Outcomes of rapid digital transformation of large-scale communications during the COVID-19 pandemic.

Objective This study examined the content and impact of a new digital communication medium, called a VIDCAST, implemented at a large hospital and health service when the COVID-19 pandemic was announced, and the key concerns held by staff at the time when the health service was preparing for the COVID-19 pandemic to arrive in this health service. Methods A mixed-methods approach was used. Thematic analysis of 20 transcripts of daily VIDCASTS broadcast between 30 March and 24 April 2020 was undertaken, in addition to descriptive analysis of feedback from an anonymous online survey. Results Survey feedback from 322 staff indicated almost universal satisfaction with this new communication method. The VIDCASTS provided a new COVID-safe method for the Executive to connect to staff at a time of uncertainty. Thematic analysis of the content of the VIDCASTS revealed three themes: 'Accurate Information', 'Reassurance and Support' and 'Innovation'. The Executive was able to reassure staff about what the organisation was doing to safeguard the health and wellbeing of all, and enabled an effective response to the pandemic. Conclusions The digital communication channel of VIDCASTS, rapidly operationalised at a major Australian hospital and health service in March 2020, provided important information and support for staff as it prepared for the anticipated COVID-19 surge. What is known about the topic? When the COVID-19 pandemic began, traditional face-to-face staff meetings were disrupted and many hospitals and their staff were left scrambling for information, and for reassurance about their safety, as they prepared to receive increasing numbers of COVID-19 patients. What does this paper add? The implementation of a digital communication tool was able to address many of the concerns raised by hospital staff in other geographic locations dealing with surging COVID-19 cases and underpinned a globally leading COVID-19 response. What are the implications for practitioners? New digitised communication methods provided an effective vehicle to inform and support staff in the early stages of pandemic preparation.

Bronchoscopic sclerotherapy combined with thoracoscopic drainage for postpneumonectomy bronchial fistula and empyema.

A postpneumonectomy bronchial fistula is a very morbid complication that often requires major surgical procedures for treatment. Since patients with postpneumonectomy bronchial fistula and empyema are physiologically compromised, corrective surgical interventions pose considerable risk. We report a case of a postpneumonectomy fistula with an associated empyema. Our patient's empyema was treated with thoracoscopic debridement and antibiotic instillation (modification of the Clagett procedure). Bronchoscopic and thoracoscopic treatment strategies that are appropriate for selected patients with postpneumonectomy bronchial fistula and empyema are discussed.

Detection of osteomyelitis in the neuropathic foot: nuclear medicine, MRI and conventional radiography.

The diagnostic efficacy of (1) combined three-phase bone scintigraphy and In-111 labeled WBC scintigraphy (Bone/WBC), (2) MRI, and (3) conventional radiography in detecting osteomyelitis of the neuropathic foot was compared. Conventional radiography was comparable to MRI for detection of osteomyelitis. MRI best depicted the presence of osteomyelitis in the forefoot. Particularly in the setting of Charcot joints, Bone/WBC was more specific than conventional radiography or MRI.

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

PURPOSE: Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS: This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS: Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION: The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

Granulocyte-macrophage colony-stimulating factor as infection prophylaxis in high-risk oncologic surgery.

BACKGROUND: A method of augmenting host defenses against bacterial pathogens could result in a decrease in postoperative infections. Given its effects on leukocyte proliferation and function, it is possible that prophylactic granulocyte-macrophage colony-stimulating factor (GM-CSF) could reduce the incidence and severity of infections in high-risk surgical patients. The current study was undertaken to determine the safety and hematologic effects of perioperative GM-CSF. METHODS: Cancer patients undergoing operations with a high risk of postoperative infection were treated perioperatively for 10 days with subcutaneous GM-CSF. Cohorts were treated with GM-CSF at 125 micrograms/m2/day (12 patients) and 250 micrograms/m2/day (11 patients). RESULTS: There were no severe or life-threatening toxicities associated with GM-CSF. Mean maximum neutrophil counts during the first 5 postoperative days were 16.3 +/- 9.14 and 24.5 +/- 7.60 at 125 and 250 micrograms/m2, respectively (P = 0.04). Only one wound infection was diagnosed during this study. CONCLUSIONS: GM-CSF may be safely administered perioperatively at doses that augment neutrophil number and function. An ongoing randomized clinical trial will determine the impact of GM-CSF on postoperative infection.

Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity.

Ten adult patients with human immunodeficiency virus (HIV)-associated malignancies (five with lymphoma and five with Kaposi's Sarcoma) were treated with a daily subcutaneous injection of interleukin-2 (IL-2) for 90 consecutive days in a phase I dose-escalation study. Seven patients had absolute CD4 counts below 200/mm3 at the time malignancy was diagnosed. Each lymphoma patient had obtained a complete or partial remission with standard chemotherapy before initiating IL-2. The daily dose of IL-2 did not change during the 90-day course of therapy. Seventeen courses of IL-2 therapy were completed at doses ranging from 0.4 x 10(6) U/m2/d to 1.2 x 10(6) U/m2/d without significant (grade III) toxicity. Two of two patients experienced grade III toxicity within 21 days of initiating IL-2 at a dose of 1.4 x 10(6) U/m2/d, but both patients subsequently completed 90 days of therapy at the maximum tolerated dose (MTD) of 1.2 x 10(6) U/m2/d. Although there were no significant increases or decreases in T-cell subsets at any dose level, there was an increase in absolute natural killer (NK) cell number at the three highest doses of IL-2 (mean percent increase 247; 95% confidence interval, 124 to 369) that was statistically significant (Wilcoxon one-sample signed rank test, P = .015). One patient developed an anti-IL-2 antibody titer that correlated with minimal NK cell expansion in vitro and in vivo. An increase in eosinophils was noted during 9 of 17 courses of IL-2 therapy without correlation to IL-2 dose, prior course of IL-2, or NK cell expansion. At the MTD, there was no consistent increase in the plasma HIV RNA level over time. Three of 10 patients had progressive disease while on study. During 50 months of IL-2 therapy, no patient was treated for an opportunistic infection. We conclude that daily low dose subcutaneous IL-2 can be self-administered safely with good compliance for prolonged periods of time to patients with HIV-associated malignancies, including those with profound immune deficiency. The majority of patients show selective expansion of innate immune effectors, ie, NK cells and/or eosinophils, in the absence of significant clinical toxicity or increased viral burden. These results suggest that low-dose IL-2 therapy should be studied further in phase II clinical trials for evidence of activity against malignancy and opportunistic infection in this patient population.

Herpes simplex viral pneumonia in the postthoracotomy patient.

Over a 6-month period, 6 of 54 postthoracotomy patients developed pneumonia and respiratory failure. Pneumonia was secondary to herpes simplex virus type 1 in 3 of the 6 patients. Diagnostic efforts including bronchoscopy with bronchial washing, viral cultures, and cytologic examination permitted early diagnosis and successful treatment with acyclovir. A high index of suspicion for herpes simplex pneumonia must be maintained in critically ill patients with undiagnosed pneumonia.

Organic anion transport in macrophage membrane vesicles.

Cells of the J774 mouse macrophage-like cell line possess organic anion transporter that transport fluorescent dyes such as Lucifer Yellow out of the cytoplasmic matrix of the cells; the dye is both sequestered in endosomes and secreted into the extracellular medium. Lucifer Yellow that is sequestered within endosomes is subsequently delivered to the lysosomal compartment. In the present studies we demonstrated that probenecid inhibited removal of Lucifer Yellow from the soluble cytoplasm and sequestration into membrane bound organelles by quantitating Lucifer Yellow fluorescence in both soluble and membrane-associated fractions of J774 cells. In addition, we examined the uptake of Lucifer Yellow into isolated subcellular organelles derived from J774 cells. Lucifer Yellow transport in the organellar fraction of J774 cell homogenates was temperature- and pH-dependent and did not require ATP. Subcellular organelles from J774 cells were fractionated into endosome- and lysosome-enriched fractions by Percoll density gradient centrifugation. Lucifer Yellow was preferentially taken up by vesicles of the endosome-enriched fraction, and this transport was inhibited by probenecid. These studies provide direct evidence that probenecid inhibits Lucifer Yellow transport out of the cytoplasmic matrix and into cytoplasmic vacuoles in J774 cells and that organic anion transport in isolated organelles derived from J774 cells occurs preferentially in endosome, rather than in lysosome-enriched fractions; they suggest that Lucifer Yellow is carried across membranes via a secondary active transport process that requires proton symptom or hydroxyl anion antiport.

