Pathology of Ketoacidosis in Emergency of Diabetic Ketoacidosis and Alcoholic Ketoacidosis: A Retrospective Study.

This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) patients hospitalized in Kawasaki Medical School General Medical Center from April 2015 to March 2021. Almost all patients in this study were brought to the emergency room in a coma and hospitalized. All patients underwent blood gas aspiration and laboratory tests. We evaluated the difference in diagnosis markers in emergencies between DKA and alcoholic ketoacidosis AKA. Compared to AKA patients, DKA patients had statistically higher values of serum acetoacetic acid and lower values of serum lactate, arterial blood pH, and base excess. In contrast, total ketone bodies, ß-hydroxybutyric acid, and ß-hydroxybutyric acid/acetoacetic acid ratio in serum did not differ between the two patient groups. It was shown that evaluation of each pathology such as low body weight, diabetes, liver dysfunction, and dehydration was important. It is important to perform differential diagnosis for taking medical histories such as insulin deficiency, alcohol abuse, or starvation as the etiology in Japanese subjects with DKA or AKA. Moreover, it is important to precisely comprehend the pathology of dehydration and alcoholic metabolism which would lead to appropriate treatment for DKA and AKA.

Comparison of clinical efficacy and safety of weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in Japanese patients with type 2 diabetes: Randomized, parallel-group, multicentre, open-label trial (COMING study).

AIM: To compare the clinical usefulness of once-weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide at the doses approved for use in Japanese patients with type 2 diabetes. METHODS: In total, 120 patients with glycated haemoglobin (HbA1c) ≥7% were randomly assigned to dulaglutide (n = 59) or semaglutide group (n = 61), and 107 participants (dulaglutide/semaglutide = 53/54) completed the 24-week trial. The primary endpoint was the difference of HbA1c level between the two groups at 24 weeks. RESULTS: HbA1c level at 24 weeks was significantly lower in the semaglutide group (7.9 ± 0.5%-6.7 ± 0.5%) compared with the dulaglutide group (8.1 ± 0.6%-7.4 ± 0.8%) (p < .0001). Reduction in body mass index and visceral fat area were also more significant in the semaglutide group (p < .05, respectively). The achievement rate of HbA1c <7% was higher in the semaglutide group (p < .0001). The parameters such as low-density lipoprotein cholesterol, alanine aminotransferase and γ-glutamyl transpeptidase were decreased in the semaglutide group. Surprisingly, only semaglutide group significantly improved the apolipoprotein B/A1 ratio, which is considered a useful myocardial infarction risk index. Using computed tomography, the liver to spleen ratio was significantly elevated only in the semaglutide group. In contrast, gastrointestinal symptoms were observed in 13.2% of dulaglutide and 46.3% of semaglutide group (p < .01). The Diabetes Treatment-Related Quality of Life scores related to pain and gastrointestinal symptoms were also superior in the dulaglutide group. CONCLUSIONS: This prospective trial showed that semaglutide has more pronounced glucose- and body mass index-lowering effects and reduces liver fat percentage and visceral fat area and that dulaglutide has less gastrointestinal symptoms and superior Diabetes Treatment-Related Quality of Life scores related to pain and gastrointestinal symptoms.

Identification of In-Droplet Multicellular Communities by Light-Induced Combinatorial DNA Barcoding.

A microdroplet co-culture system is useful for the parallel assessment of numerous possible cell-cell interactions by generating isolated subcommunities from a pool of heterogeneous cells. However, the integration of single-cell sequencing into such analysis has been limited due to the lack of effective molecular identifiers for each in-droplet subcommunity. Herein, we present a strategy for generating in-droplet subcommunity identifiers using DNA-functionalized microparticles encapsulated within microdroplets. These microparticles serve as initial information carriers, where their combinations act as distinct identifiers for in-droplet subcommunity. Upon optical trigger, DNA barcoding molecules encoding the microparticle information are once released in the microdroplets and then tag cell membranes. The tagged DNA molecules then serve as a second information carrier readable by single-cell sequencing to reconstitute the community in silico in the single-cell RNA sequencing data space.

Impact of nutritional guidance on various clinical parameters in patients with moderate obesity: A retrospective study.

