Efficacy and safety of oral semaglutide in older patients with type 2 diabetes: a retrospective observational study (the OTARU-SEMA study).

BACKGROUND: Oral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world. METHODS: We retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65-74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity. RESULTS: We studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (- 13.1 ± 7.5 mmol/mol and - 3.0 ± 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = -0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = -0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4). CONCLUSIONS: Oral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of ≥ 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence.

Comparison of water and terrestrial jumping in natural and robotic insects.

Jumping requires high actuation power for achieving high speed in a short time. Especially, organisms and robots at the insect scale jump in order to overcome size limits on the speed of locomotion. As small jumpers suffer from intrinsically small power output, efficient jumpers have devised various ingenuous schemes to amplify their power release. Furthermore, semi-aquatic jumpers have adopted specialized techniques to fully exploit the reaction from water. We review jumping mechanisms of natural and robotic insects that jump on the ground and the surface of water, and compare the performance depending on their scale. We find a general trend that jumping creatures maximize jumping speed by unique mechanisms that manage acceleration, force, and takeoff duration under the constraints mainly associated with their size, shape, and substrate.

SCGB1C1 Plays a Critical Role in Suppression of Allergic Airway Inflammation through the Induction of Regulatory T Cell Expansion.

The nanosized vesicles secreted from various cell types into the surrounding extracellular space are called extracellular vesicles (EVs). Although mesenchymal stem cell-derived EVs are known to have immunomodulatory effects in asthmatic mice, the role of identified pulmonary genes in the suppression of allergic airway inflammation remains to be elucidated. Moreover, the major genes responsible for immune regulation in allergic airway diseases have not been well documented. This study aims to evaluate the immunomodulatory effects of secretoglobin family 1C member 1 (SCGB1C1) on asthmatic mouse models. C57BL/6 mice were sensitized to ovalbumin (OVA) using intraperitoneal injection and were intranasally challenged with OVA. To evaluate the effect of SCGB1C1 on allergic airway inflammation, 5 µg/50 µL of SCGB1C1 was administrated intranasally before an OVA challenge. We evaluated airway hyperresponsiveness (AHR), total inflammatory cells, eosinophils in the bronchoalveolar lavage fluid (BALF), lung histology, serum immunoglobulin (Ig), the cytokine profiles of BALF and lung-draining lymph nodes (LLN), and the T cell populations in LLNs. The intranasal administration of SCGB1C1 significantly inhibited AHR, the presence of eosinophils in BALF, eosinophilic inflammation, goblet cell hyperplasia in the lung, and serum total and allergen-specific IgE. SCGB1C1 treatment significantly decreased the expression of interleukin (IL)-5 in the BALF and IL-4 in the LLN, but significantly increased the expression of IL-10 and transforming growth factor (TGF)-ß in the BALF. Furthermore, SCGB1C1 treatment notably increased the populations of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in asthmatic mice. The intranasal administration of SCGB1C1 provides a significant reduction in allergic airway inflammation and improvement of lung function through the induction of Treg expansion. Therefore, SCGB1C1 may be the major regulator responsible for suppressing allergic airway inflammation.

Differences in Type 2 Fiber Composition in the Vastus Lateralis and Gluteus Maximus of Patients with Hip Fractures.

