White and gray matter integrity evaluated by MRI-DTI can serve as noninvasive and reliable indicators of structural and functional alterations in chronic neurotrauma.

We aimed to evaluate whether white and gray matter microstructure changes observed with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI) can be used to reflect the progression of chronic brain trauma. The MRI-DTI parameters, neuropathologic changes, and behavioral performance of adult male Wistar rats that underwent moderate (2.1 atm on day "0") or repeated mild (1.5 atm on days "0" and "2") traumatic brain injury (TBI or rmTBI) or sham operation were evaluated at 7 days, 14 days, and 1-9 months after surgery. Neurobehavioral tests showed that TBI causes long-term motor, cognitive and neurological deficits, whereas rmTBI results in more significant deficits in these paradigms. Both histology and MRI show that rmTBI causes more significant changes in brain lesion volumes than TBI. In vivo DTI further reveals that TBI and rmTBI cause persistent microstructural changes in white matter tracts (such as the body of the corpus callosum, splenium of corpus callus, internal capsule and/or angular bundle) of both two hemispheres. Luxol fast blue measurements reveal similar myelin loss (as well as reduction in white matter thickness) in ipsilateral and contralateral hemispheres as observed by DTI analysis in injured rats. These data indicate that the disintegration of microstructural changes in white and gray matter parameters analyzed by MRI-DTI can serve as noninvasive and reliable markers of structural and functional level alterations in chronic TBI.

Mesenchymal stem cells reduce long-term cognitive deficits and attenuate myelin disintegration and microglia activation following repetitive traumatic brain injury.

The underlying mechanisms for the beneficial effects exerted by bone marrow-mesenchymal stem cells (BM-MSCs) in treating repetitive traumatic brain injury (rTBI)-induced long-term sensorimotor/cognitive impairments are not fully elucidated. Herein, we aimed to explore whether BM-MSCs therapy protects against rTBI-induced long-term neurobehavioral disorders in rats via normalizing white matter integrity and gray matter microglial response. Rats were subjected to repeated mild lateral fluid percussion on day 0 and day 3. On the fourth day post-surgery, MSCs groups received MSCs (4 × 106 cells/ml/kg, intravenously) and were assessed by the radial maze, Y maze, passive avoidance tests, and modified neurological severity scores. Hematoxylin & eosin, and Luxol fast blue stainings were used to examine the histopathology and white matter thickness. At the same time, immunofluorescence staining was used to investigate the numbers of tumor necrosis factor-alpha (TNF-α)-containing microglia in gray matter. Three to nine months after neurotrauma, rats displayed sensorimotor and cognitive impairments, reduced thickness in white matter, and over-accumulation of TNF-α-containing microglia and cellular damage in gray matter. Therapy with BM-MSCs significantly attenuated the rTBI-induced sensorimotor and cognitive impairments and all their complications. Mesenchymal stem cell therapy might accelerate the recovery of sensorimotor and cognitive impairments in rats with rTBI via normalizing myelin integrity and microglia response.

Hyperbaric oxygen preconditioning normalizes scrotal temperature, sperm quality, testicular structure, and erectile function in adult male rats subjected to exertional heat injury.

Testicular hyperthermia has been noted in men who work in high ambient temperatures. Scrotal temperatures above the normal range caused germ cell loss in the testes and resulted in male subfertility. In adult male rats, exercising at a higher environmental temperature (36 °C with relative humidity of 50%, 52 min) caused exertional heat stroke (EHS) characterized by scrotal hyperthermia, impaired sperm quality, dysmorphology in testes, prostates and bladders, and erectile dysfunction. Here, we aim to ascertain whether hyperbaric oxygen preconditioning (HBOP: 100% O2 at 2.0 atm absolute [ATA] for 2 h daily for 14 days consequently before the onset of EHS) is able to prevent the problem of EHS-induced sterility, testes, prostates, and bladders dysmorphology and erectile dysfunction. At the end of exertional heat stress compared to normobaric air (NBA or non-HBOP) rats, the HBOP rats exhibited lower body core temperature (40 °C vs. 43 °C), lower scrotal temperature (34 °C vs. 36 °C), lower neurological severity scores (2.8 vs. 5.8), higher erectile ability, (5984 mmHg-sec vs. 3788 mmHg-sec), higher plasma testosterone (6.8 ng/mL vs. 3.5 ng/mL), lower plasma follicle stimulating hormone (196.3 mIU/mL vs. 513.8 mIU/mL), lower plasma luteinizing hormone (131 IU/L vs. 189 IU/L), lower plasma adrenocorticotropic hormone (5136 pg/mL vs. 6129 pg/mL), lower plasma corticosterone (0.56 ng/mL vs. 1.18 ng/mL), lower sperm loss and lower values of histopathological scores for epididymis, testis, seminal vesicle, prostate, and bladder. Our data suggest that HBOP reduces body core and scrotal hyperthermia and improves sperm loss, testis/prostate/bladder dysmorphology, and erectile dysfunction after EHS in rats.

