CLINICAL SIGNIFICANCE OF SERUM FERRITIN IN PATIENTS WITH SYSTEMIC SCLEROSIS

BackgroundThe main systemic sclerosis (SSc) manifestations are skin thickening, microangiopathy and ischemic changes in tissues, fibrotic damage to the lungs, heart, kidneys, and digestive system, arthritis, and myopathy. Acute phase reactants (APR) like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) reflect inflammation activity in various inflammatory conditions. Ferritin is a protein bound to iron;low serum ferritin indicates iron deficiency and/or anemia. Instead, high ferritin levels are associated with inflammatory and non-inflammatory conditions such as dermatomyositis, pulmonary fibrosis, lupus, systemic COVID-19, vasculitis, tissue damage, thromboembolic complications, and metastatic cancer. The possible role of ferritin in SSc as APR is unclear.ObjectivesWe aimed to assess whether ferritin levels can reflect the severity of SSc and predict the outcome.Methods241 files of SSc patients with information on serum ferritin level (ferritin over 300 mg/dL is considered elevated) who visited the Rambam Rheumatology Institute in the years 2004-2021were used for retrospective analysis. Patients' demographic, clinical, laboratory, imaging, and respiratory function data were collected from electronic hospital files. Statistics included Student's T-test, Pearson's chi-squared test, and Kaplan-Meier curve;statistical significance was determined as p<0.05.Results36 patients (FerEl-SSc) had elevated ferritin values;the rest (n=205) represented the second group (FerNor-SSc). Significant differences were seen in gender (male 44.4% - 15.6%), disease duration (4.56 - 7.7 years), modified Rodnan skin score (12.3 - 6.9), as well as in incidence of lung (65.7% - 38.7%), heart (51.4% - 21.1%), and renal (28.6% - 5.9%) involvement. Increased ferritin correlated with elevated ESR, CRP, creatinine, creatine kinase, troponin, and reduced hemoglobin, impaired pulmonary function tests and reduced left ventricular ejection fraction on echocardiography. Patients with elevated ferritin had a significant increase in mortality rates (52.8% and 35.1%) and non-significant reduction in survival.ConclusionOur study demonstrated that ferritin has a potential as a sensitive marker for SSc severity in term of skin thickening, vital organ complications, and mortality. The ferritin test is simple and inexpensive, it can add to the complex SSc assessment and contribute to treatment decision-making in complicated SSc.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Omicron driven ECMO in a vaccinated critically ill patient

Objectives: Reporting a case of a COVID-19 vaccinated patient admitted to our intensive care unit with severe acute respiratory failure due to SARSCoV2 - Omicron variant, rapidly deteriorating requiring intubation, prone ventilation, and ECMO support. Method(s): A 62 years old Caucasian male was admitted in ICU for rapidly deranging respiratory failure and fever which occurred over the previous 24h. The patient received two doses of SARS-CoV2 vaccine (Oxford, AstraZeneca), the last one over five months before onset of symptoms. The patient was admitted to the intensive care unit (ICU) with tachypnea, low peripheral saturation (80%), elevated serum creatinine (2.4 mg/dl), and mild obesity (BMI 34,6). Pressure support ventilation trial (2 hours) failed carryng out to orotracheal intubation and protective ventilation. Worsening of respiratory exchanges (5 th day from the admission) required a rescue prone ventilation cycle, in the meantime an indication was given to the placement of veno-venous ECMO. The cannulation site was femoro-femoral and the configuration used was Vivc25- Va21, according to the current ELSO nomenclature;ECMO flow was progressively increased until a peripheral saturation of 95% was obtained. Result(s): The patient passed out after 2 month of extracorporeal support with no sign of recovery of pulmonary and renal function. Conclusion(s): Unlike evidences showing a lower symptomatic engagement of the Omicron variant SARSCoV2 positive patients, we have witnessed a rapid and massive pulmonary involvement. The short time that passed from the onset of symptoms and the rapid decay of respiratory function required rapid escalation of the intensity of care up to extracorporeal support. The patient showed previous pathologies that can lead to suspicion of a loss of immune coverage given by the vaccine, in addition to the long time elapsed since the last dose. (Figure Presented).

Extracorporeal membrane oxygenation instead of invasive ventilation in patients with COVID-19 acute respiratory distress syndrome (ARDS) and pneumomediastinum: A cohort trial