Imipenem: a new carbapenem antibiotic.

Imipenem is a new carbapenem antibiotic that has an extremely broad spectrum of antibacterial activity. It has been used to treat a variety of serious infections and an increasing volume of literature documents its value in infections due to multiresistant bacteria. This article reviews the antibacterial activity, pharmacology, and clinical uses of imipenem.

Effect of lumbar puncture on flow of cerebrospinal fluid.

The rate at which isotopes descend from the cisterna magna to the lumbar subarachnoid space is highly variable. In monkeys, with and without previous lumbar puncture, transit time was measured. In animals with a previous lumbar puncture, transit times were 10 to 120 minutes; in monkeys without a previous lumbar puncture, transit times were 120 to 180 minutes. In experimental studies of cerebrospinal fluid circulation, the effect of lumbar puncture must be controlled.

Diminished cerebrospinal fluid beta-endorphin concentration in monkeys with arachnoiditis.

Altered concentrations of brain beta endorphin and spinal cord encephalin have been reported in mice with iatrogenic arachnoiditis. We measured beta-endorphin concentration in cerebrospinal fluid (CSF) in normal monkeys and in monkeys with various degrees of arachnoiditis resulting from myelography and spinal surgery and found a significant negative correlation between the arachnoiditis score and the lumbar CSF beta-endorphin concentration. This study suggests that an assay of CSF beta endorphin can be used to detect the alterations in neurotransmitters in arachnoiditis.

Increased neutrophil elastase activity in cigarette smokers.

We compared plasma levels of the neutrophil elastase-derived fibrinopeptide A-alpha-1-21 in healthy cigarette smokers with those in nonsmokers. The mean A-alpha-1-21 concentration was fivefold higher (95% confidence interval [CI], 3.0 to 9.6) in ten cigarette smokers than in 20 healthy nonsmokers (2.0 nmol/L compared with 0.4 nmol/L; p less than 0.0001). To evaluate the acute effect of smoking on enzyme activity, a second group of ten smokers was studied. After refraining from smoking for 12 hours, each person smoked three cigarettes. The mean A-alpha-1-21 level in the second group of smokers was not different from that in the first group of smokers (1.8 nmol/L compared with 2.0 nmol/L) but was fivefold higher (95% CI, 2.6 to 8.7) than that in the nonsmokers (1.8 nmol/L compared with 0.4 nmol/L; p less than 0.0001). After smoking three cigarettes, subjects had a twofold elevation (95% CI, 1.6 to 3.5) in the mean A-alpha-1-21 concentration (from 1.8 nmol/L to 4.1 nmol/L; p = 0.002). Our data show that cigarette smoking perturbs the in-vivo elastase-antielastase balance and thus may produce lung disease through this mechanism.

Effect of arachnoiditis on pain threshold.

A model for studying the relationship between chronic arachnoiditis and pain sensitivity was developed. Thirty male ICR mice were randomly divided into three groups and the tail-flick test was done using an EMDIE-TF6 apparatus (Emdie Instrument Co., Montpelier, VA). Ten mice were injected intrathecally with 5.0 microL of a kaolin-metrizamide mixture and ten control mice were injected intrathecally with 5.0 microL of an electrolyte solution resembling CSF. A third group, (naive controls) were given no treatment. Six weeks later tail-flick tests were repeated. The kaolin-treated mice had significantly decreased tail-flick latencies (P less than .05) compared with the baseline; the controls had no significant change in tail-flick latency. Histologic examination revealed moderate to severe arachnoiditis in the kaolin-treated animals and no evidence of arachnoid abnormalities in the controls. This study suggests that arachnoiditis may be associated with decreased pain thresholds.