Context: This study aims to investigate whether there is adequate provision of nutritional guidance through interventions by registered dietitians, especially for patients with moderate obesity. This is particularly important as such interventions may prove to be more effective for Japanese patients. Methods: In Japan, since there is a system of nutritional guidance with a registered dietitian for patients with a BMI over 30 kg/m2, we recruited 636 patients with obesity who had a BMI over 30 kg/m2 admitted to the Kawasaki Medical School General Medical Center between April 2018 and March 2020 through a review of their medical records. Second, we recruited 153 patients who underwent a blood examination before receiving nutritional guidance and at least one time every 3 to 6 months thereafter after receiving it. We aimed to evaluate whether continued nutritional guidance and follow-up interventions for patients with obesity were effective. We compared the BMI and metabolic markers of the patients who received nutritional guidance from a registered dietitian against those who did not. Results: A total of 636 patients with obesity who have a BMI over 30 kg/m2 were included in this study. A total of 164 patients with obesity received nutritional guidance from a registered dietitian at least one time, but 472 patients did not. Most interventions on nutritional guidance conducted by a registered dietitian were ordered from internal medicine (81.1%). However, internal medicine was the most common department that did not perform these interventions; however, less than half of the (49.2%) received them. In the second analysis, we compared two groups of patients with obesity. The first group (n = 70) who underwent blood examinations received nutritional guidance from a registered dietitian, while the second group (n = 54) did not receive such guidance. We found that there was no significant difference in body weight and BMI between the two groups of patients. We observed a significant decrease in dyslipidemia-associated metabolic markers among the patients who received nutritional guidance compared to those who did not [total cholesterol, -9.7 ± 29.3 vs. 2.3 ± 22.0 mg/dL (p = 0.0208); low-density lipoprotein cholesterol, -10.4 ± 30.5 vs. -2.0 ± 51.0 mg/dL (p = 0.0147), respectively]. Other metabolic markers also tended to decrease, although they did not reach statistical significance. Conclusion: It is rare for patients with only obesity to receive nutritional guidance. However, when nutritional guidance from a registered dietitian is provided, improvements in BMI and metabolic parameters can be expected.

Ectopic PTH-producing parathyroid cyst inside the thymus: a case report.

BACKGROUND: The hallmark of hyperparathyroidism is hypersecretion of parathyroid hormone (PTH) which results in hypercalcemia and hypophosphatemia. While hypercalcemia due to malignancy is often brought about by PTH-related protein in adults, PTH-producing tumors are quite rare in clinical practice. Additionally, from the point of embryology, it is very difficult to examine ectopic PTH-producing tissue such as ectopic parathyroid glands. Furthermore, clear histopathological criteria are not present. CASE PRESENTATION: A 57-year-old woman was referred to our hospital for hypercalcemia. Her parathyroid hormone (PTH) level was elevated, but there were no enlarged parathyroid glands. Although 99mTc-MIBI confirmed a localized and slightly hyperfunctioning parathyroid tissue in the anterior mediastinum, it was not typical as hyperfunctioning parathyroid. We finally diagnosed her as ectopic PTH-producing cyst-like tumor with venous sampling of PTH. She underwent anterosuperior mediastinal ectopic PTH-producing cyst-like tumor resection. It is noted that intact-PTH concentration of the fluid in the cyst was very high (19,960,000 pg/mL). Based on histopathological findings, we finally diagnosed her as ectopic PTH-producing parathyroid cyst inside the thymus. After resection of anterosuperior mediastinal thymus including ectopic PTH-producing parathyroid cyst, calcium and intact-PTH levels were decreased, and this patient was discharged without any sequelae. CONCLUSIONS: We should know the possibility of superior mediastinal ectopic PTH-producing parathyroid cyst inside the thymus among subjects with ectopic PTH-producing parathyroid glands. Particularly when the cyst is present in the superior mediastinum, it is necessary to do careful diagnosis based on not only positive but also negative findings in 99mTc-MIBI. It is noted that the patient's bloody fluid in the cyst contained 19,960,000 pg/mL of intact-PTH, and its overflow into blood stream resulted in hyperparathyroidism and hypercalcemia. Moreover, in such cases, the diagnosis is usually confirmed after through histological examination of ectopic PTH-producing parathyroid glands. We think that it is very meaningful to let clinicians know this case.

