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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Objective: To show a decrease in tumor recurrence and improvement in quality of life in patients with recurrent cervical cancer.Method: A 58-year-old female patient diagnosed with recurrent cervical cancer in February 2021 was treated for 14 months with integrative cancer treatment (ICT) to decrease the tumor size and improve chemotherapy-induced peripheral neuropathy (CIPN) and nausea. The patient underwent chemotherapy or concomitant chemoradiation therapy (CCRT) with ICT. Radiologic outcomes were assessed by abdomen & pelvis computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) based on the Response Evaluation Criteria in Solid Tumors (RECIST) protocol. Clinical outcomes were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Eastern Cooperative Oncology Group (ECOG), and a numeric rating scale (NRS).Result: During the 14 months of treatment, the size and metabolic activity of the recurrent tumor decreased and underwent partial remission based on RECIST. The NRS scores for CIPN and nausea were improved, and the ECOG score improved from grade 2 to 1. No serious side effects of grade 3 or higher were noted on the NCI-CTCAE test.Conclusion: This case suggests that ICT may have a synergetic effect with chemotherapy or radiotherapy for recurrent cervical cancer.

Introduction. Hypereosinophilic syndrome (HES) is a rare disease characterized by unexplained peripheral eosinophilia along with evidence of end-organ damage. Cardiac involvement is the most life-threatening consequence and is frequently underreported with a prevalence of around 5%. The gold standard for diagnosis is myocardial biopsy, but less-invasive imaging such as cardiac MR (CMR) has been frequently used to help with the diagnosis. We are presenting a unique case of a patient diagnosed with Eosinophilic myocarditis (EM) supported by CMR with rapid improvement after starting steroid treatment. Case Presentation. A 67-year-old African American female with extensive cardiovascular disease history presenting with chest pain was diagnosed with EM secondary to hypereosinophilic syndrome (HES). Lab workup revealed absolute eosinophils of 4.70 × 10 3 / μ L (normal 0 – 0.75 × 10 3 / μ L ). Transthoracic echocardiography showed mild reduction in left ventricular function and a large obliterating thrombus in the right ventricular apex. CMR showed increased signal intensity at the left ventricular and right ventricular apex, consistent with myocardial edema. Subsequently, the patient was placed on dexamethasone 10 mg daily with significant symptomatic improvement. Discussion. EM is a rare complication of hypereosinophilic syndrome and can mimic common cardiovascular diseases such as acute exacerbation of heart failure or myocardial infarction. A high index of suspicion is essential especially in the setting of suggestive lab workup. CMR is a promising noninvasive and cost-effective alternative for myocardial biopsy in diagnosis.

s Background Giant Cell Arteritis (GCA) is a large vessel vasculitis that most commonly presents with headache, scalp tenderness, jaw claudication, and vision changes. Various other, less common, manifestations have been reported in the literature such as scalp and tongue necrosis. Though most patients respond to corticosteroids, some cases of GCA are refractory to the high doses of corticosteroids. Case presentation We present a 73-year-old female with GCA refractory to corticosteroids presenting with tongue necrosis. This patient significantly improved with a dose of tocilizumab, an IL-6 inhibitor. Conclusion To the best of our knowledge, this is the first case report of a patient with refractory GCA presenting with tongue necrosis that had rapid improvement with tocilizumab. Prompt diagnosis and treatment can prevent severe outcomes such as tongue amputation in GCA patients with tongue necrosis, and tocilizumab may be effective for corticosteroid-refractory cases.

In this case study, we describe a 25-year-old male who was admitted due to a severe traumatic brain injury, requiring invasive intracranial pressure monitoring. At 48 hours posttrauma, he developed intracranial hypertension refractory to medical treatment without tomographic changes in the brain. Subsequently, intra-abdominal hypertension and tomographic signs of abdominal surgical pathology were observed. An exploratory laparotomy was performed with an intraoperative diagnosis of acute mesenteric ischemia. After surgical intervention for the abdominal pathology, intracranial pressure was restored to physiological values with a favorable recovery of the patient. In this report, the relationship between intracranial pressure and intra-abdominal pressure is discussed, highlighting the delicate association between the brain, abdomen, and thorax. Measures should be taken to avoid increases in intra-abdominal pressure in neurocritical patients. When treating intracranial hypertension refractory to conventional measures, abdominal causes and multiple compartment syndrome must be considered. The cranial compartment has physiological interdependence with other body compartments, where one can be modified by variations from another, giving rise to the concept of multiple compartment syndrome. Understanding this relationship is fundamental for a comprehensive approach of the neurocritical patient. To the best of our knowledge, this is the first report of a comatose patient post-traumatic brain injury, who developed medically unresponsive intracranial hypertension secondary to acute mesenteric ischemia, in which surgical resolution of intra-abdominal pathology resulted in intracranial pressure normalization and restitutio ad integrum of neurological status.

