Related Pneumonia Research Articles

Performance and impact of rapid multiplex PCR on diagnosis and treatment of ventilated hospital-acquired pneumonia in patients with extended-spectrum β-lactamase-producing Enterobacterales rectal carriage

BackgroundAntimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene.MethodsThis monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP.ResultsOver the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01).ConclusionmPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.

COVID-19 vs. non-COVID-19 related nosocomial pneumonias: any differences in etiology, prevalence, and mortality?

This review explores the similarities and differences between coronavirus disease 2019 (COVID-19)-related and non-COVID-related nosocomial pneumonia, particularly hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). It critically assesses the etiology, prevalence, and mortality among hospitalized patients, emphasizing the burden of these infections during the period before and after the severe acute respiratory syndrome coronavirus 2 pandemic. Recent studies highlight an increase in nosocomial infections during the COVID-19 pandemic, with a significant rise in cases involving severe bacterial and fungal superinfections among mechanically ventilated patients. These infections include a higher incidence of multidrug-resistant organisms (MDROs), complicating treatment and recovery. Notably, COVID-19 patients have shown a higher prevalence of VAP than those with influenza or other respiratory viruses, influenced by extended mechanical ventilation and immunosuppressive treatments like corticosteroids. The findings suggest that COVID-19 has exacerbated the frequency and severity of nosocomial infections, particularly VAP. These complications not only extend hospital stays and increase healthcare costs but also lead to higher morbidity and mortality rates. Understanding these patterns is crucial for developing targeted preventive and therapeutic strategies to manage and mitigate nosocomial infections during regular or pandemic care.

A case of hypercalcemia from Pneumocystis jirovecii in an immunosuppressed non-HIV patient

BackgroundThe prevalence of non-HIV related Pneumocystis jirovecii pneumonia (PJP) is increasing with use of immunosuppressive therapies. There are case reports of solid organ transplant recipients on immunosuppressive therapy presenting with mild hypercalcemia, leading to a diagnosis of PJP. Recent studies have shown efficacy of PJP prophylaxis for patients treated with rituximab with a favourable adverse effect profile.Case PresentationA 78-year-old male with a history of PR3-ANCA vasculitis, chronic kidney disease and heart failure with reduced ejection fraction presented to our tertiary care hospital with a two-week history of confusion and non-productive cough. Background immunosuppression with rituximab was completed every six months. The patient was found to have hypercalcemia and new infiltrates and ground glass opacities on cross-sectional imaging. Bronchoscopy was performed that was positive for Pneumocystis jirovecii. He was treated with 21 days of trimethoprim-sulfamethoxazole and prednisone with resolution of symptoms and hypercalcemia.ConclusionsHerein, we present a novel case of PJP in a non-transplant recipient preceded by hypercalcemia. Our case demonstrates the importance for a high suspicion for PJP in chronically immunosuppressed patients on rituximab presenting with PTH-independent hypercalcemia.

Incidence of Pneumonia on the Nutritional Status of Young Children in the Work Room of the Antang Public Health Center, Makassar South Sulawesi

Pneumonia is infection network lungs Which nature I reason his is bacteria, virus, mold, exposure material chemistry or damage physique from bacterial lungs Which normal cause pneumonia is Streptococcus and Mycoplasma Pneumonia, whereas virus which cause pneumonia is Adenoviruses, Rhinovirus, Influenza Virus, Respiratory Syncytial Virus. The aim of this study to find out the relationship between nutritional status and the incidence of pneumonia in toddlers In Region Work Public health center Antang. Type study This is method study analytical observation with a cross sectional approach. This research was carried out in part Antang health center working area. population in study this all toddler which visit in Public health center Antang. Technique taking sample use simple random sampling. The data analysis carried out was univariate analysis and bivaruate analysis. Test that on used is the chi square statistical test with another alternative test, namely the Fisher Excat test with level meaning p=0 .02 so HA accepted Because proven to exist connection knowledge Mother pregnant with attitude with p<0.05. Concluded there is connection Between Nutritional Status and the Incidence of Pneumonia in Toddlers in Community Health Center Working Areas Antang. Based on results study this, as good as his officer health especially midwife collaborate with health agencies that hold outreach and outreach activities so that they can increase knowledge, and information person related old pneumonia treatment on toddler.

The effect of malnutrition on adult Covid-19 patient's ICU admission and mortality in Covid-19 isolation and treatment centers in Ethiopia: A prospective cohort study.