Adult acetonemic vomiting complicated with low body weight in a subject with Mycobacterium avium complex pulmonary disease: a case report.

Pulmonary diseases often cause significant health issues and nutritional disorders. Weight loss and malnutrition are related to the severity of obstructive disorders. Therefore, patients with such conditions often experience low nutritional energy. Acetonemic vomiting is caused by acetonemic syndrome. Previously, it was believe that acetonemic vomiting was observed only in childhood. However, it was recently suggested that acetonemic vomiting can also occur in adults. It is also considered that acetonemic vomiting can occur in subjects with low body weight because stored carbohydrate levels are reduced and fats are mainly used for energy. Consequently, large amounts of acetone are produced, ultimately resulting in nausea and vomiting. In this study, we report a case of adult acetonemic vomiting complicated by low body weight in a subject with Mycobacterium avium complex pulmonary disease.

Onset of Aortic Dissection Complicated with Cushing's Disease: A Case Report and Review of the Literature.

Cushing's syndrome and Cushing's disease cause various metabolic disorders associated with high cortisol levels. Some reports have shown that Cushing's syndrome is complicated with dissecting aortic aneurysm and aortic dissection after long-term exposure to high cortisol levels. We herein report a rare case of aortic dissection complicated with Cushing's disease. Aortic dissection may occur even under relatively short periods of high cortisol conditions. This case suggests that hypercortisolemia should be treated as soon as possible in order to prevent aortic dissection in subjects with Cushing's disease.

A pitfall in hemoglobin A1c measurement with high performance liquid chromatography method in the diagnosis of onset of fulminant type 1 diabetes mellitus.

We showed a case with the onset of fulminant type 1 diabetes mellitus (FT1DM) whose HbA1c could not be measured with HPLC method. We think that the reason why his HbA1c was not be detected was associated with the presence of labile hemoglobin A1c (LHbA1c). These result mean that it is possible that LHbA1c can bring about a pitfall on HPLC method in diagnosis of onset of FT1DM.

Serious diabetic ketoacidosis induced by insulin allergy and anti-insulin antibody in an individual with type 2 diabetes mellitus.

Diabetic ketoacidosis (DKA) is one of the most serious acute metabolic complications of diabetes mellitus, and is characterized by hyperglycemia, metabolic acidosis and increased total ketone body concentrations. The main mechanism of DKA is a lack of insulin in the body. It has been reported that some immunological response is associated with insulin therapy. Herein, we report a case of serious DKA, which was induced by insulin allergy and anti-insulin antibody. This case clearly shows that DKA can be induced by insulin allergy and anti-insulin antibodies in individuals with type 2 diabetes treated with insulin. Furthermore, we should know that as the required insulin dose might be very high under severe insulin resistance and serious DKA in such cases, we should increase the insulin dose appropriately while monitoring pH, base excess and other factors.

Case Report: A Patient With Neuroleptic Malignant Syndrome, Water Intoxication and Hyponatremia Associated With Severe Cerebral Edema and Coma.

Background: Water intoxication is typically caused by primary or psychogenic polydipsia that potentially may lead to fatal disturbance in brain functions. Neuroleptic malignant syndrome (NMS) is a serious complication induced by administration of antipsychotics and other psychotropic drugs. The combination of inappropriate secretion of antidiuretic hormone (SIDAH), NMS and rhabdomyolysis have been rarely reported. Our patient also developed severe water intoxication. Case presentation: Herein we report a comatose case of NMS complicated with water intoxication, syndrome of SIADH and rhabdomyolysis. This patient had severe cerebral edema and hyponatremia that were improved rapidly by the correction of hyponatremia within a couple of days. Conclusions: Malignant neuroleptic syndrome water intoxication, SIADH and rhabdomyolysis can occur simultaneously. Comatose conditions induced by cerebral edema and hyponatremia can be successfully treated by meticulous fluid management and the correction of hyponatremia.

