Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. Methods: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea.Obesity was defined as a body mass index value of ≥ 30 kg/m 2 . Results: The most common disease was IgA nephropathy (IgAN) in both obese and nonobese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37–2.17; OR, 1.96, 95% CI, 1.21–3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62–0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01–2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36–8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09–5.64). Conclusion Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.

Objective: The cutaneous manifestation of decompression sickness (DCS) known as cutis marmorata (CM) is generally mild, but it is often accompanied by severe DCS or may be a prognostic sign. We aimed to analyze the clinical course of patients with CM to improve our understanding of CM. Methods: From January 2016 to December 2020, a retrospective cohort single-center study was conducted on patients with acute DCS who underwent emergency recompression therapy. We analyzed their data and the clinical outcomes after recompression therapy. In addition, we reviewed relevant literature. Results: A total of 341 people were enrolled during the study period. Of them 94 (27.6%) patients presented with CM and the symptoms appeared at an average of about 60.5 minutes after surfacing. Among the CM patients, 76.6% had accompanying DCS type II, and in 23.4%, had accompanying DCS type I (P=0.011). With single recompression therapy, 88.3% of patients with CM immediately recovered. Among these 95.4% of patients with DCS type I and 86.1% with DCS type II recovered immediately. However, there were no statistical differences in the immediate treatment outcomes according to the delay time from the onset of symptoms to recompression therapy, accompanying symptomatic DCS classification, and recompression modalities. Ultimately, all the patients recovered from CM. Conclusion CM by itself can be considered a mild DCS in terms of treatment progress, but prompt treatment is required to prevent complications. In addition, greater focus is needed on other accompanying DCS symptoms in patients with CM, and the treatment method should be determined accordingly.

Objective: Hyperbaric oxygen therapy (HBOT) is the most crucial treatment for decompression sickness (DCS), which needs to be administered as swiftly as possible. This study evaluates the therapeutic responses of DCS patients and analyzes the major factors for clinical outcomes. Methods: This is a retrospective cohort single-center study on patients who arrived at our hospital’s emergency department for diving-related symptoms and were diagnosed with DCS and administered HBOT. Results: Totally, 337 patients were enrolled from June 2015 to May 2020. The proportion of SCUBA diving, rapid ascent, and inter-facility transport cases was higher in the recreational group, with a longer lag time from symptom onset to HBOT. The professional group had a higher proportion of cases with previous DCS history, total diving time, bottom time, in-water decompression, and repetitive diving. Examination of treatment outcomes revealed more type I cases and a shorter lag time from symptom onset to HBOT in the complete recovery group. Conversely, the incomplete recovery group had a higher proportion of type II cases and aggravation of symptoms before HBOT was administered. Conclusion DCS can occur regardless of professional or recreational divers. Both groups showed a similar level of severity. It is recommended that recreational divers should be cautious of accidents related to safety (such as rapid ascent) and receive swift treatment in case of the onset of symptoms. Occupational divers need more active efforts to get HBOT rather than just performing in-water recompression or home O2 therapy.

Objective: Early identification of patients at risk for deterioration is crucial to reduce in-hospital mortality. Various early warning scores have been widely applied in the emergency department (ED) of hospitals. This study evaluates and compares the effectiveness of three early warning scores_Modified Early Warning Score, Rapid Acute Physiology Score (RAPS), Worthing Physiological Scoring System (WPS), and Rapid Emergency Medicine Score. These scores help predict the need for critical care and 24- and 72-hour mortalities among alert patients presenting to the ED with dyspnea. Methods: This retrospective cohort study used data from electronic medical records of patients admitted between 2018 and 2020 and included all consecutive alert patients who presented with dyspnea in the ED. The primary outcome was to evaluate the performance of early warning scores regarding the need for critical care. The secondary outcomes were the prediction of 24- and 72-hour in-hospital mortalities. Results: Among 4,322 patients evaluated, 255 received critical care, and 17 and 84 died within 24 and 72 hours, respectively. The WPS had the overall highest performance for predicting the need for critical care (area under the curve [AUC], 0.781; 95% confidence interval [CI], 0.751-0.810) and 24-hour (AUC, 0.816; 95% CI, 0.738-0.894) and 72-hour mortalities (AUC, 0.794; 95% CI, 0.750-0.838), but differed significantly only from the RAPS. Conclusion The WPS might better predict the need for critical care and short-term mortality in alert patients with dyspnea in the ED. However, owing to a lack of its superiority in statistics, further studies are warranted to conclude the optimal tools applicable for these patients.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Background/Aims: Hypertension is considered a risk factor in immunoglobulin A nephropathy (IgAN). However, after IgAN diagnosis, the relationship between early blood pressure control and renal prognosis remains unclear. This study aimed to analyze the association between the prognosis of IgAN patients and a controlled status of hypertension within the first year of IgAN diagnosis. Methods: We retrospectively analyzed 2,945 patients diagnosed with IgAN by renal biopsy. The patients were divided into ‘normal,’ ‘new-onset,’ ‘well-controlled,’ and ‘poorly-controlled’ groups using blood pressure data from two consecutive measurements performed within a year. The Kaplan-Meier survival analysis and Cox proportional-hazards regression model were used to survey the independent association between recovery from hypertension and the risk of IgAN progression. The primary endpoint was IgAN progression defined as the initiation of dialysis or kidney transplantation. Results: Before IgAN diagnosis, 1,239 patients (42.1%) had been diagnosed with hypertension. In the fully adjusted Cox proportional-hazards models, the risk of IgAN progression increased by approximately 1.7-fold for the prevalence of hypertension. In the subgroup analyses, the ‘well-controlled’ group showed a statistically significant risk of IgAN progression (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.103 to 9.245; p = 0.032). Moreover, the ‘new-onset’ and ‘poorly-controlled’ groups had an increased risk of IgAN progression compared to the ‘normal’ group (HR, 2.58; 95% CI, 1.016 to 6.545; p = 0.046 and HR, 3.85;95% CI, 1.541 to 9.603; p = 0.004, respectively). Conclusions Although hypertension was well-controlled in the first year after IgAN diagnosis, it remained a risk factor for IgAN progression.

