The Japanese Guide affected the prescription of steroids for COVID-19 inpatients during the COVID-19 epidemic in Japan.

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, guidance ("Japanese Guide") has been published by a working group of several academic societies and announced by the Ministry of Health, Labour, and Welfare. Steroids as a candidate treatment for COVID-19 were noted in the Japanese Guide. However, the prescription details for steroids, and whether the Japanese Guide changed its clinical practice, were unclear. This study aimed to examine the impact of the Japanese Guide on the trends in the prescription of steroids for COVID-19 inpatients in Japan. We selected our study population using Diagnostic Procedure Combination (DPC) data from hospitals participating in the Quality Indicator/Improvement Project (QIP). The inclusion criteria were patients discharged from hospital between January 2020 and December 2020, who had been diagnosed with COVID-19, and were aged 18 years or older. The epidemiological characteristics of cases and the proportion of steroid prescriptions were described on a weekly basis. The same analysis was performed for subgroups classified by disease severity. The study population comprised 8603 cases (410 severe cases, 2231 moderate II cases, and 5962 moderate I/mild cases). The maximum proportion of cases prescribed with dexamethasone increased remarkably from 2.5 to 35.2% in the study population before and after week 29 (July 2020), when dexamethasone was included in the guidance. These increases were 7.7% to 58.7% in severe cases, 5.0% to 57.2% in moderate II cases, and 1.1% to 19.2% in moderate I/mild cases. Although the proportion of cases prescribed prednisolone and methylprednisolone decreased in moderate II and moderate I/mild cases, it remained high in severe cases. We showed the trends of steroid prescriptions in COVID-19 inpatients. The results showed that guidance can influence drug treatment provided during an emerging infectious disease pandemic.

Within-Host Evolution of SARS-CoV-2 in a B-Cell Depleted Patient With Successful Treatment.

Prolonged viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an immunocompromised host is a challenge as the treatment and infection control for chronic coronavirus disease 2019 infection is not well established and there is a potential risk of new variants emerging. A 48-year-old woman who underwent chemotherapy, including rituximab and steroid, had reactivation of SARS-CoV-2 68 days after the virus was first detected. She successfully recovered after receiving convalescent plasma and intravenous immunoglobulin. Genomic analysis demonstrated that viruses collected from the nasopharyngeal specimens at day 0 and day 68 had 18 different nucleotide mutations, implying within-host evolution after in-depth epidemiologic investigation.

Alcohol-related hepatitis: A review article.

Alcohol-related hepatitis (ARH) is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by significant alcohol use. It ranges in severity from mild to severe and carries significant morbidity and mortality. The refinement of scoring systems has enhanced prognostication and guidance of clinical decision-making in the treatment of this complex disease. Although treatment focuses on supportive care, steroids have shown benefit in select circumstances. There has been a recent interest in this disease process, as coronavirus disease 2019 pandemic led to substantial rise in cases. Although much is known regarding the pathogenesis, prognosis remains grim due to limited treatment options. This article summarizes the epidemiology, genetics, pathogenesis, diagnosis and treatment of ARH.

Blackwater Fever Treated with Steroids in Nonimmune Patient, Italy.

Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.

Parathyroid carcinoma presenting as severe hypercalcaemia responding to steroids.

A man in his 50s was referred with profound, symptomatic hypercalcaemia. He was diagnosed with primary hyperparathyroidism, confirmed on 99mTc-sestamibi scan. He was treated for the hypercalcaemia and referred to ear, nose and throat (ENT) surgeons for parathyroidectomy, which was delayed due to the COVID-19 pandemic. In the ensuing 18 months, he had five hospital admissions with severe hypercalcaemia requiring intravenous fluids and bisphosphonate infusions. During the last admission, hypercalcaemia was resistant to maximal medical management. Emergency parathyroidectomy was planned, but delayed due to intervening COVID-19 infection. Due to persistent severe hypercalcaemia (serum calcium: 4.23 mmol/L), he was commenced on intravenous steroids, following which serum calcium normalised. Subsequently, he underwent emergency parathyroidectomy, which normalised his serum parathyroid and calcium levels. On histopathological examination, a diagnosis of parathyroid carcinoma was made. On follow-up, patient remained well and normocalcaemic. In patients with primary hyperparathyroidism unresponsive to standard therapy, but responsive to steroids, underlying parathyroid malignancy should be considered.