Case Report: Onset of Type 1 Diabetes Mellitus in a Patient With Ulcerative Colitis and Sjogren's Syndrome Under Euthyroid Hashimoto's Thyroiditis.

Type 1 diabetes mellitus (T1DM) is often complicated with some other autoimmune disorders. The complication of various autoimmune disorders is known as autoimmune polyglandular syndrome (APS). Once autoimmune thyroid disease develops, various autoimmune diseases can also occur. Such phenomena are classified as APS types 3A to 3D. In this report, we show the onset of T1DM in a patient with ulcerative colitis (UC) and Sjogren's syndrome. The most important and interesting point in this case is that, if we did not check her thyroid-associated antibodies, we could not have diagnosed her as APS. From the data of this case, we assumed that the patient suffered from APS type 3A, 3B, and 3D variants. This case pointed out very clearly the importance of testing for thyroid-associated antibodies under various autoimmune disease conditions even if the thyroid hormone levels are euthyroid. Moreover, based on the strong linkage between inflammatory bowel disease and T1DM and the compatibility with both T1DM and APS type 3, we think it is possible that Hashimoto's disease is present under complicated conditions together with UC and T1DM. It would be important to repeatedly check for thyroid-associated antibodies even in euthyroid patients, especially under various autoimmune disease conditions.

Case Report: Appearance of Various Disease-Specific Antibodies After the Onset of Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid.

Bullous pemphigoid (BP) is a rare autoimmune blistering disease, and the prevalence of type 2 diabetes mellitus (T2DM) is relatively high in subjects with BP. It is known that dipeptidyl peptidase-4 inhibitor (DPP-4i), one kind of antidiabetic drugs, can cause BP, although precise mechanism of DPP-4i-related BP remains unclear. In this report, we showed a case with appearance of various disease-specific antibodies after the onset of DPP-4i-related BP. Furthermore, various disease-specific antibodies became positive and showed high titers two years after the onset of DPP-4i-related BP and discontinuation of DPP-4i. These data showed that it is possible for immune tolerance to be broken after the onset of DPP-4i-related BP, and it may be important to check autoimmune antibodies in DPP-4i-related BP subjects even when BP symptoms are improved.

Acute respiratory distress syndrome triggered by marked cytokine storm in a subject with diabetic ketoacidosis: A case report.

RATIONALE: Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury. Many causes of acute direct and indirect lung injury have been described as possible initiators of ARDS. According to the literature data, ARDS could be a rare complication associated with the acute onset of diabetic ketoacidosis (DKA). Moreover, it has been suggested that cytokine release during DKA is involved in the above-mentioned acute clinical complications of DKA. PATIENTCONCERNS: A 48-year-old Japanese woman with a 4-year history of type 1 diabetes mellitus was brought to an emergency room with symptoms of deteriorated consciousness. Three days before, she was diagnosed with influenza A infection. DIAGNOSIS: Inflammation markers were markedly elevated and she was under DKA condition. Since her respiratory conditions were suddenly and markedly aggravated 2 days later, we diagnosed her as ARDS and continued systemic management with the ventilator.Interleukin-6 (IL-6) level was markedly elevated at the onset of ARDS, although IL-6 level was high at the onset of DKA. ARDS was suggested to be caused by marked cytokine storm and DKA. INTERVENTIONS: We continued to treat her hyperglycemic crises. Moreover, we continued systemic management with the ventilator. OUTCOMES: Approximately three weeks later, her general conditions were stabilized and ventilator management was stopped. We successfully treated her ARDS and hyperglycemic crises. LESSONS: This case is very important because it shows that DKA can induce cytokine storm, which leads to the onset of ARDS. Therefore, monitoring various cytokines such as IL-6, which are associated with ARDS during the period of treatment of DKA is beneficial.

Formation of large abscess tumor including gallstone in ileum during therapy for hyperosmolar hyperglycemic syndrome: a case report.

