Efficacy of denosumab in the treatment of hypercalcemic renal dysfunction in sarcoidosis: a case report.

A 70-year-old female patient was admitted for close examination and treatment of hypercalcemia (corrected serum calcium levels: 3.04 mmol/L) and renal dysfunction (serum creatinine levels: 254.59 µmol/L). The patient had a history of sarcoidosis, diagnosed based on epithelioid cell granulomas in subcutaneous nodule biopsies, uveitis, and bilateral hilar lymphadenopathy, which had spontaneously remitted 10 years before admission. Because the patient was diagnosed with hypercalcemia associated with recurrent sarcoidosis, prednisone (20 mg/day) was initiated, and its dose was tapered following the decrease in serum calcium and creatinine levels. However, the levels of these parameters increased again when the prednisone dose was reduced to ≤ 4 mg/day. We were concerned about glucocorticoid-induced osteoporosis in the patient but hesitated to use first-line bisphosphonates because of renal dysfunction. Therefore, denosumab was initiated to reduce the risk of hypercalcemia, renal dysfunction, and glucocorticoid-induced osteoporosis. Serum creatinine and corrected serum calcium levels subsequently decreased. The prednisone dose could be reduced following repeated denosumab administration.Thus, denosumab can be a multifaceted, beneficial option for sarcoidosis-induced hypercalcemia, as it alleviates renal dysfunction indirectly by normalizing serum calcium levels, facilitates reduction of the glucocorticoid dose, and ameliorates glucocorticoid-induced osteoporosis.

Noninvasive Ambulatory Electrocardiographic Markers from Patients with COVID-19 Pneumonia: A Report of Three Cases.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes due to COVID-19 include QT prolongation and ST-T changes; however, there have not been studies on the ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All patients had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24 h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 involved a 76-year-old man with hypertension and diabetes, and Case 3 involved a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. The LP, TWA, HRV, and HRT were positive in all three cases with no significant structural cardiac disease at the initial phase of admission. The further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed. Depending on the accumulation of data, the LP, TWA, HRV, and HRT could be identified as potential risk factors for COVID-19 pneumonia in the early phase of admission.

Increasing averaging beats improves the test accuracy on Holter-based late potentials in patients with myocardial infarction.

BACKGROUND: The prevalence of Holter-based late potentials (H-LPs) in cases of fatal cardiac events has increased. Although the noise level of H-LP is higher than that of conventional real-time late potential (LP) recording, a procedure to reduce the noise severity in H-LP by increasing the averaging beats has not been investigated. METHODS: We enrolled 104 patients with post-myocardial infarction (MI) and 86 control participants. Among the patients, 30 reported sustained ventricular tachycardia (VT), and the remaining 74 had unrecorded VT. H-LPs were measured twice in all groups to evaluate the efficacy of increasing the averaging beats for H-LPs. Thereafter, the average of LP was calculated at 250 (default setting), 300, 400, 500, 600, 700, and 800 beats. RESULTS: Across all three groups (MI-VT group, MI non-VT group, and control group), the noise levels significantly decreased in consonance with the increase in averaging beats. In the MI-VT group, the H-LP positive rate considerably increased with the increase in the averaging beats from 250 to 800 both at night and daytime. In the MI-VT group, the LP parameters significantly deteriorated, which led to a positive judgment corresponding to the increment of the averaged night and day beats. The H-LP positive rates were unchanged in the MI non-VT and control groups, while the LP parameters remained consistent, despite the increased averaging beats in the MI non-VT and control groups. CONCLUSION: Increasing the calculated averaging beats in H-LPs can improve the sensitivity of predicting fatal cardiac events in patients with MI.

Diurnal Variation in and Optimal Time to Measure Holter-Based Late Potentials to Predict Lethal Arrhythmia after Myocardial Infarction.