Characteristics and outcomes for pulmonary aspergillosis in critically ill patients without influenza: A 3-year retrospective study.

BACKGROUND: Previous studies have revealed higher mortality rates in patients of severe influenza coinfected with invasive pulmonary aspergillosis (IPA) than in those without the coinfection; nonetheless, the clinical outcome of IPA in critically ill patients without influenza remains unclear. PATIENTS AND METHODS: This retrospective study was conducted in three institutes. From 2016-2018, all adult patients diagnosed with IPA in the intensive care units (ICUs) were identified. The logistic regression was used to identify the potential risk factors associated with in-hospital mortality in patients with non-influenza IPA. The stratified analysis of IPA patients with and without antifungal therapy was also performed. The final model was established using a forward approach, selecting variables with p-values less than 0.05. RESULTS: Ninety patients were included during the study period, and 63 (70%) were men. The most common comorbidity was diabetes mellitus (n = 24, 27%), followed by solid cancers (n = 22, 24%). Antifungal therapy was administered to 50 (56%) patients, mostly voriconazole (n = 44). The in-hospital mortality rate was 49% (n = 44). Univariate analysis revealed that the risk factors for mortality included daily steroid dose, APACHE II score, SOFA score, C-reactive protein (CRP) level, carbapenem use, antifungal therapy, and caspofungin use. Multiple regression analysis identified four independent risk factors for mortality: age (Odds ratio [OR], 1.052, p = 0.013), daily steroid dose (OR, 1.057, p = 0.002), APACHE II score (OR, 1.094, p = 0.012), and CRP level (OR, 1.007, p = 0.008). Furthermore, the multivariable analysis identified that more physicians would initiate antifungal therapy for patients with prolonged steroid use (p = 0.001), lower white blood cell count (p = 0.021), and higher SOFA score (p = 0.048). Thus, under the selection bias, the independent risk factors for mortality in the antifungal treatment subgroup were daily steroid dose (OR, 1.046, p = 0.001) and CRP (OR, 1.006, p = 0.018), whereas the independent risk factor for mortality in the untreated group became APACHE II score (OR, 1.232, p = 0.007). CONCLUSIONS: Patients with IPA had a substantially high mortality. Overall, age, steroid use, APACHE II score, and CRP level were identified as the independent risk factors for mortality in patients in the ICU.

Emergence and dissemination of multidrug-resistant Escherichia coli ST8346 coharboring blaNDM-5 and blaOXA-181 in Southern Taiwan, 2017-2021.

BACKGROUND: Enterobacterales carrying blaNDM represent an emerging challenge in treating infectious diseases. In this study, we aimed to investigate the characteristics of blaNDM-producing Enterobacterales from three hospitals in southern Taiwan. METHODS: Enterobacterales strains that were nonsusceptible to more than one carbapenem (ertapenem, meropenem, imipenem, or doripenem) were collected from hospitalized patients. Molecular typing for New Delhi metallo-ß-lactamase (NDM) and antibiotic susceptibility tests were performed, followed by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and plasmid analysis by PCR-based replicon typing. RESULTS: A total of 1311 carbapenem-nonsusceptible Enterobacterales were isolated from 2017 to 2021. blaNDM-encoding genes were detected in 108 isolates, with 53 (49.1%) harboring blaNDM-1 and 55 (50.9%) harboring blaNDM-5. The rate of blaNDM-1 detection among isolates decreased to 2% in 2021. However, the rate of E. coli harboring blaNDM-5 increased from 1% to 12% of total isolates during the study period. Of 47 NDM-5-positive E. coli isolates, 44 (93.6%) were ST8346 with high genetic relatedness. E. coli ST8346 isolates showed high-level resistance to both carbapenems and aminoglycosides. Most (38 out of 47, 80.9%) blaNDM-5-harboring E. coli isolates co-harbored blaOXA-181. We analyzed the regions harboring blaNDM-5 in E. coli ST8346 via PCR amplification. blaNDM-5 and blaOXA-181 were located on two separate plasmids, IncF and IncX3, respectively. CONCLUSION: The dissemination of E. coli ST8346 caused an increase in blaNDM-5 and blaOXA-181 co-harboring Enterobacterales in southern Taiwan, which show high-level resistance to both carbapenems and aminoglycosides. We identified a distinct IncF plasmid encoding blaNDM-5 that has the potential for rapid spread and needs further surveillance.

