Treatment of long COVID complicated by postural orthostatic tachycardia syndrome-Case series research.

Background: Coronavirus disease 2019 (COVID-19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID-19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS. Methods: The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits. Results: Thirty-two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow-up period was 159 days, and the interval between COVID-19 onset and initial hospital attendance was 97 days. Some patients responded to ß-blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements. Conclusions: Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context.

Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan.

PURPOSE: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters. METHODS: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal-Wallis test. Multiple comparison tests were performed using the Dunn's test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals. RESULTS: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively. CONCLUSIONS: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.

Patent Foramen Ovale Complicated With Renal Infarction and Pulmonary Embolism: A Case Report With Literature Review.

A 48-year-old man visited our emergency room after experiencing sudden left back pain, diaphoresis, and nausea. The patient underwent physical and laboratory examinations. Physical examination revealed tenderness in the left costovertebral angle. Laboratory examination revealed a slight elevation in D-dimer levels. Contrast-enhanced computed tomography revealed a bilateral pulmonary embolism and left renal infarction. Back pain was resolved following anticoagulation therapy with heparin. Transesophageal echocardiography revealed a patent foramen ovale (PFO). The patient was discharged on an anticoagulant, apixaban. Identifying the cause of paradoxical embolisms, such as an atrial septal defect or PFO, in cases with an arterial embolism in a young patient with no underlying disease is important.

Deprescribing as an Opportunity to Facilitate Patient-Centered Care: A Qualitative Study of General Practitioners and Pharmacists in Japan.

Deprescribing has recently been applied to address polypharmacy, particularly among older adults. However, the characteristics of deprescribing that are likely to improve health outcomes have not been well studied. This study explored the experiences and perspectives of general practitioners and pharmacists with regard to deprescribing in older adults with multimorbidity. A qualitative study was conducted involving eight semi-structured focus group interviews with 35 physicians and pharmacists from hospitals, clinics, and community pharmacies. Thematic analysis was applied to identify themes using the theory of planned behavior as a guide. The results illustrated a metacognitive process, as well as influencing factors, through which healthcare providers commit to shared decision making for deprescribing. Healthcare providers acted on the basis of their attitudes and beliefs on deprescribing, the influence of subjective norms, and perceived behavioral control for deprescribing. These processes are influenced by factors such as drug class, prescribers, patients, deprescribing experience, and environment/education. Healthcare providers' attitudes, beliefs, and behavioral control (along with deprescribing strategies) evolve in a dynamic interplay with experience, environment, and education. Our results can serve as a foundation for the development of effective patient-centered deprescribing to improve the safety of pharmaceutical care for older adults.

Nerve Identification Procedures Are Necessary for Complete Recovery From Recurrent Cases of Anterior Cutaneous Nerve Entrapment Syndrome: A Case Report.

Anterior cutaneous nerve entrapment syndrome (ACNES) involves pain in the abdominal wall due to nerve compression or ischemia. The diagnosis of ACNES is challenging with the pain often inclined to be diagnosed as psychological in origin. A 20-year-old woman presenting with abdominal pain was initially diagnosed with mesenteric lymphadenitis and prescribed pain relievers. However, following worsened pain, she was hospitalized. Blood examinations, abdominal and gynecological ultrasonography, and gastrocolonoscopy yielded no abnormal findings, leading to suspicions of psychological factors. As the patient experienced sharp abdominal pain on movement, but not at rest, which was temporarily relieved by lidocaine injections, she was diagnosed with ACNES. Rectus abdominal resection was performed but the pain relapsed. Laparoscopic surgery was performed to cut the nerve that caused the pain. After three surgeries, the patient was completely symptom-free. ACNES should be considered as a differential diagnosis for intractable abdominal pain. For recurrent relapses, the triggering nerves must be carefully identified for the successful treatment of ACNES.

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19.

BACKGROUND: The role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated. METHODS: We conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19. RESULTS: In this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively). CONCLUSION: Higher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.

Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID.