Hyperosmolar hyperglycemic status (HHS) is one of the most serious acute metabolic complications of diabetes mellitus (DM) and the patients with type 2 DM are immunocompromised host, especially when glycemic control is poor. Under hyperglycemic conditions, we have to pay much attention even for rare infection. Bouveret's syndrome is a rare type of gallstone ileus together with duodenal obstruction secondary to the passage of a stone through a cholecystoduodenal fistula. Herein, we reported a rare case with formation of large abscess tumor, including necrotic ileum and gallstone after taking therapy for HHS. She was under more rare conditions rather than Bouveret's syndrome, because large abscess tumor was formed not in the duodenal bulb but in the ileum together with necrotic ileitis and abdominal abscess with impacted gallstone. We should bear in mind that T2DM patients are immunocompromised host in particular under untreated or poorly controlled conditions and thereby they could have rare inflammatory diseases such as a large abscess tumor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00540-3.

Edematous wall thickening of the gallbladder induced by hyperthyroidism: A case report.

RATIONALE: Hyperthyroidism, such as Basedow disease, causes fluid retention, although the common cause is volume overload due to congestive heart failure. In addition, hyperthyroidism and Basedow disease are known to cause pulmonary hypertension. Edematous thickening of the gallbladder wall is caused by venous blood congestion. The feature of edematous wall thickening of the gallbladder on abdominal computed tomography (CT) is subserosal edema and is often accompanied by a periportal collar sign. PATIENT CONCERNS: A 30-year-old woman was referred to our hospital because of liver dysfunction, edematous gallbladder wall thickening, and fluid retention. In addition, the patient developed hyperthyroidism and heart failure. Enhanced abdominal CT revealed edematous wall thickening of the gallbladder and a periportal collar sign. DIAGNOSIS: We suspected that fluid retention and congestion were caused by hyperthyroidism and Basedow disease. INTERVENTIONS: On admission, we started thiamazole therapy for Basedow disease, and her thyroid hormone levels normalized. OUTCOMES: Abdominal CT revealed disappearance of edematous wall thickening of the gallbladder, which was likely associated with an improvement in thyroid function. The patient was discharged 10 days after admission. LESSONS: We encountered a case of hyperthyroidism and Basedow disease accompanied by edematous wall thickening of the gallbladder and various fluid retentions as the first symptoms. Such edematous wall thickening of the gallbladder and various fluid retentions were reduced, together with the improvement of hyperthyroidism.

Case Report: Markedly Long-Term Preservation of Pancreatic ß-Cell Function in a Subject With Elderly Onset of Type 1 Diabetes Mellitus Showing High-Titer Autoimmune Antibodies for Over 4 Years.

Type 1 diabetes mellitus (T1DM) is mainly triggered by autoimmune ß-cell destruction, usually leading to absolute insulin deficiency. Regarding the speed of ß-cell destruction, there are large variations depending on age. In some adult cases, sufficient ß-cell function is sometimes retained for a relatively long period and eventually they become dependent on insulin for survival. It is known that even in subjects with T1DM showing high titers of such antibodies, insulin secretory capacity is preserved under several conditions such as "honeymoon" period and slowly progressive T1DM (SPIDDM). Herein, we reported the acute onset T1DM subject with long-term preservation of ß-cell function, although his anti-GAD antibody and anti-IA-2 antibody titers were very high for more than 4 years. This case is very important in that his ß-cell function was preserved with dipeptidyl peptidase-4 inhibitor alone. This means that there are large variations in the speed of ß-cell destruction in the onset of T1DM.

Case Report: Emphysematous Cystitis and Pyelonephritis Induced by Uterine Prolapse in a Subject With Untreated Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is often accompanied by a lot of complications due to chronic hyperglycemia and inflammation. Emphysematous cystitis and pyelonephritis are rare types of urinary tract infections and are often complicated with DM. Herein, we report a case of emphysematous cystitis and pyelonephritis complicated with untreated DM. In addition, this case was very rare and interesting in that her emphysematous cystitis and pyelonephritis were induced by severe uterine prolapse, obstructive uropathy and urination disorders. Both uterine prolapse and DM should be appropriately treated because both can lead to the development of emphysematous cystitis and pyelonephritis.

Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.