Comparative efficacies of various corticosteroids for preventing postextubation stridor and reintubation: a systematic review and network meta-analysis.

Objectives: We assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned extubation. Methods: We searched the Pubmed, Embase, the Cochrane databases and ClinicalTrial.gov registration for articles published through September 29, 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacies of systemic corticosteroids and other therapeutics for preventing postextubation stridor and reintubation were included. The primary outcome was postextubation stridor and the secondary outcome was reintubation. Results: The 11 assessed RCTs reported 4 nodes: methylprednisolone, dexamethasone, hydrocortisone, and placebo, which yielded 3 possible pairs for comparing the risks of post extubation stridor and 3 possible pairs for comparing the risks of reintubation. The risk of postextubation stridor was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients (dexamethasone: OR = 0.39; 95% CI = 0.22-0.70; methylprednisolone: OR = 0.22; 95% CI = 0.11-0.41). The risk of postextubation stridor was significantly lower in methylprednisolone-treated patients than in hydrocortisone-treated: OR = 0.24; 95% CI = 0.08-0.67) and dexamethasone-treated patients: OR = 0.55; 95% CI = 0.24-1.26). The risk of reintubation was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients: (dexamethasone: OR = 0.34; 95% CI = 0.13-0.85; methylprednisolone: OR = 0.42; 95% CI = 0.25-0.70). Cluster analysis showed that dexamethasone- and methylprednisolone-treated patients had the lowest risks of stridor and reintubation. Subgroup analyses of patients with positive cuff-leak tests showed similar results. Conclusions: Methylprednisolone and dexamethasone were the most effective agents against postextubation stridor and reintubation.

Inhaled corticosteroid for patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of inhaled corticosteroid (ICS) in the treatment of patients with COVID-19 has been evaluated in randomized controlled trials (RCTs), however, their findings are not consistent. METHODS: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar were searched to June 10, 2023. Only RCTs that investigated the clinical efficacy and safety of ICS for patients with COVID-19 were included. RESULTS: Eleven RCTs were included. ICS users had significantly higher rate of symptom alleviation at day 14 than the control group (risk ratio [RR], 1.13; 95% CI, 1.04-1.23; I2 = 42%). Additionally, no significant difference between the ICS users and the control group was observed in the composite outcome of urgent care, emergency department (ED) visit or hospitalization (RR, 0.43; 95% CI, 0.08-2.48; I2 = 85%) and hospitalization or death (RR, 0.85; 95% CI, 0.64-1.12; I2 = 0%). Finally, ICS user had a non-significantly lower risk of death at day 28 than the control group (0.63% vs 0.99%; RR, 0.82; 95% CI, 0.43-1.56; I2 = 0%). CONCLUSIONS: Additional ICS use, particularly inhaled budesonide may help symptom relief in patients with COVID-19. However, ICS use did not help reduce the risk of urgent care, ED visit, hospitalization, or death.

In vitro activities of antimicrobial combinations against planktonic and biofilm forms of Stenotrophomonas maltophilia.

