Efficacy of melatonin in the treatment of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

This study investigated the effect of melatonin on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). We searched PubMed, the Web of Science, the Cochrane Library, Ovid MEDLINE, and Clinicaltrials.gov for randomized controlled trials (RCTs) published before September 11, 2021. Only RCTs that compared the clinical efficacy of melatonin with a placebo in the treatment of patients with COVID-19 were included. The primary outcome measure was the clinical recovery rate. We included three RCTs in this meta-analysis. Melatonin 3 mg three times daily was administered in one RCT, and 3 or 6 mg daily before bedtime in the other two trials. Treatment duration was 14 days in two RCTs and 7 days in one trial. The clinical recovery rates were 94.2% (81/86) and 82.4% (70/85) in the melatonin and control groups, respectively. Overall, patients receiving melatonin had a higher clinical recovery rate than did the controls (odds ratio [OR]: 3.67; 95% CI: 1.21-11.12; I2 = 0%, p = 0.02). The risk of intensive care unit admission was numerically lower in the melatonin group than in the control group (8.3% [6/72] vs. 17.6% [12/68], OR: 0.45; 95% CI: 0.16-1.25; I2 = 0%, p = 0.13), and the risk of mortality was numerically lower in the melatonin group than in the control group (1.4% [1/72] vs. 4.4% [3/68], OR: 0.32; 95% CI: 0.03-3.18; I2 = 0%, p = 0.33). In conclusion, melatonin may help improve the clinical outcomes of patients with COVID-19.

The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

BACKGROUND: The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. METHODS: We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). RESULTS: Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI - 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI - 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). CONCLUSIONS: In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.

Selective brain cooling achieves peripheral organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.

Background: Although whole-body cooling has been reported to improve the ischemic/reperfusion injury in hemorrhagic shock (HS) resuscitation, it is limited by its adverse reactions following therapeutic hypothermia. HS affects the experimental and clinical bowel disorders via activation of the brain-gut axis. It is unknown whether selective brain cooling achieves beneficial effects in HS resuscitation via preserving the integrity of the brain-gut axis. Methods: Male Sprague-Dawley rats were bled to hypovolemic HS and resuscitated with blood transfusion followed by retrograde jugular vein flush (RJVF) with 4 °C or 36 °C normal saline. The mean arterial blood pressure, cerebral blood flow, and brain and core temperature were measured. The integrity of intestinal tight junction proteins and permeability, blood pro-inflammatory cytokines, and multiple organs damage score were determined. Results: Following blood transfusion resuscitation, HS rats displayed gut barrier disruption, increased blood levels of pro-inflammatory cytokines, and peripheral vital organ injuries. Intrajugular-based infusion cooled the brain robustly with a minimal effect on body temperature. This brain cooling significantly reduced the HS resuscitation-induced gut disruption, systemic inflammation, and peripheral vital organ injuries in rats. Conclusion: Resuscitation with selective brain cooling achieves peripheral vital organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.

Multicenter Study of Azole-Resistant Aspergillus fumigatus Clinical Isolates, Taiwan1.

In a multicenter study, we determined a prevalence rate of 4% for azole-resistant Aspergillus fumigatus in Taiwan. Resistance emerged mainly from the environment (TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A mutations) but occasionally during azole treatment. A high mortality rate observed for azole-resistant aspergillosis necessitates diagnostic stewardship in healthcare and antifungal stewardship in the environment.

Therapeutic Hypothermia Protects Against Heat Stroke-Induced Arterial Hypotension via Promoting Left Ventricular Performance in Rats.