The prevalence of diabetes and obesity continues to rise in East Asia. As the risk of diabetes increases at a lower body mass index (BMI) in East Asians than in Europeans, the threshold of BMI values for metabolic and bariatric surgery (MBS) is lower in East Asians. MBS is considered upon reaching a BMI of 27.5 kg/m

T-cell large granular lymphocyte (T-LGL) leukemia is a rare and indolent clonal disorder of LGLs, associated with rheumatoid arthritis and neutropenia. The authors present a case of a 62-year-old male with rheumatoid arthritis (RA) who was diagnosed with T-LGL leukemia, with predominant neutropenia, and a poor response to conventional treatment. Subsequently, tofacitinib (a Janus Kinase 1 and 3 inhibitor, [JAK1/3 inhibitor]) resulted in improvement of the patient’s RA symptoms and temporary improvement of the neutropenia. Ultimately, upadacitinib (a specific JAK1 inhibitor) resulted in further improvement of the neutropenia and control of his RA. To the best of our knowledge, this is the first case report of coexisting RA and LGL leukemia that was treated with upadacitinib and showed clinical improvement.

Background Impaired respiratory function remains underrecognized in patients with type 2 diabetes (T2D), despite common pulmonary impairment. Meanwhile, there is little data available on the respiratory effects of sodium glucose cotransporter 2 inhibitors (SGLT2i). Hence, we examined the association between SGLT2i use and the risk of adverse respiratory events in a real-world setting. Methods We conducted a population-based, nationwide cohort study using an active-comparator new-user design and nationwide claims data of South Korea from January 2015 to December 2020. Among individuals aged 18 years or older, propensity score matching was done to match each new user of SGLT2is with dipeptidyl peptidase 4 inhibitors (DPP4is), with patients followed up according to an as-treated definition. The primary outcome was respiratory events, a composite endpoint of acute pulmonary edema, acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure. Secondary outcomes were the individual components of the primary outcome and in-hospital death. Cox models were used to estimate hazard ratios (HRs) and 95% CIs. Results Of 205,534 patient pairs in the propensity score matched cohort, the mean age of the entire cohort was 53.8 years and 59% were men, with a median follow-up of 0.66 years; all baseline covariates achieved balance between the two groups. Incidence rates for overall respiratory events were 4.54 and 7.54 per 1000 person-years among SGLT2i and DPP4i users, respectively, corresponding to a rate difference of 3 less events per 1000 person-years (95% CI − 3.44 to − 2.55). HRs (95% CIs) were 0.60 (0.55 to 0.64) for the composite respiratory endpoint, 0.35 (0.23 to 0.55) for acute pulmonary edema, 0.44 (0.18 to 1.05) for ARDS, 0.61 (0.56 to 0.66) for pneumonia, 0.49 (0.31 to 0.76) for respiratory failure, and 0.46 (0.41 to 0.51) for in-hospital death. Similar trends were found across individual SGLT2is, subgroup analyses of age, sex, history of comorbidities, and a range of sensitivity analyses. Conclusions These findings suggest a lower risk of adverse respiratory events associated with patients with T2D initiating SGLT2is versus DPP4is. This real-world evidence helps inform patients, clinicians, and guideline writers regarding the respiratory effects of SGLT2i in routine practice.

Continuous glucose monitoring systems (CGMS) are becoming increasingly popular in diabetes management compared to conventional methods of self-blood glucose monitoring systems. They help understanding physiological responses towards nutrition intake, physical activities in everyday life and glucose control. CGMS available in market are of two types based on their working principle. Needle type systems with few weeks lifespan (e.g., enzyme-based Freestyle Libre) and implant type system (e.g., fluorescence-based Senseonics) with few months of lifespan are commercially available. An alternate to both working methods, herein, we propose electromagnetic-based sensor that can be subcutaneously implanted and capable of tracking minute changes in dielectric permittivity owing to changes in blood glucose level (BGL). Proof-of-concept of proposed electromagnetic-based implant sensor has been validated in intravenous glucose tolerance test (IVGTT) conducted on swine and beagle in a controlled environment. Sensor interface modules, mobile applications, and glucose mapping algorithms are also developed for continuous measurement in a freely moving beagle during oral glucose tolerance test (OGTT). The results of the short-term (1 h, IVGTT) and long-term (52 h, OGTT) test are summarized in this work. A close trend is observed between sensor frequency and BGL during GTT experiments on both animal species.