Objectives: To investigate the in vitro activity of antibiotic combinations against Stenotrophomonas maltophilia isolates and their associated biofilms. Methods: Thirty-two S. maltophilia clinical isolates with at least twenty-five different pulsotypes were tested. The antibacterial activity of various antibiotic combinations against seven randomly selected planktonic and biofilm-embedded S. maltophilia strains with strong biofilm formation was assessed using broth methods. Extraction of bacterial genomic DNA and PCR detection of antibiotic resistance and biofilm-related genes were also performed. Results: The susceptibility rates of levofloxacin (LVX), fosfomycin (FOS), tigecycline (TGC) and sulfamethoxazole-trimethoprim (SXT) against 32 S. maltophilia isolates were 56.3, 71.9, 71.9 and 90.6%, respectively. Twenty-eight isolates were detected with strong biofilm formation. Antibiotic combinations, including aztreonam-clavulanic (ATM-CLA) with LVX, ceftazidime-avibactam (CZA) with LVX and SXT with TGC, exhibited potent inhibitory activity against these isolates with strong biofilm formation. The antibiotic resistance phenotype might not be fully caused by the common antibiotic-resistance or biofilm-formation gene. Conclusion: S. maltophilia remained resistant to most antibiotics, including LVX and ß-lactam/ß-lactamases; however, TGC, FOS and SXT still exhibited potent activity. Although all tested S. maltophilia isolates exhibited moderate-to-strong biofilm formation, combination therapies, especially ATM-CLA with LVX, CZA with LVX and SXT with TGC, exhibited a higher inhibitory activity for these isolates.

Myocardial structure and functional alterations in a preclinical model of exertional heat stroke.

AIM: Relatively little information is available about the effect of an acute exertional heat stroke (EHS) on myocardium structure and function. Herein, we used a survival male rat model of EHS to answer the question. MAIN METHODS: Adult male Wistar rats underwent forced treadmill running at a 36 °C room temperature and 50 % relative humidity until EHS onset, characterized by hyperthermia and collapse. All rats that were followed for 14 days survived. Injury severity scores of both gastrocnemius and myocardium were determined histologically. Following an EHS event, pathological echocardiography, skeletal muscle and myocardial damage scores and indicators, myocardial fibrosis, hypertrophy, and autophagy were elucidated. KEY FINDINGS: Rats with EHS onset displayed skeletal muscle damage, elevated serum levels of skeletal muscle damage indicators (e.g., creatinine kinase, myoglobin, and potassium), and myocardial injury indicators (e.g., cardiac troponin I, creatinine kinase, and lactate dehydrogenase) returning to homeostasis within 3 days post-EHS. However, EHS-induced myocardial damage, pathological echocardiography, myocardial fibrosis, hypertrophy, and deposited misfolded proteins lasted up to 14 days post-EHS at least. SIGNIFICANCE: First, we provide evidence to confirm that despite the apparent return to homeostasis, underlying processes may still be ongoing after EHS onset. Second, we provide several key findings emphasizing the pathophysiology and risk factors of EHS, highlighting gaps in knowledge with the aim of stimulating future studies.

An artificial intelligence system to predict the optimal timing for mechanical ventilation weaning for intensive care unit patients: A two-stage prediction approach.

Background: For the intensivists, accurate assessment of the ideal timing for successful weaning from the mechanical ventilation (MV) in the intensive care unit (ICU) is very challenging. Purpose: Using artificial intelligence (AI) approach to build two-stage predictive models, namely, the try-weaning stage and weaning MV stage to determine the optimal timing of weaning from MV for ICU intubated patients, and implement into practice for assisting clinical decision making. Methods: AI and machine learning (ML) technologies were used to establish the predictive models in the stages. Each stage comprised 11 prediction time points with 11 prediction models. Twenty-five features were used for the first-stage models while 20 features were used for the second-stage models. The optimal models for each time point were selected for further practical implementation in a digital dashboard style. Seven machine learning algorithms including Logistic Regression (LR), Random Forest (RF), Support Vector Machines (SVM), K Nearest Neighbor (KNN), lightGBM, XGBoost, and Multilayer Perception (MLP) were used. The electronic medical records of the intubated ICU patients of Chi Mei Medical Center (CMMC) from 2016 to 2019 were included for modeling. Models with the highest area under the receiver operating characteristic curve (AUC) were regarded as optimal models and used to develop the prediction system accordingly. Results: A total of 5,873 cases were included in machine learning modeling for Stage 1 with the AUCs of optimal models ranging from 0.843 to 0.953. Further, 4,172 cases were included for Stage 2 with the AUCs of optimal models ranging from 0.889 to 0.944. A prediction system (dashboard) with the optimal models of the two stages was developed and deployed in the ICU setting. Respiratory care members expressed high recognition of the AI dashboard assisting ventilator weaning decisions. Also, the impact analysis of with- and without-AI assistance revealed that our AI models could shorten the patients' intubation time by 21 hours, besides gaining the benefit of substantial consistency between these two decision-making strategies. Conclusion: We noticed that the two-stage AI prediction models could effectively and precisely predict the optimal timing to wean intubated patients in the ICU from ventilator use. This could reduce patient discomfort, improve medical quality, and lower medical costs. This AI-assisted prediction system is beneficial for clinicians to cope with a high demand for ventilators during the COVID-19 pandemic.