The ESCRT pathway is evolutionarily conserved across eukaryotes and plays key roles in a variety of membrane remodeling processes. A new Drosophila mutant recovered in our forward genetic screens for synaptic transmission mutants mapped to the vps24 gene encoding a subunit of the ESCRT-III complex. Molecular characterization indicated a loss of VPS24 function, however the mutant is viable and thus loss of VPS24 may be studied in a developed multicellular organism. The mutant exhibits deficits in locomotion and lifespan and, notably, these phenotypes are rescued by neuronal expression of wild-type VPS24. At the cellular level, neuronal and muscle cells exhibit marked expansion of a ubiquitin-positive lysosomal compartment, as well as accumulation of autophagic intermediates, and these phenotypes are rescued cell-autonomously. Moreover, VPS24 expression in glia suppressed the mutant phenotype in muscle, indicating a cell-nonautonomous function for VPS24 in protective intercellular signaling. Ultrastructural analysis of neurons and muscle indicated marked accumulation of the lysosomal compartment in the vps24 mutant. In the neuronal cell body, this included characteristic lysosomal structures associated with an expansive membrane compartment with a striking tubular network morphology. These findings further define the in vivo roles of VPS24 and the ESCRT pathway in lysosome homeostasis and their potential contributions to neurodegenerative diseases characterized by defective ESCRT or lysosome function.

Clinical Characteristics of Withdrawal of Basal Insulin Therapy Among Japanese Patients with Type 2 Diabetes: A Multicenter Retrospective Observational Study.

INTRODUCTION: This study aimed to examine retrospectively the clinical backgrounds of Japanese patients with type 2 diabetes (T2D) who successfully withdrew from insulin use after being started on basal insulin in an outpatient setting. METHODS: The study population comprised 376 insulin-naïve patients who were started on basal insulin (glargine U100, glargine U300, or degludec) for the management of T2D and followed the treatment regimen for at least 6 months in 13 institutions in Japan. The clinical courses of the study participants were compared based on outpatient clinic medical records for the three different types of basal insulin prescribed by categorizing the participants into two groups retrospectively: those who successfully withdrew from insulin therapy and those who did not, during a 6-month observation period. The clinical determinants for insulin withdrawal were assessed using a Cox proportional hazard model. RESULTS: Glycated hemoglobin was improved in all participants regardless of basal insulin type. Of the 376 study participants, 61 successfully withdrew from basal insulin therapy. After adjustment was made for several confounders, the positive determinant factors for successful withdrawal of insulin were short duration of diabetes and high body mass index at the start of study, and the negative determinant factor was use of insulin secretagogues at the start. The types of basal insulin used by the study participants were not significant determinants of successful insulin withdrawal in this study. CONCLUSIONS: Use of basal insulin is a powerful option for the treatment of T2D. In patients with high BMI and/or short duration of diabetes, short-term insulin therapy is a promising strategy for the treatment of T2D before the initiation of insulin secretagogues, since such patients have the potential to successfully withdraw from basal insulin use even in an outpatient setting.

Primary Epstein-Barr virus infection shortly after primary Cytomegalovirus infection: a case report.

BACKGROUND: Infectious mononucleosis (IM) and mononucleosis-like illnesses are common viral infectious diseases which are often accompanied by a high fever, pharyngitis and lymphadenopathy in adults, although such infection in childhood is generally subclinical. Most cases of IM are caused by the Epstein-Barr virus (EBV) or Cytomegalovirus (CMV). However, it is difficult to diagnose IM only with subjective symptoms, and thus EBV and CMV are nearly indistinguishable in clinical practice. CASE PRESENTATION: A 20-year-old healthy Japanese woman had a 2-day history of high fever and consulted us. She had sex for the first time 6 months earlier. Her virus antibodies showed that she was infected with primary CMV. About 5 months later, she again experienced high fever and lymph node enlargement at the posterior cervical region. Her virus antibodies showed that she was infected with primary EBV at that time. CONCLUSION: Herein, we report a healthy adult Japanese woman with primary EBV infection relatively soon after primary CMV infection. It is very interesting to compare the symptoms and/or clinical data after EBV and CMV infection in the same patient within a short period of time. Our patient was diagnosed based only on subjective symptoms, physical examination and laboratory data, without tests of such virus-related antibodies. Therefore, clinicians should bear in mind that primary EBV infection and/or primary CMV infection is possible when patients have symptoms such as high fever, pharyngitis and lymphadenopathy, even in healthy adults.