Background and Objectives: Holter-based late potentials (LPs) are useful for predicting lethal arrhythmias in organic cardiac diseases. Although Holter-based LPs exhibit diurnal variation, no studies have evaluated the optimal timing of LP measurement over 24 h for predicting lethal arrhythmia that leads to sudden cardiac death. Thus, this study aimed to validate the most effective timing for Holter-based LP testing and to explore factors influencing the diurnal variability in LP parameters. Materials and Methods: We retrospectively analyzed 126 patients with post-myocardial infarction (MI) status and 60 control participants who underwent high-resolution Holter electrocardiography. Among the 126 post-MI patients, 23 developed sustained ventricular tachycardia (VT) (the MI-VT group), while 103 did not (the MI-non-VT group) during the observation period. Holter-based LPs were measured at 0:00, 4:00, 8:00, 12:00, 16:00, and 20:00, and heart rate variability analysis was simultaneously performed to investigate factors influencing the diurnal variability in LP parameters. Results: Holter-based LP parameters showed diurnal variation with significant deterioration at night and improvement during the day. Assessment at the time with the longest duration of low-amplitude signals < 40 µV in the filtered QRS complex terminus (LAS40) gave the highest receiver operating characteristics curve (area under the curve, 0.659) and the highest odds ratio (3.75; 95% confidence interval, 1.45-9.71; p = 0.006) for predicting VT. In the multiple regression analysis, heart rate and noise were significant factors affecting the LP parameters in the MI-VT and control groups. In the non-VT group, the LP parameters were significantly influenced by noise and parasympathetic heart rate variability parameters, such as logpNN50. Conclusions: For Holter-based LP measurements, the test accuracy was higher when the LP was measured at the time of the highest or worst value of LAS40. Changes in autonomic nervous system activity, including heart rate, were factors influencing diurnal variability. Increased parasympathetic activity or bradycardia may exacerbate Holter-based LP parameters.

Iodine-containing ointment-induced hypothyroidism in a patient with anorexia nervosa and sacral decubitus ulcer: a case report with literature review.

We present a case of a 58-year-old woman with anorexia nervosa and a sacral decubitus ulcer who developed hypothyroidism because of an iodine-containing ointment. Considering the absence of autoimmune thyroid diseases, the development of hypothyroidism after the use of an iodine-containing ointment, and the recovery of thyroid function after the discontinuation of the ointment, we presumed that her hypothyroidism was induced by the iodine-containing ointment. Although the hypothyroidism improved after discontinuing the iodine-containing ointment, she developed aspiration pneumonia and required long-term hospitalization. Many patients with autoimmune thyroid diseases develop hypothyroidism after excessive iodine intake. However, anorexia nervosa may have exacerbated the iodine-induced hypothyroidism in our patient. To the best of our knowledge, no previous study has reported a case of hypothyroidism caused by iodine-containing ointment in a patient with anorexia nervosa. Hence, physicians must pay careful attention to a patient's background factors to ensure the early diagnosis of hypothyroidism due to iodine-containing ointments.

Idiopathic hypersomnia with a video recording of a spontaneous sleep attack: A case report.

RATIONALE: Although patients with central disorders of hypersomnolence (CDH) exhibit characteristic symptoms of hypersomnia frequently, it takes 5 to 15 years from the onset for its diagnosis due to the lack of symptom recognition. Here, we present a case of idiopathic hypersomnia (IH), a CDH, wherein early diagnosis was aided by a video footage of a spontaneous sleep attack. PATIENT CONCERNS: A 21-year-old man lost consciousness while driving and experienced an accident. He had complained of excessive daytime sleepiness (EDS) over half a year. During his hospitalization for close monitoring of the loss of consciousness, an in-room surveillance camera captured a 14-minutes long spontaneous sleep attack, during which he experienced general muscle weakness and loss of consciousness without warnings or convulsions leading to a fall from the bed. There were no abnormalities in vital signs. DIAGNOSES: There was no significant cataplexy and less than 2 sleep-onset rapid eye movements (SOREM) in 2 sleep latency tests, with a mean sleep latency of 2.1 and 4.6 minutes. Other sleep deprivation syndromes were excluded from differential diagnosis and finally, a diagnosis of IH was confirmed according to the criteria of the Third Edition of the International Classification of Sleep Disorders. During the course of the disease, attention-deficit/hyperactive disorder (ADHD) and a gaming disorder also diagnosed. INTERVENTIONS: Pharmacological treatment with modafinil was administered for IH and methylphenidate for ADHD. Cognitive behavioral therapy was performed for the gaming disorder. OUTCOMES: The EDS improved, and sleep attacks were no longer observed. The disruption of daily life caused by the gaming disorder was also reduced. LESSONS: Video recordings of sleep attacks are beneficial for identifying the cause of loss of consciousness. Home video recordings may be helpful in the early diagnosis of IH.