Objectives: In patients with severe respiratory failure, invasive ventilation may deteriorate the pneumomediastinum and hypoxia. This study aimed to compare the mortality and the complications of the patients with coronavirus disease 2019 (COVID-19) related severe ARDS treated with invasive ventilation or veno-venous ECMO (VV-ECMO) to avoid intubation. We hypothesized that VV-ECMO support without prior intubation is a feasible alternative strategy to invasive ventilation. Method(s): This retrospective study evaluated patients with COVID-19 related severe respiratory failure and radiological evidence of pneumomediastinum. The primary outcome was intensive care unit (ICU) survival at 90 days. Result(s): Out of 347 patients with COVID-19 disease treated in our unit, 22 patients developed spontaneous pneumomediastinum associated with deterioration of respiratory function. In 13 patients (59%), invasive ventilation was chosen as initial respiratory support;in 9 patients (41%), VV-ECMO was chosen as initial respiratory support. The median age of the patients in the invasive ventilation group was 62 years (IQR: 49-69) compared to 53 years (IQR: 46-62) in ECMO group (P=0.31). No statistically significant difference in SAPS II score between the groups was observed (39.7 (IQR: 33.2-45.3) vs. 28.9 (IQR:28.4-34.6), P=0.06). No elevated fluid balance within the first 4 days was observed in the ECMO group compared to the invasive ventilation group (162 mL (IQR: -366-2000) vs. 3905 mL (IQR: 2068-6192), P=0.07). VV-ECMO as the initial strategy for supporting patients with severe respiratory failure and pneumomediastinum, was associated with lower 90 days mortality (HR: 0.33 95%-CI: 0.11-0.97, P= 0.04) compared to patients treated with invasive ventilation (Figure). Conclusion(s): VV-ECMO can be an alternative strategy to invasive ventilation for treating patients with severe respiratory failure and spontaneous pneumomediastinum. (Figure Presented).

Sleep Promotion in a Busy Inner City High Dependency Unit

Introduction: Critical care patients commonly have disrupted sleep patterns, with reduction of REM sleep, duration of sleep, increased fragmentation and loss of circadian rhythm.1 Causes include the patients' pathophysiology, medications administered and the busy critical care environment. Data collection showed that our patients were sleeping, on average, for a single block of sleep of 3.5 hours. Delirium rates and its known deleterious effects are highly associated with poor sleep, as well as an impairment of psychomotor performance and neurocognitive dysfunction. Sleep deprivation in the healthy population impairs lymphocyte action, cytokine production and pro-inflammatory balance, as well as a reduction in respiratory function and prolongation of respiratory support.2 Objectives: To firstly measure the sleep quality and explore the reasons behind poor sleep from the patients themselves and to gauge the MDT knowledge and interest in sleep, as a fundamental component of patient management. Then using the results we aimed to improve the duration and quality of the patients sleep on high dependency unit. Method(s): The Adapted Richard Campbell Sleep Questionnaire was given to all patients in the HDU over a 4 week period. Results were analysed, then stored for post intervention comparison. The duration of sleep was documented for all patients and a staff questionnaire was done to assess knowledge and concern of staff. Interventions included a staff sleep awareness week with education and prompts attached to the charting tables promoting sleep. Face masks and ear plugs were freely available to be distributed at the evening ward round. The critical care pharmacist identified medications that could alter the patients ability to achieve REM sleep - e.g. evening administered PPIs, and melatonin was commenced early when sleep was troublesome. Estates fixed soft close doors and soft closed bins supplied for clinical areas. After interventions, there was a further 4 week study period where the above factors were repeated. The need for natural light was highlighted and thus this was optimized in the ward environment and those physiologically able were offered trips outdoors to facilitate normal day night wake cycle. With the COVID pandemic ongoing we also endeavored to limit movement overnight of venerable patients. Result(s): The original data collection was of 45 patients with multiple data points, and the second of 27 patients with multiple data points. Results from the Adapted Richard Campbell Sleep Questionnaire were compared using a one tailed students t test. There were significant increases in the subjective quality of sleep (p=0.046) and quantity of sleep (p=0.00018). Reasons given as to improvement of sleep were reduction in discomfort from monitoring and the bed (p=0.026), reduced ambient light (p=0.031) and reduced impact from the presence of other patients (p=0.002). Conclusion(s): There was marked improvement in the awareness of the importance of sleep within the critical care team after education promoting a change in attitude and culture towards sleep. We are planning a second iteration targeting sedation, noise from monitors and staff and overnight interventions. Although this has been done with level 2 patients, extension to level 3 areas would be beneficial.

Future challenges and their impact on respiratory health and lung cancer

Air pollution, climate and population health are closely related in terms of their impacts on respiratory health and lung cancer. Air pollutants contribute to the exacerbation of chronic respiratory problems such as COPD and asthma. Air pollutants are also toxic and carcinogenic, initiating and promoting lung cancer development. Climate change in relation to environmental pollution affects the geographical distribution of food supply and diseases such as pneumonia in adults and children. The threat of air pollution, and hence global warming and climate changes, and their effects on population and respiratory health, is an imminent threat to the world and deserves immediate and sustainable combating strategies and efforts. The goals are to increase public awareness and engagement in action, with alignment of international collaboration and policy, and with steering towards further research. Now is the prime time for international collaborative efforts on planning and actions to fight air pollution and climate change before it is too late.Copyright © ERS 2021.