A new coronavirus was first identified in Wuhan, China in December 2019. Since the times of the 1918 influenza pandemic, malnutrition has been known as a risk factor for severity and mortality from viral pneumonia. Similarly, the recently identified SARS-Cov2 infection (COVID-19) and related pneumonia may be closely linked to malnutrition. Therefore, this study will contribute to new knowledge and awareness of the recording and evaluation of each COVID-19 patient's nutritional status by assessing the effect of malnutrition on ICU admission and death of COVID-19 patients in developing countries. We conducted a prospective cohort study in adult COVID-19 patients admitted to selected COVID-19 Isolation and Treatment Centers, Addis Ababa, Ethiopia. Baseline data of the patients were collected using interviewer-administered structured questionnaire and data on the adverse outcomes of follow up were extracted from follow up chart. The main clinical outcomes (ICU admission and death) were captured every week of follow up. We ran a multivariate Cox's regression analysis to determine the relationship between malnutrition at admission and its effect on ICU admission and death. A total of 581 COVID-19 patients were enrolled. From the total of recruited patients, 346 (59.6%) were males and 235 (40.4%) were females. The mean age of the respondents was 55 years (16.45) years. The Cox proportional hazard model controlled for sex, age group, number of co-morbidities, and number of medications found that malnutrition at admission was associated with ICU admission and death. When compared to well-nourished patients, the rate of ICU admission was significantly associated and found to be higher among underweight [(adjusted hazard ratio (AHR) = 10.02, 95% CI: (8.64-12.10)] and overweight [(AHR = 7.7, 95% CI: (6.41-9.62)] patients. The rate of survival probability was significantly associated and was found to be better among well-nourished patients (AHR = 0.06, 95% CI : (0.01-0.44) when compared with malnourished COVID-19 patients. Malnutrition at the time of admission was shown to increase the risk of ICU admission and mortality among COVID-19 patients. Therefore, it is vital to evaluate patients' nutritional condition early in their admission and provide timely intervention to minimize the effects on patients and the healthcare system.

Pneumonie à cytomégalovirus humain

AbstractHuman Cytomegalovirus (hCMV) related pneumonia is mainly known as a potentially severe end organ disease in immunocompromised patients. However, hCMV lung reactivation can also alter the prognosis of critically ill patients, irrespective of their initial immune status. In this review, we focus on the epidemiology, physiopathology, diagnostic tools and clinical aspects of hCMV related pneumonia. We also summarize therapeutic strategies with an update on the old and new molecules to consider. Conclusion open up on research perspectives concerning the virus’s physiopathology such as SARS-CoV-2 and CMV virusvirus interactions.

Addition of Chidamide to a Sandwich Protocol, Pegaspargase, Gemcitabine and Oxaliplatin Chemotherapy Combined with Radiotherapy, As First-Line Treatment in Early Stage NK/T-Cell Lymphoma: Real World Outcomes in a Retrospective Study

