Related Pneumonia Research Articles

Incidence risk of PD-1/PD-L1-related pneumonia and diarrhea in non-small cell lung cancer (NSCLC) patients: a systematic review and meta-analysis of randomized controlled trials.

Programmed cell death-1 (PD-1) and programmed cell death ligand-1(PD-L1) inhibitor therapy have been approved for the treatment of many cancers, although their incidence of some side effects was high. We aim to fully investigate the incidence risk of PD-1/PD-L1 inhibitors-related pneumonia and diarrhea in NSCLC patients, as well as treatment-related deaths. PubMed, Medline, Cochrane Library, and Clinical trials.gov databases were searched up to Sep 17, 2020, for clinical trials of PD-1 inhibitors and PD-L1 inhibitors in the treatment of NSCLC. Randomized controlled trials and their references were screened. Seventeen trials were included in our meta-analysis, including 11,363 patients. PD-1/PD-L1 inhibitors significantly increased the risk of developing all-grade and high-grade (grade ≥ 3) pneumonia (risk ratio [RR] = 2.28; 95% CI: 1.39-3.76; P < 0.01; RR = 2.38; 95% CI: 1.72-3.29; P < 0.01, respectively). The use of PD-1/PD-L1 inhibitor did not increase the risk of developing all-grade and high-grade diarrhea (RR = 0.79; 95% CI: 0.62-1.01; P = 0.06; RR = 0.96; 95% CI: 0.70-1.31; P = 0.78, respectively). There was no significant difference between the rate of death in PD-1 and PD-L1 inhibitors (P = 0.079). These data suggest that PD-1/PD-L1 inhibitors significantly increase the risk of all-grade and high-grade pneumonia in NSCLC patients and PD-1/PD-L1 monotherapy increases the risk of all-grade pneumonia in NSCLC patients compared to PD-1/PD-L1 inhibitor combination regimens. Physicians should pay more attention to NSCLC patients who treated with PD-1/PD-L1 inhibitors.

The clinical characteristics and treatment approaches of COVID-19: a concise review

A series of cases of pneumonia occurred in China in late 2019. For this type of coronavirus, the WHO formally identified the condition as a coronavirus disease 2019 (COVID-19). They announced that this disease is the recent main concern of health problems in the world. Transfer of this novel coronavirus (nCoV) from human to human exists predominantly among family members, who have close contact with each other. This review article is provided based on the recent findings of COVID-19, which were retrieved by searching PubMed, Google Scholar, Scopus, and Web of Science until December 2020. Here, we highlighted the coronaviruses types, COVID-19 symptoms, epidemiology of the disease, transmission ways, and nCoV related pneumonia pathogenesis and continue with characteristic features and treatment methods. While no approved treatments are available for this type of infection therapy but several drugs may have potential benefits. It seems that identifying the detailed characteristics of the novel coronavirus disease offers the foundation for further research into the production of effective anti-COVID-19 drugs and vaccines.

Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU.

Rationale: Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question.Objectives: We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19.Methods: We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications.Measurements and Main Results: The study population included a total of 145 patients; the median age was 55 years old. Most of them were male (n = 104; 72%), were overweight (n = 99; 68%), and had hypertension (n = 83; 57%) and diabetes (n = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection (n = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half (n = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio, = 4.66; interquartile range, 1.98–7.34; P = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%).Conclusions: In patients with no underlying immunosuppression, severe SARS-CoV-2–related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.

A false alarm of COVID-19 pneumonia in lung cancer\xa0with anti-PD-1 related pneumonitis: a case report and review of the literature