OBJECTIVE: There are no strong guidelines on how long or how we should undertake conservative treatment during the acute period of an osteoporotic vertebral compression fracture (VCF). METHODS: We treated 202 patients with conservative treatment on VCF from March 2012 to August 2015. On inclusion criteria, 75 patients (22 males and 53 females) were included in the final analysis. After admission, a transdermal fentanyl patch with low dose (12.5 µg) application was attempted in all patients. In an unresponsive patient, the fentanyl patch was increased by 25 µg. After identifying the tolerable toilet ambulation of the patient without any assistance, hospital discharge was recommended. We classified two patient groups into one favorable group and one unfavorable group and compared several clinical and radiological factors. RESULTS: Among 75 patients, the clinical outcome of 57 patients (76%) was favorable, but that of 18 patients (24%) was unfavorable. In clinical outcomes, the numeric rating scale at 6 and 12 months and Odom's criteria at 12 months was significantly different between the favorable and the unfavorable groups. The dose of the patches used showed statistically significant differences between the two groups (p=0.001). CONCLUSION: The only statistically significant affecting factor for an unfavorable outcome was the use of a higher dose fentanyl patch. Our data inferred that the unresponsiveness to a low-dose fentanyl patch could be helpful to select patients necessary for percutaneous vertebroplasty or kyphoplasty.
Fentanyl* ; Fractures, Compression* ; Humans ; Kyphoplasty ; Male ; Transdermal Patch* ; Vertebroplasty ; Walking

We presented a patient with cerebral decompression sickness, who showed predominant vasogenic edema on a 3.0 Tesla (3T) magnetic resonance imaging (MRI) findings, including diffusion-weighted image (DWI) and apparent diffusion coefficient (ADC) mapping. Within minutes of surfacing, he developed paresis of the right lower limb. During transport, he began shivering, followed by severe spasm that eventually progressed to a tonic-clonic seizure. Emergent hyperbaric oxygen therapy (HBOT) was performed with U.S. Navy treatment table 6A after a treatment of seizure activity. Brain MRI was performed after hyperbaric oxygen therapy to detect any cerebral lesions, which showed subcortical hyperintensity signal changes in the left fronto-parietal region on the ADC map. Overlying cortical hyperintensity on DWI sequences and cortical hypointensity on the ADC map were simultaneously observed. Moreover, these findings disappeared in a followup MRI with complete resolution of symptoms. These findings indicate that vasogenic edema can cause cerebral decompression sickness (DCS) and that 3T MRI with DWI and ADC mapping may be useful for diagnosing cerebral DCS. In addition, these findings suggest that DW-MRI may also be useful in predicting the prognosis of cerebral DCS.
Brain ; Brain Edema ; Decompression Sickness* ; Decompression* ; Diffusion ; Diffusion Magnetic Resonance Imaging ; Edema ; Follow-Up Studies ; Humans ; Hyperbaric Oxygenation ; Lower Extremity ; Magnetic Resonance Imaging* ; Paresis ; Prognosis ; Seizures ; Shivering ; Spasm

Immersion pulmonary edema (IPE) is a form of pulmonary edema that can occur in divers or swimmers. IPE is a rare condition, but can be life-threatening and recurrent condition. The pathophysiology of IPE is still incompletely understood. We present a case of scuba diving induced pulmonary edema in a 46-year-old woman diving in cold seawater. After 20 minutes of diving at 18 m, she felt difficulty of breathing. Symptoms on surfacing were dyspnea, cough, and frothy sputum. Chest X-ray showed pulmonary edema and she was treated with an intravenous diuretic and supplemental oxygen. The patient showed rapid resolution of symptoms and was discharged on the same day. Sport physician should be aware of this potentially life-threatening recurrent condition.
Cough ; Diving* ; Dyspnea ; Female ; Humans ; Immersion* ; Middle Aged ; Oxygen ; Pulmonary Edema* ; Respiration ; Seawater ; Sports ; Sputum ; Thorax