LABORATORY PARAMETERS ASSOCIATED WITH CODIV-19 CYTOKINE STORM DEVELOPMENT

BackgroundSince the end of 2019, physicians became more and more familiar with SARS-CoV-2 infection and the variety of forms in which it may present and evolve. There have been a lot of studies trying to understand and predict why some patients develop a dysregulation of the immune response, with an exaggerated release of pro-inflammatory cytokines, called cytokine storm (1–4). There is scarce evidence in Romania regarding this aspect.ObjectivesThis study aims to verify the correlation between some laboratory parameters and the development of cytokine storm in SARS-CoV-2 infection in a cohort of over 200 patients admitted in a tertiary hospital from Romania, hoping that early identification of these risk factors of progression to a severe form of the disease can bring considerable benefit to patient care.MethodsThis is an analytical, observational, case-control study which includes 219 patients (all COVID-19 hospitalized patients on the Internal Medicine 3 department of Colentina Clinical Hospital, Bucharest, from 01 March 2020 to 1 April 2021). A series of data were collected, the laboratory parameters being the most important, including: albumin, lymphocyte (percentage), neutrophil (absolute value), aspartate aminotransferase, alanine aminotransferase, D-dimers, lactate dehydrogenase (LDH), anionic gap, chloremia, potassium and the BUN:creatinine ratio (BUN - blood urea nitrogen). The laboratory parameters used for the statistical analysis represent the average values of the first 7 days of hospitalization for those who did not develop cytokine storm, respectively until the day of its development, for the others. Patients were classified into these groups, those who developed cytokine storm, respectively those who did not have this complication taking into account the clinical and paraclinical criteria (impairment of respiratory function, elevations of certain markers 2-3 times above the upper limit of normal, those who died as a result of SARS-CoV-2 infection). Then Binary Univariate Logistic Regression was applied in order to verify the individual impact of every laboratory parameter on cytokine storm development. Furthermore, all laboratory parameters were subsequently included in the multivariate analysis, using the backward selection technique to achieve a model as predictive as possible.ResultsWe mention that the analysis of demographic data was previously performed, showing no statistically significant relationship between patient gender, age or comorbidities (history of neoplasm, lung diseases, cardiac pathology, obesity, type II diabetes and hypertension) and their evolution to cytokine storm. After performing binary univariate logistic regression we concluded that 8 of the 13 laboratory analyzes have had a significant change between groups (ferritin, PCR, albumin, Lymphocyte, Neutrophils, TGO, LDH, BUN:creatinine ratio). Only 150 patients were then included in the multivariate analysis. After the analysis, some of the variables lost their statistical significance, the final model including C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio. This model correctly predicts the development of cytokine storm in 88% of cases.ConclusionHigh C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio are risk factors for cytokine storm development and should be monitored in all COVID-19 patients in order to predict their evolution.References[1]Pedersen SF et all. SARS-CoV-2: A storm is raging[2]Mehta P et al. COVID-19: consider cytokine storm syndromes and immunosuppression[3]Hu B et al. The cytokine storm and COVID-19.[4]Caricchio R et al. Preliminary predictive criteria for COVID-19 cytokine stormAcknowledgements:NIL.Disclosure of InterestsNone Declared.

SAFETY AND PHARMACOKINETICS OF IGPRO20 (SUBCUTANEOUS IMMUNOGLOBULIN) AND IGPRO10 (INTRAVENOUS IMMUNOGLOBULIN) IN ADULTS WITH SYSTEMIC SCLEROSIS (SSC) – RESULTS FROM A PHASE 2 TRIAL