Background: Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is a highly invasive tumor with a short doubling time and poor prognosis. Clinically, it usually involves the upper aerodigestive tract and mainly presents with early-stage. Initially, intensity modulated radiation therapy (IMRT) has been considered the preferred first-line therapy for early-stage ENKTL due to its high response rate. In recent years, more and more studies show that adding chemotherapy, especially asparaginase (ASP)-based regimens, provide survival benefit in early-stage patients. However, the optimal chemotherapy regimen has not been fully defined. Epigenetic regulatory mechanisms related to histone deacetylase (HDAC) have been found to play a role in the evolution and progression of ENKTL. Chidamide, a new HDAC inhibitor, has been confirmed to be effective and tolerable to treat lymphoma. Recently, Xue et al showed that chidamide in combination with cisplatin, etoposide or gemcitabine showed synergistic effect and reversed the chemotherapy resistance in the relapsed/refractory B-cell lymphoma. Here, we investigate the safety and efficacy of adding chidamide to a sandwich protocol, P-GEMOX (pegaspargase/gemcitabine/oxaliplatin) regimen (CP-GEMOX) combined with IMRT as first-line treatment in early-stage ENKTL-NT patients. Methods: We retrospectively reviewed data of early-stage ENKTL-NT patients in the first affiliated hospital of Soochow University from March 2020 to April 2023. A total of 21 patients diagnosed with early-stage (stage Ⅰ or Ⅱ) ENKTL-NT were enrolled and treated with 2 cycles of CP-GEMOX followed by IMRT and 1 or 2 cycles of CP-GEMOX sequentially as consolidation. After consolidation, chidamide was administrated as a maintenance therapy for 1 year. In the induction therapy phase, chidamide was administered orally at a dose of 20 mg twice a week for two weeks, with a one-week discontinuation period; During the maintenance treatment phase, the original dose of chidamide was still maintained and used without pause. The baseline clinical features for the 21 patients were summarized in Table 1. Results: Among 21 patients, 14 were males and 7 were females, and their median age was 57 (range, 41-75) years. Elevated lactate dehydrogenase, elevated β2-microglobulin, stage II disease and primary tumor invasion were present in 4.8% (1/21), 19.0% (4/21), 61.9% (13/21) and 61.9% (13/21) patients. According to the early stage-adjusted nomogram-revised risk index, the majority of patients (76.2%, 16/21) were classified into intermediate- (1-2) and high (≥3) risk groups. The baseline clinical features for the 21 patients were summarized in Table 1. During treatment, all patients were well-tolerated and the most common adverse events were hematological toxicities with neutropenia, thrombocytopenia and anemia. Among non-hematological adverse events, nausea, vomiting and reduced appetite were most common. Other side effects included coagulation dysfunction, skin reaction, diarrhea, serum amylase and alanine aminotransferas /aspartate aminotransferase /bilirubin elevation. No anaphylactic reaction to pegaspargase, hemophagocytic syndrome, pancreatitis or sepsis were observed during chemotherapy. Some patients had mucositis and xerostomia when receiving local radiotherapy. All side effects could be reversed with proper treatment, and there were no therapy related mortality. All patients completed 2 cycles of CP-GEMOX, 19 patients achieved complete remission (CR) and 2 patients achieved partial remission (PR) with a CR rate of 90.5% (19/21) and overall response rate (ORR) of 100.0% (21/21) after 2 cycles of CP-GEMOX. Among the 21 patients, 18 patients completed treatment and CR rate was improved to 100.0% (18/18), giving an ORR of 100% (18/18). After a median follow-up of 25.6(range, 2.6-39) months , all patients were alive except one patient relapsed 20 months after treatment and died of COVID-19 related pneumonia 1 month later. The 2-year progression-free survival and overall survival were all 91.5% (Figure 1). Conclusions: This study demonstrates that sandwich CP-GEMOX chemoradiotherapy is a safe and promising approach to managing patients with early-stage ENKTL-NT. Keywords: Extranodal NK/T-cell lymphoma; chidamide; pegaspargase; gemcitabine; radiation therapy.

409. Unvaccinated Adolescents Bear the Majority of Disease Burden of Severe COVID-19 Among Those Admitted to the Intensive Care Unit (ICU)

Abstract Background COVID-19 vaccination is one of the most important public health tools to prevent severe COVID-19. Methods COVID-19 vaccine (Pfizer-BioNTech) first received the U.S. Food and Drug Administration (FDA) Emergency use authorization (EUA) for individuals 16 years of age and older on 12/11/2020 and for 12-15 years of age on 5/10/2021. We evaluated clinical and epidemiologic characteristics of critically ill adolescents with COVID-19 admitted to the intensive care unit (ICU) at our tertiary-care centers in Northwestern Iowa (encompassing Sioux City and Sergeant Bluff locations) during the 1-year post-vaccination approval period from June 1, 2021- May 31, 2022. Adolescence was defined as age-group 12-21 years per WHO definition. Results Twenty-one adolescents were admitted to the ICU with a median age of 16 years (IQR 12-20 years) and male: female ratio of 1:1.3. The majority (77%) were admitted with COVID-19 related pneumonia and 10 developed hypoxemic respiratory failure; 19 of 21 (90%) adolescent patients admitted to the ICU during this period were unvaccinated and all adolescents developing respiratory failure (10/10, 100%) were unvaccinated. Majority of patients with respiratory failure (70%) required mechanical ventilation (MV). Seventy % of patients with respiratory failure were obese (BMI of >30); 40% of patients had two or more pre-existing comorbidities; those with BMI >40 were 4.3 times more likely to develop respiratory failure (p< 0.0001). Inflammatory markers were 5-20 times higher among patients with respiratory failure (p< 0.05); 60% of those with respiratory failure developed complications including ARDS, acute renal injury and cerebral anoxic encephalopathy. All with respiratory failure required parenteral steroids. Mean duration of ICU stay was significantly longer for patients with respiratory failure [14.6 (±1.7) days versus 7.5 (± 2.6) days, p< 0.0001)]. None of the patients died. After hospital discharge, 30% patients reported post COVID-19 fatigue at 3-month follow up. Conclusion Our results showed that all of the critically ill adolescent patients with COVID-19 associated hypoxemic respiratory failure were unvaccinated and majority developed complications. These results further emphasize importance of COVID-19 vaccination efforts for adolescents. Disclosures All Authors: No reported disclosures