BackgroundPneumonitis belongs to the fatal toxicities of anti-PD-1/PD-L1 treatments. Its diagnosis is based on immunotherapeutic histories, clinical symptoms, and the computed tomography (CT) imaging. The radiological features were typically ground-glass opacities, similar to CT presentation of 2019 Novel Coronavirus (COVID-19) pneumonia. Thus, clinicians are cautious in differential diagnosis especially in COVID-19 epidemic areas.Case presentationHerein, we report a 67-year-old Han Chinese male patient presenting with dyspnea and normal body temperature on the 15th day of close contact with his son, who returned from Wuhan. He was diagnosed as advanced non-small cell lung cancer and developed pneumonitis post Sintilimab injection during COIVD-19 pandemic period. The chest CT indicated peripherally subpleural lattice opacities at the inferior right lung lobe and bilateral thoracic effusion. The swab samples were taken twice within 72 hours and real-time reverse-transcription polymerase-chain-reaction (RT-PCR) results were COVID-19 negative. The patient was thereafter treated with prednisolone and antibiotics for over 2 weeks. The suspicious lesion has almost absorbed according to CT imaging, consistent with prominently falling CRP level. The anti-PD-1 related pneumonitis mixed with bacterial infection was clinically diagnosed based on the laboratory and radiological evidences and good response to the prednisolone and antibiotics.ConclusionThe anti-PD-1 related pneumonitis and COVID-19 pneumonia possess similar clinical presentations and CT imaging features. Therefore, differential diagnosis depends on the epidemiological and immunotherapy histories, RT-PCR tests. The response to glucocorticoid is still controversial but helpful for the diagnosis.

CT characteristics and laboratory findings of COVID-19 pneumonia in relation to patient outcome

BackgroundThis study aimed to investigate the chest computed tomography (CT) characteristics and laboratory findings in patients with confirmed COVID-19 pneumonia and to evaluate their relationship with clinical outcome.This retrospective study assessed 164 consecutive CT chests of COVID-19 patients during April 2020. The chest CT and laboratory data were analyzed. The primary endpoint was patient survival either died or survived. The relationship between CT and laboratory findings was correlated to patient outcome.ResultsThe study group included 164 patients (86 male, 78 women; average age, 44.3 ± 16.5 years) whose RT-PCR were positive for COVID-19. Only 120 (73.2%) patients had pulmonary manifestations. Ground glass opacities of peripheral distribution and multifocal affection were the major CT finding in COVID-19 patients. Univariate analysis revealed that CT severity score, D-dimer level, age, total leucocytic count, and absolute lymphocytic count were predictive for death.ConclusionCT has an emerging role in the diagnosis of COVID-19 pneumonia and in assessing disease severity. CT severity score, D-dimer, total leucocytic count, and absolute lymphocytic count significantly predict patient survival.

An Ensemble of Global and Local-Attention Based Convolutional Neural Networks for COVID-19 Diagnosis on Chest X-ray Images

The recent Coronavirus Disease 2019 (COVID-19) pandemic has put a tremendous burden on global health systems. Medical practitioners are under great pressure for reliable screening of suspected cases employing adjunct diagnostic tools to standard point-of-care testing methodology. Chest X-rays (CXRs) are appearing as a prospective diagnostic tool with easy-to-acquire, low-cost and less cross-contamination risk features. Artificial intelligence (AI)-attributed CXR evaluation has shown great potential for distinguishing COVID-19-induced pneumonia from other associated clinical instances. However, one of the associated challenges with diagnostic imaging-based modeling is incorrect feature attribution, which leads the model to learn misguiding disease patterns, causing wrong predictions. Here, we demonstrate an effective deep learning-based methodology to mitigate the problem, thereby allowing the classification algorithm to learn from relevant features. The proposed deep-learning framework consists of an ensemble of convolutional neural network (CNN) models focusing on both global and local pathological features from CXR lung images, while the latter is extracted using a multi-instance learning scheme and a local attention mechanism. An inspection of a series of backbone CNN models using global and local features, and an ensemble of both features, trained from high-quality CXR images of 1311 patients, further augmented for achieving the symmetry in class distribution, to localize lung pathological features followed by the classification of COVID-19 and other related pneumonia, shows that a DenseNet161 architecture outperforms all other models, as evaluated on an independent test set of 159 patients with confirmed cases. Specifically, an ensemble of DenseNet161 models with global and local attention-based features achieve an average balanced accuracy of 91.2%, average precision of 92.4%, and F1-score of 91.9% in a multi-label classification framework comprising COVID-19, pneumonia, and control classes. The DenseNet161 ensembles were also found to be statistically significant from all other models in a comprehensive statistical analysis. The current study demonstrated that the proposed deep learning-based algorithm can accurately identify the COVID-19-related pneumonia in CXR images, along with differentiating non-COVID-19-associated pneumonia with high specificity, by effectively alleviating the incorrect feature attribution problem, and exploiting an enhanced feature descriptor.

Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: Molecular docking and DFT calculations

Structure−activity relationships for hydroxychloroquine compound and its derivatives resulted in a potent antiviral activity. Where hydroxychloroquine derivatives showed an apparent efficacy against coronavirus related pneumonia. For this reason, the current study is focused on the structural properties of hydroxychloroquine and hydroxychloroquine sulfate. Optimized structures of these molecules have been reported by using DFT method at B3LYP/6-31G* level of theory. The geometric were determined and compared with the experimental crystal structure. The intra and intermolecular interactions which exist within these compounds are analyzed by different methods namely the topological analysis AIM, ELF and the reduced gradient of the density. These approaches make it possible in particular to study the properties of hydrogen bonds. The highest occupied molecular orbital and the lowest unoccupied molecular orbital energy levels are constructed and the corresponding frontier energy gaps are determined to realize the charge transfer within the molecule. The densities of state diagrams were determined to calculate contributions to the molecular orbitals. The molecular electrostatic potential surfaces are determined to give a visual representation of charge distribution of these ligands and to provide information linked to electrophilic and nucleophilic sites localization. Finally, these derivatives were evaluated for the inhibition of COVID-19 activity by using the molecular docking method.

Использование сурфактант-терапии в комплексном лечении острого респираторного дистресс-синдрома при COVID-19

ntroduction. The COVID-19 pandemic caused an outbreak of viral lung infections with severe acute respiratory syndrome complicated with acute respiratory failure. Despite the fact that the pandemic has a lengthened run, none of the therapeutic approaches have proved to be sufficiently effective according to the evidence-based criteria. We consider the use of surfactant therapy in patients with severe viral pneumonia and acute respiratory distress syndrome (ARDS) as one of the possible methods for treating COVID-19 related pneumonia. Objective. To prove the clinical efficacy and safety of orally inhaled Surfactant-BL, an authorized drug, in the combination therapy of COVID-19 related ARDS. Materials and methods. A total of 38 patients with COVID-19 related severe pneumonia and ARDS were enrolled in the study. Of these, 20 patients received the standard therapy in accordance with the temporary guidelines for the prevention, diagnosis and treatment of the novel coronavirus infection (COVID-19) of the Ministry of Health of the Russian Federation, version 9. And 18 patients received the surfactant therapy in addition to the standard therapy. Surfactant-BL was used in accordance with the instructions on how to administer the drug for the indication – prevention of the development of acute respiratory distress syndrome. A step-by-step approach to the build-up of the respiratory therapy aggressiveness was used to manage hypoxia. We used oxygen inhalation via a face mask with an oxygen inflow of 5–15 l/min, highflow oxygen therapy via nasal cannulas using Airvo 2 devices, non-invasive lung ventilation, invasive lung ventilation in accordance with the principles of protective mechanical ventilation. Results and discussion. Significant differences in the frequency of transfers to mechanical ventilation, mortality, Intensive Care Unit (ICU) and hospitalization length of stay (p &lt;0.05) were found between the groups. Patients receiving surfactant therapy who required a transfer to mechanical ventilation accounted for 22% of cases, and the mortality rate was 16%. In the group of patients receiving standard therapy without surfactant inhalation 45% were transferred to mechanical ventilation, and 35% died. For patients receiving surfactant therapy, the hospital stay was reduced by 20% on average, and ICU stay by 30%. Conclusion. The inclusion of surfactant therapy in the treatment of COVID-19 related severe pneumonia and ARDS can reduce the progression of respiratory failure, avoid the use of mechanical ventilation, shorten the ICU and hospitalization length of stay, and improve the survival rate of this patient cohort.

Correlation between continuous Positive end-expiratory pressure (PEEP) values and occurrence of Pneumothorax and Pneumomediastinum in SARS-CoV2 patients during non-invasive ventilation with Helmet.

