epidural analgesia. Regional cerebral oxygen saturation (rSo2) was continuously monitored throughout the operation. Thirty minutes after the introduction of pneumoperitoneum with head-down position (Trendelenburg position: TP), only left rSo2 decreased from 52% to 17%. As fraction of oxygen (FI(O2)) was increased from 45% to 100%, mechanical ventilation was adjusted to keep end tidal carbon dioxide pressure at 40 mmHg and dopamine was administered to raise arterial blood pressure, left rSo, recovered to 60%. Thereafter, FIo2 was maintained at 60% and the rSo, was kept at 60% to 70% to the end of the operation. Neurological dysfunctions were not observed after the operation. In order to prevent cerebral ischemic damage from the operation with TP, monitoring of rSo, maybe essential during general anesthesia.

[Postoperative recurrence of venous thromboembolism in patients with episodes of preoperative thromboembolism].

BACKGROUND: Venous thromboembolism (VTE) has become a major health problem in Japan. METHODS: We examined, postoperative recurrence of VTE in patients with preoperative venous thromboembolic events and evaluated factors that are relevant to the occurrence of postoperative VTE. RESULTS: Forty-four cases out of 38500 had been diagnosed preoperatively as having VTE in the period of 1995-2001 at Kitasato University Hospital. Postoperative VTE was detected in four patients (9%) out of these 44 cases. Patients who had thrombophilia (antiphosholipid syndrome) or recent episode of VTE within 1 month were higher in the incidence of postoperative recurrence of VTE than the others. Temporary infra-vena cava filters were placed to prevent pulmonary thromboembolism in twelve patients. In 8 of the patients, thrombi were detected in or at the filter before explantation. Three patients (7%) had undergone thrombolysis therapy. Postoperative VTE was not found in patients who had already received anticoagulant therapy (warfarin) for 3 or more months. CONCLUSIONS: It is concluded that newly developed VTE occurred perioperatively in 9% of patients with preoperative VTE, and that thrombophilia and a recent episode of VTE were considered as risk factors of perioperative VTE. Temporary infra-vena cava filters are a valuable device for prevention of postoperative pulmonary thromboembolism.