BackgroundSystemic sclerosis (SSc) is a severe, progressive multisystem rheumatic disease with high mortality, but without approved disease-modifying treatment to stop or reverse course of disease. Intravenous immunoglobulin G (IgG) may have a positive impact on SSc based upon available literature reports. However, to date, there have been no clinical trials evaluating subcutaneous IgG (SCIG) in SSc. In particular, the impact of pathologically altered skin in SSc on local safety and pharmacokinetics (PK) of SCIG has not been explored yet.ObjectivesThe primary and secondary objectives of this trial (NCT04137224) included safety, including local infusion safety, and bioavailability of subcutaneous IgG (IgPro20) in adults with diffuse cutaneous SSc (dcSSc).MethodsThis was a randomized, open-label, crossover study. Adult subjects with dcSSc diagnosis within 5 years from first non-Raynaud's phenomenon and modified Rodnan Skin Score of 15-45 at screening were randomized 1:1 to sequence A (IgPro20, 20% normal human subcutaneous immunoglobulin followed by IgPro10, 10% normal human intravenous immunoglobulin) or sequence B (IgPro10 followed by IgPro20). Each subject was to complete two treatment periods (16 weeks each), with up to 40 weeks (including screening) study duration for an individual subject. Doses received were 0.5g/kg/week split over two sessions for IgPro20, and 2g/kg/4 weeks split over 2-5 days for IgPro10. The primary endpoint was safety of IgPro20, described as treatment-emergent adverse events (TEAEs) and changes in clinical observations.Results27 subjects were randomized, with 13 subjects to sequence A and 14 subjects to sequence B. In total, 25 subjects completed the study. Of 27 treated subjects, 107 TEAEs occurred in 22 subjects (81.5%) over the 36-week study period, the majority of which were mild or moderate. The most common TEAEs (>10% of subjects) by preferred term (PT) were headache (12 events occurring in 6 subjects [22.2%]), COVID-19 (3 events occurring in 3 subjects [11.1%]), diarrhoea (3 events occurring in 3 subjects [11.1%]), and vomiting (3 events occurring in 3 subjects [11.1%]).A total of 10 serious AEs (SAEs) were reported in 6 subjects (Viral infection, Chronic gastritis, Vomiting, Dehydration, Upper gastrointestinal haemorrhage, Chest pain, Myocardial infarction, Myocardial ischemia, Breast cancer, Interstitial lung disease). Among these, one subject experienced 2 SAEs (myocardial ischemia & myocardial infarction) and was discontinued from study treatment. None of the SAEs were considered related to study treatment by the investigator, and no deaths were reported.For IgPro20, 14 infusion site reactions (ISRs) occurred in 5 subjects (19.2%), all were mild or moderate in severity. The most common ISRs were infusion site pain and infusion site swelling (3 events in 2 subjects each, 7.7%). In total, 686 IgPro20 infusions were performed, resulting in an overall ISR rate per infusion of 0.02, ie 2 ISRs per 100 infusions. No ISRs were reported for IgPro10.No clinically relevant trends in vital signs, body weight, clinical laboratory tests, electrocardiograms, or pulmonary function tests were observed.PK profiles and bioavailability in dcSSc subjects were similar to those observed in other approved indications such as Primary Immunodeficiency. Population relative bioavailability of IgPro20, based on dose-normalized, baseline-corrected AUC0-tau was 0.761 (90% CI: 0.7033, 0.8232), ie 76.1% compared to IgPro10 (intravenous IgG).ConclusionThe overall safety profiles of IgPro20 and IgPro10 in subjects with dcSSc were consistent with that in approved indications such as CIDP, including a relatively low ISR rate for IgPro20. PK profiles and bioavailability were also similar to other indications. This study indicates that subcutaneous administration of IgPro20 has acceptable safety, bioavailability and PK profiles in patients with dcSSc. AcknowledgementsEditorial assistance was provided by Meridian HealthComms Ltd., funded by CSL Behring.Disclosure of InterestsChristopher P Denton Speakers bureau: Ja ssen, Boehringer Ingelheim, Consultant of: GSK, CSL Behring, Boehringer Ingelheim, Merck, Roche, Sanofi, Grant/research support from: GSK, CSL Behring, Inventiva, Horizon, Otylia Kowal-Bielecka Speakers bureau: Abbvie, Janssen-Cilag, Boehringer Ingelheim, Medac, MSD, Novartis, Pfizer, Sandoz, Consultant of: Boehringer Ingelheim and Novartis, Grant/research support from: Received congress support from Abbvie, Boehringer Ingelheim, and Medac, Susanna Proudman Speakers bureau: Boehringer Ingelheim, Grant/research support from: Janssen, Marzena Olesińska Consultant of: AstraZeneca, Margitta Worm Consultant of: Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc, Leo Pharma GmbH, Boehringer Ingelheim Pharma GmbH &Co.KG, ALK-Abelló Arzneimittel GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (A Viatris Company), AstraZeneca GmbH, Lilly Deutschland GmbH and GlaxoSmithKline GmbH & Co. KG., Nicoletta Del Papa Speakers bureau: Janssen Cilag, Boehringer Ingelheim., Marco Matucci-Cerinic Speakers bureau: Biogen, Sandoz, Boehringer Ingelheim, Consultant of: CSL Behring, Boehringer Ingelheim, Grant/research support from: MSD, Chemomab, Jana Radewonuk Shareholder of: CSL Behring, Employee of: CSL Behring, Jeanine Jochems Shareholder of: CSL Behring, Employee of: CSL Behring, Amgad Shebl Shareholder of: CSL Behring, Employee of: CSL Behring, Anna Krupa Shareholder of: CSL Behring, Employee of: CSL Behring, Jutta Hofmann Shareholder of: CSL Behring, Employee of: CSL Behring, Maria Gasior Shareholder of: CSL Behring, Employee of: CSL Behring.

Extracorporeal cytokine hemadsorption in severe COVID-19 respiratory failure

Background: At least 20% of coronavirus disease 2019 (COVID-19) patients develop acute hypoxemic respiratory failure requiring admission to intensive care unit in 5-32% of the cases. Hyper-inflammatory activation characterized by immune cell infiltration and elevated levels of cytokines was reported as the main mechanism leading to critical illness and severe acute respiratory distress syndrome (ARDS). CytoSorb is currently used for all the conditions where elevated levels of cytokines are present. Along with the beneficial effect on systemic inflammation, CytoSorb can be easily integrated with all extracorporeal circulation systems. Case Presentation: Here, we present the laboratory and clinical outcomes of 11 patients with microbiological confirmed SARS-CoV-2 infection. These patients were treated with CytoSorb to remove the excess of cytokine. All patients were male, overweight and only 3 (27%) were over 70 years old. Median age was 62 years and median body mass index was 28. Best supportive care was provided according to hospital guidelines of that moment and included antibiotic therapy, antiretroviral therapy and protective ventilation. Result(s): Cytokines levels were evaluated before and after treatment. A significant reduction of IL-6, IL-8, IL-10 and IL-1beta was observed. A significant drop of C-reactive protein (CRP) median levels was observed starting from 48 hours after treatment start levels. The decrease in the inflammatory status was associated with a progressive improvement in the respiratory function, with a significant increase in P/F from the first day after the end of the therapy. A similar trend was observed for procalcitonin. Conclusion(s): CytoSorb therapy proved to be safe in COVID-19 patients. A clinical improvement was observed in most of the treated patients despite the severity of the disease. In this study CytoSorb was used empirically for 24- 48 hours based on previous experience in septic shock. The persistence of significant levels of IL-6 and CRP after CytoSorb treatment may suggest that a prolonged treatment can improve the efficacy in controlling COVID-19 hyperinflammatory status.

