Identification of causative gene variants for patients with known monogenic diabetes using a targeted next-generation sequencing panel in a single-center study.

Aims: We aimed to verify the usefulness of targeted next-generation sequencing (NGS) technology for diagnosing monogenic diabetes in a single center. Methods: We designed an amplicon-based NGS panel targeting 34 genes associated with known monogenic diabetes and performed resequencing in 56 patients with autoantibody-negative diabetes mellitus diagnosed at < 50 years who had not been highly obese. By bioinformatic analysis, we filtered significant variants based on allele frequency (< 0.005 in East Asians) and functional prediction. We estimated the pathogenicity of each variant upon considering the family history. Results: Overall, 16 candidate causative variants were identified in 16 patients. Among them, two previously known heterozygous nonsynonymous single-nucleotide variants associated with monogenic diabetes were confirmed as causative variants: one each in the GCK and WFS1 genes. The former was found in two independent diabetes-affected families. Two novel putatively deleterious heterozygous variants were also assumed to be causative from the family history: one frameshift and one nonsynonymous single-nucleotide variant in the HNF4A gene. Twelve variants remained as candidates associated with the development of diabetes. Conclusion: Targeted NGS panel testing was useful to diagnose various forms of monogenic diabetes in combination with familial analysis, but additional ingenuity would be needed for practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00669-3.

Bilateral Adrenal Infarction That Developed in Latent Essential Thrombocythemia.

Bilateral adrenal infarction is an extremely rare disease, and it has been reported that some coagulation abnormalities, including essential thrombocythemia (ET), exist in the background. We herein report a 76-year-old patient in whom the platelet count had been in the normal range at the onset of adrenal infarction but subsequently increased to 102×104/µL at 7 months later, leading to the diagnosis of JAK2V617F-positive ET. As the presence of the JAK2V617F mutation increases the risk of thrombosis, Janus kinase 2 (JAK2) genetic testing should be considered in some cases of nonspecific unknown thrombosis, even if there are no obvious hematological findings, such as clonal hematopoiesis of indeterminate potential (CHIP).

Relationship between perfusion index and central temperature before and after induction of anesthesia in laparoscopic gastrointestinal surgery: A prospective cohort study.

The perfusion index (PI) cutoff value before anesthesia induction and the ratio of PI variation after anesthesia induction remain unclear. This study aimed to clarify the relationship between PI and central temperature during anesthesia induction, and the potential of PI in individualized and effective control of redistribution hypothermia. This prospective observational single center study analyzed 100 gastrointestinal surgeries performed under general anesthesia from August 2021 to February 2022. The PI was measured as peripheral perfusion, and the relationship between central and peripheral temperature values was investigated. Receiver operating characteristic curve analysis was performed to identify baseline PI before anesthesia, which predicts a decrease in central temperature 30 minutes after anesthesia induction, and the rate of change in PI that predicts the decrease in central temperature 60 minutes after anesthesia induction. In cases with a central temperature decrease of ≥ 0.6°C after 30 minutes, the area under the curve was 0.744, Youden index was 0.456, and the cutoff value of baseline PI was 2.30. In cases with a central temperature decrease of ≥ 0.6°C after 60 minutes, the area under curve was 0.857, Youden index was 0.693, and the cutoff value of the PI ratio of variation after 30 minutes of anesthesia induction was 1.58. If the baseline PI is ≤ 2.30 and the PI 30 minutes after anesthesia induction is at least 1.58-fold the PI ratio of variation, there is a high probability of a central temperature decrease of at least 0.6°C within 30 minutes after 2 time points.

Aortic arch calcification with pericardial fat mass detected on a single chest X-ray image is closely associated with the predictive variables of future cardiovascular disease.