Cardiac Outcome of Children With SARS-CoV-2 Related Multisystem Inflammatory Syndrome.

OBJECTIVE: To study the cardiac outcomes of patients with multisystem inflammatory syndrome in children (MIS-C) after 6-month of diagnosis. METHODS: This review of hospital records was conducted on MIS-C patients (aged <21 year) who completed a six-month follow up. The baseline demographic, clinical, laboratory, and treatment characteristics during the acute phase, and echocardiographic findings during follow-up were collected. RESULTS: 116 patients (61.2% male, median age 7 years) with MIS-C were included in the study. At the time of admission, cardiac abnormalities were present in 70.7% of MIS-C patients, and the most common cardiac abnormalities were valve failure (50.9%), followed by ventricular dysfunction (39.7%), and pericardial effusion (23.3%). Six month after diagnosis, cardiac abnormalities were found in 10.3% of patients, and patients had lower rates of ventricular dysfunction (P<0.001), valve failure (P<0.001), pericardial effusion (P<0.001), and coronary involvement (P<0.001) as composed to the baseline. Intravenous immunoglobulin (IVIG) and steroid treatment significantly reduced the odds of occurrence of ventricular dysfunction (P=0.002), valve failure (P=0.004), and low ejection fraction (P=0.002) in comparison to IVIG treatment. CONCLUSION: While most MIS-C patients had abnormal echocardiographic findings at admission, only 10.3% of patients had cardiac abnormalities during follow up.

Higher proinflammatory responses possibly contributing to suppressed cytotoxicity in patients with COVID-19 associated mucormycosis.

INTRODUCTION: COVID-19 Associated Mucormycosis (CAM), an opportunistic fungal infection, surged during the second wave of SARS Cov-2 pandemic. Since immune responses play an important role in controlling this infection in immunocompetent hosts, it is required to understand immune perturbations associated with this condition for devising immunotherapeutic strategies for its control. We conducted a study to determine different immune parameters altered in CAM cases as compared to COVID-19 patients without CAM. METHODOLOGY: Cytokine levels in serum samples of CAM cases (n = 29) and COVID-19 patients without CAM (n = 20) were determined using luminex assay. Flow cytometric assays were carried out in 20 CAM cases and 10 controls for determination of frequency of NK cells, DCs, phagocytes, T cells and their functionalities. The cytokine levels were analyzed for their association with each other as well as with T cell functionality. The immune parameters were also analyzed with respect to the known risk factors such as diabetes mellitus and steroid treatment. RESULTS: Significant reduction in frequencies of total and CD56 + CD16 + NK cells (cytotoxic subset) was noted in CAM cases. Degranulation responses indicative of cytotoxicity of T cell were significantly hampered in CAM cases as compared to the controls. Conversely, phagocytic functions showed no difference in CAM cases versus their controls except for migratory potential which was found to be enhanced in CAM cases. Levels of proinflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-17, IL-1ß, IL-18 and MCP-1 were significantly elevated in cases as compared to the control with IFN-γ and IL-18 levels correlating negatively with CD4 T cell cytotoxicity. Steroid administration was associated with higher frequency of CD56 + CD16- NK cells (cytokine producing subset) and higher MCP-1 levels. Whereas diabetic participants had higher phagocytic and chemotactic potential and had higher levels of IL-6, IL-17 and MCP-1. CONCLUSION: CAM cases differed from the controls in terms of higher titers of proinflammatory cytokines, reduced frequency of total and cytotoxic CD56 + CD16 + NK cell. They also had reduced T cell cytotoxicity correlating inversely with IFN-γ and IL-18 levels, possibly indicating induction of negative feedback mechanisms while diabetes mellitus or steroid administration did not affect the responses negatively.

The impact of chronic rhinosinusitis on COVID-19 risk and outcomes: A systematic review and meta-analysis.