We aimed to ascertain whether therapeutic hypothermia (TH) acts as cardioprotective management for heat stroke (HS). Adult male rats under general anesthesia were exposed to whole-body heating (43°C for 70 min) to induce HS. Rats with HS displayed hyperthermia (core body temperature 42°C vs. 36°C); hypotension (30 mmHg vs. 90 mmHg mean arterial blood pressure); suppressed left ventricular (LV) performance (stroke volume 52 µl/min vs. 125 µl/min), ejection fraction (0.29% vs. 0.69%), relaxation factor (72 ms vs. 12 ms), and arterial elastance (0.31 mmHg/ µl vs. 10 mmHg/ µl); increased myocardial injury markers (e.g., creatine kinase-MB: 86 U/L vs. 24 U/L, cardiac troponin I: 3.08 ng/ml vs. 0.57 ng/ml); increased myocardial oxidative stress markers (e.g., malondialdehyde: 6.52 nmol/mg vs. 1.06 nmol/mg, thiobarbituric acid-reactive substances: 29 nmol/g vs. 2 nmol/g); decreased myocardial antioxidants (e.g., superoxide dismutase: 6 unit/mg vs. 17 unit/mg, reduced glutathione: 0.64 nmol/mg vs. 2.53 nmol/mg); increased myocardial proinflammatory cytokines (e.g., tumor necrosis factor-α 3200 pg/ml vs. 1000 pg/ml, interleukin-6: 668 pg/ml vs. 102 pg/ml); and increased cardiac damage scores (2.2 vs. 0.3). TH therapy significantly reversed the following conditions: HS-induced hyperthermia (37.5°C core body temperature), hypotension (71 mmHg), suppressed LV performance (stroke volume: 97 µl/min, ejection fraction: 0.65%, relaxation factor: 39 ms, and arterial elastance: 0.99 mmHg/µl), increased myocardial injury markers (e.g., creatine kinase-MB: 37 U/L, cardiac troponin I: 1.06 ng/ml), increased myocardial oxidative stress markers (e.g., malondialdehyde: 2.68 nmol/mg, thiobarbituric acid-reactive substances: 12.3 nmol/g), decreased myocardial antioxidants (e.g., superoxide dismutase: 13.3 unit/mg, reduced glutathione: 2.71 mmol/mg), increased myocardial proinflammatory cytokines (e.g., tumor necrosis factor-α 1500 pg/ml, interleukin-6: 108 ng/ml); and increased cardiac damage scores (0.9). We thus conclude that TH protects against HS-induced arterial hypotension by promoting LV performance in rats. These results add to the literature regarding the use of TH as cardioprotective management for HS.

Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia.

Background: Hypoxia-inducible factor-1α (HIF-1α), heat shock protein-72 (HSP-72), hemeoxygenase-1 (HO-1), and matrix metalloproteinase-9 (MMP-9) have been identified as potential therapeutic targets in the brain for cerebral ischemia. To elucidate their underlying mechanisms, we first aimed to ascertain whether these proteins participate in the pathogenesis of heat-induced ischemic damage to the hypothalamus of rats. Second, we investigated whether hypobaric hypoxia preconditioning (HHP) attenuates heat-induced hypothalamic ischemic/hypoxic injury by modulating these proteins in situ. Methods: Anesthetized rats treated with or without HHP were subjected to heat stress. Hypothalamic ischemic/hypoxic damage was evaluated by measuring hypothalamic levels of cerebral blood flow (CBF), partial oxygen pressure (PO2), and hypothalamic temperature via an implanted probe. Hypothalamic apoptotic neurons were counted by measuring the number of NeuN/caspase-3/DAPI triple-stained cells. Hypothalamic protein expression of HIF-1α, HSP-72, HO-1, and MMP-9 was determined biochemically. Results: Before the start of the thermal experiments, rats were subjected to 5 hours of HHP (0.66 ATA or 18.3% O2) daily for 5 consecutive days per week for 2 weeks, which led to significant loss of body weight, reduced brown adipose tissue (BAT) wet weight and decreased body temperature. The animals were then subjected to thermal studies. Twenty minutes after heat stress, heat-exposed rats not treated with HHP displayed significantly higher core and hypothalamic temperatures, hypothalamic MMP-9 levels, and numbers of hypothalamic apoptotic neurons but significantly lower mean blood pressure, hypothalamic blood flow, and PO2 values than control rats not exposed to heat. In heat-exposed rats, HHP significantly increased the hypothalamic levels of HIF-1α, HSP-72, and HO-1 but significantly alleviated body and hypothalamic hyperthermia, hypotension, hypothalamic ischemia, hypoxia, neuronal apoptosis and degeneration. Conclusions: HHP may protect against hypothalamic ischemic/hypoxic injury and overexpression of MMP-9 by upregulating the hypothalamic expression of HIF-1α, HSP-72, and HO-1 in rats subjected to heatstroke.