Long-term respiratory consequences of COVID-19 related pneumonia: a cohort study

BackgroundOur aims were to describe respiratory sequelae up to 12 months after discharge in COVID-19 patients with severe pneumonia requiring non-invasive respiratory support therapies.MethodsThis study was undertaken at University Hospital Doctor Josep Trueta (Girona, Spain) between March 2020 and June 2020. Three months after discharge, we evaluated their dyspnoea and performed Saint George’s respiratory questionnaire, pulmonary function tests, blood test, 6-min walking test, and a high-resolution CT (HRCT). At the six and 12-month follow-up, we repeated all tests except for pulmonary function, 6-min walking test, and HRCT, which were performed only if abnormal findings had been previously detected.ResultsOut of the 94 patients recruited, 73% were male, the median age was 62.9 years old, and most were non-smokers (58%). When comparing data three and 12 months after discharge, the percentage of patients presenting dyspnoea ≥ 2 decreased (19% vs 7%), the quality-of-life total score improved (22.8% vs 18.9%; p = 0.019), there were less abnormal results in the pulmonary function tests (47% vs 23%), the 6-min walking test distance was enhanced (368.3 m vs 390.7 m, p = 0.020), ground glass opacities findings waned (51.6% vs 11.5%), and traction bronchiectasis increased (5.6% vs 15.9%). Only age showed significant differences between patients with and without pulmonary fibrotic-like changes.ConclusionMost patients improved their clinical condition, pulmonary function, exercise capacity and quality of life one year after discharge. Nonetheless, pulmonary fibrotic-like changes were observed during the follow-ups.

Preliminary Results of a Phase 2 Study of IMM01 Combined with Azacitidine (AZA) As the First-Line Treatment in Adult Patients with Chronic Myelomonocytic Leukemia (CMML)

Background: Patients with Chronic Myelomonocytic Leukemia (CMML) have poor prognosis and an inherent risk for transformation to acute myeloid leukemia. IMM01 is a recombinant signal regulatory protein α (SIRPα) IgG1 fusion protein that exerts anti-tumor activity via blocking “Don't eat me” signal and activating the “Eat me” signal to induce strong antibody-dependent cellular phagocytosis (ADCP). Furthermore, IMM01 activated macrophages could process and present tumor antigen to T cells and elicit long-last tumor-specific T cell immune response. Methods : This is an open-label, multi-center, phase 2 study (NCT05140811) that evaluated safety and efficacy of IMM01 in combination with AZA as the first-line treatment in patients with newly diagnosed CMML. We enrolled patients aged 18 years or older with the diagnosis of CMML, including subtypes CMML-1 and 2, not eligible for stem cell transplant. Patients with treatment-naive CMML were administered intravenous IMM01 at a dosage of 2.0mg/kg/week and subcutaneous AZA at a dosage of 75 mg/m 2 on D1-7 per 28-day cycle. Safety was assessed by CTCAE V5.0 and efficacy by IWG 2006 (MDS) criteria. Results : Between August 4, 2022 and July 7, 2023, 24 patients were enrolled: median age was 62 years, 15 (62.5%) males, 18(75.0%) ECOG≥1. Additionally, 1(4.2%), 7(29.2%) and 16(66.7%) patients were intermediate risk(IR)-1, IR-2 and high risk(HR) by CPSS-mol classification, respectively. According to World Health Organization (WHO) classification of CMML, patients enrolled included CMML-1(50.0%) and CMML-2(50.0%). Majority of patients had poor baseline hematologic conditions with a median Hb of 69.5 (32, 132) g/L and a median PLT of 73.5 (5, 667)×10 9/L. By the data cut-off date of July 7, 2023, the median follow-up for the study was 4 months (95%CI:3.3-4.8). Among the 16 efficacy evaluable patients who received initial treatment ≥3 months, overall response rate (ORR) was 87.5% (14/16), including 25.0% (4/16) complete response (CR), 18.8% (3/16) marrow CR (mCR) with hematologic improvement (HI), 6.3% (1/16) HI and 37.5% (6/16) mCR alone. Among the 9 efficacy evaluable patients who received initial treatment ≥4 months, ORR was 88.9% (8/9), including 44.4% (4/9) CR, 11.1% (1/9) mCR with HI and 33.3% (3/9) mCR alone. The CR rate of IMM01 combined with AZA is increasing with longer treatment duration. The median duration of response (DoR) was not reached. NGS analysis of bone marrow collected from responders were included in this study. The most frequent treatment related adverse events (TRAEs) (≥20%) were lymphopenia (70.8%), leukopenia (70.8%), neutropenia (70.8%), thrombocytopenia (58.3%), infusion related reaction (33.3%), anemia (25.0%), pyrexia (25.0%), pneumonia (25.0%), constipation (20.8%), nausea (20.8%), vomiting (20.8%) and leukocytosis (20.8%). The most common ≥Grade 3 TRAEs (≥10%) included lymphopenia (66.7%), neutropenia (54.2%), leukopenia (54.2%), thrombocytopenia (54.2%), anemia (20.8%) and pneumonia (16.7%), all of which were commonly reported in AZA monotherapy studies for treatment naive MDS/CMML patients in China. The study is ongoing. Conclusions: Preliminary data showed that IMM01 (without a low-dose priming) combined with AZA were well tolerated. The combo, when compared to the historical data of AZA alone, showed exciting efficacy result for patients with treatment-naive CMML1-2.