BACKGRUOUND: Aging leads to sarcopenia, which is characterized by reduced muscle mass and strength. Many factors, including altered muscle protein turnover, diminished neuromuscular function, hormonal changes, systemic inflammation, and the structure and composition of muscle fibers, play a crucial role in age-related muscle decline. This study explored differences in muscle fiber types contributing to overall muscle function decline in aging, focusing on individuals with hip fractures from falls. METHODS: A pilot study at Chungnam National University Hospital collected muscle biopsies from hip fracture patients aged 20 to 80 undergoing surgical treatment. Muscle biopsies from the vastus lateralis and gluteus maximus were obtained during hip arthroplasty or internal fixation. Handgrip strength, calf and thigh circumference, and bone mineral density were evaluated in individuals with hip fractures from falls. We analyzed the relationships between each clinical characteristic and muscle fiber type. RESULTS: In total, 26 participants (mean age 67.9 years, 69.2% male) were included in this study. The prevalence of sarcopenia was 53.8%, and that of femoral and lumbar osteoporosis was 19.2% and 11.5%, respectively. Vastus lateralis analysis revealed an age-related decrease in type IIx fibers, a higher proportion of type IIa fibers in women, and an association between handgrip strength and type IIx fibers in men. The gluteus maximus showed no significant correlations with clinical parameters. CONCLUSION: This study identified complex associations between age, sex, handgrip strength, and muscle fiber composition in hip fracture patients, offering insights crucial for targeted interventions combating age-related muscle decline and improving musculoskeletal health.

Normalization of impaired glucose tolerance after kidney transplantation is associated with improved ß-cell function.

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with ß-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). ß-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = -0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in ß-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Improvements in BUN after transplantation were associated with improvements in ß-cell function.NEW & NOTEWORTHY In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in ß-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus.

Improvement of ß-Cell Function After Switching From DPP-4 Inhibitors to Oral Semaglutide: SWITCH-SEMA2 Post Hoc Analysis.

CONTEXT: Whether continuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) or switching to oral semaglutide is more beneficial for ß-cell function is unclear. OBJECTIVE: To assess the efficacy of switching from DPP-4is to oral semaglutide for ß-cell function compared with DPP-4i continuation. METHODS: Post hoc analysis of SWITCH-SEMA 2, a multicenter prospective randomized controlled trial on the switch to oral semaglutide vs DPP-4i continuation without dose adjustment for 24 weeks in subjects with type 2 diabetes treated with DPP-4is, was conducted. Changes in markers for glucose metabolism, including homeostatic model assessment (HOMA2) scores and disposition index (DI), were compared between the groups. RESULTS: A total of 146 subjects (semaglutide group, 69; DPP-4i group, 77) were analyzed. In the semaglutide group, glycemic control, liver enzyme deviations, and lipid profiles improved after 24 weeks. Regarding indices for ß-cell function, changes in HOMA2-ß as well as DI, reflecting the ability of ß-cells to compensate for insulin resistance, were significantly higher in the semaglutide group compared with the DPP-4i group (mean change, +10.4 vs +0.6 in HOMA2-ß [P = .001] and +0.09 vs 0.0 in DI [P < .001]). Improvement in DI in the semaglutide group was correlated significantly to changes in body mass index (BMI), HbA1c, and fatty liver index reflecting liver steatosis. Multiple linear regression analysis revealed that dose of semaglutide (≥ 7 mg/day), reduction in fatty liver index, and metformin nonuse were independently associated with improvement of DI. CONCLUSION: Switching to oral semaglutide ameliorated ß-cell function compared with DPP-4is, presumably via tissue-to-tissue crosstalk between liver and ß-cells.

3D printing with a 3D printed digital material filament for programming functional gradients.

Additive manufacturing, or 3D printing attracts growing attention as a promising method for creating functionally graded materials. Fused deposition modeling (FDM) is widely available, but due to its simple process, creating spatial gradation of diverse properties using FDM is challenging. Here, we present a 3D printed digital material filament that is structured towards 3D printing of functional gradients, utilizing only a readily available FDM printer and filaments. The DM filament consists of multiple base materials combined with specific concentrations and distributions, which are FDM printed. When the DM filament is supplied to the same printer, its constituent materials are homogeneously blended during extrusion, resulting in the desired properties in the final structure. This enables spatial programming of material properties in extreme variations, including mechanical strength, electrical conductivity, and color, which are otherwise impossible to achieve with traditional FDMs. Our approach can be readily adopted to any standard FDM printer, enabling low-cost production of functional gradients.