Proximal Renal Tubular Acidosis Complicated by Severe Hypocalcemia Caused by Malnutrition and Inappropriate Long-term Use of Zoledronate: A Case Report and Review of the Literature.

An 80-year-old man presented with electrolyte abnormalities, particularly hypocalcemia (3.6 mg/dL). He was diagnosed with bone and lymph node metastases from prostate cancer seven years earlier and continuously received goserelin, bicalutamide, and zoledronate. He later developed gradually worsening hypocalcemia, hypokalemia, hypophosphatemia, hypouricemia, renal dysfunction, and weight loss. Urinary potassium and phosphate loss, renal glucosuria, metabolic acidosis, and a low urine pH (5.0) were observed. Given the acquired onset and clinical course, we diagnosed the patient with zoledronate-induced proximal renal tubular acidosis. In the present case, severe hypocalcemia may have been caused by malnutrition and inappropriate long-term use of zoledronate.

Age-related reference intervals for ambulatory electrocardiographic parameters in healthy individuals.

Background: The advent of novel monitoring technologies has dramatically increased the use of ambulatory electrocardiography (AECG) devices. However, few studies have conducted detailed large-scale investigations on the incidence of arrhythmias over 24 h, especially ectopy, in healthy individuals over a wide age range. Objectives: This study aimed to investigate the incidence of arrhythmias detected using AECG and associated factors, in healthy individuals, over a wide age range. Methods: In this cross-sectional study, we performed AECG on 365 healthy volunteers (median [interquartile range]: 48 [36, 67], 20-89 years, 165 men) under free-running conditions for 24 h. Ultrasonic echocardiography and heart rate variability analysis were performed to explore the factors associated with the incidence of arrhythmias. Results: The 97.5th percentile of single ventricular ectopy (VE) was 149/day, 254/day, and 1,682/day in the 20-39-, 40-59- and 60-89-year age groups, respectively; that of single supraventricular ectopy (SVE) was 131/day, 232/day, and 1,063/day, respectively. Multivariate analysis revealed that aging was the only independent significant factor influencing the frequency of VE (ß = 0.207, P = 0.001). Age (ß = 0.642, P < 0.001), body mass index (BMI) (ß = -0.112, P = 0.009), and the root mean square of successive differences in RR intervals (ß = 0.097, P = 0.035) were factors significantly associated with SVE frequency. Conclusions: Age-specific reference intervals of VE and SVE in a large population of healthy participants over a wide age range were generated. VE and SVE increased with age; SVE was influenced by BMI and the aging-induced decrease in parasympathetic tone activity.

Serum diiodotyrosine - a biomarker to differentiate destructive thyroiditis from Graves' disease.

OBJECTIVE: Conventional diagnostic methods are limited in their ability to differentiate destructive thyroiditis from Graves' disease. We hypothesised that serum diiodotyrosine (DIT) and monoiodotyrosine (MIT) levels could be biomarkers for differentiating destructive thyroiditis from Graves' disease. DESIGN: Patients with destructive thyroiditis (n = 13) and Graves' disease (n = 22) were enrolled in this cross-sectional study. METHODS: We assayed the serum DIT and MIT levels using liquid chromatography-tandem mass spectrometry. A receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of the serum DIT and MIT levels as biomarkers for differentiating destructive thyroiditis from Graves' disease. RESULTS: The serum DIT and MIT levels were significantly higher in patients with destructive thyroiditis than in those with Graves' disease. The ROC curve analysis showed that the serum DIT levels (≥359.9 pg/mL) differentiated destructive thyroiditis from Graves' disease, significantly, with 100.0% sensitivity and 95.5% specificity (P < 0.001). The diagnostic accuracy of the serum MIT levels (≥119.4 pg/mL) was not as high as that of the serum DIT levels (sensitivity, 84.6%; specificity, 77.3%; P = 0.001). CONCLUSIONS: The serum DIT levels may serve as a novel diagnostic biomarker for differentiating destructive thyroiditis from Graves' disease.

