Persistent BHR and its deleterious influence on lung function suggest a role for airway inflammation in perpetuation of WTC-associated airway disease. In future massive occupational exposure to inorganic dust/gases, we recommend early and serial pulmonary function testing, including measurements of bronchial reactivity, when possible, and inhaled corticosteroid therapy for those with symptoms or pulmonary function tests consistent with airway disease.

Highlights Compared to those treated with subcutaneous therapy, patients with COVID-19 treated intravenous tocilizumab has improved measurements in respiratory parameters seven days following therapy. Patients that received intravenous therapy were more likely to survive hospitalization. Laboratory markers of inflammation did not predict clinical response to tocilizumab therapy.

INTRODUCTIONRegional anaesthesia is a safe, inexpensive technique, widely used for lower limb orthopaedic surgery due to the advantage of prolonged post-operative pain relief. Combination with adjuncts [1][2][3][4][5] like epinephrine, clonidine, neostigmine, opioids, midazolam and magnesium [6][7][8][9][10][11][12][13][14][15][16][17][18][19] have been used to prolong analgesia and reduce the incidence of adverse events. These spinal adjuvants allow the use of lower dose of local anaesthetic agents, prolong and intensify the subarachnoid block and offer hemodynamic stability. Opioids such as fentanyl are commonly used as additive to local anaesthetics to prolong the duration and intensify the effects of subarachnoid block. However significant side effects of opioids such as pruritis, urinary retention, respiratory depression, hemodynamic instability and occasionally severe nausea and vomiting may limit their use. Newer methods of prolonging the duration of subarachnoid block and reducing post-operative analgesic requirements are of special interest in major surgical procedures.One of the mechanisms implicated in the persistence of postoperative pain is central sensitization, which is an activity-dependent increase in the excitability of spinal neurons . Central sensitization has been shown to depend on the activation of dorsal hornNmethyl-D aspartate (NMDA) receptors by excitatory amino acid transmitters such as aspartate and glutamate. NMDA receptor antagonists prevent central sensitization induced by peripheral nociceptive stimuli by blocking dorsal horn NMDA receptor activation. Magnesium (Mg 2+) is a non-competitive N-methyl-Daspartate (NMDA) receptor antagonist that blocks ion channels in a voltage dependent fashion. Koining reported that intravenous magnesium administration led to significant reduction in fentanyl consumption in peri and post-operative periods. Studies have evaluated use of magnesium intrathecally and shown to prolong the action of subarachnoid anaesthesia [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. However, most of these studies used an opioid along with magnesium, which could have contributed to the prolongation of blockade after subarachnoid block [6-13], Magnesium alone with LA in a dose of 50 mg and maximum upto 100 mg has been used in a few studies [14][15][16][17][18][19]. Although the results of adding MgSO 4 50 mg to IT bupivacaine are conflicting, the effect of increasing the dose of additional MgSO 4 has not been fully investigated. We used a dose of about 0.7mg/ kg (50 mg) to ≤ 1mg/kg (75 mg) of intrathecal magnesium and found similar results. The primary outcome was the duration of spinal anaesthesia, beginning of sensory and motor block, time to maximal sensory block, and duration of sensory and motor block. The secondary outcomes included hemodynamic variations and post-operative analgesic requirements . MATeRIAlS AND MeThODSWe conducted a randomized double blind study on 90 patients of either sex, belonging to ASA physical status I and II scheduled for orthopaedi...

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Septic cardiomyopathy and mortalityBackground: Patients with sepsis are at risk for developing sepsis-induced cardiomyopathy (SIC).Previous studies offer inconsistent results regarding the association of SIC and mortality. This study sought to assess whether SIC is linked to mortality in patients with sepsis and to evaluate predictors of the development of SIC.Methods: In this retrospective study, patients admitted to the medical intensive care unit with a diagnosis of sepsis in the absence of acute coronary syndrome were included. SIC was identified using transthoracic echocardiogram and was defined by a new-onset decline in left ventricular ejection fraction (LVEF) of up to 50% or a decline of at least 10% in LVEF relative to baseline in patients with a history of heart failure with reduced EF. Multivariable logistic regression analysis was performed using the R software program (R Foundation for Statistical Computing). Results: Of the 359 patients in the final analysis, 19 (5.3%) had SIC, and eight (42.1%) of these 19 patients and 60 (17.6%) of the 340 patients in the non-SIC group died. SIC was associated with an increased risk for all-cause in-hospital mortality (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.15-18.69; P=0.03). Independent predictors for the development of SIC were albumin level (OR, 0.47; 95% CI, 0.23-0.93; P=0.03) and culture positivity (OR, 8.47; 95% CI, 2.24-55.61; P=0.006). Concomitant right ventricular hypokinesis was noted in 13 (68.4%) of the 19 SIC patients.Conclusions: SIC was associated with an increased risk for all-cause in-hospital mortality. Low albumin level and culture positivity were independent predictors of SIC.

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The objective of the current study was to assess the possible pharmacokinetic interactions of spirulina with glitazones in an insulin resistance rat model. Wistar male albino rats were equally divided into five groups: insulin resistant rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500 mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg), and insulin resistant rats+spirulina (500 mg/kg). Described doses of pioglitazone, rosiglitazone, or spirulina were per orally administered and the plasma drug concentrations were determined. The pharmacokinetic parameters such as Tmax, Cmax, AUC(0-α), t1/2, and Kel were determined by plotting the drug concentration as a function of time. The data observed in this acute study indicated that there was no statistically significant difference in any of the pharmacokinetic parameters (Tmax, Cmax, AUC(0-α), t1/2, and Kel) of glitazones (pioglitazone, rosiglitazone) or spirulina, when they were coadministered. Given the promising results, this study concludes that the coadministration of spirulina does not influence the pharmacokinetics of glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are recommended to assess the real time effect.

Objectives Cefiderocol maintains activity against most MDR Gram-negative pathogens including Pseudomonas aeruginosa. In laboratory-derived isolates, down-regulation of TonB-dependent siderophore receptors have been implicated in resistance to cefiderocol. Methods In this report, the expression of seven TonB-dependent siderophore receptors was examined in 10 clinical isolates with cefiderocol MICs ranging from ≤0.03–8 mg/L. In addition, genetic sequences of the siderophore receptors were analysed to identify potentially disruptive mutations. Results There was no clear association between expression of the receptors with cefiderocol susceptibility, including the receptors piuA/piuD and pirA previously implicated in cefiderocol uptake. In addition, there were no disabling mutations identified in the receptors. Acquired β-lactamase activity also could not explain the range in cefiderocol susceptibility. Conclusions The aetiology of reduced susceptibility to cefiderocol in clinical isolates of P. aeruginosa remains an enigma and worthy of further investigation.