Background: The impact of chronic rhinosinusitis (CRS) and subsequent steroid therapy on acquiring COVID-19 and severe outcomes remains controversial. Therefore, we conducted this systematic review and meta-analysis to provide cumulative evidence regarding the risk of COVID-19 and the impact of steroid therapy, length of hospital stay, mechanical ventilation, and mortality among CRC patients. Methods: We conducted a comprehensive electronic search strategy using the relevant keywords. The outcomes and risk factors of COVID-19 in CRS patients was estimated and compared to a healthy control group when applicable. Results: A total of seven studies were included, with an estimated prevalence of 6.5% (95% confidence interval (CI): 2.5-15.7) for COVID-19 in the CRS group. COVID-19 prevalence did not differ between CRS and controls (odds ratio (OR): 0.92; 95%CI: 0.84-1.01; p = 0.08). Moreover, using steroid/immunosuppressive therapy did not significantly increase the risk of acquiring COVID-19 in CRS patients compared to the control group (OR: 3.31; 95%CI: 0.72-15.26; p = 0.12). Length of hospital stay, mechanical ventilation, and mortality rates were comparable between the two groups. Furthermore, we found that male sex, cardiovascular morbidity, renal diseases, and hypertension were inversely associated with COVID-19 infection (p < 0.01). Conclusion: CRS had a neutral effect on acquiring COVID-19 and developing severe outcomes. However, further studies are needed.

Evaluation of steroid therapy in COVID-19 patients; in the right dose at the right time to the right patients.

Background: Although there is still no universally accepted treatment agent, steroids have been administered chronologically at every dose and at every stage of the COVID-19 pandemic. Aim: We aimed to evaluate the clinical efficacy of high-dose steroid therapy and its effect on mortality in COVID-19 patients with severe pneumonia, severe Acute Respiratory Distress Syndrome (ARDS), and septic shock. Patients and Methods: : Patients with severe pneumonia, septic shock, and ARDS due to COVID-19 who were followed up in the intensive care unit were retrospectively reviewed. Results: The study population was divided into two groups; the methylprednisolone pulse group (MP) (n = 55) and the dexamethasone group (Dex) (n = 39). When the values before and after treatment were compared; there was a statistically significant increase in the neutrophil/lymphocyte ratio after treatment in the MP group (p = 0.006). Although it was not statistically significant in the MP group, There was a numerical increase in D-dimer levels (p = 0.28). Thromboembolic complications developed in 2 patients in the MP group. The mortality outcomes of the groups were statistically similar (p = 0.943). Conclusion: We recommend steroids use in the condition that it is indicated in the critically ill group with the poor general condition. Since there is no significant difference between high-dose pulse steroid treatment and standard treatment doses, we think that the risk of complications should not be taken into account and high doses should not be used.

Tinnitus cases after COVID-19 vaccine administration, one institution's observations.

OBJECTIVE: After the role out of the COVID-19 vaccine in the United States, there has been increase in case reports of tinnitus attributed to the vaccine reported. We present our institution's experience over the initial 13 month period the vaccines were available. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic otology and general otolaryngology practice. PATIENTS: Patients who received a COVID-19 vaccine and a tinnitus diagnosis code. INTERVENTIONS: Observation, steroids (oral and intratympanic), diagnostic imaging and audiometry. MAIN OUTCOME MEASURES: Patients who received a COVID-19 vaccine in the time frame of 12/1/2020-12/31/21 with a diagnosis of tinnitus, an audiogram, and at least one visit with one of our Otolaryngologists were included in the study. Twenty-seven of the 1254 patients identified met these criteria. The patients ranged in age from 41 to 84 years old including seven male and twenty female patients. Sixteen received the Pfizer vaccine, seven received the Moderna vaccine and four patients received the Janssen vaccine. CONCLUSIONS: No definite correlation could be established between COVID-19 vaccine and tinnitus. Any concurrent sudden hearing loss should be treated as usual with oral or intratympanic steroids. Health care providers should be aware of the tinnitus onset and if new or recent onset, to refer for prompt audiogram and Otolaryngology evaluation.

Enzyme Inhibitors from Gorgonians and Soft Corals.