Background:Acute Hypoxemic Respiratory Failure is a common complication of SARS-CoV2 related pneumonia, for which non-invasive ventilation (NIV) with Helmet Continuous Positive Airway Pressure (CPAP) is widely used. The frequency of pneumothorax in SARS-CoV2 was reported in 0.95% of hospitalized patients in 6% of mechanically ventilated patients, and in 1% of a post-mortem case series.Objectives:Aim of our retrospective study was to investigate the incidence of pneumothorax and pneumomediastinum (PNX/PNM) in SARS-CoV2 pneumonia patients treated with Helmet CPAP. Moreover, we examined the correlation between PNX/PNM and Positive end-expiratory pressure (PEEP) values.Methods:We collected data from patients admitted to “Luigi Sacco” University Hospital of Milan from 2 February to 5 May 2020 with SARS-CoV2 pneumonia requiring CPAP. Patients, who need NIV with bi-level pressure or endotracheal intubation (ETI) for any reason except those who needed ETI after PNX/PNM, were excluded. Population was divided in two groups according to PEEP level used (≤10 cmH2O and >10 cmH20).Results:154 patients were enrolled. In the overall population, 42 patients (27%) were treated with High-PEEP (>10 cmH2O), and 112 with Low-PEEP (≤10 cmH2O). During hospitalization 3 PNX and 2 PNM occurred (3.2%). Out of these five patients, 2 needed invasive ventilation after PNX and died. All the PNX/PNM occurred in the High-PEEP group (5/37 vs 0/112, p<0,001).Conclusion:The incidence of PNX appears to be lower in SARS-CoV2 than SARS and MERS. Considering the association of PNX/PNM with high PEEP we suggest using the lower PEEP as possible to prevent these complications.

Major Depressive Disorder as a Post COVID Infection Sequela

COVID-19 has taken the world by storm, producing a multitude of concerning sequela in all genders and age groups. One surprising finding is the onset of depression post COVID recovery in patients with no past medical history of psychiatric illness. The following case report discusses a 52-year-old female with a past medical history of pneumonia secondary to COVID-19 in April 2021, who presented with recurrent falls and a syncopal episode. On review of systems, it was discovered that the patient has new onset depression since recovering from COVID related pneumonia. Patient has yet to follow up with an outpatient psychiatrist.

Application of Rehabilitation Therapy in Pulmonary Infection of Stroke Patients

Clinical efficacy of meridian-based massage as a rehabilitation therapy for pulmonary infection in stroke patients is explored, so as to provide new ideas and methods for the prevention and rehabilitation of stroke-associated pneumonia. Forty-six patients diagnosed as stroke complicated with pulmonary infection in The Third Affiliated Hospital of Qiqihar University are randomly divided into experimental group and control group, with 23 cases in each group. The control group is treated with medication and routine rehabilitation therapy, while the experimental group is treated with meridian massage on the basis of the control group. The results show that after 12 d of intervention, the pulmonary infection score of the two groups is lower than that before treatment, and the experimental group is obviously due to the control group (p<0.05). The total effective rate is 91.3 % in the experimental group, which is significantly higher than 65.2 % in the control group (p<0.05). Therefore, massage along meridians is effective in treating stroke-associated pneumonia. It can improve the level of interleukin 4 in serum of patients with stroke related pneumonia and the ability of autoimmune regulation. It can improve the total effective rate of treatment, and effectively control the symptoms and signs of pulmonary infection. It can be used as an effective rehabilitation treatment for patients with stroke-related pneumonia. Since only 12 d of observation and treatment are carried out in this study, the prognosis is more one-sided, which cannot achieve a systematic and comprehensive evaluation of the treatment effect. In the future, the analysis of therapeutic effect should be more detailed.