The Impact of High-Flow Nasal Cannula on the Outcome of Immunocompromised Patients with Acute Respiratory Failure: A Systematic Review and Meta-Analysis.

Background and objectives: High-flow nasal cannula (HFNC) can be used as a respiratory support strategy for patients with acute respiratory failure (ARF). However, no clear evidence exists to support or oppose HFNC use in immunocompromised patients. Thus, this meta-analysis aims to assess the effects of HFNC, compared to conventional oxygen therapy (COT) and noninvasive ventilation (NIV), on the outcomes in immunocompromised patients with ARF. The Pubmed, Embase and Cochrane databases were searched up to November 2018. Materials and Methods: Only clinical studies comparing the effect of HFNC with COT or NIV for immunocompromised patients with ARF were included. The outcome included the rate of intubation, mortality and length of stay (LOS). Results: A total of eight studies involving 1433 immunocompromised patients with ARF were enrolled. The pooled analysis showed that HFNC was significantly associated with a reduced intubation rate (risk ratio (RR), 0.83; 95% confidence interval (CI), 0.74-0.94, I2 = 0%). Among subgroup analysis, HFNC was associated with a lower intubation rate than COT (RR, 0.86; 95% CI, 0.75-0.95, I2 = 0%) and NIV (RR, 0.59; 95% CI, 0.40-0.86, I2 = 0%), respectively. However, there was no significant difference between HFNC and control groups in terms of 28-day mortality (RR, 0.78; 95% CI, 0.58-1.04, I2 = 48%), and intensive care unit (ICU) mortality (RR, 0.87; 95% CI, 0.73-1.05, I2 = 57%). The ICU and hospital LOS were similar between HFNC and control groups (ICU LOS: mean difference, 0.49 days; 95% CI, -0.25-1.23, I2 = 69%; hospital LOS: mean difference, -0.12 days; 95% CI, -1.86-1.61, I2 = 64%). Conclusions: Use of HFNC may decrease the intubation rate in immunocompromised patients with ARF compared with the control group, including COT and NIV. However, HFNC could not provide additional survival benefit or shorten the LOS. Further large, randomized controlled trials are needed to confirm these findings.

Early Mobilization Reduces Duration of Mechanical Ventilation and Intensive Care Unit Stay in Patients With Acute Respiratory Failure.

OBJECTIVE: To evaluate the effects of a quality improvement program to introduce early mobilization on the outcomes of patients with mechanical ventilation (MV) in the intensive care unit (ICU). DESIGN: A retrospective observational study. SETTING: Nineteen-bed ICU at a medical center. PARTICIPANTS: Adults patients with MV (N=153) admitted to a medical ICU. INTERVENTIONS: A multidisciplinary team (critical care nurse, nursing assistant, respiratory therapist, physical therapist, patient's family) initiated the protocol within 72 hours of MV when patients become hemodynamically stable. We did early mobilization twice daily, 5d/wk during family visits (30min each time), and cooperated with family, if possible. MAIN OUTCOME MEASURES: MV duration, rate of successful weaning, and length of ICU and hospital stay. RESULTS: We enrolled 63 patients in the before protocol group and 90 in the after protocol group. The 2 groups were well matched in age, sex, body height, body weight, body mass index, disease severity, cause of intubation, number of comorbidities, and most underlying diseases. After protocol group patients had shorter MV durations (4.7d vs 7.5d; P<.001) and ICU stays (6.9d vs 9.9d; P=.001) than did before protocol group patients. Early mobilization was negatively associated with the duration of MV (ß=-.269; P<.002; 95% confidence interval [CI], -4.767 to -1.072), and the risk of MV for ≥7 days was lower in patients who underwent early mobilization (odds ratio, .082; 95% CI, .021-.311). CONCLUSIONS: The introduction of early mobilization for patients with MV in the ICU shortened MV durations and ICU stays. A multidisciplinary team that includes the patient's family can work together to improve the patient's clinical outcomes.

Traumatic Thoracic Burst Fracture Associated with Bronchial Rupture.

BACKGROUND: Rupture of, or injury to, the tracheobronchial tree is a rare occurrence in blunt chest trauma. CASE REPORT: We present a case of bronchial rupture caused by fragmented bone from a spinal burst fracture after blunt chest trauma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although tracheobronchial injury is infrequent, clinicians should be aware of this possible complication after blunt chest trauma. Bronchoscopy can help in the diagnosis.