Continuous glucose monitoring system (CGMS) is growing popular and preferred by diabetes over conventional methods of self-blood glucose monitoring (SBGM) systems. However, currently available commercial CGMS in the market is useful for few days to few months. This paper presents a durable, highly sensitive and minimally invasive implant type electromagnetic sensor for continuous glucose monitoring that is capable of tracking minute changes in blood glucose level (BGL).The proposed sensor utilizes strong oscillating nearfield to detect minute changes in dielectric permittivity of interstitial fluid (ISF) and blood due to changes in BGL. A biocompatible packaging material is used to cover the sensor. It helps in minimizing foreign body reactions (FBR) and improves stability of the sensor.The performance of the proposed sensor was evaluated on live rodent models (C57BL/6J mouse and Sprague Dawley rat) through intravenous glucose and insulin tolerance tests. Biocompatible polyolefin was used as the sensor packaging material, and the effect of packaging thickness on the sensitivity of sensor was examined in in-vivo test. Proposed sensor could track real-time BGL change measured with a commercial blood glucose meter. High linear correlation (RThe experimental results demonstrate that the proposed sensor is suitable for long term CGMS applications with a high accuracy.Present work offers a new perspective towards development of long term CGM system using electromagnetic based implant sensor. The in vivo evaluation of the sensor shows excellent tracking of BGL changes.

Upper-extremity deep venous thrombosis (UEDVT) after whole blood donation is rarely reported. Blood donation has a low rate of complications and is typically safe. A small percentage of blood donors experience donation-related events such as UEDVT, which are extremely rare. We are reporting a rare case of a UEDVT following blood donation. This is an extremely rare event; only five cases were reported to our knowledge. A 22-year-old Caucasian woman with a past medical history of provoked pulmonary embolism completed 6 months of apixaban and negative thrombophilia workup presented to the hospital with complaints of progressive pain and swelling in her right arm. The patient reports donating blood using her right arm in January 2021. Phlebotomy duration for blood donation was approximately 10minutes. She reported pain and swelling several days after blood donation. Subsequently, a duplex ultrasound showed a thrombus in the right brachial vein. The patient was started on apixaban for 6 months. Although most whole blood donors do not experience complications, DVT is a rare complication from whole blood donation with severe consequences. It should be considered in a donor with worsening pain and swelling.

Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the progression of diabetic kidney disease. However, the mechanisms underlying this renoprotective benefit are not completely understood. We evaluated whether SGLT2 inhibition reduces cellular senescence in the kidney and investigated the molecular pathways involved in the renoprotective effect. Materials and methods Dapagliflozin (1 mg/kg), glimepiride (2.5 mg/kg), or vehicle was administered daily via oral gavage for 8 weeks in db/db mice. Expression levels of ageing marker genes (p21, p16, and p53) and oxidative stress were measured in the kidney using real-time RT-PCR, immunohistochemistry, and western blot analysis. For in vitro analysis, HK-2 cells, a human renal tubular epithelial cell line, were pretreated with H2 O2 to induce cellular senescence, and the levels of ageing markers were measured after treatment with β-hydroxybutyrate (β-HB) or NRF2-specific siRNA. Results Expression levels of ageing marker genes (p21, p16, and p53) and senescence-associated secretory phenotypes of the kidney were increased in the vehicle-treated db/db (db/db+vehicle) group compared with the db/+ group, and this increase was markedly reversed in the dapagliflozin-treated db/db (db/db+SGLT2i) group, but not in the glimepiride-treated db/db (db/db+SU) group. In the kidneys of mice in the db/db+SGLT2i group, oxidative stress and DNA damage were also reduced compared with those in the db/db+vehicle and db/db+SU groups. Dapagliflozin increased plasma β-HB, which reduced H2 O2 -induced DNA damage and senescence in HK-2 cells. β-HB-induced NRF2 nuclear translocation mediated anti-senescent effects by inducing antioxidant pathways. Conclusions Dapagliflozin prevented the progression of diabetic kidney disease by inhibiting cellular senescence and oxidative stress via ketone-induced NRF2 activation. This article is protected by copyright. All rights reserved.