403. Study of early and late readmissions with COVID-19: A retrospective analysis

BackgroundMichigan was one of the severely impacted regions during the initial COVID-19 surge. An institutional protocol with early methylprednisolone (MP) to treat COVID-19 patients requiring supplemental oxygen was implemented. We sought to study characteristics of these patients who were readmitted with infectious and non-infectious diagnoses.MethodsA retrospective analysis of 21 COVID-19 readmitted patients initially admitted between 3/10/2020 and 4/20/2020 (early 0–7, late 8–30 days) was done. Total of 455 COVID-19 patients, confirmed by a positive nasopharyngeal RT-PCR were admitted during this time period. Demographic data, clinical characteristics, laboratory and radiographic results and treatments were compared among the early and late readmission groups. Univariate and logistic regression analysis were performed to study the risk factors associated with early readmission and worsening of COVID-19 pneumonia. Secondary analyses were performed comparing worsening COVID-19 pneumonia with other readmission diagnoses.Results4.6% (21/455) were readmitted, 14 early vs 7 late (median age 75 vs 65 yrs). Most early readmissions were COVID-19 related and 8 out of 14 had worsening COVID-19 pneumonia based on clinical picture, laboratory and imaging findings. Readmitted patients with worsening COVID-19 related pneumonia had significantly elevated CRP and lower ALC compared to last discharge value (Table 1). None of the late readmissions required MP. A total of 8 readmissions had bacterial coinfections (1/8 COVID-19 related) (Table 2). Bacterial infections unrelated to COVID-19 were aspiration pneumonia (2), urinary tract infection (2), enterococcal bacteremia from stercoral colitis (1), sacral osteomyelitis (1), and infected BKA stump (1). Each increasing day of MP duration during the first admission reduced the likelihood of early readmission by approximately 10% (OR 0.90, 95% CI 0.63–1.2, p=0.56) (Table 3). 1/14 and 0/7 patients died amongst early and late readmissions respectively.Table 1: Characteristics of early and late readmissions in COVID-19 patients Table 2: Readmission Diagnosis Table 3: Univariate and Multivariate Analysis of Readmissions ConclusionEarly MP in COVID-19 pneumonia was not associated with increased risk of early secondary bacterial infections in the readmitted patients. Optimal duration of MP in patients with COVID-19 pneumonia needs to be defined.Disclosures All Authors: No reported disclosures

Prolonged prothrombin time as an early prognostic indicator of severe acute respiratory distress syndrome in patients with COVID-19 related pneumonia

Background Clinical observations demonstrated that COVID-19 related pneumonia is often accompanied by hematological and coagulation abnormalities including lymphopenia, thrombocytopenia, and prolonged prothrombin time. The evaluation of laboratory findings including coagulation and inflammation parameters may represent a promising approach for early determination of COVID-19 severity. Methods and Materials In the present study, we aimed to identify laboratory parameters present upon admission in patients with COVID-19 related viral pneumonia and associated with an early in-hospital development of refractory respiratory failure or severe acute respiratory distress syndrome requiring treatment in an intensive care unit. We investigated differences in the C-reactive protein (CRP) and fibrinogen levels, prothrombin time (PT) and international normalized ratio (INR) between COVID-19 patients who had been transferred to an ICU within two weeks after admission (n = 82) and COVID-19 patients with stable course of the disease (n = 74). Results Multiple comparisons showed statistically significantly prolonged PT on admission in ICU-transferred COVID-19 patients (14.15 sec, median, CI 95% 13.4 ÷ 14.9) compared to the stable COVID-19 patients (13.25 sec, median, CI 95% 12.9 ÷ 13.6) (p-value = .0005). CRP levels upon admission were statistically significantly higher in ICU-transferred COVID-19 patients (132 mg/L, median, CI95% 113 ÷ 159) compared to the stable COVID-19 patients (51 mg/L, median, CI95% 33 ÷ 72) (p-value < .0001). On-admission fibrinogen and INR levels did not statistically significantly differ between ICU-transferred COVID-19 patients and stable COVID-19 patients. Conclusion We suggest that CRP and PT levels present on admission in COVID-19 patients may be used as early prognostic markers of severe pneumonia requiring transfer to ICU.

Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study.

The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19.This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020).During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis.In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.

Diagnostic performance of chest computed tomography during the epidemic wave of COVID-19 varied as a function of time since the beginning of the confinement in France

To evaluate the diagnostic performance of the initial chest CT to diagnose COVID-19 related pneumonia in a French population of patients with respiratory symptoms according to the time from the onset of country-wide confinement to better understand what could be the role of the chest CT in the different phases of the epidemic. Initial chest CT of 1064 patients with respiratory symptoms suspect of COVID-19 referred between March 18th, and May 12th 2020, were read according to a standardized procedure. The results of chest CTs were compared to the results of the RT-PCR. 546 (51%) patients were found to be positive for SARS-CoV2 at RT-PCR. The highest rate of positive RT-PCR was during the second week of confinement reaching 71.9%. After six weeks of confinement, the positive RT-PCR rate dropped significantly to 10.5% (p<0.001) and even 2.2% during the two last weeks. Overall, CT revealed patterns suggestive of COVID-19 in 603 patients (57%), whereas an alternative diagnosis was found in 246 patients (23%). CT was considered normal in 215 patients (20%) and inconclusive in 1 patient. The overall sensitivity of CT was 88%, specificity 76%, PPV 79%, and NPV 85%. At week-2, the same figures were 89%, 69%, 88% and 71% respectively and 60%, 84%, 30% and 95% respectively at week-6. At the end of confinement when the rate of positive PCR became extremely low the sensitivity, specificity, PPV and NPV of CT were 50%, 82%, 6% and 99% respectively. At the peak of the epidemic, chest CT had sufficiently high sensitivity and PPV to serve as a first-line positive diagnostic tool but at the end of the epidemic wave CT is more useful to exclude COVID-19 pneumonia.