Analysis of The Antibiotic Resistance Problem

Antibiotic resistance is a global health problem. Its solution requires concerted efforts on the scale of global cooperation. Programs to prevent the development of antibiotic resistance, as well as to stimulate the development of new drugs with antimicrobial activity are implemented in a lot of countries. The use of antibacterial drugs, including inappropriate use, has increased during the COVID-19 pandemic, which may contribute to the growth of antibiotic resistance. The aim of this study is to assess the measures aimed at combating the growing antibiotic resistance in the world, analyze the market of antimicrobial drugs in the Russian Federation, as well as collect and process information on the antibiotic resistance of microorganisms that cause infectious diseases that develop against the backdrop of COVID-19. The analysis of the state register of the Russian Federation for antibacterial drugs was carried out. Mathematical and statistical processing of antibiotic resistance was performed according to the data of the European Surveillance Atlas of Infectious Diseases for Klebsiella pneumonia in relation to fluoroquinolones, aminoglycosides, third-generation cephalosporins, as well as combined resistance to these antibacterial drugs over the past sixteen years.

Giant lung bulla as a late-onset complication of mild SARS-CoV-2 pneumonia.

A 49-year-old Caucasian man was admitted to the Emergency Department for shortness of breath and cough. CT imaging showed bilateral a mild COVID-19 related pneumonia. He was hospitalized in the low-intensity COVID-19 unit where he received O2 therapy and oral corticosteroids (CS). Three weeks after discharge a high-resolution computed tomography (HRCT) find a giant bulla of the inferior lobe. The bulla was resected by video-assisted thoracoscopic surgery (VATS) and the patient recovered completely. In our patient, it is reasonable to suspect that the development of the bulla is a result of SARS-CoV-2 infection, since no bulla was observed in the first HRCT two months before. SARS-CoV-2 related pneumonia may be responsible for lung remodeling due to diffuse alveolar damage and later interstitial myofibroblastic proliferation. Corticosteroids might have played a role in increasing SARS-CoV-2 dystrophic action. COVID-19 leads to pulmonary damages, which are still partially unknown and might result in development of bullae. In fit patient surgical treatment can be carried out safely.

Peripheral blood eosinophil count as a biomarker of exacerbation in stable chronic obstructive pulmonary disease outpatients: a prospective observational study

Abstract Background Peripheral blood eosinophil count is liable to many factors and has variability over time. There are few studies on the association between the rise of blood eosinophils and the exacerbation incidence in stable chronic obstructive pulmonary disease (COPD) patients. The association between the rise of blood eosinophils and the rate of exacerbation in stable COPD patients is controversial. Objective To study the relationship between the count of eosinophils in the peripheral blood and the incidence of COPD exacerbation in stable patients. Patients and methods This prospective inquiry was done on 46 patients diagnosed as suffering from stable COPD ‘on the report of the global initiative for chronic obstructive lung disease (GOLD) guidelines’ attending Ain Shams University hospital outpatient clinic. Results Forty-six stable COPD patients were classified into two groups (groups A and B) based on their median eosinophilic count of ‘250 cell/μl.’ Patients with high eosinophil count ‘group A’ (>250 cell/μl) had a significantly higher incidence of exacerbations (P=0.003), with a relative risk ratio of 2.77, as well as a higher number of exacerbations per patient (two exacerbations/patient) versus one exacerbation/three patients (P<0.001), and a shorter period to the first exacerbation (17 vs. 31 days) (P=0.024), compared with those with low eosinophil count ‘group B (≤250 cell/μl)’ during the study period. On the contrary, there was no significant difference between them in the incidence of pneumonia in relation to inhaled corticosteroid use. Conclusion The count of eosinophils in the peripheral blood is a reliable exacerbation biomarker in stable COPD patients.