For decades, gorgonians and soft corals have been considered promising sources of bioactive compounds, attracting the interest of scientists from different fields. As the most abundant bioactive compounds within these organisms, terpenoids, steroids, and alkaloids have received the highest coverage in the scientific literature. However, enzyme inhibitors, a functional class of bioactive compounds with high potential for industry and biomedicine, have received much less notoriety. Thus, we revised scientific literature (1974-2022) on the field of marine natural products searching for enzyme inhibitors isolated from these taxonomic groups. In this review, we present representative enzyme inhibitors from an enzymological perspective, highlighting, when available, data on specific targets, structures, potencies, mechanisms of inhibition, and physiological roles for these molecules. As most of the characterization studies for the new inhibitors remain incomplete, we also included a methodological section presenting a general strategy to face this goal by accomplishing STRENDA (Standards for Reporting Enzymology Data) project guidelines.

Steroid-induced secondary immune deficiency.

Despite their widespread clinical use, oral corticosteroids (OCSs) are well known to be associated with a myriad of adverse effects, including immunosuppression. By inhibiting transcription factors and affecting leukocyte function, prolonged OCS use leads to significant CD4 lymphopenia and often a decrease in serum immunoglobulin (Ig)G. Conversely, OCS use has minimal impact on circulating B cell, serum IgM, or serum IgA levels. Although there is a paucity of literature, individuals treated with prolonged OCS seem to typically maintain humoral response to various vaccinations despite hypogammaglobinemia, but this area warrants additional research, especially in the setting of the coronavirus disease 2019 pandemic. Individuals treated with prolonged OCS use are most at risk for opportunistic infections, especially those with underlying malignancy and history of bone marrow transplant. Risk mitigation strategies to decrease infectious complication with OCS use include limiting the dose and duration of therapy, appropriately completing a full vaccination series, consideration for passive immunization, and prophylaxis against opportunistic infections.

Incidence and Disease Course of COVID-19 Infection Among Unvaccinated Patients Who Received Local Corticosteroid Injections.

OBJECTIVE: There are concerns that local corticosteroid injections may increase the risk of COVID-19 infection because of the immunosuppressive effect of corticosteroids. This study aimed to examine the relationship between local corticosteroid injections and the risk of COVID-19 infection. DESIGN: The date and type of procedure as well as the dose and type of corticosteroids used in patients who underwent local corticosteroid injections within 1 yr after the first COVID-19 case in the country were examined retrospectively and recorded. Patients who did not receive corticosteroids were included in the control group. Coronavirus disease 2019 infection histories of all patients were recorded. RESULTS: There was no significant difference between the patients who received local corticosteroids and the control group in terms of the incidence of COVID-19 infections, and the number of patients who needed hospitalization or intensive care treatment. In addition, it was found that the administration of two injections, the type of procedure performed, and the dose and type of steroids were not associated with the incidence or severity of COVID-19 infections. CONCLUSIONS: It has been shown that local corticosteroid injections are not associated with the incidence of COVID-19 infections and the number of patients who need hospitalization or intensive care treatment due to COVID-19.

Safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of central nervous system: A single center experience.

Introduction: Concern of a correlation between disease relapse in patients with acquired demyelinating disorders of central nervous system (CNS) and SARS-CoV2 vaccines has been raised. In this single center study, we retrospectively evaluated safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of CNS. Materials and methods: Patients with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) with disease onset before 18 years of age were included. Demographic and clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Results: We included nine patients with MOGAD. Six patients received SARS-CoV2 vaccination and complained pain at injection site while only one had fever and fatigue. Median follow-up was 28 weeks (range 20-48). Seven patients had COVID-19 occurring with mild flu-like symptoms and median follow-up was 28 weeks (range 24-34). Nobody had disease relapse. Five patients with NMOSD were included. All patients received SARS-CoV2 vaccination (BNT162b2-Pfizer-BioNTech). The median follow-up was 20 weeks (range 14-24) and only two patients complained pain at injection site, fever and fatigue. Three patients had also COVID-19 with mild flu-like symptoms, despite two of them being under immunosuppressive treatment. Lastly, forty-three patients with MS were included. 35 out of 43 received SARS-CoV2 vaccination with a median follow-up of 24 weeks (range 8-36). Fourteen patients had no side effects, while 21 complained mild side effects (mainly pain at injection site) and one experienced a disease relapse with complete recovery after steroid therapy. At vaccination, all but one were under treatment. Sixteen patients had COVID-19 occurring with mild symptoms. Discussion: COVID-19 outcome was good although many patients were under immunosuppressive treatment. Vaccine-related side effects were frequent but were mild and self-limited. Only one MS patient had a post-vaccination relapse with complete recovery after steroid therapy. In conclusion, our data support the safety of SARS-CoV-2 vaccines in pediatric MS, MOGAD and NMOSD.