Unusual US Findings of Diffuse Large B-Cell Lymphoma of the Breast: A Case Report.

Lymphoma is an uncommon type of breast malignancy, with low prevalence. The ultrasonographic findings of breast lymphoma have been described as nonspecific. Breast lymphoma most commonly appears as a solitary hypoechoic mass on US, and usually shows hypervascularity on color Doppler US. Herein, we report an unusual case of breast lymphoma that presented as multiple bilateral hyperechoic nodules on US.

Revision Extension of Fusion Surgery in Thoracolumbar Spine Using a Newly Designed Revision Rod - Comparative Matched Cohort Study Versus Implant-Replacement Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the results of revision extension of fusion surgery using the newly designed revision rod and implant-replacement surgery in thoracolumbar spine. METHODS: Thirty-one patients who underwent extension of fusion surgery using the revision rod for adjacent segment disease were included in this study. Thirty-one patients who underwent implant-replacement revision surgery were selected as a control group by matching age, sex, preoperative diagnosis, and number of revision segments. RESULTS: The mean age was 70.7 ± 8.0 years in the revision rod (RR) group and 69.0 ± 8.4 years in the control group. Preoperative diagnoses, underlying diseases, and mean number of revision segments (2.2 ± 1.1) were similar in both groups. The change of hemoglobin (1.0 ± 1.9 vs 2.5 ± 1.5 g/dl; P < .01), hematocrit (4.1 ± 4.9 vs 7.2 ± 4.4 % P < .01) and albumin (.8 ± .9 vs 1.3 ± .4 g/dl; P < .01) levels before and after surgery showed significant differences between the two groups. Hemovac drainage was significantly less in the RR group (P = .01). The mean operative time was shorter in the RR group (203.5 ± 9.5 min vs 233.5 ± 8.7 min; P = .12) with no statistical difference. Radiological results showed that the average lumbar lordosis 2 years after surgery was lower in the RR group compared to the control group (25.1 ± 9.9° vs 32.9 ± 9.8°; P = .02). Union rates and clinical outcomes were not different between the two groups. CONCLUSIONS: Revision extension of fusion surgery using a newly designed revision rod had less hemovac drainage and superior laboratory findings compared to implant-replacement revision surgery.

The impact of the COVID-19 pandemic on infant obesity: A nationwide retrospective cohort study.

BACKGROUND: Lifestyle changes, such as those related to the COVID-19 pandemic, including alterations in physical activity and dietary habits, are known to affect pregnancy outcomes. In particular, suboptimal intrauterine conditions during pregnancy are known to influence not only fetal growth but also growth during infancy. However, research on the impact of the environmental changes caused by the COVID-19 pandemic on the growth of infants and children during their early years is lacking. To address this issue, this study evaluated the effect of the COVID-19 pandemic on obesity in infants. METHODS: This retrospective cohort study used the data collected from the Korea National Health Insurance (KNHI) claims database. The data of 1985,678 women who delivered infants between 2015 and 2021 were collected. Women who delivered during the pandemic and those who delivered during the pre-pandemic period were matched in a 1:1 frequency-matched pair procedure for factors such as age, hypertension, diabetes mellitus, preeclampsia, gestational diabetes mellitus, mode of delivery, gestational age at delivery, offspring sex, and birth weight. Finally, 197,580 women were enrolled. The weight and head circumference of infants (4-6 months of age) of the COVID-19 pandemic group were compared with those of the pre-pandemic group. RESULTS: The COVID-19 pandemic group infants exhibited significantly higher weight and prevalence of obesity at 4-6 months of age compared to infants in the pre-pandemic group. After adjustment for covariates, pandemic group infants had a higher risk of obesity (odds ratio: 1.54, 95% confidence interval: 1.51-1.57) compared to the pre-pandemic group infants. CONCLUSION: The COVID-19 pandemic has had a notable impact on the weight of infants aged 4-6 months. This suggests that pandemic conditions may influence the growth of newborns, underscoring the importance of monitoring and assessing trends in the growth of infants born during such crises.