Causal association of rheumatoid arthritis with obstructive lung disease: Evidence from Mendelian randomization study

BackgroundObservational studies have found an association between rheumatoid arthritis (RA) and risk of obstructive lung disease (ORDs). However, whether RA plays a role in ORDs development remains unclear. ObjectivesThis study aimed to explore the causal association of RA with ORDs. MethodsBoth univariable and multivariable Mendelian randomization (MR) analyses were employed. Summary statistics for RA were obtained from the genome-wide association study (GWAS) meta-analysis, and the GWAS data source of ORDs, including the chronic obstructive pulmonary disease (COPD) and asthma, was accessed from the FinnGen Biobank. Causal Analysis Using Summary Effect Estimates (CAUSE) method was used to improve statistical power. multivariable and two-step mediation MR was applied to calculate the independent and mediated effects. ResultsThe causal estimates by univariable and CAUSE results indicated genetic predisposition to RA had an effect on the increased risk of asthma/COPD (A/C) (ORCAUSE = 1.03; 95% CI: 1.02–1.04), COPD/asthma related infections (ACI) (ORCAUSE = 1.02; 95% CI: 1.01–1.03) and COPD/asthma related pneumonia or pneumonia derived septicemia (ACP) (ORCAUSE = 1.02; 95% CI: 1.01–1.03). Genetic predisposition to RA was significantly associated with early onset COPD (ORCAUSE = 1.02; 95% CI: 1.01–1.03) and asthma (ORCAUSE = 1.02; 95% CI: 1.01–1.03) risk and suggestively associated with non-allergic asthma (nAA) risk. After adjustment for confounders, independent causal effects remained for the associations of RA with risk of A/C, ACI, and ACP, as well as COPD, early-onset COPD, and asthma [total, nAA and allergic asthma (AA)] risk. Mediation analyses revealed no potential mediator. ConclusionThis study indicates a causal effect of increased genetic predisposition to RA on an increased risk of ORDs, including COPD and asthma, especially early-onset COPD and nAA, and on asthma/COPD related infections, pneumonia or pneumonia derived septicemia.

LACK OF CARDIOVASCULAR EVENTS AFTER ONE YEAR FOLLOW-UP IN PATIENTS FOLLOWED HOSPITAL ADMISSION FOR MODERATE TO SEVERE COVID-19 PNEUMONIA

Objective: There is increasing evidence that SARS-CoV-2 infection may involve many organs, including cardiovascular system, possibly causing not only acute but cardiovascular events in the long term. In this retrospective analysis we investigated cardiovascular events during a long time span since hospitalization (384 days and 848) on two different groups of patients. Design and method: This study considers two different groups: the first included 43 patients from the second-third wave (October 2020-May 2021), hospitalized in our Internal Medicine ward for moderate to severe SARS-CoV2 related pneumonia treated with high-flow oxygen support that accepted to be re-evaluated after an average period of 324 days by quality-of-life questionnaire, standard laboratory tests, chest computed tomography, spirometry with evaluation of DLCO. Mean age was 63 years, 28% (12/43) were female and 72% (31/43) were male. The second group included 82 patients from the first wave (February 2020-May 2022) over 94 that underwent a similar follow-up protocol after a mean of 4 month (no CV events at that time) and were contacted with a phone interview assessing quality of life and cardiovascular event after a mean of 848±16 days. Mean age was 66 years, 37% (30/82) were female and 63% (52/82) were male. Results: None of the first group of 43 patients had major cardiovascular events: coronary heart disease, cerebrovascular disease, peripheral arterial disease, deep vein thrombosis and pulmonary embolism. Of them, 35% suffered from heart diseases, 56% of them were hypertensives and 23% had type-2 diabetes; 12% had chronic kidney disease and 49% was obese; In the second group one patient underwent a PTCA and another had an apparently non-provoked pulmonary embolism, but no other major cardiovascular events were reported Among second group, 18% had heart diseases, 51% hypertension, 17% type 2 diabetes; 6% chronic kidney disease and 39% were obese Conclusions: This study has some limitations, anyway, failed to demonstrate a higher new-onset CV events compared with normal population. Il is plausible that longer follow-up studies with much higher numbers or more detailed analyses are needed to better define cardiovascular risk following SARS-CoV-2 infection.