A case report on recurrent alternating Tolosa-Hunt syndrome due to bacterial sphenoid sinusitis: rediscussing the diagnostic terminology and classification.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by idiopathic granulomatous inflammation involving the cavernous sinus region. Patients respond well to steroid therapy. THS is included in the differential diagnosis of cavernous sinus syndrome, so it is important to fully exclude other lesions in this area before treatment, otherwise steroid treatment may lead to fatal outcomes. Here we describe a patient who initially presented with symptoms that simulated THS symptoms and developed recurrent alternating painful ophthalmoplegia during follow-up, and the patient was finally diagnosed with cavernous sinusitis caused by bacterial sphenoid sinusitis. CASE PRESENTATION: A 34-year-old woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed abnormal signals in the left cavernous sinus area, and these abnormal signals were suspected to be THS. After steroid treatment, the patient obtained pain relief and had complete recovery of her ophthalmoplegia. However, right painful ophthalmoplegia appeared during the follow-up period. MRI showed obvious inflammatory signals in the right cavernous sinus and right sphenoid sinus. Then nasal sinus puncture and aspiration culture were performed, and the results showed a coagulase-negative staphylococcus infection. After antibiotic treatment with vancomycin, the painful ophthalmoplegia completely resolved, and the neurological examination and MRI returned to normal. CONCLUSION: Some other causes of painful ophthalmoplegia also fulfill the diagnostic criteria for THS in the International Classification of Headache Disorders third edition (ICHD-3) and respond well to steroid therapy. Early diagnosis of THS may be harmful to patients, and clinicians should exercise great caution when dealing with similar cases without a biopsy. Using "cavernous sinus syndrome" instead of "Tolosa-Hunt syndrome" as a diagnostic category may provide a better clinical thinking for etiological diagnosis.

[Dysglycemia in COVID-19 and Type 2 Diabetes Mellitus: Peculiarities of the Glycemic Profile in Hospitalized Patients and the Role of Steroid-Induced Disorders].

BACKGROUND: There is a lack of data on the features of dysglycemia in hospitalized patients with COVID-19 and concomitant diabetes mellitus (DM) confirmed by continuous glucose monitoring (CGM). AIM: to study the glycemic profile in hospitalized patients with COVID-19 and type 2 diabetes mellitus by continuous glucose monitoring and the role of steroid therapy in dysglycemiadevelopment. MATERIALS AND METHODS: We examined 21 patients with COVID-19 and DM 2 and 21 patients with DM 2 without COVID-19 (control group) using a professional 4-7-day CGM. We also compared two subgroups of patients with COVID-19 and DM 2: 1) patients received systemic glucocorticosteroids (GCS) during CGM and 2) patients in whomCGMwas performed after discontinuation of GCS. RESULTS: Compared with controls, patients with COVID-19 and DM2 had lesser values of glycemic «time in range¼ (32.7 ± 20.40 vs 48.0 ± 15.60%, p = 0.026) andhigher parameters of mean glycemia (p <0.05) but similar proportion of patients with episodes of hypoglycemia (33.3% vs 38.1%, p = 0.75). Patients who received dexamethasone during CGM were characterized by higher hyperglycemia and the absence of episodes of hypoglycemia. In patients who hadCGM after dexamethasone discontinuation, hyperglycemia was less pronounced, but 60% of them had episodes of hypoglycemia, often nocturnal, clinically significant and not detected by routine methods. CONCLUSION: Patients with COVID-19 and DM 2had severe and persistent hyperglycemia but a third of them hadalso episodes of hypoglycemia. During therapy with dexamethasone, they had the most pronounced hyperglycemia without episodes of hypoglycemia. In patients who underwent CGM after discontinuation of dexamethasone, hyperglycemia was less pronounced but 60% of them have episodes of hypoglycemia, often nocturnal, clinically significant and not diagnosed by routine methods. It would be advisable to recommend at least a 5-6-fold study of the blood glucose level (with its obligatory assessment at night) even for stable patients with COVID-19 and DM 2after the end of GCS treatment.