Brain beta-endorphin and spinal-cord enkephalin concentrations in experimental arachnoiditis.

Arachnoiditis was produced experimentally in male albino ICR mice by intrathecal injection of meglumine iocarmate . A control group received intrathecal injection of an electrolyte solution resembling CSF. Eight weeks after injection, the brains and spinal cords were removed for brain beta-endorphin and spinal cord met-enkephalin measurement by radioimmunoassay, and the dural sacs were removed for histologic examination to confirm the presence or absence of arachnoiditis. Brain beta-endorphin content was significantly reduced and spinal-cord enkephalin concentration was significantly elevated in iocarmate-treated animals. The dura and arachnoid in the treated mice were thickened and infiltrated with lymphocytes. These studies indicate that arachnoiditis alters endogenous polypeptide concentrations.

Cumulative effects of quinidine and aspirin on bleeding time and platelet alpha 2-adrenoceptors: potential mechanism of bleeding diathesis in patients receiving this combination.

We observed quinidine-induced prolongation of bleeding time without thrombocytopenia in three subjects. In addition, we noticed a cumulative prolongation of bleeding time by a combination of quinidine and aspirin. We postulated that because both quinidine and aspirin inhibit epinephrine-induced platelet aggregation, a cumulative effect of the two drugs might be responsible for the hemostatic defect. In studies using normal human platelets, we confirmed a marked reduction in epinephrine-induced platelet aggregation by the combination of these two agents. To further study the potential mechanism of this cumulative effect, platelet lysates were incubated with the alpha 2-adrenoceptor antagonist tritiated yohimbine in the presence of quinidine and aspirin. On the basis of the radioligand binding data, the dissociation constant (KD) of alpha 2-adrenoceptors was observed to increase in the presence of quinidine as well as aspirin. The combination of these two agents caused a marked increase in the KD of platelet alpha 2-adrenoceptors without alteration in the number of receptor sites. These data suggest that the cumulative effects of quinidine and aspirin on platelet alpha 2-adrenoceptor KD may relate to the significant reduction in epinephrine-induced platelet aggregation. This phenomenon, coupled with other well-known effects of aspirin on the platelet release reaction and arachidonate metabolism, may lead to bleeding problems in some patients receiving this combination.

Creatine kinase brain isoenzyme: relationship of cerebrospinal fluid concentration to the neurologic condition of newborns and cellular localization in the human brain.

Immunocytochemical study of human brain showed creatine kinase brain isoenzyme (CKBB) present in both neurons and astrocytes. Because creatine kinase brain isoenzyme is an intracellular enzyme that might be released with brain injury, its concentration in the CSF of newborns was measured using a radioimmunoassay. Infants who suffered a documented neurologic insult (a cerebroventricular hemorrhage or a CNS infection) were found to have a greater mean CSF creatine kinase brain isoenzyme concentration than those without a history of neurologic insult. Infants with a high concentration had a poor short-term outcome (death or neurologic abnormality when discharged) more frequently than did those with a lower concentration. Infants with a grade 3 or 4 cerebroventricular hemorrhage had a higher mean concentration than did those with a grade 1 or 2 hemorrhage. These data are consistent with the hypothesis that CSF creatine kinase brain isoenzyme is a metabolic indicator of brain damage in newborns.

Arachnoiditis from myelography and laminectomy in experimental animals.

Clinical reports have suggested that myelography and laminectomy may produce more arachnoiditis than myelography alone. The effect of experimental lumbar myelography and laminectomy on arachnoiditis in monkeys was studied. Arachnoiditis was as severe after myelography alone as after myelography and laminectomy. Minimal arachnoiditis was found myelographically and histologically after myelography with metrizamide 300 mg l/ml, and severe arachnoiditis was found after myelography with iophendylate whether or not laminectomy was performed. Laminectomy alone produced insignificant arachnoid changes. Experimental myelography preceding laminectomy did not increase the risk of arachnoiditis.