The effect of Lactobacillus with prebiotics on KPC-2-producing Klebsiella pneumoniae.

Objectives: This study investigated the inhibitory effect of Lactobacillus spp. with prebiotics against Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing Klebsiella pneumoniae using both in vitro experiments and animal models. Methods: Thirty-three Lactobacillus spp. strains were confirmed by 16S rDNA sequencing, and four different PFGE genotyped KPC-2-producing K. pneumoniae strains were selected for investigation. In vitro studies, including broth microdilution assays, changes in pH values in lactobacilli cultures with different prebiotics, time-kill tests of Lactobacillus spp. against KPC-2-producing K. pneumoniae and further in vivo Lactobacillus alone or in combination with prebiotics against KPC-2-producing K. pneumoniae in an animal model, were performed. Results: The lower pH value of the cell-free supernatant was associated with a lower minimal inhibitory percentage of the Lactobacillus strain against KPC-2-producing K. pneumoniae. Furthermore, lactulose/isomalto-oligosaccharide/inulin and fructo-oligosaccharide can enhance the inhibitory effect of all 107 CFU/ml Lactobacillus strains against KPC001. Three Lactobacillus strains (LYC1154, LYC1322, and LYC1511) that could be persistently detected in the stool were tested for their ability to reduce the amount of KPC001 in the feces individually or in combination. A significantly better effect in reducing the amount of KPC001 was observed for the combination of three different Lactobacillus species than for each of them alone. Furthermore, their inhibitory effect was enhanced after adding lactulose or isomalto-oligosaccharide (both p < 0.05). Conclusion: This study demonstrates the inhibitory effect of probiotic Lactobacillus, including LYC1154, LYC1322, and LYC1511, with prebiotics such as lactulose or isomalto-oligosaccharide against the colonization of KPC-2-producing K. pneumoniae.

The interrelationships between neuronal viability, synaptic integrity, microglial responses, and amyloid-beta formation in an in vitro neurotrauma model.

The interrelationships between neuronal viability, synaptic integrity, and microglial responses remain in infancy. In dealing with the question, we induced a stretch injury to evaluate the mechanical effects of trauma on rat primary cortical neurons and BV2 microglial cells in a transwell culture system. The viability of primary neurons and BV2 cells was determined by MTT. Synaptic integrity was evaluated by determining the expression of beta-secretase 1 (BACE1), amyloid-beta (Aß), microtubule-associated protein 2 (MAP2), and synaptophysin (vehicle protein). Both CD16/32-positive (CD16/32+) and CD206-positive (CD206+) microglia cells were detected by immunofluorescence staining. The phagocytic ability of the BV2 cells was determined using pHrodo E. coli BioParticles conjugates and flow cytometry. We found that stretch injury BV2 cells caused reduced viability and synaptic abnormalities characterized by Aß accumulation and reductions of BACE1, MAP2, and synaptophysin in primary neurons. Intact BV2 cells exhibited normal phagocytic ability and were predominantly CD206+ microglia cells, whereas the injured BV2 cells exhibited reduced phagocytic ability and were predominantly CD16/32+ microglial cells. Like a stretch injury, the injured BV2 cells can cause both reduced viability and synaptic abnormalities in primary neurons; intact BV2 cells, when cocultured with primary neurons, can protect against the stretch-injured-induced reduced viability and synaptic abnormalities in primary neurons. We conclude that CD206+ and CD16/32+ BV-2 cells can produce neuroprotective and cytotoxic effects on primary cortical neurons.