ResNetFed: Federated Deep Learning Architecture for Privacy-Preserving Pneumonia Detection from COVID-19 Chest Radiographs

Personal health data is subject to privacy regulations, making it challenging to apply centralized data-driven methods in healthcare, where personalized training data is frequently used. Federated Learning (FL) promises to provide a decentralized solution to this problem. In FL, siloed data is used for the model training to ensure data privacy. In this paper, we investigate the viability of the federated approach using the detection of COVID-19 pneumonia as a use case. 1411 individual chest radiographs, sourced from the public data repository COVIDx8 are used. The dataset contains radiographs of 753 normal lung findings and 658 COVID-19 related pneumonias. We partition the data unevenly across five separate data silos in order to reflect a typical FL scenario. For the binary image classification analysis of these radiographs, we propose ResNetFed, a pre-trained ResNet50 model modified for federation so that it supports Differential Privacy. In addition, we provide a customized FL strategy for the model training with COVID-19 radiographs. The experimental results show that ResNetFed clearly outperforms locally trained ResNet50 models. Due to the uneven distribution of the data in the silos, we observe that the locally trained ResNet50 models perform significantly worse than ResNetFed models (mean accuracies of 63% and 82.82%, respectively). In particular, ResNetFed shows excellent model performance in underpopulated data silos, achieving up to +34.9 percentage points higher accuracy compared to local ResNet50 models. Thus, with ResNetFed, we provide a federated solution that can assist the initial COVID-19 screening in medical centers in a privacy-preserving manner.

P92 PERIMYOCARDITIS AS FIRST MANIFESTATION OF DYSTHYROIDISM: AN UNUSUAL CASE

Abstract Thyroid and cardiovascular system are inextricably related and cardiovascular complications can occur in both subclinical and overt thyroid dysfunction. We report the case of a 42–year–old woman presenting with chest pain. She had a positive SARS–CoV–2 swab in June and she was hospitalised in suspicion of COVID–related pneumonia and pericarditis in July: treatment with ibuprofen and colchicine was started and patient was discharged. On July 26th, the patient came back to emergency department due to worsening chest pain and myalgias after therapy decalage. She had face edema and hoarse voice. 12–leads EKG was normal; echocardiography showed 8 mm pericardial effusion and normal ejection fraction. Blood testing revealed no inflammatory signs, a mild increase of Troponin (peak value 19.1 ng/L, n.v. 0–14) and a high value of CPK (peak value 2299 U/L, 464 U/L at time of discharge, n.v. 30–150). Moreover, she had a biohumoral profile of Hashimoto thyroiditis: severe hypothyroidism with increase in TSH levels (538 microU/ml peak value, 322 microU/ml at time of discharge, n.v. 0.27–4.2) and positivity to thyroid autoantibodies. The patient underwent a cardiac magnetic resonance imaging that was suggestive for acute perimyocarditis with biventricular diffuse myocardial edema, preserved biventricular function and mild–to–moderate pericardial effusion. Low dose L–T4 therapy was started together with liothyronine that was stopped after few days, once acceptable FT3 concentrations were obtained. At echocardiography control after 8 days, we registered a significant reduction of pericardial effusion (2 mm). Myocarditis is an inflammatory disease of the myocardium and it is predominantly mediated by viral infection. A rare cause of myocarditis is represented by dysthyroidism. In our case, the severe hypothyroidism seems to be the cause of myocardial and pericardial edema. The failure in diagnosis of this endocrinological disorder can determine a delay in specific therapy with possible serious cardiovascular manifestations. So, it would be reasonable to check the thyroid status of all patients presenting with myopericarditis, in the absence of another clearly identifiable aetiology. The role of to the prior SARS–CoV–2 infection in not certain in our case, but the quick recovery after specific endocrinological therapy suggests the low probability of perimyocarditis as SARS–CoV2 related manifestation.