Proteomic analysis of hypothalamic injury in heatstroke rats.

Ischemic and oxidative damage to the hypothalamus may be associated with decreased heat tolerance as well as heatstroke formation. The present study explores the hypothalamic proteome mechanisms associated with heatstroke-mediated hypothalamic ischemia, and oxidative damage. Heatstroke rats had hypotension, hypothalamic ischemia, and lethality. In addition, they had hyperthermia and hypothalamic blood-brain-barrier disruption, oxidative stress, activated inflammation, and neuronal apoptosis and degeneration. 2DE combined LC-MS/MS revealed that heatstroke-induced ischemic injury and apoptosis were associated with upregulation of L-lactate dehydrogenase but downregulation of both dihydropyriminase-related protein and 14-3-3 Zeta isoform protein. Heat-induced blood-brain-barrier disruption might be related to upregulation of glial fibrillary acidic protein. Oxidative stress caused by heatstroke might be related to upregulation of cytosolic dehydrogenase-1. Also, heat-induced overproduction of proinflammatory cytokines might be associated with downregulation of stathmin 1. Heat-induced hypothalamic ischemia, apoptosis, injury (or upregulation of L-lactate dehydrogenase), blood-brain-barrier disruption (or upregulation of glial fibrillary acidic protein), oxidative stress (or upregulation of cytosolic dehydrogenase-1), and activated inflammation (or downregulation of stathmin 1) were all significantly reversed by whole body cooling. Our data indicate that cooling therapy improves outcomes of heatstroke by modulating hypothalamic proteome mechanisms.

Appropriateness of Parenteral Nutrition Usage in Cancer Patients.

This study is to investigate the indication appropriateness of parenteral nutrition (PN) administration in cancer patients. Between December 2013 and August 2014, all cancer patients who received PN (including total PN and Kabiven) in a regional hospital of Southern Taiwan were included in this retrospective study. A total of 107 cancer patients received PN. Among them, colorectal cancer was the most common type of cancer (n = 45, 42.1%), followed by gastric cancer, head and neck cancer, and esophageal cancer. After evaluation of the appropriateness of PN administration, 88 (82.2%) PN episodes were considered appropriate and unavoidable, 4 (3.7%) as appropriate and avoidable but 15 (14.1%) as inappropriate. In conclusion, PN could be inappropriately used by some oncologic physicians. Physicians and nutrition support team specialists should carefully evaluate the indication of PN administration for cancer patients to obey the generally acknowledged usage rule.

Ceftolozane/tazobactam: Literature review of its activity on Taiwanese isolates before its launch in Taiwan (2012-2021).

Ceftolozane, a novel cephalosporin, combined with tazobactam, a known ß-lactamase inhibitor, shows robust antipseudomonal activity, although it doesn't cover carbapenemases. Our review of data from 2012 to 2021 in Taiwan highlights TOL/TAZ's in-vitro performance. TOL/TAZ is most effective against Pseudomonas aeruginosa (91.3-94.4 % susceptible, with an MIC <4 µg/mL). It also demonstrates good activity against Enterobacterales, including Escherichia coli (88-94.3 % susceptible), Klebsiella pneumoniae (72.6-84.1 % susceptible), Citrobacter koseri (93.3 % susceptible), Klebsiella oxytoca (98.1-100 % susceptible), and Proteus mirabilis (100 % susceptible). However, its efficacy varies among species typically associated with chromosomally-mediated AmpC production, such as Morganella morganii (100 % susceptible), Serratia marcescens (81.3-90.0 % susceptible), Enterobacter cloacae species complex (76.6-76.7 % susceptible), Klebsiella aerogenes (66.7-89.6% susceptible), and Citrobacter freundii (60.0 % susceptible). For carbapenem-nonsusceptible isolates, TOL/TAZ is less effective against K. pneumoniae and E. coli (susceptibility <10 %) but remains useful for P. aeruginosa (susceptibility 81.3-91.8 %). In conclusion, TOL/TAZ shows potent activity against P. aeruginosa and carbapenem-susceptible Enterobacterales in Taiwan.

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.