Clinical outcomes, virological efficacy and safety of nitazoxanide in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study investigated the clinical outcomes, virological efficacy and safety of nitazoxanide in the treatment of patients with COVID-19. RESEARCH DESIGN AND METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before August 23, 2022. Only randomized controlled trials (RCTs) that assessed the usefulness and safety of nitazoxanide in patients with COVID-19 were included. RESULTS: Five RCTs were included. The overall mortality of COVID-19 patients receiving nitazoxanide (study group) was 1.3% (9/670), which was lower than the control group (1.8%, 12/681), but this difference did not reach statistical significance (risk difference [RD], 0.00; 95% CI: -0.01 to 0.01; P =0.97). However, nitazoxanide was associated with a higher virological eradication rate than placebo or standard care (RD, 0.09; 95% CI: 0.01 to 0.17; P = 0.03). Compared with the placebo or standard care, nitazoxanide were associated with a similar risk of any adverse event (RD, -0.02; 95% CI: -0.07 to 0.03; P = 0.44). CONCLUSIONS: Although nitazoxanide can help virological eradication and is also tolerable, it does not provide additional clinical benefits. Based on these evidences, the use of nitazoxanide in the treatment of patients with COVID-19 is not recommended.

Effect of fluvoxamine on outcomes of nonhospitalized patients with COVID-19: A systematic review and meta-analysis.

OBJECTIVES: This meta-analysis investigated the use of fluvoxamine for the treatment of nonhospitalized patients with COVID-19. METHODS: PubMed, Web of Science, Ovid medline, Embase, Scopus, Cochrane Library databases, and ClinicalTrials.gov were searched for studies published before June 25, 2022. Only clinical studies that compared the efficacy and safety of fluvoxamine with other alternatives or placebos in the treatment of nonhospitalized patients with COVID-19 were included. RESULTS: Four studies with 1814 patients, of whom 912 received fluvoxamine, were included in this study. Compared with the control group receiving placebo or no therapy, the study group receiving fluvoxamine demonstrated a lower risk of hospitalization and emergency department (ED) visits (odds ratio [OR], 0.59; 95 % CI, 0.44-0.79; I2 = 26 %). In addition, the rate of hospitalization remained significantly lower in patients who received fluvoxamine than in the control group (OR, 0.69; 95 % CI, 0.51-0.94; I2 = 36 %). Although the study group demonstrated a lower risk of requirement of mechanical ventilation and intensive care unit admission, and mortality than the control group, these differences were nonsignificant. Finally, fluvoxamine use was associated with a similar risk of adverse events as that observed in the control group. CONCLUSION: Fluvoxamine can be safely used in nonhospitalized patients with COVID-19 and can reduce the hospitalization rate or ED visits in these patients.

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to global health. In addition to SARS-CoV-2 itself, clinicians should be alert to the possible occurrence of co-infection or secondary infection among patients with COVID-19. The possible co-pathogens include bacteria, viruses, and fungi, but COVID-19-associated cryptococcosis is rarely reported. This review provided updated and comprehensive information about this rare clinical entity of COVID-19-associated cryptococcosis. Through an updated literature search till 23 August 2022, we identified a total of 18 culture-confirmed case reports with detailed information. Half (n = 9) of them were elderly. Fifteen (83.3%) of them had severe COVID-19 and ever received systemic corticosteroid. Disseminated infection with cryptococcemia was the most common type of cryptococcosis, followed by pulmonary and meningitis. Except one case of C. laurentii, all other cases are by C. neoformans. Liposomal amphotericin B and fluconazole were the most commonly used antifungal agents. The overall mortality was 61.1% (11/18) and four of them did not receive antifungal agents before death. Improving the poor outcome requires a physician's high suspicion, early diagnosis, and prompt treatment.

Clinical efficacy and safety of topical difamilast in the treatment of patients with atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD). METHODS: Only randomized controlled trials (RCTs) that compared topical difamilast with vehicle treatment for patients with AD were included. PubMed, Web of Science, Ovid Medline, Cochrane Library, ClinicalTrials.gov and JapicCTI were searched to 10 April 2022. RESULTS: Five studies enrolling a total of 1009 patients with mild-to-moderate AD were identified. Compared with the topical vehicle, topical difamilast was associated with a significantly higher success rate according to the Investigator's Global Assessment score at week 4 (relative risk, 2.82; 95% confidence interval [CI]: 2.11-3.77). Compared with the vehicle, difamilast was associated with a significant decrease in day 28 eczema area and severity index scores (mean difference [MD], -4.10; 95% CI: -5.32 to -2.87), verbal rating scale scores (MD, -0.51; 95% CI: -0.71 to -0.32), visual analog scale scores (MD, -12.15; 95% CI: -19.70 to -4.61), patient-oriented eczema measure values (MD, -3.99; 95% CI: -4.91 to -3.07), and total affected body surface area (MD, -6.48; 95% CI: -8.09 to -4.87). No difference in treatment-related adverse events was identified. CONCLUSIONS: This meta-analysis suggests that topical difamilast is an effective and safe treatment for mild-to-moderate AD.