Association between Covid-19 and Diabetes Mellitus

Aim: To determine the association between Covid-19 and diabetes mellitus. Study Design: Retrospective study. Place and Duration of Study: Department of Medicine & Respiratory Physiology, Independent Medical College Faisalabad from 1st July 2022 to 31st December 2022. Methodology: Fifty five patients received at outdoor patient department of Independent University Hospital with confirmed diagnosis for Covid-19 through naso-pharyngeal reverse transcription polymerase chain reaction (RT-PCR) and aged 13-65 years were included. The complete medical files of each confirmed Covid-19 case was completely studied in relevance to diabetes mellitus association and compared with normal matched controls that only visited the OPD against the suspicion of the disease and underwent complete biochemical profiling. The baseline levels of HbA1C and glucose monitoring in each patient and control was done and compared. Result(s): The mean age of the CoVid-19 cases was 39.5+/-5.3 years while of controls as 25.65+/-4.3 years. There was an obvious significant variance in the odds ratio of Covid-19 patients and those of controls in reference to diabetes mellitus. A significant increase was observed in Odds Ratio of Covid-19 cases within the age group of 51-65 years. The Elixhauser Comorbidity Index (ECI) categories also presented, ECI >5 to be higher in Covid-19 cases than controls. Conclusion(s): There is a higher risk of diabetes new onset in Covid-19 confirmed cases as compared to matched controls.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Thoracic Mobilization and Respiratory Muscle Endurance Training Improve Diaphragm Thickness and Respiratory Function in Patients with a History of COVID-19.

Background and Objectives: Common problems in people with COVID-19 include decreased respiratory strength and function. We investigated the effects of thoracic mobilization and respiratory muscle endurance training (TMRT) and lower limb ergometer (LE) training on diaphragm thickness and respiratory function in patients with a history of COVID-19. Materials and Methods: In total, 30 patients were randomly divided into a TMRT training group and an LE training group. The TMRT group performed thoracic mobilization and respiratory muscle endurance training for 30 min three times a week for 8 weeks. The LE group performed lower limb ergometer training for 30 min three times a week for 8 weeks. The participants' diaphragm thickness was measured via rehabilitative ultrasound image (RUSI) and a respiratory function test was conducted using a MicroQuark spirometer. These parameters were measured before the intervention and 8 weeks after the intervention. Results: There was a significant difference (p < 0.05) between the results obtained before and after training in both groups. Right diaphragm thickness at rest, diaphragm thickness during contraction, and respiratory function were significantly more improved in the TMRT group than in the LE group (p < 0.05). Conclusions: In this study, we confirmed the effects of TMRT training on diaphragm thickness and respiratory function in patients with a history of COVID-19.

Acute care treatment of COVID-19 pneumonia with acute respiratory failure

Treatment of COVID-19 patients and their extreme numbers represented an unprecedented challenge for the intensive care system in healthcare facilities throughout the Czech Republic, a country particularly affected by the new coronavirus SARS-CoV-2 pandemic. A steep increase in the need for intensive care placed an excess burden on bed and staff capacity. For a severe and critical course of COVID-19, bilateral pneumonia with acute hypoxemic respiratory failure is pathognomonic. In the intensive care setting, COVID-19 therapy is primarily symptomatic, supporting failing respiratory function to gain time needed to restore it and to repair the lungs. The aggressiveness and comprehensiveness of respiratory support depend on the severity of failure, ranging from simple oxygen therapy, to non-invasive support and mechanical ventilation, to extracorporeal support. By contrast, specific COVID-19 therapy is directly targeted against SARS-CoV-2 or modulates the organism's response to the virus. Primary, virus-induced lung injury may be secondarily complicated by coinfection or superinfection, most commonly bacterial, increasing the severity and lethality of the disease. Therefore, anti-infective therapy is crucial for the prognosis and outlook of intensive care COVID-19 patients. Among nosocomial infections com-plicating COVID-19, ventilator-associated pneumonia (developing in mechanically ventilated patients) is particularly important and challenging, and so are issues related to bacterial resistance and rational antibiotic therapy.Copyright © 2021, Trios spol. s.r.o.. All rights reserved.