OBJECTIVE To investigate the effects of patient-driven lifestyle modification using intermittently scanned continuous glucose monitoring (isCGM) in patients with type 2 diabetes mellitus (T2D). RESEARCH DESIGN AND METHODS We conducted a 12-week, open-label, randomized controlled trial. A total of 126 participants were 1:1 randomized to either the intervention group (structured education + isCGM) or the control group (standard care with blood glucose monitoring). The Self-Evaluation Of Unhealthy foods by Looking at the postprandial glucose (SEOUL) algorithm was developed and applied to aid structured education by guiding patients to follow healthy eating behavior depending on the postprandial glycemic response. The primary endpoint was the change in HbA1c level from baseline. RESULTS Implementation of the SEOUL algorithm with isCGM was associated with a greater improvement in HbA1c than standard care (risk-adjusted difference, –0.50%, 95% CI, –0.74 to –0.26%, P < 0.001). Participants in the intervention group had a greater reduction in fasting blood glucose and body weight (−16.5 mg/dL, 95% CI, −30.0 to −3.0 mg/dL, P = 0.017; −1.5 kg, 95% CI, −2.7 to −0.3 kg, P = 0.013, respectively). The score sum for the Korean version of the revised summary of diabetes self-care activities increased in both groups but to a greater extent in the intervention group (mean difference 4.8, 95% CI, 1.7–8.0, P = 0.003). No severe hyperglycemia or hypoglycemia was reported in either group of patients. CONCLUSIONS Patient-driven lifestyle modification primarily focused on eating behavior using isCGM effectively lowered HbA1c levels in patients with T2D.

Lignin has different structural characteristics depending on the extraction conditions. In this study, three types of ethanol organosolv lignin (EOL) were produced under different extraction conditions involving the reaction temperature (140, 160, 180 °C), sulfuric acid concentration (0.5, 1, 1.5 %), and ethanol concentration (40, 60, 80 %) to compare the difference in properties when mixed with polylactic acid (PLA) matrix after atom transfer radical polymerization (ATRP). ATRP of EOL was conducted to improve its compatibility with PLA using methyl methacrylate (MMA) as a monomer. The molecular weight of each EOL increased significantly, and the glass transition temperature (T

Glucagon-like peptide-1 (GLP-1) receptor agonists are efficacious glucose-lowering medications with salient benefits for body weight and cardiovascular events. This class of medications is now recommended as the top priority for patients with established cardiovascular disease or indicators of high risk. Until the advent of oral semaglutide, however, GLP-1 receptor agonists were available only in the form of subcutaneous injections. Aversion to needles, discomfort with self-injection, or skin problems at the injection site are commonly voiced problems in people with diabetes, and thus, attempts for non-invasive delivery strategies have continued. Herein, we review the evolution of GLP-1 therapy from its discovery and the development of currently approved drugs to the unprecedented endeavor to administer GLP-1 receptor agonists via the oral route. We focus on the pharmacokinetic and pharmacodynamic properties of the recently approved oral GLP-1 receptor agonist, oral semaglutide. Small molecule oral GLP-1 receptor agonists are currently in development, and we introduce how these chemicals have addressed the challenge posed by interactions with the large extracellular ligand binding domain of the GLP-1 receptor. We specifically discuss the structure and pharmacological properties of TT-OAD2, LY3502970, and PF-06882961, and envision an era where more patients could benefit from oral GLP-1 receptor agonist therapy.

Vertical sleeve gastrectomy (VSG) is the most commonly performed bariatric/metabolic surgery, exhibiting a high rate of diabetes remission in humans. To elucidate the molecular mechanisms of VSG, we performed transcriptomic analysis of the liver, fat, and muscle in VSG mice. C57BL/6 mice fed a high-fat diet were randomly assigned to sham or VSG surgery. The sham-operated mice were fed ad libitum (sham group) or pair-fed (sham-PF group) matching their food intake to the VSG-operated mice. Comparative transcriptomic analysis of the liver, fat, and muscle using RNA sequencing was performed. VSG reduced body weight and improved glucose tolerance compared to the sham group, but not more than the sham-PF group. Improvement in fatty liver and adipose tissue inflammation was comparable between VSG and sham-PF. However, global gene expression profiles showed distinctive changes in the liver, fat, and muscle of the VSG group compared to both the sham or sham-PF groups. The liver showed the most prominent gene expression changes. Immune response-related pathways were commonly upregulated in the three organs of the VSG group compared to the sham or sham-PF. VSG induces organ-specific gene expression changes in the liver, fat, and muscle, which may play critical roles in metabolic improvements after VSG.