Rapid progression of marginal zone B-cell lymphoma after COVID-19 vaccination (BNT162b2): A case report.

B-cell lymphomas are neoplastic diseases occasionally associated with chronic inflammation. mRNA vaccines for coronavirus disease 2019 (COVID-19) induce inflammatory responses, which often lead to fever and lymphadenopathies indistinguishable from lymphomas. Although both lymphadenopathies and lymphomas can be influential, the correlation between them is unclear. Herein, we present the first case of marginal zone B-cell lymphoma following mRNA COVID-19 vaccination. An 80-year-old Japanese woman presented with a right temporal mass that appeared the morning after she was administered her first mRNA COVID-19 vaccination (BNT162b2). The mass gradually decreased in size but persisted over 6 weeks after her first vaccination (3 weeks after her second vaccination). At her first visit to our hospital, ultrasound revealed the size of the mass to be 28.5 × 5.7 mm, and computed tomography revealed multiple lymphadenopathies in the right parotid, submandibular, jugular, and supraclavicular regions. Initially, we suspected head-and-neck benign lymphadenopathy as a side effect of vaccination. Nine weeks later, the number of swollen submandibular and parotid glands increased, and the lymph nodes further enlarged. Finally, the right temporal mass was diagnosed as marginal zone B-cell lymphoma based on immunohistochemical and flow cytometry findings of biopsy specimens. Our findings suggest that although 4-6 weeks of observation for lymph node inflammation after the second vaccination is recommended, malignancy should also be considered in the differential diagnosis of lymphadenopathy following vaccination.

Fulminant elderly adult-onset Still disease effectively treated with tocilizumab and methotrexate: A case report.

RATIONALE: Adult-onset Still disease (AOSD) is a rare inflammatory disease of unknown etiology. AOSD is common in young or middle-aged adults; however, in recent years, there have been increasing reports of elderly AOSD. Differentiating AOSD from diseases such as infections and malignancies is difficult. Moreover, rare fulminant AOSD cases with resistance to corticosteroids and immunosuppressive drugs have been reported. PATIENT CONCERNS: An 80-year-old woman presented with flaccid fever, generalized arthralgia, and erythema of the anterior chest for 2 weeks. On day 5 of hospitalization, the patient developed pleural effusion with hypoxemia and her vital signs indicated rapid progression to shock. During the clinical course, the levels of inflammatory markers, including maximum level of ferritin and white blood cells (WBCs) were elevated (252,796 ng/mL and 86,500/µV, respectively) with disseminated intravascular coagulation syndrome (DIC) and macrophage activation syndrome (MAS). DIAGNOSIS: The patient was diagnosed with elderly AOSD as per the Yamaguchi criteria for AOSD. The state of disease was extremely severe with rapid progression and was, thus, categorized as a fulminant form of elderly AOSD. INTERVENTIONS: The patient was treated with prednisolone (PSL) pulse therapy (1000 mg/d) twice and plasma exchange in the intensive care unit for the primary disease and shock. Although she recovered from shock, she developed DIC and MAS. Methotrexate (MTX; 10 mg/d) improved the DIC and MAS. However, severe pleuritis recurred and the patient developed pericarditis; her primary disease was poorly controlled. Finally, tocilizumab (TCZ) was introduced using interleukin-18 (IL-18) as a surrogate marker. The IL-18 level was measured repeatedly following admission, with the peak level (170,000 pg/mL) recorded on the 75th day of hospitalization, immediately prior to introducing TCZ. OUTCOMES: The combined use of MTX, TCZ, and PSL was effective in suppressing elderly AOSD, which was unsuccessfully controlled with MTX and PSL. Frequent monitoring of IL-18 levels proved useful for differentiating elderly AOSD from other diseases. LESSONS: A fulminant form of elderly AOSD was treated with a combination of MTX, TCZ, and PSL. Repeated monitoring of IL-18 levels can be useful for decision-making in treating elderly AOSD.