American College of Nuclear Medicine (ACNM) 2022 ACNM Annual Meeting Abstracts

The proceedings contain 91 papers. The topics discussed include: the new approach of COVID-19 patients with deteriorating respiratory functions using perfusion SPECT/CT imaging;increasing interest in nuclear medicine: evaluation of an educational workshop;cost-benefit analysis recommends further utilization of cardiac PET/MR for sarcoidosis evaluation;development of a nomogram model for predicting the recurrence of differentiated thyroid carcinoma patients based on a thyroid cancer database from a tertiary hospital in China;multi-center validation of radiomic models in new data using ComBat-based harmonization of features;bone scan with Tc99m-MDP, the missing link in the initial staging of muscle-invasive bladder carcinoma;and comparison of absorbed doses to kidneys calculated employing three time points and employing two time points in neuroendocrine patients undergoing Lu-177 DOTATATE therapy using planar images.

Trends in Medicare funded respiratory function testing in Australian laboratories

Introduction/Aim: Our study aimed to quantitate trends in Medicare funded respiratory function testing (RFT) in Australian laboratories over recent years, including assessing the impact of Medicare item number changes and the COVID-19 pandemic. Method(s): We interrogated the online Medicare database from July 1994 through to July 2022. All laboratory-based Medicare items related to RFTs were included, both before and after Medicare item changes that occurred in late 2018. Result(s): There was a steady increase in RFTs from ~25,000 tests in 1994 to ~114,000 prior to Medicare changes in 2018, corresponding to per-capita increase from ~140 to 450/100,000 Medicare registrants. A 16% dip in testing post 2018 Medicare item changes was followed by a small increase, then a sharp 46% decrease in testing during the early stages of the COVID-19 pandemic in 2020. Testing levels increased sharply towards the end of 2020 but have not consistently recovered to levels seen prior to COVID-19. The most recent quarter analysed represents 372 tests / 100,000 Medicare registrants. Conclusion(s): Australian Medicare funded laboratory RFTs increased steadily for 24 years before a small decline in 2018, related to Medicare item number changes, and a sharp decline in 2020 due to COVID-19. There has been a recovery since then, however numbers are more variable since the sharp COVID-19 decline.

Clinical and respiratory function outcomes 6-months following diagnosis of COVID-19

Introduction/Aim: As health systems emerge through successive waves of COVID-19, focus shifts to the management of Post-COVID-19 conditions. The aim of this prospective observational study was to characterise and evaluate the respiratory sequelae affecting patients 6-months post-diagnosis of COVID-19. SIGNFICANT MODELLING PREDICTORS Outcome Predictors MMRC>= 1 Disease severity Moderate: OR 16.5 +/- 1.02 (SE) p = 0.006 Impaired DLCO (%predicted) Disease severity B=-1.51+/-0.67 (SE) p = 0.010 Impaired TLC (%predicted) D-Dimer B= -0.305 +/- 0.001 (SE), p = 0.05 TLC below LLN Diabetes B=-1.28 +/- 0.32 (SE), p = 0.044 Methods: Patients were evaluated for symptom burden and lung function at 6-months post-diagnosis of COVID-19 in an outpatient setting. Result(s): Fifty-eight (45 inpatients and 13 outpatients;median age 59 years, 28 females) patients attended 6-month clinic appointment. Whilst nearly half (28,48.3%) were asymptomatic at 6-months, 24 (41.3%) patients reported a modified medical research council dyspnoea scale (MMRC) >= 1 and 21 (36.2%) patient-reported fatigue (n= 21, 36.2%). Reduced TLC (n= 11/50, 22.0%) and DLCO (n = 12/51, 23.5%) were common at 6-months. Results of predictive modelling analyses are described in adjacent table. Conclusion(s): Patients presenting with increased disease severity are at risk of persistent dyspnoea and impaired diffusion capacity, 6-months following acute COVID-19 illness. Research guided management of this growing at risk cohort, while paramount, poses a formidable challenge to stretched healthcare systems.

Current status of hydroxychloroquine and azithromycin for the treatment of COVID-19: an observational review

Though the effect of the coronavirus has known to be a catastrophic pandemic since a 100 years ago, severe acute respiratory syndrome-2 coronavirus (SARS2-CoV) was first claimed to be emerged in December 2019 at the city of Wuhan, China. Abruptly, the virus dominated more than 218 countries with 157,566,607 confirmed cases and the death figure has reached nearly 3,284,551 till time. Recently the pandemic is getting worse day-by-day, people are suffering from hypoxia and severe respiratory problems despite the continuous services provided by the healthcare sector. Prior concern behind this emergency is that, till date, researchers and scientists failed to invent any productive pharmaceutical treatment to weed out the infection completely. Although vaccination is publicly available, it is applicable only for precautionary purposes and not evident of preventive measures. This review focuses on the therapeutic status to control the severity of SAS2-CoV agent. The approach aims at implicating a low toxic metabolite anti-malarial drug, hydroxychloroquine combined with an antibiotic called azithromycin for the treatment of acute respiratory disturbance and hypoxia. This article briefly demonstrates the phramaco-potential of both these medications, their effects on patients based on a clinical observation and ongoing status of dosage to validate its implication.