Switching from Conventional Fibrates to Pemafibrate Has Beneficial Effects on the Renal Function of Diabetic Subjects with Chronic Kidney Disease.

BACKGRUOUND: Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting. METHODS: We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status. RESULTS: Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05). CONCLUSION: A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.

The Risk of Hypertension and Diabetes Mellitus According to Offspring's Birthweight in Women With Normal Body Mass Index: A Nationwide Population-Based Study.

BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.

Pro-SMP finder-A systematic approach for discovering small membrane proteins in prokaryotes.

Prokaryotic chromosomes contain numerous small open reading frames (ORFs) of less than 200 bases. Since high-throughput proteomics methods often miss proteins containing fewer than 60 amino acids, it is difficult to decern if they encode proteins. Recent studies have revealed that many small proteins are membrane proteins with a single membrane-anchoring α-helix. As membrane anchoring or transmembrane motifs are accurately identifiable with high confidence using computational algorithms like Phobius and TMHMM, small membrane proteins (SMPS) can be predicted with high accuracy. This study employed a systematic approach, utilizing well-verified algorithms such as Orfipy, Phobius, and Blast to identify SMPs in prokaryotic organisms. Our main search parameters targeted candidate SMPs with an open reading frame between 60-180 nucleotides, a membrane-anchoring or transmembrane region 15 and 30 amino acids long, and sequence conservation among other microorganisms. Our findings indicate that each prokaryote possesses many SMPs, with some identified in the intergenic regions of currently annotated chromosomes. More extensively studied microorganisms, such as Escherichia coli and Bacillus subtilis, have more SMPs identified in their genomes compared to less studied microorganisms, suggesting the possibility of undiscovered SMPs in less studied microorganisms. In this study, we describe the common SMPs identified across various microorganisms and explore their biological roles. We have also developed a software pipeline and an accompanying online interface for discovering SMPs (http://cs.indstate.edu/pro-smp-finder). This resource aims to assist researchers in identifying new SMPs encoded in microbial genomes of interest.

Sarcopenia in paraspinal muscle as a risk factor of proximal junctional kyphosis and proximal junctional failure after adult spinal deformity surgery.

OBJECTIVE: The aim of this study was to identify the risk factors for proximal junctional kyphosis (PJK) and proximal junctional failure (PJF), including paraspinal muscle atrophy. METHODS: Fifty-seven consecutive patients who underwent a long-instrumented fusion for adult spinal deformity (ASD) with a minimum follow-up of 2 years were included in the study. Patient, surgical, and radiological factors were evaluated. Muscle volume was measured using the muscle/vertebra ratio of the multifidus, erector spinae (ES), and psoas muscles, and muscle function was evaluated using the degree of fat infiltration at the L4-5 level. RESULTS: The study included 57 consecutive patients: 25 patients in the combined PJK/PJF group (13 with PJK and 12 with PJF) and 32 in the control group (without PJK or PJF). The mean time to onset of PJK and PJF was 15.7 and 1.7 months, respectively. Multivariate analysis showed that greater pre- and postoperative sagittal vertical axis was associated with the occurrence of PJK/PJF. ES muscle atrophy was more significant in the PJK/PJF group than in the control group, and more severe in the PJF than in the PJK group. CONCLUSIONS: This study showed that PJF occurred much earlier than PJK after ASD surgery. Paraspinal muscle atrophy was identified as a significant risk factor for PJK and PJF, especially PJF. The possibility of PJK and PJF development should be considered when long-segment fusion is planned for patients with paraspinal muscle atrophy.

Glycaemic control efficacy of switching from dipeptidyl peptidase-4 inhibitors to oral semaglutide in subjects with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 2 study).