Immunomodulation with Thymalin in the COVID-19 Re-lated Cytokine Storm: Case Reports

Here we present two patients (the first a 72-year-old male and the second a 69-year-old female) with severe COVID-19 related bilateral pneumonia. In both cases we observed the increased levels of acute-phase reactants and an inflammatory biomarker profile with marked lymphopenia, therefore cytokine storm due to COVID-19 was diagnosed. Both patients were first treated with hydroxychloroquine, cefoperazone/sulbactam, and tocilizumab without any clinical benefit; and was then given thymalin treatment with impressive clinical and laboratory improvement. We performed immunophenotyping of peripheral blood mononuclear cells to assess the dynamics of these cells during COVID-19 related cytokine storm, tocilizumab, and thymalin administration. We observed a decline of CD4+, B-Lymphocytes, and NK-cells after tolicuzimab administration. CD8+ T-cell levels were negatively correlated with inflammatory indicators ESR, CRP, and IL-6.

Early nutrition protocol during Covid-19 pandemic

Rationale: At the end of February 2020 the first SARS-COV2 related pneumonia was diagnosed in Italy and soon the disease spread all over the country. It is well demonstrated that malnutrition is related to worse outcomes in many acute and chronic diseases and that ICU stay is often associated to worsening of nutritional status leading to ICU acquired weakness. Peculiar COVID-19 clinical feature is the Cytokine Storm leading to a Systemic Inflammatory Response Syndrome with multiple organ impairment and metabolic imbalances.

QT Interval Prolongation in COVID-19: Hypercytokinaemia is the Forgotten Culprit and Hydroxychloroquine Simply Add Fuel to the Fire

The prevalence of arrhythmias varies in COVID-19. In a study of 138 patients from Wuhan, who were hospitalized with COVID-19 related pneumonia, arrhythmias were reported in 17% of the general cohort and in 44% of patients admitted to an intensive care unit

Lower limb deep vein thrombosis in COVID-19 patients admitted to intermediate care respiratory units

COVID-19 has been associated with an increased risk of thrombotic events; however, the reported incidence of deep vein thrombosis varies depending, at least in part, on the severity of the disease. Aim of this prospective, multicenter, observational study was to investigate the incidence of lower limb deep vein thrombosis as assessed by compression ultrasound in consecutive patients admitted to three pulmonary medicine wards designated to care for patients with COVID-19 related pneumonia, with or without respiratory failure but not requiring admission to an intensive care unit.Consecutive patients admitted between March 27 and May 6, 2020 were enrolled. Patients were excluded if they were less than 18-year-old or if compression ultrasound could not be performed for any reason. Patients were assessed at admission (t0) and after 7 days (t1). Major and non-major clinically relevant bleedings were recorded.Sixty-eight patients were enrolled. Two were excluded due to anatomical abnormalities that prevented compression ultrasound; sixty patients were retested at (t1). All patients were started on antithrombotic prophylaxis, unless therapeutic anticoagulation was required.Deep vein thrombosis as assessed by compression ultrasound was observed in 2 patients (3%); one of them was later deemed to represent a previous episode. No new episodes were detected at t1. One major and 2 non-major clinically relevant bleedings were observed.In the setting of patients with COVID-related pneumonia not requiring admission to an intensive care unit, the incidence of deep vein thrombosis is low and our data support not screening asymptomatic patients.