Hydroxychloroquine and Mortality in SARS-Cov-2 Infection; the HOPECovid- 19 Registry

Background: Hydroxychloroquine (HCQ) may be an effective, safe, and affordable treatment for Covid-19 that can be used in selected patients. However, more evidence on its association when it is used in different stages of the disease with clinical outcomes is required. This observational study investigates the association between treatment with HCQ and mortality in patients with Covid-19. Methods: The data from 6217 patients who died or were discharged from 24 Spanish hospitals were analyzed. Propensity matching scores (PMS) were used. Results: 5094 patients received HCQ. Death was recorded for 17.5% of those who had HCQ and 34.1% of those who did not have it. Mortality was lower for those who had HCQ, OR=0.41 (95% CI=0.34-0.48). The PMS analysis also showed that mortality was lower for those receiving HCQ, OR=0.47 (95%CI=0.36-0.62). PMS analysis for categories revealed an association between HCQ and lowered mortality for patients over 65 years of age, with a past medical history of hypertension, for those who were diagnosed during admission with sepsis related organ failure or pneumonia, and for those with lymphocytopenia, raised troponin, LDH, ferritin and D-dimer. No increase in mortality associated with HCQ was observed in any category of any of the variables investigated. Conclusions: HCQ could be associated with lower mortality for older patients, those with more severe disease and raised inflammatory markers. Further RCTs, observational studies, and summaries of both types of evidence on this topic are necessary to select the precise profile of patients that may benefit from HCQ.

Hypocapnia as a predictor of the need for non-invasive mechanical ventilation in subjects with SARS-CoV-2 related pneumonia

Background: SARS-CoV-2 related pneumonia is characterized by moderate-to severe hypoxemia often associated with hypocapnia the prognostic role of which is poorely documented.
 Aims: evaluate if hypocapnia can predict the need for non-invasive mechanical ventilation (NIMV) in this setting.
 Materials and methods: we prospectively studied 52 subjects with moderate-severe SARS-CoV-2 related pneumonia. All the following data were collected at admission to the Emergency Department and processed by univariate and multivariate analysis: clinical and laboratory data, blood gas analysis in room air and lung ultrasound.
 Results: 33/52 subjects (63,4%) underwent NIMV. At univariate analysis PaCO2 was inversely associated to the need for NIMV (OR 0,82, CI 95% 0,689-0,976, p .025). At multivariate analysis PaCO2 predicted the need for NIMV independently from age, gender, number of comorbidities, d-dimer, CRP, PaO2 and LUS SCORE (OR 0,838, CI 95% 0,710-0,988, p .035).
 Conclusions: our data suggest that hypocapnia could be an early predictor of clinical worsening in these patients independently from other known predictors of unfavourable outcome, reflecting the occurrence of a deep and frequent respiratory pattern possibly related to the generation of excessive transpulmonary pressure swings leading to a self-induced lung injury (P-SILI). Further studies are needed for validating these data on greater populations.

Clinical features and diagnostic value of metagenomic next -generation sequencing in five cases of non-HIV related Pneumocystis jirovecii pneumonia in children.

Pneumocystis jirovecii (PJ) is an opportunistic pathogenic fungus, and PJ pneumonia (PJP) is a commonly problem in HIV-positive patients. While PJP is not caused by HIV, it generally advances rapidly and can quickly lead to severe respiratory failure. To improve pediatricians' understanding of the condition and aid early accurate diagnoses and therapy, we examined the clinical characteristics of five instances of non-HIV related PJP (NH-PJP) in children and the efficacy of metagenomic next-generation sequencing (mNGS) in its diagnosis. From January 2020 to June 2022, five children with NH-PJP were admitted to the PICU of the First Affiliated Hospital of Zhengzhou University. We retrospectively summarize the clinical presentation, previous histories, routine laboratory findings, treatment, outcome of regression, and results of mNGS in these five children. Five male children between the ages of 11 months and 14 years had an acute onset on NH-PJP, three of the children had chest tightness after activity, shortness of breath and paroxysmal dry cough, - and two had high fever and dry cough. All five of the children had several flocculent high-density pictures in both lungs at the beginning of the disease, and lung auscultation revealed coarse breath sounds in both lungs, one of which was accompanied by a modest quantity of dry rales. PJ nuclear sequences were found in one patient and four patients' blood and alveolar lavage fluid. All five children were treated with Trimethoprim-sulfamethoxazole (TMP-SMX) in combination with Caspofungin and corresponding symptomatic treatment. Four patients were cured and one patient died. Children commonly encounter an initial exposure to NH-PJP, which manifests as a high fever, dry cough, chest discomfort, dyspnea that worsens over time, fast disease progression, and a high death rate. The clinical presentation of children with PJ infection should be taken into consideration along with the results for diagnose. mNGS has higher sensitivity and a shorter detection period compared to identification of PJP.