Coronavirus disease 2019 (COVID-19) is spreading worldwide; there is a need to address its sequelae known as Long COVID. This study evaluated postvaccination changes in symptoms and antibody titers in patients with Long COVID. Patients visiting the outpatient department specializing in Long COVID at our hospital were enrolled. Changes in symptoms were evaluated before and 14-21 days after first vaccination. Antibody titers were measured using ARCHITECT SARS-CoV-2 IgG II Quant at the same time. This study included 42 patients (median age: 45 years; 17 [40.5%] men). Median pre- and postvaccination antibody titers were 456 and 28,963 AU/ml, respectively. Postvaccination symptoms (fatigue, joint pain, and taste and olfactory abnormalities) were relieved, worsened, and unchanged in 7 (16.7%), 9 (21.4%), and 26 (61.9%) patients, respectively. Ratios of pre- and postvaccination antibody titers were 53, 40, and 174 in the unchanged, relief, and worsened groups, respectively. The worsened group had the significantly highest antibody titer ratio (p = 0.02). The higher increased rate of the antibody titer in the worsened group than in the nonworsened group suggests an excessive immune response to vaccination associated with worsening of sequelae. Although patients with Long COVID should be vaccinated, additional concerns should be addressed.

A Long-term Persistent Vascular Fluorodeoxyglucose Uptake in a Patient with Large-vessel Vasculitis.

We herein report a case of large-vessel vasculitis in a 57-year-old woman who developed an intermittent fever and weight loss. While contrast-enhanced computed tomography was noncontributory, positron emission tomography-computed tomography (PET-CT) revealed the diffuse, intense uptake of fluorodeoxyglucose (FDG) in the aorta and its branches. Although she had no signs of relapse after successful oral corticosteroid therapy, PET-CT at 30 months revealed a persistent FDG uptake in the large vessels, which warranted regular follow-up imaging for vascular complications. In cases with an intense FDG uptake at the diagnosis, PET-CT follow-up after clinical remission may help predict the risk of relapse and vascular complications.

Comparison of the 2011 and 2019 Kampo Medicine Curricula Across All Japanese Medical Schools.

OBJECTIVE: To examine how Kampo education in Japanese medical schools changed between 2011 and 2019. METHODS: We administered nationwide postal questionnaire surveys about current characteristics of Kampo medicine education in all 82 Japanese medical schools, directed to the persons responsible for Kampo education at each university. One survey was conducted in 2011 and one in 2019. Analysis used Welch's t-test and a chi-squared test. RESULTS: The average class meeting time was shorter in 2019 than in 2011. The proportion of class meetings that were about Kampo saw a statistically significant increase in the third year and a significant decrease in the fourth and sixth years of medical school. Curriculum standardisation, preparation of simple textbooks, and fostering Kampo medicine instructors were the primary problems in both years. The proportion of mainstream medical education contents focusing on traditional Japanese Kampo medicine did not change over time, nor did the percentage of those considering using standardised textbooks. Other changes were statistically nonsignificant. CONCLUSION: In Japanese medical schools, the number of class meetings teaching Kampo medicine has increased; however, this number is not statistically significant. Persistent problems in Kampo education, including curriculum standardisation, need to be addressed.

Development of Kampo（traditional Japanese medicine）e-learning program: evaluation of the flipped classroom for medical students.