Oral Janus kinase inhibitors for treating hospitalized patients with COVID-19: An updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study investigated the clinical efficacy and safety of oral Janus kinase inhibitors (JAKis) in the treatment of hospitalized patients with COVID-19. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before January 29, 2022. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of oral JAKis in patients with COVID-19 were included. RESULTS: In the pooled analysis of the 7 RCTs, the all-cause 28-day mortality rate in the study group receiving JAKis was significantly lower than that in the control group (9.4% [183/1941] vs. 10.9% [184/1687], risk ratio [RR] = 0.69, 95% confidence interval [CI], 0.58-0.81, I2 = 0%). In addition, the risk of 14-day mortality was in the study group was lower than that in the control group (RR = 0.65, 95% CI, 0.46-0.92, I2 = 0%). Finally, the study group and the control group exhibited similar risks of any adverse events (RR = 0.96, 95% CI, 0.89-1.04, I2 = 0%). CONCLUSIONS: Oral JAKis can significantly reduce the risk of death among patients with COVID-19. In addition, JAKis are tolerable for hospitalized patients with COVID-19.

Clinical efficacy of sofosbuvir/daclatasvir in patients with COVID-19: a systematic review and meta-analysis of randomized trials.

BACKGROUND: This study investigated the clinical efficacy sofosbuvir/daclatasvir (SOF-DCV) in patients with COVID-19. RESEARCH DESIGN AND METHODS: PubMed, Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before January 6, 2022. Only randomized controlled trials (RCTs) comparing the clinical efficacy of SOF-DCV (study group) with alternative treatments (control group) in patients with COVID-19 were included. RESULTS: A total of 9 RCTs were included. The all-cause mortality rate in the study group was 10.7% (96/898), which was lower than that in the control group (12.3%, 108/871). However, this difference was not statistically significant (odds ratio [OR] = 0.83; 95% CI, 0.62-1.12; I2 = 49%). The overall clinical recovery rate was significantly higher in the study group than in the control group (OR = 2.34; 95% CI, 1.47-3.72; I2 = 20%). Furthermore, the average length of hospital stay was shorter in the study group than in the control group (mean deviation = -1.84; 95% CI, -3.42 to -0.26, I2 = 68%). CONCLUSIONS: Although SOF-DCV did not confer a survival benefit in patients with COVID-19, it may increase a patient's odds of clinical recovery, and shorten the length of their hospital stay.

The clinical efficacy and safety of mesenchymal stromal cells for patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This meta-analysis of randomized controlled trials (RCTs) investigated the usefulness of mesenchymal stromal cells (MSCs) to treat patients with COVID-19. METHODS: PubMed, Embase, Ovid MEDLINE, the Cochrane Library, and Clinicaltrials.gov were searched for RCTs published before November 7, 2021. Only RCTs that compared the clinical efficacy and safety of MSCs with other alternative treatments or placebos in the treatment of patients with COVID-19 were included. RESULTS: Six RCTs were included, in which the MSC and control groups consisted of 158 and 135 patients, respectively. The patients who received MSCs had a significantly lower 28-day mortality rate (7.6% vs 21.5%; OR, 0.18; 95% CI, 0.06-0.52; I2 = 0%) and significantly higher clinical improvement rate (OR, 6.05; 95% CI, 2.31-15.83; I2 = 0%) than the controls. The patients who received MSCs were associated with a similar risk of adverse events (AEs) and serious AEs to the control group (AEs: OR, 33; 95% CI, 0.09-1.18; I2 = 59%; serious AEs: OR, 0.30; 95% CI, 0.02-4.41; I2 = 53%). CONCLUSIONS: MSC treatment may help to improve the clinical outcomes of patients with COVID-19. In addition, MSC treatment appears to be a safe therapeutic option for patients with COVID-19.