Ibrutinib in Combination with R-Gemox-D in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Phase II Clinical Trial of the Geltamo Group

BACKGROUND Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), non-candidates for autologous stem-cell transplantation (ASCT), have few treatment options. Ibrutinib is an oral Bruton's tyrosine kinase inhibitor that has shown increased antitumor activity in patients with DLBCL of different subtype from germinal center B-cell like (non-GCB). In the present phase II clinical trial (NCT02692248), we investigated the efficacy and toxicity of the combination of Ibrutinib with the R-GEMOX-D regimen (rituximab, gemcitabine, oxaliplatin and dexamethasone), in patients with non- GCB DLBCL. METHODS We included patients with histological diagnosis of non-GCB DLBCL (according to Hans algorithm), with relapsed or refractory disease after at least 1 line of immunochemotherapy and non-candidates for ASCT. Patients received an induction treatment consisting of 6 (in case of complete remission [CR] after cycle 4) or 8 (in case of partial response [PR] or stable disease after cycle 4) cycles of R-GEMOX-D at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles, and the secondary objectives were: CR rate, progression-free survival (PFS), overall survival (OS) and toxicity. Analyses were performed in the intention to treat population (data cut-off 10th April 2020). RESULTS Sixty-four patients (59.4% male) were included between March 2016 and November 2018. Median age was 67 (25-84) years. Patients had received a median of 2 previous lines of treatment; 56.3% were refractory (&amp;lt;PR) to the last regimen, whereas 43.7% had relapsed disease after a previous CR. Eleven (17.2%) patients had received a previous ASCT. IPI at study entry was 0-1, 2-3, and 4-5 in 9.4%, 67.2%, and 20.3% of patients, respectively (missing data in 2 patients). Of the 64 patients who started study treatment, 44 and 35 patients, respectively, were evaluated for response after 4th cycle and at the end of induction. Twenty-four (37%) patients started maintenance with ibrutinib, 7 of whom continue or have completed it. Causes of withdrawal from the trial (n=57) were progression (n=40), adverse event (n=6), transplantation (n=5), withdrawal of consent (n=3) and other causes (n=3). ORR and CR rate after 4th cycle were 53.2% and 35.9%, respectively. Patients with relapsed disease had significantly higher ORR (67.9% vs 41.7%, p=0.037) and CR rate (57.1% vs 19.4%, p=0.002) than patients with refractory disease. At the end of induction, ORR and CR rate were 35.9% and 29.7%, respectively. After a median follow-up of 22 months (range: 1 to 39 months), the estimated 2-year PFS and OS were 21% and 25%, respectively (Figure 1A and 1B), being significantly better in patients with relapsed disease (Figure 1C and 1D). In the multivariate analysis, status of lymphoma at study entry significantly influenced PFS (HR 0.45; 95% CI 0.25-0.82; p=0.009) and OS (HR 0.51; 95% CI 0.27-0.94; p=0.0031) independently from the IPI and the number of previous treatment lines. The most frequent adverse events (AE) (present in at least 20% of patients) were thrombocytopenia (67.2%), diarrhea (51.6%), neutropenia (46.9%), anemia (37.5%), fatigue (34.4%), nausea (29.7%) and paresthesia (20.3%). The most frequent grade 3-5 AE (present in at least 10% of patients) were thrombocytopenia (46.9%), neutropenia (35.9%), diarrhea (15.6%) and anemia (14.1%). Three patients presented a grade 5 AE, two of them related (aspergillosis and pneumonia, respectively) and one unrelated (heart failure). CONCLUSIONS The combination of ibrutinib with R-GEMOX-D as salvage therapy for patients with non-GCB DLBCL is associated with high response rates, especially in relapsed patients. The vast majority of refractory patients progress very early, so this regimen could be considered as a bridge to other consolidation therapies. Biological studies analyzing cell of origin by gene expression profiling, minimal residual disease and mutational spectrum are in progress. Disclosures Abrisqueta: Roche: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. Giné:Janssen: Research Funding; Gilead: Research Funding; Roche: Research Funding. Grande:Janssen: Research Funding. Caballero:Roche: Other: travel; Gilead: Other: travel; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel; BMS: Other: travel; Takeda: Other: travel; Kite: Membership on an entity's Board of Directors or advisory committees. Martin Garcia-Sancho:Roche, Celgene, Janssen, Servier, Gilead: Honoraria; Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy. OffLabel Disclosure: Off-label use of a new combination in the context of a clinical trial. New combination (Ibrutinib + R-GEMOX)