AIM: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) continuation, in people with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-label, prospective, randomized, parallel-group comparison study, participants receiving DPP-4is were either switched to oral semaglutide (3-14 mg/day) or continued on DPP-4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored. RESULTS: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP-4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP-4i continuation [-0.65 (95% confidence interval: -0.79, -0.51) vs. +0.05 (95% confidence interval: -0.07, 0.16) (p < .001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP-4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2-R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms. CONCLUSIONS: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP-4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance.

Predictors of surgical outcomes for limited palatal muscle resection in patients with obstructive sleep apnea.

OBJECTIVE: Limited palatal muscle resection (LPMR) is a modified palatal surgical technique to correct retropalatal obstruction without complications. This study aims to determine the associated factors affecting the success and cure rate of LPMR in patients with obstructive sleep apnea (OSA), thus guiding patient selection and improving surgical outcome. METHODS: Thirty-five OSA patients underwent LPMR were enrolled. All patients received routine physical examination, preoperative drug-induced sleep endoscopy (DISE), and polysomnography (PSG). Clinical, polysomnographic, cephalometric variables, and DISE findings were evaluated. These measurements were compared between the surgical success and failure group based on the results of preoperative and postoperative PSG. Furthermore, we compared the cured and non-cured groups in the surgical success group. RESULTS: Among 35 patients, the overall success rate was 57 % with a cure rate of 31.4 %. Patients with Friedman stage II had a significantly higher success rate (p = 0.032). According to DISE results, tongue base obstruction affected the surgical outcome (p < 0.001). The success rate was 100 % in the no tongue base obstruction during DISE, 72.2 % in the partial obstruction, and 9.1 % in the total obstruction. Tonsil size is also helpful in predicting surgical success rate (p = 0.041). Furthermore, patients with mild AHI were more likely to be surgical cures. when compared with patients with severe AHI (p = 0.044). CONCLUSION: Patients with larger tonsil size and no tongue base obstruction during DISE may have a higher chance of surgical success with LPMR. The lower AHI may be predictors of surgical cure after LPMR.

Positive association between proinsulin and fatty liver index in people with type 2 diabetes.

The post-hoc study, derived from our previous prospective observational study, investigated the association between fasting serum proinsulin levels and hepatic steatosis in people with type 2 diabetes. The severity of hepatic steatosis was assessed using the fatty liver index. A total of 268 participants were divided into three groups: low (n = 110), moderate (n = 75), and high fatty liver index (n = 83). In both the crude and age/sex-adjusted analysis, logarithm-transformed proinsulin was significantly higher in the high fatty liver index group than in the low or moderate groups (all p < 0.01). The moderate fatty liver index group showed higher logarithm-transformed proinsulin than the low group (both p < 0.01). Positive associations between proinsulin and fatty liver index shown in this study would support an involvement of hepato-pancreatic crosstalk in the pathophysiology of type 2 diabetes.

Tumor Heterogeneity of Breast Cancer Assessed with Computed Tomography Texture Analysis: Association with Disease-Free Survival and Clinicopathological Prognostic Factor.

Breast cancer is a heterogeneous disease, and computed tomography texture analysis (CTTA), which reflects the tumor heterogeneity, may predict the prognosis. We investigated the usefulness of CTTA for the prediction of disease-free survival (DFS) and prognostic factors in patients with invasive breast cancer. A total of 256 consecutive women who underwent preoperative chest CT and surgery in our institution were included. The Cox proportional hazards model was used to determine the relationship between textural features and DFS. Logistic regression analysis was used to reveal the relationship between textural features and prognostic factors. Of 256 patients, 21 (8.2%) had disease recurrence over a median follow-up of 60 months. For the prediction of shorter DFS, higher histological grade (hazard ratio [HR], 6.12; p < 0.001) and lymphovascular invasion (HR, 2.93; p = 0.029) showed significance, as well as textural features such as lower mean attenuation (HR, 4.71; p = 0.003) and higher entropy (HR, 2.77; p = 0.036). Lower mean attenuation showed a correlation with higher tumor size, and higher entropy showed correlations with higher tumor size and Ki-67. In conclusion, CTTA-derived textural features can be used as a noninvasive imaging biomarker to predict shorter DFS and prognostic factors in patients with invasive breast cancer.