In May 2019, the World Health Assembly, in an unprecedented move, endorsed the inclusion of traditional medicine in the International Classification of Diseases, 11th Revision. In Japan, traditional medicine (known as Kampo) is regulated by the government and prescribed by over 90% of physicians along with modern medicine under the national health insurance system. Although Kampo education must be included in Japan's core medical curricula, there are significant challenges to implementation. In the educational context, the flipped classroom teaching method has received considerable attention in recent years. This study developed a Kampo e-learning program and verified the effectiveness of a flipped classroom using Kampo e-learning. The Kampo e-learning Committee determined three courses and assigned an administrator for each. The administrators appointed lecturers who developed Kampo e-learning lessons. Physicians, pharmacists, medical students, and pharmacy students were asked to participate in the e-learning program, and their comments and suggestions were collected after program completion. The flipped classroom was evaluated by implementing Kampo e-learning in the Kampo session with fourth-year students at Keio University School of Medicine in Japan. Seven courses were created, including four based on volunteer suggestions. The 'Systematic Kampo Curricula' featured 88 lessons developed by 54 Kampo specialists. Out of 118 fourth-year medical students who participated in the flipped classroom, 113 registered for the Kampo e-learning program, 100 attended the session, and 88 answered the post-session questionnaire. Among the students who answered the questionnaire, 86.4% were satisfied with the flipped classroom, 79.5% replied that the program made them understand Kampo and 80.7% stated that it should be adopted. The flipped classroom using Kampo e-learning program was shown to be attractive in one medical school. Further expanded study is necessary in the near future to reveal the usefulness of the flipped classroom of Kampo learning.

Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

BACKGROUND: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. METHODS: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. RESULTS: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days). CONCLUSION: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.

Determining the factors affecting serum presepsin level and its diagnostic utility: A cross-sectional study.

INTRODUCTION: This study aimed to identify factors affecting presepsin levels and to determine their diagnostic utility. METHODS: This cross-sectional study was conducted at an outpatient clinic and emergency department at an acute care hospital in Japan between January 2015 and December 2017. We enrolled 1,840 consecutive outpatients with at least one measurement of serum presepsin, who were suspected of having bacterial infection. The outcome variables were bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections diagnoses, based on the chart review. We collected blood analysis data on the patients' presepsin levels. RESULTS: There was a significant association between presepsin level and the diagnosis of bacterial infection even when adjusted for age, sex, renal function, and biliary enzyme levels. An increase of 1 unit in the log of presepsin values resulted in a relative risk ratio of 1.71 (1.09-2.66), 2.1 (1.58-2.79), 2.93 (2.05-4.19), 4.7(2.90-7.61), and 2.41(1.70-3.43), for bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections, respectively. CONCLUSIONS: Presepsin showed a statistically significant increase in the diagnosis of bacterial infections (lower respiratory tract infections, urinary tract infections, cholangitis, and non-severe patients) in a community hospital setting. However, in patients with renal dysfunction, presepsin levels should be interpreted with caution.

Protocol of a randomised controlled trial on the efficacy of medication optimisation in elderly inpatients: medication optimisation protocol efficacy for geriatric inpatients (MPEG) trial.

INTRODUCTION: Whether medication optimisation improves clinical outcomes in elderly individuals remains unclear. The current study aims to evaluate the effect of multidisciplinary team-based medication optimisation on survival, rehospitalisation and unscheduled hospital visits in elderly patients. METHODS AND ANALYSIS: We report the protocol of a single-centre, open-label, randomised controlled trial. The enrolled subjects will be medical inpatients, aged 65 years or older, admitted to a community hospital and receiving five or more regular medications. The participants will be randomly assigned to receive either an intervention for medication optimisation or the usual care. The intervention will consist of a multidisciplinary team-based medication review, followed by a medication optimisation proposal based on the Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment criteria and an implicit medication optimisation protocol. Medication optimisation summaries will be sent to primary care physicians and community pharmacists on discharge. The primary outcome will be a composite of death, unscheduled hospital visits and rehospitalisation until 48 weeks after randomisation. Secondary outcomes will include each of the primary endpoints, the number of prescribed medications, quality of life score, level of long-term care required, drug-related adverse events, death during hospitalisation and falls. Participants will be followed up for 48 weeks with bimonthly telephone interviews to assess the primary and secondary outcomes. A log-rank test stratified by randomisation factors will be used to compare the incidence of the composite endpoint. The study was initiated in 2019 and a minimum of 500 patients will be enrolled. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Ethical Committee of St. Marianna University School of Medicine (No. 4129). The results of the current study will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000035265.

Isolated superior mesenteric artery dissection and median arcuate ligament syndrome.

Our case underscores the importance of recognizing MALS not only as a cause of postprandial epigastric pain but a rare facilitating factor in the development of isolated SMA dissection.