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor therapy: An Italian center experience

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), a triple CFTR modulator combination, has proved to be highly effective in Phe508del homozygous and Phe508del/minimal function compound heterozygous people with cystic fibrosis (PwCF).We report preliminary data on the realworld effectiveness and safety of ELX/TEZ/IVA after 6 months of treatment. Method(s):We collected prospective data on PwCF who started ELX/TEZ/IVA and evaluated changes in pulmonary function (spirometry and lung clearance index [LCI]), nutritional status (body mass index [BMI]), sweat chloride, and rate of hospitalization from baseline to 6 months of treatment. Result(s): Between August 2021 and October 2021, ELX/TEZ/IVAwas started in 24 PwCF (12 female,10 Phe508del-homozygous, median age 20.5 (range 13-37), all with pancreatic insufficiency). After 6 months of treatment, all respiratory function indicators improved (median change: +16% percentage predicted forced expiratory volume in 1 second, +12% percentage predicted forced vital capacity, +23% percentage predicted forced expiratory flow at 25/75%, -2 lung clearance index). Improvement was also observed in BMI (+0.41 z-score) and sweat chloride concentrations (-54 mMol/L, 6 PwCF had Cl concentrations within the limit of normality) (Table 1). Over a 6-month period, only one hospitalization due to pulmonary exacerbations was observed, compared with 22 hospitalizations observed in the 6 months before starting ELX/TEZ/IVA (rate per 100 patient-months 15.3 vs 0.7, rate ratio 0.05, 95% CI, 0.01-0.29). Treatment was well tolerated, with only mild and transient adverse events consisting of headache (n = 4), cutaneous rash (n = 2), and mild hemoptysis (n = 2). One PwCF had intestinal subocclusion and required hospitalization. One patient had liver function test elevation after 6 months of therapy during an Changes in clinical variables and sweat test results from baseline through 6 months in patients treated with elexacaftor, tezacaftor and ivacaftor. Data are medians (interquartile ranges). Baseline vs 6 months compared usingWilcoxon signed-rank test. ppFEV1, percentage predicted forced expiratory volume in 1 second;ppFVC, percentage predicted forced vital capacity;ppFEV25/75, percentage predicted forced expiratory flow at 25/75%;LCI, lung clearance index;BMI, body mass index;Cl, chloride. (Table Presented) episode of SARS-COV2 infection, which required adjustment of the dose administered. Conclusion(s): Our data confirm that ELX/TEZ/IVA treatment is safe, well tolerated, and effective in PwCF. ELX/TEZ/IVA improved pulmonary function and nutritional status and remarkably reduced hospitalization rate. Our data indicate that introduction of ELX/TEZ/IVA in CF care will radically change the natural history of and management approach to the disease.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Respiratory function and symptoms after acute COVID-19 infection in children and adolescents

Introduction/Aim: Significant long-term effects on both symptomatology and respiratory function have been recognised in adult populations after COVID-19 infection, termed 'Long COVID'. These have caused loss of productivity and increased need for healthcare services. This study aimed to measure symptoms and lung function in children and adolescents after acute COVID-19 infection Methods: Between June 1 and 31 October 2021 there were 144 children admitted to hospital across the Sydney Children's Hospital Network, Australia. Of these, 63 children were referred to the respiratory clinic with symptoms of ongoing cough, shortness of breath and fatigue, 3-6 months post COVID infection. 20 of these children performed reliable lung function. For these children, body plethysmography and double diffusion testing were performed within 3-6 months of their infection. The Liverpool respiratory questionnaire and PROMIS paediatric sleep questionnaires were also administered. Result(s): Of the 20 patients tested, 7 had COVID pneumonitis requiring hospitalisation during the acute illness. 6 of the 20 patients had significant persistent symptoms as measured by the Liverpool respiratory questionnaire, while none of the children had any significant sleep symptoms. All children had preserved spirometry within normal limits. Of note, 2 children with persistent respiratory symptoms had DLNO/DLCO ratio >1.15, suggesting pulmonary vascular disease. The same two children who had elevated DLNO / DLCO had high ventilator equivalents on CPET testing suggesting increased physiological dead space ventilation. Despite this, their peak aerobic capacity was within normal limits. There were no significant differences between the alpha and delta cohorts or between children treated at home vs those requiring hospitalisation during their infection. Conclusion(s): COVID-19 may cause long-lasting effects in children. In this cohort, all children maintained spirometry results within normal limits despite significant symptoms impacting daily activities. Double diffusion testing may shed some light on lung changes leading to persistent symptomatology after COVID infection.