Sleep time on back as a predictor of adherence to positive airway pressure therapy.

Upper airway collapse can be effectively dealt with positive airway pressure (PAP), and patient adherence is considered as a major determining factor for success of PAP therapy. This study was performed to determine the potential factors affecting the adherence to PAP in patients with OSA by using polysomnography (PSG) parameters recorded for diagnosis of OSA. The data of 158 patients between December 2018 and July 2021 were collected. They were prescribed with PAP and used the device during the adaptation period for 90 days. They were categorized into adherent and non-adherent group according to the criteria of good adherence as use of PAP ≥ 4 h per night on 70% of nights. Demographic, clinical characteristics, and PSG results were reviewed. Among 158 patients engaged in PAP therapy, 121 patients (76.6%) met the criteria of good adherence. No significant differences were found in good adherence rate regarding demographic and clinical characteristics. None of the polysomnographic factors showed significant differences between adherent and non-adherent groups. However, the percentage of sleep time on back in the adherent group was significantly higher than non-adherent group (p = 0.041). The cut-off value was determined to be 41.45% (95% confidence interval 0.43 to 0.79) by receiver operating characteristic curve analysis and the odds ratio was calculated as 2.97. Only the percentage of sleep time on back appeared to be polysomnographic predictor for identifying good adherence to PAP therapy in OSA patients. However, the conclusions may be limited in generalization due to the small sample size.

Fulminant ACTH decrease following diabetic ketoacidosis induced by immune checkpoint inhibitor combination therapy with nivolumab and ipilimumab: A case report.

RATIONALE: The increasing use of immune checkpoint inhibitors (ICIs) for treating malignant tumors result in the concomitant rise of immune-related adverse events (irAEs). This case report may provide useful insight to understanding the etiology of ICI-induced hypophysitis, a severe irAE leading to potentially fatal secondary adrenal insufficiency. PATIENT CONCERNS: An 81-year-old Japanese man was hospitalized for diabetic ketoacidosis following 4 courses of ICI combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma. DIAGNOSIS: Insulin secretion was depleted, leading to diagnosis of fulminant type 1 diabetes. Adrenocorticotropic hormone (ACTH) and cortisol levels were very high (60.8 pmol/L and 1575 nmol/L, respectively) upon admission. ACTH and cortisol returned to normal ranges on the 2nd day. On the 8th day, an ACTH loading test showed intact cortisol response (peak value 519 nmol/L). However, on the 14th day, there was a sharp decrease in ACTH and cortisol levels (10.5 pmol/L and 47 nmol/L, respectively) accompanied by fatigue and a drop in blood pressure to 97/63 mm Hg. As secondary adrenal insufficiency was suspected, hydrocortisone replacement was initiated. An ACTH loading test on the 17th day revealed low cortisol peak (peak value 232 nmol/L), indicating sudden disruption of adrenal function. Magnetic resonance imaging showed no abnormal findings and there was no other pituitary hormone deficiency. These findings, along with the patient clinical course, suggest that secondary adrenal insufficiency was caused by acute ACTH producing cell destruction as an irAE associated with ICI therapy. INTERVENTIONS: The patient hyperglycemia and ketoacidosis were treated using extracellular fluid and insulin therapy. After development of adrenal insufficiency, hydrocortisone 20 mg was started, and the patient symptoms improved. OUTCOMES: He was continued on insulin therapy, hydrocortisone, and reinitiated nivolumab. LESSONS: This case provides a detailed course of the fulminant onset of ACTH deficiency during ICI administration, emphasizing the importance of close monitoring.