Thoracic Aortic Graft Infection due to Candida Albicans with Multiple Embolism in the Left-side Vessels of the Body.

A 79-year-old Japanese man who had undergone thoracic aortic replacement 10 years prior presented with a 3-day history of sore throat. He was initially diagnosed with pharyngitis; however, multiple emboli in the vessels of the left side of the body were recognized. He was diagnosed with thoracic aortic graft infection caused by Candida albicans, with multiple embolisms. Anti-fungal therapy was initiated, but surgical removal of the graft was not performed because of the high risk associated with the operation, and he eventually died. Inappropriate use of antibiotics might have led to a severe fungal infection. As such, the inappropriate use of antimicrobial agents should be avoided.

Factors predicting the cause and prognosis of central line-associated bloodstream infections.

The increased use of indwelling catheters has led to an increased number of deaths due to central line-associated bloodstream infection (CLABSI). Improving CLABSI outcomes requires the identification of clinical characteristics affecting drug selection and factors associated with poor prognosis. The medical records of inpatients admitted to St. Marianna University School of Medicine between April 1, 2010 and March 31, 2013 were evaluated for the results of catheter tip cultures. The clinical characteristics of these cases and the characteristics of the pathogens involved were investigated to identify prognostic factors. Of the 1629 catheter cultures investigated, 183 were CLABSIs. Among them, 105 were caused by gram-positive bacteria, 43 by gram-negative bacteria, and 35 by fungi. Gram-negative CLABSIs were more common in cases with prior colonization by gram-negative bacteria and post-surgical cases. Fungal CLASBIs were more common in the cases with prior colonization by fungi, high-calorie infusion enforcement, broad-spectrum antibiotic treatment, and post-surgical cases. Death was significantly more likely in cases with findings of inflammation at the catheter insertion site and in those with abnormal body temperature, tachycardia, or abnormal white blood cell count. Thus, when treating CLABSI in post-surgical cases and in cases with prior colonization by gram-negative bacteria, therapy should include anti-pseudomonal agents. Considering the factors predicting poor prognostic identified in this study, clinicians must check the vital signs and catheter insertion site in patients with indwelling catheters.

[A case of Streptococcus gallolyticus subsp. gallolyticus infective endocarditis with colon adenoma].

An 80-year-old Japanese man had a fall presented with a 3-week history of right lumbago exacerbated by body movement as well as a 1-week history of anomalous behavior and appetite loss. He visited our hospital complaining of difficulty in standing up. He had a history of mitral prolapse due to an unknown rupture of the chordae tendineae 3 years earlier, which resulted in moderate mitral valve regurgitation and atrial fibrillation. Upon visiting the hospital, he had petechial hemorrhage and jaundice of the conjunctiva, a systolic murmur (Levine II/VI) at the apex and 4th interspace of the left sternal border, and a positive right straight leg raising test result. Moderate bilirubinemia and disseminated intravascular coagulation which were considered to have been produced secondarily were observed. Infective endocarditis was suspected, and 3 sets of blood culture were extracted. The patient was admitted on the same day. Blood cultures were positive for Streptococcus gallolyticus subsp. gallolyticus (6/6) on the following day. Transesophagela echocardiography was carried out on the same day, and vegetation with a diameter of 4mm was observed in the anterior mitral leaflet; the patient was subsequently diagnosed as having infective endocarditis. Colonic endoscopy was performed after hospitalization. Twelve colonic adenomata were found, and endoscopic mucosal resection was performed on one polyp. The bacterium found in the culture was classified as Streptococcus bovis type I, which causes infective endocarditis and bacteremia. Furthermore, this bacteria is a relatively rare causative organism of infective endocarditis. Tolerance to macrolide and tetracycline are reported in the literature. Moreover, the cell wall of this bacterium may have low pathogenicity as well as cause chronic inflammation in the large intestine mucous membrane, colonic polyps, and colorectal cancer. Several colonic adenomata and a partial shift to a malignant pathology were observed in this case. When this bacterium is detected, searching for a pathological change in the large intestine is believed to be indispensable.