Strategies to reduce risk of SARS-CoV-2 in respiratory function laboratories

Introduction: SARS-CoV-2 is a highly infectious disease transmitted by aerosol and droplet particles. Respiratory function tests are aerosol generating procedures. Consequently, this increases the risk of exposure to SARS-Cov-2 to healthcare workers and patients visiting respiratory function laboratories. Proposed recommendations on pulmonary function testing during the SARS-CoV-2 pandemic were published by the ERS and the ANZSRS/TSANZ. Aim(s): To identify strategies implemented in respiratory function laboratories to reduce the risk of SARS-CoV-2 transmission. Method(s): An electronic questionnaire of respiratory laboratories on infection control measures implemented during the SARS-CoV-2 pandemic was sent to active ANZSRS members in an explanatory email. All data obtained was de-identified with only one response per laboratory included in the analysis. Result(s): Responses were received from 32 laboratories. 81% were from a hospital setting, 61% were TSANZ accredited. 94% and 78% of laboratories identified that they had read the ANZSRS/TSANZ statement and the ERS statements, respectively. 25% and 22% of laboratories implemented modifications based on these statements while 13% and 9% indicated barriers prevented changes being made. Infrastructure was the main barrier identified following both statements. The main strategies implemented are summarised in the below table. Strategy implemented Laboratories (%) Triage patients on clinical urgency 91 Screening prior to appointment or on arrival 100 Scientist wearing fit-tested masks during tests 78 Scientist wearing eyewear during tests 75 Wait time post close contacts (routine-14 days) 50 Wait time post positive infection (routine-14 days) 43 Wait time post close contacts (urgent-10 days) 31 Wait time post positive infection (urgent-10 days) 22 Investigated air room changes/hour 66 Allow at least a 15-min washout period between patients 34 Investigated best cleaning methods for their equipment 65 Utilise telehealth 21 Conclusion(s): Laboratories in Australia and New Zealand have put in place a variety of changes in accordance with recommendations made in position statements to reduce risk of SARS-CoV-2 transmission. While some laboratories had already implemented strategies, the ERS and ANZSRS/TSANZ publications have given clear guidelines to reduce aerosolised transmission of SARS-CoV-2.

Non-depolarizing neuromuscular blockade in patients with severe acute respiratory distress syndrome associated with COVID-19: profile of usage and potential deleterious impact on morbidity and mortality

Introduction: Nondepolarizing neuromuscular blockade (NDMB) is a key intervention to avoid ventilation-induced lung injury in acute respiratory distress syndrome (ARDS). In patients with moderatesevere ARDS associated with SARS-CoV-2 infection (CARDS), NDMB were used for prolonged periods of time, with high cumulative doses. We hypothesize that administration of NDMB might contribute to an increased incidence of risk factors later associated with long COVID-19. Method(s): We designed a non-interventional, retrospective study in a large university urban hospital. From January to December 2021, data related to prescription of NDMB, respiratory physiology, mechanical ventilation (IMV) and clinical outcomes were collected from patients' electronic records with a diagnosis of CARDS. Primary outcome was day-90 mortality. Secondary outcomes were ICU length of stay (LOS), ICU-acquired weakness and days of IMV. Mann-Whitney U test was used to compare continuous variables and logistic regression was used to evaluate the association of NDMB use with outcomes, adjusted or not for confounders. Result(s): 116 patients diagnosed with CARDS were included, 87% with severe ARDS and overall mortality was 37.1%. Median age was 57 years (IQ:47-67) and 65.5% were male. P:F ratio at day-1 was 86 (IQ:43). Ventilator-free days (VFDs) at 28 days was 13 (IQ:0-19) in survivors and ICU-LOS was 19 (IQ:10-36). Median time and cumulative dose of NDMB were, respectively, 117 h and 1177.468 mg in patients who survived (n = 70) compared to 197 h and 1898.775 mg in patients who died (n = 41). In addition to days of NDMB exposure (OR 1.05, CI 95% 1.00-1.11), the cumulative dose of cisatracurium, expressed in logs, was correlated with risk of mortality in the ICU, with odds ratio 1.49 (CI 95% 1.08-2.04). Conclusion(s): Patients with severe forms of CARDS received prolonged infusions of NDMB, with high cumulative doses. Both time of exposure and total doses were independently associated with higher risk of mortality.

Long-term respiratory outcomes after COVID-19: a Brazilian cohort study.

Objective: To investigate the prevalence and risk factors for persistent symptoms up to 12 months after hospital discharge in COVID-19 survivors. Methods: This prospective cohort study included patients with COVID-19 discharged from a university hospital in Brazil. Follow-up was performed 2, 6, and 12 months after discharge. Lung function tests and chest computed tomography (CT) were performed 2 months after discharge and were repeated if abnormal. The primary outcomes were the symptoms present, work status, and limitations in daily activities. Results: Eighty-eight patients were included. Dyspnea (54.5%), fatigue (50.0%), myalgia, and muscle weakness (46.6%) were the most common symptoms, which decreased over time. Anxiety was frequent (46.6%) and remained unchanged. One year after discharge, 43.2% of the patients reported limitations in daily activities, and 17.6% had not returned to work. Corticosteroid use was significantly associated with dyspnea and limitations in daily activities. Females had an increased risk of fatigue at the 12-month assessment, with marginal significance after multivariable adjustment. Young age and bronchial wall thickening on admission CT were also risk factors for dyspnea at follow-up. The most common lung function abnormalities were reduced diffusion capacity and small airway disease, which partially improved over time. Conclusions: One year after hospital discharge, more than one-third of patients still had persistent COVID-19-related symptoms, remarkable dyspnea, fatigue, and limitations in daily activities, regardless of acute disease severity. Age, female sex, corticosteroid use during hospitalization, and bronchial thickening on admission CT were associated with an increased risk of sequelae.