This study evaluated the associations between aortic arch calcification (AAC) with pericardial fat (PF) mass detected on a single chest X-ray image and predictive variables of future cardiovascular disease (CVD). The subjects were 353 patients treated with at least one of the hypertension, dyslipidemia or diabetes. All subjects were evaluated for AAC; divided into 3 groups with AAC grades of 0, 1, or 2; and examined for the presence of PF. Carotid intima-media thickness (IMT, n = 353), cardio-ankle vascular index (CAVI, n = 218), the Suita score (n = 353), and cardiovascular risk points defined in the Hisayama study (n = 353), an assessment of the risk of future cardiovascular disease, were measured. The relationship of AAC grades, with or without PF, and CVD risks was evaluated. The IMT (1.62 ± 0.74 mm, 2.33 ± 1.26, and 2.43 ± 0.89 in patients with AAC grade 0, 1 and 2, respectively, p < 0.001), CAVI (8.09 ± 1.32, 8.71 ± 1.32, and 9.37 ± 1.17, respectively, p < 0.001), the Suita score (46.6 ± 10.7, 51.8 ± 8.3, and 54.2 ± 8.2, respectively, p < 0.001), and cardiovascular risk points (8.5 ± 2.6, 10.6 ± 2.3, and 11.5 ± 2.3, respectively, p < 0.001) were significantly elevated with AAC progression. Multinomial logistic regression analysis adjusted for clinical characteristics showed that the relative risk ratios of the Suita score or cardiovascular risk points were elevated according to the progress of AAC grade with PF. Therefore, aortic arch calcification with pericardial mass detected on a single chest X-ray image is closely associated with the predictive variables of future CVD.

Structure of water incorporated in amphoteric polymer thin films as revealed by FT-IR spectroscopy.

The structure and hydrogen bonding of water incorporated in a thin film of amphoteric terpolymers composed of various ratios of MA, DMAPMA, and BMA were analyzed using the band shapes of the O--H stretching in the IR spectra. At an early stage of sorption of water, the IR spectrum for the water incorporated in the film with comparative contents of MA and DMAPMA residues was similar to that for free water. This is consistent with the tendency for zwitterionic polymers, but is in contrast with the drastic change in the IR spectrum of water incorporated in non-ionic polymer films such as polyBMA. These results suggest a correlation between the mildness of the charge-balanced polymers to the structure of incorporated water and their blood compatibilities.

Structure of water in the vicinity of amphoteric polymers as revealed by Raman spectroscopy.

The structure and hydrogen bonding of water in an aqueous solution of amphoteric copolymers (poly(MA-r-DMAPMA), 3x10(3)

[Anesthetic management of a pregnant patient with congenitally corrected transposition of the great arteries for emergency cesarean delivery].

A 30-year-old woman at 35 weeks' gestation with congenitally corrected transposition of the great arteries (CCTGA), whose associated anomalies were VSD, ASD and pulmonary stenosis, underwent emergency cesarean delivery under general anesthesia. She had hypoxemia due to right-to-left shunt. We discussed with obstetricians and pediatric cardiologists about her at 25 weeks' gestation. Discussed points included: 1) delivery after 30 weeks' gestation, 2) her cardiac function and anomalies, 3) cesarean delivery under general anesthesia in case of emergency, 4) management of a sleeping baby after cesarean delivery by pediatricians. Cyanosis and heart failure were noted worsening during pregnancy. General anesthesia was induced by midazolam and fentanyl following cannulation of radial artery and right internal jugular vein for blood pressure and CVP monitoring. Anesthesia was maintained with sevoflurane and fentnyl. Dopamine and dobutamine were used to support blood pressure and cardiac function. After delivery, because of decreased CVP, lactated Ringer's solution was administrated. After operation, the patient was hemodynamically stable and trachea was extubated. Anesthetic management of the patient depends on the anatomical defects of CCTGA and associated conditions. Anesthesiologist should obtain information about a pregnant woman with CCTGA from cardiologists and obstetricians in early gestation to manage patient successfully.

[Anesthetic management of a neonate with laryngotracheoesophageal cleft and tracheoesophageal fistula].

Laryngotracheoesophageal cleft (LTEC) is an extremely rare congenital anomaly characterized by an absence of all or a part of the tracheoesophageal septum producing an abnormal communication between the trachea and esophagus, and is often difficult to be diagnosed. A 2-day-old male baby was tentatively diagnosed as tracheoesophageal fistula type Gross C, and underwent gastrostomy. The trachea was intubated before anesthetic induction. When a balloon of gastrostomy catheter was inflated, the lung could not be ventilated. After extubation of endotracheal tube and removal of gastrostomy catheter, the lung could be ventilated with mask. When endotracheal tube was intubated again, the lung could not be ventilated at all. Thus the surgery was performed under mask ventilation. Endoscopic examination performed 2 weeks later gave diagnosis of LTEC type 3. It is likely that the endotracheal tube might have been advanced into the end of the esophagus due to absence of the tracheoesophageal septum. In spite of a rare disease, LTEC should be considered as an extreme case of transesophageal fistula with a high risk of difficult airway.